CA2328895A1 - Secreted and transmembrane polypeptides and nucleic acids encoding the same - Google Patents
Secreted and transmembrane polypeptides and nucleic acids encoding the same Download PDFInfo
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- CA2328895A1 CA2328895A1 CA002328895A CA2328895A CA2328895A1 CA 2328895 A1 CA2328895 A1 CA 2328895A1 CA 002328895 A CA002328895 A CA 002328895A CA 2328895 A CA2328895 A CA 2328895A CA 2328895 A1 CA2328895 A1 CA 2328895A1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The present invention is directed to polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.
Description
t DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTS PARTiE DE CETTE DEMANDS OU CE BREVET
COMPREND PLUS D'UN TOME.
CECI EST LE TOME 'I DE
NOTE: ~ Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets THAN ONE VOLUME
THIS IS VOLUME ~ , OF
NOTE: For additional volumes please contact the Canadian Patent Office NOVEL POLYPEPTIDES AND NUCLEIC ACIDS ENCODirIG TIC SAME
FIELD OF THE INVENTION
The present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides.
BACKGROUND OF THE INVENTION
Extracellular proteins play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenicfactors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. These secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the exuacellular environment.
Secreted proteins have various industrial applications, including as pharmaceuticals, diagnostics, biosensors and bioreactors. Most protein drugs available at present, such as thrombolytic agents, interferons, interleukins, erythropoietins, colony stimulating factors, and various other cytokines, are secretory proteins.
Their receptors, which are membrane proteins, also have potential as therapeutic or diagnostic agents. Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad. Sci. 93:7108-7113 (1996); U.S. Patent No. 5,536,637)].
Membrane-bound proteins and receptors can play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins.
Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance,, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interactions. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.
Efforts are being undertaken by both industry and academia to identify new, native receptor or membrane-bound proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor or membrane-bound proteins.
1. PR0281 A novel gene designated testis enhanced gene transcript (TEGT) has recently been identified in humans (Walter et al., Genomics 20:301-304 (1995)). Recent results have shown that TEGT protein is developmentally regulated in the mammalian testis and possesses a nuclear targeting motif that allows the protein to localize to the nucleus (Walter et al., Mamm. Genome 5:216-221 (1994)). As such, it is believed that the TEGT protein plays an important role in testis development. There is, therefore, substantial interest in identifying and characterizing novel polypeptides having homology to the TEGT protein. We herein describe the identification and characterization of novel polypeptides having homology to TEGT protein, designated herein as PR0281 poIypeptides.
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CECI EST LE TOME 'I DE
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NOTE: For additional volumes please contact the Canadian Patent Office NOVEL POLYPEPTIDES AND NUCLEIC ACIDS ENCODirIG TIC SAME
FIELD OF THE INVENTION
The present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides.
BACKGROUND OF THE INVENTION
Extracellular proteins play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenicfactors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. These secreted polypeptides or signaling molecules normally pass through the cellular secretory pathway to reach their site of action in the exuacellular environment.
Secreted proteins have various industrial applications, including as pharmaceuticals, diagnostics, biosensors and bioreactors. Most protein drugs available at present, such as thrombolytic agents, interferons, interleukins, erythropoietins, colony stimulating factors, and various other cytokines, are secretory proteins.
Their receptors, which are membrane proteins, also have potential as therapeutic or diagnostic agents. Efforts are being undertaken by both industry and academia to identify new, native secreted proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. Examples of screening methods and techniques are described in the literature [see, for example, Klein et al., Proc. Natl. Acad. Sci. 93:7108-7113 (1996); U.S. Patent No. 5,536,637)].
Membrane-bound proteins and receptors can play important roles in, among other things, the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins.
Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance,, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interactions. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.
Efforts are being undertaken by both industry and academia to identify new, native receptor or membrane-bound proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor or membrane-bound proteins.
1. PR0281 A novel gene designated testis enhanced gene transcript (TEGT) has recently been identified in humans (Walter et al., Genomics 20:301-304 (1995)). Recent results have shown that TEGT protein is developmentally regulated in the mammalian testis and possesses a nuclear targeting motif that allows the protein to localize to the nucleus (Walter et al., Mamm. Genome 5:216-221 (1994)). As such, it is believed that the TEGT protein plays an important role in testis development. There is, therefore, substantial interest in identifying and characterizing novel polypeptides having homology to the TEGT protein. We herein describe the identification and characterization of novel polypeptides having homology to TEGT protein, designated herein as PR0281 poIypeptides.
2. PR0276 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0276 polypeptides.
3. PR0189 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0189 polypeptides.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0189 polypeptides.
4. PR 1 Of particular interest are proteins having seven transmembrane domains (7TM), or more generally, all multiple transmembrane spanning proteins. Among multiple transmembrane spanning proteins are ion channels and transporters. Examples of transporters are the UDP-galactose transporter described in Ishida, et al., J.
Biochem., 120(6):1074-1078 (1996), and the CMP-sialic acid transporter described in Eckhardt, et al., PNAS, 93(15):7572-7576 (1996). We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0190 polypeptides.
Biochem., 120(6):1074-1078 (1996), and the CMP-sialic acid transporter described in Eckhardt, et al., PNAS, 93(15):7572-7576 (1996). We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0190 polypeptides.
5. PR0341 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0341 polypeptides.
6. PR 180 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0180 polypeptides.
7. PR0194 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0194 polypeptides.
8. PR0203 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled release and utilization of chemical energy, and other processes necessary to sustain life. ATPases are a family of enzymes that play a variety of important roles, including energizing transport of ions and molecules, across cellular membranes.
Transport mechanisms that employ ATPases often involve excluding xeno- and endobiotic toxins from the cellular environment, thereby protecting cells from toxicity of these compounds. Lu et al. report a detoxification mechanism where glutathione S-transferase (GST) catalyzes glutathionation of plant toxins, and a specific Mg'-+ -ATPase is involved in the transport of the glutathione S-conjugates from the cytosol. Proc. Natl . Acad.
Sci. USA 94( 15):8243-8248 ( 1997).
This study and others indicate the importance of the identification of ATPases, such as GST ATPases, and of novel proteins having sequence identity with ATPases.
More generally, and also of interest are novel membrane-bound proteins, including those which may be involved in the transport of ions and molecules across membranes. Membrane-bound proteins and receptors can play an important role in the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins.
Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
In light of the important physiological roles played by ATPases and membrane-bound proteins efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins, and proteins having sequence identity to ATPases. We herein describe the identification and characterization of novel polypeptides having sequence identity to GST ATPase, designated herein as PR0203 polypeptides.
Transport mechanisms that employ ATPases often involve excluding xeno- and endobiotic toxins from the cellular environment, thereby protecting cells from toxicity of these compounds. Lu et al. report a detoxification mechanism where glutathione S-transferase (GST) catalyzes glutathionation of plant toxins, and a specific Mg'-+ -ATPase is involved in the transport of the glutathione S-conjugates from the cytosol. Proc. Natl . Acad.
Sci. USA 94( 15):8243-8248 ( 1997).
This study and others indicate the importance of the identification of ATPases, such as GST ATPases, and of novel proteins having sequence identity with ATPases.
More generally, and also of interest are novel membrane-bound proteins, including those which may be involved in the transport of ions and molecules across membranes. Membrane-bound proteins and receptors can play an important role in the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiation factors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins.
Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
In light of the important physiological roles played by ATPases and membrane-bound proteins efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins, and proteins having sequence identity to ATPases. We herein describe the identification and characterization of novel polypeptides having sequence identity to GST ATPase, designated herein as PR0203 polypeptides.
9. PR0290 Of particular interest are novel proteins and nucleic acids which have sequence identity with known proteins and nucleic acids. Proteins of interest which are well known in the art include NTII-1, a nerve protein which facilitates regeneration, FAN, and beige. Beige, or bg, is a murine analog related to Chediak-Higashi Syndrome (CHS), a rare autosomal recessive disease in which neutrophils, monocytes and lymphocytes contain giant cytoplasmic granules. See Perou et al., J. Biol. Chem. 272(47):29790 (1997) and Barbosa et al., Nature 382:262 ( 1996).
We herein describe the identificationand characterization of novel polypeptides having sequence identity to NTII-1, FAN and beige, designated herein as PR0290 polypeptides.
We herein describe the identificationand characterization of novel polypeptides having sequence identity to NTII-1, FAN and beige, designated herein as PR0290 polypeptides.
10. PR0874 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0194 polypeptides.
11. PR0710 In Saccharomyces cerevisiae, the chromatin structure of DNA replication origins changes as cells become competent for DNA replication, suggesting that G 1 phase-specific association of replication factors with origin DNA regulates entry into S phase (Aparicio et al., Cell 91:59-69 (1997)). In fact, it has been shown that the initiation of DNA replication in Saccharomyces cerevisiae requires the protein product of the CDC45 gene which encodes a protein that stays at relatively constant levels throughout the cell cycle (Owens et al., Proc.
Natl. Acad. Sci USA 94:12521-12526 (1997)). The CDC45 protein is part of a prereplication complex that may move with DNA replication forks in yeast. Given the obvious importance of the CDC45 protein in DNA
replication, there is significant interest in identifying and characterizing novel polypeptides having homology to CDC45. We herein describe the identification and characterization of novel polypeptides having homology to the CDC45 protein, designated herein as PR0710 polypeptides.
Natl. Acad. Sci USA 94:12521-12526 (1997)). The CDC45 protein is part of a prereplication complex that may move with DNA replication forks in yeast. Given the obvious importance of the CDC45 protein in DNA
replication, there is significant interest in identifying and characterizing novel polypeptides having homology to CDC45. We herein describe the identification and characterization of novel polypeptides having homology to the CDC45 protein, designated herein as PR0710 polypeptides.
12. PR01151 The complement proteins comprise a large group of serum proteins some of which act in an enzymatic cascade, producing effector molecules involved in inflammation. The complement proteins are of particular importance in regulating movement and function of cells involved in inflammation. One of the complement proteins, Clq, has been shown to be involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement (Shapiro et al., Curr. Biol.
8(6):335-338 (1998)).
Given the physiological importance of inflammation and related mechanisms in vivo and in the specific physiological activities of complement C lq protein, efforts are currently being undertaken to identify new, native proteins which share sequence similarity to the complement proteins. We herein describe the identification and characterization of novel polypeptides having homology to complement C 1 q protein, designated herein as PR01151 polypeptides.
I3. PROl 2 All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Trends Biochem. Sci.. 19(10):415-421 (Oct. 1994);
Kobe and Deisenhofer, Curr.
O,~in. Struct. Biol., 5(3):409-416 (1995).
A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem.
Mol. Biol., 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome, Chlemetson, K. J., Thromb.
aemost. (Germany), 74(1):111-116 (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factory has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the IGF complex in vivo.
Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland), 125(1-2):65 70 (Dec. 1996) (gonadotropin receptor involvement); Miura, Y. , et al. , Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J. Am. Soc.
Nephrol., 6(4):1125-1133 (Oct. 1995) (kidney disease involvement).
Leucine rich repeat proteins are further discussed in Kajava, J. Mol. Biol., 277(3):519-527 (1998), Nagasawa, et al., en mics, 44(3):273-279 (1997), Bengtsson, J. Biol. Chem., 270(43):25639-25644 (1995), Gaillard, et al., Cell, 65(7):1127-1141 (1991) and Ohkura and Yanagida. Cell, 64(1):149-157 (1991), all incorporated herein by reference.
Thus, due to all the reasons listed above, new members of the leucine rich repeat superfamily are of interest. On a more general level, all novel proteins are of interest. We herein describe the identification and characterization of novel leucine-rich repeat-containing polypeptides, designated herein as PR01282 polypeptides.
14. PR0358 The cloning of the Toll gene of Drosophila, a maternal effect gene that plays a central role in the establishment of the embryonic dorsal-ventral pattern, has been reported by Hashimoto et al. , Cell 52:269-279 (1988). The Drosophila Toll gene encodes an integral membrane protein with an extracytoplasmic domain of 803 amino acids and a cytoplasmic domain of 269 amino acids. The extracytoplasmic domain has a potential membrane-spanning segment, and contains multiple copies of a leucine-rich segment, a structural motif found in many transmembrane proteins. The Toll protein controls dorsal-ventral patterning in Drosophila embryos and activates the transcription factor Dorsal upon binding to its ligand Spatzle. (Morisato and Anderson, Cell 76:677-688 (1994)). In adult Drosophila, the Toll/Dorsal signaling pathway participates in the anti-fungal immune response. (Lenaitre et al., Cell 86:973-983 (1996)).
A human homologue of the Drosophila Toll protein has been described by Medzhitov et al., Nature 388:394-397 (1997). This human Toll, just as Drosophila Toll, is a type i transmembrane protein, with an extracellular domain consisting of 21 tandemly repeated leucine-rich motifs (leucine-rich region - LRR), separated by a non-LRR region, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin-1 (IL-1 ) receptor. A constitutively active mutant of the human Toll transfected into human cell lines was shown to be able to induce the activation of NF-xB and the expression of NF-xB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the constimulatory molecule B7.1, which is required for the activation of native T cells. It has been suggested that Toll functions in vertebrates as a non-clonal receptor of the immune system, which can induce signals for activating both an innate and an adaptive immune response in vertebrates. The human Toll gene reported by Medzhitov et al., supra was most strongly expressed in spleen and peripheral blood leukocytes (PBL), and the authors suggested that its expression in other tissues may be due to the presence of macrophages and dendritic cells, in which it could act as an early-warning system for infection. The public GenBank database contains the following Toll sequences: Tolll (DNAX# HSU88540-i , which is identical with the random sequenced full-lengthcDNA #HUMRSC786-1 ); To112 (DNAX# HSU88878-1); To113 (DNAX# HSU88879-1); and To114 (DNAX# HSU88880-1, which is identical with the DNA sequence reported by Medzhitov et al., supra). A partial Toll sequence (To115) is available from GenBank under DNAX# HSU88881-1.
Further human homologues of the Drosophila Toll protein, designated as Toll-like receptors (huTLRs 1 5) were recently cloned and shown to mirror the topographic structure of the Drosophila counterpart (Rock et al., Proc. Natl. Acad. Sci. USA 95:588-593 [1998]). Overexpression of a constitutively active mutant of one human TLR (Toll-protein homologue - Medzhitov et al., supra; TLR4 - Rock et al., supra) leads to the activation of NF-xB and induction of the inflammatory cytokines and constimulatory molecules. Medzhitov et al., supra.
We herein describe the identification and characterization of novel polypeptides having homology to Toll, designated herein as PR0358 polypeptides.
15. PR01310 Of interest are proteins related to carboxypeptidases. Various carboxypeptidases are described in the literature, i.e., ICrause et al., Immunol. Rev. 161:119-127 (1998) and Leiter, J. Endocrinol. 155(2):211-214 (1997). We herein describe the identification and characterization of novel polypeptides having homology to a carboxypeptidase, designated herein as PR01310 polypeptides.
16. PR0698 The extracellular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transduction machinery. The major protein component of this extracellular matrix is olfactomedin, a glycoprotein that is expressed in olfactory neuroepithelium and which form intermolecular disulfide bonds so as to produce a polymer (Yokoe et al. , Proc. Natl. Acad. Sci. USA
9(?:4655-4659 (1993), Bal et al., Biochemistry 32:1047-1053 (1993) and Snyder et al., Biochemistry 30:9143-9153 ( 1991 )). It has been suggested that olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. Given this important role, there is significant interest in identifying and characterizing novel polypeptides having homology to olfactomedin. We herein describe the identification and characterization of novel polypeptides having homology to olfactomedin protein, designated herein as PR0698 polypeptides.
17. PR0732 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides having sequence identity to the Diff33 protein, designated herein as PR0732 polypeptides.
18. PR01120 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the conuolled release and utilization of chemical energy, and other processes necessary to sustain life. Sulfatases are a family of secreted enzymatic proteins that play a variety of important metabolic roles and thus are the subject of interest in research and industry (see, e.g., Sleat et al., Biochem J., 324(Pt. 1):33-39 (1997)). Deficiencies of certain sulfatases have been implicated in various human disorders including Sanfilippo D syndrome (see, Litjens et al., Biochem J. 327(Pt 1):899-94 (1997); Leipprandt et al. J.
lrtherit Metab. Dis. 18(5):647-648 (1995); and Freeman et al. Biochem J.
282(pt2):605-614 (1992)). We herein describe the identification and characterization of novel polypeptides having sequence identity to sulfatase protein, designated herein as PR01120 polypeptides.
19. PR0537 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0537 polypeptides.
20. PRO 36 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0536 polypeptides.
21. PR0535 Isomerase proteins play many important physiological rotes in the mammal. Many different types of isomerase proteins have been identified and characterized including, for example, protein disulfide isomerases and peptidyl-prolyl isomerases. It has been reported that many immunophilin proteins, i.e., proteins that serves as receptors for immunosuppressant drugs, exhibit peptidyl-prolyl isomerase activity in that they function to catalyze the interconversion of the cis and trans isomerase of peptide and protein substrates for immunophilin proteins. As such, there is significant interest in identifying and characterizing novel polypeptides having sequence similarity to peptidyl-prolyl isomerase proteins. We herein describe the identification and characterization of novel polypeptides having homology to a putative peptidyl-prolyl isomerase protein, designated herein as PR0535 polypeptides.
22. PR0718 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0718 polypeptides.
23. PR0872 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled release and utilization of chemical energy, and other processes necessary to sustain life. Dehydrogenases and desaturases are a family of enzymes that play a variety of important metabolic roles and thus are the subject of interest in research and industry (see Hable et al., Mol.
Gen. Genet. 257(2):167-176 (1998); Schneider, C. et al., Prot. Expr. Purif.
10(2):175-179 (1997)). We herein describe the identification and characterization of novel polypeptides having sequence identity to dehydrogenase proteins, designated herein as PR0872 polypeptides.
24. P801063 Collagens constitute the most abundant proteins of the extracellular matrix (ECM) in mammalian organisms. Collagen and other macromolecules of the ECM are deposited by resident cells and organized into a three-dimensional meshwork. This ECM environment plays an essential role in guiding cell migration and in cell-to-cell communication during morphogenic processes. The restructuring of the ECM during remodeling occurs as a cooperative multistep process involving a localized degradation of existing macromolecules, rearrangement of the cytoskeleton, cell translocation, and deposition of new ECM components. Involved in this restructuring are enzymes such as coilagenases and gelatinases which play important roles in the degradation of the ECM. In light of the obviously important roles played by the collagenase enzymes, there is substantial interest in identifying and characterizing novel polypeptides having homology to these proteins. We herein describe the identification and characterization of novel polypeptides having homology to human type IV
collagenase protein, designated herein as PR01063 polypeptides.
25. PR0619 Immunoglobulins are antibody molecules, the proteins that function both as receptors for antigen on the B-cell membrane and as the secreted products of the plasma cell. Like all antibody molecules, immunoglobulins perform two major functions: they bind specifically to an antigen and they participate in a limited number of biological effector functions. Therefore, new members of the Ig superfamily are always of interest.
Of particular interest are novel gene products associated with mu chains in immature B cells.
Shirasawa, et al., EMBO J., 12(5):1827-1834 (1993); Dul, et al., Eur. J.
Immunol., 26(4):906-913 (1996).
Moreover, the molecular components and assembly of mu surrogate light chain complexes in pre-B cell lines are of interest. Ohnishi and Takemori, J. Biol. Chem., 269(45):28347-28353 (1994); Bauer, et al., Curr. Ton.
Microbiol., 137:130-135 (1988). Novel nucleic acids and peptides related to VpreBl, VpreB2 and VpreB3 by sequence identity are of particular interest. The assembly and manipulation of immunoglobulins can effect the entire industry related to antibodies and vaccines.
We herein describe the identification and characterization of novel polypeptides having homology to VpreB proteins, designated herein as PR0619 polypeptides.
26. PR0943 Fibroblast growth factor (FGF) proteins exhibit a variety of activities and act by binding to cell surface fibroblast growth factor receptors. Many different fibroblast growth factor receptors have been identified and characterized, including the fibroblast growth factor receptor-4, which has been shown to be a high affinity receptor for both acidic and basic FGF (Ron et al. , J. Biol. Chem. 268:5388-5394 ( 1993) and Stark et al. , Development 113:641-651 (1991)). Given the obvious importance of the FGF
family of proteins and the cell surface receptors to which they bind, there is significant interest in identifying novel polypeptides having homology to the FGF receptor family. We herein describe the identification and characterization of novel polypeptides having homology to the fibroblast growth factor receptor-4 protein, designated herein as PR0943 polypeptides.
27. PR01188 The identification of nucleotide pyrophosphohydrolases has been of interest because of the potential roles these secreted molecules play in calcium pyrophosphate dihydrate (CPPD) deposition disease, arthritis, and other joint diseases (see Masuda et al. J. Rheumatol. (997) 24(8):1588-1594;
and Terkeltaub et al., Arthritis Rheum (1998) 37(6):934-941). We herein describe the identification and characterization of novel polypeptides having homology to nucleotide pyrophosphohydrolases, designated herein as PROI
188 polypeptides.
28. PR01133 Netrins are molecules that guide growing axons and that are strikingly similar in sequence and in function in flies, nematodes and vertebrates. Additionally, netrin receptors have been identified in all three animal groups and shown to have crucial, conserved roles in axon navigation.
Netrins and their receptors are further described in the literature, i.e., Varela-Echavarria and Guthrie, Genes Dev., 11(5):545-557 (1997);
Guthrie, Curr. Biol., 7(i):R6-R9 (1997); and Keynes and Cook, Neuron, 17(6):1031-1034 (1996). Due to their relation to neurons, netrins and their related proteins are of interest. Of particular interest are molecules having sequence identity or similarity with netrin. We herein describe the identification and characterization of novel polypeptides having homology to netrins, designated herein as PR01133 polypeptides.
29. PR0784 Of interest are membrane-bound and receptor proteins involved in intracellular signaling, metabolism, transport, and other pathways. For example, membrane-bound proteins of the endoplasmic reticulum and golgi apparatus play important roles in the transport of proteins. The sec22 protein is an endoplasmic reticulum membrane-bound protein involved in fundamental membrane trafficking reactions where secretory products are routed from their site of synthesis to their final destination. The roles of sec22 in transport pathways have been reported by numerous investigators (see Tang et al., Biochem Biophvs Res Commun 243(3):885-891 (1998);
Hay et al., J. Biol. Chem. 271(10):5671-5679 (1996); and Newman et al., Mol.
Cell. Biol. 10(7):3405-3414 (1990)). We herein describe the identification and characterization of novel polypeptides having homology to sec22, designated herein as PR0784 polypeptides.
30. PR0783 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0783 polypeptides.
31. PR0820 Immunoglobulin molecules play roles in many important mammalian physiological processes. The structure of immunogIobulin molecules has been extensively studied and it has been well documented that intact immunoglobulins possess distinct domains, one of which is the constant domain or F~ region of the immunoglobulin molecule. The F~ domain of an immunoglobulin, while not being directly involved in antigen recognition and binding, does mediate the ability of the immunoglobulin molecule, either uncomplexed or complexed with its respective antigen, to bind to F~ receptors either circulating in the serum or on the surface of cells. The ability of an F~ domain of an immunoglobulin to bind to an F~
receptor molecule results in a variety of important activities, including for example, in mounting an immune response against unwanted foreign particles. Thus, molecules related to F~ receptors are of interest. F~
receptors are further described in Tominaga et al., Biochem. Biophvs. Res. Commun., 168(2):683-689 (1990); Zhang et al., Immuno., 39(6):423-427 (1994). We herein describe the identification and characterization of novel polypeptides having homology to F~ receptor, designated herein as PR0820 polypeptides.
32. PR01080 The folding of proteins and the assembly of protein complexes within subcompartments of the eukaryotic cell is catalysed by different members of the Hsp70 protein family. The chaperone function of Hsp70 proteins in these events is regulated by members of the DnaJ-like protein family, which occurs through direct interaction of different Hsp70 and Dna1-like protein pairs that appear to be specifically adapted to each other. The diversity of functions of DnaJ-like proteins using specific examples of DnaJ-Hsp70 interactions with polypeptides in yeast protein-biogenesis pathways is further described in Cyr et al., Trends Biochem. Sci., 19(4):176-181 (1994).
DnaJ proteins and their involvement in the binding of secretory precursor polypeptides to a translocon subcomplex and polypeptide translocation machinery in the yeast endoplasmic reticulum are further described in Lyman and Schekman, Cell 88(1):85-96 (1997) and Lyman and Schekman, Experientia 52(12):1042-1049 (1996), respectively. Thus, DnaJ proteins are of interest, as are proteins related to DnaJ proteins, particularly those having sequence identity with Dna3 proteins. We herein describe the identification and characterization of novel polypeptides having homology to DnaJ proteins, designated herein as PR01080 polypeptides.
33. PR01079 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01079 polypeptides.
34. PR07 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0793 polypeptides.
35. PR01016 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled ielease and utilization of chemical energy, and other processes necessary to sustain life. Acyltransferases are enzymes which acylate moieties. Acyl-glycerol-phosphate acyltransferases can act on lysophosphatidic acid as a substrate. The lysophosphatidic acid is converted to phophatidic acid and thus plays a role in forming phosphatidylethanolamine found in membranes. See, Brown, et al., Plant Mol. Biol., 26(1):211-223 (1994). Thus, acyltransferases play an important role in the biosynthesis of molecules requiring acylation. We herein describe the identification and characterization of novel polypeptides having homology to acyltransferase proteins, designated herein as PR01016 polypeptides.
36. PR01013 Efforts are being undertaken by both industry and academia to identify new, native proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel proteins. We herein describe the identification and characterization of novel polypeptides, designated herein as PR01013 polypeptides.
37. PR0937 The glypican family of heparan sulfate proteoglycans are major cell-surface proteogiycans of the developing nervous system. It is believed that members of the glypican family play a role in regulating cell cycle progression during the transition of proliferating neuronal progenitor cells to differentiated neurons. Larder et al. Perspect Dev. Neurobiol 3~4,~:347-358 ( 1996). It is likely that proteoglycans of the glypican family play other important roles in neural development (Larder et al., supra), and as well as other tissues, as glypican family members have also been found in the developing kidney (Watanabe et al. J. Cell Biol. 130(5):1207-1218 (1995)).
Accordingly, the identification of new members of the glypican family of proteins is of interest in research and in industry.
Described herein is the identificationand characterization of novel polypeptides having sequence identity with glypican family proteins, designated herein as PR0937 polypeptides.
38. PR 2 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0842 polypeptides.
39. PR0839 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0839 polypeptides.
40. PR01180 Methyltransferase enzymes catalyze the transfer of methyl groups from a donor molecule to an acceptor molecule Methyltransferase enzymes play extremely important roles in a number of different biological processes including, for example, in the electron transport chain in the plasma membrane in prokaryotes and in the inner mitochondria) membrane in eukaryotic cells (see, e.g. , Barkovich et al. , J. Biol. Chem. 272:9182-9188 (1997), Dibrov et al., J. Biol. Chem. 272:9175-9181 (1997), Lee et al., J.
Bacteriol.. 179:1748-1754 (1997) and Marbois et al., Arch. Biochem. Biophvs. 313:83-88 (1994)).
Methyltransferase enzymes have been shown to be essential for the biosynthesis of ubiquinone (coenzyme Q) and menaquinone (vitamin IC2), both of which are essential isoprenoid quinone components of the respiratory electron transport chain. Given the obvious importance of the methyltransferase enzymes, there is substantial interest in identifying novel polypeptide homologs of the methyltransferases. We herein describe the identification and characterization of a novel polypeptide having homology to methyltransferase enzymes, designated herein as PRO1180 polypeptides..
41. PR01134 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01134 polypeptides.
42. PR0830 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0830 polypeptides.
8(6):335-338 (1998)).
Given the physiological importance of inflammation and related mechanisms in vivo and in the specific physiological activities of complement C lq protein, efforts are currently being undertaken to identify new, native proteins which share sequence similarity to the complement proteins. We herein describe the identification and characterization of novel polypeptides having homology to complement C 1 q protein, designated herein as PR01151 polypeptides.
I3. PROl 2 All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Trends Biochem. Sci.. 19(10):415-421 (Oct. 1994);
Kobe and Deisenhofer, Curr.
O,~in. Struct. Biol., 5(3):409-416 (1995).
A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem.
Mol. Biol., 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome, Chlemetson, K. J., Thromb.
aemost. (Germany), 74(1):111-116 (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factory has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the IGF complex in vivo.
Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland), 125(1-2):65 70 (Dec. 1996) (gonadotropin receptor involvement); Miura, Y. , et al. , Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J. Am. Soc.
Nephrol., 6(4):1125-1133 (Oct. 1995) (kidney disease involvement).
Leucine rich repeat proteins are further discussed in Kajava, J. Mol. Biol., 277(3):519-527 (1998), Nagasawa, et al., en mics, 44(3):273-279 (1997), Bengtsson, J. Biol. Chem., 270(43):25639-25644 (1995), Gaillard, et al., Cell, 65(7):1127-1141 (1991) and Ohkura and Yanagida. Cell, 64(1):149-157 (1991), all incorporated herein by reference.
Thus, due to all the reasons listed above, new members of the leucine rich repeat superfamily are of interest. On a more general level, all novel proteins are of interest. We herein describe the identification and characterization of novel leucine-rich repeat-containing polypeptides, designated herein as PR01282 polypeptides.
14. PR0358 The cloning of the Toll gene of Drosophila, a maternal effect gene that plays a central role in the establishment of the embryonic dorsal-ventral pattern, has been reported by Hashimoto et al. , Cell 52:269-279 (1988). The Drosophila Toll gene encodes an integral membrane protein with an extracytoplasmic domain of 803 amino acids and a cytoplasmic domain of 269 amino acids. The extracytoplasmic domain has a potential membrane-spanning segment, and contains multiple copies of a leucine-rich segment, a structural motif found in many transmembrane proteins. The Toll protein controls dorsal-ventral patterning in Drosophila embryos and activates the transcription factor Dorsal upon binding to its ligand Spatzle. (Morisato and Anderson, Cell 76:677-688 (1994)). In adult Drosophila, the Toll/Dorsal signaling pathway participates in the anti-fungal immune response. (Lenaitre et al., Cell 86:973-983 (1996)).
A human homologue of the Drosophila Toll protein has been described by Medzhitov et al., Nature 388:394-397 (1997). This human Toll, just as Drosophila Toll, is a type i transmembrane protein, with an extracellular domain consisting of 21 tandemly repeated leucine-rich motifs (leucine-rich region - LRR), separated by a non-LRR region, and a cytoplasmic domain homologous to the cytoplasmic domain of the human interleukin-1 (IL-1 ) receptor. A constitutively active mutant of the human Toll transfected into human cell lines was shown to be able to induce the activation of NF-xB and the expression of NF-xB-controlled genes for the inflammatory cytokines IL-1, IL-6 and IL-8, as well as the expression of the constimulatory molecule B7.1, which is required for the activation of native T cells. It has been suggested that Toll functions in vertebrates as a non-clonal receptor of the immune system, which can induce signals for activating both an innate and an adaptive immune response in vertebrates. The human Toll gene reported by Medzhitov et al., supra was most strongly expressed in spleen and peripheral blood leukocytes (PBL), and the authors suggested that its expression in other tissues may be due to the presence of macrophages and dendritic cells, in which it could act as an early-warning system for infection. The public GenBank database contains the following Toll sequences: Tolll (DNAX# HSU88540-i , which is identical with the random sequenced full-lengthcDNA #HUMRSC786-1 ); To112 (DNAX# HSU88878-1); To113 (DNAX# HSU88879-1); and To114 (DNAX# HSU88880-1, which is identical with the DNA sequence reported by Medzhitov et al., supra). A partial Toll sequence (To115) is available from GenBank under DNAX# HSU88881-1.
Further human homologues of the Drosophila Toll protein, designated as Toll-like receptors (huTLRs 1 5) were recently cloned and shown to mirror the topographic structure of the Drosophila counterpart (Rock et al., Proc. Natl. Acad. Sci. USA 95:588-593 [1998]). Overexpression of a constitutively active mutant of one human TLR (Toll-protein homologue - Medzhitov et al., supra; TLR4 - Rock et al., supra) leads to the activation of NF-xB and induction of the inflammatory cytokines and constimulatory molecules. Medzhitov et al., supra.
We herein describe the identification and characterization of novel polypeptides having homology to Toll, designated herein as PR0358 polypeptides.
15. PR01310 Of interest are proteins related to carboxypeptidases. Various carboxypeptidases are described in the literature, i.e., ICrause et al., Immunol. Rev. 161:119-127 (1998) and Leiter, J. Endocrinol. 155(2):211-214 (1997). We herein describe the identification and characterization of novel polypeptides having homology to a carboxypeptidase, designated herein as PR01310 polypeptides.
16. PR0698 The extracellular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transduction machinery. The major protein component of this extracellular matrix is olfactomedin, a glycoprotein that is expressed in olfactory neuroepithelium and which form intermolecular disulfide bonds so as to produce a polymer (Yokoe et al. , Proc. Natl. Acad. Sci. USA
9(?:4655-4659 (1993), Bal et al., Biochemistry 32:1047-1053 (1993) and Snyder et al., Biochemistry 30:9143-9153 ( 1991 )). It has been suggested that olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. Given this important role, there is significant interest in identifying and characterizing novel polypeptides having homology to olfactomedin. We herein describe the identification and characterization of novel polypeptides having homology to olfactomedin protein, designated herein as PR0698 polypeptides.
17. PR0732 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides having sequence identity to the Diff33 protein, designated herein as PR0732 polypeptides.
18. PR01120 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the conuolled release and utilization of chemical energy, and other processes necessary to sustain life. Sulfatases are a family of secreted enzymatic proteins that play a variety of important metabolic roles and thus are the subject of interest in research and industry (see, e.g., Sleat et al., Biochem J., 324(Pt. 1):33-39 (1997)). Deficiencies of certain sulfatases have been implicated in various human disorders including Sanfilippo D syndrome (see, Litjens et al., Biochem J. 327(Pt 1):899-94 (1997); Leipprandt et al. J.
lrtherit Metab. Dis. 18(5):647-648 (1995); and Freeman et al. Biochem J.
282(pt2):605-614 (1992)). We herein describe the identification and characterization of novel polypeptides having sequence identity to sulfatase protein, designated herein as PR01120 polypeptides.
19. PR0537 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0537 polypeptides.
20. PRO 36 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0536 polypeptides.
21. PR0535 Isomerase proteins play many important physiological rotes in the mammal. Many different types of isomerase proteins have been identified and characterized including, for example, protein disulfide isomerases and peptidyl-prolyl isomerases. It has been reported that many immunophilin proteins, i.e., proteins that serves as receptors for immunosuppressant drugs, exhibit peptidyl-prolyl isomerase activity in that they function to catalyze the interconversion of the cis and trans isomerase of peptide and protein substrates for immunophilin proteins. As such, there is significant interest in identifying and characterizing novel polypeptides having sequence similarity to peptidyl-prolyl isomerase proteins. We herein describe the identification and characterization of novel polypeptides having homology to a putative peptidyl-prolyl isomerase protein, designated herein as PR0535 polypeptides.
22. PR0718 Efforts are being undertaken by both industry and academia to identify new, native transmembrane proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0718 polypeptides.
23. PR0872 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled release and utilization of chemical energy, and other processes necessary to sustain life. Dehydrogenases and desaturases are a family of enzymes that play a variety of important metabolic roles and thus are the subject of interest in research and industry (see Hable et al., Mol.
Gen. Genet. 257(2):167-176 (1998); Schneider, C. et al., Prot. Expr. Purif.
10(2):175-179 (1997)). We herein describe the identification and characterization of novel polypeptides having sequence identity to dehydrogenase proteins, designated herein as PR0872 polypeptides.
24. P801063 Collagens constitute the most abundant proteins of the extracellular matrix (ECM) in mammalian organisms. Collagen and other macromolecules of the ECM are deposited by resident cells and organized into a three-dimensional meshwork. This ECM environment plays an essential role in guiding cell migration and in cell-to-cell communication during morphogenic processes. The restructuring of the ECM during remodeling occurs as a cooperative multistep process involving a localized degradation of existing macromolecules, rearrangement of the cytoskeleton, cell translocation, and deposition of new ECM components. Involved in this restructuring are enzymes such as coilagenases and gelatinases which play important roles in the degradation of the ECM. In light of the obviously important roles played by the collagenase enzymes, there is substantial interest in identifying and characterizing novel polypeptides having homology to these proteins. We herein describe the identification and characterization of novel polypeptides having homology to human type IV
collagenase protein, designated herein as PR01063 polypeptides.
25. PR0619 Immunoglobulins are antibody molecules, the proteins that function both as receptors for antigen on the B-cell membrane and as the secreted products of the plasma cell. Like all antibody molecules, immunoglobulins perform two major functions: they bind specifically to an antigen and they participate in a limited number of biological effector functions. Therefore, new members of the Ig superfamily are always of interest.
Of particular interest are novel gene products associated with mu chains in immature B cells.
Shirasawa, et al., EMBO J., 12(5):1827-1834 (1993); Dul, et al., Eur. J.
Immunol., 26(4):906-913 (1996).
Moreover, the molecular components and assembly of mu surrogate light chain complexes in pre-B cell lines are of interest. Ohnishi and Takemori, J. Biol. Chem., 269(45):28347-28353 (1994); Bauer, et al., Curr. Ton.
Microbiol., 137:130-135 (1988). Novel nucleic acids and peptides related to VpreBl, VpreB2 and VpreB3 by sequence identity are of particular interest. The assembly and manipulation of immunoglobulins can effect the entire industry related to antibodies and vaccines.
We herein describe the identification and characterization of novel polypeptides having homology to VpreB proteins, designated herein as PR0619 polypeptides.
26. PR0943 Fibroblast growth factor (FGF) proteins exhibit a variety of activities and act by binding to cell surface fibroblast growth factor receptors. Many different fibroblast growth factor receptors have been identified and characterized, including the fibroblast growth factor receptor-4, which has been shown to be a high affinity receptor for both acidic and basic FGF (Ron et al. , J. Biol. Chem. 268:5388-5394 ( 1993) and Stark et al. , Development 113:641-651 (1991)). Given the obvious importance of the FGF
family of proteins and the cell surface receptors to which they bind, there is significant interest in identifying novel polypeptides having homology to the FGF receptor family. We herein describe the identification and characterization of novel polypeptides having homology to the fibroblast growth factor receptor-4 protein, designated herein as PR0943 polypeptides.
27. PR01188 The identification of nucleotide pyrophosphohydrolases has been of interest because of the potential roles these secreted molecules play in calcium pyrophosphate dihydrate (CPPD) deposition disease, arthritis, and other joint diseases (see Masuda et al. J. Rheumatol. (997) 24(8):1588-1594;
and Terkeltaub et al., Arthritis Rheum (1998) 37(6):934-941). We herein describe the identification and characterization of novel polypeptides having homology to nucleotide pyrophosphohydrolases, designated herein as PROI
188 polypeptides.
28. PR01133 Netrins are molecules that guide growing axons and that are strikingly similar in sequence and in function in flies, nematodes and vertebrates. Additionally, netrin receptors have been identified in all three animal groups and shown to have crucial, conserved roles in axon navigation.
Netrins and their receptors are further described in the literature, i.e., Varela-Echavarria and Guthrie, Genes Dev., 11(5):545-557 (1997);
Guthrie, Curr. Biol., 7(i):R6-R9 (1997); and Keynes and Cook, Neuron, 17(6):1031-1034 (1996). Due to their relation to neurons, netrins and their related proteins are of interest. Of particular interest are molecules having sequence identity or similarity with netrin. We herein describe the identification and characterization of novel polypeptides having homology to netrins, designated herein as PR01133 polypeptides.
29. PR0784 Of interest are membrane-bound and receptor proteins involved in intracellular signaling, metabolism, transport, and other pathways. For example, membrane-bound proteins of the endoplasmic reticulum and golgi apparatus play important roles in the transport of proteins. The sec22 protein is an endoplasmic reticulum membrane-bound protein involved in fundamental membrane trafficking reactions where secretory products are routed from their site of synthesis to their final destination. The roles of sec22 in transport pathways have been reported by numerous investigators (see Tang et al., Biochem Biophvs Res Commun 243(3):885-891 (1998);
Hay et al., J. Biol. Chem. 271(10):5671-5679 (1996); and Newman et al., Mol.
Cell. Biol. 10(7):3405-3414 (1990)). We herein describe the identification and characterization of novel polypeptides having homology to sec22, designated herein as PR0784 polypeptides.
30. PR0783 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0783 polypeptides.
31. PR0820 Immunoglobulin molecules play roles in many important mammalian physiological processes. The structure of immunogIobulin molecules has been extensively studied and it has been well documented that intact immunoglobulins possess distinct domains, one of which is the constant domain or F~ region of the immunoglobulin molecule. The F~ domain of an immunoglobulin, while not being directly involved in antigen recognition and binding, does mediate the ability of the immunoglobulin molecule, either uncomplexed or complexed with its respective antigen, to bind to F~ receptors either circulating in the serum or on the surface of cells. The ability of an F~ domain of an immunoglobulin to bind to an F~
receptor molecule results in a variety of important activities, including for example, in mounting an immune response against unwanted foreign particles. Thus, molecules related to F~ receptors are of interest. F~
receptors are further described in Tominaga et al., Biochem. Biophvs. Res. Commun., 168(2):683-689 (1990); Zhang et al., Immuno., 39(6):423-427 (1994). We herein describe the identification and characterization of novel polypeptides having homology to F~ receptor, designated herein as PR0820 polypeptides.
32. PR01080 The folding of proteins and the assembly of protein complexes within subcompartments of the eukaryotic cell is catalysed by different members of the Hsp70 protein family. The chaperone function of Hsp70 proteins in these events is regulated by members of the DnaJ-like protein family, which occurs through direct interaction of different Hsp70 and Dna1-like protein pairs that appear to be specifically adapted to each other. The diversity of functions of DnaJ-like proteins using specific examples of DnaJ-Hsp70 interactions with polypeptides in yeast protein-biogenesis pathways is further described in Cyr et al., Trends Biochem. Sci., 19(4):176-181 (1994).
DnaJ proteins and their involvement in the binding of secretory precursor polypeptides to a translocon subcomplex and polypeptide translocation machinery in the yeast endoplasmic reticulum are further described in Lyman and Schekman, Cell 88(1):85-96 (1997) and Lyman and Schekman, Experientia 52(12):1042-1049 (1996), respectively. Thus, DnaJ proteins are of interest, as are proteins related to DnaJ proteins, particularly those having sequence identity with Dna3 proteins. We herein describe the identification and characterization of novel polypeptides having homology to DnaJ proteins, designated herein as PR01080 polypeptides.
33. PR01079 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01079 polypeptides.
34. PR07 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR0793 polypeptides.
35. PR01016 Enzymatic proteins play important roles in the chemical reactions involved in the digestion of foods, the biosynthesis of macromolecules, the controlled ielease and utilization of chemical energy, and other processes necessary to sustain life. Acyltransferases are enzymes which acylate moieties. Acyl-glycerol-phosphate acyltransferases can act on lysophosphatidic acid as a substrate. The lysophosphatidic acid is converted to phophatidic acid and thus plays a role in forming phosphatidylethanolamine found in membranes. See, Brown, et al., Plant Mol. Biol., 26(1):211-223 (1994). Thus, acyltransferases play an important role in the biosynthesis of molecules requiring acylation. We herein describe the identification and characterization of novel polypeptides having homology to acyltransferase proteins, designated herein as PR01016 polypeptides.
36. PR01013 Efforts are being undertaken by both industry and academia to identify new, native proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel proteins. We herein describe the identification and characterization of novel polypeptides, designated herein as PR01013 polypeptides.
37. PR0937 The glypican family of heparan sulfate proteoglycans are major cell-surface proteogiycans of the developing nervous system. It is believed that members of the glypican family play a role in regulating cell cycle progression during the transition of proliferating neuronal progenitor cells to differentiated neurons. Larder et al. Perspect Dev. Neurobiol 3~4,~:347-358 ( 1996). It is likely that proteoglycans of the glypican family play other important roles in neural development (Larder et al., supra), and as well as other tissues, as glypican family members have also been found in the developing kidney (Watanabe et al. J. Cell Biol. 130(5):1207-1218 (1995)).
Accordingly, the identification of new members of the glypican family of proteins is of interest in research and in industry.
Described herein is the identificationand characterization of novel polypeptides having sequence identity with glypican family proteins, designated herein as PR0937 polypeptides.
38. PR 2 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0842 polypeptides.
39. PR0839 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0839 polypeptides.
40. PR01180 Methyltransferase enzymes catalyze the transfer of methyl groups from a donor molecule to an acceptor molecule Methyltransferase enzymes play extremely important roles in a number of different biological processes including, for example, in the electron transport chain in the plasma membrane in prokaryotes and in the inner mitochondria) membrane in eukaryotic cells (see, e.g. , Barkovich et al. , J. Biol. Chem. 272:9182-9188 (1997), Dibrov et al., J. Biol. Chem. 272:9175-9181 (1997), Lee et al., J.
Bacteriol.. 179:1748-1754 (1997) and Marbois et al., Arch. Biochem. Biophvs. 313:83-88 (1994)).
Methyltransferase enzymes have been shown to be essential for the biosynthesis of ubiquinone (coenzyme Q) and menaquinone (vitamin IC2), both of which are essential isoprenoid quinone components of the respiratory electron transport chain. Given the obvious importance of the methyltransferase enzymes, there is substantial interest in identifying novel polypeptide homologs of the methyltransferases. We herein describe the identification and characterization of a novel polypeptide having homology to methyltransferase enzymes, designated herein as PRO1180 polypeptides..
41. PR01134 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01134 polypeptides.
42. PR0830 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0830 polypeptides.
43. P 1115 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PRO1115 polypeptides.
44. PR01277 Efforts are being undertaken by both industry and academia to identify new, native proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor and other proteins. Of interest is the identification of proteins that may play roles in various human disorders and dysfunction. For example, the identification of proteins of the ear and the functions they play in hearing may lead to an understanding of the causes of hearing loss and deafness. Coch-B2 is one such protein that has been found to be specifically expressed in the inner ear (cochlea). It has been characterized and studied for its possible role in hearing loss (Robertson et al. Genomics (1994) 23(1):52-50; Robertson et al.
Genomics (1997) 46(3):345-354). We herein describe the identification and characterization of novel polypeptides having sequence identity to Coch-B2, designated herein as PR01277 polypeptides.
45. PR01135 Glycosylation is an important mechanism for modulating the physiochemical and biological properties of proteins in a stage- and tissue-specific manner. One of the important enzymes involved in glycosylation in Saccharomyces cerevisiae is alpha 1,2-mannosidase, an enzyme that catalyzes the conversion of Man9GlcNAc2 to Man8GlcNAc2 during the formation of N-linked oligosaccharides. The Saccharomyces cerevisiae alpha 1,2-mannosidase enzyme of is a member of the Class I alpha 1,2-mannosidases that are conserved from yeast to mammals. Given the important roles played by the alpha 1,2-mannosidases in glycosylation and the physiochemical activity regulated by glycosylation, there is significant interest in identifying novel polypeptides having homology to one or more mannosidases. We herein describe the identification and characterization of novel polypeptides having homology to alpha 1,2-mannosidase protein, designated herein as PR01135 polypeptides.
46. PR01114 Interferons (IFNs) encompass a large family of secreted proteins occurring in vertebrates. Although they were originally named for their antiviral activity, growing evidence supports a critical role for IFNs in cell growth and differentiation (Jaramillo et al., Cancer Investieation 13(3):327-338 ( 1995)). IFNs belong to a class of negative growth factors having the ability to inhibit the growth of a wide variety of cells with both normal and transformed phenotypes. IFN therapy has been shown to be beneficial in the treatment of human malignancies such as Karposi's sarcoma, chronic myelogenous leukemia, non-Hodgkin's lymphoma, and hairy cell leukemia as well as in the treatment of infectious diseases such as hepatitis B
(Gamliel et al., Scannine Microscopy 2(1):485-492 (1988), Einhorn et al., Med. Oncol. & Tumor Pharmacother. 10:25-29 (1993), Ringenberg et al., Missouri Medicine 85(1):21-26 (1988), Saracco et al., Journal of Gastroenteroloev and Hepatologv 10:668-673 (1995), Gonzalez-Mateos et al., Henato-Gastroenterologv 42:893-899 (1995) and Malaguarnera et al., Pharmacotheranv 17(5):998-1005 (1997)).
Interferons can be classified into two major groups based upon their primary sequence. Type I
interferons, IFN-a and IFN-(3, are encoded by a superfamily of intronless genes consisting of the IFN-a gene family and a single IFN-p gene that are thought to have arisen from a common ancestral gene. Type I
interferons may be produced by most cell types. Type II IFN, or IFN-y, is restricted to lymphocytes (T cells and natural killer cells) and is stimulated by nonspecific T cell activators or specific antigens in vivo.
Although both type I and type II IFNs produce similar antiviral and antiproliferative effects, they act on distinct cell surface receptors, wherein the binding is generally species specific (Larger et al., Immunol.
Todav 9:393-400 (1988)). Both IFN-a and IFN-~i bind competitively to the same high affinity type I receptor, whereas IFN-y binds to a distinct type II receptor. The presence and number of IFN receptors on the surface of a cell does not generally reflect the sensitivity of the cell to IFN, although it is clear that the effects of the IFN
protein is mediated through binding to a cell surface interferon receptor. As such, the identification and characterization of novel interferon receptor proteins is of extreme interest.
We herein describe the identification and characterization of novel interferon receptor polypeptides, designated herein as "PR01114 interferon receptor" polypeptides. Thus, the PR01114 polypeptides of the present invention represents a novel cell surface interferon receptor.
47. PR0828 Glutathione peroxidases are of interest because they play important roles in protection against risk of coronary disease, atherosclerosis, platelet hyperaggregation and synthesis of proaggregant and proinflammatory compounds. Glutathione peroxidases are involved in the reduction of hydrogen peroxides and lipid peroxides, which in turn regulate the activities of cyclooxygenase and lipooxygenase pathways. This ultimately influences the production of eicosanoids and modulates the balance between a proaggregatory and antiaggregatory state of platelets. These and other activities and functions of glutathione peroxidases are discussed in greater detail by Ursini et al., Biomed. Environ. Sci 10(2-3): 327-332 (1997); Vitoux et al., Ann. Biol. Clin (Paris) 54(5): 181-187 (1996); and Mirault et al., Ann N.Y. Acad. Sci 738: 104-115 (1994).
We herein describe the identification and characterization of novel polypeptides having sequence identity with glutathione peroxidases, designated herein as PR0828 polypeptides.
48. PR01009 Long chain acyl-CoA synthetase converts free fatty acids to acyl-CoA esters.
This synthetase has been reported to have interesting characteristics. Specifically, it has been reported that two boys having Alport syndrome, elliptocytosis and mental retardation carried a large deletion where long chain acyl-CoA synthetase 4 would have been located. Thus, the absence of this enzyme is believed to play a role in the development of mental retardation or other signs associated with Alport syndrome in the family. Piccini, et al., Genomics, 47(3):350-358 (1998). Moreover, it has been reported that an inhibitor of acyl coenzyme A synthetase, triacsin C, inhibits superoxide anion generation and degranulation by human neutrophils. Thus, it is suggested that there is a role for acyl-CoA esters in regulating activation of 02 generation and degranulation at the G protein or subsequent step(s). Korchak, et al., J. Biol. Chem., 269(48):30281-30287 (1994). Long chain acyl-CoA
synthetase is also briefly discussed in a report which describes very long chain acyl-CoA synthetase. Uchiyama, et al., J. Biol. Chem., 271(48):30360 (1994). Thus, long chain aryl-CoA
synthetase and particular novel polypeptides having sequence identity therewith are of interest.
We herein describe the identification and characterization of novel polypeptides having sequence identity with long chain acyl-CoA synthetase, designated herein as PR01009 polypeptides.
49. PR01007 Glycosylphosphatidylinositol (GPI) anchored proteoglycans are generally localized to the cell surface and are thus known to be involved in the regulation of responses of cells to numerous growth factors; cell adhesion molecules and extracellular matrix components. The metastasis-associated GPI-anchored protein (MAGPIAP) is one of these cell surface proteins which appears to be involved in metastasis. Metastasis is the form of cancer wherein the transformed or malignant cells are traveling and spreading the cancer from one site to another. Therefore, identifying the polypeptides related to metastasis and MAGPIAP is of interest.
We herein describe the identificationand characterization of novel polypeptides having sequence identity with MAGPIAP, designated herein as PR01007 polypeptides.
50. PR01056 Mammalian cell membranes perform very important functions relating to the structural integrity and activity of various cells and tissues. Of particular interest in membrane physiology is the study of trans-membrane ion channels which act to directly control a variety of physiological, pharmacological and cellular processes. Numerous ion channels have been identified including calcium (Ca), sodium (Na), chloride (CI) and potassium (K) channels, each of which have been analyzed in detail to determine their roles in physiological processes in vertebrate and insect cells. These roles include such things as maintaining cellular homeostasis, intracellular signaling, and the like. Given the obvious importance of the ion channels, there is significant interest in identifying and characterizing novel polypeptides having homology to one or more ion channels. We herein describe the identification and characterization of novel polypeptides having homology to a chloride channel protein, designated herein as PR01056 polypeptides..
51. PR0826 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0826 polypeptides.
52. PRO 19 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0819 polypeptides.
53. PR01006 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01006 polypeptides.
54. PR01112 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01112 polypeptides.
55. PR01074 Many membrane-bound enzymatic proteins play important roles in the chemical reactions involved in metabolism, including the biosynthesis of macromolecules, the controlled release and utilization of chemical energy, development of tissues, and other processes necessary to sustain life.
Galactosyltransferases are a family of enzymes that play a variety of important metabolic roles and thus are the subject of interest in research and industry. Numerous references have been published on the identification of galactosyltransferases and the roles they play in cellular development, maintenance, and dysfunction.
We herein describe the identification and characterization of novel polypeptides having homology to galactosyltransferases, designated herein as PR01074 polypeptides.
56. PR01005 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PRO1005 polypeptides.
57. PR01073 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01073 polypeptides.
58. PR01152 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01152 polypeptides.
59. PR01136 PDZ domain-containing proteins assist formation of cell-cell junctions and localization of membrane protein receptors and ion channels (Daniels et al., Nat. Struct. Biol. 5:317-325 (1998) and Ullmer et al., FEBS
I~,t~. 424:63-68 (1998)). PDZ domains interact with the C-terminal residues of a particular target membrane protein. Based on their binding specificities and sequence homologies, PDZ
domains fall into two classes, class I and class II. In light of the obvious importance of the PDZ domain-containing proteins, there is significant interest in identifying novel polypeptides that have homology to those proteins. We herein describe the identification and characterization of novel polypeptides having homology to PDZ domain-containing proteins, designated herein as PR01136 polypeptides.
60. PR0813 Surfactant proteins play extremely important biological roles in the mammalian pulmonary system. One mammalian protein that has been studied and well characterized is pulmonary surfactant-associated protein C.
For example, Qanbar et al., Am. J. Physiol. 271:L572-L580 (1996) studied the effect of palmitoylation of pulmonary surfactant-associated protein C on the surface activity of phospholipid mixtures. Specifically, the authors demonstrated that palmitoylation of pulmonary surfactant-associated protein C greatly enhanced lipid respreading and film stability and, therefore, was extremely important for surfactant function. Given the obvious important roles played by surfactant protein in the mammalian organism, there is significant interest in identifying novel polypeptides having homology to one or more surfactant enzymes. We herein describe the identification and characterization of novel polypeptides having homology to pulmonary surfactant-associated protein, designated herein as PR0813 polypeptides.
61. PR0809 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0809 polypeptides.
62. PR07 1 Of particular interest are novel proteins which have sequence identity with known proteins. For example, novel proteins having some sequence identity with the major histocompatibility complex (MHC) are of interest. The MHC complex is a region of multiple loci that play major roles in determining whether transplanted tissue will be accepted as self (histocompatible) or rejected as foreign (histoincompatible).
Moreover, the MHC plays a central role in the development of both humoral and cell-mediated immune responses. There are class I, II and III MHC antigens, all known in the art.
Class I antigens are glycoproteins expressed on the surface of nearly all nucleated cells, where they present peptide antigens of altered self cells necessary for the activation of Tc cells. The assembly of MHC class I antigens is further described in Kvist and Levy, Semin. Immunol., 5(2):105-116 (1993) and Maffei, et al., Hum. Immunol., 54(2):91-103 (1997).
We herein describe the identification and characterization of novel polypeptides having sequence identity to various MHC-I antigens, designated herein as PR0791 polypeptides.
63. PR01004 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01004 polypeptides.
64. PROl l l l Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Trends Biochem. Sci., 19(10):415-421 (Oct. 1994).
A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem.
Mol. Biol., 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome, Chlemetson, K. J., Thromb.
Haemost. (Germany), 74( 1 ):111-116 (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factor(3 has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the IGF complex in vivo.
Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland), 125(1-2):65-70 (Dec. 1996) (gonadotropinreceptor involvement); Miura, Y., et al., Ninnon Rinsho (Japan), 54(7):1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J. Am. Soc.
Nephrol., 6(4):1125-1133 (Oct. 1995) (kidney disease involvement).
We herein describe the identification and characterization of novel polypeptides having homology to LIG, designated herein as PRO1111 polypeptides.
65. PR01344 Factor C is a protein that is intimately involved with the coagulation cascade in a variety of organisms.
The coagulation cascade has been shown to involve numerous different intermediate proteins, including factor C, all of whose activity is essential to the proper functioning of this cascade. Abnormal coagulation cascade function can result in a variety of serious abnormalities and, as such, the activities of the coagulation cascade proteins is of particular interest. As such, efforts are currently being undertaken to identify novel polypeptides having homology to one or more of the coagulation cascade proteins.
We herein describe the identification and characterization of novel polypeptides having homology to factor C protein, designated herein as PR01344 polypeptides.
66. PR01109 Carbohydrate chains on glycoproteins are important not only for protein conformation, transport and stability, but also for cell-cell and cell-matrix interactions. ~i-1,4-galactosyltransferase is an enzyme that is involved in producing carbohydrate chains on proteins, wherein the (3-1,4-galactosyltransferase enzyme acts to transfer galactose to the terminal N-acetylglucosamine of complex-type N-glycans in the Golgi apparatus (Asano et al., EMBO J. 16:1850-1857 (1997)). In addition, it has been suggested that (3-1,4-galactosyltransferase is invloved directly in cell-cell interactions during fertilization and early embryogenesis through a subpopulation of this enzyme distributed on the cell surface. Specifically, Lu et al., Development 124:4121-4131 (1997) and Larson et al., Biol. Renrod. 57:442-453 ( 1997) have demonstrated that ~3-1,4-galactosyltransferase is expressed on the surface of sperm from a variety of mammalian species, thereby suggesting an important role in fertilization. In light of the above, novel polypeptides having sequence identity to (3-1,4-galactosyltransferase are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to (i-1,4-galactosyltransferase, designated herein as PR01109 polypeptides.
67. PR01383 The nmb gene is a novel gene that encodes a putative transmembrane glycoprotein which is differentially expressed in metastatic human melanoma cell lines and which shows substantial homology to the precursor of pMELl7, a melanocyte-specific protein (Weterman et al., Int. J. Cancer 60:73-81 (1995)). Given the interest in identifying tumor-specific cell-surface polypeptide markers, there is substantial interest in novel polypeptides having homology to tunb. We herein describe the identification and characterization of novel polypeptides having homology to the nmb protein, designated herein as PR01383 polypeptides.
68. PR01003 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01003 polypeptides.
69. PR01108 Lysophosphatidic acid acyltransferase (LPAAT) is an enzyme that in lipid metabolism converts lysophosphatidic acid (LPA) into phosphatidic acid (PA). LPA is a phospholipid that acts as an intermediate in membrane phospholipid metabolism. Various LPAAT enzymes have been identified in a variety of species (see, e.g., Aguado et al., J. Biol. Chem. 273:4096-4105 (1998), Stamps et al., Biochem. J. 326:455-461 (1997), Eberhart et al., J. Biol. Chem. 272:20299-20305 (1997) and West et al., DNA
Cell Biol. 16:691-701 (1997)).
Given the obvious importance of LPAAT in a variety of different applications including cell membrane maintenance, there is substantial interest in identifying and characterizing novel polypeptides having homology to LPAAT. We herein describe the identification and characterization of novel polypeptides having homology to LPAAT protein, designated herein as PR01108 polypeptides.
70. PR01137 A particular class of secreted polypeptides that are of interest in research and industry are ribosyltransferases. Braren et aI. described the use of EST databases for the identification and cloning of novel ribosyltransferase gene family members (Adv. Exp. Med. Biol. 419:163-168 (1997)). Ribosyltransferases have been identified playing roles in a variety of metabolic functions including posttranslational modification of proteins (Saxty et al., J. Leukoc. Biol., 63(1):15-21 (1998)), and mediation of the assembly of filamentous actin and chemotaxis in polymorphonuclear neutrophil leukocytes (Kefalas et al. Adv.
Exp. Med. Biol. 419:241-244 ( 1997)).
Described herein is the identification and characterization of novel polypeptides having homology to ribosyltransferase, designated herein as PR01137 polypeptides.
71. PR01138 Efforts are being undertaken by both industry and academia to identify new, native receptor proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel receptor proteins. Of particular interest is the identification of membrane-bound proteins found in cells of the hematopoietic system, as they often play important roles in fighting infection, repair of t0 injured tissues, and other activities of cells of the hematopoietic system.
For instance, CD84 leukocyte antigen has recently been identified as a new member of the Ig superfamily (de la Fuente et al. , Blood, 90(6):2398-2405 ( 1997)).
Described herein is the identification and characterization of a novel polypeptide having homology to CD84 leukocyte antigen, designated herein as PR01138 polypeptides.
72. PR01054 The proteins of the major urinary protein complex (MUP), proteins which are members of the lipocalin family, function to bind to volatile pheromones and interact with the vomeronasal neuroepithelium of the olfactory system. As such, proteins in the MUP family are intimately involved in the process of attraction between mammals of different sexes. Many different MUP family members have been identified and characterized and shown to possess varying degrees of amino acid sequence homology (see, e.g., Mucignat et al., Chem. Senses 23:67-70 (1998), Ferrari et al., FEBS Lett. 401:73-77 (1997) and Bishop et al., EMBO J.
1:615-620 (1982)). Given the physiological and biological importance of the MUP family of proteins, there is significant interest in identifying and characterizing novel members of this family. We herein describe the identification and characterization of novel polypeptides having homology to MUP family of proteins, designated herein as PR01054 polypeptides.
73. PR0994 The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a potential therapeutic target for murine monoclonal antibodies and their humanized counterparts (Marken et al., Proc. Natl. Acad. Sci. USA 89:3503-3507 (1992)).
The cDNA encoding this tumor-associated cell surface antigen has been expressed in COS cells and shown to encode a 202 amino acid polypeptide having three transmembrane domains. The L6 antigen has been shown to be related to a number of cell surface proteins that have been implicated in the regulation of cell growth, including for example CD63 and CO-029, proteins which are also highly expressed on tumor cells. As such, there is significant interest in identifying novel polypeptides having homology to the L6 tumor cell antigen as potential targets for cancer therapy. We herein describe the identification and characterization of novel polypeptides having homology to the L6 cell surface tumor cell-associated antigen, designated herein as PR0994 polypeptides.
74. PR0812 Steroid binding proteins play important roles in numerous physiological processes associated with steroid function. Specifically, one steroid binding protein-associated polypeptide that has been well characterized is component 1 of the prostatic binding protein. Component 1 of the prostatic binding protein has been shown to be specific for subunit F of the prostatic binding protein, the major secretory glycoprotein of the rat ventral prostate (Peelers et al., Eur. J. Biochem. 123:55-62 (1982) and Liao et al., J. Biol. Chem. 257:122-125 (1982)).
The amino acid sequence of component 1 of the prostatic binding protein has been determined, wherein the sequence is highly rich in glutamic acid residues and is overall highly acidic. This protein plays an important role in the response of the prostate gland to steioid hormones. We herein describe the identification and characterization of novel polypeptides having homology to prostatic steroid-binding protein c 1, designated herein as PR0812 polypeptides.
75. PR01069 Of particular interest is the identification of new membrane-bound proteins involved in ion conductance such as channel inhibitory factor (CHIF) and MAT-8, which have recently been reported (see Wald et al., Am.
J. Phvsiol, 272(5 pt 2): F617-F623 (1997); Capurro et al., Am. J. Phi, 271(3 pt 1): C753-C762 (1996);
Wald et al., Am. J. Physiol, 271(2 pt 2): F322-F329 (1996); and Morrison et al., J. Biol. Chem 270(5):2176-2182 (1995)).
Described herein is the identification and characterization of novel polypeptides having homology to CHIF and MAT-8 polypeptides, designated herein as PR01069 polypeptides.
?6. PR 1129 Cytochromes P-450 are a superfamily of hemoproteins which represent the main pathway for drug and chemical oxidation (Horsmans, Acta Gastroenterol. Bel~. 60:2-10 (1997)). This superfamily is divided into families, subfamilies and/or single enzymes. Recent reports have provided a great deal of information concerning the cytochrome P-450 isozymes and increased awareness of life threatening interactions with such commonly prescribed drugs as cisapride and some antihistamines (Michalets, Pharmacotheranv 18:84-112 ( 1998) and Singer et al., J. Am. Acad. Dermatol. 37:765-771 (1997)). Given this information, there is significant interest in identifying novel members of the cytochrome P-450 family of proteins. We herein describe the identification and characterization of novel polypeptides having homology to cytochrome P-450 proteins, designated herein as PR01129 polypeptides.
77. PR01068 Urotensins are neurosecretory proteins that are of interest because of their potential roles in a variety of physiological processes including smooth muscle contraction (Yano et al.
Gen. Comp. Endocrinol. 96(3): 412-413 (1994)), regulation of arterial blood pressure and heart rate (Le Mevel et al. Am. J. Physiol. 271(5 Pt 2):
81335-81343 (1996)), and corticosteroid secretion (Feuilloley et al. J.
Steroid Biochem Mol. Biol. 48(2-3): 287-292 (1994)).
We herein describe the identification and characterization of novel polypeptides having homology to urotensin, designated herein as PR01068 polypeptides.
S 78. PR01066 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01066 polypeptides.
79. PR01184 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01184 polypeptides.
80. PR01360 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01360 polypeptides.
81. PR01029 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01029 polypeptides.
82. PROI139 Obesity is the most common nutritional disorder which, according to recent epidemiologic studies, affects about one third of all Americans 20 years of age or older. Kuczmarski et al., J. Am. Med. Assoc. 272, 205-11 ( 1994). Obesity is responsible for a variety of serious health problems, including cardiovascular disorders, type II diabetes, insulin-resistance, hypertension, hypertriglyceridemia, dyslipoproteinemia, and some forms of cancer. Pi-Sunyer, F.X., Anns. Int. Med. 119, 655-60 (1993); Colfitz, G.A., Am. J. Clin. Nutr. 55, 503S-5075 (1992). A single-gene mutation (the obesity or "ob" mutation) has been shown to result in obesity and type II diabetes in mice. Friedman, Genomics 11, 1054-1062 (1991). Zhang et al., Nature 372, 425-431 (1994) have recently reported the cloning and sequencing of the mouse ob gene and its human homologue, and suggested that the ob gene product may function as part of a signaling pathway from adipose tissue that acts to regulate the size of the body fat depot. Parabiosis experiments performed more than 20 years ago predicted that the genetically obese mouse containing two mutant copies of the ob gene (oblob mouse) does not produce a satiety factor which regulates its food intake, while the diabetic (dbldb) mouse produces but does not respond to a satiety factor. Coleman and Hummal, Am. J. Ph~rsiol. 217, 1298-1304 ( 1969); Coleman, Diabetol. 9, 294-98 (1973). OB proteins are disclosed, for example, in U.S. patent Nos.
5,532,336; 5,552,522; 5,552,523;
5,552,514; 5,554,727. Recent reports by three independent research teams have demonstrated that daily injections of recombinant OB protein inhibit food intake and reduce body weight and fat in grossly obese oblob mice but not indbldb mice (Pelleymounter et al., Science 269, 540-43 (1995];
Halaas et al., Science 269, 543-46 [1995]; Campfield et al., Sc_ fence 269, 546-49 [1995]), suggesting that the ob protein is such a satiety factor as proposed in early cross-circulation studies.
A receptor of the OB protein (OB-R) is disclosed in Tartaglia et al. , Cell 83, 1263-71 ( i 995). The OB-R is a single membrane-spanning receptor homologous to members of the class I
cytokine receptor family (Tartaglia et al., supra; Bazan, Proc. Natl. Acad. Sci. USA 87, 6934-6938 [
1990]). Two 5'-untranslated regions and several 3'-alternative splice variants encoding OB-R with cytoplasmic domains of different lengths have been described in mouse, rat and human (Chen et al., Cell 84, 491-495 [1996]; Chua et al., Science 271, 994-996 [1996]; Tartaglia et al., supra; Wang et al., FEBS Lett. 392:87-90 ( 1996];
Phillips et al., Nature Genet. 13, 18-19 [1996]; Cioffi et al., Nature Med., 2 585-589 [1996]). A human hematopoetin receptor, which might be a receptor of the OB protein, is described in PCT application Publication No. WO
96/08510, published 21 March 1996.
Bailleul et al., Nucl. Acids Res. 25, 2752-2758 (1997) identified a human mRNA
splice variant of the OB-R gene that potentially encodes a novel protein, designated as leptin receptor gene-related protein (OB-RGRP). This protein displays no sequence similarity to the leptin receptor itself. The authors found that the OB-RGRP gene shares its promoter and two exons with the OB-R gene, and suggested that there is a requirement for a coordinate expression of OB-R and OB-RGRP to elicit the full physiological response to leptin in vivo.
83. PR01309 Protein-protein interactions include receptor and antigen complexes and signalingmechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Ttends Biochem. Sci.. 19( 10):415-421 (Oct. 1994);
Kobe and Deisenhofer, Curr.
O~in. Struct. Biol., 5(3):409-416 (1995).
A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem.
Mol. Biol., 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome, Chlemetson, K. J., Thromb.
Haemost. (Germany), 74(1):1 I 1-116 (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factor~i has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the IGF complex in vivo.
Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland), 125(1-2):65-70 (Dec. 1996) (gonadotropin receptorinvolvement); Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J. Am. Soc.
Nephrol., 6(4):1125-1133 (Oct. 1995) (kidney disease involvement).
Efforts are therefore being undertaken by both industry and academia to identify new proteins having leucine rich repeats to better understand protein-protein interactions. Of particular interest are those proteins having leucine rich repeats and homology to known proteins having leucine rich repeats such as platelet glycoprotein V, SLIT and ALS. Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel membrane-bound proteins having leucine rich repeats.
84. PR01028 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01028 polypeptides.
85. PR01027 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01027 polypeptides.
86. PR01107 Of particular interest are novel proteins having some sequence identity to known proteins. Known proteins include PC-1, an ecto-enzyme possessing alkaline phosphodiesterase I
and nucleotide pyrophosphatase activities, further described in Belli et al., Eur. J. Biochem., 228(3):669-676 (1995). Phosphodiesterases are also described in Fuss et al., J. Neurosci., 17(23j:9095-9103 (1997) and Scott et al., Hematology. 25(4):995-1002 (1997). Phosphodiesterase I, is described as a novel adhesin molecule and/or cytokine (related to autotaxin) involved in oligodendrocyte function. Fuss, supra.
We herein describe the identification and characterization of novel polypeptides having homology nto PC-1, designated herein as PR01107 polypeptides.
8'7. PR01140 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PRO) 140 polypeptides.
88. PR01106 As the mitochondria is primarily responsible for generating energy, proteins associated with the mitochondria are of interest. Recently, a cDNA from a novel Ca++-dependent member of the mitochondria) solute carrier superfamily was isolated from a rabbit small intestinal cDNA
library as described in Weber, et al. , PNAS USA, 94(16):8509-8514 (1997). It was reported that this transporter has four elongation factor-hand motifs in the N-terminal and is localized in the peroxisome, although a fraction can be found in the mitochondria.
Thus, this transporter, and proteins which have sequence identity to this and other members of the mitochondria) solute carrier superfamily are of particular interest.
We herein describe the identification and characterization of novel polypeptides having homology to a peroxisomal calcium dependent solute carrier protein, designated herein as PR01106 polypeptides.
89. PR01291 Butyrophilin is a milk glycoprotein that constitutes more than 40% of the total protein associated with the fat globule membrane in mammalian milk. Expression of butyrophilin mRNA
has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation.
Butyrophilin has been identified in bovine, murine and human (see Taylor et al., Biochim. Biophvs. Acta 1306:1-4 (1996), Ishii et al., Biochim. Biophvs. Acta 1245:285-292 (1995), Mather et al., J. Dairy 76:3832-3850 (1993) and Banghart et al., J. Biol. Chem. 273:4171-4179 (1998)) and is a type I transmembrane protein that is incorporated into the fat globulin membrane. It has been suggested that butyrophilin may play a role as the principle scaffold for the assembly of a complex with xanthine dehydrogenase/oxidase and other proteins that function in the budding and release of milk-fat globules from the apical surface during lactation (Banghart et al., su ra .
Given that butyrophilin plays an obviously important role in mammalian milk production, there is substantial interest in identifying novel butyrophilin homologs. We herein describe the identification and characterization of novel polypeptides having homology to butyrophilin, designated herein as PR01291 polypeptides.
90. PRO1105 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PRO1105 polypeptides.
91. PRO511 Proteins of interest include those having sequence identity with RoBo-1, a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family selectively expressed in bone and growth plate cartilage as described in Noel et al., J. Biol. Chem. 273(7):3878-3883 ( 1998). RoBo-1 is believed to play a novel role in the growth or remodeling of bone. Proteins also of interest include those having sequence identity with phospholipase inhibitors.
We herein describe the identification and characterization of novel polypeptides having homology to urokinase plasminogen activator receptors and phospholipase inhibitors, designated herein as PRO511 polypeptides.
92. PR01104 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01104 polypeptides.
93. PRO1100 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PRO1100 polypeptides.
94. P_R0836 Of interest are lamina) proteins, or proteins specific to the endoplasmic reticultttn (ER). Of particular interest are proteins having sequence identity with known proteins. Known proteins include proteins such as SLS1. In Saccharomyces cerevisiae, SLS1 has been reported to be a mitochondria) integral membrane protein involved in mitochondria) metabolism. Rouillard, et al., Mol. Gen. Genet., 252(6):700-708 (1996). In yeast Yarrowia lipolytica, it has been reported that the SLS1 gene product (SLSIp) behaves as a lumenal protein of the ER. It is believed that SPSlp acts in the preprotein translocation process, interacting directly with translocating polypeptides to facilitate their transfer and/or help their folding in the ER. Bosirame, et al., J.
Biol. Chem., 271(20):11668-11675 (1996).
We herein describe the identification and characterization of novel polypeptides having homology to SLSl, designated herein as PR0836 polypeptides.
95. PR01141 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01141 polypeptides.
96. PR01132 Proteases are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian protease enzymes play important roles in biological processes such as, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system. Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocampal plasticity. Neuropsin has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., Neurosci., 7(2):5088-5097 (1995) and Chen, et al., J. Histochem.
Cvtochem., 46:313-320 (1998).
Another serine protease of interest is the enamel matrix serine proteinase.
The maturation of dental enamel succeeds the degradation of organic matrix. Inhibition studies have shown that this degradation is accomplished by a serine-type proteinase. Proteases associated with enamel maturation are described in, i.e., Simmer, et al., 1. Dent. Res., 77(2):377-386 (1998), Overall and Limeback, Biochem J., 256(3):965-972 (1988), and Moradian-Oldak, Connect. Tissue Res., 35(1-4):231-238 (1996).
We herein describe the identification and characterization of novel poiypeptides having homology to serine proteases, designated herein as PR01132 polypeptides.
97. PR01346 The abbreviations "TIE° or "tie" are acronyms, which stand for "tyrosine kinase containing Ig and EGF homology domains" and were coined to designate a new family of receptor tyrosine kinases which are almost exclusively expressed in vascular endothelial cells and early hemopoietic cells, and are characterized by the presence of an EGF-like domain, and extracellular folding units stabilized by intra-chain disulfide bonds, generally referred to as "immunoglobulin (IG)-like" folds. A tyrosine kinase homologous cDNA fragment from htunan leukemia cells (tie) was described by Partanen et al., Proc. Natl.
Acad. Sci. USA 87, 8913-8917 (1990).
The mRNA of this human "TIE" receptor has been detected in all human fetal and mouse embryonic tissues, and has been reported to be localized in the cardiac and vascular endothelial cells. Korhonen et al., Bl~od 80, 2548-2555 (1992); PCT Application Publication No. WO 93/14124 (published 22 July 1993). The rat homolog of human TIE, referred to as "TIE-1", was identified by Maisonpierre et al., Oncoeene 8_, 1631-1637 (1993)).
Another TIE receptor, designated "TIE-2" was originally identified in rats (Dumont et al. , Onco ene 8_, 1293-1301 (1993)), while the human homolog of TIE-2, referred to as "ork" was described in U.S. Patent No.
5,447,860 (Ziegler). The marine homolog of TIE-2 was originally termed "tek. "
The cloning of a mouse TIE-2 receptor from a brain capillary cDNA library is disclosed in PCT Application Publication No. WO 95/13387 (published 18 May 1995). TIE-2 is a receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Tie-2 knockout mice die by defects in the formation of microvassels. Accordingly, the TIE
receptors are believed to be actively involved in angiogenesis, and may play a role in hemopoiesis as well.
Indeed, recent results (Lin et al., J. Clin. Invest. 100(8), 2072-2078 [1997J) demonstrating the ability of a soluble TIE-2 receptor to inhibit tumor angiogenesis have been interpreted to indicate that TIE-2 plays a role in pathologic vascular growth. In another study, TIE-2 expression was examined in adult tissues undergoing angiogenesis and in quiescent tissues. TIE2 expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation and uterine development and in healing wounds. TIE-2 was also reported to be expressed in the entire spectrum of the quiescent vasculature (arteries, veins, and capillaries) in a wide range of adult tissues.
Wong et al., Circ. Res. 81(4), 567-574 (1997). It has been suggested that TIE-2 has a dual function in adult angiogenesis and vascular maintenance.
The expression cloning of human TIE-2 ligands has been described in PCT
Application Publication No.
WO 96/11269 (published 18 April 1996) and in U.S. Patent No. 5,521,073 (published 28 May 1996). A vector designated as ~.gt 10 encoding a TIE-2 ligand NL7d "htie-2 ligand I " or "hTL
1 " has been deposited under ATCC
Accession No. 75928. A plasmid encoding another TIE-2 ligand designated "htie-2 2" or "hTL2" is available under ATCC Accession No. 75928. This second ligand has been described as an antagonist of the TAI-2 receptor. The identification of secreted human and mouse ligands for the TIE-2 receptor has been reported by Davis et al., Cell 87, 1161-1169 (1996). The human ligand designated "Angiopoietin-1", to reflect its role in angiogenesis and potential action during hemopoiesis, is the same ligand as the ligand variously designated as "htie-2 1 " or "hTL-1 " in WO 96/ 11269. Angiopoietin-1 has been described to play an angiogenic role later and distinct from that of VEGF (Sari et al., Cell 87, 1171-1180 (1996)). Since TIE-2 is apparently upregulated during the pathologic .angiogenesis requisite for tumor growth (Kaipainen et al., Cancer Res. 54, 6571-6577 (1994)) angiopoietin-1 has been suggested to be additionally useful for specifically targeting tumor vasculature (Davis et al., su ra .
We herein describe the identification and characterization of novel TIE ligand polypeptides, designated herein as PR01346 polypeptides.
98. PR01131 The low density lipoprotein (LDL) receptor is a membrane-bound protein that plays a key role in cholesterol homeostasis, mediating cellular uptake of lipoprotein particles by high affinity binding to its ligands, apolipoprotein (apo) B-100 and apoE. The ligand-binding domain of the LDL
receptor contains 7 cysteine-rich repeats of approximately 40 amino acids, wherein each repeat contains 6 cysteines, which form 3 infra-repeat disulfide bonds. These unique structural features provide the LDL receptor with its ability to specifically interact with apo B-100 and apoE, thereby allowing for transport of these lipoprotein particles across cellular membranes and metabolism of their components. Soluble fragments containing the extracellular domain of the LDL receptor have been shown to retain the ability to interact with its specific lipoprotein ligands (Simmons et al., J. Biol.
Chem. 272:25531-25536 (1997)). LDL receptors are further described in Javitt, FASEB J., 9(13):1378-1381 (1995), van Berkel, et al., Atherosclerosis, 118 Supp1:S43-S50 (1995) and Herz and Willnow, Ann. NY Acad.
Sci., 737:14-19 (1994). Thus, proteins having sequence identity with LDL
receptors are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to LDL receptors, designated herein as PR01131 polypeptides.
99. PR01281 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01281 polypeptides.
100. PR01064 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01064 polypeptides.
101. PR01379 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01379 polypeptides.
102. PR0844 Proteases are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized. The mammalian protease enrymes play important roles in many different biological processes including, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes. Thus, proteases are of interest.
Also of interest are protease inhibitors.
Of particular interest are serine proteases. In one study it was reported that when the serine protease inhibitor antileukoproteinase (aLP) is injected, it accumulates in articular and extraarticular cartilage of normal rats. This physiological pathway of cartilage accumulation, lost in proteoglycan depleted arthritic cartilage is believed to serve to maintain the local balance between proteinase function and inhibition. Burkhardt, et al., J.
Rheumatol, 24(6):1145-1154 (1997). Moreover, aLP and other protease inhibitors have been reported to play a role in the in vitro growth of hematopoietc cells by the neutralization of proteinases produced by bone marrow accessory cells. Gosklink, et al., J. Exp. Med., 184(4):1305-1312 (1996). Also of interest are mutants of aLP.
Oxidation resistant mutants of aLPe have been reported to have significant therapeutic effects on animal models having emphysema. Steffens, et al., Agents Actions Sup~l., 42:111-121 (1993).
Thus, serine protease inhibitors are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to serine protease inhibitors, designated herein as PR0844 polypeptides.
103. PR0848 Membrane-bound proteins of interest include channels such as ion channels.
Furthermore, membrane-bound proteins of interest include enzymes bound to intracellular vacuoles or organelles, such as transferases.
For example, a peptide of interest is the GaINAc alpha 2, 6-sailytransferase as described in Kurosawa, et al., J. Biol. Chem., 269(2):1402-1409 (I994). This peptide was constructed to be secreted, and retained its catalytic activity. The expressed enzyme exhibited activity toward asialomucin and asialofetuin, but not other glycoproteins tested. As sialylation is an important function, sialyltransferases such as this one, and peptides related by sequence identity, are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to sialyltransferases, designated herein as PR0848 polypeptides.
104. PR01097 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01097 polypeptides.
105. PR01153 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01153 polypeptides.
106. PR01154 Aminopeptidase N causes enzymatic degradation of perorally administered peptide drugs. Thus, aminopeptidase N has been used in studies to develop and identify inhibitors so as to increase the efficacy of peptide drugs by inhibiting their degradation. Aminopeptidases are also generally of interest to use to degrade peptides. Aminopeptidases, particularly novel aminopeptidases are therefore of interest. Aminopeptidase N and inhibitors thereof are further described in Bernkop-Schnurch and Marschutz, Pharm. Res., 14(2):181-185 ((1997); Lerche, et al., Mamm. Genome, 7(9):712-713 (1996); Papapetropoulos, et al., I_mmunopharmacolog~
32(1-3):153-156 (1996); Miyachi, et al., J. Med. Chem., 41(3):263-265 (1998);
and Olsen, et al., Adv. Exn.
Med. Biol., 421:47-57 (1997).
We herein describe the identification and characterization of novel polypeptides having homology to aminopeptidase N, designated herein as PR01154 polypeptides.
107. PR01181 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01181 polypeptides.
108. PR01182 Conglutinin is a bovine serum protein that was originally described as a vertebrate lectin protein and which belongs to the family of C-type lectins that have four characteristic domains, (1) an N-terminal cysteine-rich domain, (2) a collagen-like domain, (3) a neck domain and (4) a carbohydrate recognition domain (CRD).
Recent reports have demonstrated that bovine conglutinin can inhibit hemagglutination by influenza A viruses as a result of their lectin properties (Eda et al., Biochem. J. 316:43-48 (1996)). It has also been suggested that lectins such as conglutinin can function as immunoglobulin-independent defense molecules due to complement-mediated mechanisms. Thus, conglutinin has been shown to be useful for purifying immune complexes in vitro and for removing circulating immune complexes from patients plasma in vivo (Lim et al., Biochem. Bio_phvs.
Res. Commun. 218:260-266 (1996)). We herein describe the identification and characterization of novel polypeptides having homology to conglutinin protein, designated herein as PR01182 polypeptides.
109. PR 1155 Substance P and the related proteins, neurokinin A and neurokinin B have been reported as compounds which elicit contraction of the ileum both directly through action on a muscle cell receptor and indirectly through stimulation of a neuronal receptor. This action leads to the release of acetylcholine which causes muscle contraction via muscarinic receptors. It has also been reported that neurokinin B was found to be the most potent agonist for the neuronal Substance P receptor and that neurokinin B can be inhibited by enkephalinamide.
Laufer, et al., PNAS USA, 82(21):74444-7448 (1985). Moreover, neurokinin B has been reported to provide neuroprotection and cognitive enhancement, and therefore believed to be useful for the treatment of neurodegenerative disorders, including alzheimers disease. Wenk, et al., Behav. Brain Res., 83(1-2):129-133 (1997). Tachykinins are also described in Chawla, et al., J. Comp. Neurol., 384(3):429-442 (1997). Thus, tachykinins, particularly those related to neurokittiii B are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to neurokinin B protein, designated herein as PRO1155 polypeptides.
110. PR01156 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01181 polypeptides.
111. PR01098 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01098 polypeptides.
112. PR01127 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01127 polypeptides.
113. PR01126 The extracellular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transduction machinery. The major protein component of this extracellular matrix is olfactomedin, a glycoprotein that is expressed in olfactory neuroepithelium and which form intermolecular disulfide bonds so as to produce a polymer (Yokoe et al. , Proc. Natl. Acad. Sci. USA
90:4655-4659 (1993), Bal et al., Biochemistry 32:1047-1053 (1993) and Snyder et al., Biochemistry 30:9143-9153 (1991)). It has been suggested that olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. Given this important role, there is significant interest in identifying and characterizing novel polypeptides having homology to olfactomedin. We herein describe the identification and characterization of novel polypeptides having homology to olfactomedin protein, designated herein as PR01126 polypeptides.
114. PR 1125 Of particular interest are proteins which have multiple Trp-Asp (WD) repeats.
WD proteins are made up of highly conserved repeating units usually ending with WD. They are found in eukaryotes but not in prokaryotes. They regulate cellular functions, such as cell division, cell-fate determination, gene transcription, gene transcription, transmembrane signaling, mRNA modification and vesicle fusion. WD are further described in Neer, et al., Nature, 371(6495):297-300 (1994); Jiang and Struhl, Nature, 391(6666):493-496(1998); and DeSilva, et al., Genetics, 148(2):657-667(1998). Thus, new members of this superfamily are all of interest.
115. PR01186 Protein A from Dendroaspis polylepis polylepis (black mamba) venom comprises 81 amino acids, including ten half-cystine residues. Venoms are of interest on the one hand as weapons in war, and on the other hand, to use in assays to determine agents which reverse or inhibit the effects of the venom or a similar poison.
Black mamba venom is further described in Int. J. Biochem., 17(6):695-699 (1985) and Joubert and Strydom, Hoppe Seylers Z Physiol. Chem., 361(12):1787-1794 (1980).
We herein describe the identification and characterization of novel polypeptides having homology to snake venom protein A, designated herein as PR01186 polypeptides.
116. PR01198 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01198 polypeptides.
117. PR01158 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01158 polypeptides.
118. PR01159 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01159 polypeptides.
119. PR01124 Ion channels are considered to be the gateway to the final frontier, the brain. Ion channels and the receptors which control these channels are responsible for the passage of ions, or nerve impulses to be communicated from cell to cell, thus, ion channels are responsible for communication. In addition to their critical role in the brain, ion channels play a critical role in the heart as well as blood pressure. lon channels have also been linked to other important bodily functions and conditions, as well as disorders, such as cystic fibrosis. For all of these reasons, ion channels, such as sodium, potassium and chloride channels, as well as all of their related proteins and receptors are of interest. For example, it has been reported that cystic fibrosis results from a defect in the chloride channel protein, cystic fibrosis transmembrane conductance regulator.
McGill, et al., D1E. Dis. Sci., 41(3):540-542 (1996). Chloride channels are further described in at least Finn, et al., PNAS USA, 90(12):5691-569 (1993) and Finn, et al., Mol. Cell Biochem., 114(1-2):2F-26 (1992).
Also of interest are molecules related to adhesion molecules, as adhesion molecules are known to be involved in cell-cell signaling and interactions. More generally, all novel membrane bound-proteins are of interest. Membrane-bound proteins and receptors can play an important role in the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiationfactors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, channels, transporters, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
Membrane-bound proteins include those which are bound to the outer membrane and intracellular membranes and organelles. Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interaction. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.
Efforts are being undertaken by both industry and academia to identify new, native receptor proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel receptor proteins. Herein is presented a polypeptide and nucleic acid encoding therefor which has sequence identity with a chloride channel protein chloride channei protein and lung-endothelial cell adhesion molecule-1 (SCAM-1).
120. PR01287 Fringe is a protein which specifically blocks serrate-mediated activation of notch in the dorsal comparunent of the Drosophila wing imaginal disc. Fleming et al., Development.
124(15):2973-81 (1997).
Therefore, fringe protein is of interest for both its role in development as well as its ability to regulate senate, particularly serrate's signaling abilities. Also of interest are novel polypeptides which may have a rote in development and/or the regulation of serrate-like molecules. Of particular interest are novel polypeptides having homology to fringe.
We herein describe the identification and characterization of novel polypeptides having homology to fringe protein, designated herein as PR01287 polypeptides.
121. PR01312 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01312 polypeptides.
122. PR01192 Membrane-bound proteins of myelin are of interest because of their possible implications in various nervous system disorders associated with improper myelination. Myelin is a cellular sheath, formed by glial cells, that surrounds axons and axonal processes that enhances various electrochemical properties and provides trophic support to the neuron. Myelin is formed by Schwann cells in the peripheral nervous system (PNS) and by oligodendrocytes in the central nervous system (CNS). Improper myelination of central and peripheral neurons occurs in a number of pathologies and leads to improper signal conduction within the nervous systems.
Among the various demyelinating diseases Multiple Sclerosis is the most notable.
The predominant integral membrane protein of the CNS myelin of amphibians, reptiles, birds and mammals are proteolipid protein (PLP) and P0, the main glycoprotein in PNS
myelin. (Schlieess and Stoffel, Biol. Chem. Hogoe Seyler (1991) 372(9):865-874). In view of the importance of membrane-bound proteins of the myelin, efforts are being undertaken by both industry and academia to identify and characterize various myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995) 64(6):2427-2436).
123. PR01160 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01160 polypeptides.
124. PR 1187 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01187 polypeptides.
125. PR01185 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01185 polypeptides.
126. PR0345 Human tetranectin is a 202 amino acid protein encoded by a gene spanning approximately 12 kbp of DNA (Berglund et al., FEBS L,ett. 309:15-19 (1992)). Tetranectin has been shown to be expressed in a variety of tissues and functions primarily as a plasminogen binding protein.
Tetranectin has been classified in a distinct group of the C-type lectin superfamily but has structural and possibly functional similarity to the collectin proteins (Nielsen et al., FEBS Ixtt. 412(2):388-396 (1997)). Recent studies have retorted that variability in serum tetranectin levels may be predictive of the presence of various types of cancers including, for example, ovarian and colorectal cancers (Hogdall et al., Acta Oncol. 35:63-69 ( 1996), Hogdall et al., Eur. J. Cancer 31A(6):888-894 (1995) and Tuxen et al., Cancer Treat. Rev. 21(3):215-245 (1995)). As such, there is significant interest in identifying and characterizing novel polypeptides having structural and functional similarity to the teuanectin protein.
We herein describe the identification and characterization of novel polypeptides having homology to tetranectin protein, designated herein as PR01345 polypeptides.
127. PR01245 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01245 polypeptides.
128. PR0358 Serine protease inhibitors are of interest because they inhibit catabolism and are sometimes associated with regeneration of tissue. For example, a gene encoding a plasma protein associated with liver regeneration has been cloned and termed regeneration-associated serpin-1 (RASP-1). New, et al., Biochem. Biophys. Res.
Commun., 223(2):404-412 (1996). While serine protease inhibitors are of interest, particularly of interest are those which have sequence identity with known serine protease inhibitors such as RASP-1.
We herein describe the identification and characterization of novel polypeptides having homology to RASP-1, designated herein as PR01245 polypeptides.
129. PR01195 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01195 polypeptides.
130. PR01270 The recognition of carbohydrates by lectins has been found to play an important role in various aspects of eukaryotic physiology. A number of different animal and plant lectin families exist, but it is the calcium dependent, or type C, lectins that have recently garnered the most attention.
For example, the recognition of carbohydrate residues on either endothelial cells or leukocytes by the selectin family of calcium dependent lectins has been found to be of profound importance to the trafficking of leukocytes to inflammatory sites. Lanky, L., Ann. Rev. Biochem.. 64 113-139 ( 1995). The biophysical analysis of these adhesive interactions has suggested that lectin-carbohydrate binding evolved in this case to allow for the adhesion between leukocytes and the endothelium under the high shear conditions of the vasculature. Thus, the rapid on rates of carbohydrate recognition by such lectins allows for a hasty acquisition of ligand, a necessity under the high shear of the vascular flow. The physiological use of type C lectins in this case is also supported by the relatively low affinities of these interactions, a requirement for the leukocyte rolling phenomenon that has been observed to occur at sites of acute inflammation. The crystal structures of the mannose binding protein (Weis et al., Science 254, 1608-1615 [1991]; Weis et al., Nature 360 127-134 [1992]) and E-selectin (Graves et al., Nature 367(6463), 532-538 [1994]), together with various mutagenesis analyses (Erbe et al., J. Cell.
Biol. 119(1), 215-227 [1992];
Drickamer, Nature 360, 183-186 [1992]; Iobst et al., J. Biol. Chem. 169(22), 15505-15511 [1994]; Kogan et al., J. Biol. Chem. 270(23), 14047-14055 [1995]), is consistent with the supposition that the type C lectins are, in general, involved with the rapid recognition of clustered carbohydrates.
Together, these data suggest that type C lectins perform a number of critical physiological phenomena through the rapid, relatively low affinity recognition of carbohydrates.
Given the obvious importance of the lectin proteins in numerous biological processes, efforts are currently being made to identify novel lectin proteins or proteins having sequence homology to lectin proteins.
We herein describe the identification and characterization of novel polypeptides having homology to a lectin protein, designated herein as PR01270 polypeptides.
131. PR01271 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01271 polypeptides.
132. PR01375 The proteins L1CAM, G6PD and P55 are each associated with various known disease states. Thus, the genomic loci of Fugu rubripes homologs of the human disease genes Ll CAM, G6PD and P55 were analyzed.
This analysis led to the the identification of putative protein 2 (PUT2), GENBANK locus AF026198, accession AF026198. (See GENBANK submission data). Thus, PUT2 and proteins which have sequence identity with PUT2, are of interest.
133. PR01385 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01385 polypeptides.
134. PR01387 Membrane-bound proteins of myelin are of interest because of their possible implications in various nervous system disorders associated with improper myelination. Myelin is a cellular sheath, formed by glial cells, that surrounds axons and axonal processes that enhances various electrochemical properties and provides trophic support to the neuron. Myelin is formed by Schwann cells in the peripheral nervous system (PNS) and by oligodendrocytes in the central nervous system (CNS). Improper myelination of central and peripheral neurons occurs in a number of pathologies and leads to improper signal conduction within the nervous systems.
Among the various demyelinating diseases Multiple Sclerosis is the most notable.
The predominant integral membrane protein of the CNS myelin of amphibians, reptiles, birds and mammals are proteolipid protein (PLP) and P0, the main glycoprotein in PNS
myelin. (Schlieess and Stoffel, Biol. Chem. Hoppe Seyler (1991) 372!9):865-874). In view of the importance of membrane-bound proteins of the myelin, efforts are being undertaken by both industry and academia to identify and characterize various myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995) 64(6):2427-2436).
We herein describe the identification and characterization of novel polypeptides having homology to myelin protein, designated herein as PR01387 poIypeptides.
135. PR01384 One class of receptor proteins that has been of interest is the NKG2 family of type II transmembrane molecules that are expressed in natural killer cells. These proteins, which have been shown to be covalently associated with CD94, are involved in natural killer cell-mediated recognition of different HLA-allotypes (Plougastel, B. et al., Eur. J. Immunol. (1997) 27(11):2835-2839), and interact with major histocompatibility complex (MHC) class I to either inhibit or activate functional activity (Ho, EL. et al., Proc. Natl. Acad. Sci.
(1998) 95111):6320-6325). Accordingly, the identification and characterization of new members of this family of receptor proteins is of interest (see Houchins JP, et al. J. Exp. Med.
(1991) 173(4):1017-1020).
SUMMARY OF THE INVENTION
1. PR 281 A cDNA clone (DNA16422-1209) has been identified, having homology to nucleic acid encoding testis enhanced gene transcript (TEGT) protein that encodes a novel polypeptide, designated in the present application as "PR0281".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0281 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0281 polypeptide having the sequence of amino acid residues from about 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID
N0:2), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0281 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 80 or about 122 and about 1114, inclusive, of Figure 1 (SEQ ID NO:1). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209929 (DNA16422-1209) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209929 (DNA16422-1209).
In still a farther aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about IS to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0281 polypeptide having the sequence of amino acid residues from 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85%a sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0281 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 14 in the sequence of Figure 2 (SEQ ID
N0:2). The multiple transmembrane domains have been tentatively identified as extending from about amino acid position 83 to about amino acid position 105, from about amino acid position 126 to about amino acid position 146, from about amino acid position 158 to about amino acid position 177, from about amino acid position 197 to about amino acid position 216, from about amino acid position 218 to about amino acid position 238, from about amino acid position 245 to about amino acid position 265, and from about amino acid position 271 to about amino acid position 290 in the PR0281 amino acid sequence (Figure 2, SEQ ID N0:2).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0281 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 1 (SEQ ID NO:1 ).
In another embodiment, the invention provides isolated PR0281 poiypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0281 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 15 to about 345 of Figure 2 (SEQ ID N0:2).
In another aspect, the invention concerns an isolated PR0281 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2).
In a further aspect, the invention concerns an isolated PR0281 polypeptide, comprising an amino acid sequence scoring at least about 8090 positives, preferably at least about 85%
positives, more preferably at least about 90°~ positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues I or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2).
In yet another aspect, the invention concerns an isolated PR0281 polypeptide, comprising the sequence of amino acid residues 1 or about 15 to about 345, inclusive of Figure 2 (SEQ
ID N0:2), or a fragment thereof sufficient to provide a binding site for an anti-PR0281 antibody. Preferably, the PR0281 fragment retains a qualitative biological activity of a native PR0281 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0281 polypeptide having the sequence of amino acid residues from about I or about IS to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0281 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0281 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0281 polypeptide by contacting the native PR0281 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
in a still further embodiment, the invention concerns a composition comprising a PR0281 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
Z. PR0276 A cDNA clone (DNA16435-1208) has been identified that encodes a novel polypeptide having two transmembrane domains and designated in the present application as "PR0276."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0276 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0276 polypeptide having the sequence of amino acid residues from about I to about 251, inclusive of Figure 4 (SEQ ID N0:6), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0276 pvlypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 180 and about 932, inclusive, of Figure 3 (SEQ ID NO:S). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209930 (DNA16435-1208), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209930 (DNA16435-1208).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at Least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 251, inclusive of Figure 4 (SEQ ID N0:6), or the complement of the DNA of (a).
$ In a further aspect, the invention concerns an isolated nucleic acid molecule having at Least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0276 polypeptide having the sequence of amino acid residues from about 1 to about 251, inclusive of Figure 4 (SEQ ID
N0:6), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0276 polypeptide in its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains are at about amino acds 98-116 and 152-172.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about Z51, inclusive of Figure 4 (SEQ ID
N0:6), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0276 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0276 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0276 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 251 of Figure 4 (SEQ ID N0:6).
In another aspect, the invention concerns an isolated PR0276 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 251, inclusive of Figure 4 (SEQ ID
N0:6).
In a further aspect, the invention concerns an isolated PR0276 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at Least 3$ about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 251 of Figure 4 (SEQ ID N0:6).
In yet another aspect, the invention concerns an isolated PR0276 polypeptide, comprising the sequence of amino acid residues 1 to about 251, inclusive of Figure 4 (SEQ ID N0:6), or a fragment thereof sufficient to provide a binding site for an anti-PR0276 antibody. Preferably, the PR0276 fragment retains a qualitative biological activity of a native PR0276 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0276 polypeptide having the sequence of amino acid residues from about 1 to about 251, inclusive of Figure 4 (SEQ ID N0:6), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80~ sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0276 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0276 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0276 polypeptide, by contacting the native PR0276 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0276 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
3. PR0189 A cDNA clone (DNA21624-1391) has been identified that encodes a novel polypeptide, designated in the present application as "PR0189". PR0189 polypeptides have a cytosolic fatty-acid binding domain.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0189 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 h sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0189 polypeptide having the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0189 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 200 and about 1300, inclusive, of Figure 5 (SEQ ID N0:7). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80°h sequence identity, preferably at least about 85%
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209917 (DNA21624-1391), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209917 (DNA21624-1391).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0189 polypeptide having the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 367, inclusive of Figure 6 (SEQ ID
N0:8), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0189 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0189 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 367 of Figure 6 (SEQ ID N0:8).
In another aspect, the invention concerns an isolated PR0189 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 367, inclusive of Figure 6 (SEQ ID
N0:8).
In a further aspect, the invention concerns an isolated PR0189 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 %a positives when compared with the amino acid sequence of residues 1 through 367 of Figure 6 (SEQ ID N0:8).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0189 polypeptide having the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0189 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0189 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a S native PR0189 polypeptide, by contacting the native PR0189 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0189 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
4. PR0190 Applicants have identified a cDNA clone that encodes a novel polypeptide having seven transmembrane domains and having sequence identity with CMP-sialic acid and UDP-galactose transporters, wherein the polypeptide is designated in the present application as "PR0190".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0190 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0190 polypeptide having amino acid residues 1 through 424 of Figure 9 (SEQ ID
N0:14), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA23334-1392 which includes the nucleotide sequence encoding PR0190.
In another embodiment, the invention provides isolated PR0190 polypeptide. In particular, the invention provides isolated native sequence PR0190 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 424 of Figure 9 (SEQ ID N0:14). An additional embodiment of the present invention is directed to an isolated PR0190 polypeptide, excluding the transmembrane domains.
Optionally, the PR0190 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA23334-1392.
In another embodiment, the invention provides an expressed sequence tag (EST) comprising the nucleotide sequence of SEQ ID NO:15.
5. PR0341 A cDNA clone (DNA26288-1239) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR0341".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0341 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0341 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID
N0:20), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0341 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 380 or about 431 and about 1753, inclusive, of Figure 11 (SEQ ID N0:19).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209792 (DNA26288-1239) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209792 (DNA26288-1239).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues i or about 18 to about 458, inclusive of Figure 12 (SEQ ID
N0:20), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 165 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0341 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID NO:ZO), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0341 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 12 (SEQ
ID N0:20). The transmembrane domains have been tentatively identified as extending from about amino acid position 171 to about amino acid position 190, from about amino acid position 220 to about amino acid position 239, from about amino acid position 259 to about amino acid position 275, from about amino acid position 286 to about amino acid position 305, from about amino acid position 316 to about amino acid position 335, from about amino acid position 353 to about amino acid position 378 and from about amino acid position 396 to about amino acid position 417 in the PR0341 amino acid sequence (Figure 12, SEQ ID N0:20).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about I8 to about 458, inclusive of Figure 12 (SEQ ID N0:20), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0341 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 11 (SEQ ID N0:19).
In another embodiment, the invention provides isolated PR0341 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
IO In a specific aspect, the invention provides isolated native sequence PR0341 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 458 of Figure 12 (SEQ ID N0:20).
In another aspect, the invention concerns an isolated PR0341 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID N0:20).
In a further aspect, the invention concerns an isolated PR0341 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 18 to about 458, inclusive of Figure I2 (SEQ ID N0:20).
In yet another aspect, the invention concerns an isolated PR0341 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 458, inclusive of Figure 12 (SEQ
ID N0:20), or a fragment thereof sufficient to provide a binding site for an anti-PR0341 antibody.
Preferably, the PR0341 fragment retains a qualitative biological activity of a native PR0341 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0341 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID N0:20), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA12920 comprising the nucleotide sequence of SEQ ID N0:21 (see Figure 13).
6. PR0180 A cDNA clone (DNA26843-1389) has been identified that encodes a novel polypeptide having multiple transmembrane domains designated in the present application as "PR0180".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0180 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 180 polypeptide having the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID N0:23), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0180 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 121 and about 918, inclusive, of Figure 14 (SEQ ID N0:22). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at ~ least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203099 (DNA26843-1389), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203099 (DNA26843-1389).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0180 polypeptide having the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO180 polypeptide in its soluble form, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains are shown in Figure 15.
It is believed that PR0180 has a type II transmembrane domain from about amino acids 13-33 of SEQ ID
N0:23.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0180 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0180 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
1n a specific aspect, the invention provides isolated native sequence PRO 180 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues i through 266 of Figure 15 (SEQ ID N0:23).
In another aspect, the invention concerns an isolated PR0180 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23).
In a further aspect, the invention concerns an isolated PR0180 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 266 of Figure 15 (SEQ ID N0:23).
In yet another aspect, the invention concerns an isolated PRO 180 polypeptide, comprising the sequence of amino acid residues 1 to about 266, inclusive of Figure 15 (SEQ ID N0:23), or a fragment thereof sufficient to provide a binding site for an anti-PR0180 antibody. Preferably, the PR0180 fragment retains a qualitative biological activity of a native PR0180 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0180 polypeptide having the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID N0:23), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0180 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0180 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0180 polypeptide, by contacting the native PR0180 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0180 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) (DNA12922) comprising the nucleotide sequence of Figure 16 (SEQ ID N0:24).
7. PR0194 Applicants have identified a cDNA clone that encodes a novel transmembrane polypeptide, wherein the polypeptide is designated in the present application as "PR0194".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0194 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0194 polypeptide having amino acid residues 1 to 264 of Figure 18 (SEQ ID N0:28), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0194 polypeptide having amino acid residues about 18 to 264 of Figure 18 (SEQ ID
N0:28) or amino acid 1 or about 18 to X of Figure 18 (SEQ ID N0:28), where X is any amino acid from 96 to 105 of Figure 18 (SEQ ID
N0:28), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA26844-1394 vector deposited on June 2, 1998 as ATCC 209926 which includes the nucleotide sequence encoding PR0194.
In another embodiment, the invention provides isolated PR0194 polypeptide. In particular, the invention provides isolated native sequence PR0194 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 264 of Figure I8 (SEQ ID N0:28).
Additional embodiments of the present invention are directed to PR0194 polypeptides comprising amino acids about 18 to 264 of Figure 18 (SEQ ID N0:28) or amino acid 1 or about 18 to X of Figure 18 (SEQ ID N0:28), where X is any amino acid from 96 to 105 of Figure 18 (SEQ ID N0:28). Optionally, the PR0194 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA26844-1394 vector deposited on June 2, 1998 as ATCC 209926.
8. PR0203 Applicants have identified a cDNA clone that encodes a novel polypeptide having sequence identity to glutathione-S-transferase, wherein the polypeptide is designated in the present application as "PR0203".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0203 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0203 polypeptide having amino acid residues 1 to 347 of Figure 20 (SEQ ID N0:30), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0203 polypeptide having amino acid residues X to 347 of Figure 20 (SEQ ID N0:30), where X is any amino acid from 83 to 92 of Figure 20 (SEQ ID N0:30), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA30862-1396 vector deposited on June 2, 1998, as ATCC 209920 which includes the nucleotide sequence encoding PR0203.
In another embodiment, the invention provides isolated PR0203 polypeptide. In particular, the invention provides isolated native sequence PR0203 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 347 of Figure 20 (SEQ ID N0:30).
Additional embodiments of the present invention are directed to PR0203 polypeptides comprising amino acid X
to 347 of Figure 20 (SEQ ID
N0:30), where X is any amino acid from 83 to 92 of Figure 20 (SEQ ID N0:30).
Optionally, the PR0203 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA30862-1396 vector deposited on June 2, 1998, as ATCC 209920.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA15618 which comprises the nucleotide sequence of Figure 21 (SEQ ID N0:31) 9. PR0290 A cDNA clone (DNA35680-1212) has been identified which encodes a polypeptide designated in the present application as "PR0290." PR0290 polypeptides have sequence identity with NTII-l, FAN and beige.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0290 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at Least about 95 % sequence identity to (a) a DNA molecule encoding a PR0290 polypeptide having the sequence of amino acid residues from about 1 to about 1003, inclusive of Figure 23 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0290 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 293 and about 3301, inclusive, of Figure 22 (SEQ ID N0:32). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at Least about 85 ~ sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 °6 sequence identity to (a} a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209790 (DNA35680-1212), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209790 (DNA35680-1212).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 1003, inclusive of Figure 23 (SEQ ID
N0:33), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0290 polypeptide having the sequence of amino acid residues from about I to about 1003, inclusive of Figure 23 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at Ieast about 95 %
positives when compared with the amino acid sequence of residues 1 to about 1003, inclusive of Figure 23 (SEQ
ID N0:33), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0290 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0290 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 1003 of Figure 23 (SEQ ID
N0:33).
In another aspect, the invention concerns an isolated PR0290 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 1003, inclusive of Figure 23 (SEQ
ID N0:33).
In a further aspect, the invention concerns an isolated PR0290 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 1003 of Figure 23 (SEQ ID N0:33).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0290 polypeptide having the sequence of amino acid residues from about 1 to about 1003, inclusive of Figure 23 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0290 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0290 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0290 polypeptide, by contacting the native PR0290 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0290 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
10. PR0874 Applicants have identified a cDNA clone that encodes a novel multi-span transmembrane polypeptide, which is designated in the present application as "PR0874".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0874 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0874 polypeptide having amino acid residues 1 to 321 of Figure 25 (SEQ ID N0:36), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0874 polypeptide having amino acid from about X to 321 of Figure 25 (SEQ ID N0:36), where X is any amino acid from about 270 to about 279 of Figure 25 (SEQ ID N0:36), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA40621-1440 vector deposited on June 2, 1998, as ATCC 209922 which includes the nucleotide sequence encoding PR0874.
In another embodiment, the invention provides isolated PR0874 polypeptide. In particular, the invention provides isolated native sequence PR0874 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 321 of Figure 25 (SEQ ID N0:36).
Additional embodiments of the present invention are directed to PR0874 polypeptides comprising amino acids X
to 321 of Figure 25 (SEQ ID
N0:36), where X is any amino acid from about 270 to about 279 of Figure 25 (SEQ ID N0:36). Optionally, the PR0874 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA40621-1440 vector deposited on June 2, 1998, as ATCC 209922.
11. PR0710 Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to CDC45 protein, wherein the polypeptide is designated in the present application as "PR0710".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0710 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0710 polypeptide having amino acid residues 1 to 566 of Figure 27 (SEQ ID N0:41), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects> the isolated nucleic acid comprises DNA encoding the PR0710 polypeptide having amino acid residues about 33 to 566 of Figure 27 (SEQ ID
N0:41) or amino acid 1 or about 33 to X of Figure 27 (SEQ ID N0:41), where X is any amino acid from 449 to 458 of Figure 27 (SEQ ID
N0:41), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA44161-1434 vector deposited on May 27, 1998 as ATCC 209907 which SS
includes the nucleotide sequence encoding PR0710.
In another embodiment, the invention provides isolated PR0710 polypeptide. In particular, the invention provides isolated native sequence PR0710 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 566 of Figure 27 (SEQ ID N0:41).
Additional embodiments of the present invention are directed to PR0710 polypeptides comprising amino acids about 33 to 566 of Figure 27 (SEQ ID N0:41) or amino acid 1 or about 33 to X of Figure 27 (SEQ ID N0:41), where X is any amino acid from 449 to 458 of Figure 27 (SEQ ID N0:41). Optionally, the PR0710 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA44161-1434 vector deposited on May 27, 1998 as ATCC 209907.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA38190 comprising the nucleotide sequence of Figure 28 (SEQ ID N0:42).
12. PR01151 A cDNA clone (DNA44694-1500) has been identified, having homology to nucleic acid encoding Clq protein, that encodes a novel polypeptide, designated in the present application as "PRO1151".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1151 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO11 S 1 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID
N0:47), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1151 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 272 or about 332 and about 1048, inclusive, of Figure 29 (SEQ ID N0:46).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203114 (DNA44694-1500) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203114 (DNA44694-1500).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID
N0:47), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PROI 151 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01151 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as e~ttending from about amino acid position 1 to about amino acid position 20 in the sequence of Figure 30 (SEQ
ID N0:47).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1151 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 29 (SEQ ID N0:46).
In another embodiment, the invention provides isolated PRO1151 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01151 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 21 to about 259 of Figure (SEQ ID N0:47).
In another aspect, the invention concerns an isolated PR01151 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 %a sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 30 sequence of amino acid residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47).
In a further aspect, the invention concerns an isolated PR01151 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47).
In yet another aspect, the invention concerns an isolated PRO 1151 polypeptide, comprising the sequence of amino acid residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ
ID N0:47), or a fragment thereof sufficient to provide a binding site for an anti-PR01151 antibody.
Preferably, the PR01151 fragment retains a qualitative biological activity of a native PR01151 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01151 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID
N0:47), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01151 polypeptide. In a particular embodiment, the agoriist or antagonist is an anti-PR01151 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01151 polypeptide by contacting the native PR01151 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01151 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
13. PR01282 A cDNA clone (DNA45495-1550) has been identified that encodes a novel polypeptide having sequence identity with leucine rich repeat proteins and designated in the present application as "PR01282."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01282 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01282 polypeptide having the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID N0:52), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01282 polypeptide comprising DNA hyhridizing to the complement of the nucleic acid between about residues 189 and about 2138, inclusive, of Figure 31 (SEQ ID N0:51). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°h sequence identity, most preferably at least about 95%
sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203156 (DNA45495-1550), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203156 (DNA45495-1550).
WO 99/63088 PC'T/US99/12252 In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID
N0:52), or the complement of the DNA of (a).
$ In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01282 polypeptide having the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID
N0:52), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01282 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 32 (SEQ ID
N0:52). The transmembrane domain has been tentatively identified as extending from about amino acid position 579 through about amino acid position 599 in the PR01282 amino acid sequence (Figure 32, SEQ ID N0:52).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 24 to about 673, inclusive of Figure 32 (SEQ
ID N0:52), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1282 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01282 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01282 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 through 673 of Figure 32 (SEQ ID
N0:52).
In another aspect, the invention concerns an isolated PR01282 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 24 to about 673, inclusive of Figure 32 (SEQ
ID N0:52).
WO 99/(,3pgg PCT/US99/12252 In a further aspect, the invention concerns an isolated PR01282 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 °h positives, most preferably at least about 95 k positives when compared with the amino acid sequence of residues 24 through 673 of Figure 32 (SEQ ID N0:52).
In yet another aspect, the invention concerns an isolated PR01282 polypeptide, comprising the sequence of amino acid residues 24 to about 673, inclusive of Figure 32 (SEQ ID N0:52), or a fragment thereof sufficient to provide a binding site for an anti-PR01282 antibody. Preferably, the PRO
1282 fragment retains a qualitative biological activity of a native PR01282 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01282 polypeptide having the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID N0:52), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 °h sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01282 polypeptide. In a particular embodiment, the agortist or antagonist is an anti-PR01282 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01282 polypeptide, by contacting the native PR01282 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1282 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
14. PR0358 Applicants have identified a novel cDNA clone that encodes novel human Toll polypeptides, designated in the present application as PR0358.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising a DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0358 polypeptide having amino acids 20 to 575 of Figure 34 (SEQ
ID N0:57), or (b) the complement of the DNA molecule of (a). The complementary DNA molecule preferably remains stably bound to such encoding nucleic acid sequence under at least moderate, and optionally, under high stringency conditions.
In a further embodiment, the isolated nucleic acid molecule comprises a polynucleotide that has at least about 90%, preferably at least about 95% sequence identity with a polynucleotide encoding a polypeptide comprising the sequence of amino acids 1 to 811 of Figure 34 (SEQ ID N0:57).
In a specific embodiment, the invention provides an isolated nucleic acid molecule comprising DNA
encoding native or variant PR0358 polypeptide, with or without the N-terminal signal sequence, and with or without the transmembrane regions of the respective full-length sequences. In one aspect, the isolated nucleic acid comprises DNA encoding a mature, full-length native PR0358 polypeptide having amino acid residues 1 to 811 of Figure 34 (SEQ ID N0:57), or is complementary to such. encoding nucleic acid sequence. In another aspect, the invention concerns an isolated nucleic acid molecule that comprises DNA encoding a native PR0358 polypeptide without an N-terminal signal sequence, or is complementary to such encoding nucleic acid sequence.
In yet another embodiment, the invention concerns nucleic acid encoding transmembrane-domain deleted or inactivated forms of the full-length native PR0358 protein.
In another embodiment, the invention provides an isolated nucleic acid molecule which comprises the clone (DNA 47361-1249) deposited on November 7, 1997, under ATCC number 209431.
In a specific embodiment, the invention provides a vector comprising a polynucleotide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity with a polynucleotide encoding a polypeptide comprising the sequence of amino acids 20 to 811 of Figure 34 (SEQ
ID N0:57), or the complement of such polynucleotide. In a particular embodiment, the vector comprises DNA
encoding the novel Toll homologue (PR0358), with or without the N-terminal signal sequence (about amino acids 1 to 19), or a transmembrane-domain (about amino acids 576-595) deleted or inactivated variant thereof, or the eztracellular domain (about amino acids 20 to 595) of the mature protein, or a protein comprising any one of these sequences.
A host cell comprising such a vector is also provided.
In another embodiment, the invention provides isolated PR0358 polypeptides.
The invention further provides an isolated native sequence PR0358 polypeptide, or variants thereof.
In particular, the invention provides an isolated native sequence PR0358 polypeptide, which in certain embodiments, includes the amino acid sequence comprising residues 20 to 575, or 20 to 811, or 1 to 811 of Figure 34 (SEQ ID N0:57).
In yet another embodiment, the invention concerns agonists and antagonists of the native PR0358 polypeptide. In a particuiar embodiment, the agonist or antagonist is an anti-PR0358 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of the native PR0358 polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0358 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
The invention further concerns a composition comprising an antibody specifically binding a PR0358 polypeptide, in combination with a pharmaceutically acceptable carrier.
The invention also concerns a method of treating septic shock comprising administering to a patient an effective amount of an antagonist of a PR0358 polypeptide. In a specific embodiment, the antagonist is a blocking antibody specifically binding a native PR0358 polypeptide.
15. PR01310 A cDNA clone (DNA47394-1572) has been identified that encodes a novel polypeptide having sequence identity with carbozypeptidase X2 and designated in the present application as "PR01310."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01310 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1310 polypeptide having the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID N0:62), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01310 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 401 and about 2593, inclusive, of Figures 35A-B (SEQ ID N0:61). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a firrtkter aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203109 (DNA47394-1572), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203109 (DNA47394-1572).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID
N0:62), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01310 polypeptide having the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID
N0:62), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 26 to about 765, inclusive of Figure 36 (SEQ
ID N0:62), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01310 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01310 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 through 765 of Figure 36 (SEQ ID
N0:62).
In another aspect, the invention concerns an isolated PR01310 polypeptide, comprising an amino acid sequence having at least about 80°k sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 26 to about 765, inclusive of Figure 36 (SEQ
ID N0:62).
In a further aspect, the invention concerns an isolated PRO 1310 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95~ positives when compared with the amino acid sequence of residues 26 through 765 of Figure 36 (SEQ ID N0:62).
In yet another aspect, the invention concerns an isolated PRO 1310 polypeptide, comprising the sequence of amino acid residues 26 to about 765, inclusive of Figure 36 (SEQ ID N0:62), or a fragment thereof sufficient to provide a binding site for an anti-PR01310 antibody. Preferably, the PR01310 fragment retains a qualitative biological activity of a native PR01310 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01310 polypeptide having the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID N0:62), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity; most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01310 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01310 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01310 polypeptide, by contacting the native PR01310 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01310 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
44. PR01277 Efforts are being undertaken by both industry and academia to identify new, native proteins. Many efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel receptor and other proteins. Of interest is the identification of proteins that may play roles in various human disorders and dysfunction. For example, the identification of proteins of the ear and the functions they play in hearing may lead to an understanding of the causes of hearing loss and deafness. Coch-B2 is one such protein that has been found to be specifically expressed in the inner ear (cochlea). It has been characterized and studied for its possible role in hearing loss (Robertson et al. Genomics (1994) 23(1):52-50; Robertson et al.
Genomics (1997) 46(3):345-354). We herein describe the identification and characterization of novel polypeptides having sequence identity to Coch-B2, designated herein as PR01277 polypeptides.
45. PR01135 Glycosylation is an important mechanism for modulating the physiochemical and biological properties of proteins in a stage- and tissue-specific manner. One of the important enzymes involved in glycosylation in Saccharomyces cerevisiae is alpha 1,2-mannosidase, an enzyme that catalyzes the conversion of Man9GlcNAc2 to Man8GlcNAc2 during the formation of N-linked oligosaccharides. The Saccharomyces cerevisiae alpha 1,2-mannosidase enzyme of is a member of the Class I alpha 1,2-mannosidases that are conserved from yeast to mammals. Given the important roles played by the alpha 1,2-mannosidases in glycosylation and the physiochemical activity regulated by glycosylation, there is significant interest in identifying novel polypeptides having homology to one or more mannosidases. We herein describe the identification and characterization of novel polypeptides having homology to alpha 1,2-mannosidase protein, designated herein as PR01135 polypeptides.
46. PR01114 Interferons (IFNs) encompass a large family of secreted proteins occurring in vertebrates. Although they were originally named for their antiviral activity, growing evidence supports a critical role for IFNs in cell growth and differentiation (Jaramillo et al., Cancer Investieation 13(3):327-338 ( 1995)). IFNs belong to a class of negative growth factors having the ability to inhibit the growth of a wide variety of cells with both normal and transformed phenotypes. IFN therapy has been shown to be beneficial in the treatment of human malignancies such as Karposi's sarcoma, chronic myelogenous leukemia, non-Hodgkin's lymphoma, and hairy cell leukemia as well as in the treatment of infectious diseases such as hepatitis B
(Gamliel et al., Scannine Microscopy 2(1):485-492 (1988), Einhorn et al., Med. Oncol. & Tumor Pharmacother. 10:25-29 (1993), Ringenberg et al., Missouri Medicine 85(1):21-26 (1988), Saracco et al., Journal of Gastroenteroloev and Hepatologv 10:668-673 (1995), Gonzalez-Mateos et al., Henato-Gastroenterologv 42:893-899 (1995) and Malaguarnera et al., Pharmacotheranv 17(5):998-1005 (1997)).
Interferons can be classified into two major groups based upon their primary sequence. Type I
interferons, IFN-a and IFN-(3, are encoded by a superfamily of intronless genes consisting of the IFN-a gene family and a single IFN-p gene that are thought to have arisen from a common ancestral gene. Type I
interferons may be produced by most cell types. Type II IFN, or IFN-y, is restricted to lymphocytes (T cells and natural killer cells) and is stimulated by nonspecific T cell activators or specific antigens in vivo.
Although both type I and type II IFNs produce similar antiviral and antiproliferative effects, they act on distinct cell surface receptors, wherein the binding is generally species specific (Larger et al., Immunol.
Todav 9:393-400 (1988)). Both IFN-a and IFN-~i bind competitively to the same high affinity type I receptor, whereas IFN-y binds to a distinct type II receptor. The presence and number of IFN receptors on the surface of a cell does not generally reflect the sensitivity of the cell to IFN, although it is clear that the effects of the IFN
protein is mediated through binding to a cell surface interferon receptor. As such, the identification and characterization of novel interferon receptor proteins is of extreme interest.
We herein describe the identification and characterization of novel interferon receptor polypeptides, designated herein as "PR01114 interferon receptor" polypeptides. Thus, the PR01114 polypeptides of the present invention represents a novel cell surface interferon receptor.
47. PR0828 Glutathione peroxidases are of interest because they play important roles in protection against risk of coronary disease, atherosclerosis, platelet hyperaggregation and synthesis of proaggregant and proinflammatory compounds. Glutathione peroxidases are involved in the reduction of hydrogen peroxides and lipid peroxides, which in turn regulate the activities of cyclooxygenase and lipooxygenase pathways. This ultimately influences the production of eicosanoids and modulates the balance between a proaggregatory and antiaggregatory state of platelets. These and other activities and functions of glutathione peroxidases are discussed in greater detail by Ursini et al., Biomed. Environ. Sci 10(2-3): 327-332 (1997); Vitoux et al., Ann. Biol. Clin (Paris) 54(5): 181-187 (1996); and Mirault et al., Ann N.Y. Acad. Sci 738: 104-115 (1994).
We herein describe the identification and characterization of novel polypeptides having sequence identity with glutathione peroxidases, designated herein as PR0828 polypeptides.
48. PR01009 Long chain acyl-CoA synthetase converts free fatty acids to acyl-CoA esters.
This synthetase has been reported to have interesting characteristics. Specifically, it has been reported that two boys having Alport syndrome, elliptocytosis and mental retardation carried a large deletion where long chain acyl-CoA synthetase 4 would have been located. Thus, the absence of this enzyme is believed to play a role in the development of mental retardation or other signs associated with Alport syndrome in the family. Piccini, et al., Genomics, 47(3):350-358 (1998). Moreover, it has been reported that an inhibitor of acyl coenzyme A synthetase, triacsin C, inhibits superoxide anion generation and degranulation by human neutrophils. Thus, it is suggested that there is a role for acyl-CoA esters in regulating activation of 02 generation and degranulation at the G protein or subsequent step(s). Korchak, et al., J. Biol. Chem., 269(48):30281-30287 (1994). Long chain acyl-CoA
synthetase is also briefly discussed in a report which describes very long chain acyl-CoA synthetase. Uchiyama, et al., J. Biol. Chem., 271(48):30360 (1994). Thus, long chain aryl-CoA
synthetase and particular novel polypeptides having sequence identity therewith are of interest.
We herein describe the identification and characterization of novel polypeptides having sequence identity with long chain acyl-CoA synthetase, designated herein as PR01009 polypeptides.
49. PR01007 Glycosylphosphatidylinositol (GPI) anchored proteoglycans are generally localized to the cell surface and are thus known to be involved in the regulation of responses of cells to numerous growth factors; cell adhesion molecules and extracellular matrix components. The metastasis-associated GPI-anchored protein (MAGPIAP) is one of these cell surface proteins which appears to be involved in metastasis. Metastasis is the form of cancer wherein the transformed or malignant cells are traveling and spreading the cancer from one site to another. Therefore, identifying the polypeptides related to metastasis and MAGPIAP is of interest.
We herein describe the identificationand characterization of novel polypeptides having sequence identity with MAGPIAP, designated herein as PR01007 polypeptides.
50. PR01056 Mammalian cell membranes perform very important functions relating to the structural integrity and activity of various cells and tissues. Of particular interest in membrane physiology is the study of trans-membrane ion channels which act to directly control a variety of physiological, pharmacological and cellular processes. Numerous ion channels have been identified including calcium (Ca), sodium (Na), chloride (CI) and potassium (K) channels, each of which have been analyzed in detail to determine their roles in physiological processes in vertebrate and insect cells. These roles include such things as maintaining cellular homeostasis, intracellular signaling, and the like. Given the obvious importance of the ion channels, there is significant interest in identifying and characterizing novel polypeptides having homology to one or more ion channels. We herein describe the identification and characterization of novel polypeptides having homology to a chloride channel protein, designated herein as PR01056 polypeptides..
51. PR0826 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0826 polypeptides.
52. PRO 19 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0819 polypeptides.
53. PR01006 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01006 polypeptides.
54. PR01112 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01112 polypeptides.
55. PR01074 Many membrane-bound enzymatic proteins play important roles in the chemical reactions involved in metabolism, including the biosynthesis of macromolecules, the controlled release and utilization of chemical energy, development of tissues, and other processes necessary to sustain life.
Galactosyltransferases are a family of enzymes that play a variety of important metabolic roles and thus are the subject of interest in research and industry. Numerous references have been published on the identification of galactosyltransferases and the roles they play in cellular development, maintenance, and dysfunction.
We herein describe the identification and characterization of novel polypeptides having homology to galactosyltransferases, designated herein as PR01074 polypeptides.
56. PR01005 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PRO1005 polypeptides.
57. PR01073 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01073 polypeptides.
58. PR01152 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01152 polypeptides.
59. PR01136 PDZ domain-containing proteins assist formation of cell-cell junctions and localization of membrane protein receptors and ion channels (Daniels et al., Nat. Struct. Biol. 5:317-325 (1998) and Ullmer et al., FEBS
I~,t~. 424:63-68 (1998)). PDZ domains interact with the C-terminal residues of a particular target membrane protein. Based on their binding specificities and sequence homologies, PDZ
domains fall into two classes, class I and class II. In light of the obvious importance of the PDZ domain-containing proteins, there is significant interest in identifying novel polypeptides that have homology to those proteins. We herein describe the identification and characterization of novel polypeptides having homology to PDZ domain-containing proteins, designated herein as PR01136 polypeptides.
60. PR0813 Surfactant proteins play extremely important biological roles in the mammalian pulmonary system. One mammalian protein that has been studied and well characterized is pulmonary surfactant-associated protein C.
For example, Qanbar et al., Am. J. Physiol. 271:L572-L580 (1996) studied the effect of palmitoylation of pulmonary surfactant-associated protein C on the surface activity of phospholipid mixtures. Specifically, the authors demonstrated that palmitoylation of pulmonary surfactant-associated protein C greatly enhanced lipid respreading and film stability and, therefore, was extremely important for surfactant function. Given the obvious important roles played by surfactant protein in the mammalian organism, there is significant interest in identifying novel polypeptides having homology to one or more surfactant enzymes. We herein describe the identification and characterization of novel polypeptides having homology to pulmonary surfactant-associated protein, designated herein as PR0813 polypeptides.
61. PR0809 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR0809 polypeptides.
62. PR07 1 Of particular interest are novel proteins which have sequence identity with known proteins. For example, novel proteins having some sequence identity with the major histocompatibility complex (MHC) are of interest. The MHC complex is a region of multiple loci that play major roles in determining whether transplanted tissue will be accepted as self (histocompatible) or rejected as foreign (histoincompatible).
Moreover, the MHC plays a central role in the development of both humoral and cell-mediated immune responses. There are class I, II and III MHC antigens, all known in the art.
Class I antigens are glycoproteins expressed on the surface of nearly all nucleated cells, where they present peptide antigens of altered self cells necessary for the activation of Tc cells. The assembly of MHC class I antigens is further described in Kvist and Levy, Semin. Immunol., 5(2):105-116 (1993) and Maffei, et al., Hum. Immunol., 54(2):91-103 (1997).
We herein describe the identification and characterization of novel polypeptides having sequence identity to various MHC-I antigens, designated herein as PR0791 polypeptides.
63. PR01004 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01004 polypeptides.
64. PROl l l l Protein-protein interactions include receptor and antigen complexes and signaling mechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Trends Biochem. Sci., 19(10):415-421 (Oct. 1994).
A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem.
Mol. Biol., 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome, Chlemetson, K. J., Thromb.
Haemost. (Germany), 74( 1 ):111-116 (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factor(3 has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the IGF complex in vivo.
Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland), 125(1-2):65-70 (Dec. 1996) (gonadotropinreceptor involvement); Miura, Y., et al., Ninnon Rinsho (Japan), 54(7):1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J. Am. Soc.
Nephrol., 6(4):1125-1133 (Oct. 1995) (kidney disease involvement).
We herein describe the identification and characterization of novel polypeptides having homology to LIG, designated herein as PRO1111 polypeptides.
65. PR01344 Factor C is a protein that is intimately involved with the coagulation cascade in a variety of organisms.
The coagulation cascade has been shown to involve numerous different intermediate proteins, including factor C, all of whose activity is essential to the proper functioning of this cascade. Abnormal coagulation cascade function can result in a variety of serious abnormalities and, as such, the activities of the coagulation cascade proteins is of particular interest. As such, efforts are currently being undertaken to identify novel polypeptides having homology to one or more of the coagulation cascade proteins.
We herein describe the identification and characterization of novel polypeptides having homology to factor C protein, designated herein as PR01344 polypeptides.
66. PR01109 Carbohydrate chains on glycoproteins are important not only for protein conformation, transport and stability, but also for cell-cell and cell-matrix interactions. ~i-1,4-galactosyltransferase is an enzyme that is involved in producing carbohydrate chains on proteins, wherein the (3-1,4-galactosyltransferase enzyme acts to transfer galactose to the terminal N-acetylglucosamine of complex-type N-glycans in the Golgi apparatus (Asano et al., EMBO J. 16:1850-1857 (1997)). In addition, it has been suggested that (3-1,4-galactosyltransferase is invloved directly in cell-cell interactions during fertilization and early embryogenesis through a subpopulation of this enzyme distributed on the cell surface. Specifically, Lu et al., Development 124:4121-4131 (1997) and Larson et al., Biol. Renrod. 57:442-453 ( 1997) have demonstrated that ~3-1,4-galactosyltransferase is expressed on the surface of sperm from a variety of mammalian species, thereby suggesting an important role in fertilization. In light of the above, novel polypeptides having sequence identity to (3-1,4-galactosyltransferase are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to (i-1,4-galactosyltransferase, designated herein as PR01109 polypeptides.
67. PR01383 The nmb gene is a novel gene that encodes a putative transmembrane glycoprotein which is differentially expressed in metastatic human melanoma cell lines and which shows substantial homology to the precursor of pMELl7, a melanocyte-specific protein (Weterman et al., Int. J. Cancer 60:73-81 (1995)). Given the interest in identifying tumor-specific cell-surface polypeptide markers, there is substantial interest in novel polypeptides having homology to tunb. We herein describe the identification and characterization of novel polypeptides having homology to the nmb protein, designated herein as PR01383 polypeptides.
68. PR01003 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01003 polypeptides.
69. PR01108 Lysophosphatidic acid acyltransferase (LPAAT) is an enzyme that in lipid metabolism converts lysophosphatidic acid (LPA) into phosphatidic acid (PA). LPA is a phospholipid that acts as an intermediate in membrane phospholipid metabolism. Various LPAAT enzymes have been identified in a variety of species (see, e.g., Aguado et al., J. Biol. Chem. 273:4096-4105 (1998), Stamps et al., Biochem. J. 326:455-461 (1997), Eberhart et al., J. Biol. Chem. 272:20299-20305 (1997) and West et al., DNA
Cell Biol. 16:691-701 (1997)).
Given the obvious importance of LPAAT in a variety of different applications including cell membrane maintenance, there is substantial interest in identifying and characterizing novel polypeptides having homology to LPAAT. We herein describe the identification and characterization of novel polypeptides having homology to LPAAT protein, designated herein as PR01108 polypeptides.
70. PR01137 A particular class of secreted polypeptides that are of interest in research and industry are ribosyltransferases. Braren et aI. described the use of EST databases for the identification and cloning of novel ribosyltransferase gene family members (Adv. Exp. Med. Biol. 419:163-168 (1997)). Ribosyltransferases have been identified playing roles in a variety of metabolic functions including posttranslational modification of proteins (Saxty et al., J. Leukoc. Biol., 63(1):15-21 (1998)), and mediation of the assembly of filamentous actin and chemotaxis in polymorphonuclear neutrophil leukocytes (Kefalas et al. Adv.
Exp. Med. Biol. 419:241-244 ( 1997)).
Described herein is the identification and characterization of novel polypeptides having homology to ribosyltransferase, designated herein as PR01137 polypeptides.
71. PR01138 Efforts are being undertaken by both industry and academia to identify new, native receptor proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel receptor proteins. Of particular interest is the identification of membrane-bound proteins found in cells of the hematopoietic system, as they often play important roles in fighting infection, repair of t0 injured tissues, and other activities of cells of the hematopoietic system.
For instance, CD84 leukocyte antigen has recently been identified as a new member of the Ig superfamily (de la Fuente et al. , Blood, 90(6):2398-2405 ( 1997)).
Described herein is the identification and characterization of a novel polypeptide having homology to CD84 leukocyte antigen, designated herein as PR01138 polypeptides.
72. PR01054 The proteins of the major urinary protein complex (MUP), proteins which are members of the lipocalin family, function to bind to volatile pheromones and interact with the vomeronasal neuroepithelium of the olfactory system. As such, proteins in the MUP family are intimately involved in the process of attraction between mammals of different sexes. Many different MUP family members have been identified and characterized and shown to possess varying degrees of amino acid sequence homology (see, e.g., Mucignat et al., Chem. Senses 23:67-70 (1998), Ferrari et al., FEBS Lett. 401:73-77 (1997) and Bishop et al., EMBO J.
1:615-620 (1982)). Given the physiological and biological importance of the MUP family of proteins, there is significant interest in identifying and characterizing novel members of this family. We herein describe the identification and characterization of novel polypeptides having homology to MUP family of proteins, designated herein as PR01054 polypeptides.
73. PR0994 The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a potential therapeutic target for murine monoclonal antibodies and their humanized counterparts (Marken et al., Proc. Natl. Acad. Sci. USA 89:3503-3507 (1992)).
The cDNA encoding this tumor-associated cell surface antigen has been expressed in COS cells and shown to encode a 202 amino acid polypeptide having three transmembrane domains. The L6 antigen has been shown to be related to a number of cell surface proteins that have been implicated in the regulation of cell growth, including for example CD63 and CO-029, proteins which are also highly expressed on tumor cells. As such, there is significant interest in identifying novel polypeptides having homology to the L6 tumor cell antigen as potential targets for cancer therapy. We herein describe the identification and characterization of novel polypeptides having homology to the L6 cell surface tumor cell-associated antigen, designated herein as PR0994 polypeptides.
74. PR0812 Steroid binding proteins play important roles in numerous physiological processes associated with steroid function. Specifically, one steroid binding protein-associated polypeptide that has been well characterized is component 1 of the prostatic binding protein. Component 1 of the prostatic binding protein has been shown to be specific for subunit F of the prostatic binding protein, the major secretory glycoprotein of the rat ventral prostate (Peelers et al., Eur. J. Biochem. 123:55-62 (1982) and Liao et al., J. Biol. Chem. 257:122-125 (1982)).
The amino acid sequence of component 1 of the prostatic binding protein has been determined, wherein the sequence is highly rich in glutamic acid residues and is overall highly acidic. This protein plays an important role in the response of the prostate gland to steioid hormones. We herein describe the identification and characterization of novel polypeptides having homology to prostatic steroid-binding protein c 1, designated herein as PR0812 polypeptides.
75. PR01069 Of particular interest is the identification of new membrane-bound proteins involved in ion conductance such as channel inhibitory factor (CHIF) and MAT-8, which have recently been reported (see Wald et al., Am.
J. Phvsiol, 272(5 pt 2): F617-F623 (1997); Capurro et al., Am. J. Phi, 271(3 pt 1): C753-C762 (1996);
Wald et al., Am. J. Physiol, 271(2 pt 2): F322-F329 (1996); and Morrison et al., J. Biol. Chem 270(5):2176-2182 (1995)).
Described herein is the identification and characterization of novel polypeptides having homology to CHIF and MAT-8 polypeptides, designated herein as PR01069 polypeptides.
?6. PR 1129 Cytochromes P-450 are a superfamily of hemoproteins which represent the main pathway for drug and chemical oxidation (Horsmans, Acta Gastroenterol. Bel~. 60:2-10 (1997)). This superfamily is divided into families, subfamilies and/or single enzymes. Recent reports have provided a great deal of information concerning the cytochrome P-450 isozymes and increased awareness of life threatening interactions with such commonly prescribed drugs as cisapride and some antihistamines (Michalets, Pharmacotheranv 18:84-112 ( 1998) and Singer et al., J. Am. Acad. Dermatol. 37:765-771 (1997)). Given this information, there is significant interest in identifying novel members of the cytochrome P-450 family of proteins. We herein describe the identification and characterization of novel polypeptides having homology to cytochrome P-450 proteins, designated herein as PR01129 polypeptides.
77. PR01068 Urotensins are neurosecretory proteins that are of interest because of their potential roles in a variety of physiological processes including smooth muscle contraction (Yano et al.
Gen. Comp. Endocrinol. 96(3): 412-413 (1994)), regulation of arterial blood pressure and heart rate (Le Mevel et al. Am. J. Physiol. 271(5 Pt 2):
81335-81343 (1996)), and corticosteroid secretion (Feuilloley et al. J.
Steroid Biochem Mol. Biol. 48(2-3): 287-292 (1994)).
We herein describe the identification and characterization of novel polypeptides having homology to urotensin, designated herein as PR01068 polypeptides.
S 78. PR01066 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01066 polypeptides.
79. PR01184 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01184 polypeptides.
80. PR01360 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01360 polypeptides.
81. PR01029 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01029 polypeptides.
82. PROI139 Obesity is the most common nutritional disorder which, according to recent epidemiologic studies, affects about one third of all Americans 20 years of age or older. Kuczmarski et al., J. Am. Med. Assoc. 272, 205-11 ( 1994). Obesity is responsible for a variety of serious health problems, including cardiovascular disorders, type II diabetes, insulin-resistance, hypertension, hypertriglyceridemia, dyslipoproteinemia, and some forms of cancer. Pi-Sunyer, F.X., Anns. Int. Med. 119, 655-60 (1993); Colfitz, G.A., Am. J. Clin. Nutr. 55, 503S-5075 (1992). A single-gene mutation (the obesity or "ob" mutation) has been shown to result in obesity and type II diabetes in mice. Friedman, Genomics 11, 1054-1062 (1991). Zhang et al., Nature 372, 425-431 (1994) have recently reported the cloning and sequencing of the mouse ob gene and its human homologue, and suggested that the ob gene product may function as part of a signaling pathway from adipose tissue that acts to regulate the size of the body fat depot. Parabiosis experiments performed more than 20 years ago predicted that the genetically obese mouse containing two mutant copies of the ob gene (oblob mouse) does not produce a satiety factor which regulates its food intake, while the diabetic (dbldb) mouse produces but does not respond to a satiety factor. Coleman and Hummal, Am. J. Ph~rsiol. 217, 1298-1304 ( 1969); Coleman, Diabetol. 9, 294-98 (1973). OB proteins are disclosed, for example, in U.S. patent Nos.
5,532,336; 5,552,522; 5,552,523;
5,552,514; 5,554,727. Recent reports by three independent research teams have demonstrated that daily injections of recombinant OB protein inhibit food intake and reduce body weight and fat in grossly obese oblob mice but not indbldb mice (Pelleymounter et al., Science 269, 540-43 (1995];
Halaas et al., Science 269, 543-46 [1995]; Campfield et al., Sc_ fence 269, 546-49 [1995]), suggesting that the ob protein is such a satiety factor as proposed in early cross-circulation studies.
A receptor of the OB protein (OB-R) is disclosed in Tartaglia et al. , Cell 83, 1263-71 ( i 995). The OB-R is a single membrane-spanning receptor homologous to members of the class I
cytokine receptor family (Tartaglia et al., supra; Bazan, Proc. Natl. Acad. Sci. USA 87, 6934-6938 [
1990]). Two 5'-untranslated regions and several 3'-alternative splice variants encoding OB-R with cytoplasmic domains of different lengths have been described in mouse, rat and human (Chen et al., Cell 84, 491-495 [1996]; Chua et al., Science 271, 994-996 [1996]; Tartaglia et al., supra; Wang et al., FEBS Lett. 392:87-90 ( 1996];
Phillips et al., Nature Genet. 13, 18-19 [1996]; Cioffi et al., Nature Med., 2 585-589 [1996]). A human hematopoetin receptor, which might be a receptor of the OB protein, is described in PCT application Publication No. WO
96/08510, published 21 March 1996.
Bailleul et al., Nucl. Acids Res. 25, 2752-2758 (1997) identified a human mRNA
splice variant of the OB-R gene that potentially encodes a novel protein, designated as leptin receptor gene-related protein (OB-RGRP). This protein displays no sequence similarity to the leptin receptor itself. The authors found that the OB-RGRP gene shares its promoter and two exons with the OB-R gene, and suggested that there is a requirement for a coordinate expression of OB-R and OB-RGRP to elicit the full physiological response to leptin in vivo.
83. PR01309 Protein-protein interactions include receptor and antigen complexes and signalingmechanisms. As more is known about the structural and functional mechanisms underlying protein-protein interactions, protein-protein interactions can be more easily manipulated to regulate the particular result of the protein-protein interaction.
Thus, the underlying mechanisms of protein-protein interactions are of interest to the scientific and medical community.
All proteins containing leucine-rich repeats are thought to be involved in protein-protein interactions.
Leucine-rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. The crystal structure of ribonuclease inhibitor protein has revealed that leucine-rich repeats correspond to beta-alpha structural units. These units are arranged so that they form a parallel beta-sheet with one surface exposed to solvent, so that the protein acquires an unusual, nonglubular shape. These two features have been indicated as responsible for the protein-binding functions of proteins containing leucine-rich repeats.
See, Kobe and Deisenhofer, Ttends Biochem. Sci.. 19( 10):415-421 (Oct. 1994);
Kobe and Deisenhofer, Curr.
O~in. Struct. Biol., 5(3):409-416 (1995).
A study has been reported on leucine-rich proteoglycans which serve as tissue organizers, orienting and ordering collagen fibrils during ontogeny and are involved in pathological processes such as wound healing, tissue repair, and tumor stroma formation. Iozzo, R. V., Crit. Rev. Biochem.
Mol. Biol., 32(2):141-174 (1997). Others studies implicating leucine rich proteins in wound healing and tissue repair are De La Salle, C., et al., Vouv. Rev. Fr. Hematol. (Germany), 37(4):215-222 (1995), reporting mutations in the leucine rich motif in a complex associated with the bleeding disorder Bernard-Soulier syndrome, Chlemetson, K. J., Thromb.
Haemost. (Germany), 74(1):1 I 1-116 (July 1995), reporting that platelets have leucine rich repeats and Ruoslahti, E. L, et al., W09110727-A by La Jolla Cancer Research Foundation reporting that decorin binding to transforming growth factor~i has involvement in a treatment for cancer, wound healing and scarring. Related by function to this group of proteins is the insulin like growth factor (IGF), in that it is useful in wound-healing and associated therapies concerned with re-growth of tissue, such as connective tissue, skin and bone; in promoting body growth in humans and animals; and in stimulating other growth-related processes. The acid labile subunit of IGF (ALS) is also of interest in that it increases the half life of IGF and is part of the IGF complex in vivo.
Another protein which has been reported to have leucine-rich repeats is the SLIT protein which has been reported to be useful in treating neuro-degenerative diseases such as Alzheimer's disease, nerve damage such as in Parkinson's disease, and for diagnosis of cancer, see, Artavanistsakonas, S. and Rothberg, J. M., W09210518-A1 by Yale University. Of particular interest is LIG-1, a membrane glycoprotein that is expressed specifically in glial cells in the mouse brain, and has leucine rich repeats and immunoglobulin-like domains.
Suzuki, et al., J. Biol. Chem. (U.S.), 271(37):22522 (1996). Other studies reporting on the biological functions of proteins having leucine rich repeats include: Tayar, N., et al., Mol. Cell Endocrinol., (Ireland), 125(1-2):65-70 (Dec. 1996) (gonadotropin receptorinvolvement); Miura, Y., et al., Nippon Rinsho (Japan), 54(7):1784-1789 (July 1996) (apoptosis involvement); Harris, P. C., et al., J. Am. Soc.
Nephrol., 6(4):1125-1133 (Oct. 1995) (kidney disease involvement).
Efforts are therefore being undertaken by both industry and academia to identify new proteins having leucine rich repeats to better understand protein-protein interactions. Of particular interest are those proteins having leucine rich repeats and homology to known proteins having leucine rich repeats such as platelet glycoprotein V, SLIT and ALS. Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel membrane-bound proteins having leucine rich repeats.
84. PR01028 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01028 polypeptides.
85. PR01027 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01027 polypeptides.
86. PR01107 Of particular interest are novel proteins having some sequence identity to known proteins. Known proteins include PC-1, an ecto-enzyme possessing alkaline phosphodiesterase I
and nucleotide pyrophosphatase activities, further described in Belli et al., Eur. J. Biochem., 228(3):669-676 (1995). Phosphodiesterases are also described in Fuss et al., J. Neurosci., 17(23j:9095-9103 (1997) and Scott et al., Hematology. 25(4):995-1002 (1997). Phosphodiesterase I, is described as a novel adhesin molecule and/or cytokine (related to autotaxin) involved in oligodendrocyte function. Fuss, supra.
We herein describe the identification and characterization of novel polypeptides having homology nto PC-1, designated herein as PR01107 polypeptides.
8'7. PR01140 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PRO) 140 polypeptides.
88. PR01106 As the mitochondria is primarily responsible for generating energy, proteins associated with the mitochondria are of interest. Recently, a cDNA from a novel Ca++-dependent member of the mitochondria) solute carrier superfamily was isolated from a rabbit small intestinal cDNA
library as described in Weber, et al. , PNAS USA, 94(16):8509-8514 (1997). It was reported that this transporter has four elongation factor-hand motifs in the N-terminal and is localized in the peroxisome, although a fraction can be found in the mitochondria.
Thus, this transporter, and proteins which have sequence identity to this and other members of the mitochondria) solute carrier superfamily are of particular interest.
We herein describe the identification and characterization of novel polypeptides having homology to a peroxisomal calcium dependent solute carrier protein, designated herein as PR01106 polypeptides.
89. PR01291 Butyrophilin is a milk glycoprotein that constitutes more than 40% of the total protein associated with the fat globule membrane in mammalian milk. Expression of butyrophilin mRNA
has been shown to correlate with the onset of milk fat production toward the end pregnancy and is maintained throughout lactation.
Butyrophilin has been identified in bovine, murine and human (see Taylor et al., Biochim. Biophvs. Acta 1306:1-4 (1996), Ishii et al., Biochim. Biophvs. Acta 1245:285-292 (1995), Mather et al., J. Dairy 76:3832-3850 (1993) and Banghart et al., J. Biol. Chem. 273:4171-4179 (1998)) and is a type I transmembrane protein that is incorporated into the fat globulin membrane. It has been suggested that butyrophilin may play a role as the principle scaffold for the assembly of a complex with xanthine dehydrogenase/oxidase and other proteins that function in the budding and release of milk-fat globules from the apical surface during lactation (Banghart et al., su ra .
Given that butyrophilin plays an obviously important role in mammalian milk production, there is substantial interest in identifying novel butyrophilin homologs. We herein describe the identification and characterization of novel polypeptides having homology to butyrophilin, designated herein as PR01291 polypeptides.
90. PRO1105 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PRO1105 polypeptides.
91. PRO511 Proteins of interest include those having sequence identity with RoBo-1, a novel member of the urokinase plasminogen activator receptor/CD59/Ly-6/snake toxin family selectively expressed in bone and growth plate cartilage as described in Noel et al., J. Biol. Chem. 273(7):3878-3883 ( 1998). RoBo-1 is believed to play a novel role in the growth or remodeling of bone. Proteins also of interest include those having sequence identity with phospholipase inhibitors.
We herein describe the identification and characterization of novel polypeptides having homology to urokinase plasminogen activator receptors and phospholipase inhibitors, designated herein as PRO511 polypeptides.
92. PR01104 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01104 polypeptides.
93. PRO1100 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PRO1100 polypeptides.
94. P_R0836 Of interest are lamina) proteins, or proteins specific to the endoplasmic reticultttn (ER). Of particular interest are proteins having sequence identity with known proteins. Known proteins include proteins such as SLS1. In Saccharomyces cerevisiae, SLS1 has been reported to be a mitochondria) integral membrane protein involved in mitochondria) metabolism. Rouillard, et al., Mol. Gen. Genet., 252(6):700-708 (1996). In yeast Yarrowia lipolytica, it has been reported that the SLS1 gene product (SLSIp) behaves as a lumenal protein of the ER. It is believed that SPSlp acts in the preprotein translocation process, interacting directly with translocating polypeptides to facilitate their transfer and/or help their folding in the ER. Bosirame, et al., J.
Biol. Chem., 271(20):11668-11675 (1996).
We herein describe the identification and characterization of novel polypeptides having homology to SLSl, designated herein as PR0836 polypeptides.
95. PR01141 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01141 polypeptides.
96. PR01132 Proteases are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized, including the serine proteases which exhibit specific activity toward various serine-containing proteins. The mammalian protease enzymes play important roles in biological processes such as, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes.
Neuropsin is a novel serine protease whose mRNA is expressed in the central nervous system. Mouse neuropsin has been cloned, and studies have shown that it is involved in the hippocampal plasticity. Neuropsin has also been indicated as associated with extracellular matrix modifications and cell migrations. See, generally, Chen, et al., Neurosci., 7(2):5088-5097 (1995) and Chen, et al., J. Histochem.
Cvtochem., 46:313-320 (1998).
Another serine protease of interest is the enamel matrix serine proteinase.
The maturation of dental enamel succeeds the degradation of organic matrix. Inhibition studies have shown that this degradation is accomplished by a serine-type proteinase. Proteases associated with enamel maturation are described in, i.e., Simmer, et al., 1. Dent. Res., 77(2):377-386 (1998), Overall and Limeback, Biochem J., 256(3):965-972 (1988), and Moradian-Oldak, Connect. Tissue Res., 35(1-4):231-238 (1996).
We herein describe the identification and characterization of novel poiypeptides having homology to serine proteases, designated herein as PR01132 polypeptides.
97. PR01346 The abbreviations "TIE° or "tie" are acronyms, which stand for "tyrosine kinase containing Ig and EGF homology domains" and were coined to designate a new family of receptor tyrosine kinases which are almost exclusively expressed in vascular endothelial cells and early hemopoietic cells, and are characterized by the presence of an EGF-like domain, and extracellular folding units stabilized by intra-chain disulfide bonds, generally referred to as "immunoglobulin (IG)-like" folds. A tyrosine kinase homologous cDNA fragment from htunan leukemia cells (tie) was described by Partanen et al., Proc. Natl.
Acad. Sci. USA 87, 8913-8917 (1990).
The mRNA of this human "TIE" receptor has been detected in all human fetal and mouse embryonic tissues, and has been reported to be localized in the cardiac and vascular endothelial cells. Korhonen et al., Bl~od 80, 2548-2555 (1992); PCT Application Publication No. WO 93/14124 (published 22 July 1993). The rat homolog of human TIE, referred to as "TIE-1", was identified by Maisonpierre et al., Oncoeene 8_, 1631-1637 (1993)).
Another TIE receptor, designated "TIE-2" was originally identified in rats (Dumont et al. , Onco ene 8_, 1293-1301 (1993)), while the human homolog of TIE-2, referred to as "ork" was described in U.S. Patent No.
5,447,860 (Ziegler). The marine homolog of TIE-2 was originally termed "tek. "
The cloning of a mouse TIE-2 receptor from a brain capillary cDNA library is disclosed in PCT Application Publication No. WO 95/13387 (published 18 May 1995). TIE-2 is a receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Tie-2 knockout mice die by defects in the formation of microvassels. Accordingly, the TIE
receptors are believed to be actively involved in angiogenesis, and may play a role in hemopoiesis as well.
Indeed, recent results (Lin et al., J. Clin. Invest. 100(8), 2072-2078 [1997J) demonstrating the ability of a soluble TIE-2 receptor to inhibit tumor angiogenesis have been interpreted to indicate that TIE-2 plays a role in pathologic vascular growth. In another study, TIE-2 expression was examined in adult tissues undergoing angiogenesis and in quiescent tissues. TIE2 expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation and uterine development and in healing wounds. TIE-2 was also reported to be expressed in the entire spectrum of the quiescent vasculature (arteries, veins, and capillaries) in a wide range of adult tissues.
Wong et al., Circ. Res. 81(4), 567-574 (1997). It has been suggested that TIE-2 has a dual function in adult angiogenesis and vascular maintenance.
The expression cloning of human TIE-2 ligands has been described in PCT
Application Publication No.
WO 96/11269 (published 18 April 1996) and in U.S. Patent No. 5,521,073 (published 28 May 1996). A vector designated as ~.gt 10 encoding a TIE-2 ligand NL7d "htie-2 ligand I " or "hTL
1 " has been deposited under ATCC
Accession No. 75928. A plasmid encoding another TIE-2 ligand designated "htie-2 2" or "hTL2" is available under ATCC Accession No. 75928. This second ligand has been described as an antagonist of the TAI-2 receptor. The identification of secreted human and mouse ligands for the TIE-2 receptor has been reported by Davis et al., Cell 87, 1161-1169 (1996). The human ligand designated "Angiopoietin-1", to reflect its role in angiogenesis and potential action during hemopoiesis, is the same ligand as the ligand variously designated as "htie-2 1 " or "hTL-1 " in WO 96/ 11269. Angiopoietin-1 has been described to play an angiogenic role later and distinct from that of VEGF (Sari et al., Cell 87, 1171-1180 (1996)). Since TIE-2 is apparently upregulated during the pathologic .angiogenesis requisite for tumor growth (Kaipainen et al., Cancer Res. 54, 6571-6577 (1994)) angiopoietin-1 has been suggested to be additionally useful for specifically targeting tumor vasculature (Davis et al., su ra .
We herein describe the identification and characterization of novel TIE ligand polypeptides, designated herein as PR01346 polypeptides.
98. PR01131 The low density lipoprotein (LDL) receptor is a membrane-bound protein that plays a key role in cholesterol homeostasis, mediating cellular uptake of lipoprotein particles by high affinity binding to its ligands, apolipoprotein (apo) B-100 and apoE. The ligand-binding domain of the LDL
receptor contains 7 cysteine-rich repeats of approximately 40 amino acids, wherein each repeat contains 6 cysteines, which form 3 infra-repeat disulfide bonds. These unique structural features provide the LDL receptor with its ability to specifically interact with apo B-100 and apoE, thereby allowing for transport of these lipoprotein particles across cellular membranes and metabolism of their components. Soluble fragments containing the extracellular domain of the LDL receptor have been shown to retain the ability to interact with its specific lipoprotein ligands (Simmons et al., J. Biol.
Chem. 272:25531-25536 (1997)). LDL receptors are further described in Javitt, FASEB J., 9(13):1378-1381 (1995), van Berkel, et al., Atherosclerosis, 118 Supp1:S43-S50 (1995) and Herz and Willnow, Ann. NY Acad.
Sci., 737:14-19 (1994). Thus, proteins having sequence identity with LDL
receptors are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to LDL receptors, designated herein as PR01131 polypeptides.
99. PR01281 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01281 polypeptides.
100. PR01064 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel membrane-bound proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01064 polypeptides.
101. PR01379 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01379 polypeptides.
102. PR0844 Proteases are enzymatic proteins which are involved in a large number of very important biological processes in mammalian and non-mammalian organisms. Numerous different protease enzymes from a variety of different mammalian and non-mammalian organisms have been both identified and characterized. The mammalian protease enrymes play important roles in many different biological processes including, for example, protein digestion, activation, inactivation, or modulation of peptide hormone activity, and alteration of the physical properties of proteins and enzymes. Thus, proteases are of interest.
Also of interest are protease inhibitors.
Of particular interest are serine proteases. In one study it was reported that when the serine protease inhibitor antileukoproteinase (aLP) is injected, it accumulates in articular and extraarticular cartilage of normal rats. This physiological pathway of cartilage accumulation, lost in proteoglycan depleted arthritic cartilage is believed to serve to maintain the local balance between proteinase function and inhibition. Burkhardt, et al., J.
Rheumatol, 24(6):1145-1154 (1997). Moreover, aLP and other protease inhibitors have been reported to play a role in the in vitro growth of hematopoietc cells by the neutralization of proteinases produced by bone marrow accessory cells. Gosklink, et al., J. Exp. Med., 184(4):1305-1312 (1996). Also of interest are mutants of aLP.
Oxidation resistant mutants of aLPe have been reported to have significant therapeutic effects on animal models having emphysema. Steffens, et al., Agents Actions Sup~l., 42:111-121 (1993).
Thus, serine protease inhibitors are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to serine protease inhibitors, designated herein as PR0844 polypeptides.
103. PR0848 Membrane-bound proteins of interest include channels such as ion channels.
Furthermore, membrane-bound proteins of interest include enzymes bound to intracellular vacuoles or organelles, such as transferases.
For example, a peptide of interest is the GaINAc alpha 2, 6-sailytransferase as described in Kurosawa, et al., J. Biol. Chem., 269(2):1402-1409 (I994). This peptide was constructed to be secreted, and retained its catalytic activity. The expressed enzyme exhibited activity toward asialomucin and asialofetuin, but not other glycoproteins tested. As sialylation is an important function, sialyltransferases such as this one, and peptides related by sequence identity, are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to sialyltransferases, designated herein as PR0848 polypeptides.
104. PR01097 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01097 polypeptides.
105. PR01153 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01153 polypeptides.
106. PR01154 Aminopeptidase N causes enzymatic degradation of perorally administered peptide drugs. Thus, aminopeptidase N has been used in studies to develop and identify inhibitors so as to increase the efficacy of peptide drugs by inhibiting their degradation. Aminopeptidases are also generally of interest to use to degrade peptides. Aminopeptidases, particularly novel aminopeptidases are therefore of interest. Aminopeptidase N and inhibitors thereof are further described in Bernkop-Schnurch and Marschutz, Pharm. Res., 14(2):181-185 ((1997); Lerche, et al., Mamm. Genome, 7(9):712-713 (1996); Papapetropoulos, et al., I_mmunopharmacolog~
32(1-3):153-156 (1996); Miyachi, et al., J. Med. Chem., 41(3):263-265 (1998);
and Olsen, et al., Adv. Exn.
Med. Biol., 421:47-57 (1997).
We herein describe the identification and characterization of novel polypeptides having homology to aminopeptidase N, designated herein as PR01154 polypeptides.
107. PR01181 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01181 polypeptides.
108. PR01182 Conglutinin is a bovine serum protein that was originally described as a vertebrate lectin protein and which belongs to the family of C-type lectins that have four characteristic domains, (1) an N-terminal cysteine-rich domain, (2) a collagen-like domain, (3) a neck domain and (4) a carbohydrate recognition domain (CRD).
Recent reports have demonstrated that bovine conglutinin can inhibit hemagglutination by influenza A viruses as a result of their lectin properties (Eda et al., Biochem. J. 316:43-48 (1996)). It has also been suggested that lectins such as conglutinin can function as immunoglobulin-independent defense molecules due to complement-mediated mechanisms. Thus, conglutinin has been shown to be useful for purifying immune complexes in vitro and for removing circulating immune complexes from patients plasma in vivo (Lim et al., Biochem. Bio_phvs.
Res. Commun. 218:260-266 (1996)). We herein describe the identification and characterization of novel polypeptides having homology to conglutinin protein, designated herein as PR01182 polypeptides.
109. PR 1155 Substance P and the related proteins, neurokinin A and neurokinin B have been reported as compounds which elicit contraction of the ileum both directly through action on a muscle cell receptor and indirectly through stimulation of a neuronal receptor. This action leads to the release of acetylcholine which causes muscle contraction via muscarinic receptors. It has also been reported that neurokinin B was found to be the most potent agonist for the neuronal Substance P receptor and that neurokinin B can be inhibited by enkephalinamide.
Laufer, et al., PNAS USA, 82(21):74444-7448 (1985). Moreover, neurokinin B has been reported to provide neuroprotection and cognitive enhancement, and therefore believed to be useful for the treatment of neurodegenerative disorders, including alzheimers disease. Wenk, et al., Behav. Brain Res., 83(1-2):129-133 (1997). Tachykinins are also described in Chawla, et al., J. Comp. Neurol., 384(3):429-442 (1997). Thus, tachykinins, particularly those related to neurokittiii B are of interest.
We herein describe the identification and characterization of novel polypeptides having homology to neurokinin B protein, designated herein as PRO1155 polypeptides.
110. PR01156 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01181 polypeptides.
111. PR01098 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01098 polypeptides.
112. PR01127 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01127 polypeptides.
113. PR01126 The extracellular mucous matrix of olfactory neuroepithelium is a highly organized structure in intimate contact with chemosensory cilia that house the olfactory transduction machinery. The major protein component of this extracellular matrix is olfactomedin, a glycoprotein that is expressed in olfactory neuroepithelium and which form intermolecular disulfide bonds so as to produce a polymer (Yokoe et al. , Proc. Natl. Acad. Sci. USA
90:4655-4659 (1993), Bal et al., Biochemistry 32:1047-1053 (1993) and Snyder et al., Biochemistry 30:9143-9153 (1991)). It has been suggested that olfactomedin may influence the maintenance, growth or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. Given this important role, there is significant interest in identifying and characterizing novel polypeptides having homology to olfactomedin. We herein describe the identification and characterization of novel polypeptides having homology to olfactomedin protein, designated herein as PR01126 polypeptides.
114. PR 1125 Of particular interest are proteins which have multiple Trp-Asp (WD) repeats.
WD proteins are made up of highly conserved repeating units usually ending with WD. They are found in eukaryotes but not in prokaryotes. They regulate cellular functions, such as cell division, cell-fate determination, gene transcription, gene transcription, transmembrane signaling, mRNA modification and vesicle fusion. WD are further described in Neer, et al., Nature, 371(6495):297-300 (1994); Jiang and Struhl, Nature, 391(6666):493-496(1998); and DeSilva, et al., Genetics, 148(2):657-667(1998). Thus, new members of this superfamily are all of interest.
115. PR01186 Protein A from Dendroaspis polylepis polylepis (black mamba) venom comprises 81 amino acids, including ten half-cystine residues. Venoms are of interest on the one hand as weapons in war, and on the other hand, to use in assays to determine agents which reverse or inhibit the effects of the venom or a similar poison.
Black mamba venom is further described in Int. J. Biochem., 17(6):695-699 (1985) and Joubert and Strydom, Hoppe Seylers Z Physiol. Chem., 361(12):1787-1794 (1980).
We herein describe the identification and characterization of novel polypeptides having homology to snake venom protein A, designated herein as PR01186 polypeptides.
116. PR01198 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01198 polypeptides.
117. PR01158 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01158 polypeptides.
118. PR01159 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01159 polypeptides.
119. PR01124 Ion channels are considered to be the gateway to the final frontier, the brain. Ion channels and the receptors which control these channels are responsible for the passage of ions, or nerve impulses to be communicated from cell to cell, thus, ion channels are responsible for communication. In addition to their critical role in the brain, ion channels play a critical role in the heart as well as blood pressure. lon channels have also been linked to other important bodily functions and conditions, as well as disorders, such as cystic fibrosis. For all of these reasons, ion channels, such as sodium, potassium and chloride channels, as well as all of their related proteins and receptors are of interest. For example, it has been reported that cystic fibrosis results from a defect in the chloride channel protein, cystic fibrosis transmembrane conductance regulator.
McGill, et al., D1E. Dis. Sci., 41(3):540-542 (1996). Chloride channels are further described in at least Finn, et al., PNAS USA, 90(12):5691-569 (1993) and Finn, et al., Mol. Cell Biochem., 114(1-2):2F-26 (1992).
Also of interest are molecules related to adhesion molecules, as adhesion molecules are known to be involved in cell-cell signaling and interactions. More generally, all novel membrane bound-proteins are of interest. Membrane-bound proteins and receptors can play an important role in the formation, differentiation and maintenance of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides (for instance, mitogenic factors, survival factors, cytotoxic factors, differentiationfactors, neuropeptides, and hormones) which are, in turn, received and interpreted by diverse cell receptors or membrane-bound proteins. Such membrane-bound proteins and cell receptors include, but are not limited to, cytokine receptors, receptor kinases, receptor phosphatases, receptors involved in cell-cell interactions, channels, transporters, and cellular adhesin molecules like selectins and integrins. For instance, transduction of signals that regulate cell growth and differentiation is regulated in part by phosphorylation of various cellular proteins. Protein tyrosine kinases, enzymes that catalyze that process, can also act as growth factor receptors. Examples include fibroblast growth factor receptor and nerve growth factor receptor.
Membrane-bound proteins include those which are bound to the outer membrane and intracellular membranes and organelles. Membrane-bound proteins and receptor molecules have various industrial applications, including as pharmaceutical and diagnostic agents. Receptor immunoadhesins, for instance, can be employed as therapeutic agents to block receptor-ligand interaction. The membrane-bound proteins can also be employed for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction.
Efforts are being undertaken by both industry and academia to identify new, native receptor proteins.
Many efforts are focused on the screening of mammalian recombinant DNA
libraries to identify the coding sequences for novel receptor proteins. Herein is presented a polypeptide and nucleic acid encoding therefor which has sequence identity with a chloride channel protein chloride channei protein and lung-endothelial cell adhesion molecule-1 (SCAM-1).
120. PR01287 Fringe is a protein which specifically blocks serrate-mediated activation of notch in the dorsal comparunent of the Drosophila wing imaginal disc. Fleming et al., Development.
124(15):2973-81 (1997).
Therefore, fringe protein is of interest for both its role in development as well as its ability to regulate senate, particularly serrate's signaling abilities. Also of interest are novel polypeptides which may have a rote in development and/or the regulation of serrate-like molecules. Of particular interest are novel polypeptides having homology to fringe.
We herein describe the identification and characterization of novel polypeptides having homology to fringe protein, designated herein as PR01287 polypeptides.
121. PR01312 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01312 polypeptides.
122. PR01192 Membrane-bound proteins of myelin are of interest because of their possible implications in various nervous system disorders associated with improper myelination. Myelin is a cellular sheath, formed by glial cells, that surrounds axons and axonal processes that enhances various electrochemical properties and provides trophic support to the neuron. Myelin is formed by Schwann cells in the peripheral nervous system (PNS) and by oligodendrocytes in the central nervous system (CNS). Improper myelination of central and peripheral neurons occurs in a number of pathologies and leads to improper signal conduction within the nervous systems.
Among the various demyelinating diseases Multiple Sclerosis is the most notable.
The predominant integral membrane protein of the CNS myelin of amphibians, reptiles, birds and mammals are proteolipid protein (PLP) and P0, the main glycoprotein in PNS
myelin. (Schlieess and Stoffel, Biol. Chem. Hogoe Seyler (1991) 372(9):865-874). In view of the importance of membrane-bound proteins of the myelin, efforts are being undertaken by both industry and academia to identify and characterize various myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995) 64(6):2427-2436).
123. PR01160 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01160 polypeptides.
124. PR 1187 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01187 polypeptides.
125. PR01185 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01185 polypeptides.
126. PR0345 Human tetranectin is a 202 amino acid protein encoded by a gene spanning approximately 12 kbp of DNA (Berglund et al., FEBS L,ett. 309:15-19 (1992)). Tetranectin has been shown to be expressed in a variety of tissues and functions primarily as a plasminogen binding protein.
Tetranectin has been classified in a distinct group of the C-type lectin superfamily but has structural and possibly functional similarity to the collectin proteins (Nielsen et al., FEBS Ixtt. 412(2):388-396 (1997)). Recent studies have retorted that variability in serum tetranectin levels may be predictive of the presence of various types of cancers including, for example, ovarian and colorectal cancers (Hogdall et al., Acta Oncol. 35:63-69 ( 1996), Hogdall et al., Eur. J. Cancer 31A(6):888-894 (1995) and Tuxen et al., Cancer Treat. Rev. 21(3):215-245 (1995)). As such, there is significant interest in identifying and characterizing novel polypeptides having structural and functional similarity to the teuanectin protein.
We herein describe the identification and characterization of novel polypeptides having homology to tetranectin protein, designated herein as PR01345 polypeptides.
127. PR01245 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01245 polypeptides.
128. PR0358 Serine protease inhibitors are of interest because they inhibit catabolism and are sometimes associated with regeneration of tissue. For example, a gene encoding a plasma protein associated with liver regeneration has been cloned and termed regeneration-associated serpin-1 (RASP-1). New, et al., Biochem. Biophys. Res.
Commun., 223(2):404-412 (1996). While serine protease inhibitors are of interest, particularly of interest are those which have sequence identity with known serine protease inhibitors such as RASP-1.
We herein describe the identification and characterization of novel polypeptides having homology to RASP-1, designated herein as PR01245 polypeptides.
129. PR01195 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01195 polypeptides.
130. PR01270 The recognition of carbohydrates by lectins has been found to play an important role in various aspects of eukaryotic physiology. A number of different animal and plant lectin families exist, but it is the calcium dependent, or type C, lectins that have recently garnered the most attention.
For example, the recognition of carbohydrate residues on either endothelial cells or leukocytes by the selectin family of calcium dependent lectins has been found to be of profound importance to the trafficking of leukocytes to inflammatory sites. Lanky, L., Ann. Rev. Biochem.. 64 113-139 ( 1995). The biophysical analysis of these adhesive interactions has suggested that lectin-carbohydrate binding evolved in this case to allow for the adhesion between leukocytes and the endothelium under the high shear conditions of the vasculature. Thus, the rapid on rates of carbohydrate recognition by such lectins allows for a hasty acquisition of ligand, a necessity under the high shear of the vascular flow. The physiological use of type C lectins in this case is also supported by the relatively low affinities of these interactions, a requirement for the leukocyte rolling phenomenon that has been observed to occur at sites of acute inflammation. The crystal structures of the mannose binding protein (Weis et al., Science 254, 1608-1615 [1991]; Weis et al., Nature 360 127-134 [1992]) and E-selectin (Graves et al., Nature 367(6463), 532-538 [1994]), together with various mutagenesis analyses (Erbe et al., J. Cell.
Biol. 119(1), 215-227 [1992];
Drickamer, Nature 360, 183-186 [1992]; Iobst et al., J. Biol. Chem. 169(22), 15505-15511 [1994]; Kogan et al., J. Biol. Chem. 270(23), 14047-14055 [1995]), is consistent with the supposition that the type C lectins are, in general, involved with the rapid recognition of clustered carbohydrates.
Together, these data suggest that type C lectins perform a number of critical physiological phenomena through the rapid, relatively low affinity recognition of carbohydrates.
Given the obvious importance of the lectin proteins in numerous biological processes, efforts are currently being made to identify novel lectin proteins or proteins having sequence homology to lectin proteins.
We herein describe the identification and characterization of novel polypeptides having homology to a lectin protein, designated herein as PR01270 polypeptides.
131. PR01271 Efforts are being undertaken by both industry and academia to identify new, native membrane-bound proteins. Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel transmembrane proteins. We herein describe the identification and characterization of novel transmembrane polypeptides, designated herein as PR01271 polypeptides.
132. PR01375 The proteins L1CAM, G6PD and P55 are each associated with various known disease states. Thus, the genomic loci of Fugu rubripes homologs of the human disease genes Ll CAM, G6PD and P55 were analyzed.
This analysis led to the the identification of putative protein 2 (PUT2), GENBANK locus AF026198, accession AF026198. (See GENBANK submission data). Thus, PUT2 and proteins which have sequence identity with PUT2, are of interest.
133. PR01385 Efforts are being undertaken by both industry and academia to identify new, native secreted proteins.
Many of these efforts are focused on the screening of mammalian recombinant DNA libraries to identify the coding sequences for novel secreted proteins. We herein describe the identification and characterization of novel secreted polypeptides, designated herein as PR01385 polypeptides.
134. PR01387 Membrane-bound proteins of myelin are of interest because of their possible implications in various nervous system disorders associated with improper myelination. Myelin is a cellular sheath, formed by glial cells, that surrounds axons and axonal processes that enhances various electrochemical properties and provides trophic support to the neuron. Myelin is formed by Schwann cells in the peripheral nervous system (PNS) and by oligodendrocytes in the central nervous system (CNS). Improper myelination of central and peripheral neurons occurs in a number of pathologies and leads to improper signal conduction within the nervous systems.
Among the various demyelinating diseases Multiple Sclerosis is the most notable.
The predominant integral membrane protein of the CNS myelin of amphibians, reptiles, birds and mammals are proteolipid protein (PLP) and P0, the main glycoprotein in PNS
myelin. (Schlieess and Stoffel, Biol. Chem. Hoppe Seyler (1991) 372!9):865-874). In view of the importance of membrane-bound proteins of the myelin, efforts are being undertaken by both industry and academia to identify and characterize various myelin proteins (see Stratmann and Jeserich, J. Neurochem (1995) 64(6):2427-2436).
We herein describe the identification and characterization of novel polypeptides having homology to myelin protein, designated herein as PR01387 poIypeptides.
135. PR01384 One class of receptor proteins that has been of interest is the NKG2 family of type II transmembrane molecules that are expressed in natural killer cells. These proteins, which have been shown to be covalently associated with CD94, are involved in natural killer cell-mediated recognition of different HLA-allotypes (Plougastel, B. et al., Eur. J. Immunol. (1997) 27(11):2835-2839), and interact with major histocompatibility complex (MHC) class I to either inhibit or activate functional activity (Ho, EL. et al., Proc. Natl. Acad. Sci.
(1998) 95111):6320-6325). Accordingly, the identification and characterization of new members of this family of receptor proteins is of interest (see Houchins JP, et al. J. Exp. Med.
(1991) 173(4):1017-1020).
SUMMARY OF THE INVENTION
1. PR 281 A cDNA clone (DNA16422-1209) has been identified, having homology to nucleic acid encoding testis enhanced gene transcript (TEGT) protein that encodes a novel polypeptide, designated in the present application as "PR0281".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0281 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0281 polypeptide having the sequence of amino acid residues from about 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID
N0:2), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0281 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 80 or about 122 and about 1114, inclusive, of Figure 1 (SEQ ID NO:1). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209929 (DNA16422-1209) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209929 (DNA16422-1209).
In still a farther aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about IS to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0281 polypeptide having the sequence of amino acid residues from 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85%a sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0281 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 14 in the sequence of Figure 2 (SEQ ID
N0:2). The multiple transmembrane domains have been tentatively identified as extending from about amino acid position 83 to about amino acid position 105, from about amino acid position 126 to about amino acid position 146, from about amino acid position 158 to about amino acid position 177, from about amino acid position 197 to about amino acid position 216, from about amino acid position 218 to about amino acid position 238, from about amino acid position 245 to about amino acid position 265, and from about amino acid position 271 to about amino acid position 290 in the PR0281 amino acid sequence (Figure 2, SEQ ID N0:2).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0281 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 1 (SEQ ID NO:1 ).
In another embodiment, the invention provides isolated PR0281 poiypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0281 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 15 to about 345 of Figure 2 (SEQ ID N0:2).
In another aspect, the invention concerns an isolated PR0281 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2).
In a further aspect, the invention concerns an isolated PR0281 polypeptide, comprising an amino acid sequence scoring at least about 8090 positives, preferably at least about 85%
positives, more preferably at least about 90°~ positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues I or about 15 to about 345, inclusive of Figure 2 (SEQ ID N0:2).
In yet another aspect, the invention concerns an isolated PR0281 polypeptide, comprising the sequence of amino acid residues 1 or about 15 to about 345, inclusive of Figure 2 (SEQ
ID N0:2), or a fragment thereof sufficient to provide a binding site for an anti-PR0281 antibody. Preferably, the PR0281 fragment retains a qualitative biological activity of a native PR0281 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0281 polypeptide having the sequence of amino acid residues from about I or about IS to about 345, inclusive of Figure 2 (SEQ ID N0:2), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0281 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0281 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0281 polypeptide by contacting the native PR0281 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
in a still further embodiment, the invention concerns a composition comprising a PR0281 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
Z. PR0276 A cDNA clone (DNA16435-1208) has been identified that encodes a novel polypeptide having two transmembrane domains and designated in the present application as "PR0276."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0276 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0276 polypeptide having the sequence of amino acid residues from about I to about 251, inclusive of Figure 4 (SEQ ID N0:6), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0276 pvlypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 180 and about 932, inclusive, of Figure 3 (SEQ ID NO:S). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209930 (DNA16435-1208), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209930 (DNA16435-1208).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at Least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 251, inclusive of Figure 4 (SEQ ID N0:6), or the complement of the DNA of (a).
$ In a further aspect, the invention concerns an isolated nucleic acid molecule having at Least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0276 polypeptide having the sequence of amino acid residues from about 1 to about 251, inclusive of Figure 4 (SEQ ID
N0:6), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0276 polypeptide in its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains are at about amino acds 98-116 and 152-172.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about Z51, inclusive of Figure 4 (SEQ ID
N0:6), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0276 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0276 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0276 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 251 of Figure 4 (SEQ ID N0:6).
In another aspect, the invention concerns an isolated PR0276 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 251, inclusive of Figure 4 (SEQ ID
N0:6).
In a further aspect, the invention concerns an isolated PR0276 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at Least 3$ about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 251 of Figure 4 (SEQ ID N0:6).
In yet another aspect, the invention concerns an isolated PR0276 polypeptide, comprising the sequence of amino acid residues 1 to about 251, inclusive of Figure 4 (SEQ ID N0:6), or a fragment thereof sufficient to provide a binding site for an anti-PR0276 antibody. Preferably, the PR0276 fragment retains a qualitative biological activity of a native PR0276 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0276 polypeptide having the sequence of amino acid residues from about 1 to about 251, inclusive of Figure 4 (SEQ ID N0:6), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80~ sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0276 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0276 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0276 polypeptide, by contacting the native PR0276 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0276 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
3. PR0189 A cDNA clone (DNA21624-1391) has been identified that encodes a novel polypeptide, designated in the present application as "PR0189". PR0189 polypeptides have a cytosolic fatty-acid binding domain.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0189 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 h sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0189 polypeptide having the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0189 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 200 and about 1300, inclusive, of Figure 5 (SEQ ID N0:7). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80°h sequence identity, preferably at least about 85%
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209917 (DNA21624-1391), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209917 (DNA21624-1391).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0189 polypeptide having the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 367, inclusive of Figure 6 (SEQ ID
N0:8), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0189 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0189 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 367 of Figure 6 (SEQ ID N0:8).
In another aspect, the invention concerns an isolated PR0189 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 367, inclusive of Figure 6 (SEQ ID
N0:8).
In a further aspect, the invention concerns an isolated PR0189 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 %a positives when compared with the amino acid sequence of residues 1 through 367 of Figure 6 (SEQ ID N0:8).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0189 polypeptide having the sequence of amino acid residues from about 1 to about 367, inclusive of Figure 6 (SEQ ID N0:8), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0189 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0189 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a S native PR0189 polypeptide, by contacting the native PR0189 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0189 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
4. PR0190 Applicants have identified a cDNA clone that encodes a novel polypeptide having seven transmembrane domains and having sequence identity with CMP-sialic acid and UDP-galactose transporters, wherein the polypeptide is designated in the present application as "PR0190".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0190 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0190 polypeptide having amino acid residues 1 through 424 of Figure 9 (SEQ ID
N0:14), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA23334-1392 which includes the nucleotide sequence encoding PR0190.
In another embodiment, the invention provides isolated PR0190 polypeptide. In particular, the invention provides isolated native sequence PR0190 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 424 of Figure 9 (SEQ ID N0:14). An additional embodiment of the present invention is directed to an isolated PR0190 polypeptide, excluding the transmembrane domains.
Optionally, the PR0190 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA23334-1392.
In another embodiment, the invention provides an expressed sequence tag (EST) comprising the nucleotide sequence of SEQ ID NO:15.
5. PR0341 A cDNA clone (DNA26288-1239) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR0341".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0341 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0341 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID
N0:20), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0341 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 380 or about 431 and about 1753, inclusive, of Figure 11 (SEQ ID N0:19).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209792 (DNA26288-1239) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209792 (DNA26288-1239).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues i or about 18 to about 458, inclusive of Figure 12 (SEQ ID
N0:20), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 165 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0341 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID NO:ZO), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0341 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 12 (SEQ
ID N0:20). The transmembrane domains have been tentatively identified as extending from about amino acid position 171 to about amino acid position 190, from about amino acid position 220 to about amino acid position 239, from about amino acid position 259 to about amino acid position 275, from about amino acid position 286 to about amino acid position 305, from about amino acid position 316 to about amino acid position 335, from about amino acid position 353 to about amino acid position 378 and from about amino acid position 396 to about amino acid position 417 in the PR0341 amino acid sequence (Figure 12, SEQ ID N0:20).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about I8 to about 458, inclusive of Figure 12 (SEQ ID N0:20), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0341 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 11 (SEQ ID N0:19).
In another embodiment, the invention provides isolated PR0341 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
IO In a specific aspect, the invention provides isolated native sequence PR0341 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 458 of Figure 12 (SEQ ID N0:20).
In another aspect, the invention concerns an isolated PR0341 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID N0:20).
In a further aspect, the invention concerns an isolated PR0341 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 18 to about 458, inclusive of Figure I2 (SEQ ID N0:20).
In yet another aspect, the invention concerns an isolated PR0341 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 458, inclusive of Figure 12 (SEQ
ID N0:20), or a fragment thereof sufficient to provide a binding site for an anti-PR0341 antibody.
Preferably, the PR0341 fragment retains a qualitative biological activity of a native PR0341 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0341 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 458, inclusive of Figure 12 (SEQ ID N0:20), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA12920 comprising the nucleotide sequence of SEQ ID N0:21 (see Figure 13).
6. PR0180 A cDNA clone (DNA26843-1389) has been identified that encodes a novel polypeptide having multiple transmembrane domains designated in the present application as "PR0180".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0180 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 180 polypeptide having the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID N0:23), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0180 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 121 and about 918, inclusive, of Figure 14 (SEQ ID N0:22). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at ~ least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203099 (DNA26843-1389), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203099 (DNA26843-1389).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0180 polypeptide having the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO180 polypeptide in its soluble form, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains are shown in Figure 15.
It is believed that PR0180 has a type II transmembrane domain from about amino acids 13-33 of SEQ ID
N0:23.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0180 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0180 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
1n a specific aspect, the invention provides isolated native sequence PRO 180 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues i through 266 of Figure 15 (SEQ ID N0:23).
In another aspect, the invention concerns an isolated PR0180 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 266, inclusive of Figure 15 (SEQ ID
N0:23).
In a further aspect, the invention concerns an isolated PR0180 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 266 of Figure 15 (SEQ ID N0:23).
In yet another aspect, the invention concerns an isolated PRO 180 polypeptide, comprising the sequence of amino acid residues 1 to about 266, inclusive of Figure 15 (SEQ ID N0:23), or a fragment thereof sufficient to provide a binding site for an anti-PR0180 antibody. Preferably, the PR0180 fragment retains a qualitative biological activity of a native PR0180 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0180 polypeptide having the sequence of amino acid residues from about 1 to about 266, inclusive of Figure 15 (SEQ ID N0:23), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0180 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0180 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0180 polypeptide, by contacting the native PR0180 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0180 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) (DNA12922) comprising the nucleotide sequence of Figure 16 (SEQ ID N0:24).
7. PR0194 Applicants have identified a cDNA clone that encodes a novel transmembrane polypeptide, wherein the polypeptide is designated in the present application as "PR0194".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0194 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0194 polypeptide having amino acid residues 1 to 264 of Figure 18 (SEQ ID N0:28), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0194 polypeptide having amino acid residues about 18 to 264 of Figure 18 (SEQ ID
N0:28) or amino acid 1 or about 18 to X of Figure 18 (SEQ ID N0:28), where X is any amino acid from 96 to 105 of Figure 18 (SEQ ID
N0:28), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA26844-1394 vector deposited on June 2, 1998 as ATCC 209926 which includes the nucleotide sequence encoding PR0194.
In another embodiment, the invention provides isolated PR0194 polypeptide. In particular, the invention provides isolated native sequence PR0194 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 264 of Figure I8 (SEQ ID N0:28).
Additional embodiments of the present invention are directed to PR0194 polypeptides comprising amino acids about 18 to 264 of Figure 18 (SEQ ID N0:28) or amino acid 1 or about 18 to X of Figure 18 (SEQ ID N0:28), where X is any amino acid from 96 to 105 of Figure 18 (SEQ ID N0:28). Optionally, the PR0194 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA26844-1394 vector deposited on June 2, 1998 as ATCC 209926.
8. PR0203 Applicants have identified a cDNA clone that encodes a novel polypeptide having sequence identity to glutathione-S-transferase, wherein the polypeptide is designated in the present application as "PR0203".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0203 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0203 polypeptide having amino acid residues 1 to 347 of Figure 20 (SEQ ID N0:30), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0203 polypeptide having amino acid residues X to 347 of Figure 20 (SEQ ID N0:30), where X is any amino acid from 83 to 92 of Figure 20 (SEQ ID N0:30), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA30862-1396 vector deposited on June 2, 1998, as ATCC 209920 which includes the nucleotide sequence encoding PR0203.
In another embodiment, the invention provides isolated PR0203 polypeptide. In particular, the invention provides isolated native sequence PR0203 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 347 of Figure 20 (SEQ ID N0:30).
Additional embodiments of the present invention are directed to PR0203 polypeptides comprising amino acid X
to 347 of Figure 20 (SEQ ID
N0:30), where X is any amino acid from 83 to 92 of Figure 20 (SEQ ID N0:30).
Optionally, the PR0203 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA30862-1396 vector deposited on June 2, 1998, as ATCC 209920.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA15618 which comprises the nucleotide sequence of Figure 21 (SEQ ID N0:31) 9. PR0290 A cDNA clone (DNA35680-1212) has been identified which encodes a polypeptide designated in the present application as "PR0290." PR0290 polypeptides have sequence identity with NTII-l, FAN and beige.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0290 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at Least about 95 % sequence identity to (a) a DNA molecule encoding a PR0290 polypeptide having the sequence of amino acid residues from about 1 to about 1003, inclusive of Figure 23 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0290 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 293 and about 3301, inclusive, of Figure 22 (SEQ ID N0:32). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at Least about 85 ~ sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 °6 sequence identity to (a} a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209790 (DNA35680-1212), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209790 (DNA35680-1212).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 1003, inclusive of Figure 23 (SEQ ID
N0:33), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0290 polypeptide having the sequence of amino acid residues from about I to about 1003, inclusive of Figure 23 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at Ieast about 95 %
positives when compared with the amino acid sequence of residues 1 to about 1003, inclusive of Figure 23 (SEQ
ID N0:33), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0290 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0290 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 1003 of Figure 23 (SEQ ID
N0:33).
In another aspect, the invention concerns an isolated PR0290 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 1003, inclusive of Figure 23 (SEQ
ID N0:33).
In a further aspect, the invention concerns an isolated PR0290 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 1003 of Figure 23 (SEQ ID N0:33).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0290 polypeptide having the sequence of amino acid residues from about 1 to about 1003, inclusive of Figure 23 (SEQ ID N0:33), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0290 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0290 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0290 polypeptide, by contacting the native PR0290 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0290 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
10. PR0874 Applicants have identified a cDNA clone that encodes a novel multi-span transmembrane polypeptide, which is designated in the present application as "PR0874".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0874 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0874 polypeptide having amino acid residues 1 to 321 of Figure 25 (SEQ ID N0:36), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0874 polypeptide having amino acid from about X to 321 of Figure 25 (SEQ ID N0:36), where X is any amino acid from about 270 to about 279 of Figure 25 (SEQ ID N0:36), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA40621-1440 vector deposited on June 2, 1998, as ATCC 209922 which includes the nucleotide sequence encoding PR0874.
In another embodiment, the invention provides isolated PR0874 polypeptide. In particular, the invention provides isolated native sequence PR0874 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 321 of Figure 25 (SEQ ID N0:36).
Additional embodiments of the present invention are directed to PR0874 polypeptides comprising amino acids X
to 321 of Figure 25 (SEQ ID
N0:36), where X is any amino acid from about 270 to about 279 of Figure 25 (SEQ ID N0:36). Optionally, the PR0874 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA40621-1440 vector deposited on June 2, 1998, as ATCC 209922.
11. PR0710 Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to CDC45 protein, wherein the polypeptide is designated in the present application as "PR0710".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0710 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0710 polypeptide having amino acid residues 1 to 566 of Figure 27 (SEQ ID N0:41), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects> the isolated nucleic acid comprises DNA encoding the PR0710 polypeptide having amino acid residues about 33 to 566 of Figure 27 (SEQ ID
N0:41) or amino acid 1 or about 33 to X of Figure 27 (SEQ ID N0:41), where X is any amino acid from 449 to 458 of Figure 27 (SEQ ID
N0:41), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA44161-1434 vector deposited on May 27, 1998 as ATCC 209907 which SS
includes the nucleotide sequence encoding PR0710.
In another embodiment, the invention provides isolated PR0710 polypeptide. In particular, the invention provides isolated native sequence PR0710 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 566 of Figure 27 (SEQ ID N0:41).
Additional embodiments of the present invention are directed to PR0710 polypeptides comprising amino acids about 33 to 566 of Figure 27 (SEQ ID N0:41) or amino acid 1 or about 33 to X of Figure 27 (SEQ ID N0:41), where X is any amino acid from 449 to 458 of Figure 27 (SEQ ID N0:41). Optionally, the PR0710 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA44161-1434 vector deposited on May 27, 1998 as ATCC 209907.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA38190 comprising the nucleotide sequence of Figure 28 (SEQ ID N0:42).
12. PR01151 A cDNA clone (DNA44694-1500) has been identified, having homology to nucleic acid encoding Clq protein, that encodes a novel polypeptide, designated in the present application as "PRO1151".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1151 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO11 S 1 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID
N0:47), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1151 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 272 or about 332 and about 1048, inclusive, of Figure 29 (SEQ ID N0:46).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203114 (DNA44694-1500) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203114 (DNA44694-1500).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID
N0:47), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PROI 151 polypeptide having the sequence of amino acid residues from 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01151 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as e~ttending from about amino acid position 1 to about amino acid position 20 in the sequence of Figure 30 (SEQ
ID N0:47).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1151 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 29 (SEQ ID N0:46).
In another embodiment, the invention provides isolated PRO1151 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01151 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 21 to about 259 of Figure (SEQ ID N0:47).
In another aspect, the invention concerns an isolated PR01151 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 %a sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the 30 sequence of amino acid residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47).
In a further aspect, the invention concerns an isolated PR01151 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID N0:47).
In yet another aspect, the invention concerns an isolated PRO 1151 polypeptide, comprising the sequence of amino acid residues 1 or about 21 to about 259, inclusive of Figure 30 (SEQ
ID N0:47), or a fragment thereof sufficient to provide a binding site for an anti-PR01151 antibody.
Preferably, the PR01151 fragment retains a qualitative biological activity of a native PR01151 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01151 polypeptide having the sequence of amino acid residues from about 1 or about 21 to about 259, inclusive of Figure 30 (SEQ ID
N0:47), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01151 polypeptide. In a particular embodiment, the agoriist or antagonist is an anti-PR01151 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01151 polypeptide by contacting the native PR01151 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01151 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
13. PR01282 A cDNA clone (DNA45495-1550) has been identified that encodes a novel polypeptide having sequence identity with leucine rich repeat proteins and designated in the present application as "PR01282."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01282 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01282 polypeptide having the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID N0:52), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01282 polypeptide comprising DNA hyhridizing to the complement of the nucleic acid between about residues 189 and about 2138, inclusive, of Figure 31 (SEQ ID N0:51). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°h sequence identity, most preferably at least about 95%
sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203156 (DNA45495-1550), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203156 (DNA45495-1550).
WO 99/63088 PC'T/US99/12252 In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID
N0:52), or the complement of the DNA of (a).
$ In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01282 polypeptide having the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID
N0:52), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01282 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 32 (SEQ ID
N0:52). The transmembrane domain has been tentatively identified as extending from about amino acid position 579 through about amino acid position 599 in the PR01282 amino acid sequence (Figure 32, SEQ ID N0:52).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 24 to about 673, inclusive of Figure 32 (SEQ
ID N0:52), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1282 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01282 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01282 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 through 673 of Figure 32 (SEQ ID
N0:52).
In another aspect, the invention concerns an isolated PR01282 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 24 to about 673, inclusive of Figure 32 (SEQ
ID N0:52).
WO 99/(,3pgg PCT/US99/12252 In a further aspect, the invention concerns an isolated PR01282 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 °h positives, most preferably at least about 95 k positives when compared with the amino acid sequence of residues 24 through 673 of Figure 32 (SEQ ID N0:52).
In yet another aspect, the invention concerns an isolated PR01282 polypeptide, comprising the sequence of amino acid residues 24 to about 673, inclusive of Figure 32 (SEQ ID N0:52), or a fragment thereof sufficient to provide a binding site for an anti-PR01282 antibody. Preferably, the PRO
1282 fragment retains a qualitative biological activity of a native PR01282 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01282 polypeptide having the sequence of amino acid residues from about 24 to about 673, inclusive of Figure 32 (SEQ ID N0:52), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 °h sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01282 polypeptide. In a particular embodiment, the agortist or antagonist is an anti-PR01282 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01282 polypeptide, by contacting the native PR01282 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1282 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
14. PR0358 Applicants have identified a novel cDNA clone that encodes novel human Toll polypeptides, designated in the present application as PR0358.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising a DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0358 polypeptide having amino acids 20 to 575 of Figure 34 (SEQ
ID N0:57), or (b) the complement of the DNA molecule of (a). The complementary DNA molecule preferably remains stably bound to such encoding nucleic acid sequence under at least moderate, and optionally, under high stringency conditions.
In a further embodiment, the isolated nucleic acid molecule comprises a polynucleotide that has at least about 90%, preferably at least about 95% sequence identity with a polynucleotide encoding a polypeptide comprising the sequence of amino acids 1 to 811 of Figure 34 (SEQ ID N0:57).
In a specific embodiment, the invention provides an isolated nucleic acid molecule comprising DNA
encoding native or variant PR0358 polypeptide, with or without the N-terminal signal sequence, and with or without the transmembrane regions of the respective full-length sequences. In one aspect, the isolated nucleic acid comprises DNA encoding a mature, full-length native PR0358 polypeptide having amino acid residues 1 to 811 of Figure 34 (SEQ ID N0:57), or is complementary to such. encoding nucleic acid sequence. In another aspect, the invention concerns an isolated nucleic acid molecule that comprises DNA encoding a native PR0358 polypeptide without an N-terminal signal sequence, or is complementary to such encoding nucleic acid sequence.
In yet another embodiment, the invention concerns nucleic acid encoding transmembrane-domain deleted or inactivated forms of the full-length native PR0358 protein.
In another embodiment, the invention provides an isolated nucleic acid molecule which comprises the clone (DNA 47361-1249) deposited on November 7, 1997, under ATCC number 209431.
In a specific embodiment, the invention provides a vector comprising a polynucleotide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity with a polynucleotide encoding a polypeptide comprising the sequence of amino acids 20 to 811 of Figure 34 (SEQ
ID N0:57), or the complement of such polynucleotide. In a particular embodiment, the vector comprises DNA
encoding the novel Toll homologue (PR0358), with or without the N-terminal signal sequence (about amino acids 1 to 19), or a transmembrane-domain (about amino acids 576-595) deleted or inactivated variant thereof, or the eztracellular domain (about amino acids 20 to 595) of the mature protein, or a protein comprising any one of these sequences.
A host cell comprising such a vector is also provided.
In another embodiment, the invention provides isolated PR0358 polypeptides.
The invention further provides an isolated native sequence PR0358 polypeptide, or variants thereof.
In particular, the invention provides an isolated native sequence PR0358 polypeptide, which in certain embodiments, includes the amino acid sequence comprising residues 20 to 575, or 20 to 811, or 1 to 811 of Figure 34 (SEQ ID N0:57).
In yet another embodiment, the invention concerns agonists and antagonists of the native PR0358 polypeptide. In a particuiar embodiment, the agonist or antagonist is an anti-PR0358 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of the native PR0358 polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0358 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
The invention further concerns a composition comprising an antibody specifically binding a PR0358 polypeptide, in combination with a pharmaceutically acceptable carrier.
The invention also concerns a method of treating septic shock comprising administering to a patient an effective amount of an antagonist of a PR0358 polypeptide. In a specific embodiment, the antagonist is a blocking antibody specifically binding a native PR0358 polypeptide.
15. PR01310 A cDNA clone (DNA47394-1572) has been identified that encodes a novel polypeptide having sequence identity with carbozypeptidase X2 and designated in the present application as "PR01310."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01310 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1310 polypeptide having the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID N0:62), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01310 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 401 and about 2593, inclusive, of Figures 35A-B (SEQ ID N0:61). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a firrtkter aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203109 (DNA47394-1572), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203109 (DNA47394-1572).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID
N0:62), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01310 polypeptide having the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID
N0:62), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 26 to about 765, inclusive of Figure 36 (SEQ
ID N0:62), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01310 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01310 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 26 through 765 of Figure 36 (SEQ ID
N0:62).
In another aspect, the invention concerns an isolated PR01310 polypeptide, comprising an amino acid sequence having at least about 80°k sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 26 to about 765, inclusive of Figure 36 (SEQ
ID N0:62).
In a further aspect, the invention concerns an isolated PRO 1310 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95~ positives when compared with the amino acid sequence of residues 26 through 765 of Figure 36 (SEQ ID N0:62).
In yet another aspect, the invention concerns an isolated PRO 1310 polypeptide, comprising the sequence of amino acid residues 26 to about 765, inclusive of Figure 36 (SEQ ID N0:62), or a fragment thereof sufficient to provide a binding site for an anti-PR01310 antibody. Preferably, the PR01310 fragment retains a qualitative biological activity of a native PR01310 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01310 polypeptide having the sequence of amino acid residues from about 26 to about 765, inclusive of Figure 36 (SEQ ID N0:62), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity; most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01310 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01310 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01310 polypeptide, by contacting the native PR01310 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01310 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
16. PR0698 Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to olfactomedin, wherein the polypeptide is designated in the present application as "PR0698".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0698 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0698 WO 99/63088 PCT/US99/t2252 polypeptide having amino acid residues 1 to 510 of Figure 38 (SEQ ID N0:67), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0698 polypeptide having amino acid residues about 21 to 510 of Figure 38 (SEQ ID
N0:67), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA48320-1433 vector deposited on May 27, 1998 as ATCC 209904 which includes the nucleotide sequence encoding PR0698.
In another embodiment, the invention provides isolated PR0698 polypeptide. In particular, the invention provides isolated native sequence PR0698 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 510 of Figure 38 (SEQ ID N0:67).
Additional embodiments of the present invention are directed to PR0698 polypeptides comprising amino acids about 21 to 510 of Figure 38 (SEQ ID N0:67). Optionally, the PR0698 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA48320-1433 vector deposited on May 27, 1998 as ATCC 209904.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA39906 comprising the nucleotide sequence of Figure 39 (SEQ ID N0:68).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0698 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0698 WO 99/63088 PCT/US99/t2252 polypeptide having amino acid residues 1 to 510 of Figure 38 (SEQ ID N0:67), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0698 polypeptide having amino acid residues about 21 to 510 of Figure 38 (SEQ ID
N0:67), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA48320-1433 vector deposited on May 27, 1998 as ATCC 209904 which includes the nucleotide sequence encoding PR0698.
In another embodiment, the invention provides isolated PR0698 polypeptide. In particular, the invention provides isolated native sequence PR0698 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 510 of Figure 38 (SEQ ID N0:67).
Additional embodiments of the present invention are directed to PR0698 polypeptides comprising amino acids about 21 to 510 of Figure 38 (SEQ ID N0:67). Optionally, the PR0698 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA48320-1433 vector deposited on May 27, 1998 as ATCC 209904.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA39906 comprising the nucleotide sequence of Figure 39 (SEQ ID N0:68).
17. PR07 2 Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to the human placental protein Diff33, wherein the polypeptide is designated in the present application as "PR0732" .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0732 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0732 polypeptide having amino acid residues 1 to 453 of Figure 41 (SEQ ID N0:73), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0732 polypeptide having amino acid residues about 29 to 453 of Figure 41 (SEQ ID
N0:73) or amino acid 1 or about 29 to X of Figure 41 (SEQ ID N0:73), where X is any amino acid from 31 to 40 of Figure 41 (SEQ ID N0:73), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high suingency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA48334-1435 vector deposited on June 2, 1998 as ATCC
209924 which includes the nucleotide sequence encoding PR0732.
In another embodiment, the invention provides isolated PR0732 polypeptide. In particular, the invention provides isolated native sequence PR0732 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 453 of Figure 41 (SEQ ID N0:73).
Additional embodiments of the present invention are directed to PR0732 polypeptides comprising amino acids about 29 to 453 of Figure 41 (SEQ ID N0:73) or amino acid 1 or about 29 to X of Figure 41 (SEQ ID N0:73), where X is any amino acid from 31 to 40 of Figure 41 (SEQ ID N0:73). Optionally, the PR0732 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA48334-1435 vector deposited on June 2, 1998 as ATCC 209924.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA20239 comprising the nucleotide sequence of Figure 42 (SEQ ID N0:74).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA38050 comprising the nucleotide sequence of Figure 43 (SEQ ID N0:75).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA40683 comprising the nucleotide sequence of Figure 44 (SEQ ID N0:76).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA42580 comprising the nucleotide sequence of Figure 45 (SEQ ID N0:77).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0732 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0732 polypeptide having amino acid residues 1 to 453 of Figure 41 (SEQ ID N0:73), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0732 polypeptide having amino acid residues about 29 to 453 of Figure 41 (SEQ ID
N0:73) or amino acid 1 or about 29 to X of Figure 41 (SEQ ID N0:73), where X is any amino acid from 31 to 40 of Figure 41 (SEQ ID N0:73), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high suingency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA48334-1435 vector deposited on June 2, 1998 as ATCC
209924 which includes the nucleotide sequence encoding PR0732.
In another embodiment, the invention provides isolated PR0732 polypeptide. In particular, the invention provides isolated native sequence PR0732 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 453 of Figure 41 (SEQ ID N0:73).
Additional embodiments of the present invention are directed to PR0732 polypeptides comprising amino acids about 29 to 453 of Figure 41 (SEQ ID N0:73) or amino acid 1 or about 29 to X of Figure 41 (SEQ ID N0:73), where X is any amino acid from 31 to 40 of Figure 41 (SEQ ID N0:73). Optionally, the PR0732 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA48334-1435 vector deposited on June 2, 1998 as ATCC 209924.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA20239 comprising the nucleotide sequence of Figure 42 (SEQ ID N0:74).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA38050 comprising the nucleotide sequence of Figure 43 (SEQ ID N0:75).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA40683 comprising the nucleotide sequence of Figure 44 (SEQ ID N0:76).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA42580 comprising the nucleotide sequence of Figure 45 (SEQ ID N0:77).
18. PR01120 A cDNA clone (DNA48606-1479) has been identifiedthat encodes a novel polypeptide having homology sulfatases, designated in the present application as "PR01120."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01120 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01120 polypeptide having the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID N0:84), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01120 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 659 and about 3208, inclusive, of Figures 46A-B (SEQ ID N0:83). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203040 (DNA48606-1479), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203040 (DNA48606-1479).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID
N0:84), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01120 polypeptide having the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID
N0:84), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80Y6 sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 ~
sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01120 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 47 (SEQ ID
N0:84).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85~ positives, more preferably at least about 90% positives, most preferably at least about 95~
positives when compared with the amino acid sequence of residues 18 to about 867, inclusive of Figure 47 (SEQ
ID N0:84), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1120 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01120 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1120 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 to 867 of Figure 47 (SEQ ID N0:84).
In another aspect, the invention concerns an isolated PRO 1120 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95°k sequence identity to the sequence of amino acid residues 18 to about 867, inclusive of Figure 47 (SEQ
ID N0:84).
In a further aspect, the invention concerns an isolated PRO 1120 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 to 867 of Figure 47 (SEQ ID N0:84).
In yet another aspect, the invention concerns an isolated PRO 1120 polypeptide, comprising the sequence of amino acid residues 18 to about 867, inclusive of Figure 47 (SEQ ID N0:84), or a fragment thereof sufficient to provide a binding site for an anti-PR01120 antibody. Preferably, the PR01120 fragment retains a qualitative biological activity of a native PR01120 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01120 polypeptide having the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID N0:84), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 ~6 sequence identity, most preferably at least about a 95 96 sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01120 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01120 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01120 polypeptide, by contacting the native PR01120 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1120 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01120 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01120 polypeptide having the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID N0:84), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01120 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 659 and about 3208, inclusive, of Figures 46A-B (SEQ ID N0:83). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203040 (DNA48606-1479), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203040 (DNA48606-1479).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID
N0:84), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01120 polypeptide having the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID
N0:84), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80Y6 sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 ~
sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01120 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 47 (SEQ ID
N0:84).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85~ positives, more preferably at least about 90% positives, most preferably at least about 95~
positives when compared with the amino acid sequence of residues 18 to about 867, inclusive of Figure 47 (SEQ
ID N0:84), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1120 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01120 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1120 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 to 867 of Figure 47 (SEQ ID N0:84).
In another aspect, the invention concerns an isolated PRO 1120 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95°k sequence identity to the sequence of amino acid residues 18 to about 867, inclusive of Figure 47 (SEQ
ID N0:84).
In a further aspect, the invention concerns an isolated PRO 1120 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 to 867 of Figure 47 (SEQ ID N0:84).
In yet another aspect, the invention concerns an isolated PRO 1120 polypeptide, comprising the sequence of amino acid residues 18 to about 867, inclusive of Figure 47 (SEQ ID N0:84), or a fragment thereof sufficient to provide a binding site for an anti-PR01120 antibody. Preferably, the PR01120 fragment retains a qualitative biological activity of a native PR01120 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01120 polypeptide having the sequence of amino acid residues from about 18 to about 867, inclusive of Figure 47 (SEQ ID N0:84), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 ~6 sequence identity, most preferably at least about a 95 96 sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01120 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01120 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01120 polypeptide, by contacting the native PR01120 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1120 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
19. PR0537 A cDNA clone (DNA49141-1431) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0537".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0537 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0537 polypeptide having the sequence of amino acid residues from about 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID
N0:95), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0537 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 97 or about 190 and about 441, inclusive, of Figure 48 (SEQ ID N0:94).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203003 (DNA49141-1431) or (b) the complement of the nucleic acid molecule of (a}. In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203003 (DNA49141-1431).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I or about 32 to about 115, inclusive of Figure 49 (SEQ ID
N0:95), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0537 polypeptide having the sequence of amino acid residues from 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0537 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 31 in the sequence of Figure 49 (SEQ
ID N0:95).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85~ positives, more preferably at least about 909b positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0537 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 48 (SEQ ID N0:94).
In another embodiment, the invention provides isolated PR0537 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0537 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 32 to about 115 of Figure 49 (SEQ ID N0:95).
In another aspect, the invention concerns an isolated PR0537 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 k sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 32 to about I15, inclusive of Figure 49 (SEQ ID N0:95).
In a further aspect, the invention concerns an isolated PR0537 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95).
In yet another aspect, the invention concerns an isolated PR0537 polypeptide, comprising the sequence of amino acid residues 1 or about 32 to about 115, inclusive of Figure 49 (SEQ
ID N0:95), or a fragment thereof sufficient to provide a binding site for an anti-PR0537 antibody.
Preferably, the PR0537 fragment retains a qualitative biological activity of a native PR0537 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0537 polypeptide having the sequence of amino acid residues from about 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0537 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0537 polypeptide having the sequence of amino acid residues from about 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID
N0:95), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0537 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 97 or about 190 and about 441, inclusive, of Figure 48 (SEQ ID N0:94).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203003 (DNA49141-1431) or (b) the complement of the nucleic acid molecule of (a}. In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203003 (DNA49141-1431).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I or about 32 to about 115, inclusive of Figure 49 (SEQ ID
N0:95), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0537 polypeptide having the sequence of amino acid residues from 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0537 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 31 in the sequence of Figure 49 (SEQ
ID N0:95).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85~ positives, more preferably at least about 909b positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0537 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 48 (SEQ ID N0:94).
In another embodiment, the invention provides isolated PR0537 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0537 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 32 to about 115 of Figure 49 (SEQ ID N0:95).
In another aspect, the invention concerns an isolated PR0537 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 k sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 32 to about I15, inclusive of Figure 49 (SEQ ID N0:95).
In a further aspect, the invention concerns an isolated PR0537 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95).
In yet another aspect, the invention concerns an isolated PR0537 polypeptide, comprising the sequence of amino acid residues 1 or about 32 to about 115, inclusive of Figure 49 (SEQ
ID N0:95), or a fragment thereof sufficient to provide a binding site for an anti-PR0537 antibody.
Preferably, the PR0537 fragment retains a qualitative biological activity of a native PR0537 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0537 polypeptide having the sequence of amino acid residues from about 1 or about 32 to about 115, inclusive of Figure 49 (SEQ ID N0:95), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
20. PR0536 A cDNA clone (DNA49142-1430) has been identified, that encodes a novel secreted polypeptide, designated in the present application as "PR0536".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0536 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0536 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID
N0:97), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0536 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 48 or about 123 and about 986, inclusive, of Figure 50 (SEQ ID N0:96).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203002 (DNA49142-1430) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203002 (DNA49142-1430).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID
N0:97), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0536 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0536 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 51 (SEQ
ID N0:97).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0536 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 50 (SEQ ID N0:96).
In another embodiment, the invention provides isolated PR0536 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0536 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 313 of Figure 51 (SEQ ID N0:97).
In another aspect, the invention concerns an isolated PR0536 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97).
In a further aspect, the invention concerns an isolated PR0536 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97).
In yet another aspect, the invention concerns an isolated PR0536 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ
ID N0:97), or a fragment thereof sufficient to provide a binding site for an anti-PR0536 antibody.
Preferably, the PR0536 fragment retains a qualitative biological activity of a native PR0536 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0536 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 859b sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0536 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0536 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID
N0:97), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0536 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 48 or about 123 and about 986, inclusive, of Figure 50 (SEQ ID N0:96).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203002 (DNA49142-1430) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203002 (DNA49142-1430).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID
N0:97), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0536 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0536 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 51 (SEQ
ID N0:97).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0536 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 50 (SEQ ID N0:96).
In another embodiment, the invention provides isolated PR0536 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0536 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 313 of Figure 51 (SEQ ID N0:97).
In another aspect, the invention concerns an isolated PR0536 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97).
In a further aspect, the invention concerns an isolated PR0536 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97).
In yet another aspect, the invention concerns an isolated PR0536 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 313, inclusive of Figure 51 (SEQ
ID N0:97), or a fragment thereof sufficient to provide a binding site for an anti-PR0536 antibody.
Preferably, the PR0536 fragment retains a qualitative biological activity of a native PR0536 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0536 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 313, inclusive of Figure 51 (SEQ ID N0:97), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 859b sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
21. I'R0535 A cDNA clone (DNA49143-1429) has been identified, having homology to nucleic acid encoding a putative peptidyl-prolyl isomerase that encodes a novel polypeptide, designated in the present application as "PR0535".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRb535 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0535 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID
N0:99), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0535 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 78 or about 153 and about 680, inclusive, of Figure 52 (SEQ ID N0:98).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90 h sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203013 (DNA49143-1429) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203013 (DNA49143-1429).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID
N0:99), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0535 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0535 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 53 (SEQ
ID N0:99). The transmembrane domain has been tentatively identified as extending from about amino acid position 155 to about amino acid position 174 in the PR0535 amino acid sequence (Figure 53, SEQ ID N0:99).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0535 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 52 (SEQ ID N0:98).
In another embodiment, the invention provides isolated PR0535 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0535 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 201 of Figure 53 (SEQ ID N0:99).
In another aspect, the invention concerns an isolated PR0535 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99).
In a fwther aspect, the invention concerns an isolated PR0535 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99).
In yet another aspect, the invention concerns an isolated PR0535 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ
ID N0:99), or a fragment thereof sufficient to provide a binding site for an anti-PR0535 antibody.
Preferably, the PR0535 fragment retains a qualitative biological activity of a native PR0535 polypeptide.
In a still farther aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0535 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85~'o sequence identity, more preferably at least about a 9096 sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0535 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0535 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0535 polypeptide by contacting the native PR0535 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0535 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA30861 comprising the nucleotide sequence of Figure 54 (SEQ ID NO:100).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA36351 comprising the nucleotide sequence of Figure 55 (SEQ ID NO:101).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRb535 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0535 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID
N0:99), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0535 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 78 or about 153 and about 680, inclusive, of Figure 52 (SEQ ID N0:98).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90 h sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203013 (DNA49143-1429) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203013 (DNA49143-1429).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID
N0:99), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0535 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0535 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 53 (SEQ
ID N0:99). The transmembrane domain has been tentatively identified as extending from about amino acid position 155 to about amino acid position 174 in the PR0535 amino acid sequence (Figure 53, SEQ ID N0:99).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0535 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 52 (SEQ ID N0:98).
In another embodiment, the invention provides isolated PR0535 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0535 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 201 of Figure 53 (SEQ ID N0:99).
In another aspect, the invention concerns an isolated PR0535 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99).
In a fwther aspect, the invention concerns an isolated PR0535 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99).
In yet another aspect, the invention concerns an isolated PR0535 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 201, inclusive of Figure 53 (SEQ
ID N0:99), or a fragment thereof sufficient to provide a binding site for an anti-PR0535 antibody.
Preferably, the PR0535 fragment retains a qualitative biological activity of a native PR0535 polypeptide.
In a still farther aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0535 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 201, inclusive of Figure 53 (SEQ ID N0:99), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85~'o sequence identity, more preferably at least about a 9096 sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0535 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0535 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0535 polypeptide by contacting the native PR0535 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0535 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA30861 comprising the nucleotide sequence of Figure 54 (SEQ ID NO:100).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA36351 comprising the nucleotide sequence of Figure 55 (SEQ ID NO:101).
22. PR0718 Applicants have identified a cDNA clone that encodes a novel tetraspan membrane polypeptide, wherein the polypeptide is designated in the present application as "PR07I8".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0718 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0718 polypeptide having amino acid residues 1 to 157 of Figure 57 (SEQ ID N0:103), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0718 polypeptide having amino acid residues X to 157 of Figure 57 (SEQ ID N0:103), where X is any amino acid from 143 to 152 of Figure 57 (SEQ ID N0:103), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA49647-1398 vector deposited on June 2, 1998 as ATCC 209919 which includes the nucleotide sequence encoding PR0718.
In another embodiment, the invention provides isolated PR0718 polypeptide. In particular, the invention provides isolated native sequence PR0718 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 157 of Figure 57 (SEQ ID N0:103).
Additional embodiments of the present invention are directed to isolated PR0718 polypeptides comprising amino acids X to 157 of Figure 57 (SEQ ID N0:103), where X is any amino acid from 143 to 152 of Figure 57 (SEQ
ID N0:103). Optionally, the PR0718 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA49647-1398 vector deposited on June 2, 1998 as ATCC 209919.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA15386 which comprises the nucleotide sequence of Figure 58 (SEQ ID N0:104).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA16630 which comprises the nucleotide sequence of Figure 59 (SEQ ID NO:105).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA16829 which comprises the nucleotide sequence of Figure 60 (SEQ ID N0:106).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA28357 which comprises the nucleotide sequence of Figure 61 (SEQ ID N0:107).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA43512 which comprises the nucleotide sequence of Figure 62 (SEQ ID N0:108).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0718 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0718 polypeptide having amino acid residues 1 to 157 of Figure 57 (SEQ ID N0:103), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0718 polypeptide having amino acid residues X to 157 of Figure 57 (SEQ ID N0:103), where X is any amino acid from 143 to 152 of Figure 57 (SEQ ID N0:103), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA49647-1398 vector deposited on June 2, 1998 as ATCC 209919 which includes the nucleotide sequence encoding PR0718.
In another embodiment, the invention provides isolated PR0718 polypeptide. In particular, the invention provides isolated native sequence PR0718 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 157 of Figure 57 (SEQ ID N0:103).
Additional embodiments of the present invention are directed to isolated PR0718 polypeptides comprising amino acids X to 157 of Figure 57 (SEQ ID N0:103), where X is any amino acid from 143 to 152 of Figure 57 (SEQ
ID N0:103). Optionally, the PR0718 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA49647-1398 vector deposited on June 2, 1998 as ATCC 209919.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA15386 which comprises the nucleotide sequence of Figure 58 (SEQ ID N0:104).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA16630 which comprises the nucleotide sequence of Figure 59 (SEQ ID NO:105).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA16829 which comprises the nucleotide sequence of Figure 60 (SEQ ID N0:106).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA28357 which comprises the nucleotide sequence of Figure 61 (SEQ ID N0:107).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA43512 which comprises the nucleotide sequence of Figure 62 (SEQ ID N0:108).
23. PR0872 Applicants have identified a cDNA clone, DNA49819-1439, that encodes a novel polypeptide having homology to dehydrogenases wherein the polypeptide is designated in the present application as "PR0872".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0872 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85%a sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0872 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 610, inclusive of Figure 64 (SEQ ID N0:113), or (b) the complement of the DNA molecule of (a}.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0872 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid between about residues 68 and about 1843, inclusive of Figwe 63 (SEQ ID N0:112). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209931 (DNA49819-1439), which was deposited on June 2, 1998. In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209931 (DNA49819-1439).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 610, inclusive of Figure 64 (SEQ ID
N0:113).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0872 extracellular domain (ECD), with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 18 in the sequence of Figure 64 (SEQ ID N0:113). The first transmembrane domain region has been tentatively identified as extending from about amino acid position 70 to about amino acid position 87 in the PR0872 amino acid sequence (Figure 64, SEQ ID N0:113).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives,~preferably at least about 90% positives, most preferably at least about 95%a positives when compared with the amino acid sequence of residues 1 or about 19 to about 610, inclusive of Figure 64 (SEQ ID N0:113).
Another embodiment is directed to fragments of a PR0872 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0872 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0872 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 19 to 610 of Figure 64 (SEQ ID
N0:113).
In another aspect, the invention concerns an isolated PR0872 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to 610, inclusive of Figure 64 (SEQ ID N0:113).
In a fitrther aspect, the invention concerns an isolated PR0872 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85~
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 19 to 610 of Figure 64 (SEQ ID N0:113).
In another aspect, the invention concerns a PR0872 extracelluiar domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 k sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to X of Figure 64 (SEQ TD
N0:113), wherein X is any one of amino acid residues 66 to 75 of Figure 64 (SEQ ID N0:113).
In yet another aspect, the invention concerns an isolated PR0872 polypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 610, inclusive of Figure 64 (SEQ
ID N0:113), or a fragment thereof sufficient to provide a binding site for an anti-PR0872 antibody.
Preferably, the PR0872 fragment WO 99/63088 PC'T/US99/12252 retains a qualitative biological activity of a native PR0872 polypeptide.
In another aspect, the present invention is directed to fragments of a PR0872 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PR0872 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR0872 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR0872 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR0872 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0872 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85%a sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0872 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 610, inclusive of Figure 64 (SEQ ID N0:113), or (b) the complement of the DNA molecule of (a}.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0872 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid between about residues 68 and about 1843, inclusive of Figwe 63 (SEQ ID N0:112). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209931 (DNA49819-1439), which was deposited on June 2, 1998. In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209931 (DNA49819-1439).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 610, inclusive of Figure 64 (SEQ ID
N0:113).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0872 extracellular domain (ECD), with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 18 in the sequence of Figure 64 (SEQ ID N0:113). The first transmembrane domain region has been tentatively identified as extending from about amino acid position 70 to about amino acid position 87 in the PR0872 amino acid sequence (Figure 64, SEQ ID N0:113).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives,~preferably at least about 90% positives, most preferably at least about 95%a positives when compared with the amino acid sequence of residues 1 or about 19 to about 610, inclusive of Figure 64 (SEQ ID N0:113).
Another embodiment is directed to fragments of a PR0872 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0872 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0872 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 19 to 610 of Figure 64 (SEQ ID
N0:113).
In another aspect, the invention concerns an isolated PR0872 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to 610, inclusive of Figure 64 (SEQ ID N0:113).
In a fitrther aspect, the invention concerns an isolated PR0872 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85~
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 19 to 610 of Figure 64 (SEQ ID N0:113).
In another aspect, the invention concerns a PR0872 extracelluiar domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 k sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to X of Figure 64 (SEQ TD
N0:113), wherein X is any one of amino acid residues 66 to 75 of Figure 64 (SEQ ID N0:113).
In yet another aspect, the invention concerns an isolated PR0872 polypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 610, inclusive of Figure 64 (SEQ
ID N0:113), or a fragment thereof sufficient to provide a binding site for an anti-PR0872 antibody.
Preferably, the PR0872 fragment WO 99/63088 PC'T/US99/12252 retains a qualitative biological activity of a native PR0872 polypeptide.
In another aspect, the present invention is directed to fragments of a PR0872 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PR0872 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR0872 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR0872 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR0872 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
24. PR01063 Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to human type IV collagenase, wherein the polypeptide is designated in the present application as "PR01063".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01063 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01063 polypeptide having amino acid residues 1 to 301 of Figure 66 (SEQ ID NO:115), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR01063 polypeptide having amino acid residues about 22 to 301 of Figure 66 (SEQ ID
NO:115), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA49820-1427 vector deposited on June 2, 1998 as ATCC 209932 which includes the nucleotide sequence encoding PR01063.
In another embodiment, the invention provides isolated PR01063 polypeptide. In particular, the invention provides isolated native sequence PR01063 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 301 of Figure 66 (SEQ ID NO:115).
Additional embodiments of the present invention are directed to PR01063 polypeptides comprising amino acids about 22 to 301 of Figure 66 (SEQ ID NO:115). Optionally, the PR01063 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA49820-1427 vector deposited on June 2, 1998 as ATCC
209932.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01063 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01063 polypeptide having amino acid residues 1 to 301 of Figure 66 (SEQ ID NO:115), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR01063 polypeptide having amino acid residues about 22 to 301 of Figure 66 (SEQ ID
NO:115), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA49820-1427 vector deposited on June 2, 1998 as ATCC 209932 which includes the nucleotide sequence encoding PR01063.
In another embodiment, the invention provides isolated PR01063 polypeptide. In particular, the invention provides isolated native sequence PR01063 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 301 of Figure 66 (SEQ ID NO:115).
Additional embodiments of the present invention are directed to PR01063 polypeptides comprising amino acids about 22 to 301 of Figure 66 (SEQ ID NO:115). Optionally, the PR01063 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA49820-1427 vector deposited on June 2, 1998 as ATCC
209932.
25. PR0619 A cDNA clone (DNA49821-1562) has been identified that encodes a novel polypeptide, designated in the present application as "PR0619." PR0619 polypeptides have sequence identity with VpreB genes, particularly to VpreB3.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0619 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0619 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID N0:117), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0619 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 81 or 141 and about 449, inclusive, of Figure 67 (SEQ ID N0:116). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209981 (DNA49821-1562), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209981 (DNA49821-1562).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ
ID N0:117), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0619 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID
N0:117), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0619 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, which is in a soluble form. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 68 (SEQ ID
N0:117).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID NO:1I7), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0619 polypeptide coding sequence that tray find use as hybridization probes. Such nucleic acid fragments are from about 40 through about 80 nucleotides in length, preferably from about 20 through about 60 nucleotides in length, more preferably from about 20 through about 50 nucleotides in length, and most preferably from about 20 through about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0619 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0619 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 21 through 123 of Figure 68 (SEQ ID
N0:117).
In another aspect, the invention concerns an isolated PR0619 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 21 through about 123, inclusive of Figure 68 (SEQ ID N0:117).
In a further aspect, the invention concerns an isolated PR0619 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 21 through 123 of Figure 68 (SEQ ID NO: I 17).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0619 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID N0:117), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0619 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0619 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0619 polypeptide, by contacting the native PR0619 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0619 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0619 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0619 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID N0:117), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0619 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 81 or 141 and about 449, inclusive, of Figure 67 (SEQ ID N0:116). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209981 (DNA49821-1562), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209981 (DNA49821-1562).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ
ID N0:117), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0619 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID
N0:117), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0619 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, which is in a soluble form. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 68 (SEQ ID
N0:117).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID NO:1I7), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0619 polypeptide coding sequence that tray find use as hybridization probes. Such nucleic acid fragments are from about 40 through about 80 nucleotides in length, preferably from about 20 through about 60 nucleotides in length, more preferably from about 20 through about 50 nucleotides in length, and most preferably from about 20 through about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0619 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0619 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 21 through 123 of Figure 68 (SEQ ID
N0:117).
In another aspect, the invention concerns an isolated PR0619 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 21 through about 123, inclusive of Figure 68 (SEQ ID N0:117).
In a further aspect, the invention concerns an isolated PR0619 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 21 through 123 of Figure 68 (SEQ ID NO: I 17).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0619 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 123, inclusive of Figure 68 (SEQ ID N0:117), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0619 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0619 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0619 polypeptide, by contacting the native PR0619 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0619 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
26. PR0943 A cDNA clone (DNA52192-1369) has been identified, having homology to nucleic acid encoding fibroblast growth factor receptor-4 that encodes a novel polypeptide, designated in the present application as "PR0943".
WO 99/b3088 PC'T/US99/12252 In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0943 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0943 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0943 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 150 or about 201 and about 1661, inclusive, of Figure 69 (SEQ ID N0:118).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203042 (DNA52192-1369) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203042 (DNA52192-1369).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0943 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID N0:119), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0943 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 70 (SEQ
ID N0:119). The transmembrane domain has been tentatively identified as extending from about amino acid position 376 to about amino acid position 396 in the PR0943 amino acid sequence (Figure 70, SEQ ID N0:119).
WO 99/63088 PC'T/US99/12252 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID N0:119), or (b) the complement of the DNA of (a).
S Another embodiment is directed to fragments of a PR0943 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 69 (SEQ ID N0:118).
In another embodiment, the invention provides isolated PR0943 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0943 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 504 of Figure 70 (SEQ ID N0:119).
In another aspect, the invention concerns an isolated PR0943 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID N0:119).
In a further aspect, the invention concerns an isolated PR0943 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119).
In yet another aspect, the invention concerns an isolated PR0943 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ
ID N0:119), or a fragment thereof sufficient to provide a binding site for an anti-PR0943 antibody.
Preferably, the PR0943 fragment retains a qualitative biological activity of a native PR0943 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0943 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0943 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0943 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0943 polypeptide by contacting the native PR0943 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0943 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
WO 99/b3088 PC'T/US99/12252 In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0943 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0943 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0943 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 150 or about 201 and about 1661, inclusive, of Figure 69 (SEQ ID N0:118).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203042 (DNA52192-1369) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203042 (DNA52192-1369).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0943 polypeptide having the sequence of amino acid residues from 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID N0:119), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0943 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 17 in the sequence of Figure 70 (SEQ
ID N0:119). The transmembrane domain has been tentatively identified as extending from about amino acid position 376 to about amino acid position 396 in the PR0943 amino acid sequence (Figure 70, SEQ ID N0:119).
WO 99/63088 PC'T/US99/12252 In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID N0:119), or (b) the complement of the DNA of (a).
S Another embodiment is directed to fragments of a PR0943 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 69 (SEQ ID N0:118).
In another embodiment, the invention provides isolated PR0943 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0943 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 18 to about 504 of Figure 70 (SEQ ID N0:119).
In another aspect, the invention concerns an isolated PR0943 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID N0:119).
In a further aspect, the invention concerns an isolated PR0943 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119).
In yet another aspect, the invention concerns an isolated PR0943 polypeptide, comprising the sequence of amino acid residues 1 or about 18 to about 504, inclusive of Figure 70 (SEQ
ID N0:119), or a fragment thereof sufficient to provide a binding site for an anti-PR0943 antibody.
Preferably, the PR0943 fragment retains a qualitative biological activity of a native PR0943 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0943 polypeptide having the sequence of amino acid residues from about 1 or about 18 to about 504, inclusive of Figure 70 (SEQ ID
N0:119), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0943 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0943 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0943 polypeptide by contacting the native PR0943 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0943 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
27. PR01188 A cDNA clone (DNA52598-1518)has been identified that encodes a novel polypeptide having homology to nucleotide pyrophosphohydrolase and designated in the present application as "PR01188."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01188 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01188 polypeptide having the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ ID N0:124), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01188 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 199 and about 3b87, inclusive, of Figure 71 (SEQ ID N0:123). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203107 (DNA52598-1518), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203107 (DNA52598-1518).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ ID
N0:124), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01188 polypeptide having the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ
ID N0:124), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 °~ sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01188 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 21 in the sequence of Figure 72 (SEQ
ID N0:124).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 22 to about 1184, inclusive of Figure 72 (SEQ
ID N0:124), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01188 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1188 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 22 to 1184 of Figure 72 (SEQ ID N0:124).
In another aspect, the invention concerns an isolated PR01188 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 1184, inclusive of Figure 72 (SEQ
ID N0:124).
In a further aspect, the invention concerns an isolated PRO 1188 polypeptide, comprising an amino acid sequence scoring at least about 80 l positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 to 1184 of Figure 72 (SEQ ID N0:124).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01188 polypeptide having the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ ID N0:124), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01188 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01188 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01188 polypeptide, by contacting the native PR01188 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01188 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01188 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01188 polypeptide having the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ ID N0:124), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01188 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 199 and about 3b87, inclusive, of Figure 71 (SEQ ID N0:123). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203107 (DNA52598-1518), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203107 (DNA52598-1518).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ ID
N0:124), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01188 polypeptide having the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ
ID N0:124), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 °~ sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01188 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 21 in the sequence of Figure 72 (SEQ
ID N0:124).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 22 to about 1184, inclusive of Figure 72 (SEQ
ID N0:124), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01188 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1188 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 22 to 1184 of Figure 72 (SEQ ID N0:124).
In another aspect, the invention concerns an isolated PR01188 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 22 to about 1184, inclusive of Figure 72 (SEQ
ID N0:124).
In a further aspect, the invention concerns an isolated PRO 1188 polypeptide, comprising an amino acid sequence scoring at least about 80 l positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 22 to 1184 of Figure 72 (SEQ ID N0:124).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01188 polypeptide having the sequence of amino acid residues from about 22 to about 1184, inclusive of Figure 72 (SEQ ID N0:124), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01188 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01188 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01188 polypeptide, by contacting the native PR01188 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01188 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
28. P_ 801133 A cDNA clone (DNA53913-1490) has been identified that encodes a novel polypeptide having sequence identity with netrin-la and designated in the present application as "PR01133."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 133 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1133 polypeptide having the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID N0:129), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concertis an isolated nucleic acid molecule encoding a PR01133 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 320 and about 1579, inclusive, of Figure 73 (SEQ ID N0:128). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203162 (DNA53913-1490), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203162 (DNA53913-1490).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID
N0:129), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01133 polypeptide having the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID
N0:129), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 438, inclusive of Figure 74 (SEQ
ID N0:129), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01133 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01133 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1133 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 through 438 of Figure 74 (SEQ ID
N0:129).
In another aspect, the invention concerns an isolated PR01133 polypeptide, comprising an amino acid sequence having at least about 8096 sequence idezitity, preferably at least about 85% sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 19 to about 438, inclusive of Figure 74 (SEQ
ID N0:129).
In a further aspect, the invention concerns an isolated PRO 1133 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 through 438 of Figure 74 (SEQ ID N0:129).
In yet another aspect, the invention concerns an isolated PRO 1133 polypeptide, comprising the sequence of amino acid residues 19 to about 438, inclusive of Figure 74 (SEQ ID
N0:129), or a fragment thereof sufficient to provide a binding site for an anti-PR01133 antibody. Preferably, the PR01133 fragment retains a qualitative biological activity of a native PR01133 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01133 polypeptide having the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID N0:129), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01133 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01133 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01133 polypeptide, by contacting the native PR01133 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01133 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 133 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1133 polypeptide having the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID N0:129), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concertis an isolated nucleic acid molecule encoding a PR01133 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 320 and about 1579, inclusive, of Figure 73 (SEQ ID N0:128). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203162 (DNA53913-1490), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203162 (DNA53913-1490).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID
N0:129), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01133 polypeptide having the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID
N0:129), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 19 to about 438, inclusive of Figure 74 (SEQ
ID N0:129), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01133 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01133 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1133 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 19 through 438 of Figure 74 (SEQ ID
N0:129).
In another aspect, the invention concerns an isolated PR01133 polypeptide, comprising an amino acid sequence having at least about 8096 sequence idezitity, preferably at least about 85% sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 19 to about 438, inclusive of Figure 74 (SEQ
ID N0:129).
In a further aspect, the invention concerns an isolated PRO 1133 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 19 through 438 of Figure 74 (SEQ ID N0:129).
In yet another aspect, the invention concerns an isolated PRO 1133 polypeptide, comprising the sequence of amino acid residues 19 to about 438, inclusive of Figure 74 (SEQ ID
N0:129), or a fragment thereof sufficient to provide a binding site for an anti-PR01133 antibody. Preferably, the PR01133 fragment retains a qualitative biological activity of a native PR01133 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01133 polypeptide having the sequence of amino acid residues from about 19 to about 438, inclusive of Figure 74 (SEQ ID N0:129), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01133 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01133 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01133 polypeptide, by contacting the native PR01133 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01133 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
29. PR0784 A cDNA clone (DNA53978-1443) has been identified that encodes a novel polypeptide, designated in the present application as "PR0784".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0784 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90°~ sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0784 polypeptide having the sequence of amino acid residues from about 16 to about 228, inclusive of Figure 76 (SEQ ID N0:135), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0784 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 182 and about 820, inclusive, of Figure 75 (SEQ ID N0:134). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209983 (DNA53978-1443), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209983 (DNA53978-1443).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°k sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 16 to about 228, inclusive of Figwe 76 (SEQ ID
N0:135), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50, and preferably at least 100 nucleotides and produced by hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0784 polypeptide having the sequence of amino acid residues from about 16 to about 228, inclusive of Figure 76 (SEQ ID N0:135), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85%
sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 %
sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0784 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position about I to about amino acid position 15 in the sequence of Figure 76 (SEQ ID NO:
135). The first transmembrane domain has been tentatively identified as extending from about amino acid position 68 to about amino acid position 87 in the PR0784 amino acid sequence (Figure 76, SEQ ID N0:135).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80°o positives, preferably at least about 8596 positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 16 to about 228, inclusive of Figure 76 (SEQ
ID N0:135), or (b) the complement of the DNA of (a).
In another aspect, the invention concerns hybridization probes that comprise fragments of the PR0784 coding sequence, or complementary sequence thereof. The hybridization probes preferably have at least about 20 nucleotides to about 80 nucleotides, and more preferably, at least about 40 to about 80 nucleotides.
In another embodiment, the invention provides isolated PR0784 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0784 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 to 228 of Figure 76 (SEQ ID N0:135).
In another aspect, the invention concerns an isolated PR0784 polypeptide, comprising an amino acid sequence having at least about 80°k sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 228, inclusive of Figure 76 (SEQ
ID N0:135).
In a further aspect, the invention concerns an isolated PR0784 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 ~ positives when compared with the amino acid sequence of residues 16 to 228 of Figure 76 (SEQ ID N0:135).
In yet another aspect, the invention concerns an isolated PR0784 polypeptide, comprising the sequence of amino acid residues 16 to about 228, inclusive of Figure 76 (SEQ ID
N0:135), or a fragment thereof sufficient to provide a binding site for an anti-PR0784 antibody. Preferably, the PR0784 fragment retains a qualitative biological activity of a native PR0784 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0784 polypeptide having the sequence of amino acid residues from about 16 to about 228, inclusive of Figure 76 (SEQ ID N0:135), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80°! sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90°~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0784 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0784 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0784 poiypeptide, by contacting the native PR0784 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0784 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0784 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90°~ sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0784 polypeptide having the sequence of amino acid residues from about 16 to about 228, inclusive of Figure 76 (SEQ ID N0:135), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0784 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 182 and about 820, inclusive, of Figure 75 (SEQ ID N0:134). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209983 (DNA53978-1443), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209983 (DNA53978-1443).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°k sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 16 to about 228, inclusive of Figwe 76 (SEQ ID
N0:135), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50, and preferably at least 100 nucleotides and produced by hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0784 polypeptide having the sequence of amino acid residues from about 16 to about 228, inclusive of Figure 76 (SEQ ID N0:135), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85%
sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 %
sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0784 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position about I to about amino acid position 15 in the sequence of Figure 76 (SEQ ID NO:
135). The first transmembrane domain has been tentatively identified as extending from about amino acid position 68 to about amino acid position 87 in the PR0784 amino acid sequence (Figure 76, SEQ ID N0:135).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80°o positives, preferably at least about 8596 positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 16 to about 228, inclusive of Figure 76 (SEQ
ID N0:135), or (b) the complement of the DNA of (a).
In another aspect, the invention concerns hybridization probes that comprise fragments of the PR0784 coding sequence, or complementary sequence thereof. The hybridization probes preferably have at least about 20 nucleotides to about 80 nucleotides, and more preferably, at least about 40 to about 80 nucleotides.
In another embodiment, the invention provides isolated PR0784 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0784 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 to 228 of Figure 76 (SEQ ID N0:135).
In another aspect, the invention concerns an isolated PR0784 polypeptide, comprising an amino acid sequence having at least about 80°k sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 228, inclusive of Figure 76 (SEQ
ID N0:135).
In a further aspect, the invention concerns an isolated PR0784 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 ~ positives when compared with the amino acid sequence of residues 16 to 228 of Figure 76 (SEQ ID N0:135).
In yet another aspect, the invention concerns an isolated PR0784 polypeptide, comprising the sequence of amino acid residues 16 to about 228, inclusive of Figure 76 (SEQ ID
N0:135), or a fragment thereof sufficient to provide a binding site for an anti-PR0784 antibody. Preferably, the PR0784 fragment retains a qualitative biological activity of a native PR0784 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0784 polypeptide having the sequence of amino acid residues from about 16 to about 228, inclusive of Figure 76 (SEQ ID N0:135), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80°! sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90°~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0784 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0784 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0784 poiypeptide, by contacting the native PR0784 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0784 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
30. PRm83 Applicants have identified a cDNA clone that encodes a novel mufti-span transmembrane polypeptide, wherein the polypeptide is designated in the present application as "PR0783 ° .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0783 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0783 polypeptide having amino acid residues 1 to 489 of Figure 79 (SEQ ID N0:138), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0783 polypeptide having amino acid residues 1 to X of Figure 79 (SEQ ID N0:138), where X is any amino acid from 19 to 28 of Figure 79 (SEQ ID N0:138), or is complementary to such encoding nucleic acid sequence, and reraains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA53996-1442 vector deposited on June 2, 1998 as ATCC 209921 which includes the nucleotide sequence encoding PR0783.
In another embodiment, the invention provides isolated PR0783 polypeptide. In particular, the invention provides isolated native sequence PR0783 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 489 of Figure 79 (SEQ ID N0:138).
Additional embodiments of the present invention are directed to PR0783 polypeptides comprising amino acid 1 to about X of Figure 79 (SEQ
ID N0:138), where X is any amino acid from 19 to 28 of Figure 79 (SEQ ID
N0:138). Optionally, the PR0783 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA53996-1442 vector deposited on June 2, 1998, as ATCC 209921.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA45201 which comprises the nucleic acid sequence shown in Figure 80 (SEQ ID
N0:139).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA14575 which comprises the nucleic acid sequence shown in Figure 81 (SEQ ID
N0:140).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0783 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0783 polypeptide having amino acid residues 1 to 489 of Figure 79 (SEQ ID N0:138), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0783 polypeptide having amino acid residues 1 to X of Figure 79 (SEQ ID N0:138), where X is any amino acid from 19 to 28 of Figure 79 (SEQ ID N0:138), or is complementary to such encoding nucleic acid sequence, and reraains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA53996-1442 vector deposited on June 2, 1998 as ATCC 209921 which includes the nucleotide sequence encoding PR0783.
In another embodiment, the invention provides isolated PR0783 polypeptide. In particular, the invention provides isolated native sequence PR0783 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 489 of Figure 79 (SEQ ID N0:138).
Additional embodiments of the present invention are directed to PR0783 polypeptides comprising amino acid 1 to about X of Figure 79 (SEQ
ID N0:138), where X is any amino acid from 19 to 28 of Figure 79 (SEQ ID
N0:138). Optionally, the PR0783 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA53996-1442 vector deposited on June 2, 1998, as ATCC 209921.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA45201 which comprises the nucleic acid sequence shown in Figure 80 (SEQ ID
N0:139).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA14575 which comprises the nucleic acid sequence shown in Figure 81 (SEQ ID
N0:140).
31. PR0820 A cDNA clone (DNA56041-1416) has been identified, having sequence identity with immunoglobulin gamma Fc receptors that encodes a novel polypeptide, designated in the present application as "PR0820" .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0820 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 k sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0820 polypeptide having the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-124, or in another embodiment, 16-124.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0820 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 115 or 160 and about 486, inclusive, of Figure 82 (SEQ ID N0:145). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203021 (DNA56041-1416), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. (DNA56041-1416).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ
ID N0:146), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0820 polypeptide having the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID
N0:146), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0820 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0820 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 16 through 124 of Figure 83 (SEQ ID
N0:146).
In another aspect, the invention concerns an isolated PR0820 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146).
In a further aspect, the invention concerns an isolated PR0820 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 16 through 124 of Figure 83 (SEQ ID N0:146).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0820 polypeptide having the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85'% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0820 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0820 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0820 polypeptide, by contacting the native PR0820 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0820 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0820 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 k sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0820 polypeptide having the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-124, or in another embodiment, 16-124.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0820 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 115 or 160 and about 486, inclusive, of Figure 82 (SEQ ID N0:145). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203021 (DNA56041-1416), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. (DNA56041-1416).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ
ID N0:146), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0820 polypeptide having the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID
N0:146), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0820 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0820 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 16 through 124 of Figure 83 (SEQ ID
N0:146).
In another aspect, the invention concerns an isolated PR0820 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146).
In a further aspect, the invention concerns an isolated PR0820 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 16 through 124 of Figure 83 (SEQ ID N0:146).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0820 polypeptide having the sequence of amino acid residues from about 1 or 16 to about 124, inclusive of Figure 83 (SEQ ID N0:146), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85'% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0820 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0820 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0820 polypeptide, by contacting the native PR0820 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0820 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
32. PR01080 A cDNA clone (DNA56047-1456) has been identified that encodes a novel polypeptide, designated in the present application as "PR01080." PR01080 polypeptides have sequence identity with DnaJ proteins.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01080 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1080 polypeptide having the sequence of amino acid residues from about I or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., I-358, or in another embodiment, 23-358.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROi080 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 159 or 225 and about 1232, inclusive, of Figure 84 (SEQ ID N0:147). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 809'o sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209948 (DNA56047-1456), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209948 (DNA5604'7-1456).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 23 to about 358, inclusive of Figure 85 (SEQ
ID N0:148), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01080 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID
N0:148), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01080 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 22 in the sequence of Figure 85 (SEQ ID N0:148).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01080 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01080 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 23 through 358 of Figure 85 (SEQ ID
N0:148).
In another aspect, the invention concerns an isolated PR01080 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148).
In a fiirttter aspect, the invention concerns an isolated PRO 1080 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 23 through 358 of Figure 85 (SEQ ID N0:148).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01080 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01080 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01080 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01080 polypeptide, by contacting the native PR01080 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1080 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA36527 comprising the nucleotide sequence of Figure 86 (SEQ ID N0:149).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01080 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1080 polypeptide having the sequence of amino acid residues from about I or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., I-358, or in another embodiment, 23-358.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROi080 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 159 or 225 and about 1232, inclusive, of Figure 84 (SEQ ID N0:147). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 809'o sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209948 (DNA56047-1456), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209948 (DNA5604'7-1456).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 23 to about 358, inclusive of Figure 85 (SEQ
ID N0:148), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01080 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID
N0:148), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01080 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 22 in the sequence of Figure 85 (SEQ ID N0:148).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01080 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01080 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 23 through 358 of Figure 85 (SEQ ID
N0:148).
In another aspect, the invention concerns an isolated PR01080 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148).
In a fiirttter aspect, the invention concerns an isolated PRO 1080 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 23 through 358 of Figure 85 (SEQ ID N0:148).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01080 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 358, inclusive of Figure 85 (SEQ ID N0:148), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01080 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01080 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01080 polypeptide, by contacting the native PR01080 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1080 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA36527 comprising the nucleotide sequence of Figure 86 (SEQ ID N0:149).
33. PR01079 A cDNA clone (DNA56050-1455) has been identified that encodes a novel polypeptide, designated in the present application as "PR01079".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01079 polypeptide.
1n one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01079 polypeptide having the sequence of amino acid residues from about 30 to about 226, inclusive of Figure 88 (SEQ ID NO:151), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01079 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 270 and about 860, inclusive, of Figure 87 (SEQ ID NO:150). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203011 (DNA56050-1455), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203011 (DNA56050-1455).
$ In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 226, inclusive of Figure 88 (SEQ ID
N0:151), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides and preferably at least about 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01079 polypeptide having the sequence of amino acid residues from about 30 to about 226, inclusive of Figuce 88 (SEQ ID
N0:151), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 1$ preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01079 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 29 in the sequence of Figure 88 (SEQ ID N0:151).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 30 to about 226, inclusive of Figure 88 (SEQ
ID N0:151), or (b) the 2$ complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01079 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01079 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1079 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 30 to 226 of Figure 88 (SEQ ID N0:151).
In another aspect, the invention concerns an isolated PR01079 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 30 to about 226, inclusive of Figure 88 (SEQ
ID N0:151).
In a further aspect, the invention concerns an isolated PR01079 polypeptide,comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%
positives, more preferably at least about 90 °6 positives, most preferably at least about 95 ~ positives when compared with the amino acid sequence of residues 30 to 226 of Figure 88 (SEQ ID NO:151).
In yet another aspect, the invention concerns an isolated PR01079 polypeptide, comprising the sequence of amino acid residues 30 to about 226, inclusive of Figure 88 (SEQ ID
NO:151), or a fragment thereof sufficient to provide a binding site for an anti-PR01079 antibody. Preferably, the PR01079 fragment retains a qualitative biological activity of a native PR01079 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01079 polypeptide having the sequence of amino acid residues from about 30 to about 226, inclusive of Figure 88 (SEQ ID NO:151), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80~ sequence identity, preferably at least about an 85~ sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 3b sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01079 polypeptide.
1n one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01079 polypeptide having the sequence of amino acid residues from about 30 to about 226, inclusive of Figure 88 (SEQ ID NO:151), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01079 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 270 and about 860, inclusive, of Figure 87 (SEQ ID NO:150). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203011 (DNA56050-1455), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203011 (DNA56050-1455).
$ In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 226, inclusive of Figure 88 (SEQ ID
N0:151), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides and preferably at least about 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01079 polypeptide having the sequence of amino acid residues from about 30 to about 226, inclusive of Figuce 88 (SEQ ID
N0:151), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, 1$ preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01079 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 29 in the sequence of Figure 88 (SEQ ID N0:151).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 30 to about 226, inclusive of Figure 88 (SEQ
ID N0:151), or (b) the 2$ complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01079 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01079 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1079 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 30 to 226 of Figure 88 (SEQ ID N0:151).
In another aspect, the invention concerns an isolated PR01079 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 30 to about 226, inclusive of Figure 88 (SEQ
ID N0:151).
In a further aspect, the invention concerns an isolated PR01079 polypeptide,comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%
positives, more preferably at least about 90 °6 positives, most preferably at least about 95 ~ positives when compared with the amino acid sequence of residues 30 to 226 of Figure 88 (SEQ ID NO:151).
In yet another aspect, the invention concerns an isolated PR01079 polypeptide, comprising the sequence of amino acid residues 30 to about 226, inclusive of Figure 88 (SEQ ID
NO:151), or a fragment thereof sufficient to provide a binding site for an anti-PR01079 antibody. Preferably, the PR01079 fragment retains a qualitative biological activity of a native PR01079 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01079 polypeptide having the sequence of amino acid residues from about 30 to about 226, inclusive of Figure 88 (SEQ ID NO:151), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80~ sequence identity, preferably at least about an 85~ sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 3b sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
34. PR0793 A cDNA clone (DNA56110-1437) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR0793".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0793 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0793 polypeptide having the sequence of amino acid residues from about 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0793 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 77 and about 490, inclusive, of Figure 89 (SEQ ID N0:152). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203113 (DNA56110-1437) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203113 (DNA56110-1437).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0793 polypeptide having the sequence of amino acid residues from 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0793 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid position 12 to about amino acid position 30, from about amino acid position 33 to about amino acid position 52, from about amino acid position 69 to about amino acid position 89 and from about amino acid position 93 to about amino acid position 109 in the PR0793 amino acid sequence (Figure 90, SEQ ID N0:153).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 138, inclusive of Figure 90 (SEQ ID
N0:153), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0793 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 89 (SEQ ID N0:152).
In another embodiment, the invention provides isolated PR0793 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0793 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 138 of Figure 90 (SEQ
ID N0:153).
In another aspect, the invention concerns an isolated PR0793 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 138, inclusive of Figure 90 (SEQ ID
N0:153).
In a further aspect, the invention concerns an isolated PR0793 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153).
In yet another aspect, the invention concerns an isolated PR0793 polypeptide, comprising the sequence of amino acid residues 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or a fragment thereof sufficient to provide a binding site for an anti-PR0793 antibody. Preferably, the PR0793 fragment retains a qualitative biological activity of a native PR0793 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0793 polypeptide having the sequence of amino acid residues from about 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85%a sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA50177 comprising the nucleotide sequence of Figure 91 (SEQ ID N0:154).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0793 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0793 polypeptide having the sequence of amino acid residues from about 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0793 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 77 and about 490, inclusive, of Figure 89 (SEQ ID N0:152). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203113 (DNA56110-1437) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203113 (DNA56110-1437).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0793 polypeptide having the sequence of amino acid residues from 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0793 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid position 12 to about amino acid position 30, from about amino acid position 33 to about amino acid position 52, from about amino acid position 69 to about amino acid position 89 and from about amino acid position 93 to about amino acid position 109 in the PR0793 amino acid sequence (Figure 90, SEQ ID N0:153).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 138, inclusive of Figure 90 (SEQ ID
N0:153), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0793 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 89 (SEQ ID N0:152).
In another embodiment, the invention provides isolated PR0793 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0793 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 138 of Figure 90 (SEQ
ID N0:153).
In another aspect, the invention concerns an isolated PR0793 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 138, inclusive of Figure 90 (SEQ ID
N0:153).
In a further aspect, the invention concerns an isolated PR0793 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153).
In yet another aspect, the invention concerns an isolated PR0793 polypeptide, comprising the sequence of amino acid residues 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or a fragment thereof sufficient to provide a binding site for an anti-PR0793 antibody. Preferably, the PR0793 fragment retains a qualitative biological activity of a native PR0793 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0793 polypeptide having the sequence of amino acid residues from about 1 to about 138, inclusive of Figure 90 (SEQ ID N0:153), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85%a sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA50177 comprising the nucleotide sequence of Figure 91 (SEQ ID N0:154).
35. PR01016 A cDNA clone (DNA56113-1378) has been identified, having sequence identity with acyltransferases that encodes a novel polypeptide, designated in the present application as "PR01016".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01016 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01016 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156), or (b) the complement of the DNA molecule of (a). The term "or° as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-378, or in another embodiment, 19-378.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01016 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 168 or 222 and about 1301, inclusive, of Figure 92 (SEQ ID NO:155). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203049 (DNA56113-1378), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203049 (DNA56113-1378).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ
ID N0:156), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01016 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID
N0:156), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01016 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 93 (SEQ ID
N0:156). The transmembrane domains have been tentatively identified as extending from about amino acid position 305 through about amino acid position 330 and from about amino acid position 332 through about amino acid position 352 in the PR01016 amino acid sequence (Figure 93, SEQ ID N0:156).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156), or (b) the complement of the DNA of (a).
in another embodiment, the invention provides isolated PR01016 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01016 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 19 through 378 of Figure 93 (SEQ ID
N0:156).
In another aspect, the invention concerns an isolated PR01016 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156).
In a further aspect, the invention concerns an isolated PR01016 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 19 through 378 of Figure 93 (SEQ ID N0:156).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01016 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01016 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01016 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01016 polypeptide, by contacting the native PR01016 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1016 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01016 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01016 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156), or (b) the complement of the DNA molecule of (a). The term "or° as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-378, or in another embodiment, 19-378.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01016 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 168 or 222 and about 1301, inclusive, of Figure 92 (SEQ ID NO:155). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203049 (DNA56113-1378), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203049 (DNA56113-1378).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ
ID N0:156), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01016 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID
N0:156), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01016 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 18 in the sequence of Figure 93 (SEQ ID
N0:156). The transmembrane domains have been tentatively identified as extending from about amino acid position 305 through about amino acid position 330 and from about amino acid position 332 through about amino acid position 352 in the PR01016 amino acid sequence (Figure 93, SEQ ID N0:156).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156), or (b) the complement of the DNA of (a).
in another embodiment, the invention provides isolated PR01016 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01016 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 19 through 378 of Figure 93 (SEQ ID
N0:156).
In another aspect, the invention concerns an isolated PR01016 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156).
In a further aspect, the invention concerns an isolated PR01016 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 19 through 378 of Figure 93 (SEQ ID N0:156).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01016 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 378, inclusive of Figure 93 (SEQ ID N0:156), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01016 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01016 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01016 polypeptide, by contacting the native PR01016 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1016 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
36. PR01013 Applicants have identified a cDNA clone that encodes a novel polypeptide having sequence identity with P120, wherein the polypeptide is designated in the present application as "PR01013".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01013 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01013 polypeptide having amino acid residues 1 through 409 of Figure 95 (SEQ ID
N0:158), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA56410-1414 which includes the nucleotide sequence encoding PR01013.
In another embodiment, the invention provides isolated PR01013 polypeptide. In particular, the invention provides isolated native sequence PRO 1013 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 409 of Figure 95 (SEQ ID N0:158).
Optionally, the PR01013 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA56410-1414.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01013 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01013 polypeptide having amino acid residues 1 through 409 of Figure 95 (SEQ ID
N0:158), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA56410-1414 which includes the nucleotide sequence encoding PR01013.
In another embodiment, the invention provides isolated PR01013 polypeptide. In particular, the invention provides isolated native sequence PRO 1013 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 409 of Figure 95 (SEQ ID N0:158).
Optionally, the PR01013 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited on June 2, 1998 with the ATCC as DNA56410-1414.
37. PR0937 Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to glypican family proteins, wherein the polypeptide is designated in the present application as "PR0937".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0937 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0937 polypeptide having amino acid residues 1 to 556 of Figure 97 (SEQ ID N0:160), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0937 polypeptide having amino acid residues about 23 to 556 of Figure 97 (SEQ ID
N0:160), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA56436-1448 vector deposited on May 27, 1998, as ATCC 209902 which includes the nucleotide sequence encoding PR0937.
In another embodiment, the invention provides isolated PR0937 polypeptide. In particular, the invention provides isolated native sequence PR0937 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 556 of Figure 97 (SEQ ID N0:160).
Additional embodiments of the present invention are directed to PR0937 polypeptides comprising amino acids about 23 to 556 of Figure 97 (SEQ ID N0:160). Optionally, the PR0937 polypeptide is obtained or is obtainable by . expressing the polypeptide encoded by the cDNA insert of the DNA56436-1448 vector deposited on May 27, 1998 as ATCC
209902.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0937 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0937 polypeptide having amino acid residues 1 to 556 of Figure 97 (SEQ ID N0:160), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0937 polypeptide having amino acid residues about 23 to 556 of Figure 97 (SEQ ID
N0:160), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA56436-1448 vector deposited on May 27, 1998, as ATCC 209902 which includes the nucleotide sequence encoding PR0937.
In another embodiment, the invention provides isolated PR0937 polypeptide. In particular, the invention provides isolated native sequence PR0937 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 556 of Figure 97 (SEQ ID N0:160).
Additional embodiments of the present invention are directed to PR0937 polypeptides comprising amino acids about 23 to 556 of Figure 97 (SEQ ID N0:160). Optionally, the PR0937 polypeptide is obtained or is obtainable by . expressing the polypeptide encoded by the cDNA insert of the DNA56436-1448 vector deposited on May 27, 1998 as ATCC
209902.
38. PR0842 A cDNA clone (DNA56855-1447) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0842."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0842 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95°k sequence identity to (a) a DNA molecule encoding a PR0842 polypeptide having the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID N0:165), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0842 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 219 and about 509, inclusive, of Figure 98 (SEQ ID N0:164). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203004 (DNA56855-1447), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203004 (DNA56855-1447).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID
N0:165), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0842 polypeptide having the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID
N0:165), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0842 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position I
through about amino acid position 22 in the sequence of Figure 99 (SEQ ID
N0:165).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80%a positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 23 to about 119, inclusive of Figure 99 (SEQ
ID N0:165), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0842 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0842 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0842 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 to 119 of Figure 99 (SEQ ID N0:165).
In another aspect, the invention concerns an isolated PR0842 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 23 to about 119, inclusive of Figure 99 (SEQ
ID N0:165).
In a further aspect, the invention concerns an isolated PR0842 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 23 to 119 of Figure 99 (SEQ ID N0:165).
In yet another aspect, the invention concerns an isolated PR0842 polypeptide, comprising the sequence of amino acid residues 23 to about 119, inclusive of Figure 99 (SEQ ID
N0:165), or a fragment thereof sufficient to provide a binding site for an anti-PR0842 antibody. Preferably, the PR0842 fragment retains a qualitative biological activity of a native PR0842 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0842 polypeptide having the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID N0:165), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0842 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95°k sequence identity to (a) a DNA molecule encoding a PR0842 polypeptide having the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID N0:165), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0842 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 219 and about 509, inclusive, of Figure 98 (SEQ ID N0:164). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203004 (DNA56855-1447), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203004 (DNA56855-1447).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID
N0:165), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0842 polypeptide having the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID
N0:165), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0842 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position I
through about amino acid position 22 in the sequence of Figure 99 (SEQ ID
N0:165).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80%a positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 23 to about 119, inclusive of Figure 99 (SEQ
ID N0:165), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0842 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0842 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0842 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 to 119 of Figure 99 (SEQ ID N0:165).
In another aspect, the invention concerns an isolated PR0842 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 23 to about 119, inclusive of Figure 99 (SEQ
ID N0:165).
In a further aspect, the invention concerns an isolated PR0842 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 23 to 119 of Figure 99 (SEQ ID N0:165).
In yet another aspect, the invention concerns an isolated PR0842 polypeptide, comprising the sequence of amino acid residues 23 to about 119, inclusive of Figure 99 (SEQ ID
N0:165), or a fragment thereof sufficient to provide a binding site for an anti-PR0842 antibody. Preferably, the PR0842 fragment retains a qualitative biological activity of a native PR0842 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0842 polypeptide having the sequence of amino acid residues from about 23 to about 119, inclusive of Figure 99 (SEQ ID N0:165), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
39. PR0839 A cDNA clone (DNA56859-1445) has been identified that encodes a novel polypeptide, designated in the present application as "PR0839."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0839 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0839 polypeptide having the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID NO: I67), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0839 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 71 and about 262, inclusive, of Figure 100 (SEQ ID N0:166). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203019 (DNA56859-1445), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic s acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203019 (DNA56859-1445).
in a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID
N0:167), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, and preferably at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0839 polypeptide having the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID NO: 167}, or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0839 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 101 (SEQ ID
N0:167).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 24 to about 87, inclusive of Figure 101 (SEQ
ID N0:167), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0839 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0839 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0839 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 to 87 of Figure 101 (SEQ ID N0:167).
In another aspect, the invention concerns an isolated PR0839 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 24 to about 87, inclusive of Figure 101 (SEQ
ID N0:167).
In a further aspect, the invention concerns an isolated PR0839 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 24 to 87 of Figure 101 (SEQ ID N0:167).
In yet another aspect, the invention concerns an isolated PR0839 polypeptide, comprising the sequence of amino acid residues 24 to about 87, inclusive of Figure 101 (SEQ ID
N0:167), or a fragment thereof sufficient to provide a binding site for an anti-PR0839 antibody. Preferably, the PR0839 fragment retains a qualitative biological activity of a native PR0839 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0839 polypeptide having the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID N0:167), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0839 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0839 polypeptide having the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID NO: I67), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0839 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 71 and about 262, inclusive, of Figure 100 (SEQ ID N0:166). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203019 (DNA56859-1445), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic s acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203019 (DNA56859-1445).
in a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID
N0:167), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, and preferably at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0839 polypeptide having the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID NO: 167}, or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0839 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 23 in the sequence of Figure 101 (SEQ ID
N0:167).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 24 to about 87, inclusive of Figure 101 (SEQ
ID N0:167), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0839 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR0839 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0839 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 24 to 87 of Figure 101 (SEQ ID N0:167).
In another aspect, the invention concerns an isolated PR0839 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 24 to about 87, inclusive of Figure 101 (SEQ
ID N0:167).
In a further aspect, the invention concerns an isolated PR0839 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 24 to 87 of Figure 101 (SEQ ID N0:167).
In yet another aspect, the invention concerns an isolated PR0839 polypeptide, comprising the sequence of amino acid residues 24 to about 87, inclusive of Figure 101 (SEQ ID
N0:167), or a fragment thereof sufficient to provide a binding site for an anti-PR0839 antibody. Preferably, the PR0839 fragment retains a qualitative biological activity of a native PR0839 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0839 polypeptide having the sequence of amino acid residues from about 24 to about 87, inclusive of Figure 101 (SEQ ID N0:167), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
40. PR01180 Applicants have identified a cDNA clone (DNA56860-1510) having homology to nucleic acid encoding methyltransferase enzymes that encodes a novel polypeptide, designated in the present application as "PR01180" .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01180 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1180 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID
N0:169), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01180 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 78 or about 147 and about 908, inclusive of Figure 102 (SEQ ID N0:168).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209952 (DNA56860-1510). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209952 (DNA56860-1510).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID
N0:169).
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01180 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 103 (SEQ
ID N0:169).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ
ID N0:169).
Another embodiment is directed to fragments of a PROI 180 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01180 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PROI 180 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 24 to about 277 of Figure 103 (SEQ ID N0:169).
In another aspect, the invention concerns an isolated PRO 1180 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID N0:169).
In a further aspect, the invention concerns an isolated PRO 1180 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID
N0:169).
In yet another aspect, the invention concerns an isolated PRO 1180 polypeptide, comprising the sequence of amino acid residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID N0:169), or a fragment thereof sufficient to provide a binding site for an anti-PR01180 antibody.
Preferably, the PR01180 fragment retains a qualitative biological activity of a native PR01180 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01180 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01180 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01180 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01180 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PRO 1180 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01180 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1180 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID
N0:169), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01180 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 78 or about 147 and about 908, inclusive of Figure 102 (SEQ ID N0:168).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209952 (DNA56860-1510). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209952 (DNA56860-1510).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID
N0:169).
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01180 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 103 (SEQ
ID N0:169).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ
ID N0:169).
Another embodiment is directed to fragments of a PROI 180 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01180 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PROI 180 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 24 to about 277 of Figure 103 (SEQ ID N0:169).
In another aspect, the invention concerns an isolated PRO 1180 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID N0:169).
In a further aspect, the invention concerns an isolated PRO 1180 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID
N0:169).
In yet another aspect, the invention concerns an isolated PRO 1180 polypeptide, comprising the sequence of amino acid residues 1 or about 24 to about 277, inclusive of Figure 103 (SEQ ID N0:169), or a fragment thereof sufficient to provide a binding site for an anti-PR01180 antibody.
Preferably, the PR01180 fragment retains a qualitative biological activity of a native PR01180 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01180 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01180 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01180 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01180 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PRO 1180 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
41. PR01134 A cDNA clone (DNA56865-1491) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01134".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01134 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8591; sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PROI 134 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01134 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 153 or about 222 and about 1265, inclusive, of Figure 104 (SEQ ID N0:170).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 °k sequence identity, more preferably at least about 90 k sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203022 (DNA56865-1491) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203022 (DNA56865-1491).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95°~ sequence identity to the sequence of amino acid residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01134 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 °o sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01134 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 105 (SEQ
ID N0:171).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1134 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 104 (SEQ ID N0:170).
In another embodiment, the invention provides isolated PR01134 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01134 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 24 to about 371 of Figure 105 (SEQ ID N0:171).
In another aspect, the invention concerns an isolated PRO I 134 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171).
In a further aspect, the invention concerns an isolated PR01134 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171).
In yet another aspect, the invention concerns an isolated PRO 1134 polypeptide, comprising the sequence of amino acid residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171), or a fragment thereof sufficient to provide a binding site for an anti-PR01134 antibody.
Preferably, the PR01134 fragment retains a qualitative biological activity of a native PR01134 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01134 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA52352 comprising the nucleotide sequence of SEQ ID N0:172 (see Figure 106).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA55725 comprising the nucleotide sequence of SEQ ID N0:173 (see Figure 107).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01134 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8591; sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PROI 134 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01134 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 153 or about 222 and about 1265, inclusive, of Figure 104 (SEQ ID N0:170).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 °k sequence identity, more preferably at least about 90 k sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203022 (DNA56865-1491) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203022 (DNA56865-1491).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95°~ sequence identity to the sequence of amino acid residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01134 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 °o sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01134 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 105 (SEQ
ID N0:171).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1134 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 104 (SEQ ID N0:170).
In another embodiment, the invention provides isolated PR01134 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01134 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 24 to about 371 of Figure 105 (SEQ ID N0:171).
In another aspect, the invention concerns an isolated PRO I 134 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171).
In a further aspect, the invention concerns an isolated PR01134 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171).
In yet another aspect, the invention concerns an isolated PRO 1134 polypeptide, comprising the sequence of amino acid residues 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID N0:171), or a fragment thereof sufficient to provide a binding site for an anti-PR01134 antibody.
Preferably, the PR01134 fragment retains a qualitative biological activity of a native PR01134 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01134 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 371, inclusive of Figure 105 (SEQ ID
N0:171), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA52352 comprising the nucleotide sequence of SEQ ID N0:172 (see Figure 106).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA55725 comprising the nucleotide sequence of SEQ ID N0:173 (see Figure 107).
42. PR 0 A cDNA clone (DNA56866-1342} has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0830".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0830 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a)-a DNA molecule encoding a PR0830 polypeptide having the sequence of amino acid residues from about 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0830 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 154 or about 253 and about 414, inclusive, of Figure 108 (SEQ ID N0:174).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203023 (DNA56866-1342) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203023 (DNA56866-1342).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0830 polypeptide having the sequence of amino acid residues from 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID N0:175), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isotated nucleic acid molecule comprising DNA encoding a PR0830 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 33 in the sequence of Figure 109 (SEQ
ID N0:175).
$ In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 34 to about 87, inclusive of Figtue 109 (SEQ ID N0:175), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0830 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 108 (SEQ ID N0:174).
In another embodiment, the invention provides isolated PR0830 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0830 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 34 to about 87 of Figure 109 (SEQ ID N0:175).
In another aspect, the invention concerns an isolated PR0830 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID N0:175).
In a further aspect, the invention concerns an isolated PR0830 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175).
In yet another aspect, the invention concerns an isolated PR0830 polypeptide, comprising the sequence of amino acid residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ
ID N0:175), or a fragment thereof sufficient to provide a binding site for an anti-PR0830 antibody.
Preferably, the PR0830 fragment retains a qualitative biological activity of a native PR0830 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0830 polypeptide having the sequence of amino acid residues from about 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0830 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a)-a DNA molecule encoding a PR0830 polypeptide having the sequence of amino acid residues from about 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0830 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 154 or about 253 and about 414, inclusive, of Figure 108 (SEQ ID N0:174).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203023 (DNA56866-1342) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203023 (DNA56866-1342).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0830 polypeptide having the sequence of amino acid residues from 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID N0:175), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isotated nucleic acid molecule comprising DNA encoding a PR0830 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 33 in the sequence of Figure 109 (SEQ
ID N0:175).
$ In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 34 to about 87, inclusive of Figtue 109 (SEQ ID N0:175), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0830 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 108 (SEQ ID N0:174).
In another embodiment, the invention provides isolated PR0830 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0830 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 34 to about 87 of Figure 109 (SEQ ID N0:175).
In another aspect, the invention concerns an isolated PR0830 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID N0:175).
In a further aspect, the invention concerns an isolated PR0830 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175).
In yet another aspect, the invention concerns an isolated PR0830 polypeptide, comprising the sequence of amino acid residues 1 or about 34 to about 87, inclusive of Figure 109 (SEQ
ID N0:175), or a fragment thereof sufficient to provide a binding site for an anti-PR0830 antibody.
Preferably, the PR0830 fragment retains a qualitative biological activity of a native PR0830 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0830 polypeptide having the sequence of amino acid residues from about 1 or about 34 to about 87, inclusive of Figure 109 (SEQ ID
N0:175), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
43. PRO1115 A cDNA clone (DNA56868-1478) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PRO1115".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1I IS polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1115 polypeptide having the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID N0:177), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1115 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 249 and about 1523, inclusive, of Figure 110 (SEQ ID N0:176). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203024 (DNA56868-1478), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203024 (DNA56868-1478).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID
N0:177), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1115 polypeptide having the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID NO:
177), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1115 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and one or more of its transmembrane domains deleted or inactivated, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 111 (SEQ ID NO:
177). Transmembrane domains have been tentatively identified as extending from about amino acid positions 35-54, 75-97, 126-146, 185-204, 333-350, and 352-371 in the PR01115 amino acid sequence (Figure 111, SEQ ID NO: 177).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 21 to about 445, inclusive of Figure 111 (SEQ
ID N0:177), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01115 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO1115 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1115 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 445 of Figure 111 (SEQ ID N0:177).
In another aspect, the invention concerns an isolated PR01115 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 445, inclusive of Figure 111 (SEQ
ID N0:177).
In a further aspect, the invention concerns an isolated PRO 1115 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to 445 of Figure 111 (SEQ ID N0:177).
In yet another aspect, the invention concerns an isolated PRO 1115 polypeptide, comprising the sequence of amino acid residues 21 to about 445, inclusive of Figure 111 (SEQ ID
N0:177), or a fragment thereof sufficient to provide a binding site for an anti-PR01115 antibody. Preferably, the PR01115 fragment retains a qualitative biological activity of a native PR01115 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under suingent conditions with (a) a DNA molecule encoding a PR01115 polypeptide having the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID N0:177), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 ~'o sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
WO 99/63088 PCTlUS99/12252 44. PR01277 A cDNA clone (DNA56869-1545) has been identified that encodes a novel polypeptidehaving homology to Coch-SB2 and designated in the present application as "PRO 1277. "
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01277 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01277 polypeptide having the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ ID N0:179), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01277 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 266 and about 2221, inclusive, of Figure 112 (SEQ ID N0:178). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203161 (DNA56869-1545), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203161 (DNA56869-1545).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ ID
N0:179), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01277 polypeptide having the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ
ID N0:179), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01277 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 26 in the sequence of Figure 113 (SEQ ID
N0:179). The transmembrane domain has been tentatively identified as extending from about amino acid position 181 to about amino acid position 200 in the PR01277 amino acid sequence (Figure 113, SEQ ID N0:179).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 27 to about 678, inclusive of Figure I13 (SEQ
ID N0:179), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1277 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01277 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1277 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 27 to 678 of Figure 113 (SEQ ID N0:179).
In another aspect, the invention concerns an isolated PR01277 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 27 to about 678; inclusive of Figure 113 (SEQ
ID N0:179).
In a further aspect, the invention concerns an isolated PR01277 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 27 to 678 of Figure 113 (SEQ ID N0:179).
In yet another aspect, the invention concerns an isolated PRO 1277 polypeptide, comprising the sequence of amino acid residues 27 to about 678, inclusive of Figure 113 (SEQ ID
N0:179), or a fragment thereof sufficient to provide a binding site for an anti-PR01277 antibody. Preferably, the PR01277 fragment retains a qualitative biological activity of a native PR01277 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01277 polypeptide having the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ ID N0:179), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PROI277 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01277 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01277 polypeptide, by contacting the native PR01277 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1277 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1I IS polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1115 polypeptide having the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID N0:177), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1115 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 249 and about 1523, inclusive, of Figure 110 (SEQ ID N0:176). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203024 (DNA56868-1478), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203024 (DNA56868-1478).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID
N0:177), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1115 polypeptide having the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID NO:
177), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1115 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and one or more of its transmembrane domains deleted or inactivated, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 111 (SEQ ID NO:
177). Transmembrane domains have been tentatively identified as extending from about amino acid positions 35-54, 75-97, 126-146, 185-204, 333-350, and 352-371 in the PR01115 amino acid sequence (Figure 111, SEQ ID NO: 177).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 21 to about 445, inclusive of Figure 111 (SEQ
ID N0:177), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01115 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO1115 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1115 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 445 of Figure 111 (SEQ ID N0:177).
In another aspect, the invention concerns an isolated PR01115 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 445, inclusive of Figure 111 (SEQ
ID N0:177).
In a further aspect, the invention concerns an isolated PRO 1115 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to 445 of Figure 111 (SEQ ID N0:177).
In yet another aspect, the invention concerns an isolated PRO 1115 polypeptide, comprising the sequence of amino acid residues 21 to about 445, inclusive of Figure 111 (SEQ ID
N0:177), or a fragment thereof sufficient to provide a binding site for an anti-PR01115 antibody. Preferably, the PR01115 fragment retains a qualitative biological activity of a native PR01115 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under suingent conditions with (a) a DNA molecule encoding a PR01115 polypeptide having the sequence of amino acid residues from about 21 to about 445, inclusive of Figure 111 (SEQ ID N0:177), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 ~'o sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
WO 99/63088 PCTlUS99/12252 44. PR01277 A cDNA clone (DNA56869-1545) has been identified that encodes a novel polypeptidehaving homology to Coch-SB2 and designated in the present application as "PRO 1277. "
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01277 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01277 polypeptide having the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ ID N0:179), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01277 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 266 and about 2221, inclusive, of Figure 112 (SEQ ID N0:178). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203161 (DNA56869-1545), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203161 (DNA56869-1545).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ ID
N0:179), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01277 polypeptide having the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ
ID N0:179), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01277 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 26 in the sequence of Figure 113 (SEQ ID
N0:179). The transmembrane domain has been tentatively identified as extending from about amino acid position 181 to about amino acid position 200 in the PR01277 amino acid sequence (Figure 113, SEQ ID N0:179).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 27 to about 678, inclusive of Figure I13 (SEQ
ID N0:179), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1277 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01277 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1277 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 27 to 678 of Figure 113 (SEQ ID N0:179).
In another aspect, the invention concerns an isolated PR01277 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 27 to about 678; inclusive of Figure 113 (SEQ
ID N0:179).
In a further aspect, the invention concerns an isolated PR01277 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 27 to 678 of Figure 113 (SEQ ID N0:179).
In yet another aspect, the invention concerns an isolated PRO 1277 polypeptide, comprising the sequence of amino acid residues 27 to about 678, inclusive of Figure 113 (SEQ ID
N0:179), or a fragment thereof sufficient to provide a binding site for an anti-PR01277 antibody. Preferably, the PR01277 fragment retains a qualitative biological activity of a native PR01277 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01277 polypeptide having the sequence of amino acid residues from about 27 to about 678, inclusive of Figure 113 (SEQ ID N0:179), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PROI277 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01277 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01277 polypeptide, by contacting the native PR01277 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1277 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
45. PR01135 Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to alpha 1,2-mannosidase, wherein the polypeptide is designated in the present application as "PR01135".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01135 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01135 polypeptide having amino acid residues 1 to 541 of Figure 115 (SEQ ID N0:181), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR01135 polypeptide having amino acid residues about 22 to 541 of Figure 115 (SEQ ID
N0:181), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA56870-1492 vector deposited on June 2, 1998 as ATCC 209925 which includes the nucleotide sequence encoding PR01135.
In another embodiment, the invention provides isolated PR01135 poiypeptide. In particular, the invention provides isolated native sequence PRO I 135 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 541 of Figure 115 (SEQ ID N0:181).
Additional embodiments of the present invention are directed to PR01135 polypeptides comprising amino acids about 22 to 541 of Figure 115 (SEQ ID N0:181). Optionally, the PR01135 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA56870-1492 vector deposited on June 2, 1998 as ATCC
209925.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01135 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01135 polypeptide having amino acid residues 1 to 541 of Figure 115 (SEQ ID N0:181), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR01135 polypeptide having amino acid residues about 22 to 541 of Figure 115 (SEQ ID
N0:181), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA56870-1492 vector deposited on June 2, 1998 as ATCC 209925 which includes the nucleotide sequence encoding PR01135.
In another embodiment, the invention provides isolated PR01135 poiypeptide. In particular, the invention provides isolated native sequence PRO I 135 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 541 of Figure 115 (SEQ ID N0:181).
Additional embodiments of the present invention are directed to PR01135 polypeptides comprising amino acids about 22 to 541 of Figure 115 (SEQ ID N0:181). Optionally, the PR01135 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA56870-1492 vector deposited on June 2, 1998 as ATCC
209925.
46. PR01114 A cDNA clone (DNA57033-1403) has been identified that encodes a novel interferon receptor polypeptide, designated in the present application as "PR01114 interferon receptor".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01114 interferon receptor polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80°k sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01114 interferon receptor polypeptide having the sequence of amino acid residues from about 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01114 interferon receptor polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 250 or about 337 and about 1 I82, inclusive, of Figure 116 (SEQ ID N0:182). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209905 (DNA57033-1403) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209905 (DNA57033-1403).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID
N0:183), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01114 interferon receptor polypeptide having the sequence of amino acid residues from 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA
molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01114 interferon receptor polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 29 in the sequence of Figure 117 (SEQ ID N0:183).
The transmembrane domain has been tentatively identified as extending from about amino acid position 230 to about amino acid position 255 in the PR01114 interferon receptor amino acid sequence (Figure 117, SEQ ID
N0:183).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01114 interferon receptor polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 116 (SEQ ID N0:182).
In another embodiment, the invention provides isolated PR01114 interferon receptor polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01114 interferon receptor polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 30 to about 311 of Figure 117 (SEQ ID N0:183).
In another aspect, the invention concerns an isolated PR01114 interferon receptor polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%
sequence identity to the sequence of amino acid residues 1 or about 30 to about 31 I , inclusive of Figure 117 (SEQ ID N0:183).
In a further aspect, the invention concerns an isolated PR01114 interferon receptor polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183).
In yet another aspect, the invention concerns an isolated PR01114 interferon receptor polypeptide, comprising the sequence of amino acid residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID
N0:183), or a fragment thereof sufficient to provide a binding site for an anti-PR01114 interferon receptor antibody. Preferably, the PR01114 interferon receptor fragment retains a qualitative biological activity of a native PR01114 interferon receptor polypeptide.
In a still fiirther aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01114 interferon receptor polypeptide having the sequence of amino acid residues from about 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 %
sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 %
sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01114 interferon receptor polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01114 interferon receptor antibody:
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01114 interferon receptor polypeptide by contacting the native PR01114 interferon receptor polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01114 interferon receptor polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA48466 comprising the nucleotide sequence of SEQ ID N0:184 (see Figure 118).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01114 interferon receptor polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80°k sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01114 interferon receptor polypeptide having the sequence of amino acid residues from about 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01114 interferon receptor polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 250 or about 337 and about 1 I82, inclusive, of Figure 116 (SEQ ID N0:182). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209905 (DNA57033-1403) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209905 (DNA57033-1403).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID
N0:183), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01114 interferon receptor polypeptide having the sequence of amino acid residues from 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA
molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01114 interferon receptor polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 29 in the sequence of Figure 117 (SEQ ID N0:183).
The transmembrane domain has been tentatively identified as extending from about amino acid position 230 to about amino acid position 255 in the PR01114 interferon receptor amino acid sequence (Figure 117, SEQ ID
N0:183).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01114 interferon receptor polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 116 (SEQ ID N0:182).
In another embodiment, the invention provides isolated PR01114 interferon receptor polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01114 interferon receptor polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 30 to about 311 of Figure 117 (SEQ ID N0:183).
In another aspect, the invention concerns an isolated PR01114 interferon receptor polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%
sequence identity to the sequence of amino acid residues 1 or about 30 to about 31 I , inclusive of Figure 117 (SEQ ID N0:183).
In a further aspect, the invention concerns an isolated PR01114 interferon receptor polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183).
In yet another aspect, the invention concerns an isolated PR01114 interferon receptor polypeptide, comprising the sequence of amino acid residues 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID
N0:183), or a fragment thereof sufficient to provide a binding site for an anti-PR01114 interferon receptor antibody. Preferably, the PR01114 interferon receptor fragment retains a qualitative biological activity of a native PR01114 interferon receptor polypeptide.
In a still fiirther aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01114 interferon receptor polypeptide having the sequence of amino acid residues from about 1 or about 30 to about 311, inclusive of Figure 117 (SEQ ID N0:183), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 %
sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 %
sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01114 interferon receptor polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01114 interferon receptor antibody:
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01114 interferon receptor polypeptide by contacting the native PR01114 interferon receptor polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01114 interferon receptor polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA48466 comprising the nucleotide sequence of SEQ ID N0:184 (see Figure 118).
47. PRO~$'Z
Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to glutathione peroxidases wherein the polypeptide is designated in the present application as "PR0828".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0828 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0828 polypeptide having amino acid residues 1 to 187 of Figure 120 (SEQ ID N0:189), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0828 polypeptide having amino acid residues about 22 to 187 of Figure 120 (SEQ ID
N0:189), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA57037-1444 vector deposited on May 27, 1998 as ATCC 209903 which includes the nucleotide sequence encoding PR0828.
In another embodiment, the invention provides isolated PR0828 polypeptide. In particular, the invention provides isolated native sequence PR0828 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 187 of Figure 120 (SEQ ID N0:189).
Additional embodiments of the present invention are directed to PR0828 polypeptides comprising amino acids about 22 to 187 of Figure 120 (SEQ ID N0:189). Optionally, the PR0828 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA57037-1444 vector deposited on May 27, 1998 as ATCC
209903.
Applicants have identified a cDNA clone that encodes a novel polypeptide having homology to glutathione peroxidases wherein the polypeptide is designated in the present application as "PR0828".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0828 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR0828 polypeptide having amino acid residues 1 to 187 of Figure 120 (SEQ ID N0:189), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR0828 polypeptide having amino acid residues about 22 to 187 of Figure 120 (SEQ ID
N0:189), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA57037-1444 vector deposited on May 27, 1998 as ATCC 209903 which includes the nucleotide sequence encoding PR0828.
In another embodiment, the invention provides isolated PR0828 polypeptide. In particular, the invention provides isolated native sequence PR0828 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 187 of Figure 120 (SEQ ID N0:189).
Additional embodiments of the present invention are directed to PR0828 polypeptides comprising amino acids about 22 to 187 of Figure 120 (SEQ ID N0:189). Optionally, the PR0828 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA57037-1444 vector deposited on May 27, 1998 as ATCC
209903.
48. PR01009 A cDNA clone (DNA57129-1413) has been identified, having sequence identity with a long chain acyl-CoA synthetase homologue, a long chain acyl-CoA synthetase and a long chain acyl-CoA synthetase ligase that encodes a novel polypeptide, designated in the present application as "PR01009."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01009 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01009 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID N0:194), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two separate alternative embodiments provided herein, i.e., 1-615 or 23-615.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01009 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 41 or 107 and about 1885, inclusive, of Figure 121 (SEQ ID N0:193). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209977 (DNA57129-1413), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209977 (DNA57129-1413).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 23 to about 615, inclusive of Figure 122 (SEQ
ID N0:194), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01009 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID
N0:194), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01009 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 22 in the sequence of Figure 122 (SEQ ID
N0:194). The transmembrane domains have been tentatively identified as extending from about amino acid positions 140-161, 213-229 and 312-334 in the PR01009 amino acid sequence (Figure 122, SEQ ID N0:194).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID N0:194), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01009 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01009 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 23 to 615 of Figure 122 (SEQ ID
N0:194).
In another aspect, the invention concerns an isolated PRO 1009 polypeptide, comprising an amino acid sequence having at least about 8096 sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 k sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID N0:194).
In a further aspect, the invention concerns an isolated PR01009 polypeptide, comprising an amino acid sequence scoring at least about 8096 positives, preferably at least about 85 %
positives, more preferably at least about 90 ~ positives, most preferably at least about 95 k positives when compared with the amino acid sequence of residues 1 or 23 to 615 of Figure 122 (SEQ ID N0:194).
In yet another aspect, the invention concerns an isolated PRO 1009 polypeptide, comprising the sequence of amino acid residues 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID
N0:194), or a fragment thereof sufficient to provide a binding site for an anti-PR01009 antibody. Preferably, the PR01009 fragment retains a qualitative biological activity of a native PR01009 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01~9 polypeptide having the sequence of amino acid residues from about 1 or 23 through about 615, inclusive of Figure 122 (SEQ ID
N0:194), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 909b sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01009 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01009 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01009 polypeptide, by contacting the native PR01009 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01009 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA50853 comprising the nucleotide sequence of Figure 123 (SEQ ID N0:195).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01009 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01009 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID N0:194), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two separate alternative embodiments provided herein, i.e., 1-615 or 23-615.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01009 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 41 or 107 and about 1885, inclusive, of Figure 121 (SEQ ID N0:193). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209977 (DNA57129-1413), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209977 (DNA57129-1413).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 23 to about 615, inclusive of Figure 122 (SEQ
ID N0:194), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01009 polypeptide having the sequence of amino acid residues from about 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID
N0:194), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01009 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 22 in the sequence of Figure 122 (SEQ ID
N0:194). The transmembrane domains have been tentatively identified as extending from about amino acid positions 140-161, 213-229 and 312-334 in the PR01009 amino acid sequence (Figure 122, SEQ ID N0:194).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID N0:194), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01009 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01009 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 23 to 615 of Figure 122 (SEQ ID
N0:194).
In another aspect, the invention concerns an isolated PRO 1009 polypeptide, comprising an amino acid sequence having at least about 8096 sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 k sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID N0:194).
In a further aspect, the invention concerns an isolated PR01009 polypeptide, comprising an amino acid sequence scoring at least about 8096 positives, preferably at least about 85 %
positives, more preferably at least about 90 ~ positives, most preferably at least about 95 k positives when compared with the amino acid sequence of residues 1 or 23 to 615 of Figure 122 (SEQ ID N0:194).
In yet another aspect, the invention concerns an isolated PRO 1009 polypeptide, comprising the sequence of amino acid residues 1 or 23 to about 615, inclusive of Figure 122 (SEQ ID
N0:194), or a fragment thereof sufficient to provide a binding site for an anti-PR01009 antibody. Preferably, the PR01009 fragment retains a qualitative biological activity of a native PR01009 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01~9 polypeptide having the sequence of amino acid residues from about 1 or 23 through about 615, inclusive of Figure 122 (SEQ ID
N0:194), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 909b sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01009 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01009 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01009 polypeptide, by contacting the native PR01009 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01009 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA50853 comprising the nucleotide sequence of Figure 123 (SEQ ID N0:195).
49. PR01007 Applicants have identified a cDNA clone that encodes a novel polypeptide having sequence identity with MAGPIAP, wherein the polypeptide is designated in the present application as "PR01007".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01007 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01007 polypeptide having amino acid residues 1 through 346 of Figure 125 (SEQ ID
N0:197), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 9, 1998 with the ATCC as DNA57690-1374 which includes the nucleotide sequence encoding PR01007.
In another embodiment, the invention provides isolated PR01007 polypeptide. In particular, the invention provides isolated native sequence PRO 1007 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 346 of Figure 125 (SEQ ID N0:197).
An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR01007 polypeptide. Optionally, the PR01007 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited with the ATCC on June 9, 1998 as DNA57690-1374.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01007 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01007 polypeptide having amino acid residues 1 through 346 of Figure 125 (SEQ ID
N0:197), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 9, 1998 with the ATCC as DNA57690-1374 which includes the nucleotide sequence encoding PR01007.
In another embodiment, the invention provides isolated PR01007 polypeptide. In particular, the invention provides isolated native sequence PRO 1007 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 346 of Figure 125 (SEQ ID N0:197).
An additional embodiment of the present invention is directed to an isolated extracellular domain of a PR01007 polypeptide. Optionally, the PR01007 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited with the ATCC on June 9, 1998 as DNA57690-1374.
50. PR01056 A cDNA clone (DNA57693-1424) has been identified, having homology to nucleic acid encoding a chloride channel protein that encodes a novel polypeptide, designated in the present application as "PR01056".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01056 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01056 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01056 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 56 or about 110 and about 415, inclusive, of Figure 126 (SEQ ID NO: I98).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a fitrttter aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203008 (DNA57693-1424) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203008 (DNA57693-1424).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199), or (b) the complement of the DNA of (a).
In ~ further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01056 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID N0:199), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01056 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., uansmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 18 in the sequence of Figure 127 (SEQ
ID N0:199). The transmembrane domain has been tentatively identified as extending from about amino acid position 39 to about amino acid position 58 in the PR01056 amino acid sequence (Figure 127, SEQ ID N0:199).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ 1D N0:199), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO1056 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 126 (SEQ ID N0:198).
In another embodiment, the invention provides isolated PR01056 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01056 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 19 to about 120 of Figure 127 (SEQ ID N0:199).
In another aspect, the invention concerns an isolated PR01056 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID N0:199).
In a further aspect, the invention concerns an isolated PRO 1056 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199).
In yet another aspect, the invention concerns an isolated PR01056 polypeptide, comprising the sequence of amino acid residues I or about 19 to about 120, inclusive of Figure 127 (SEQ ID N0:199), or a fragment thereof sufficient to provide a binding site for an anti-PR01056 antibody.
Preferably, the PR01056 fragment retains a qualitative biological activity of a native PR01056 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01056 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199), or (b) the complement of the DNA molecule of (a), and if~the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90y6 sequence identity, most preferably at least about a 95% sequence identity to (a} or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01056 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01056 antibody.
In a further embodiment, the invention concerns a method of identifying agorusts or antagonists of a native PR01056 polypeptide by contacting the native PR01056 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01056 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01056 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01056 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01056 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 56 or about 110 and about 415, inclusive, of Figure 126 (SEQ ID NO: I98).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a fitrttter aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203008 (DNA57693-1424) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203008 (DNA57693-1424).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199), or (b) the complement of the DNA of (a).
In ~ further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01056 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID N0:199), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01056 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., uansmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 18 in the sequence of Figure 127 (SEQ
ID N0:199). The transmembrane domain has been tentatively identified as extending from about amino acid position 39 to about amino acid position 58 in the PR01056 amino acid sequence (Figure 127, SEQ ID N0:199).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ 1D N0:199), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO1056 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 126 (SEQ ID N0:198).
In another embodiment, the invention provides isolated PR01056 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01056 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 19 to about 120 of Figure 127 (SEQ ID N0:199).
In another aspect, the invention concerns an isolated PR01056 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID N0:199).
In a further aspect, the invention concerns an isolated PRO 1056 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199).
In yet another aspect, the invention concerns an isolated PR01056 polypeptide, comprising the sequence of amino acid residues I or about 19 to about 120, inclusive of Figure 127 (SEQ ID N0:199), or a fragment thereof sufficient to provide a binding site for an anti-PR01056 antibody.
Preferably, the PR01056 fragment retains a qualitative biological activity of a native PR01056 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01056 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 120, inclusive of Figure 127 (SEQ ID
N0:199), or (b) the complement of the DNA molecule of (a), and if~the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90y6 sequence identity, most preferably at least about a 95% sequence identity to (a} or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01056 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01056 antibody.
In a further embodiment, the invention concerns a method of identifying agorusts or antagonists of a native PR01056 polypeptide by contacting the native PR01056 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01056 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
51. PR0826 A cDNA clone (DNA57694-1341) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0826".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0826 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0826 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0826 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 13 or about 79 and about 309, inclusive, of Figure 128 (SEQ ID N0:200).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203017 (DNA57694-1341) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the mtcleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203017 (DNA57694-1341).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0826 polypeptide having the sequence of amino acid residues from I or about 23 to about 99, inclusive of Figure 129 (SEQ ID N0:201), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0826 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from about amino acid position 1 to about amino acid position 22 in the sequence of Figure 129 (SEQ
ID N0:201).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at (east about 95%
positives when compared with the amino acid sequence of residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID N0:201), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0826 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 128 (SEQ ID N0:200).
In another embodiment, the invention provides isolated PR0826 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0826 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 23 to about 99 of Figure 129 (SEQ ID N0:201).
In another aspect, the invention concerns an isolated PR0826 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID N0:201).
In a further aspect, the invention concerns an isolated PR0826 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 959b positives when compared with the amino acid sequence of residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201).
In yet another aspect, the invention concerns an isolated PR0826 polypeptide, comprising the sequence of amino acid residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ
ID N0:201), or a fragment thereof sufficient to provide a binding site for an anti-PR0826 antibody.
Preferably, the PR0826 fragment retains a qualitative biological activity of a native PR0826 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0826 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0826 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0826 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0826 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 13 or about 79 and about 309, inclusive, of Figure 128 (SEQ ID N0:200).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203017 (DNA57694-1341) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the mtcleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203017 (DNA57694-1341).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0826 polypeptide having the sequence of amino acid residues from I or about 23 to about 99, inclusive of Figure 129 (SEQ ID N0:201), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, prefereably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0826 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from about amino acid position 1 to about amino acid position 22 in the sequence of Figure 129 (SEQ
ID N0:201).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at (east about 95%
positives when compared with the amino acid sequence of residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID N0:201), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0826 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 128 (SEQ ID N0:200).
In another embodiment, the invention provides isolated PR0826 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0826 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 23 to about 99 of Figure 129 (SEQ ID N0:201).
In another aspect, the invention concerns an isolated PR0826 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID N0:201).
In a further aspect, the invention concerns an isolated PR0826 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 959b positives when compared with the amino acid sequence of residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201).
In yet another aspect, the invention concerns an isolated PR0826 polypeptide, comprising the sequence of amino acid residues 1 or about 23 to about 99, inclusive of Figure 129 (SEQ
ID N0:201), or a fragment thereof sufficient to provide a binding site for an anti-PR0826 antibody.
Preferably, the PR0826 fragment retains a qualitative biological activity of a native PR0826 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0826 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 99, inclusive of Figure 129 (SEQ ID
N0:201), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
52. PR0819 A cDNA clone (DNA57695-1340) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR0819".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0819 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0819 polypeptide having the sequence of amino acid residues from about I or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0819 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 46 or about 118 and about 201, inclusive, of Figure 130 (SEQ ID N0:202).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203006 (DNA57695-1340) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203006 (DNA57695-1340).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0819 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID N0:203), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 9'o sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0819 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 131 (SEQ
ID N0:203).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID N0:203), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0819 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 130 (SEQ ID N0:202).
In another embodiment, the invention provides isolated PR0819 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0819 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 52 of Figure 131 (SEQ ID N0:203).
In another aspect, the invention concerns an isolated PR0819 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID N0:203).
In a further aspect, the invention concerns an isolated PR0819 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203).
In yet another aspect, the invention concerns an isolated PR0819 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ
ID N0:203), or a fragment thereof sufficient to provide a binding site for an anti-PR0819 antibody.
Preferably, the PR0819 fragment retains a qualitative biological activity of a native PR0819 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0819 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0819 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0819 polypeptide having the sequence of amino acid residues from about I or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0819 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 46 or about 118 and about 201, inclusive, of Figure 130 (SEQ ID N0:202).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203006 (DNA57695-1340) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203006 (DNA57695-1340).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0819 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID N0:203), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 9'o sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0819 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 131 (SEQ
ID N0:203).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID N0:203), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0819 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 130 (SEQ ID N0:202).
In another embodiment, the invention provides isolated PR0819 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0819 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 52 of Figure 131 (SEQ ID N0:203).
In another aspect, the invention concerns an isolated PR0819 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID N0:203).
In a further aspect, the invention concerns an isolated PR0819 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203).
In yet another aspect, the invention concerns an isolated PR0819 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 52, inclusive of Figure 131 (SEQ
ID N0:203), or a fragment thereof sufficient to provide a binding site for an anti-PR0819 antibody.
Preferably, the PR0819 fragment retains a qualitative biological activity of a native PR0819 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0819 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 52, inclusive of Figure 131 (SEQ ID
N0:203), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
53. PR01006 A cDNA clone (DNA57699-1412) has been identified, having sequence identity with a virud protein believed to be a tyrosine protein kinase, that encodes a novel polypeptide, designated in the present application as "PRO 1006. "
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01006 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01006 polypeptide having the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-392, or in another embodiment, 24-392.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01006 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 28 or 97 and about 1203, inclusive, of Figure 132 (SEQ ID N0:204). Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203020 (DNA57699-1412), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203020 (DNA57699-1412).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ
ID N0:205), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01006 polypeptide having the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID
N0:205), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01006 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1006 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 24 through 392 of Figure 133 (SEQ ID
N0:205).
In another aspect, the invention concerns an isolated PR01006 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205).
In a further aspect, the invention concerns an isolated PR01006 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 24 through 392 of Figure 133 (SEQ ID N0:205).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01006 polypeptide having the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01006 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01006 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01006 polypeptide, by contacting the native PR01006 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01006 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01006 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01006 polypeptide having the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-392, or in another embodiment, 24-392.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01006 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 28 or 97 and about 1203, inclusive, of Figure 132 (SEQ ID N0:204). Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203020 (DNA57699-1412), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203020 (DNA57699-1412).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ
ID N0:205), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01006 polypeptide having the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID
N0:205), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01006 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1006 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 24 through 392 of Figure 133 (SEQ ID
N0:205).
In another aspect, the invention concerns an isolated PR01006 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205).
In a further aspect, the invention concerns an isolated PR01006 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 24 through 392 of Figure 133 (SEQ ID N0:205).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01006 polypeptide having the sequence of amino acid residues from about 1 or 24 to about 392, inclusive of Figure 133 (SEQ ID N0:205), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01006 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01006 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01006 polypeptide, by contacting the native PR01006 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01006 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
54. PR01112 Applicants have identified a cDNA clone that encodes a novel polypeptide having multiple transmembranedomains and having some sequence identity with a Mycobacterium tuberculosis peptide, a peptide found in a Dayhoff database designated as "MTY20B11-13", wherein the novel polypeptide is designated in the present application as "PR01112".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01112 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01112 polypeptide having the sequence of amino acid residues from 1 or about 14 through about 262 of Figure 135 (SEQ ID N0:207), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01112 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues about 20 or 59 through 809 of Figure 134 (SEQ ID N0:206). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in the ATCC Deposit of DNA57702-1476 made on June 9, 1998. In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in the ATCC Deposit of DNA57702-1476 made on June 9, 1998.
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 14 through about 262 of Figure 135 (SEQ ID
N0:207).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01112 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 13 of Figure 135 (SEQ ID N0:207). The transmembrane domains have been tentatively identified as extending from about amino acid positions 58-76, 99-113, 141-159 and 203-222 of Figure 135 (SEQ ID N0:207).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 14 through 262 of Figure 135 (SEQ ID N0:207).
Another embodiment is directed to fragments of a PRO 1112 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 60 to about 100 nucleotides in length.
In another embodiment, the invention provides isolated PR01112 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01112 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 14 through about 262 of Figure 135 (SEQ ID N0:207).
In another aspect, the invention concerns an isolated PR01112 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 14 through about 262 of Figure 135 (SEQ ID N0:207).
In a further aspect, the invention concerns an isolated PRO 1112 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 14 through about 262 of Figure 135 (SEQ ID N0:207).
In yet another aspect, the invention concerns an isolated PRO 1112 polypeptide, comprising the sequence of amino acid residues 1 or about 14 through about 262 of Figure 135 (SEQ ID
N0:207), or a fragment thereof sufficient to provide a binding site for an anti-PR01112 antibody. Preferably, the PR01112 fragment retains a qualitative biological activity of a native PR01112 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01112 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01112 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01112 polypeptide having the sequence of amino acid residues from 1 or about 14 through about 262 of Figure 135 (SEQ ID N0:207), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01112 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues about 20 or 59 through 809 of Figure 134 (SEQ ID N0:206). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in the ATCC Deposit of DNA57702-1476 made on June 9, 1998. In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in the ATCC Deposit of DNA57702-1476 made on June 9, 1998.
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 14 through about 262 of Figure 135 (SEQ ID
N0:207).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01112 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 13 of Figure 135 (SEQ ID N0:207). The transmembrane domains have been tentatively identified as extending from about amino acid positions 58-76, 99-113, 141-159 and 203-222 of Figure 135 (SEQ ID N0:207).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 14 through 262 of Figure 135 (SEQ ID N0:207).
Another embodiment is directed to fragments of a PRO 1112 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 60 to about 100 nucleotides in length.
In another embodiment, the invention provides isolated PR01112 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01112 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 14 through about 262 of Figure 135 (SEQ ID N0:207).
In another aspect, the invention concerns an isolated PR01112 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 14 through about 262 of Figure 135 (SEQ ID N0:207).
In a further aspect, the invention concerns an isolated PRO 1112 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 14 through about 262 of Figure 135 (SEQ ID N0:207).
In yet another aspect, the invention concerns an isolated PRO 1112 polypeptide, comprising the sequence of amino acid residues 1 or about 14 through about 262 of Figure 135 (SEQ ID
N0:207), or a fragment thereof sufficient to provide a binding site for an anti-PR01112 antibody. Preferably, the PR01112 fragment retains a qualitative biological activity of a native PR01112 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01112 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
55. PR01074 Applicants have identified a cDNA clone, DNA57704-1452, that encodes a novel polypeptide having homology to galactosyltransferase, wherein the polypeptide is designated in the present application as "PR01074".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01074 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 8S ~ sequence identity, more preferably at least about 90 R6 sequence identity, and most preferably at least about 9S 3b sequence identity to (a) a DNA molecule encoding a PRO 1074 polypeptide having the sequence of amino acid residues from 1 to about 331, inclusive of Figure 137 (SEQ ID N0:209), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01074 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 322 to 1314, inclusive of Figure 136 (SEQ ID N0:208). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209953 (DNAS7704-1452), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209953 (DNA57704-1452).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 9S % sequence identity to the sequence of amino acid residues 1 to about 331, inclusive of Figure 137 (SEQ ID N0:209).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01074 extracellular domain (ECD), with or without the initiating methionine, and its soluble variants (i.e.
transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule.
A type II transmembrane domain region has been tentatively identified as extending from about amino acid position 20 to 39 in the PR01074 amino acid sequence (Figure 137, SEQ ID
N0:209).
In another aspect; the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, and most preferably at least about 9S% positives when compared with the amino acid sequence of residues 1 to about 331, inclusive of Figure 137 (SEQ ID N0:209).
Another embodiment is directed to fragments of a PR01074 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PROI074 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention grovides isolated native sequence PRO 1074 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 331 of Figure 137 (SEQ ID N0:209).
In another aspect, the invention concerns an isolated PR01074 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to 331, inclusive of Figure 137 (SEQ ID
N0:209).
In a further aspect, the invention concerns an isolated PR01074 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, and most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 331 of Figure 137 (SEQ ID N0:209).
In another aspect, the invention concerns a PR01074 extracellular domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues X to 331 of Figure 2 (SEQ ID N0:3), wherein X
is any one of amino acid residues 35 to 44 of Figure 137 (SEQ ID N0:209).
In yet another aspect, the invention concerns an isolated PRO 1074 polypeptide, comprising the sequence of amino acid residues 1 to about 331, inclusive of Figure 137 (SEQ ID
N0:209), or a fragment thereof sufficient to provide a binding site for an anti-PR01074 antibody. Preferably, the PR01074 fragment retains a qualitative biological activity of a native PR01074 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01074 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PR01074 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01074 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01074 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01074 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01074 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 8S ~ sequence identity, more preferably at least about 90 R6 sequence identity, and most preferably at least about 9S 3b sequence identity to (a) a DNA molecule encoding a PRO 1074 polypeptide having the sequence of amino acid residues from 1 to about 331, inclusive of Figure 137 (SEQ ID N0:209), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01074 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 322 to 1314, inclusive of Figure 136 (SEQ ID N0:208). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209953 (DNAS7704-1452), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209953 (DNA57704-1452).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 8S% sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 9S % sequence identity to the sequence of amino acid residues 1 to about 331, inclusive of Figure 137 (SEQ ID N0:209).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01074 extracellular domain (ECD), with or without the initiating methionine, and its soluble variants (i.e.
transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule.
A type II transmembrane domain region has been tentatively identified as extending from about amino acid position 20 to 39 in the PR01074 amino acid sequence (Figure 137, SEQ ID
N0:209).
In another aspect; the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, and most preferably at least about 9S% positives when compared with the amino acid sequence of residues 1 to about 331, inclusive of Figure 137 (SEQ ID N0:209).
Another embodiment is directed to fragments of a PR01074 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PROI074 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention grovides isolated native sequence PRO 1074 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 331 of Figure 137 (SEQ ID N0:209).
In another aspect, the invention concerns an isolated PR01074 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to 331, inclusive of Figure 137 (SEQ ID
N0:209).
In a further aspect, the invention concerns an isolated PR01074 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, and most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 331 of Figure 137 (SEQ ID N0:209).
In another aspect, the invention concerns a PR01074 extracellular domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues X to 331 of Figure 2 (SEQ ID N0:3), wherein X
is any one of amino acid residues 35 to 44 of Figure 137 (SEQ ID N0:209).
In yet another aspect, the invention concerns an isolated PRO 1074 polypeptide, comprising the sequence of amino acid residues 1 to about 331, inclusive of Figure 137 (SEQ ID
N0:209), or a fragment thereof sufficient to provide a binding site for an anti-PR01074 antibody. Preferably, the PR01074 fragment retains a qualitative biological activity of a native PR01074 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01074 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PR01074 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01074 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01074 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01074 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
56. PR01005 A cDNA clone (DNA57708-1411) has been identified that encodes a novel polypeptide, designated in the present application as "PR01005."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01005 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01005 polypeptide having the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID N0:211), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01005 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 90 and about 584, inclusive, of Figure 138 (SEQ ID N0:210). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203021 (DNA57708-1411), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATQC
Deposit No. 203021 (DNA57708-1411).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID
N0:211}, or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, and preferably at least 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1005 polypeptide having the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID
N0:211), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01005 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 139 (SEQ ID
N0:211).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 21 to about 185, inclusive of Figure 139 (SEQ
ID N0:211), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1005 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01005 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1005 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 185 of Figure 139 (SEQ ID N0:211).
In another aspect, the invention concerns an isolated PRO 1005 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 21 to about 185, inclusive of Figure 139 (SEQ
ID N0:211).
In a further aspect, the invention concerns an isolated PRO1005 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably ai least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 21 to 185 of Figure 139 (SEQ ID N0:211).
In yet another aspect, the invention concerns an isolated PRO 1005 polypeptide, comprising the sequence of amino acid residues 21 to about 185, inclusive of Figure 139 (SEQ ID
N0:211), or a fragment thereof sufficient to provide a binding site for an anti-PRO1005 antibody. Preferably, the PR01005 fragment retains a qualitative biological activity of a native PRO1005 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1005 polypeptide having the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID N0:211), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01005 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01005 polypeptide having the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID N0:211), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01005 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 90 and about 584, inclusive, of Figure 138 (SEQ ID N0:210). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203021 (DNA57708-1411), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATQC
Deposit No. 203021 (DNA57708-1411).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID
N0:211}, or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, and preferably at least 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO 1005 polypeptide having the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID
N0:211), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01005 polypeptide, with or without the N-terminal signal sequence, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 139 (SEQ ID
N0:211).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 21 to about 185, inclusive of Figure 139 (SEQ
ID N0:211), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1005 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01005 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1005 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 185 of Figure 139 (SEQ ID N0:211).
In another aspect, the invention concerns an isolated PRO 1005 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 21 to about 185, inclusive of Figure 139 (SEQ
ID N0:211).
In a further aspect, the invention concerns an isolated PRO1005 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably ai least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 21 to 185 of Figure 139 (SEQ ID N0:211).
In yet another aspect, the invention concerns an isolated PRO 1005 polypeptide, comprising the sequence of amino acid residues 21 to about 185, inclusive of Figure 139 (SEQ ID
N0:211), or a fragment thereof sufficient to provide a binding site for an anti-PRO1005 antibody. Preferably, the PR01005 fragment retains a qualitative biological activity of a native PRO1005 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1005 polypeptide having the sequence of amino acid residues from about 21 to about 185, inclusive of Figure 139 (SEQ ID N0:211), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
57. PR01073 A cDNA clone (DNA57710-1451) has been identified that encodes a novel polypeptide, designated in the present application as "PR01073."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01073 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01073 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 141 (SEQ ID N0:2I3), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01073 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 438 and about 1241, inclusive, of Figure 140 (SEQ ID N0:212). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203048 (DNA57710-1451), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203048 (DNA57710-1451).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 141 (SEQ ID
N0:213), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01073 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 141 (SEQ
ID N0:213), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01073 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 31 in the sequence of Figure 141 (SEQ
ID N0:213).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 32 to about 299, inclusive of Figure 141 (SEQ
ID N0:213), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1073 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01073 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1073 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 32 to 299 of Figure 141 (SEQ ID N0:213).
In another aspect, the invention concerns an isolated PR01073 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 32 to about 299, inclusive of Figure 141 (SEQ
ID N0:213).
In a further aspect, the invention concerns an isolated PRO 1073 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90%a positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 32 to 299 of Figure 141 (SEQ ID N0:213).
In yet another aspect, the invention concerns an isolated PRO 1073 polypeptide, comprising the sequence of amino acid residues 32 to about 299, inclusive of Figure 141 (SEQ ID
N0:213), or a fragment thereof sufficient to provide a binding site for an anti-PR01073 antibody. Preferably, the PR01073 fragment retains a qualitative biological activity of a native PR01073 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01073 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive. of Figure 141 (SEQ ID N0:213), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01073 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01073 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 141 (SEQ ID N0:2I3), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01073 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 438 and about 1241, inclusive, of Figure 140 (SEQ ID N0:212). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203048 (DNA57710-1451), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203048 (DNA57710-1451).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 141 (SEQ ID
N0:213), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01073 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive of Figure 141 (SEQ
ID N0:213), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01073 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 31 in the sequence of Figure 141 (SEQ
ID N0:213).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 32 to about 299, inclusive of Figure 141 (SEQ
ID N0:213), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1073 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01073 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1073 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 32 to 299 of Figure 141 (SEQ ID N0:213).
In another aspect, the invention concerns an isolated PR01073 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 32 to about 299, inclusive of Figure 141 (SEQ
ID N0:213).
In a further aspect, the invention concerns an isolated PRO 1073 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90%a positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 32 to 299 of Figure 141 (SEQ ID N0:213).
In yet another aspect, the invention concerns an isolated PRO 1073 polypeptide, comprising the sequence of amino acid residues 32 to about 299, inclusive of Figure 141 (SEQ ID
N0:213), or a fragment thereof sufficient to provide a binding site for an anti-PR01073 antibody. Preferably, the PR01073 fragment retains a qualitative biological activity of a native PR01073 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01073 polypeptide having the sequence of amino acid residues from about 32 to about 299, inclusive. of Figure 141 (SEQ ID N0:213), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
58. PR01152 A cDNA clone (DNA57711-1501 ) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01152".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01152 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1152 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01152 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 58 or about 142 and about 1494, inclusive, of Figure 143 (SEQ ID N0:215).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203047 (DNA57711-1501) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203047 (DNA57711-1501).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 ~ sequence identity, preferably at least about 85 R6 sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 300 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01152 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01152 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 144 (SEQ
ID N0:216). The various transmembrane domains have been tentatively identified as extending from about amino acid position 133 to about amino acid position 155, from about amino acid position 168 to about amino acid position 187, from about amino acid position 229 to about amino acid position 247, from about amino acid position 264 to about amino acid position 285, from about amino acid position 309 to about amino acid position 330, from about amino acid position 371 to about amino acid position 390 and from about amino acid position 441 to about amino acid position 464 in the PROI 152 amino acid sequence (Figure 144, SEQ ID N0:216).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1152 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 143 (SEQ ID N0:215).
In another embodiment, the invention provides isolated PR01152 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01152 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 479 of Figure 144 (SEQ ID N0:216).
In another aspect, the invention concerns an isolated PR01152 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216).
In a further aspect, the invention concerns an isolated PR01152 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216).
In yet another aspect, the invention concerns an isolated PRO 1152 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216), or a fragment thereof sufficient to provide a binding site for an anti-PR01152 antibody.
Preferably, the PR01152 fragment retains a qualitative biological activity of a native PR01152 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01152 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides a nucleic aid molecule designated herein as DNA55807 comprising the nucleotide sequence of SEQ ID N0:217 (see Figure 145).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01152 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1152 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01152 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 58 or about 142 and about 1494, inclusive, of Figure 143 (SEQ ID N0:215).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203047 (DNA57711-1501) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203047 (DNA57711-1501).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 ~ sequence identity, preferably at least about 85 R6 sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 300 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01152 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01152 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 144 (SEQ
ID N0:216). The various transmembrane domains have been tentatively identified as extending from about amino acid position 133 to about amino acid position 155, from about amino acid position 168 to about amino acid position 187, from about amino acid position 229 to about amino acid position 247, from about amino acid position 264 to about amino acid position 285, from about amino acid position 309 to about amino acid position 330, from about amino acid position 371 to about amino acid position 390 and from about amino acid position 441 to about amino acid position 464 in the PROI 152 amino acid sequence (Figure 144, SEQ ID N0:216).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1152 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 143 (SEQ ID N0:215).
In another embodiment, the invention provides isolated PR01152 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01152 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 479 of Figure 144 (SEQ ID N0:216).
In another aspect, the invention concerns an isolated PR01152 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216).
In a further aspect, the invention concerns an isolated PR01152 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216).
In yet another aspect, the invention concerns an isolated PRO 1152 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID N0:216), or a fragment thereof sufficient to provide a binding site for an anti-PR01152 antibody.
Preferably, the PR01152 fragment retains a qualitative biological activity of a native PR01152 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01152 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 479, inclusive of Figure 144 (SEQ ID
N0:216), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides a nucleic aid molecule designated herein as DNA55807 comprising the nucleotide sequence of SEQ ID N0:217 (see Figure 145).
59. PR01136 A cDNA clone (DNA57827-1493) has been identified, having homology to nucleic acid encoding PDZ
domain-containing proteins that encodes a novel polypeptide, designated in the present application as "PR01136".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01136 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01136 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:219), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01136 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 216 or about 261 and about 2111, inclusive, of Figure 146 (SEQ ID N0:218).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 °9 sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203045 (DNA57827-1493) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203045 (DNA57827-1493).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°k sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:2I9), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01136 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI 136 poiypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 147 (SEQ
ID N0:219).
in another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85~ positives, more preferably at least about 90 % positives, most preferably at least about 95 ~
positives when compared with the amino acid sequence of residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01136 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 146 (SEQ ID N0:218).
In another embodiment, the invention provides isolated PROI 136 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01136 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 632 of Figure 147 (SEQ ID N0:219).
In another aspect, the invention concerns an isolated PR01136 polypeptide, comprising an amino acid sequence having at least about 80R'o sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 9b sequence identity to the sequence of amino acid residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219).
In a further aspect, the invention concerns an isolated PRO 1136 polypeptide, comprising an amino acid sequence scoring at least about 80 ro positives, preferably at least about 85 % positives, more preferably at least about 906 positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:219).
In yet another aspect, the invention concerns an isolated PRO 1136 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219), or a fragment thereof sufficient to provide a binding site for an anti-PR01136 antibody.
Preferably, the PR01136 fragment retains a qualitative biological activity of a native PR01136 poiypeptide.
In a still further aspect, the invention provides a polypeptide produced by.(i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01136 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:219), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80~ sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90 ~ sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agoniscs and antagonists of a native PR01136 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01136 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01136 polypeptide by contacting the native PR01136 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PROI 136 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
domain-containing proteins that encodes a novel polypeptide, designated in the present application as "PR01136".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01136 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01136 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:219), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01136 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 216 or about 261 and about 2111, inclusive, of Figure 146 (SEQ ID N0:218).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 °9 sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203045 (DNA57827-1493) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203045 (DNA57827-1493).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°k sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:2I9), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01136 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROI 136 poiypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 147 (SEQ
ID N0:219).
in another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85~ positives, more preferably at least about 90 % positives, most preferably at least about 95 ~
positives when compared with the amino acid sequence of residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01136 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 146 (SEQ ID N0:218).
In another embodiment, the invention provides isolated PROI 136 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01136 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 632 of Figure 147 (SEQ ID N0:219).
In another aspect, the invention concerns an isolated PR01136 polypeptide, comprising an amino acid sequence having at least about 80R'o sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 9b sequence identity to the sequence of amino acid residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219).
In a further aspect, the invention concerns an isolated PRO 1136 polypeptide, comprising an amino acid sequence scoring at least about 80 ro positives, preferably at least about 85 % positives, more preferably at least about 906 positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:219).
In yet another aspect, the invention concerns an isolated PRO 1136 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID N0:219), or a fragment thereof sufficient to provide a binding site for an anti-PR01136 antibody.
Preferably, the PR01136 fragment retains a qualitative biological activity of a native PR01136 poiypeptide.
In a still further aspect, the invention provides a polypeptide produced by.(i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01136 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 632, inclusive of Figure 147 (SEQ ID
N0:219), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80~ sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90 ~ sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agoniscs and antagonists of a native PR01136 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01136 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01136 polypeptide by contacting the native PR01136 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PROI 136 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
60. PR0813 Applicants have identified a cDNA clone (DNA57834-I 339) having homology to pulmonary surfactant-associated protein C that encodes a novel polypeptide, designated in the present application as "PR0813".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0813 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80°h sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR0813 polypeptide having the sequence of amino acid residues from about 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID
N0:221), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0813 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 109 or about 187 and about 636, inclusive, of Figure 148 (SEQ ID N0:220).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90°~ sequence identity, most preferably at least about 95%
sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209954 (DNA57834-1339). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same matwe polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209954 (DNA57834-1339).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID
N0:221).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0813 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from about amino acid position 1 to about amino acid position 26 in the sequence of Figure 149 (SEQ
ID N0:221).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 909b positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ
ID N0:221).
Another embodiment is directed to fragments of a PR0813 poiypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
~ In another embodiment, the invention provides isolated PR0813 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0813 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 27 to about 176 of Figure 149 (SEQ ID N0:221).
In another aspect, the invention concerns an isolated PR0813 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID N0:221).
In a further aspect, the invention concerns an isolated PR0813 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID
N0:221).
In yet another aspect, the invention concerns an isolated PR0813 polypeptide, comprising the sequence of amino acid residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID N0:221), or a fragment thereof sufficient to provide a binding site for an anti-PR0813 antibody.
Preferably, the PR0813 fragment retains a qualitative biological activity of a native PR0813 polypeptide.
In another aspect, the present invention is directed to fragments of a PR0813 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0813 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0813 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR0813 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR0813 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0813 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80°h sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR0813 polypeptide having the sequence of amino acid residues from about 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID
N0:221), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0813 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 109 or about 187 and about 636, inclusive, of Figure 148 (SEQ ID N0:220).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90°~ sequence identity, most preferably at least about 95%
sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209954 (DNA57834-1339). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same matwe polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209954 (DNA57834-1339).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID
N0:221).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0813 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from about amino acid position 1 to about amino acid position 26 in the sequence of Figure 149 (SEQ
ID N0:221).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 909b positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ
ID N0:221).
Another embodiment is directed to fragments of a PR0813 poiypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
~ In another embodiment, the invention provides isolated PR0813 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0813 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 27 to about 176 of Figure 149 (SEQ ID N0:221).
In another aspect, the invention concerns an isolated PR0813 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID N0:221).
In a further aspect, the invention concerns an isolated PR0813 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID
N0:221).
In yet another aspect, the invention concerns an isolated PR0813 polypeptide, comprising the sequence of amino acid residues 1 or about 27 to about 176, inclusive of Figure 149 (SEQ ID N0:221), or a fragment thereof sufficient to provide a binding site for an anti-PR0813 antibody.
Preferably, the PR0813 fragment retains a qualitative biological activity of a native PR0813 polypeptide.
In another aspect, the present invention is directed to fragments of a PR0813 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0813 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0813 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR0813 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR0813 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
61. PR0809 A cDNA clone (DNA57836-1338) has been identified, having sequence identity with heparan sulfate proteoglycans, that encodes a novel polypeptiiie, designated in the present application as "PR0809. "
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0809 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0809 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., I-265, or in another embodiment, 19-265.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0809 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 63 or 117 and about 867, inclusive, of Figure 150 (SEQ ID N0:222). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203025 (DNA57836-1338), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203025 (DNA57836-1338).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % ~ sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 19 to about 265, inclusive of Figure 151 (SEQ
ID N0:223), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0809 polypeptide having the sequence of amino acid residues from about I or 19 to about 265, inclusive of Figure 151 (SEQ ID
N0:223), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0809 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0809 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 19 through 265 of Figure 151 (SEQ ID
N0:223).
In another aspect, the invention concerns an isolated PR0809 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223).
In a further aspect, the invention concerns an isolated PR0809 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 19 through 265 of Figure 151 (SEQ ID N0:223).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0809 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0809 polypeptide. In a particular embodiment, the agotiist or antagonist is an anti-PR0809 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0809 polypeptide, by contacting the native PR0809 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0809 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0809 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0809 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., I-265, or in another embodiment, 19-265.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0809 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 63 or 117 and about 867, inclusive, of Figure 150 (SEQ ID N0:222). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203025 (DNA57836-1338), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203025 (DNA57836-1338).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % ~ sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 19 to about 265, inclusive of Figure 151 (SEQ
ID N0:223), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0809 polypeptide having the sequence of amino acid residues from about I or 19 to about 265, inclusive of Figure 151 (SEQ ID
N0:223), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0809 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0809 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 19 through 265 of Figure 151 (SEQ ID
N0:223).
In another aspect, the invention concerns an isolated PR0809 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223).
In a further aspect, the invention concerns an isolated PR0809 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 19 through 265 of Figure 151 (SEQ ID N0:223).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0809 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 265, inclusive of Figure 151 (SEQ ID N0:223), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0809 polypeptide. In a particular embodiment, the agotiist or antagonist is an anti-PR0809 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0809 polypeptide, by contacting the native PR0809 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0809 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
62. PR0791 A cDNA clone (DNA57838-1337) has been identified, having sequence identity with MHC class I
antigens that encodes a novel polypeptide, designated in the present application as "PR0791."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0791 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0791 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-246, or in another embodiment, 26-246.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0791 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 9 or 84 and about 746, inclusive, of Figure 152 (SEQ ID N0:224). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203014 (DNA57838-1337), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic WO 99/b3088 PCT/US99/12252 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203014 (DNA57838-1337).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ
ID N0:225), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0791 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID
IO N0:225), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0791 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0791 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 26 through 246 of Figure 153 (SEQ ID
N0:225).
In another aspect, the invention concerns an isolated PRO791 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225).
In a further aspect, the invention concerns an isolated PR0791 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 26 through 246 of Figure 153 (SEQ ID N0:225).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0791 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0791 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0791 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0791 polypeptide, by contacting the native PR0791 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0791 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
antigens that encodes a novel polypeptide, designated in the present application as "PR0791."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0791 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0791 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-246, or in another embodiment, 26-246.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0791 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 9 or 84 and about 746, inclusive, of Figure 152 (SEQ ID N0:224). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203014 (DNA57838-1337), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic WO 99/b3088 PCT/US99/12252 acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203014 (DNA57838-1337).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ
ID N0:225), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0791 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID
IO N0:225), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0791 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0791 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 26 through 246 of Figure 153 (SEQ ID
N0:225).
In another aspect, the invention concerns an isolated PRO791 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225).
In a further aspect, the invention concerns an isolated PR0791 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 26 through 246 of Figure 153 (SEQ ID N0:225).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0791 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 246, inclusive of Figure 153 (SEQ ID N0:225), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0791 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0791 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0791 polypeptide, by contacting the native PR0791 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0791 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
63. PR01004 A cDNA clone (DNA57844-1410) has been identified that encodes a novel polypeptide, designated in the present application as "PR01004."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01004 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1004 polypeptide having the sequence of amino acid residues from about 25 to about 115, inclusive of Figure 155 (SEQ ID N0:227), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01004 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 191 and about 463, inclusive, of Figure 154 (SEQ ID N0:226). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203010 (DNA57844-1410), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203010 (DNA57844-1410).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 25 to about I 15, inclusive of Figure 155 (SEQ ID
N0:227), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, and preferably at least 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01004 polypeptide having the sequence of amino acid residues from about 25 to about I 15, inclusive of Figure 155 (SEQ ID
N0:227), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 ro sequence identity, preferably at least about an 85~ sequence identity, more preferably at least about a 90~
sequence identity, most preferably at least about a 9596 sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01004 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as euending from about amino acid position 1 through about amino acid position 24 in the sequence of Figure 155 (SEQ ID N0:227).
In another aspect, the invemion concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85 k positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 25 to about 115, inclusive of Figure 155 (SEQ
ID N0:227), or (b) the complement of the DNA of (a).
Another embodiment of the invention is directed to fragments of a PR01004 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01004 polypeptide encoded by any of the 20 isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1004 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 25 to 115 of Figure 155 (SEQ ID N0:227).
In another aspect, the invention concerns an isolated PR01004 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 25 to about 115, inclusive of Figure 155 (SEQ
ID N0:227).
In a further aspect, the invention concerns an isolated PR01004 polypeptide, comprising an amino acid sequence scoring at least about 80°k positives, preferably at least about 85 ro positives, more preferably at least about 90 ~ positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 25 to 115 of Figure 155 (SEQ ID N0:227).
In yet another aspect, the invention concerns an isolated PR01004 polypeptide, comprising the sequence of amino acid residues 25 to about 115, inclusive of Figure 155 (SEQ ID
N0:227), or a fragment thereof sufficient to provide a binding site for an anti-PR01004 antibody. Preferably, the PR01004 fragment retains a qualitative biological activity of a native PR01004 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01004 polypeptide having the sequence of amino acid residues from about 25 to about 115, inclusive of Figure 155 (SEQ ID N0:227), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01004 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1004 polypeptide having the sequence of amino acid residues from about 25 to about 115, inclusive of Figure 155 (SEQ ID N0:227), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01004 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 191 and about 463, inclusive, of Figure 154 (SEQ ID N0:226). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203010 (DNA57844-1410), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203010 (DNA57844-1410).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 25 to about I 15, inclusive of Figure 155 (SEQ ID
N0:227), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, and preferably at least 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01004 polypeptide having the sequence of amino acid residues from about 25 to about I 15, inclusive of Figure 155 (SEQ ID
N0:227), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 ro sequence identity, preferably at least about an 85~ sequence identity, more preferably at least about a 90~
sequence identity, most preferably at least about a 9596 sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01004 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as euending from about amino acid position 1 through about amino acid position 24 in the sequence of Figure 155 (SEQ ID N0:227).
In another aspect, the invemion concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85 k positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 25 to about 115, inclusive of Figure 155 (SEQ
ID N0:227), or (b) the complement of the DNA of (a).
Another embodiment of the invention is directed to fragments of a PR01004 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01004 polypeptide encoded by any of the 20 isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1004 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 25 to 115 of Figure 155 (SEQ ID N0:227).
In another aspect, the invention concerns an isolated PR01004 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 25 to about 115, inclusive of Figure 155 (SEQ
ID N0:227).
In a further aspect, the invention concerns an isolated PR01004 polypeptide, comprising an amino acid sequence scoring at least about 80°k positives, preferably at least about 85 ro positives, more preferably at least about 90 ~ positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 25 to 115 of Figure 155 (SEQ ID N0:227).
In yet another aspect, the invention concerns an isolated PR01004 polypeptide, comprising the sequence of amino acid residues 25 to about 115, inclusive of Figure 155 (SEQ ID
N0:227), or a fragment thereof sufficient to provide a binding site for an anti-PR01004 antibody. Preferably, the PR01004 fragment retains a qualitative biological activity of a native PR01004 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01004 polypeptide having the sequence of amino acid residues from about 25 to about 115, inclusive of Figure 155 (SEQ ID N0:227), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
64. PROllll A cDNA clone (DNA58721-1475) has been identified that encodes a novel polypeptide having sequence identity with LIG and designated in the present application as "PRO1111."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1111 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at Ieast about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1111 polypeptide having the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID N0:229), or (b) the complement of the DNA molecuie of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROllll polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 57 and about 2015, inclusive, of Figure 156 (SEQ ID N0:228). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203110 (DNA58721-1475), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203110 (DNA58721-1475).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID
N0:229), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1111 polypeptide having the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID
N0:229), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1111 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains has been tentatively identified as extending from about amino acid positions 21-40 (type II) and 528-548 in the PRO1111 amino acid sequence (Figure 157, SEQ ID N0:229).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 653, inclusive of Figure 157 (SEQ
ID N0:229), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO1111 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO11 I 1 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1111 polypeptide,. which in one embodiment, includes an amino acid sequence comprising residues I through 653 of Figure 157 (SEQ ID
N0:229).
In another aspect, the invention concerns an isolated PR01111 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 653, inclusive of Figure 157 (SEQ
ID N0:229).
In a further aspect, the invention concerns an isolated PRO1111 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%a positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 through 653 of Figure 157 (SEQ ID N0:229).
In yet another aspect, the invention concerns an isolated PRO1111 polypeptide, comprising the sequence of amino acid residues 1 to about 653, inclusive of Figure 157 (SEQ ID
N0:229), or a fragment thereof sufficient to provide a binding site for an anti-PRO1111 antibody. Preferably, the PROI 111 fragment retains a qualitative biological activity of a native PR01111 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROl l l l polypeptide having the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID N0:229), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PRO1111 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO1111 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1111 polypeptide, by contacting the native PRO11 l l polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1111 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1111 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at Ieast about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1111 polypeptide having the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID N0:229), or (b) the complement of the DNA molecuie of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PROllll polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 57 and about 2015, inclusive, of Figure 156 (SEQ ID N0:228). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203110 (DNA58721-1475), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203110 (DNA58721-1475).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID
N0:229), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1111 polypeptide having the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID
N0:229), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1111 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains has been tentatively identified as extending from about amino acid positions 21-40 (type II) and 528-548 in the PRO1111 amino acid sequence (Figure 157, SEQ ID N0:229).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 653, inclusive of Figure 157 (SEQ
ID N0:229), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO1111 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO11 I 1 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1111 polypeptide,. which in one embodiment, includes an amino acid sequence comprising residues I through 653 of Figure 157 (SEQ ID
N0:229).
In another aspect, the invention concerns an isolated PR01111 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 653, inclusive of Figure 157 (SEQ
ID N0:229).
In a further aspect, the invention concerns an isolated PRO1111 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%a positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 through 653 of Figure 157 (SEQ ID N0:229).
In yet another aspect, the invention concerns an isolated PRO1111 polypeptide, comprising the sequence of amino acid residues 1 to about 653, inclusive of Figure 157 (SEQ ID
N0:229), or a fragment thereof sufficient to provide a binding site for an anti-PRO1111 antibody. Preferably, the PROI 111 fragment retains a qualitative biological activity of a native PR01111 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PROl l l l polypeptide having the sequence of amino acid residues from about 1 to about 653, inclusive of Figure 157 (SEQ ID N0:229), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PRO1111 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO1111 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1111 polypeptide, by contacting the native PRO11 l l polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1111 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
65. PR01344 A cDNA clone (DNA58723-1588) has been identified, having homology to nucleic acid encoding factor C that encodes a novel polypeptide, designated in the present application as "PR01344".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01344 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01344 polypeptide having the sequence of amino acid residues from about I or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01344 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 26 or about 95 and about 2185, inclusive, of Figure 158 (SEQ ID N0:230).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95 h sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203133 (DNA58723-1588) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203133 (DNA58723-1588).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90'~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01344 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01344 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 159 (SEQ
ID N0:231).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231 ), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1344 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 158 (SEQ ID N0:230).
In another embodiment, the invention provides isolated PR01344 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01344 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 24 to about 720 of Figure 159 (SEQ ID N0:231).
In another aspect, the invention concerns an isolated PR01344 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231).
In a further aspect, the invention concerns an isolated PRO 1344 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231).
In yet another aspect, the invention concerns an isolated PRO 1344 polypeptide, comprising the sequence of amino acid residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231), or a fragment thereof sufficient to provide a binding site for an anti-PR01344 antibody.
Preferably, the PR01344 fragment retains a qualitative biological activity of a native PR01344 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01344 polypeptide having the sequence of amino acid residues from about I or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the poiypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01344 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01344 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01344 polypeptide by contacting the native PR01344 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still furtherembodiment, the invention concerns a composition comprising a PR01344 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01344 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01344 polypeptide having the sequence of amino acid residues from about I or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01344 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 26 or about 95 and about 2185, inclusive, of Figure 158 (SEQ ID N0:230).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95 h sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203133 (DNA58723-1588) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203133 (DNA58723-1588).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90'~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01344 polypeptide having the sequence of amino acid residues from 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01344 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 159 (SEQ
ID N0:231).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231 ), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1344 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 158 (SEQ ID N0:230).
In another embodiment, the invention provides isolated PR01344 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01344 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 24 to about 720 of Figure 159 (SEQ ID N0:231).
In another aspect, the invention concerns an isolated PR01344 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231).
In a further aspect, the invention concerns an isolated PRO 1344 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231).
In yet another aspect, the invention concerns an isolated PRO 1344 polypeptide, comprising the sequence of amino acid residues 1 or about 24 to about 720, inclusive of Figure 159 (SEQ ID N0:231), or a fragment thereof sufficient to provide a binding site for an anti-PR01344 antibody.
Preferably, the PR01344 fragment retains a qualitative biological activity of a native PR01344 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01344 polypeptide having the sequence of amino acid residues from about I or about 24 to about 720, inclusive of Figure 159 (SEQ ID
N0:231), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the poiypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01344 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01344 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01344 polypeptide by contacting the native PR01344 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still furtherembodiment, the invention concerns a composition comprising a PR01344 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
66. PR01109 A cDNA clone (DNA58737-1473) has been identified, having homology to nucleic acid encoding p-1,4-galactosyltransferase, that encodes a novel polypeptide, designated in the present application as "PR01109".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01109 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01109 polypeptide having the sequence of amino acid residues from about 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01109 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 119 or about 200 and about 1150, inclusive, of Figure 160 (SEQ ID N0:235).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80°7 sequence identity, preferably at least about 85%
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203136 (DNA58737-1473) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203136 (DNA58737-1473).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8(?% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01109 polypeptide having the sequence of amino acid residues from 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at Ieast about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01109 polypeptide, with or without the N-terminal signal sequence and/or the initiating methiorune, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from about amino acid position 1 to about amino acid position 27 in the sequence of Figure 161 (SEQ
ID N0:236).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1109 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 160 (SEQ ID N0:235).
In another embodiment, the invention provides isolated PR01109 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01109 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 28 to about 344 of Figure 161 (SEQ ID N0:236).
In another aspect, the invention concerns an isolated PR01109 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236).
In a further aspect, the invention concerns an isolated PRO1109 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236).
In yet another aspect, the invention concerns an isolated PR01109 polypeptide, comprising the sequence of amino acid residues I or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236), or a fragment thereof sufficient to provide a binding site for an anti-PR01109 antibody.
Preferably, the PR01109 fragment retains a qualitative biological activity of a native PR01109 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01109 polypeptide having the sequence of amino acid residues from about 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least abouf an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01109 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01109 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01109 polypeptide by contacting the native PR01109 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1109 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01109 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01109 polypeptide having the sequence of amino acid residues from about 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01109 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 119 or about 200 and about 1150, inclusive, of Figure 160 (SEQ ID N0:235).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80°7 sequence identity, preferably at least about 85%
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203136 (DNA58737-1473) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203136 (DNA58737-1473).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8(?% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01109 polypeptide having the sequence of amino acid residues from 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at Ieast about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01109 polypeptide, with or without the N-terminal signal sequence and/or the initiating methiorune, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from about amino acid position 1 to about amino acid position 27 in the sequence of Figure 161 (SEQ
ID N0:236).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1109 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 160 (SEQ ID N0:235).
In another embodiment, the invention provides isolated PR01109 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01109 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 28 to about 344 of Figure 161 (SEQ ID N0:236).
In another aspect, the invention concerns an isolated PR01109 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236).
In a further aspect, the invention concerns an isolated PRO1109 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236).
In yet another aspect, the invention concerns an isolated PR01109 polypeptide, comprising the sequence of amino acid residues I or about 28 to about 344, inclusive of Figure 161 (SEQ ID N0:236), or a fragment thereof sufficient to provide a binding site for an anti-PR01109 antibody.
Preferably, the PR01109 fragment retains a qualitative biological activity of a native PR01109 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01109 polypeptide having the sequence of amino acid residues from about 1 or about 28 to about 344, inclusive of Figure 161 (SEQ ID
N0:236), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least abouf an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01109 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01109 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01109 polypeptide by contacting the native PR01109 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1109 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
67. PR01383 A cDNA clone (DNA58743-1609) has been identified, having homology to nucleic acid encoding the human melanoma cell-expressed protein nmb, that encodes a novel polypeptide, designated in the present application as "PR01383".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01383 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01383 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:241), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01383 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 or about 194 and about 1390, inclusive, of Figure 162 (SEQ ID N0:240).
Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80~ sequence identity, preferably at least about 85 k sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203154 (DNA58743-1609) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203154 (DNA58743-1609).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80°o sequence identity, preferably at least about 8591; sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:241), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01383 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 k sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95 °! sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01383 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 163 (SEQ
ID N0:241 ). The transmembrane domain has been tentatively identified as extending from about amino acid position 339 to about amino acid position 362 in the PR01383 amino acid sequence (Figure 163, SEQ ID N0:241).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 ~ positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01383 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 162 (SEQ ID N0:240).
In another embodiment, the invention provides isolated PR01383 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01383 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 423 of Figure 163 (SEQ ID N0:241).
In another aspect, the invention concerns an isolated PR01383 polypeptide, comprising an amino acid sequence having at least about 806 sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 953b sequence identity to the sequence of amino acid residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241):
In a further aspect, the invention concerns an isolated PR01383 polypeptide, comprising an amino acid sequence scoring at least about 80Rh positives, preferably at least about 859b positives, more preferably at least about 90 ~ positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:2A1).
In yet another aspect, the invention concerns an isolated PR01383 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241), or a fragment thereof sufficient to provide a binding site for an anti-PR01383 antibody.
Preferably, the PR01383 fragment retains a qualitative biological activity of a native PR01383 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01383 polypeptide having the sequence of amino acid residues from about I or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:241), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80~ sequence identity, preferably at least about an 85 k sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01383 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01383 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01383 polypeptide by contacting the native PR01383 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1383 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01383 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01383 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:241), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01383 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 122 or about 194 and about 1390, inclusive, of Figure 162 (SEQ ID N0:240).
Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80~ sequence identity, preferably at least about 85 k sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203154 (DNA58743-1609) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203154 (DNA58743-1609).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80°o sequence identity, preferably at least about 8591; sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:241), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01383 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 k sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95 °! sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01383 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 163 (SEQ
ID N0:241 ). The transmembrane domain has been tentatively identified as extending from about amino acid position 339 to about amino acid position 362 in the PR01383 amino acid sequence (Figure 163, SEQ ID N0:241).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 ~ positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01383 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 162 (SEQ ID N0:240).
In another embodiment, the invention provides isolated PR01383 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01383 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 423 of Figure 163 (SEQ ID N0:241).
In another aspect, the invention concerns an isolated PR01383 polypeptide, comprising an amino acid sequence having at least about 806 sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 953b sequence identity to the sequence of amino acid residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241):
In a further aspect, the invention concerns an isolated PR01383 polypeptide, comprising an amino acid sequence scoring at least about 80Rh positives, preferably at least about 859b positives, more preferably at least about 90 ~ positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:2A1).
In yet another aspect, the invention concerns an isolated PR01383 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 423, inclusive of Figure 163 (SEQ ID N0:241), or a fragment thereof sufficient to provide a binding site for an anti-PR01383 antibody.
Preferably, the PR01383 fragment retains a qualitative biological activity of a native PR01383 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01383 polypeptide having the sequence of amino acid residues from about I or about 25 to about 423, inclusive of Figure 163 (SEQ ID
N0:241), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80~ sequence identity, preferably at least about an 85 k sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01383 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01383 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01383 polypeptide by contacting the native PR01383 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1383 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
68. PR01003 Applicants have identified a cDNA clone, DNA58846-1409, that encodes a novel secreted polypeptide wherein the polypeptide is designated in the present application as "PR01003".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01003 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01003 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 84, inclusive of Figure 165 (SEQ ID N0:246), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01003 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid between about residues 41 or about 113 and about 292 inclusive of Figure 164 (SEQ ID N0:245).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209957 (DNA58846-1409), which was deposited on June 9, 1998. In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209957 (DNA58846-1409).
In an additional aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 84, inclusive of Figure 165 (SEQ ID
N0:246).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 84, inclusive of Figure 165 (SEQ ID N0:246).
Another embodiment is directed to fragments of a PR01003 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1003 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01003 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 25 to 84 of Figure 165 (SEQ ID
N0:246).
In another aspect, the invention concerns an isolated PR01003 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to 84, inclusive of Figure 165 (SEQ ID N0:246).
In a further aspect, the invention concerns an isolated PRO 1003 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 25 to about 84 of Figure 165 (SEQ ID N0:246).
In yet another aspect, the invention concerns an isolated PR01003 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 84, inclusive of Figure 165 (SEQ
ID N0:246), or a fragment thereof sufficient to provide a binding site for an anti-PR01003 antibody.
Preferably, the PR01003 fragment retains a qualitative biological activity of a native PR01003 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01003 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01003 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01003 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 84, inclusive of Figure 165 (SEQ ID N0:246), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01003 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid between about residues 41 or about 113 and about 292 inclusive of Figure 164 (SEQ ID N0:245).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209957 (DNA58846-1409), which was deposited on June 9, 1998. In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209957 (DNA58846-1409).
In an additional aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 84, inclusive of Figure 165 (SEQ ID
N0:246).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 84, inclusive of Figure 165 (SEQ ID N0:246).
Another embodiment is directed to fragments of a PR01003 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1003 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01003 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 25 to 84 of Figure 165 (SEQ ID
N0:246).
In another aspect, the invention concerns an isolated PR01003 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to 84, inclusive of Figure 165 (SEQ ID N0:246).
In a further aspect, the invention concerns an isolated PRO 1003 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 25 to about 84 of Figure 165 (SEQ ID N0:246).
In yet another aspect, the invention concerns an isolated PR01003 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 84, inclusive of Figure 165 (SEQ
ID N0:246), or a fragment thereof sufficient to provide a binding site for an anti-PR01003 antibody.
Preferably, the PR01003 fragment retains a qualitative biological activity of a native PR01003 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01003 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
69. PRO1108 Applicants have identified a cDNA clone (DNA58848-1472) having homology to nucleic acid encoding the LPAAT protein that encodes a novel polypeptide, designated in the present application as ~PR01108".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01108 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1108 polypeptide having the sequence of amino acid residues from about 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01108 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 77 and about 1444, inclusive, of Figure 166 (SEQ ID N0:247). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209955 (DNA58848-1472). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209955 (DNA58848-1472).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01108 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as being type 1I domains extending from about amino acid position 22 to about amino acid position 42, from about amino acid position 156 to about amino acid position 176, from about amino acid position 180 to about amino acid position 199 and from about amino acid position 369 to about amino acid position 388 in the PR01108 amino acid sequence (Figure 167, SEQ ID
N0:248).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248).
Another embodiment is directed to fragments of a PR01108 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01108 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01108 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to about 456 of Figure 167 (SEQ ID
N0:248).
In another aspect, the invention concerns an isolated PRO1108 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 456, inclusive of Figure 167 (SEQ
ID N0:248).
In a further aspect, the invention concerns an isolated PRO 1108 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 %a positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248).
In yet another aspect, the invention concerns an isolated PR01108 polypeptide, comprising the sequence of amino acid residues 1 to about 456, inclusive of Figure 167 (SEQ ID
N0:248), or a fragment thereof sufficient to provide a binding site for an anti-PR01108 antibody. Preferably, the PR01108 fragment retains a qualitative biological activity of a native PR01108 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01108 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01108 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01108 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01108 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01108 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01108 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1108 polypeptide having the sequence of amino acid residues from about 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01108 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 77 and about 1444, inclusive, of Figure 166 (SEQ ID N0:247). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209955 (DNA58848-1472). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209955 (DNA58848-1472).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01108 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as being type 1I domains extending from about amino acid position 22 to about amino acid position 42, from about amino acid position 156 to about amino acid position 176, from about amino acid position 180 to about amino acid position 199 and from about amino acid position 369 to about amino acid position 388 in the PR01108 amino acid sequence (Figure 167, SEQ ID
N0:248).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248).
Another embodiment is directed to fragments of a PR01108 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01108 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01108 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to about 456 of Figure 167 (SEQ ID
N0:248).
In another aspect, the invention concerns an isolated PRO1108 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 456, inclusive of Figure 167 (SEQ
ID N0:248).
In a further aspect, the invention concerns an isolated PRO 1108 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 %a positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 456, inclusive of Figure 167 (SEQ ID N0:248).
In yet another aspect, the invention concerns an isolated PR01108 polypeptide, comprising the sequence of amino acid residues 1 to about 456, inclusive of Figure 167 (SEQ ID
N0:248), or a fragment thereof sufficient to provide a binding site for an anti-PR01108 antibody. Preferably, the PR01108 fragment retains a qualitative biological activity of a native PR01108 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01108 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01108 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01108 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01108 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01108 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
70. PR01137 Applicants have identified a cDNA clone, DNA58849-1494, that encodes a novel polypeptide having homology to ribosyltransferase wherein the polypeptide is designated in the present application as "PR01137".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01137 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1137 polypeptide having the sequence of amino acid residues from 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID N0:250), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01137 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 77 or about 119 to about 796, inclusive of Figure 168 (SEQ ID
N0:249). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209958 (DNA58849-1494), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209958 (DNA58849-1494).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID
N0:250).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01137 polypeptide with or without the N-terminal signal sequence and/or the initiating methionine, or the complement of such encoding DNA molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 14 in the sequence of Figure 169 (SEQ ID
N0:250).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, and most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID N0:250).
Another embodiment is directed to fragments of a PRO 1137 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01137 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PRO 1137 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 15 to 240 of Figure 169 (SEQ ID
N0:250).
In another aspect, the invention concerns an isotated PR01137 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 909b sequence identity, and most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues 1 or about 15 to 240, inclusive of Figure 169 (SEQ ID N0:250).
In a further aspect, the invention concerns an isolated PRO 1137 polypeptide, comprising an amino acid sequence scoring at least about 809b positives, preferably at least about 85~
positives, more preferably at least about 90 ~ positives, and most preferably at least about 95 ~ positives when compared with the amino acid sequence of residues 1 or about 15 to about 240 of Figure 169 (SEQ ID N0:250).
In yet another aspect, the invention concerns an isolated PRO 1137 polypeptide, comprising the sequence of amino acid residues 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID N0:250), or a fragment thereof sufficient to provide a binding site for an anti-PR01137 antibody.
Preferably, the PROl 137 fragment retains a qualitative biological activity of a native PR01137 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01137 polypeptide which are su~ciently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PROl 137 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01137 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01137 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01137 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01137 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1137 polypeptide having the sequence of amino acid residues from 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID N0:250), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01137 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 77 or about 119 to about 796, inclusive of Figure 168 (SEQ ID
N0:249). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209958 (DNA58849-1494), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209958 (DNA58849-1494).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID
N0:250).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01137 polypeptide with or without the N-terminal signal sequence and/or the initiating methionine, or the complement of such encoding DNA molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 14 in the sequence of Figure 169 (SEQ ID
N0:250).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, and most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID N0:250).
Another embodiment is directed to fragments of a PRO 1137 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01137 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PRO 1137 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 15 to 240 of Figure 169 (SEQ ID
N0:250).
In another aspect, the invention concerns an isotated PR01137 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 909b sequence identity, and most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues 1 or about 15 to 240, inclusive of Figure 169 (SEQ ID N0:250).
In a further aspect, the invention concerns an isolated PRO 1137 polypeptide, comprising an amino acid sequence scoring at least about 809b positives, preferably at least about 85~
positives, more preferably at least about 90 ~ positives, and most preferably at least about 95 ~ positives when compared with the amino acid sequence of residues 1 or about 15 to about 240 of Figure 169 (SEQ ID N0:250).
In yet another aspect, the invention concerns an isolated PRO 1137 polypeptide, comprising the sequence of amino acid residues 1 or about 15 to about 240, inclusive of Figure 169 (SEQ ID N0:250), or a fragment thereof sufficient to provide a binding site for an anti-PR01137 antibody.
Preferably, the PROl 137 fragment retains a qualitative biological activity of a native PR01137 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01137 polypeptide which are su~ciently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PROl 137 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01137 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01137 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01137 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
71. PR01138 Applicants have identified a cDNA clone, DNA58850-1495, that encodes a novel polypeptide having homology to CD84 leukocyte antigen wherein the polypeptide is designated in the present application as "PR01138".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01138 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 909'o sequence identity, and most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PRO 1138 polypeptide having the sequence of amino acid residues from 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID N0:253), or (b) the complement of the DNA molecule of (a).
WO ~/~~8 PCT/US99/I2252 In another aspect, the invention corxerns an isolated nucleic acid molecule encoding a PR01138 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 38 or about I04 to about 1042, inclusive of Figure 170 (SEQ ID
N0:252). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209956 (DNA58850-1495), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209956 (DNA58850-1495).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID
N0:253).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01138 extracellular domain (ECD), with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 22 in the sequence of Figure 171 (SEQ ID N0:253). A
transmembrane domain region has been tentatively identified as extending from about amino acid position 224 to about amino acid position 250 in the PR01138 amino acid sequence (Figure 171, SEQ ID N0:253).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 909'o positives, and most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID N0:253).
Another embodiment is directed to fragments of a PR01138 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01138 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01138 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 23 to 335 of Figure 171 (SEQ ID
N0:253).
In another aspect, the invention concerns an isolated PR01138 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90'~ sequence identity, and most preferably at least about 95~ sequence identity to the sequence of amino acid residues 1 or about 23 to 335, inclusive of Figure 171 (SEQ ID N0:253).
In a further aspect, the invention concerns an isolated PR01138 polypeptide, comprising an amino acid sequence scoring at least about 809b positives, preferably at least about 85~
positives, more preferably at least about 90~ positives, and most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 23 to about 335 of Figure 171 (SEQ ID N0:253).
In another aspect, the invention concerns a PR01138 eatracellular domain comprising an amino acid sequence having at least about 80 k sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90~c sequence identity, and most preferably at least about 95°~ sequence identity to the sequence of amino acid residues 1 or about 23 to X of Figure 171 (SEQ ID
N0:253), wherein X is any one of amino acid residues 219 to 228 of Figure 171 (SEQ ID N0:253).
In yet another aspect, the invention concerns an isolated PRO 1138 polypeptide, comprising the sequence of amino acid residues 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID N0:253), or a fragment thereof sufficient to provide a binding site for an anti-PR01138 antibody.
Preferably, the PR01138 fragment retains a qualitative biological activity of a native PR01138 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01138 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PRO I 138 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01138 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01138 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PRO 1138 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides a nucleotide sequence designated herein as DNA49140 comprising the nucleotide sequence of Figure 172 (SEQ ID N0:254).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01138 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 909'o sequence identity, and most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PRO 1138 polypeptide having the sequence of amino acid residues from 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID N0:253), or (b) the complement of the DNA molecule of (a).
WO ~/~~8 PCT/US99/I2252 In another aspect, the invention corxerns an isolated nucleic acid molecule encoding a PR01138 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 38 or about I04 to about 1042, inclusive of Figure 170 (SEQ ID
N0:252). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209956 (DNA58850-1495), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209956 (DNA58850-1495).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID
N0:253).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01138 extracellular domain (ECD), with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e. transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 22 in the sequence of Figure 171 (SEQ ID N0:253). A
transmembrane domain region has been tentatively identified as extending from about amino acid position 224 to about amino acid position 250 in the PR01138 amino acid sequence (Figure 171, SEQ ID N0:253).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 909'o positives, and most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID N0:253).
Another embodiment is directed to fragments of a PR01138 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01138 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01138 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 23 to 335 of Figure 171 (SEQ ID
N0:253).
In another aspect, the invention concerns an isolated PR01138 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90'~ sequence identity, and most preferably at least about 95~ sequence identity to the sequence of amino acid residues 1 or about 23 to 335, inclusive of Figure 171 (SEQ ID N0:253).
In a further aspect, the invention concerns an isolated PR01138 polypeptide, comprising an amino acid sequence scoring at least about 809b positives, preferably at least about 85~
positives, more preferably at least about 90~ positives, and most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 23 to about 335 of Figure 171 (SEQ ID N0:253).
In another aspect, the invention concerns a PR01138 eatracellular domain comprising an amino acid sequence having at least about 80 k sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90~c sequence identity, and most preferably at least about 95°~ sequence identity to the sequence of amino acid residues 1 or about 23 to X of Figure 171 (SEQ ID
N0:253), wherein X is any one of amino acid residues 219 to 228 of Figure 171 (SEQ ID N0:253).
In yet another aspect, the invention concerns an isolated PRO 1138 polypeptide, comprising the sequence of amino acid residues 1 or about 23 to about 335, inclusive of Figure 171 (SEQ ID N0:253), or a fragment thereof sufficient to provide a binding site for an anti-PR01138 antibody.
Preferably, the PR01138 fragment retains a qualitative biological activity of a native PR01138 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01138 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PRO I 138 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01138 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01138 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PRO 1138 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides a nucleotide sequence designated herein as DNA49140 comprising the nucleotide sequence of Figure 172 (SEQ ID N0:254).
72. PR01054 A cDNA clone (DNA58853-1423) has been idemified, having homology to nucleic acid encoding majaor urinary proteins (MUPs) that encodes a novel polypeptide, designated in the present application as "PR01054".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01054 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 °~ sequence identity to (a) a DNA molecule encoding a PR01054 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01054 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 46 WO 99/b3088 PCT/US99/12252 or about 100 and about 585, inclusive, of Figure 173 (SEQ ID N0:255).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at Least about 80~ sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9596 sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203016 (DNA58853-1423) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203016 (DNA58853-1423).
1n still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90 h sequence identity, most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01054 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 ~ sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 9086 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01054 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 18 in the sequence of Figure 174 (SEQ
ID N0:256).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 809'o positives, preferably at least about 85~ positives, more preferably at least about 90% positives, most preferably at least about 95~
positives when compared with the amino acid sequence of residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01054 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 173 (SEQ ID N0:255).
In another embodiment, the invention provides isolated PR01054 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01054 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 19 to about 180 of Figure 174 (SEQ ID N0:256).
In another aspect, the invention concerns an isolated PR01054 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 ~o sequence identity to the sequence of amino acid residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256).
In a further aspect, the invention concerns an isolated PR01054 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256).
In yet another aspect, the invention concerns an isolated PRO 1054 polypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256), or a fragment thereof sufficient to provide a binding site for an anti-PR01054 antibody.
Preferably, the PR01054 fragment retains a qualitative biological activity of a native PR01054 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01054 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01054 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01054 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01054 polypeptide by contacting the native PR01054 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1054 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01054 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 °~ sequence identity to (a) a DNA molecule encoding a PR01054 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01054 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 46 WO 99/b3088 PCT/US99/12252 or about 100 and about 585, inclusive, of Figure 173 (SEQ ID N0:255).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at Least about 80~ sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9596 sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203016 (DNA58853-1423) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203016 (DNA58853-1423).
1n still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90 h sequence identity, most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01054 polypeptide having the sequence of amino acid residues from 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 ~ sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 9086 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01054 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 18 in the sequence of Figure 174 (SEQ
ID N0:256).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 809'o positives, preferably at least about 85~ positives, more preferably at least about 90% positives, most preferably at least about 95~
positives when compared with the amino acid sequence of residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01054 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 173 (SEQ ID N0:255).
In another embodiment, the invention provides isolated PR01054 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01054 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 19 to about 180 of Figure 174 (SEQ ID N0:256).
In another aspect, the invention concerns an isolated PR01054 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 ~o sequence identity to the sequence of amino acid residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256).
In a further aspect, the invention concerns an isolated PR01054 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256).
In yet another aspect, the invention concerns an isolated PRO 1054 polypeptide, comprising the sequence of amino acid residues 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID N0:256), or a fragment thereof sufficient to provide a binding site for an anti-PR01054 antibody.
Preferably, the PR01054 fragment retains a qualitative biological activity of a native PR01054 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01054 polypeptide having the sequence of amino acid residues from about 1 or about 19 to about 180, inclusive of Figure 174 (SEQ ID
N0:256), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), {ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01054 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01054 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01054 polypeptide by contacting the native PR01054 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1054 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
73. PR0994 A cDNA clone (DNA58855-1422) has been identified, having homology to nucleic acid encoding the tumor-associated antigen L6 that encodes a novel polypeptide, designated in the present application as "PR0994" .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0994 polypeptide.
WO 99/b3088 PCT/US99/12252 In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 9096 sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR0994 polypeptide having the sequence of amino acid residues from about i to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0994 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 31 and about 717, inclusive, of Figure 175 (SEQ ID N0:257). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85°h sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203018 (DNA58855-1422) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203018 (DNA58855-1422).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9596 sequence identity to the sequence of amino acid residues 1 to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least IO
nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0994 polypeptide having the sequence of amino acid residues from 1 to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 9b sequence identity, prefereably at least about an 859b sequence identity, more preferably at least about a 9096 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0994 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The multiple transmembrane domains have been tentatively identified as extending from about amino acid position 10 to about amino acid position 31, from about amino acid position 50 to about amino acid position 72, from about amino acid position 87 to about amino acid position 110 and from about amino acid position 191 to about amino acid position 213 in the PR0994 amino acid sequence (Figure 176, SEQ ID N0:258).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85% positives, more preferably at least about 90 h positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 229, inclusive of Figure 176 (SEQ
ID N0:258), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0994 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 mtcleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 175 (SEQ ID N0:257).
In another embodiment, the invention provides isolated PR0994 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0994 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 229 of Figure 176 (SEQ
ID N0:258).
In another aspect, the invention concerns an isolated PR0994 polypeptide, comprising an amino acid sequence having at least about 80'~ sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 h sequence identity, most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues 1 to about 229, inclusive of Figure 176 (SEQ
ID N0:258).
In a further aspect, the invention concerns an isolated PR0994 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85~
positives, more preferably at least about 90~ positives, most preferably at least about 95 ro positives when compared with the amino acid sequence of residues 1 to about 229, inclusive of Figure I76 (SEQ ID N0:258).
In yet another aspect, the invention concerns an isolated PR0994 polypeptide, comprising the sequence of amino acid residues 1 to about 229, inclusive of Figure 176 (SEQ ID
N0:258), or a fragment thereof sufficient to provide a binding site for an anti-PR0994 antibody. Preferably, the PR0994 fragment retains a qualitative biological activity of a native PR0994 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under suingent conditions with (a) a DNA molecule encoding a PR0994 polypeptide having the sequence of amino acid residues from about 1 to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA molecule of (a), and if the test DNA moiecule has at least about an 80~ sequence identity, preferably at least about an 85 Y6 sequence identity, more preferably at least about a 90qb sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for ezpression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0994 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0994 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0994 polypeptide by contacting the native PR0994 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0994 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0994 polypeptide.
WO 99/b3088 PCT/US99/12252 In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 9096 sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR0994 polypeptide having the sequence of amino acid residues from about i to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0994 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 31 and about 717, inclusive, of Figure 175 (SEQ ID N0:257). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85°h sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203018 (DNA58855-1422) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203018 (DNA58855-1422).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9596 sequence identity to the sequence of amino acid residues 1 to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least IO
nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0994 polypeptide having the sequence of amino acid residues from 1 to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 9b sequence identity, prefereably at least about an 859b sequence identity, more preferably at least about a 9096 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0994 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The multiple transmembrane domains have been tentatively identified as extending from about amino acid position 10 to about amino acid position 31, from about amino acid position 50 to about amino acid position 72, from about amino acid position 87 to about amino acid position 110 and from about amino acid position 191 to about amino acid position 213 in the PR0994 amino acid sequence (Figure 176, SEQ ID N0:258).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85% positives, more preferably at least about 90 h positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 229, inclusive of Figure 176 (SEQ
ID N0:258), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0994 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 mtcleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 175 (SEQ ID N0:257).
In another embodiment, the invention provides isolated PR0994 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0994 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 to about 229 of Figure 176 (SEQ
ID N0:258).
In another aspect, the invention concerns an isolated PR0994 polypeptide, comprising an amino acid sequence having at least about 80'~ sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 h sequence identity, most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues 1 to about 229, inclusive of Figure 176 (SEQ
ID N0:258).
In a further aspect, the invention concerns an isolated PR0994 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85~
positives, more preferably at least about 90~ positives, most preferably at least about 95 ro positives when compared with the amino acid sequence of residues 1 to about 229, inclusive of Figure I76 (SEQ ID N0:258).
In yet another aspect, the invention concerns an isolated PR0994 polypeptide, comprising the sequence of amino acid residues 1 to about 229, inclusive of Figure 176 (SEQ ID
N0:258), or a fragment thereof sufficient to provide a binding site for an anti-PR0994 antibody. Preferably, the PR0994 fragment retains a qualitative biological activity of a native PR0994 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under suingent conditions with (a) a DNA molecule encoding a PR0994 polypeptide having the sequence of amino acid residues from about 1 to about 229, inclusive of Figure 176 (SEQ ID N0:258), or (b) the complement of the DNA molecule of (a), and if the test DNA moiecule has at least about an 80~ sequence identity, preferably at least about an 85 Y6 sequence identity, more preferably at least about a 90qb sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for ezpression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0994 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0994 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0994 polypeptide by contacting the native PR0994 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0994 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
74. PR0812 A cDNA clone (DNA59205-142i) has been identified, having homology to nucleic acid encoding prostatic steroid-binding protein cl that encodes a novel polypeptide, designated in the present application as "PR0812".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0812 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0812 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID
N0:260), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0812 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 55 or about 100 and about 303, inclusive, of Figure 177 (SEQ ID N0:259).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203009 (DNA59205-1421) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203009 (DNA59205-1421).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID
N0:260), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0812 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID N0:260), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0812 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position 15 in the sequence of Figure 178 (SEQ
ID N0:260).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID N0:260), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0812 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 177 (SEQ ID N0:259).
In another embodiment, the invention provides isolated PR0812 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0812 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 83 of Figure 178 (SEQ ID N0:260).
In another aspect, the invention concerns an isolated PR0812 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID N0:260).
In a further aspect, the invention concerns an isolated PR08I2 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID
N0:260).
In yet another aspect, the invention concerns an isolated PR0812 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ
ID N0:260), or a fragment thereof sufficient to provide a binding site for an anti-PR0812 antibody.
Preferably, the PR0812 fragment retains a qualitative biological activity of a native PR0812 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0812 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 83>
inclusive of Figure 178 (SEQ ID
N0:260), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0812 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0812 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0812 polypeptide by contacting the native PR0812 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0812 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0812 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0812 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID
N0:260), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0812 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 55 or about 100 and about 303, inclusive, of Figure 177 (SEQ ID N0:259).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203009 (DNA59205-1421) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203009 (DNA59205-1421).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID
N0:260), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR0812 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID N0:260), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
1n a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0812 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position 15 in the sequence of Figure 178 (SEQ
ID N0:260).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID N0:260), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR0812 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 177 (SEQ ID N0:259).
In another embodiment, the invention provides isolated PR0812 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR0812 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 83 of Figure 178 (SEQ ID N0:260).
In another aspect, the invention concerns an isolated PR0812 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID N0:260).
In a further aspect, the invention concerns an isolated PR08I2 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ ID
N0:260).
In yet another aspect, the invention concerns an isolated PR0812 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 83, inclusive of Figure 178 (SEQ
ID N0:260), or a fragment thereof sufficient to provide a binding site for an anti-PR0812 antibody.
Preferably, the PR0812 fragment retains a qualitative biological activity of a native PR0812 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0812 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 83>
inclusive of Figure 178 (SEQ ID
N0:260), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR0812 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0812 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0812 polypeptide by contacting the native PR0812 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0812 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
75. PR01069 Applicants have identified a cDNA clone, DNA59211-1450, that encodes a novel polypeptide having homology to CHIF wherein the polypeptide is designated in the present application as "PR01069".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01069 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01069 polypeptide having the sequence of amino acid residues from 1 or about 17 to about 89, inclusive of Figure 180 (SEQ ID N0:262), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01069 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 197 or about 245 to about 463, inclusive of Figure 179 (SEQ ID
N0:261). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209960 (DNA59211-1450), which was deposited on June 9, 1998. In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209960 (DNA59211-1450).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 17 to about 89, inclusive of Figure 180 (SEQ ID
N0:262).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01069 extracellular domain (ECD), with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e, transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 16 in the sequence of Figure 180 (SEQ ID N0:262). A
transmembrane domain region has been tentatively identified as extending from about amino acid position 36 to about amino acid position 59 in the PR01069 amino acid sequence (Figure 180, SEQ ID N0:262).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypepiide scoring at least about 80% positives, preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 17 to about 89, inclusive of Figure 180 (SEQ ID N0:262).
Another embodiment is directed to fragments of a PR01069 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1069 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01069 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 17 to 89 of Figure 180 (SEQ ID
N0:262).
In another aspect, the invention concerns an isolated PRO 1069 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to 89, inclusive of Figure 180 (SEQ ID N0:262).
In a further aspect, the invention concerns an isolated PRO 1069 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 17 to about 89 of Figure 180 (SEQ ID N0:262).
In another aspect, the invention concerns a PR01069 extracellular domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to X of Figure 180 (SEQ ID
N0:262), wherein X is any one of amino acid residues 32 to 41 of Figure 180 (SEQ ID N0:262).
In yet another aspect, the invention concerns an isolated PRO 1069 polypeptide, comprising the sequence of amino acid residues 1 or about 17 to about 89, inclusive of Figure 180 (SEQ
ID N0:262), or a fragment thereof sufficient to provide a binding site for an anti-PR01069 antibody.
Preferably, the PR01069 fragment retains a qualitative biological activity of a native PR01069 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01069 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PR01069 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01069 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01069 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01069 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01069 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01069 polypeptide having the sequence of amino acid residues from 1 or about 17 to about 89, inclusive of Figure 180 (SEQ ID N0:262), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01069 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 197 or about 245 to about 463, inclusive of Figure 179 (SEQ ID
N0:261). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209960 (DNA59211-1450), which was deposited on June 9, 1998. In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209960 (DNA59211-1450).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 17 to about 89, inclusive of Figure 180 (SEQ ID
N0:262).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01069 extracellular domain (ECD), with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants (i.e, transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 16 in the sequence of Figure 180 (SEQ ID N0:262). A
transmembrane domain region has been tentatively identified as extending from about amino acid position 36 to about amino acid position 59 in the PR01069 amino acid sequence (Figure 180, SEQ ID N0:262).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypepiide scoring at least about 80% positives, preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 17 to about 89, inclusive of Figure 180 (SEQ ID N0:262).
Another embodiment is directed to fragments of a PR01069 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1069 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01069 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 17 to 89 of Figure 180 (SEQ ID
N0:262).
In another aspect, the invention concerns an isolated PRO 1069 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to 89, inclusive of Figure 180 (SEQ ID N0:262).
In a further aspect, the invention concerns an isolated PRO 1069 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 17 to about 89 of Figure 180 (SEQ ID N0:262).
In another aspect, the invention concerns a PR01069 extracellular domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 17 to X of Figure 180 (SEQ ID
N0:262), wherein X is any one of amino acid residues 32 to 41 of Figure 180 (SEQ ID N0:262).
In yet another aspect, the invention concerns an isolated PRO 1069 polypeptide, comprising the sequence of amino acid residues 1 or about 17 to about 89, inclusive of Figure 180 (SEQ
ID N0:262), or a fragment thereof sufficient to provide a binding site for an anti-PR01069 antibody.
Preferably, the PR01069 fragment retains a qualitative biological activity of a native PR01069 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01069 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonist and antagonists of the PR01069 polypeptide.
In a particular embodiment, the agonist or antagonist is an anti-PR01069 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01069 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PR01069 polypeptide as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
76. PR01129 Applicants have identified a cDNA clone (DNA59213-1487) having homology to nucleic acid encoding cytochrome P-450 family members that encodes a novel polypeptide, designated in the present application as "PRO 1129" .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01129 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01129 polypeptide having the sequence of amino acid residues from about 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01129 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 42 and about 1613, inclusive, of Figure 181 (SEQ ID N0:263). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209959 (DNA59213-1487). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209959 (DNA59213-1487).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01129 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The type II
transmembrane domains have been tentatively identified as extending from about amino acid position 13 to about amino acid position 32 and from about amino acid position 77 to about amino acid position 102 in the PR01129 amino acid sequence (Figure 182, SEQ ID N0:264).
WO 99/63088 PC'T/US99/12252 In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264).
Another embodiment is directed to fragments of a PR01129 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01129 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01129 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to about 524 of Figure 182 (SEQ ID
N0:264).
In another aspect, the invention concerns an isolated PR01129 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 524, inclusive of Figure 182 (SEQ
ID N0:264).
In a further aspect, the invention concerns an isolated PRO 1129. polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264).
In yet another aspect, the invention concerns an isolated PRO 1129 polypeptide, comprising the sequence of amino acid residues 1 to about 524, inclusive of Figure 182 (SEQ ID
N0:264), or a fragment thereof sufficient to provide a binding site for an anti-PR01129 antibody. Preferably, the PR01129 fragment retains a qualitative biological activity of a native PR01129 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01129 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01129 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01129 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01129 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PRO 1129 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01129 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01129 polypeptide having the sequence of amino acid residues from about 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01129 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 42 and about 1613, inclusive, of Figure 181 (SEQ ID N0:263). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209959 (DNA59213-1487). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209959 (DNA59213-1487).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01129 polypeptide, with or without the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The type II
transmembrane domains have been tentatively identified as extending from about amino acid position 13 to about amino acid position 32 and from about amino acid position 77 to about amino acid position 102 in the PR01129 amino acid sequence (Figure 182, SEQ ID N0:264).
WO 99/63088 PC'T/US99/12252 In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264).
Another embodiment is directed to fragments of a PR01129 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01129 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01129 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to about 524 of Figure 182 (SEQ ID
N0:264).
In another aspect, the invention concerns an isolated PR01129 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to about 524, inclusive of Figure 182 (SEQ
ID N0:264).
In a further aspect, the invention concerns an isolated PRO 1129. polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 to about 524, inclusive of Figure 182 (SEQ ID N0:264).
In yet another aspect, the invention concerns an isolated PRO 1129 polypeptide, comprising the sequence of amino acid residues 1 to about 524, inclusive of Figure 182 (SEQ ID
N0:264), or a fragment thereof sufficient to provide a binding site for an anti-PR01129 antibody. Preferably, the PR01129 fragment retains a qualitative biological activity of a native PR01129 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01129 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01129 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01129 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01129 polypeptide.
In still a further embodiment, the invention concerns a composition comprising a PRO 1129 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
77. PR01068 A cDNA clone (DNA59214-1449) has been identified, that encodes a novel polypeptide having homology to urotensin and designated the present application as "PR01068."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01068 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1068 polypeptide having the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ ID N0:266), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01068 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 102 and about 413, inclusive, of Figure 183 (SEQ ID N0:265). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203046 (DNA59214-1449), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203046 (DNA592I4-1449).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypepdde having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ ID
N0:266), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01068 polypeptide having the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ
ID N0:266), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01068 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 184 (SEQ
ID N0:266).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 21 to about 124, inclusive of Figure 184 (SEQ
ID N0:266), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01068 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01068 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1068 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 124 of Figure 184 (SEQ ID N0:266).
In another aspect, the invention concerns an isolated PR01068 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 124, inclusive of Figure 184 (SEQ
ID N0:266).
In a further aspect, the invention concerns an isolated PRO 1068 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to 124 of Figure 184 (SEQ ID N0:266).
In yet another aspect, the invention concerns an isolated PRO 1068 polypeptide, comprising the sequence of amino acid residues 21 to about 124, inclusive of Figure 184 (SEQ ID
N0:266), or a fragment thereof sufficient to provide a binding site for an anti-PR01068 antibody. Preferably, the PR01068 fragment retains a qualitative biological activity of a native PR01068 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01068 polypeptide having the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ ID N0:266), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01068 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01068 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01068 polypeptide, by contacting the native PR01068 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1068 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01068 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1068 polypeptide having the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ ID N0:266), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01068 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 102 and about 413, inclusive, of Figure 183 (SEQ ID N0:265). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203046 (DNA59214-1449), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203046 (DNA592I4-1449).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypepdde having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ ID
N0:266), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01068 polypeptide having the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ
ID N0:266), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01068 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 184 (SEQ
ID N0:266).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 21 to about 124, inclusive of Figure 184 (SEQ
ID N0:266), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01068 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01068 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1068 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 21 to 124 of Figure 184 (SEQ ID N0:266).
In another aspect, the invention concerns an isolated PR01068 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 21 to about 124, inclusive of Figure 184 (SEQ
ID N0:266).
In a further aspect, the invention concerns an isolated PRO 1068 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 21 to 124 of Figure 184 (SEQ ID N0:266).
In yet another aspect, the invention concerns an isolated PRO 1068 polypeptide, comprising the sequence of amino acid residues 21 to about 124, inclusive of Figure 184 (SEQ ID
N0:266), or a fragment thereof sufficient to provide a binding site for an anti-PR01068 antibody. Preferably, the PR01068 fragment retains a qualitative biological activity of a native PR01068 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01068 polypeptide having the sequence of amino acid residues from about 21 to about 124, inclusive of Figure 184 (SEQ ID N0:266), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01068 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01068 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01068 polypeptide, by contacting the native PR01068 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1068 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
78. PR01066 Applicants have identified a cDNA clone (DNA59215-1425) that encodes a novel secreted polypeptide, designated in the present application as "PR01066".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01066 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 '~ sequence identity, preferably at least. about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01066 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID
N0:268), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01066 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 176 or about 245 and about 527, inclusive, of Figure 185 (SEQ ID N0:267).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209961 (DNA59215-1425). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209961 (DNA59215-1425).
In stilt a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID
N0:268).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01066 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 186 (SEQ
ID N0:268).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 k positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about I 17, inclusive of Figure 186 (SEQ
ID N0:268).
Another embodiment is directed to fragments of a PR01066 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01066 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01066 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 24 to about 117 of Figure 186 (SEQ ID N0:268).
In another aspect, the invention concerns an isolated PRO 1066 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID N0:268).
In a further aspect, the invention concerns an isolated PRO 1066 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID
N0:268).
In yet another aspect, the invention concerns an isolated PRO 1066 polypeptide, comprising the sequence of amino acid residues I or about 24 to about 117, inclusive of Figure 186 (SEQ ID N0:268), or a fragment thereof sufficient to provide a binding site for an anti-PR01066 antibody.
Preferably, the PR01066 fragment retains a qualitative biological activity of a native PR01066 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01066 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01066 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 '~ sequence identity, preferably at least. about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01066 polypeptide having the sequence of amino acid residues from about 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID
N0:268), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01066 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 176 or about 245 and about 527, inclusive, of Figure 185 (SEQ ID N0:267).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209961 (DNA59215-1425). In a preferred embodiment, the nucleic acid comprises a DNA
encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209961 (DNA59215-1425).
In stilt a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID
N0:268).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01066 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 23 in the sequence of Figure 186 (SEQ
ID N0:268).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 k positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about I 17, inclusive of Figure 186 (SEQ
ID N0:268).
Another embodiment is directed to fragments of a PR01066 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01066 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01066 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 24 to about 117 of Figure 186 (SEQ ID N0:268).
In another aspect, the invention concerns an isolated PRO 1066 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID N0:268).
In a further aspect, the invention concerns an isolated PRO 1066 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 24 to about 117, inclusive of Figure 186 (SEQ ID
N0:268).
In yet another aspect, the invention concerns an isolated PRO 1066 polypeptide, comprising the sequence of amino acid residues I or about 24 to about 117, inclusive of Figure 186 (SEQ ID N0:268), or a fragment thereof sufficient to provide a binding site for an anti-PR01066 antibody.
Preferably, the PR01066 fragment retains a qualitative biological activity of a native PR01066 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01066 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
79. PR01184 Applicants have identified a cDNA clone (DNA59220-1514) that encodes a novel secreted polypeptide, designated in the present application as "PR01184".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01184 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~o sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1184 polypeptide having the sequence of amino acid residues from 1 or about 39 through 142 of Figure 188 (SEQ ID N0:270), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01184 polypeptide comprising DNA hybridizing to the complement of the nucleic acid at about residues 106 or 220 through 531 of SEQ ID N0:269. In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01184 polypeptide comprising DNA hybridizing to the complement of the nucleic of SEQ ID
N0:269. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 1?4 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
of DNA59220-1514. In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit of DNA59220-1514.
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85%a sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues i or about 39 through 142 of SEQ ID N0:270.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01184 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants, or is complementary to such an encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 38 of SEQ ID
N0:270.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 39 through 142 of SEQ ID N0:270.
Another embodiment is directed to fragments of a PRO 1184 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01184 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PRO 1184 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 39 through 142 of SEQ ID
N0:270.
In another aspect, the invention concerns an isolated PR01184 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 39 through 142 of SEQ ID N0:270.
In a fiirttter aspect, the invention concerns an isolated PRO 1184 polypeptide, comprising an amino acid sequence scoring at least about 80 ~ positives, preferably at least about 85 ~
positives, more preferably at least about 90Rb positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 39 through 142 of SEQ ID N0:270.
In yet another aspect, the invention concerns an isolated PR01184 polypeptide, comprising the sequence of amino acid residues 1 or about 39 through 142 of SEQ ID N0:270, or a fragment thereof sufficient to provide a binding site for an anti-PR01184 antibody. Preferably, the PR01184 fragment retains a qualitative biological activity of a native PR01184 polvpeptide.
In another aspect, the present invention is directed to fragments of a PR01184 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
80. PR01360 A cDNA clone (DNA59488-1603) has been identified that encodes a novel polypeptide designated in the present application as "PR01360."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01360 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 8096 sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1360 polypeptide having the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ ID N0:272), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01360 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 140 and about 908, inclusive, of Figure 189 (SEQ ID N0:271). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203157 (DNA59488-1603), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203157 (DNA59488-1603).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ ID
N0:272), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01360 polypeptide having the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ
ID N0:272), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more WO 99/63088 PC'T/US99/12252 preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 30 to about 285, inclusive of Figure 190 (SEQ
ID N0:272), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01360 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01360 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1360 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 30 through 285 of Figure 190 (SEQ ID
N0:272).
In another aspect, the invention concerns an isolated PRO 1360 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 k sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues 30 to about 285, inclusive of Figure 190 (SEQ
ID N0:272).
In a further aspect, the invention concerns an isolated PRO 1360 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 30 through 285 of Figure 190 (SEQ ID N0:272).
In yet another aspect, the invention concerns an isolated PRO 1360 polypeptide, comprising the sequence of amino acid residues 30 to about 285, inclusive of Figure 190 (SEQ 1D
N0:272), or a fragment thereof sufficient to provide a binding site for an anti-PROi360 antibody. Preferably, the PR01360 fragment retains a qualitative biological activity of a native PR01360 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01360 polypeptide having the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ ID N0:272), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 856 sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the poiypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01360 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01360 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01360 polypeptide, by contacting the native PR01360 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01360 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01184 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~o sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1184 polypeptide having the sequence of amino acid residues from 1 or about 39 through 142 of Figure 188 (SEQ ID N0:270), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01184 polypeptide comprising DNA hybridizing to the complement of the nucleic acid at about residues 106 or 220 through 531 of SEQ ID N0:269. In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01184 polypeptide comprising DNA hybridizing to the complement of the nucleic of SEQ ID
N0:269. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule 1?4 encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
of DNA59220-1514. In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit of DNA59220-1514.
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85%a sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 ~ sequence identity to the sequence of amino acid residues i or about 39 through 142 of SEQ ID N0:270.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01184 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble variants, or is complementary to such an encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 38 of SEQ ID
N0:270.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or about 39 through 142 of SEQ ID N0:270.
Another embodiment is directed to fragments of a PRO 1184 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01184 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PRO 1184 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 39 through 142 of SEQ ID
N0:270.
In another aspect, the invention concerns an isolated PR01184 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 39 through 142 of SEQ ID N0:270.
In a fiirttter aspect, the invention concerns an isolated PRO 1184 polypeptide, comprising an amino acid sequence scoring at least about 80 ~ positives, preferably at least about 85 ~
positives, more preferably at least about 90Rb positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 39 through 142 of SEQ ID N0:270.
In yet another aspect, the invention concerns an isolated PR01184 polypeptide, comprising the sequence of amino acid residues 1 or about 39 through 142 of SEQ ID N0:270, or a fragment thereof sufficient to provide a binding site for an anti-PR01184 antibody. Preferably, the PR01184 fragment retains a qualitative biological activity of a native PR01184 polvpeptide.
In another aspect, the present invention is directed to fragments of a PR01184 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
80. PR01360 A cDNA clone (DNA59488-1603) has been identified that encodes a novel polypeptide designated in the present application as "PR01360."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01360 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 8096 sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1360 polypeptide having the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ ID N0:272), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01360 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 140 and about 908, inclusive, of Figure 189 (SEQ ID N0:271). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203157 (DNA59488-1603), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203157 (DNA59488-1603).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ ID
N0:272), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01360 polypeptide having the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ
ID N0:272), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more WO 99/63088 PC'T/US99/12252 preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 30 to about 285, inclusive of Figure 190 (SEQ
ID N0:272), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01360 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01360 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1360 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 30 through 285 of Figure 190 (SEQ ID
N0:272).
In another aspect, the invention concerns an isolated PRO 1360 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85 k sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues 30 to about 285, inclusive of Figure 190 (SEQ
ID N0:272).
In a further aspect, the invention concerns an isolated PRO 1360 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 30 through 285 of Figure 190 (SEQ ID N0:272).
In yet another aspect, the invention concerns an isolated PRO 1360 polypeptide, comprising the sequence of amino acid residues 30 to about 285, inclusive of Figure 190 (SEQ 1D
N0:272), or a fragment thereof sufficient to provide a binding site for an anti-PROi360 antibody. Preferably, the PR01360 fragment retains a qualitative biological activity of a native PR01360 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01360 polypeptide having the sequence of amino acid residues from about 30 to about 285, inclusive of Figure 190 (SEQ ID N0:272), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 856 sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the poiypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01360 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01360 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01360 polypeptide, by contacting the native PR01360 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01360 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
81. PR01029 A cDNA clone (DNA59493-1420) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01029".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01029 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01029 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01029 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 39 or about 96 and about 296, inclusive, of Figure 191 (SEQ ID N0:274).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203050 (DNA59493-1420) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203050 (DNA59493-1420).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01029 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID N0:274), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01029 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 192 (SEQ
ID N0:274).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 ~ positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID N0:274), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01029 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 191 (SEQ ID N0:273).
In another embodiment, the invention provides isolated PR01029 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01029 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 86 of Figure 192 (SEQ ID N0:274).
In another aspect, the invention concerns an isolated PR01029 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID N0:274).
In a further aspect, the invention concerns an isolated PR01029 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%a positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274).
In yet another aspect, the invention concerns an isolated PRO 1029 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ
ID N0:274), or a fragment thereof sufficient to provide a binding site for an anti-PR01029 antibody.
Preferably, the PR01029 fragment retains a qualitative biological activity of a native PR01029 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01029 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 %a sequence identity, more preferably at least about a 90 R6 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01029 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01029 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01029 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 39 or about 96 and about 296, inclusive, of Figure 191 (SEQ ID N0:274).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203050 (DNA59493-1420) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203050 (DNA59493-1420).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01029 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID N0:274), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01029 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 192 (SEQ
ID N0:274).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 ~ positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID N0:274), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01029 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 191 (SEQ ID N0:273).
In another embodiment, the invention provides isolated PR01029 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01029 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 86 of Figure 192 (SEQ ID N0:274).
In another aspect, the invention concerns an isolated PR01029 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID N0:274).
In a further aspect, the invention concerns an isolated PR01029 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85%a positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274).
In yet another aspect, the invention concerns an isolated PRO 1029 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 86, inclusive of Figure 192 (SEQ
ID N0:274), or a fragment thereof sufficient to provide a binding site for an anti-PR01029 antibody.
Preferably, the PR01029 fragment retains a qualitative biological activity of a native PR01029 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01029 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 86, inclusive of Figure 192 (SEQ ID
N0:274), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 %a sequence identity, more preferably at least about a 90 R6 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
82. )E'R01139 Applicants have identified a novel cDNA clone (DNA59497-1496) that encodes a novel human protein originally designated as PR01139.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01139 polypeptide having the sequence of amino acid residues from about 29 to about 131 of Figure 194 (SEQ ID N0:276), or (b) the complement of the DNA molecule of (a).
In another embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
hybridizing to the complement of the polynucleotide sequence between about residues 80 and 391, inclusive, of Figure 193 (SEQ ID N0:275). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
having at least about 80% sequence identity, preferably at least about 85%
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%
sequence identity to (a) a DNA
molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
209941 (DNA59497-1496). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
209941 (DNA59497-1496).
In a still further embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 29 to about 131 of Figure 194 (SEQ ID N0:276).
In a specific embodiment, the invention provides an isolated nucleic acid molecule comprising DNA
encoding a native or variant PR01139 polypeptide, with or without the N-terminal signal sequence, and with or without the transmembrane regions which have been identified as stretching from about amino acid position 33 to about amino acid position 52; from about amino acid position 71 to about amino acid position 89; and from about amino acid position 98 to about amino acid position 120, respectively of the amino acid sequence of Figure 194, SEQ ID N0:276. In one aspect, the isolated nucleic acid comprises DNA
encoding a mature, full-length native PR01139 polypeptide having amino acid residues 1 to 131 of Figure 194, SEQ ID N0:276, or is complementary to such encoding nucleic acid sequence.
In another embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues from about 29 to about 131 of Figure 194 (SEQ
ID N0:276).
In another embodiment, the invention provides isolated PR01139 poiypeptides.
In particular, the invention provides isolated native sequence PROI 139 polypeptide, which in one embodiment, include the amino acid sequence comprising residues 29 to 131 of Figure 194 (SEQ ID N0:276). The invention also provides for variants of the PR01139 polypeptide which are encoded by any of the isolated nucleic acid molecules WO 99/63088 PCTlUS99/12252 hereinabove defined. Specific variants include, but are not limited to, deletion (truncated) variants of the full-length native sequence PR01139 which lack the N-terminal signal sequence and/or have at least one transmembrane domain deleted or inactivated. The variants specifically include variants of the full-length mature polypeptide of Figure 194 (SEQ ID N0:276) in which one or more of the transmembrane regions between amino acid residues 33-52, 71-8, and 98-120, respectively have been deleted or inactivated, and which may additionally have the N-terminal signal sequence (amino acid residues 1-28) and/or the initiating methionine deleted.
In a further embodiment, the invention concerns an isolated PRO 1139 polypeptide, comprising an amino acid sequence scoring at least about 80 h positives, preferably at least about 85 % positives, more preferably at least about 90°6 positives, most preferably at least about 95~
positives when compared with the amino acid sequence of residues from about 29 to about 131 of Figure 194 (SEQ ID N0:276).
In yet another aspect, the invention concerns an isolated PRO 1139 polypeptide, comprising the sequence of amino acid residues 29 to about 131, inclusive of Figure 194 (SEQ ID
N0:276) or a fragment thereof sufficient to provide a binding site for an anti-PR01139 antibody. Preferably, the PR01139 fragment retains a qualitative biological activity of a native PR01139 polypeptide.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01139 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01139 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01139 polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01139 polypeptide (including variants), or an agonist or antagonist as hereinabove defcned, in combination with a pharmaceutically acceptable carrier.
The invention also concerns a method of treating obesity comprising administering to a patient an effective amount of an antagonist of a PR01139 polypeptide. In a specific embodiment, the antagonist is a blocking antibody specifically binding a native PROI139 polypeptide.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR01139 polypeptide having the sequence of amino acid residues from about 29 to about 131 of Figure 194 (SEQ ID N0:276), or (b) the complement of the DNA molecule of (a).
In another embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
hybridizing to the complement of the polynucleotide sequence between about residues 80 and 391, inclusive, of Figure 193 (SEQ ID N0:275). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
having at least about 80% sequence identity, preferably at least about 85%
sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%
sequence identity to (a) a DNA
molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
209941 (DNA59497-1496). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No.
209941 (DNA59497-1496).
In a still further embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 29 to about 131 of Figure 194 (SEQ ID N0:276).
In a specific embodiment, the invention provides an isolated nucleic acid molecule comprising DNA
encoding a native or variant PR01139 polypeptide, with or without the N-terminal signal sequence, and with or without the transmembrane regions which have been identified as stretching from about amino acid position 33 to about amino acid position 52; from about amino acid position 71 to about amino acid position 89; and from about amino acid position 98 to about amino acid position 120, respectively of the amino acid sequence of Figure 194, SEQ ID N0:276. In one aspect, the isolated nucleic acid comprises DNA
encoding a mature, full-length native PR01139 polypeptide having amino acid residues 1 to 131 of Figure 194, SEQ ID N0:276, or is complementary to such encoding nucleic acid sequence.
In another embodiment, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues from about 29 to about 131 of Figure 194 (SEQ
ID N0:276).
In another embodiment, the invention provides isolated PR01139 poiypeptides.
In particular, the invention provides isolated native sequence PROI 139 polypeptide, which in one embodiment, include the amino acid sequence comprising residues 29 to 131 of Figure 194 (SEQ ID N0:276). The invention also provides for variants of the PR01139 polypeptide which are encoded by any of the isolated nucleic acid molecules WO 99/63088 PCTlUS99/12252 hereinabove defined. Specific variants include, but are not limited to, deletion (truncated) variants of the full-length native sequence PR01139 which lack the N-terminal signal sequence and/or have at least one transmembrane domain deleted or inactivated. The variants specifically include variants of the full-length mature polypeptide of Figure 194 (SEQ ID N0:276) in which one or more of the transmembrane regions between amino acid residues 33-52, 71-8, and 98-120, respectively have been deleted or inactivated, and which may additionally have the N-terminal signal sequence (amino acid residues 1-28) and/or the initiating methionine deleted.
In a further embodiment, the invention concerns an isolated PRO 1139 polypeptide, comprising an amino acid sequence scoring at least about 80 h positives, preferably at least about 85 % positives, more preferably at least about 90°6 positives, most preferably at least about 95~
positives when compared with the amino acid sequence of residues from about 29 to about 131 of Figure 194 (SEQ ID N0:276).
In yet another aspect, the invention concerns an isolated PRO 1139 polypeptide, comprising the sequence of amino acid residues 29 to about 131, inclusive of Figure 194 (SEQ ID
N0:276) or a fragment thereof sufficient to provide a binding site for an anti-PR01139 antibody. Preferably, the PR01139 fragment retains a qualitative biological activity of a native PR01139 polypeptide.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01139 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01139 antibody.
In a further embodiment, the invention concerns screening assays to identify agonists or antagonists of a native PR01139 polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01139 polypeptide (including variants), or an agonist or antagonist as hereinabove defcned, in combination with a pharmaceutically acceptable carrier.
The invention also concerns a method of treating obesity comprising administering to a patient an effective amount of an antagonist of a PR01139 polypeptide. In a specific embodiment, the antagonist is a blocking antibody specifically binding a native PROI139 polypeptide.
83. PR01309 A cDNA clone (DNA59588-1571) has been identified that encodes a novel polypeptide having leucine rich repeats and designated in the present application as "PR01309."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01309 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1309 polypeptide having the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ ID N0:278), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01309 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 822 and about 2285, inclusive, of Figure 195 (SEQ ID N0:277). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203106 (DNA59588-1571), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203106 (DNA59588-1571).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ ID
N0:278), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01309 polypeptide having the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ
ID N0:278), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01309 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 34 in the sequence of Figure 196 (SEQ ID
N0:278). The transmembrane domain has been tentatively identified as extending from about amino acid position 428 through about amino acid position 450 in the PR01309 amino acid sequence (Figure 196, SEQ ID N0:278).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 35 to about 522, inclusive of Figure 196 (SEQ
ID N0:278), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1309 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleosides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01309 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
WO 99/63088 PC'T/US99/12252 In a specific aspect, the invention provides isolated native sequence PR01309 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 35 through 522 of Figure 196 (SEQ ID
N0:278).
In another aspect, the invention concerns an isolated PR01309 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 35 to about 522, inclusive of Figure 196 (SEQ
ID N0:278).
In a further aspect, the invention concerns an isolated PRO 1309 polypeptide, comprising an amino acid sequence scoring at least about 80 %a positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 35 through 522 of Figure 196 (SEQ ID N0:278).
In yet another aspect, the invention concerns an isolated PR01309 polypeptide, comprising the sequence of amino acid residues 35 to about 522, inclusive of Figure 196 (SEQ ID
N0:278), or a fragment thereof sufficient to provide a binding site for an anti-PR01309 antibody. Preferably, the PR01309 fragment retains a qualitative biological activity of a native PR01309 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01309 polypeptide having the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ ID N0:278), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01309 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01309 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01309 polypeptide, by contacting the native PR01309 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01309 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01309 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1309 polypeptide having the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ ID N0:278), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01309 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 822 and about 2285, inclusive, of Figure 195 (SEQ ID N0:277). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203106 (DNA59588-1571), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203106 (DNA59588-1571).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ ID
N0:278), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01309 polypeptide having the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ
ID N0:278), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01309 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 34 in the sequence of Figure 196 (SEQ ID
N0:278). The transmembrane domain has been tentatively identified as extending from about amino acid position 428 through about amino acid position 450 in the PR01309 amino acid sequence (Figure 196, SEQ ID N0:278).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 35 to about 522, inclusive of Figure 196 (SEQ
ID N0:278), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1309 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleosides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01309 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
WO 99/63088 PC'T/US99/12252 In a specific aspect, the invention provides isolated native sequence PR01309 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 35 through 522 of Figure 196 (SEQ ID
N0:278).
In another aspect, the invention concerns an isolated PR01309 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 35 to about 522, inclusive of Figure 196 (SEQ
ID N0:278).
In a further aspect, the invention concerns an isolated PRO 1309 polypeptide, comprising an amino acid sequence scoring at least about 80 %a positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 35 through 522 of Figure 196 (SEQ ID N0:278).
In yet another aspect, the invention concerns an isolated PR01309 polypeptide, comprising the sequence of amino acid residues 35 to about 522, inclusive of Figure 196 (SEQ ID
N0:278), or a fragment thereof sufficient to provide a binding site for an anti-PR01309 antibody. Preferably, the PR01309 fragment retains a qualitative biological activity of a native PR01309 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01309 polypeptide having the sequence of amino acid residues from about 35 to about 522, inclusive of Figure 196 (SEQ ID N0:278), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01309 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01309 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01309 polypeptide, by contacting the native PR01309 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01309 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
84. PR01028 Applicants have identified a cDNA clone that encodes a secreted novel polypeptide, wherein the poIypeptide is designated in the present application as "PRO 1028" .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01028 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01028 polypeptide having amino acid residues 1 through 197 of Figure 198 (SEQ ID
N0:281), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 9, 1998 with the ATCC as DNA59603-1419 which includes the nucleotide sequence encoding PR01028.
In another embodiment, the invention provides isolated PR01028 polypeptide. In particular, the invention provides isolated native sequence PR01028 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 197 of Figure 198 (SEQ ID N0:281).
Optionaliy, the PR01028 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited on June 9, 1998 with the ATCC as DNA59603-1419.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01028 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01028 polypeptide having amino acid residues 1 through 197 of Figure 198 (SEQ ID
N0:281), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the vector deposited on June 9, 1998 with the ATCC as DNA59603-1419 which includes the nucleotide sequence encoding PR01028.
In another embodiment, the invention provides isolated PR01028 polypeptide. In particular, the invention provides isolated native sequence PR01028 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 197 of Figure 198 (SEQ ID N0:281).
Optionaliy, the PR01028 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the vector deposited on June 9, 1998 with the ATCC as DNA59603-1419.
85. PR01027 A cDNA clone (DNA59605-1418) has been identified, having a type II fibronectin collagen-binding domain that encodes a novel polypeptide, designated in the present application as "PR01027."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01027 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01027 polypeptide having the sequence of amino acid residues from about 1 or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-77, or in another embodiment, 34-77.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01027 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 31 or 130 and about 261, inclusive, of Figure 199 (SEQ ID N0:282}. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203005 (DNA59605-1418), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203005 (DNA59605-1418).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 34 to about 77, inclusive of Figure 200 (SEQ
ID N0:283), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01027 polypeptide having the sequence of amino acid residues from about I or 34 to about 77, inclusive of Figure 200 (SEQ ID
N0:283), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01027 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1027 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues I or 34 through 77 of Figure 200 (SEQ ID
N0:283).
In another aspect, the invention concerns an isolated PRO 1027 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283).
In a further aspect, the invention concerns an isolated PRO 1027 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 34 through 77 of Figure 200 (SEQ ID N0:283).
~ In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01027 polypeptide having the sequence of amino acid residues from about 1 or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01027 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01027 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01027 polypeptide, by contacting the native PR01027 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01027 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01027 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01027 polypeptide having the sequence of amino acid residues from about 1 or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-77, or in another embodiment, 34-77.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01027 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 31 or 130 and about 261, inclusive, of Figure 199 (SEQ ID N0:282}. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203005 (DNA59605-1418), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203005 (DNA59605-1418).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 34 to about 77, inclusive of Figure 200 (SEQ
ID N0:283), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01027 polypeptide having the sequence of amino acid residues from about I or 34 to about 77, inclusive of Figure 200 (SEQ ID
N0:283), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01027 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1027 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues I or 34 through 77 of Figure 200 (SEQ ID
N0:283).
In another aspect, the invention concerns an isolated PRO 1027 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues I or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283).
In a further aspect, the invention concerns an isolated PRO 1027 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 34 through 77 of Figure 200 (SEQ ID N0:283).
~ In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01027 polypeptide having the sequence of amino acid residues from about 1 or 34 to about 77, inclusive of Figure 200 (SEQ ID N0:283), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01027 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01027 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01027 polypeptide, by contacting the native PR01027 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01027 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
86. hR01107 Applicants have identified a cDNA clone that encodes a novel polypeptide having sequence identity with PC-1, wherein the polypeptide is designated in the present application as "PR01107".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01107 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01107 polypeptide having amino acid residues 1 through 477 of Figure 202 (SEQ ID
N0:285), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR01107 polypeptide having amino acid residues about 23 through 477 of Figure 202 (SEQ ID N0:285) or amino acids about 1 or 23 through 428 t 5 of Figure 202 (SEQ ID N0:285), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA59606-1471 vector deposited on June 9, 1998 with the ATCC, which includes the nucleotide sequence encoding PR01107.
In another embodiment, the invention provides isolated PR01107 polypeptide. In particular, the invention provides isolated native sequence PR01107 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 477 of Figure 202 (SEQ ID N0:285).
Additional embodiments of the present invention are directed to PR01107 polypeptides comprising amino acids about 23 through 477 of Figure 202 (SEQ ID N0:285) or amino acids about 1 or 23 through 428 t 5 of Figwe 202 (SEQ ID N0:285).
Optionally, the PR01107 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA59606-1471 vector deposited with the ATCC on June 9, 1998.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01107 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01107 polypeptide having amino acid residues 1 through 477 of Figure 202 (SEQ ID
N0:285), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PR01107 polypeptide having amino acid residues about 23 through 477 of Figure 202 (SEQ ID N0:285) or amino acids about 1 or 23 through 428 t 5 of Figure 202 (SEQ ID N0:285), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA59606-1471 vector deposited on June 9, 1998 with the ATCC, which includes the nucleotide sequence encoding PR01107.
In another embodiment, the invention provides isolated PR01107 polypeptide. In particular, the invention provides isolated native sequence PR01107 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 477 of Figure 202 (SEQ ID N0:285).
Additional embodiments of the present invention are directed to PR01107 polypeptides comprising amino acids about 23 through 477 of Figure 202 (SEQ ID N0:285) or amino acids about 1 or 23 through 428 t 5 of Figwe 202 (SEQ ID N0:285).
Optionally, the PR01107 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA59606-1471 vector deposited with the ATCC on June 9, 1998.
87. PR01140 Applicants have identified a cDNA clone, DNA59607-1497, that encodes a novel multi-span transmembrane polypeptide wherein the polypeptide is designated in the present application as "PR01140".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01140 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 959 sequence identity to (a) a DNA molecule encoding a PR01140 polypeptide having the sequence of amino acid residues from 1 to about 255, inclusive of Figure 204 (SEQ ID N0:287), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01140 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 210 to about 974, inclusive of Figure 203 (SEQ ID N0:286).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209946 (DNA59607-1497), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209946 (DNA59607-1497).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 255, inclusive of Figure 2(?4 (SEQ ID N0:287).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01140 extracellular domain (ECD), with or without the initiating methionine, and its soluble variants (i.e.
transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule.
Referring to the PR01140 amino acid sequence (SEQ ID N0:287) shown in Figure 204, transmembrane domain regions have been tentatively identified as extending from about amino acid positions 101 to about 118, about I41 to about 161, and from about 172 to about 191.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, and most preferably at least about 95 % positives when compared with the amino acid sequence of residues I to about 255, inclusive of Figure 204 (SEQ ID N0:287).
Another embodiment is directed to fragments of a PRO 1140 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01140 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01140 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 255 of Figure 204 (SEQ ID N0:287).
In another aspect, the invention concerns an isolated PR01140 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to 255, inclusive of Figure 204 (SEQ ID
N0:287).
In a further aspect, the invention concerns an isolated PRO 1140 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, and most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 255 of Figure 204 (SEQ ID N0:287).
In another aspect, the invention concerns a PR01140 extracellular domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to X of Figure 204 (SEQ ID N0:287), wherein X is any one of amino acid residues 96 to 105 of Figure 204 (SEQ ID N0:287).
In yet another aspect, the invention concerns an isolated PRO 1140 polypeptide, comprising the sequence of amino acid residues 1 to about 255, inclusive of Figure 204 (SEQ ID
N0:287), or a fragment thereof sufficient to provide a binding site for an anti-PR01140 antibody. Preferably, the PR01140 fragment retains a qualitative biological activity of a native PR01140 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01140 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
88. PR01106 Applicants have identified a cDNA clone that encodes a novel polypeptide having sequence identity with a peroxisomal calcium-dependent solute carrier, wherein the polypeptide is designated in the present application as "PR01106".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01106 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01106 polypeptide having amino acid residues 1 through 469 of Figure 206 (SEQ ID
N0:289), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA59609-1470 vector deposited on June 9, 1998 with the ATCC, which includes the nucleotide sequence encoding PR01106.
In another embodiment, the invention provides isolated PR01106 polypeptide. In particular, the invention provides isolated native sequence PRO1106 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 469 of Figure 206 (SEQ ID N0:289).
Optionally, the PR01106 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA59609-1470 vector deposited with the ATCC on June 9, 1998.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01140 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 959 sequence identity to (a) a DNA molecule encoding a PR01140 polypeptide having the sequence of amino acid residues from 1 to about 255, inclusive of Figure 204 (SEQ ID N0:287), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01140 polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence having about residues 210 to about 974, inclusive of Figure 203 (SEQ ID N0:286).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209946 (DNA59607-1497), which was deposited on June 9, 1998, or (b) the complement of the DNA molecule of (a).
In a preferred embodiment, the nucleic acid comprises a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209946 (DNA59607-1497).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 255, inclusive of Figure 2(?4 (SEQ ID N0:287).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01140 extracellular domain (ECD), with or without the initiating methionine, and its soluble variants (i.e.
transmembrane domains) deleted or inactivated) or is complementary to such encoding nucleic acid molecule.
Referring to the PR01140 amino acid sequence (SEQ ID N0:287) shown in Figure 204, transmembrane domain regions have been tentatively identified as extending from about amino acid positions 101 to about 118, about I41 to about 161, and from about 172 to about 191.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising DNA encoding a polypeptide scoring at least about 80% positives, preferably at least about 90% positives, and most preferably at least about 95 % positives when compared with the amino acid sequence of residues I to about 255, inclusive of Figure 204 (SEQ ID N0:287).
Another embodiment is directed to fragments of a PRO 1140 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01140 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01140 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 255 of Figure 204 (SEQ ID N0:287).
In another aspect, the invention concerns an isolated PR01140 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to 255, inclusive of Figure 204 (SEQ ID
N0:287).
In a further aspect, the invention concerns an isolated PRO 1140 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, and most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 to about 255 of Figure 204 (SEQ ID N0:287).
In another aspect, the invention concerns a PR01140 extracellular domain comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, and most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 to X of Figure 204 (SEQ ID N0:287), wherein X is any one of amino acid residues 96 to 105 of Figure 204 (SEQ ID N0:287).
In yet another aspect, the invention concerns an isolated PRO 1140 polypeptide, comprising the sequence of amino acid residues 1 to about 255, inclusive of Figure 204 (SEQ ID
N0:287), or a fragment thereof sufficient to provide a binding site for an anti-PR01140 antibody. Preferably, the PR01140 fragment retains a qualitative biological activity of a native PR01140 polypeptide.
In another aspect, the present invention is directed to fragments of a PR01140 polypeptide which are sufficiently long to provide an epitope against which an antibody may be generated.
88. PR01106 Applicants have identified a cDNA clone that encodes a novel polypeptide having sequence identity with a peroxisomal calcium-dependent solute carrier, wherein the polypeptide is designated in the present application as "PR01106".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01106 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PR01106 polypeptide having amino acid residues 1 through 469 of Figure 206 (SEQ ID
N0:289), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA insert of the DNA59609-1470 vector deposited on June 9, 1998 with the ATCC, which includes the nucleotide sequence encoding PR01106.
In another embodiment, the invention provides isolated PR01106 polypeptide. In particular, the invention provides isolated native sequence PRO1106 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 469 of Figure 206 (SEQ ID N0:289).
Optionally, the PR01106 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA59609-1470 vector deposited with the ATCC on June 9, 1998.
89. PR01291 A cDNA clone (DNA59610-1556) has been identified, having homology to nucleic acid encoding butyrophilin that encodes a novel polypeptide, designated in the present application as "PR01291".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01291 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01291 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01291 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 61 or about 145 and about 906, inclusive, of Figure 207 (SEQ ID N0:290).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209990 (DNA59610-1556) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209990 (DNA59610-1556).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01291 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01291 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified~as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 208 (SEQ
ID N0:291). The transmembrane domain has been tentatively identified as extending from about amino acid position 258 to about amino acid position 281 in the PR01291 amino acid sequence (Figure 208, SEQ ID N0:291).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1291 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 207 (SEQ ID N0:290).
In another embodiment, the invention provides isolated PR01291 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01291 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 282 of Figure 208 (SEQ ID N0:291).
In another aspect, the invention concerns an isolated PR01291 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291).
In a further aspect, the invention concerns an isolated PR01291 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291).
In yet another aspect, the invention concerns an isolated PRO 1291 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291), or a fragment thereof sufficient to provide a binding site for an anti-PR01291 antibody.
Preferably, the PR01291 fragment retains a qualitative biological activity of a native PR01291 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01291 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide,'and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01291 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01291 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01291 polypeptide by contacting the native PR01291 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01291 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
90. PR_ 01105 Applicants have identified a cDNA clone that encodes a novel polypeptide having two transmembrane domains, wherein the polypeptide is designated in the present application as "PRO1105".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1105 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PRO1105 polypeptide having amino acid residues 1 through 180 of Figure 210 (SEQ ID
N0:293), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PROI105 polypeptide having amino acid residues about 20 through 180 of Figure 210 (SEQ ID N0:293), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA
insert of the DNA59612-1466 vector deposited on June 9, 1998 with the ATCC, which includes the nucleotide sequence encoding PRO1105.
In another embodiment, the invention provides isolated PRO1105 polypeptide. In particular, the invention provides isolated native sequence PRO1105 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 180 of Figure 210 (SEQ ID N0:293).
Additional embodiments of the present invention are directed to PRO1105 polypeptides comprising amino acids about 20 through 180 of Figure 210 (SEQ ID N0:293). Other embodiments of the present invention are directed to PRO1105 polypeptides comprising amino acids about 1 through 79 and 100 through about 144 of Figure 210 (SEQ ID
N0:293). Optionally, the PRO1105 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA59612-1466 vector deposited with the ATCC
on June 9, 1998.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01291 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01291 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01291 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 61 or about 145 and about 906, inclusive, of Figure 207 (SEQ ID N0:290).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209990 (DNA59610-1556) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209990 (DNA59610-1556).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01291 polypeptide having the sequence of amino acid residues from 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01291 polypeptide, with or without the N-terminal signal sequence andlor the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified~as extending from about amino acid position 1 to about amino acid position 28 in the sequence of Figure 208 (SEQ
ID N0:291). The transmembrane domain has been tentatively identified as extending from about amino acid position 258 to about amino acid position 281 in the PR01291 amino acid sequence (Figure 208, SEQ ID N0:291).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1291 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 207 (SEQ ID N0:290).
In another embodiment, the invention provides isolated PR01291 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01291 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 29 to about 282 of Figure 208 (SEQ ID N0:291).
In another aspect, the invention concerns an isolated PR01291 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291).
In a further aspect, the invention concerns an isolated PR01291 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291).
In yet another aspect, the invention concerns an isolated PRO 1291 polypeptide, comprising the sequence of amino acid residues 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID N0:291), or a fragment thereof sufficient to provide a binding site for an anti-PR01291 antibody.
Preferably, the PR01291 fragment retains a qualitative biological activity of a native PR01291 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01291 polypeptide having the sequence of amino acid residues from about 1 or about 29 to about 282, inclusive of Figure 208 (SEQ ID
N0:291), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide,'and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01291 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01291 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01291 polypeptide by contacting the native PR01291 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01291 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
90. PR_ 01105 Applicants have identified a cDNA clone that encodes a novel polypeptide having two transmembrane domains, wherein the polypeptide is designated in the present application as "PRO1105".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1105 polypeptide. In one aspect, the isolated nucleic acid comprises DNA
encoding the PRO1105 polypeptide having amino acid residues 1 through 180 of Figure 210 (SEQ ID
N0:293), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. In other aspects, the isolated nucleic acid comprises DNA encoding the PROI105 polypeptide having amino acid residues about 20 through 180 of Figure 210 (SEQ ID N0:293), or is complementary to such encoding nucleic acid sequence, and remains stably bound to it under at least moderate, and optionally, under high stringency conditions. The isolated nucleic acid sequence may comprise the cDNA
insert of the DNA59612-1466 vector deposited on June 9, 1998 with the ATCC, which includes the nucleotide sequence encoding PRO1105.
In another embodiment, the invention provides isolated PRO1105 polypeptide. In particular, the invention provides isolated native sequence PRO1105 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 180 of Figure 210 (SEQ ID N0:293).
Additional embodiments of the present invention are directed to PRO1105 polypeptides comprising amino acids about 20 through 180 of Figure 210 (SEQ ID N0:293). Other embodiments of the present invention are directed to PRO1105 polypeptides comprising amino acids about 1 through 79 and 100 through about 144 of Figure 210 (SEQ ID
N0:293). Optionally, the PRO1105 polypeptide is obtained or is obtainable by expressing the polypeptide encoded by the cDNA insert of the DNA59612-1466 vector deposited with the ATCC
on June 9, 1998.
91. PRO511 A cDNA clone (DNA59613-1417) has been identified, having some sequence identity with RoBo-1 and phospholipase inhibitors that encodes a novel polypeptide, designated in the present application as "PR01026. "
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01026 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1026 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-237, or in another embodiment, 26-237.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01026 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 233 or 308 and about 943, inclusive, of Figure 212 (SEQ ID N0:295). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule etxoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203007 (DNA59613-1417), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203007 (DNA59613-1417).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 26 to about 237, inclusive of Figure 212 (SEQ
ID N0:295), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01026 polypeptide having the sequence of amino acid residues from about I or 26 to about 237, inclusive of Figure 212 (SEQ ID
N0:295), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01026 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1026 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 26 through 237 of Figure 212 (SEQ ID
N0:295).
In another aspect, the invention concerns an isolated PRO 1026 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295).
In a further aspect, the invention concerns an isolated PR01026 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 26 through 237 of Figure 212 (SEQ ID N0:295).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01026 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 °k sequence identity, more preferably at least about a 90 k sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01026 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01026 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01026 polypeptide, by contacting the native PR01026 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01026polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01026 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1026 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-237, or in another embodiment, 26-237.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01026 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 233 or 308 and about 943, inclusive, of Figure 212 (SEQ ID N0:295). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule etxoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203007 (DNA59613-1417), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203007 (DNA59613-1417).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 26 to about 237, inclusive of Figure 212 (SEQ
ID N0:295), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01026 polypeptide having the sequence of amino acid residues from about I or 26 to about 237, inclusive of Figure 212 (SEQ ID
N0:295), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01026 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1026 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 26 through 237 of Figure 212 (SEQ ID
N0:295).
In another aspect, the invention concerns an isolated PRO 1026 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to the sequence of amino acid residues 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295).
In a further aspect, the invention concerns an isolated PR01026 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 26 through 237 of Figure 212 (SEQ ID N0:295).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01026 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 237, inclusive of Figure 212 (SEQ ID N0:295), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 °k sequence identity, more preferably at least about a 90 k sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01026 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01026 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01026 polypeptide, by contacting the native PR01026 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01026polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
92. PR01104 A cDNA clone (DNA59616-1465) has been identified, that encodes a novel polypeptide, designated in the present application as °PR01104."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01104 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO I 104 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID
N0:297), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-341, or in another embodiment, 23-341.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01104 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 109 or 175 and about 1131, inclusive, of Figure 213 (SEQ ID N0:296). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209991 (DNA59616-1465), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209991 (DNA59616-1465).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID N0:297), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01104 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ
ID N0:297), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID N0:297), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated P.R01104 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1104 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 23 through 341 of Figure 214 (SEQ ID N0:297).
In another aspect, the invention concerns an isolated PR01104 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 23 through about 341, inclusive of Figure 214 (SEQ ID N0:297).
In a further aspect, the invention concerns an isolated PRO 1104 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 23 through 341 of Figure 214 (SEQ ID N0:297).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01104 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID
N0:297), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01104 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO I 104 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID
N0:297), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-341, or in another embodiment, 23-341.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01104 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 109 or 175 and about 1131, inclusive, of Figure 213 (SEQ ID N0:296). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95%a sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209991 (DNA59616-1465), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209991 (DNA59616-1465).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID N0:297), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01104 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ
ID N0:297), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID N0:297), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated P.R01104 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1104 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or about 23 through 341 of Figure 214 (SEQ ID N0:297).
In another aspect, the invention concerns an isolated PR01104 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 23 through about 341, inclusive of Figure 214 (SEQ ID N0:297).
In a further aspect, the invention concerns an isolated PRO 1104 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 23 through 341 of Figure 214 (SEQ ID N0:297).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01104 polypeptide having the sequence of amino acid residues from about 1 or about 23 to about 341, inclusive of Figure 214 (SEQ ID
N0:297), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
93. PROlI00 A cDNA clone (DNA59619-1464) has been identified that encodes a novel polypeptide having multiple transmembrane domains, designated in the present application as "PRO 1100. "
S In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1100 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PRO1100 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-320, or in another embodiment, 21-320.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1100 1S polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 33 or 93 and about 992, inclusive, of Figure 215 (SEQ ID N0:298). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203041 (DNA59619-1464), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203041 (DNA59619-1464).
2S In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ
ID N0:299), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1100 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID
N0:299), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
3S sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
WO 99/63088 PC'T/US99/12252 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1100 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PRO1100 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1100 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 21 through 320 of Figure 216 (SEQ ID
N0:299).
In another aspect, the invention concerns an isolated PRO1100 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues I or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299).
In a further aspect, the invention concerns an isolated PRO 1100 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 21 through 320 of Figure 216 (SEQ ID N0:299).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1100 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PRO1100 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO1100 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1100 polypeptide, by contacting the native PRO1100 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO1100 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
S In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1100 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 9S % sequence identity to (a) a DNA molecule encoding a PRO1100 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-320, or in another embodiment, 21-320.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1100 1S polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 33 or 93 and about 992, inclusive, of Figure 215 (SEQ ID N0:298). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203041 (DNA59619-1464), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203041 (DNA59619-1464).
2S In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ
ID N0:299), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PRO1100 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID
N0:299), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
3S sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
WO 99/63088 PC'T/US99/12252 In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1100 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domains deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PRO1100 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1100 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 21 through 320 of Figure 216 (SEQ ID
N0:299).
In another aspect, the invention concerns an isolated PRO1100 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues I or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299).
In a further aspect, the invention concerns an isolated PRO 1100 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 21 through 320 of Figure 216 (SEQ ID N0:299).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO1100 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 320, inclusive of Figure 216 (SEQ ID N0:299), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PRO1100 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PRO1100 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PRO1100 polypeptide, by contacting the native PRO1100 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO1100 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
94. PR0836 A cDNA clone (DNA59620-1463) has been identified, having some sequence identity with SLS1 that encodes a novel polypeptide, designated in the present application as "PR0836."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0836 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0836 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 461, inclusive of Figure 2I8 (SEQ ID N0:301), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-461, or in another embodiment, 30-461.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0836 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 65 or 152 and about 1447, inclusive; of Figure 217 (SEQ ID N0:300). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209989 (DNA59620-1463), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209989 (DNA59620-1463).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 30 to about 461, inclusive of Figure 218 (SEQ
ID N0:301), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0836 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 461, inclusive of Figure 218 (SEQ ID
N0:301), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the WO 99/63088 PC'T/US99/12252 amino acid sequence of residues 1 or 30 to about 461, inclusive of Figure 218 (SEQ ID N0:301), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0836 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0836 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 30 through 461 of Figure 218 (SEQ ID
N0:301).
In another aspect, the invention concerns an isolated PR0836 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 30 to about 461, inclusive of Figure 218 (SEQ ID N0:301).
In a further aspect, the invention concerns an isolated PR0836 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 30 through 461 of Figure 218 (SEQ ID N0:301 ).
1n a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0836 polypeptide having the sequence of amino acid residues from about I or 30 to about 461, inclusive of Figure 218 (SEQ ID N0:301), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0836 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0836 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0836 polypeptide, by contacting the native PR0836 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0836 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0836 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding a PR0836 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 461, inclusive of Figure 2I8 (SEQ ID N0:301), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-461, or in another embodiment, 30-461.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0836 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 65 or 152 and about 1447, inclusive; of Figure 217 (SEQ ID N0:300). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209989 (DNA59620-1463), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209989 (DNA59620-1463).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 30 to about 461, inclusive of Figure 218 (SEQ
ID N0:301), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0836 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 461, inclusive of Figure 218 (SEQ ID
N0:301), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the WO 99/63088 PC'T/US99/12252 amino acid sequence of residues 1 or 30 to about 461, inclusive of Figure 218 (SEQ ID N0:301), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0836 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0836 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 30 through 461 of Figure 218 (SEQ ID
N0:301).
In another aspect, the invention concerns an isolated PR0836 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 30 to about 461, inclusive of Figure 218 (SEQ ID N0:301).
In a further aspect, the invention concerns an isolated PR0836 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 30 through 461 of Figure 218 (SEQ ID N0:301 ).
1n a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0836 polypeptide having the sequence of amino acid residues from about I or 30 to about 461, inclusive of Figure 218 (SEQ ID N0:301), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0836 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0836 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0836 polypeptide, by contacting the native PR0836 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0836 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
95. PR01141 A cDNA clone (DNA59625-1498) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01141".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01141 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to (a) a DNA molecule encoding a PR01141 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01141 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 204 S or about 261 and about 944, inclusive, of Figure 219 (SEQ ID N0:302).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80q6 sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209992 {DNA59625-1498) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209992 (DNA59625-1498).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01141 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID N0:303), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01141 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position 19 in the sequence of Figure 220 (SEQ
ID N0:303). The transmembrane domains have been tentatively identified as extending from about amino acid position 38 to about amino acid position 57, from about amino acid position 67 to about amino acid position 83, from about amino acid position 117 to about amino acid position 139 and from about amino acid position 153 to about amino acid position 170, in the PR01141 amino acid sequence (Figure 220, SEQ ID N0:303).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 20 to about 247, inclusive of Figure 22.0 (SEQ ID N0:303), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01141 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 219 (SEQ ID N0:302).
In another embodiment, the invention provides isolated PR01141 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01141 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 247 of Figure 220 (SEQ ID N0:303).
In another aspect, the invention concerns an isolated PR01141 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID N0:303).
In a further aspect, the invention concerns an isolated PRO t 141 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303).
In yet another aspect, the invention concerns an isolated PRO 1141 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID N0:303), or a fragment thereof sufficient to provide a binding site for an anti-PR01141 antibody.
Preferably, the PRO1141 fragment retains a qualitative biological activity of a native PROI141 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01141 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA33128 comprising the nucleotide sequence of SEQ ID N0:304 (see Figure 221).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA34256 comprising the nucleotide sequence of SEQ ID N0:305 (see Figure 222).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA47941 comprising the nucleotide sequence of SEQ ID N0:306 (see Figure 223).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA54389 comprising the nucleotide sequence of SEQ ID N0:307 (see Figure 224):
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01141 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to (a) a DNA molecule encoding a PR01141 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01141 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 204 S or about 261 and about 944, inclusive, of Figure 219 (SEQ ID N0:302).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80q6 sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209992 {DNA59625-1498) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209992 (DNA59625-1498).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 ~ sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01141 polypeptide having the sequence of amino acid residues from 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID N0:303), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01141 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I to about amino acid position 19 in the sequence of Figure 220 (SEQ
ID N0:303). The transmembrane domains have been tentatively identified as extending from about amino acid position 38 to about amino acid position 57, from about amino acid position 67 to about amino acid position 83, from about amino acid position 117 to about amino acid position 139 and from about amino acid position 153 to about amino acid position 170, in the PR01141 amino acid sequence (Figure 220, SEQ ID N0:303).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80~ positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 20 to about 247, inclusive of Figure 22.0 (SEQ ID N0:303), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01141 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 219 (SEQ ID N0:302).
In another embodiment, the invention provides isolated PR01141 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01141 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 20 to about 247 of Figure 220 (SEQ ID N0:303).
In another aspect, the invention concerns an isolated PR01141 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID N0:303).
In a further aspect, the invention concerns an isolated PRO t 141 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303).
In yet another aspect, the invention concerns an isolated PRO 1141 polypeptide, comprising the sequence of amino acid residues 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID N0:303), or a fragment thereof sufficient to provide a binding site for an anti-PR01141 antibody.
Preferably, the PRO1141 fragment retains a qualitative biological activity of a native PROI141 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01141 polypeptide having the sequence of amino acid residues from about 1 or about 20 to about 247, inclusive of Figure 220 (SEQ ID
N0:303), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA33128 comprising the nucleotide sequence of SEQ ID N0:304 (see Figure 221).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA34256 comprising the nucleotide sequence of SEQ ID N0:305 (see Figure 222).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA47941 comprising the nucleotide sequence of SEQ ID N0:306 (see Figure 223).
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA54389 comprising the nucleotide sequence of SEQ ID N0:307 (see Figure 224):
96. PR01132 A cDNA clone (DNA59767-1489) has been identified that encodes a novel polypeptide having sequence identity with serine proteases and trypsinogen and designated in the present application as "PR01132."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01132 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01132 polypeptide having the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ ID N0:309), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01132 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 420 and about 1232, inclusive, of Figure 225 (SEQ ID N0:308). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203108 (DNA59767-1489), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203108 (DNA59767-1489).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ ID
N0:309), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01132 polypeptide having the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ
ID N0:309), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 953'o positives when compared with the amino acid sequence of residues 23 to about 293, inclusive of Figure 226 (SEQ
ID N0:309), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01132 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01132 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO1132 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 through 293 of Figure 226 (SEQ ID
N0:309).
In another aspect, the invention concerns an isolated PRO1132 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 23 to about 293, inclusive of Figure 226 (SEQ
ID N0:309).
In a further aspect, the invention concerns an isolated PRO 1132 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 23 through 293 of Figure 226 (SEQ ID N0:309).
In yet another aspect, the invention concerns an isolated PRO 1132 polypeptide, comprising the sequence of amino acid residues 23 to about 293, inclusive of Figure 226 (SEQ ID
N0:309), or a fragment thereof sufficient to provide a binding site for an anti-PR01132 antibody. Preferably, the PR01132 fragment retains a qualitative biological activity of a native PR01132 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01132 polypeptide having the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ ID N0:309), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%a sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01132 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01132 antibody.
1n a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01132 polypeptide, by contacting the native PR01132 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01132 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01132 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01132 polypeptide having the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ ID N0:309), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01132 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 420 and about 1232, inclusive, of Figure 225 (SEQ ID N0:308). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203108 (DNA59767-1489), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203108 (DNA59767-1489).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ ID
N0:309), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01132 polypeptide having the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ
ID N0:309), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 953'o positives when compared with the amino acid sequence of residues 23 to about 293, inclusive of Figure 226 (SEQ
ID N0:309), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01132 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01132 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO1132 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 through 293 of Figure 226 (SEQ ID
N0:309).
In another aspect, the invention concerns an isolated PRO1132 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 23 to about 293, inclusive of Figure 226 (SEQ
ID N0:309).
In a further aspect, the invention concerns an isolated PRO 1132 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 23 through 293 of Figure 226 (SEQ ID N0:309).
In yet another aspect, the invention concerns an isolated PRO 1132 polypeptide, comprising the sequence of amino acid residues 23 to about 293, inclusive of Figure 226 (SEQ ID
N0:309), or a fragment thereof sufficient to provide a binding site for an anti-PR01132 antibody. Preferably, the PR01132 fragment retains a qualitative biological activity of a native PR01132 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01132 polypeptide having the sequence of amino acid residues from about 23 to about 293, inclusive of Figure 226 (SEQ ID N0:309), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%a sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01132 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01132 antibody.
1n a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01132 polypeptide, by contacting the native PR01132 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01132 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
97. PR01346 A cDNA clone (DNA59776-1600) has been identified, that encodes a novel polypeptide, designated in the present application as PR01346 (or NL7), having homology to known TIE
ligands.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding an NL7 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding an NL7 polypeptide having the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding an NL7 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides I-3 (ATG) and about 1381-1383 (CGC, preceding the TAG stop codon), inclusive, of Figure 227 (SEQ ID N0:313).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203128 (DNA59776-1600), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203128 (DNA59776-1600).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8(?% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID
N0:314), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 1000 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding an NL7 polypeptide having the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding an NL7 polypeptide, with or without the initiating methionine, or its soluble forms, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 31 to about amino acid position 50 in the NL7 amino acid sequence (Figure 228, SEQ ID N0:314).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 51 to about 461, inclusive of Figure 228 (SEQ
ID N0:314), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule, at least about 200 bases in length, which encodes a fragment of a native NL7 polypeptide.
In another embodiment, the invention provides an isolated NL7 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides an isolated native sequence NL7 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues from about 51 to about 461 of Figure 228 (SEQ ID N0:314).
In another aspect, the invention concerns an isolated NL7 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314).
In a further aspect, the invention concerns an isolated NL7 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 51 to 461 of Figure 228 (SEQ ID N0:314).
In yet another aspect, the invention concerns an isolated NL7 polypeptide, comprising the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or a fragment thereof sufficient to provide a binding site for an anti-NL7 antibody.
Preferably, the NL7 fragment retains a qualitative biological activity of a native NL7 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
mol~ule under stringent conditions with (a) a DNA molecule encoding an NL7 polypeptide having the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native NL7 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-NL7 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native NL? polypeptide, by contacting the native NL7 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising an NL7 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
ligands.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding an NL7 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding an NL7 polypeptide having the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding an NL7 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides I-3 (ATG) and about 1381-1383 (CGC, preceding the TAG stop codon), inclusive, of Figure 227 (SEQ ID N0:313).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203128 (DNA59776-1600), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203128 (DNA59776-1600).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8(?% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID
N0:314), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 1000 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding an NL7 polypeptide having the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or (b) the complement of the DNA
molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding an NL7 polypeptide, with or without the initiating methionine, or its soluble forms, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain has been tentatively identified as extending from about amino acid position 31 to about amino acid position 50 in the NL7 amino acid sequence (Figure 228, SEQ ID N0:314).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 51 to about 461, inclusive of Figure 228 (SEQ
ID N0:314), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule, at least about 200 bases in length, which encodes a fragment of a native NL7 polypeptide.
In another embodiment, the invention provides an isolated NL7 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides an isolated native sequence NL7 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues from about 51 to about 461 of Figure 228 (SEQ ID N0:314).
In another aspect, the invention concerns an isolated NL7 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314).
In a further aspect, the invention concerns an isolated NL7 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 51 to 461 of Figure 228 (SEQ ID N0:314).
In yet another aspect, the invention concerns an isolated NL7 polypeptide, comprising the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or a fragment thereof sufficient to provide a binding site for an anti-NL7 antibody.
Preferably, the NL7 fragment retains a qualitative biological activity of a native NL7 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
mol~ule under stringent conditions with (a) a DNA molecule encoding an NL7 polypeptide having the sequence of amino acid residues from about 51 to about 461, inclusive of Figure 228 (SEQ ID N0:314), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native NL7 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-NL7 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native NL? polypeptide, by contacting the native NL7 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising an NL7 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
98. PR01131 A cDNA clone (DNA59777-1480) has been identified that encodes a novel polypeptide having sequence identity with LDL receptors and designated in the present application as "PR01131."
In one embodiment, the invention provides an isoiated nucleic acid molecule comprising DNA encoding a PR01131 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85°k sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01131 polypeptide having the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID N0:319), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01131 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 144 and about 983, inclusive, of Figure 229 (SEQ ID N0:318). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203111 (DNA59777-1480), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203111 (DNA59777-1480).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 9~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID
N0:319), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01131 polypeptide having the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID
N0:319), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01131 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain (type II) has been tentatively identified as eztending from about amino acid positions 49-74 in the amino acid sequence of Figure 230, SEQ ID N0:319.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85%a positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 280, inclusive of Figure 230 (SEQ
ID N0:319), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01131 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1131 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1131 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 280 of Figure 230 (SEQ ID
N0:319).
In another aspect, the invention concerns an isolated PROI 131 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 280, inclusive of Figure 230 (SEQ
ID N0:319).
In a further aspect, the invention concerns an isolated PR01131 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 280 of Figure 230 (SEQ ID N0:319).
In yet another aspect, the invention concerns an isolated PRO 1131 polypeptide, comprising the sequence of amino acid residues 1 to about 280, inclusive of Figure 230 (SEQ ID
N0:319), or a fragment thereof sufficient to provide a binding site for an anti-PR01131 antibody. Preferably, the PR01131 fragment retains a qualitative biological activity of a native PR01131 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01131 polypeptide having the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID N0:319), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%a sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01131 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01131 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01131 polypeptide, by contacting the native PR01131 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01131 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as IO DNA43546 comprising the nucleotide sequence of Figure 231 (SEQ ID N0:320).
In one embodiment, the invention provides an isoiated nucleic acid molecule comprising DNA encoding a PR01131 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85°k sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01131 polypeptide having the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID N0:319), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01131 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 144 and about 983, inclusive, of Figure 229 (SEQ ID N0:318). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203111 (DNA59777-1480), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203111 (DNA59777-1480).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 9~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID
N0:319), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01131 polypeptide having the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID
N0:319), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01131 polypeptide in its soluble form, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domain (type II) has been tentatively identified as eztending from about amino acid positions 49-74 in the amino acid sequence of Figure 230, SEQ ID N0:319.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85%a positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 to about 280, inclusive of Figure 230 (SEQ
ID N0:319), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01131 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1131 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1131 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 through 280 of Figure 230 (SEQ ID
N0:319).
In another aspect, the invention concerns an isolated PROI 131 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 280, inclusive of Figure 230 (SEQ
ID N0:319).
In a further aspect, the invention concerns an isolated PR01131 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 280 of Figure 230 (SEQ ID N0:319).
In yet another aspect, the invention concerns an isolated PRO 1131 polypeptide, comprising the sequence of amino acid residues 1 to about 280, inclusive of Figure 230 (SEQ ID
N0:319), or a fragment thereof sufficient to provide a binding site for an anti-PR01131 antibody. Preferably, the PR01131 fragment retains a qualitative biological activity of a native PR01131 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01131 polypeptide having the sequence of amino acid residues from about 1 to about 280, inclusive of Figure 230 (SEQ ID N0:319), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%a sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01131 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01131 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01131 polypeptide, by contacting the native PR01131 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01131 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as IO DNA43546 comprising the nucleotide sequence of Figure 231 (SEQ ID N0:320).
99. PR01281 A cDNA clone (DNA59820-1549) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01281".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01281 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01281 polypeptide having the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ ID N0:326), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01281 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 273 and about 2552, inclusive, of Figure 232 (SEQ ID N0:325). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203129 (DNA59820-1549), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203129 (DNA59820-1549).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ ID
N0:326), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01281 polypeptide having the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ
ID N0:326), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01281 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 15 in the sequence of Figure 233 (SEQ
ID N0:326).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 16 to about 775, inclusive of Figure 233 (SEQ
ID N0:326), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1281 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1281 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1281 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 to 775 of Figure 233 (SEQ ID N0:326).
In another aspect, the invention concerns an isolated PR01281 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 775, inclusive of Figure 233 (SEQ
ID N0:326).
In a further aspect, the invention concerns an isolated PRO 1281 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 16 to 775 of Figure 233 (SEQ ID N0:326).
In yet another aspect, the invention concerns an isolated PRO 1281 polypeptide, comprising the sequence of amino acid residues 16 to about 775, inclusive of Figure 233 (SEQ ID
N0:326), or a fragment thereof sufficient to provide a binding site for an anti-PR01281 antibody. Preferably, the PR01281 fragment retains a qualitative biological activity of a native PR01281 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01281 polypeptide having the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ ID N0:326), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferabiy at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01281 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01281 polypeptide having the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ ID N0:326), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01281 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 273 and about 2552, inclusive, of Figure 232 (SEQ ID N0:325). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203129 (DNA59820-1549), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203129 (DNA59820-1549).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ ID
N0:326), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01281 polypeptide having the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ
ID N0:326), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01281 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 15 in the sequence of Figure 233 (SEQ
ID N0:326).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 16 to about 775, inclusive of Figure 233 (SEQ
ID N0:326), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1281 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PRO 1281 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1281 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 16 to 775 of Figure 233 (SEQ ID N0:326).
In another aspect, the invention concerns an isolated PR01281 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 16 to about 775, inclusive of Figure 233 (SEQ
ID N0:326).
In a further aspect, the invention concerns an isolated PRO 1281 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 16 to 775 of Figure 233 (SEQ ID N0:326).
In yet another aspect, the invention concerns an isolated PRO 1281 polypeptide, comprising the sequence of amino acid residues 16 to about 775, inclusive of Figure 233 (SEQ ID
N0:326), or a fragment thereof sufficient to provide a binding site for an anti-PR01281 antibody. Preferably, the PR01281 fragment retains a qualitative biological activity of a native PR01281 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01281 polypeptide having the sequence of amino acid residues from about 16 to about 775, inclusive of Figure 233 (SEQ ID N0:326), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferabiy at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
100. PR01064 A cDNA clone (DNA59827-1426) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PR01064".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01064 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01064 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01064 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 532 or about 604 and about 990, inclusive, of Figure 234 (SEQ ID N0:333).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203089 (DNA59827-1426) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203089 (DNA59827-1426).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01064 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID N0:334), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01064 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 235 (SEQ
ID N0:334). The transmembrane domain has been tentatively identified as extending from about amino acid position 89 to about amino acid position 110 in the PR01064 amino acid sequence (Figure 235, SEQ ID N0:334).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID N0:334), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01064 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 234 (SEQ ID N0:333).
In another embodiment, the invention provides isolated PR01064 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01064 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 153 of Figure 235 (SEQ ID N0:334).
In another aspect, the invention concerns an isolated PR01064 polypeptide, comprising an amino acid sequence having at least about 80 fo sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 25 to about 153, inclusive of Figure 235 {SEQ ID N0:334).
In a further aspect, the invention concerns an isolated PRO 1064 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334).
In yet another aspect, the invention concerns an isolated PRO 1064 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID N0:334), or a fragment thereof sufficient to provide a binding site for an anti-PR01064 antibody.
Preferably, the PR01064 fragment retains a qualitative biological activity of a native PR01064 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01064 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence idenEity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA45288 comprising the nucleotide sequence of SEQ ID N0:335 (see Figure 236).
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01064 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01064 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01064 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 532 or about 604 and about 990, inclusive, of Figure 234 (SEQ ID N0:333).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203089 (DNA59827-1426) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203089 (DNA59827-1426).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01064 polypeptide having the sequence of amino acid residues from 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID N0:334), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01064 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e., transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 24 in the sequence of Figure 235 (SEQ
ID N0:334). The transmembrane domain has been tentatively identified as extending from about amino acid position 89 to about amino acid position 110 in the PR01064 amino acid sequence (Figure 235, SEQ ID N0:334).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID N0:334), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01064 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 234 (SEQ ID N0:333).
In another embodiment, the invention provides isolated PR01064 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01064 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 25 to about 153 of Figure 235 (SEQ ID N0:334).
In another aspect, the invention concerns an isolated PR01064 polypeptide, comprising an amino acid sequence having at least about 80 fo sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or about 25 to about 153, inclusive of Figure 235 {SEQ ID N0:334).
In a further aspect, the invention concerns an isolated PRO 1064 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334).
In yet another aspect, the invention concerns an isolated PRO 1064 polypeptide, comprising the sequence of amino acid residues 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID N0:334), or a fragment thereof sufficient to provide a binding site for an anti-PR01064 antibody.
Preferably, the PR01064 fragment retains a qualitative biological activity of a native PR01064 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01064 polypeptide having the sequence of amino acid residues from about 1 or about 25 to about 153, inclusive of Figure 235 (SEQ ID
N0:334), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence idenEity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In another embodiment, the invention provides an expressed sequence tag (EST) designated herein as DNA45288 comprising the nucleotide sequence of SEQ ID N0:335 (see Figure 236).
101. PR01379 A cDNA clone (DNA59828-1608) has been identified that encodes a novel secreted polypeptide designated in the present application as "PR01379."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01379 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01379 polypeptide having the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ ID N0:340), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01379 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 61 and about 1731, inclusive, of Figure 237 (SEQ ID N0:339). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203158 (DNA59828-1608), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203158 (DNA59828-1608).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ ID
N0:340), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01379 polypeptide having the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ
ID N0:340), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 859b sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01379 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 238 (SEQ
ID N0:340).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 9090 positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 18 to about 574, inclusive of Figure 238 (SEQ
ID N0:340), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1379 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01379 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1379 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 to 574 of Figure 238 (SEQ ID N0:340).
In another aspect, the invention concerns an isolated PR01379 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 9096 sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 18 to about 574, inciusive of Figure 238 (SEQ
ID N0:340).
In a further aspect, the invention concerns an isolated PR01379 polypeptide, comprising an amino acid sequence scoring at least about 80°o positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 to 574 of Figure 238 (SEQ ID N0:340).
In yet another aspect, the invention concerns an isolated PRO 1379 polypeptide, comprising the sequence of amino acid residues 18 to about 574, inclusive of Figure 238 (SEQ ID
N0:340), or a fragment thereof sufficient to provide a binding site for an anti-PR01379 antibody. Preferably, the PR01379 fragment retains a qualitative biological activity of a native PR01379 polypeptide.
In a still farther aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01379 polypeptide having the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ ID N0:340), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence S identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01379 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01379 polypeptide having the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ ID N0:340), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01379 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 61 and about 1731, inclusive, of Figure 237 (SEQ ID N0:339). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203158 (DNA59828-1608), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203158 (DNA59828-1608).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ ID
N0:340), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01379 polypeptide having the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ
ID N0:340), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 859b sequence identity, more preferably at least about a 90~ sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01379 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 17 in the sequence of Figure 238 (SEQ
ID N0:340).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 9090 positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 18 to about 574, inclusive of Figure 238 (SEQ
ID N0:340), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1379 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01379 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1379 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 18 to 574 of Figure 238 (SEQ ID N0:340).
In another aspect, the invention concerns an isolated PR01379 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 9096 sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 18 to about 574, inciusive of Figure 238 (SEQ
ID N0:340).
In a further aspect, the invention concerns an isolated PR01379 polypeptide, comprising an amino acid sequence scoring at least about 80°o positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 18 to 574 of Figure 238 (SEQ ID N0:340).
In yet another aspect, the invention concerns an isolated PRO 1379 polypeptide, comprising the sequence of amino acid residues 18 to about 574, inclusive of Figure 238 (SEQ ID
N0:340), or a fragment thereof sufficient to provide a binding site for an anti-PR01379 antibody. Preferably, the PR01379 fragment retains a qualitative biological activity of a native PR01379 polypeptide.
In a still farther aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01379 polypeptide having the sequence of amino acid residues from about 18 to about 574, inclusive of Figure 238 (SEQ ID N0:340), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence S identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
102. PR0844 A cDNA clone (DNA59838-1462) has been identified, having sequence identity with protease inhibitors, that encodes a novel polypeptide, designated in the present application as "PR0844."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0844 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0844 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID N0:345), or (b) the complement of the DNA molecule of (a). The term °or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-111, or in another embodiment, 20-111.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0844 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 5 or 62 and about 337, inclusive, of Figure 239 (SEQ ID N0:344). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209976 (DNA59838-1462), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209976 (DNA59838-1462).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 20 to about 111, inclusive of Figure 240 (SEQ
1D N0:345), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0844 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID
N0:345), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID N0:345), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0844 poIypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0844 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 20 through 111 of Figure 240 (SEQ ID
N0:345).
In another aspect, the invention concetvs an isolated PR0844 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID N0:345).
In a further aspect, the invention concerns an isolated PR0844 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 20 through 1 I1 of Figure 240 (SEQ ID N0:345).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0844 polypeptide having the sequence of amino acid residues from about I or 20 to about l I l, inclusive of Figure 240 (SEQ ID N0:345), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0844 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0844 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0844 polypeptide, by contacting the native PR0844 polypeptide with a candidate molecule and monitoriing a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0844 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR0844 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0844 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID N0:345), or (b) the complement of the DNA molecule of (a). The term °or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-111, or in another embodiment, 20-111.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0844 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 5 or 62 and about 337, inclusive, of Figure 239 (SEQ ID N0:344). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209976 (DNA59838-1462), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209976 (DNA59838-1462).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90%a sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 20 to about 111, inclusive of Figure 240 (SEQ
1D N0:345), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0844 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID
N0:345), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID N0:345), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0844 poIypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0844 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 20 through 111 of Figure 240 (SEQ ID
N0:345).
In another aspect, the invention concetvs an isolated PR0844 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 20 to about 111, inclusive of Figure 240 (SEQ ID N0:345).
In a further aspect, the invention concerns an isolated PR0844 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 20 through 1 I1 of Figure 240 (SEQ ID N0:345).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0844 polypeptide having the sequence of amino acid residues from about I or 20 to about l I l, inclusive of Figure 240 (SEQ ID N0:345), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0844 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0844 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0844 polypeptide, by contacting the native PR0844 polypeptide with a candidate molecule and monitoriing a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0844 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
103. ~R0848 A cDNA clone (DNA59839-1461) has been identified, having sequence identity with sialytransferases that encodes a novel polypeptide, designated in the present application as "PR0848."
In one embodiment, the invention provides an isolated nucleic acid molecule coraprising DNA encoding a PR0848 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0848 polypeptide having the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-600, or in another embodiment, 36-600.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0848 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 1 or 251 and about 1945, inclusive, of Figure 241 (SEQ ID N0:346). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209988 (DNA59839-1461), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209988 (DNA59839-1461).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ
ID N0:347), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0848 polypeptide having the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID
N0:347), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0848 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0848 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 36 through 600 of Figure 242 (SEQ ID
N0:347).
In another aspect, the invention concerns an isolated PR0848 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347).
In a further aspect, the invention concerns an isolated PR0848 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 36 through 600 of Figure 242 (SEQ ID N0:347).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0848 polypeptide having the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0848 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0848 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0848 polypeptide, by contacting the native PR0848 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0848 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule coraprising DNA encoding a PR0848 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR0848 polypeptide having the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-600, or in another embodiment, 36-600.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR0848 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 1 or 251 and about 1945, inclusive, of Figure 241 (SEQ ID N0:346). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209988 (DNA59839-1461), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209988 (DNA59839-1461).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ
ID N0:347), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR0848 polypeptide having the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID
N0:347), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR0848 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR0848 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 36 through 600 of Figure 242 (SEQ ID
N0:347).
In another aspect, the invention concerns an isolated PR0848 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347).
In a further aspect, the invention concerns an isolated PR0848 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 36 through 600 of Figure 242 (SEQ ID N0:347).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR0848 polypeptide having the sequence of amino acid residues from about 1 or 36 to about 600, inclusive of Figure 242 (SEQ ID N0:347), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR0848 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR0848 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR0848 polypeptide, by contacting the native PR0848 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR0848 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
104. PR01097 Applicants have identified a cDNA clone (DNA59841-1460) that encodes a novel secreted polypeptide having domains therein from the glycoprotease family proteins and the acyltransferase ChoActase/COT/CPT
family, wherein the polypeptide is designated in the present application as "PR01097".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01097 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1097 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-91, or in another embodiment, 21-91.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01097 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 3 or 63 and about 275, inclusive, of Figure 243 (SEQ ID N0:348). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203044 (DNA59841-1460), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203044 (DNA59841-1460).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ
ID N0:349), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01097 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID
N0:349), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01097 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 244 (SEQ ID N0:349).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01097 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
, In a specific aspect, the invention provides isolated native sequence PRO
1097 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 21 through 91 of Figure 244 (SEQ ID
N0:349).
In another aspect, the invention concerns an isolated PR01097 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349).
In a further aspect, the invention concerns an isolated PR01097 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 21 through 91 of Figure 244 (SEQ ID N0:349).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01097 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01097 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01097 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01097 poiypeptide, by contacting the native PR01097 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1097 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
family, wherein the polypeptide is designated in the present application as "PR01097".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01097 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1097 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-91, or in another embodiment, 21-91.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01097 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 3 or 63 and about 275, inclusive, of Figure 243 (SEQ ID N0:348). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203044 (DNA59841-1460), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203044 (DNA59841-1460).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ
ID N0:349), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01097 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID
N0:349), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01097 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 20 in the sequence of Figure 244 (SEQ ID N0:349).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01097 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
, In a specific aspect, the invention provides isolated native sequence PRO
1097 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 21 through 91 of Figure 244 (SEQ ID
N0:349).
In another aspect, the invention concerns an isolated PR01097 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349).
In a further aspect, the invention concerns an isolated PR01097 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 21 through 91 of Figure 244 (SEQ ID N0:349).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01097 polypeptide having the sequence of amino acid residues from about 1 or 21 to about 91, inclusive of Figure 244 (SEQ ID N0:349), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01097 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01097 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01097 poiypeptide, by contacting the native PR01097 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1097 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
105. PR01153 A cDNA clone (DNA59842-1502) has been identified, having two transmembrane domains and being very proline rich, that encodes a novel polypeptide, designated in the present application as "PR01153."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01153 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1153 polypeptide having the sequence of amino acid residues from about 1 to about 197, inclusive of Figure 246 (SEQ ID N0:351), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01153 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 92 and about 682, inclusive, of Figure 245 (SEQ ID N0:350). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209982 (DNA59842-1502), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209982 (DNA59842-1502).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 197, inclusive of Figure 246 (SEQ ID
N0:351), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01153 polypeptide having the sequence of amino acid residues from about I to about 197, inclusive of Figure 246 (SEQ ID
N0:351), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01153 polypeptide, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid positions 10-28 and 85-110 in the PR01153 amino acid sequence (Figure 246, SEQ ID N0:351).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 197, inclusive of Figure 246 (SEQ
ID N0:351), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01153 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01153 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 197 of Figure 246 (SEQ ID N0:351).
In another aspect, the invention concerns an isolated PR01153 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 197, inclusive of Figure 246 (SEQ
ID N0:351).
In a further aspect, the invention concerns an isolated PR01153 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 197 of Figure 246 (SEQ ID N0:351).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01153 polypeptide having the sequence of amino acid residues from about 1 to about 197, inclusive of Figure 246 (SEQ ID N0:351), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01153 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1153 polypeptide having the sequence of amino acid residues from about 1 to about 197, inclusive of Figure 246 (SEQ ID N0:351), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01153 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 92 and about 682, inclusive, of Figure 245 (SEQ ID N0:350). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209982 (DNA59842-1502), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209982 (DNA59842-1502).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 to about 197, inclusive of Figure 246 (SEQ ID
N0:351), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01153 polypeptide having the sequence of amino acid residues from about I to about 197, inclusive of Figure 246 (SEQ ID
N0:351), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01153 polypeptide, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The transmembrane domains have been tentatively identified as extending from about amino acid positions 10-28 and 85-110 in the PR01153 amino acid sequence (Figure 246, SEQ ID N0:351).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 to about 197, inclusive of Figure 246 (SEQ
ID N0:351), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01153 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01153 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 to 197 of Figure 246 (SEQ ID N0:351).
In another aspect, the invention concerns an isolated PR01153 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 to about 197, inclusive of Figure 246 (SEQ
ID N0:351).
In a further aspect, the invention concerns an isolated PR01153 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 through 197 of Figure 246 (SEQ ID N0:351).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01153 polypeptide having the sequence of amino acid residues from about 1 to about 197, inclusive of Figure 246 (SEQ ID N0:351), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b}, (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
106. PR01154 A cDNA clone (DNA59846-1503) has been identified that encodes a novel aminopeptidase, designated in the present application as "PR01154."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01154 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01154 polypeptide having the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01154 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 86 or 188 and about 2908, inclusive, of Figure 247 (SEQ ID N0:35 2). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209978 (DNA59846-1503), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209978 (DNA59846-1503).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 248 (SEQ
ID N0:353), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01154 polypeptide having the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 258 (SEQ ID
N0:353), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353), or (b) the complement of the DNA of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule consisting essentially of DNA
encoding a polypeptide having amino acids 1 or 35 through about 73 of SEQ ID
N0:353.
In another embodiment, the invention provides isolated PR01154 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1154 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 35 to 941 of Figure 248 (SEQ ID
N0:353).
In a specific aspect, the invention provides a polypeptide having amino acids 1 or 35 through about 73 of SEQ ID N0:353.
In another aspect, the invention concerns an isolated PR01154 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353).
In a further aspect, the invention concerns an isolated PR01154 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 35 through 941 of Figure 248 (SEQ ID N0:353).
WO 99/63088 PC'T/US99/12252 In yet another aspect, the invention concerns an isolated PRO 1154 polypeptide, comprising the sequence of amino acid residues 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID
N0:353), or a fragment thereof sufficient to provide a binding site for an anti-PR01154 antibody. Preferably, the PR01154 fragment retains a qualitative biological activity of a native PR01154 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
S molecule under stringent conditions with (a) a DNA molecule encoding a PR01154 polypeptide having the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 ~
sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01154 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01154 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01154 polypeptide, by contacting the native PR01154 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1154 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01154 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01154 polypeptide having the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01154 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 86 or 188 and about 2908, inclusive, of Figure 247 (SEQ ID N0:35 2). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209978 (DNA59846-1503), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209978 (DNA59846-1503).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 248 (SEQ
ID N0:353), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01154 polypeptide having the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 258 (SEQ ID
N0:353), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353), or (b) the complement of the DNA of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule consisting essentially of DNA
encoding a polypeptide having amino acids 1 or 35 through about 73 of SEQ ID
N0:353.
In another embodiment, the invention provides isolated PR01154 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1154 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 35 to 941 of Figure 248 (SEQ ID
N0:353).
In a specific aspect, the invention provides a polypeptide having amino acids 1 or 35 through about 73 of SEQ ID N0:353.
In another aspect, the invention concerns an isolated PR01154 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353).
In a further aspect, the invention concerns an isolated PR01154 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 35 through 941 of Figure 248 (SEQ ID N0:353).
WO 99/63088 PC'T/US99/12252 In yet another aspect, the invention concerns an isolated PRO 1154 polypeptide, comprising the sequence of amino acid residues 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID
N0:353), or a fragment thereof sufficient to provide a binding site for an anti-PR01154 antibody. Preferably, the PR01154 fragment retains a qualitative biological activity of a native PR01154 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
S molecule under stringent conditions with (a) a DNA molecule encoding a PR01154 polypeptide having the sequence of amino acid residues from about 1 or 35 to about 941, inclusive of Figure 248 (SEQ ID N0:353), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 ~
sequence identity, most preferably at least about a 95~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01154 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01154 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01154 polypeptide, by contacting the native PR01154 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1154 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
107. PR01181 A cDNA clone (DNA59847-1511) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01181".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01181 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 °r~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01181 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01181 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 17 or about 62 and about 1327, inclusive, of Figure 249 (SEQ ID N0:354).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 k sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203098 (DNA59847-1511) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203098 (DNA59847-1511).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01181 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID N0:355), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01181 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 250 (SEQ
ID N0:355). The transmembrane domain is at amino acids positions 243-260 of Figure 250.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about I6 to about 437, inclusive of Figure 250 (SEQ ID N0:355), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1181 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 249 (SEQ ID N0:354).
In another embodiment, the invention provides isolated PROI 181 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PROI 181 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 437 of Figure 250 (SEQ ID N0:355).
In another aspect, the invention concerns an isolated PR01181 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID N0:355).
In a further aspect, the invention concerns an isolated PRO 1181 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85°6 positives, more preferably at least about 9096 positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355).
In yet another aspect, the invention concerns an isolated PRO 1181 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID N0:355), or a fragment thereof sufficient to provide a binding site for an anti-PR01181 antibody.
Preferably, the PR01181 fragment retains a qualitative biological activity of a native PR01181 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01181 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 ~ sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 h sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01181 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 °r~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01181 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01181 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 17 or about 62 and about 1327, inclusive, of Figure 249 (SEQ ID N0:354).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 k sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203098 (DNA59847-1511) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203098 (DNA59847-1511).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01181 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID N0:355), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01181 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 250 (SEQ
ID N0:355). The transmembrane domain is at amino acids positions 243-260 of Figure 250.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about I6 to about 437, inclusive of Figure 250 (SEQ ID N0:355), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1181 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 249 (SEQ ID N0:354).
In another embodiment, the invention provides isolated PROI 181 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PROI 181 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 437 of Figure 250 (SEQ ID N0:355).
In another aspect, the invention concerns an isolated PR01181 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID N0:355).
In a further aspect, the invention concerns an isolated PRO 1181 polypeptide, comprising an amino acid sequence scoring at least about 80~ positives, preferably at least about 85°6 positives, more preferably at least about 9096 positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355).
In yet another aspect, the invention concerns an isolated PRO 1181 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID N0:355), or a fragment thereof sufficient to provide a binding site for an anti-PR01181 antibody.
Preferably, the PR01181 fragment retains a qualitative biological activity of a native PR01181 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01181 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 437, inclusive of Figure 250 (SEQ ID
N0:355), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 ~ sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 h sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
108. PROl l 2 A cDNA clone (DNA59848-1512) has been identified, having homology to nucleic acid encoding conglutinin that encodes a novel polypeptide, designated in the present application as "PR01182".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01182 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01182 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01182 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 67 or about 142 and about 879, inclusive, of Figure 251 (SEQ ID N0:356).
Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 h sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203088 (DNA59848-1512) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203088 (DNA59848-1512).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01182 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 9036 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01182 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 252 (SEQ
ID N0:357).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1182 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 251 (SEQ ID N0:356).
In another embodiment, the invention provides isolated PROI 182 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
- In a specific aspect, the invention provides isolated native sequence PR01182 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 271 of Figure 252 (SEQ ID N0:357).
In another aspect, the invention concerns an isolated PR01182 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357).
In a further aspect, the invention concerns an isolated PR01182 polypeptide, comprising an amino acid sequence scoring at least about 80°~ positives, preferably at least about 859b positives, more preferably at least about 90 % positives, most preferably at least about 95 9~ positives when compared with the amino acid sequence of residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357).
In yet another aspect, the invention concerns an isolated PR01182 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357), or a fragment thereof sufficient to provide a binding site for an anti-PR01182 antibody.
Preferably, the PR01182 fragment retains a qualitative biological activity of a native PR01182 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01182 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90 R6 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01182 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01182 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01182 polypeptide by contacting the native PR01182 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01182 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01182 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 8596 sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01182 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01182 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 67 or about 142 and about 879, inclusive, of Figure 251 (SEQ ID N0:356).
Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 h sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203088 (DNA59848-1512) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203088 (DNA59848-1512).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01182 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 9036 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01182 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 252 (SEQ
ID N0:357).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1182 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 251 (SEQ ID N0:356).
In another embodiment, the invention provides isolated PROI 182 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
- In a specific aspect, the invention provides isolated native sequence PR01182 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 271 of Figure 252 (SEQ ID N0:357).
In another aspect, the invention concerns an isolated PR01182 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357).
In a further aspect, the invention concerns an isolated PR01182 polypeptide, comprising an amino acid sequence scoring at least about 80°~ positives, preferably at least about 859b positives, more preferably at least about 90 % positives, most preferably at least about 95 9~ positives when compared with the amino acid sequence of residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357).
In yet another aspect, the invention concerns an isolated PR01182 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID N0:357), or a fragment thereof sufficient to provide a binding site for an anti-PR01182 antibody.
Preferably, the PR01182 fragment retains a qualitative biological activity of a native PR01182 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01182 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 271, inclusive of Figure 252 (SEQ ID
N0:357), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90 R6 sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01182 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01182 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01182 polypeptide by contacting the native PR01182 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01182 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
109. PR_ 01155 A cDNA clone (DNA59849-1504) has been identified, having sequence identity with neurolcinin B that encodes a novel polypeptide, designated in the present application as "PRO1155."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1155 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 859b sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1155 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to nucleic or amino acids is meant to convey alternative embodiments, i.e., 1-135 or alternatively in another embodiment, 19-135.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1155 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 158 or 212 and about 562, inclusive, of Figure 253 (SEQ ID N0:358). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209986 (DNA59849-1504), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209986 (DNA59849-1504).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 19 to about 135, inclusive of Figure 254 (SEQ
ID N0:359), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01155 polypeptide having the sequence of amino acid residues from about 19 to about 135, inclusive of Figure 254 (SEQ ID
N0:359), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01155 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1155 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 19 through 135 of Figure 254 (SEQ ID
N0:359).
In another aspect, the invention concerns an isolated PR01155 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85%a sequence identity, more preferably at Least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359).
In a further aspect, the invention concerns an isolated PR01155 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 19 through 135 of Figure 254 (SEQ ID N0:359).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01155 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01155 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01155 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01155 polypeptide, by contacting the native PR01155 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1155 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PRO1155 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 859b sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO1155 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to nucleic or amino acids is meant to convey alternative embodiments, i.e., 1-135 or alternatively in another embodiment, 19-135.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PRO1155 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 158 or 212 and about 562, inclusive, of Figure 253 (SEQ ID N0:358). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209986 (DNA59849-1504), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209986 (DNA59849-1504).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 19 to about 135, inclusive of Figure 254 (SEQ
ID N0:359), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01155 polypeptide having the sequence of amino acid residues from about 19 to about 135, inclusive of Figure 254 (SEQ ID
N0:359), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01155 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1155 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 19 through 135 of Figure 254 (SEQ ID
N0:359).
In another aspect, the invention concerns an isolated PR01155 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85%a sequence identity, more preferably at Least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359).
In a further aspect, the invention concerns an isolated PR01155 polypeptide, comprising an amino acid sequence scoring at least about 80 % positives, preferably at least about 85 %
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or 19 through 135 of Figure 254 (SEQ ID N0:359).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01155 polypeptide having the sequence of amino acid residues from about 1 or 19 to about 135, inclusive of Figure 254 (SEQ ID N0:359), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01155 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01155 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01155 polypeptide, by contacting the native PR01155 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1155 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
110. PROll 6 A cDNA clone (DNA59853-1505) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01156."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01156 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01156 polypeptide having the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID N0:361), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01156 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 281 and about 688, inclusive, of Figure 255 (SEQ ID N0:360). Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80%a sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209985 (DNA59853-1505), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209985 (DNA59853-1505).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8096 sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90°6 sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID
N0:361), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, preferably at least 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01156 polypeptide having the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID
N0:361), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01156 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from amino acid position 1 to about amino acid position 22 in the sequence of Figure 256 (SEQ ID
N0:361).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85 k positives, more preferably at least about 9096 positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 23 to about 159, inclusive of Figure 256 (SEQ
ID N0:361), or (b) the complement of the DNA of (a).
In another aspect, the invention concerns hybridization probes that comprise fragments of the PR0784 coding sequence, or complementary sequence thereof. The hybridization probes preferably have at least about 20 nucleotides to about 80 nucleotides, and more preferably, at least about 20 to about 50 nucleotides.
In another embodiment, the invention provides isolated PRO 1156 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1156 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 to 159 of Figure 256 {SEQ ID N0:361).
In another aspect, the invention concerns an isolated PR01156 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°6 sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 23 to about 159, inclusive of Figure 256 (SEQ
ID N0:361).
In a further aspect, the invention concerns an isolated PR01156 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 9596 positives when compared with the amino acid sequence of residues 23 to 159 of Figure 256 (SEQ ID N0:361).
In yet another aspect, the invention concerns an isolated PRO 1156 polypeptide, comprising the sequence of amino acid residues 23 to about 159, inclusive of Figure 256 (SEQ ID
N0:361), or a fragment thereof sufficient to provide a binding site for an anti-PR01156 antibody. Preferably, the PR01156 fragment retains a qualitative biological activity of a native PR01156 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01156 polypeptide having the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID N0:361), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01156 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01156 polypeptide having the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID N0:361), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01156 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 281 and about 688, inclusive, of Figure 255 (SEQ ID N0:360). Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80%a sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209985 (DNA59853-1505), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209985 (DNA59853-1505).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8096 sequence identity, preferably at least about 85°6 sequence identity, more preferably at least about 90°6 sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID
N0:361), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 50 nucleotides, preferably at least 100 nucleotides, and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01156 polypeptide having the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID
N0:361), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 %
sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01156 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as eztending from amino acid position 1 to about amino acid position 22 in the sequence of Figure 256 (SEQ ID
N0:361).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85 k positives, more preferably at least about 9096 positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 23 to about 159, inclusive of Figure 256 (SEQ
ID N0:361), or (b) the complement of the DNA of (a).
In another aspect, the invention concerns hybridization probes that comprise fragments of the PR0784 coding sequence, or complementary sequence thereof. The hybridization probes preferably have at least about 20 nucleotides to about 80 nucleotides, and more preferably, at least about 20 to about 50 nucleotides.
In another embodiment, the invention provides isolated PRO 1156 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1156 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 23 to 159 of Figure 256 {SEQ ID N0:361).
In another aspect, the invention concerns an isolated PR01156 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90°6 sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 23 to about 159, inclusive of Figure 256 (SEQ
ID N0:361).
In a further aspect, the invention concerns an isolated PR01156 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 9596 positives when compared with the amino acid sequence of residues 23 to 159 of Figure 256 (SEQ ID N0:361).
In yet another aspect, the invention concerns an isolated PRO 1156 polypeptide, comprising the sequence of amino acid residues 23 to about 159, inclusive of Figure 256 (SEQ ID
N0:361), or a fragment thereof sufficient to provide a binding site for an anti-PR01156 antibody. Preferably, the PR01156 fragment retains a qualitative biological activity of a native PR01156 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01156 polypeptide having the sequence of amino acid residues from about 23 to about 159, inclusive of Figure 256 (SEQ ID N0:361), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 ~ sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
111. PR01098 A cDNA clone (DNA59854-1459) has been identified which encodes a novel polypeptide, designated in the present application as "PR01098."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01098 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01098 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-78, or in another embodiment, 20-78.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01098 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 58 or 115 and about 291, inclusive, of Figure 257 (SEQ ID N0:362). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209974 (DNA59854-1459), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209974 (DNA59854-1459).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ
ID N0:363), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01098 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID
N0:363), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01098 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1098 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 20 through 78 of Figure 258 (SEQ ID
N0:363).
In another aspect, the invention concerns an isolated PR01098 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363).
In a further aspect, the invention concerns an isolated PR01098 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 20 through 78 of Figure 258 (SEQ ID N0:363).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01098 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%a sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01098 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80~ sequence identity, preferably at least about 85 ~ sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01098 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363), or (b) the complement of the DNA molecule of (a). The term "or" as used herein to refer to amino or nucleic acids is meant to refer to two alternative embodiments provided herein, i.e., 1-78, or in another embodiment, 20-78.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01098 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 58 or 115 and about 291, inclusive, of Figure 257 (SEQ ID N0:362). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209974 (DNA59854-1459), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209974 (DNA59854-1459).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ
ID N0:363), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01098 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID
N0:363), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01098 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1098 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 20 through 78 of Figure 258 (SEQ ID
N0:363).
In another aspect, the invention concerns an isolated PR01098 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363).
In a further aspect, the invention concerns an isolated PR01098 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 20 through 78 of Figure 258 (SEQ ID N0:363).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01098 polypeptide having the sequence of amino acid residues from about 1 or 20 to about 78, inclusive of Figure 258 (SEQ ID N0:363), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%a sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
112. PR01127 A cDNA clone (DNA60283-1484) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01127."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01127 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01127 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365), or (b) the complement of the DNA molecule of (a). The term "or° in reference to amino or nucleic acids as used herein refers to two alternative embodiments, i.e., 1-67 in one embodiment, or alternatively, 30-67.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01127 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 126 or 213 and about 326, inclusive, of Figure 259 (SEQ ID N0:364). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203043 (DNA60283-1484), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203043 (DNA60283-1484).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85°k sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ
ID N0:365), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01127 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID
N0:365), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 ~ sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 ~
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01127 polypeptide without the N-terminal signal sequence and/or the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position I through about amino acid position 29 in the sequence of Figure 260 (SEQ ID N0:365).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 ~ positives, preferably at least about 85 ~ positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365), or (b) the complement of the DNA of (a).
$ Another embodiment is directed to fragments of a PRO 1 I27 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 through about 80 nucleotides in length, preferably from about 20 through about 60 nucleotides in length, more preferably from about 20 through about 50 nucleotides in length, and most preferably from about 20 through about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01127 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1127 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 30 through 67 of Figure 260 (SEQ ID
N0:365).
In another aspect, the invention concerns an isolated PRO 1127 polypeptide, comprising an amino acid sequence having at least about 80~ sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365).
In a further aspect, the invention concerns an isolated PRO 1127 polypeptide, comprising an amino acid sequence scoring at least about 809b positives, preferably at least about 85%
positives, more preferably at least about 90'ib positives, most preferably at least about 95 9b positives when compared with the amino acid sequence of residues 1 or 30 through 67 of Figure 260 (SEQ ID N0:365).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01127 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85~ sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01127 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01127 antibody.
In a further embodiment, the invention concerns a method of identifying agorusts or antagonists of a native PR01127 polypeptide, by contacting the native PR01127 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1127 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01127 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 ~ sequence identity to (a) a DNA molecule encoding a PR01127 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365), or (b) the complement of the DNA molecule of (a). The term "or° in reference to amino or nucleic acids as used herein refers to two alternative embodiments, i.e., 1-67 in one embodiment, or alternatively, 30-67.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01127 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 126 or 213 and about 326, inclusive, of Figure 259 (SEQ ID N0:364). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203043 (DNA60283-1484), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203043 (DNA60283-1484).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85°k sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ
ID N0:365), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01127 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID
N0:365), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 ~ sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 ~
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01127 polypeptide without the N-terminal signal sequence and/or the initiating methionine. The signal peptide has been tentatively identified as extending from amino acid position I through about amino acid position 29 in the sequence of Figure 260 (SEQ ID N0:365).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 ~ positives, preferably at least about 85 ~ positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365), or (b) the complement of the DNA of (a).
$ Another embodiment is directed to fragments of a PRO 1 I27 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 through about 80 nucleotides in length, preferably from about 20 through about 60 nucleotides in length, more preferably from about 20 through about 50 nucleotides in length, and most preferably from about 20 through about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01127 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1127 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 30 through 67 of Figure 260 (SEQ ID
N0:365).
In another aspect, the invention concerns an isolated PRO 1127 polypeptide, comprising an amino acid sequence having at least about 80~ sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365).
In a further aspect, the invention concerns an isolated PRO 1127 polypeptide, comprising an amino acid sequence scoring at least about 809b positives, preferably at least about 85%
positives, more preferably at least about 90'ib positives, most preferably at least about 95 9b positives when compared with the amino acid sequence of residues 1 or 30 through 67 of Figure 260 (SEQ ID N0:365).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01127 polypeptide having the sequence of amino acid residues from about 1 or 30 to about 67, inclusive of Figure 260 (SEQ ID N0:365), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85~ sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01127 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01127 antibody.
In a further embodiment, the invention concerns a method of identifying agorusts or antagonists of a native PR01127 polypeptide, by contacting the native PR01127 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PRO 1127 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
113. PR01126 A cDNA clone (DNA60615-1483) has been identified, having homology to nucleic acid encoding olfactomedin that encodes a novel polypeptide, designated in the present application as "PR01126".
In one embodiment, the invention provides an isol-ated nucleic acid molecule comprising DNA encoding a PRO1 X26 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01126 polypeptide having the sequence of amino acid residues from about I or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01126 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 110 or about 185 and about 1315, inclusive, of Figure 261 (SEQ ID N0:366).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209980 (DNA60615-1483) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209980 (DNA60615-1483).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01126 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 126 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 262 (SEQ
ID N0:367).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01126 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 261 (SEQ ID N0:366).
In another embodiment, the invention provides isolated PR01126 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01126 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 402 of Figure 262 (SEQ ID N0:367).
In another aspect, the invention concerns an isolated PR01126 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367).
In a further aspect, the invention concerns an isolated PRO 1126 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367).
In yet another aspect, the invention concerns an isolated PRO 1126 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367), or a fragment thereof sufficient to provide a binding site for an anti-PR01126 antibody.
Preferably, the PR01126 fragment retains a qualitative biological activity of a native PR01126 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under suingent conditions with (a) a DNA molecule encoding a PR01126 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01126 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01126 antibody.
WO 99/63088 PCTlUS99/12252 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01126 polypeptide by contacting the native PR01126 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01126 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable Garner.
In one embodiment, the invention provides an isol-ated nucleic acid molecule comprising DNA encoding a PRO1 X26 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01126 polypeptide having the sequence of amino acid residues from about I or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01126 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 110 or about 185 and about 1315, inclusive, of Figure 261 (SEQ ID N0:366).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209980 (DNA60615-1483) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 209980 (DNA60615-1483).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01126 polypeptide having the sequence of amino acid residues from 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PROl 126 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 25 in the sequence of Figure 262 (SEQ
ID N0:367).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01126 polypeptide coding sequence that may fmd use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 261 (SEQ ID N0:366).
In another embodiment, the invention provides isolated PR01126 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01126 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 26 to about 402 of Figure 262 (SEQ ID N0:367).
In another aspect, the invention concerns an isolated PR01126 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367).
In a further aspect, the invention concerns an isolated PRO 1126 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367).
In yet another aspect, the invention concerns an isolated PRO 1126 polypeptide, comprising the sequence of amino acid residues 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID N0:367), or a fragment thereof sufficient to provide a binding site for an anti-PR01126 antibody.
Preferably, the PR01126 fragment retains a qualitative biological activity of a native PR01126 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under suingent conditions with (a) a DNA molecule encoding a PR01126 polypeptide having the sequence of amino acid residues from about 1 or about 26 to about 402, inclusive of Figure 262 (SEQ ID
N0:367), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of a native PR01126 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01126 antibody.
WO 99/63088 PCTlUS99/12252 In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01126 polypeptide by contacting the native PR01126 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01126 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable Garner.
114. PR 1125 A cDNA clone (DNA60619-1482) has been identified, having beta-transducin family Trp-Asp (WD) conserved regions, that encodes a novel polypeptide, designated in the present application as "PR01125."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01125 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1125 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369), or (b) the complement of the DNA molecule of (a). As used herein, "or" when referring to nucleic acids or amino acids, refers to two alternative embodiments, i.e., 1-447 and 26-447.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01125 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 47 or 122 and about 1387, inclusive, of Figure 263 (SEQ ID N0:368). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a} a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209993 (DNA60619-1482), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209993 (DNA60619-1482).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 26 to about 447, inclusive of Figure 264 (SEQ
ID N0:369), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01125 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID
N0:369), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR41125 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 25 in the sequence of Figure 264 (SEQ ID
N0:369).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01125 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01125 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 26 to 447 of Figure 264 (SEQ ID
N0:369).
In another aspect, the invention concerns an isolated PR01125 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369).
In a further aspect, the invention concerns an isolated PRO 1125 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 26 through 447 of Figure 264 (SEQ ID N0:369).
In yet another aspect, the invention concerns an isolated PRO 1125 polypeptide, comprising the sequence of amino acid residues 26 to about 447, inclusive of Figure 264 (SEQ ID
N0:369), or a fragment thereof sufficient to provide a binding site for an anti-PR01125 antibody. Preferably, the PR01125 fragment retains a qualitative biological activity of a native PROI125 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01125 polypeptide having the sequence of amino acid residues from about 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01125 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01125 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01125 polypeptide, by contacting the native PR01125 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01125 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1125 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369), or (b) the complement of the DNA molecule of (a). As used herein, "or" when referring to nucleic acids or amino acids, refers to two alternative embodiments, i.e., 1-447 and 26-447.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01125 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 47 or 122 and about 1387, inclusive, of Figure 263 (SEQ ID N0:368). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a} a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209993 (DNA60619-1482), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209993 (DNA60619-1482).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 26 to about 447, inclusive of Figure 264 (SEQ
ID N0:369), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01125 polypeptide having the sequence of amino acid residues from about 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID
N0:369), or (b) the complement of the DNA molecule of (a), and, if the DNA
molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 %
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA
molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR41125 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from amino acid position 1 through about amino acid position 25 in the sequence of Figure 264 (SEQ ID
N0:369).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01125 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01125 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 26 to 447 of Figure 264 (SEQ ID
N0:369).
In another aspect, the invention concerns an isolated PR01125 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369).
In a further aspect, the invention concerns an isolated PRO 1125 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 26 through 447 of Figure 264 (SEQ ID N0:369).
In yet another aspect, the invention concerns an isolated PRO 1125 polypeptide, comprising the sequence of amino acid residues 26 to about 447, inclusive of Figure 264 (SEQ ID
N0:369), or a fragment thereof sufficient to provide a binding site for an anti-PR01125 antibody. Preferably, the PR01125 fragment retains a qualitative biological activity of a native PROI125 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01125 polypeptide having the sequence of amino acid residues from about 26 to about 447, inclusive of Figure 264 (SEQ ID N0:369), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01125 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01125 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01125 polypeptide, by contacting the native PR01125 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
115. PR01186 A cDNA clone (DNA60621-1516) has been identified that encodes a novel polypepdde having sequence identity with venom protein A and designated in the present application as "PR01186."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01186 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1186 polypeptide having the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ ID N0:371), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01186 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 148 and about 405, inclusive, of Figure 265 (SEQ ID N0:370). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203091 (DNA60621-1516), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203091 (DNA60621-1516).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ ID
N0:371), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01186 polypeptide having the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ
ID N0:371), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 8096 positives, preferably at least about 8536 positives, more preferably at least about 909b positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 20 to about 105, inclusive of Figure 266 (SEQ
ID N0:371), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01186 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 through about 80 nucleotides in length, preferably from about 20 through about 60 nucleotides in length, more preferably from about 20 through about 50 nucleotides in length, and most preferably from about 20 through about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01186 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01186 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 105 of Figure 266 (SEQ ID
N0:371).
In another aspect, the invention concerns an isolated PR01186 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 105, inclusive of Figure 266 (SEQ
ID N0:371).
In a further aspect, the invention concerns an isolated PR01186 polypeptide, comprising an amino acid sequence scoring at least about 80 R~ positives, preferably at least about 85 % positives, more preferably at least about 9096 positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 through 105 of Figure 266 (SEQ ID N0:371).
In yet another aspect, the invention concerns an isolated PR01186 polypeptide, comprising the sequence of amino acid residues 20 to about 105, inclusive of Figure 266 (SEQ ID
N0:371), or a fragment thereof sufficient to provide a binding site for an anti-PR01186 antibody. Preferably, the PR01186 fragment retains a qualitative biological activity of a native PR01186 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01186 polypeptide having the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ ID N0:371), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01186 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01186 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01186 polypeptide, by contacting the native PR01186 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01186 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable Garner.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01186 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1186 polypeptide having the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ ID N0:371), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01186 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 148 and about 405, inclusive, of Figure 265 (SEQ ID N0:370). Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203091 (DNA60621-1516), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203091 (DNA60621-1516).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ ID
N0:371), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01186 polypeptide having the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ
ID N0:371), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 8096 positives, preferably at least about 8536 positives, more preferably at least about 909b positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 20 to about 105, inclusive of Figure 266 (SEQ
ID N0:371), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PR01186 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 through about 80 nucleotides in length, preferably from about 20 through about 60 nucleotides in length, more preferably from about 20 through about 50 nucleotides in length, and most preferably from about 20 through about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01186 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PR01186 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 20 through 105 of Figure 266 (SEQ ID
N0:371).
In another aspect, the invention concerns an isolated PR01186 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 105, inclusive of Figure 266 (SEQ
ID N0:371).
In a further aspect, the invention concerns an isolated PR01186 polypeptide, comprising an amino acid sequence scoring at least about 80 R~ positives, preferably at least about 85 % positives, more preferably at least about 9096 positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 20 through 105 of Figure 266 (SEQ ID N0:371).
In yet another aspect, the invention concerns an isolated PR01186 polypeptide, comprising the sequence of amino acid residues 20 to about 105, inclusive of Figure 266 (SEQ ID
N0:371), or a fragment thereof sufficient to provide a binding site for an anti-PR01186 antibody. Preferably, the PR01186 fragment retains a qualitative biological activity of a native PR01186 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01186 polypeptide having the sequence of amino acid residues from about 20 to about 105, inclusive of Figure 266 (SEQ ID N0:371), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 ~ sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01186 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01186 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01186 polypeptide, by contacting the native PR01186 polypeptide with a candidate molecule and monitoring a biological activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01186 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable Garner.
116. PR01198 A cDNA clone (DNA60622-1525) has been . identified that encodes a novel secreted polypeptide designated in the present application as "PR01198."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01198 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 909 sequence identity, most preferably at least about 95 ib sequence identity to (a) a DNA molecule encoding a PRO 1198 polypeptide having the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ ID N0:373), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01198 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 156 and about 740, inclusive, of Figure 268 (SEQ ID N0:373). Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 803a sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203090 (DNA60622-1525), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203090 (DNA60622-1525).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8(?% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ ID
N0:373), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01198 polypeptide having the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ
ID N0:373), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01198 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I through about amino acid position 35 in the sequence of Figure 268 (SEQ ID N0:373).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 35 to about 229, inclusive of Figure 268 (SEQ
ID N0:373), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1198 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01198 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1198 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 35 to 229 of Figure 268 (SEQ ID N0:373).
In another aspect, the invention concerns an isolated PRO 1198 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 35 to about 229, inclusive of Figure 268 (SEQ
ID N0:373).
In a further aspect, the invention concerns an isolated_PRO1198 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 35 to 229 of Figure 268 (SEQ ID N0:373).
In yet another aspect, the invention concerns an isolated PRO 1198 polypeptide, comprising the sequence of amino acid residues 35 to about 229, inclusive of Figure 268 (SEQ ID
N0:373), or a fragment thereof sufficient to provide a binding site for an anti-PROI 198 antibody.
Preferably, the PR01198 fragment retains a qualitative biological activity of a native PR01198 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01198 polypeptide having the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ ID N0:373), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01198 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 909 sequence identity, most preferably at least about 95 ib sequence identity to (a) a DNA molecule encoding a PRO 1198 polypeptide having the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ ID N0:373), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01198 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 156 and about 740, inclusive, of Figure 268 (SEQ ID N0:373). Preferably, hybridization occurs under suingent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 803a sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203090 (DNA60622-1525), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203090 (DNA60622-1525).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 8(?% sequence identity, preferably at least about 85~ sequence identity, more preferably at least about 90~ sequence identity, most preferably at least about 95~ sequence identity to the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ ID
N0:373), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01198 polypeptide having the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ
ID N0:373), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01198 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position I through about amino acid position 35 in the sequence of Figure 268 (SEQ ID N0:373).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90 % positives, most preferably at least about 95 %
positives when compared with the amino acid sequence of residues 35 to about 229, inclusive of Figure 268 (SEQ
ID N0:373), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO 1198 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about 50 nucleotides in length, and most preferably from about 20 to about 40 nucleotides in length.
In another embodiment, the invention provides isolated PR01198 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1198 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 35 to 229 of Figure 268 (SEQ ID N0:373).
In another aspect, the invention concerns an isolated PRO 1198 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 35 to about 229, inclusive of Figure 268 (SEQ
ID N0:373).
In a further aspect, the invention concerns an isolated_PRO1198 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 35 to 229 of Figure 268 (SEQ ID N0:373).
In yet another aspect, the invention concerns an isolated PRO 1198 polypeptide, comprising the sequence of amino acid residues 35 to about 229, inclusive of Figure 268 (SEQ ID
N0:373), or a fragment thereof sufficient to provide a binding site for an anti-PROI 198 antibody.
Preferably, the PR01198 fragment retains a qualitative biological activity of a native PR01198 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01198 polypeptide having the sequence of amino acid residues from about 35 to about 229, inclusive of Figure 268 (SEQ ID N0:373), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
117. PR01158 A cDNA clone (DNA60625-1507) has been identified that encodes a novel transmembrane polypeptide, designated in the present application as "PRO 1158" .
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01158 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01158 polypeptide having the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ ID N0:375), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01158 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 220 and about 531, inclusive, of Figure 269 (SEQ ID N0:374). Preferably, hybridization occurs under stringent 1 S hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209975 (DNA60625-1507), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209975 (DNA60625-1507).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ ID
N0:375), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01158 polypeptide having the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ
ID N0:375), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01158 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 270 (SEQ
ID N0:375). The transmembrane domain has been tentatively identified as extending from about amino acid position 56 to about amino acid position 80 in the PR01158 amino acid sequence (Figure 270, SEQ ID N0:375).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 20 to about 123, inclusive of Figure 270 (SEQ
ID N0:375}, or (b) the complement of the DNA of (a).
In another aspect, the invention concerns hybridization probes that comprise fragments of the PR01158 coding sequence, or complementary sequence thereof. The hybridization probes preferably have at least about nucleotides to about 80 nucleotides, and more preferably, at least about 20 to about 50 nucleotides.
In another embodiment, the invention provides isolated PR01158 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1158 polypeptide, which in one 15 embodiment, includes an amino acid sequence comprising residues 20 to 123 of Figure 270 (SEQ ID N0:375).
In another aspect, the invention concerns an isolated PRO 1158 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 123, inclusive of Figure 270 (SEQ
ID N0:375).
20 In a further aspect, the invention concerns an isolated PRO1158 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to 123 of Figure 270 (SEQ ID N0:375).
In yet another aspect, the invention concerns an isolated PRO 1158 polypeptide, comprising the sequence of amino acid residues 20 to about 123, inclusive of Figure 270 (SEQ ID
N0:375), or a fragment thereof sufficient to provide a binding site for an anti-PR01158 antibody. Preferably, the PR01158 fragment retains a qualitative biological activity of a native PR01158 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01158 polypeptide having the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ ID N0:375), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01158 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80 % sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01158 polypeptide having the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ ID N0:375), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01158 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 220 and about 531, inclusive, of Figure 269 (SEQ ID N0:374). Preferably, hybridization occurs under stringent 1 S hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209975 (DNA60625-1507), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209975 (DNA60625-1507).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ ID
N0:375), or the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least about 50 nucleotides, and preferably at least about 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a PR01158 polypeptide having the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ
ID N0:375), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01158 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 19 in the sequence of Figure 270 (SEQ
ID N0:375). The transmembrane domain has been tentatively identified as extending from about amino acid position 56 to about amino acid position 80 in the PR01158 amino acid sequence (Figure 270, SEQ ID N0:375).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 85 % positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 20 to about 123, inclusive of Figure 270 (SEQ
ID N0:375}, or (b) the complement of the DNA of (a).
In another aspect, the invention concerns hybridization probes that comprise fragments of the PR01158 coding sequence, or complementary sequence thereof. The hybridization probes preferably have at least about nucleotides to about 80 nucleotides, and more preferably, at least about 20 to about 50 nucleotides.
In another embodiment, the invention provides isolated PR01158 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1158 polypeptide, which in one 15 embodiment, includes an amino acid sequence comprising residues 20 to 123 of Figure 270 (SEQ ID N0:375).
In another aspect, the invention concerns an isolated PRO 1158 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 20 to about 123, inclusive of Figure 270 (SEQ
ID N0:375).
20 In a further aspect, the invention concerns an isolated PRO1158 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 20 to 123 of Figure 270 (SEQ ID N0:375).
In yet another aspect, the invention concerns an isolated PRO 1158 polypeptide, comprising the sequence of amino acid residues 20 to about 123, inclusive of Figure 270 (SEQ ID
N0:375), or a fragment thereof sufficient to provide a binding site for an anti-PR01158 antibody. Preferably, the PR01158 fragment retains a qualitative biological activity of a native PR01158 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01158 polypeptide having the sequence of amino acid residues from about 20 to about 123, inclusive of Figure 270 (SEQ ID N0:375), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80% sequence identity, preferably at least about an 85 % sequence identity, more preferably at least about a 90 % sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
118. PR01159 A cDNA clone (DNA60627-1508) has been identified that encodes a novel secreted polypeptide, designated in the present application as "PR01159".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01159 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1159 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01159 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 92 or about 137 and about 361, inclusive, of Figure 271 (SEQ ID N0:376).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203092 (DNA60627-1508) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203092 (DNAfi0627-1508).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01159 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID N0:377), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01159 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 272 (SEQ
ID N0:377).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 8S % positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID N0:377), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO11S9 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 271 (SEQ ID N0:376).
In another embodiment, the invention provides isolated PRO11S9 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01159 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 90 of Figure 272 (SEQ ID N0:377).
In another aspect, the invention concerns an isolated PRO11S9 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID N0:377).
In a further aspect, the invention concerns an isolated PRO 1159 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377).
In yet another aspect, the invention concerns an isolated PRO 11 S9 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ
ID N0:377), or a fragment thereof sufficient to provide a binding site for an anti-PRO11S9 antibody.
Preferably, the PROlIS9 fragment retains a qualitative biological activity of a native PRO11S9 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO11S9 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 8S% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
WO 99/b3088 PCT/US99/12252 119. )PR01124 A cDNA clone (DNA60629-1481) has been identified, having sequence identity with a chloride channel protein and lung-endothelial cell adhesion molecule-1 (EAM-1) that encodes a novel polypeptide, designated in the present application as "PR01124."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01124 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01124 polypeptide having the sequence of amino acid residues from about 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379), or (b) the complement of the DNA molecule of (a): As used herein, "or°, i.e., 1 or 22 and 25 or 88, is used to describe two alternative embodiments. For example, the invention includes amino acids 1 through 919 and in an alternative embodiment, provides amino acids 22 through 919, etc.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01124 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 25 or 88 and about 2781, inclusive, of Figure 273 (SEQ ID N0:378). In another aspect, the invention concerns an isolated nucleic acid molecule hybridizing to the complement of the nucleic acid of SEQ ID N0:378. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209979 (DNA60629-1481), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209979 (DNA60629-1481).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 22 to about 919, inclusive of Figure 274 (SEQ
ID N0:379), or the complement of the DNA of (a).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01124 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The cytoplasmic end can be excluded as well. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 21 in the sequence of Figure 274 (SEQ ID NO: 379). The transmembrane domains have been tentatively identified as extending from about amino acid position 284 to about amino acid position 300 and from about amino acid position 617 to about amino acid position 633 in the amino acid sequence (Figure 274, SEQ ID N0:379).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01124 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1124 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 22 through 919 of Figure 274 (SEQ ID
N0:379).
In another aspect, the invention concerns an isolated PR01124 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379).
In a further aspect, the invention concerns an isolated PRO 1124 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 22 to 919 of Figure 274 (SEQ ID N0:379).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01124 polypeptide having the sequence of amino acid residues from about 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01124 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01124 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01124 polypeptide, by contacting the native PR01124 polypeptide with a candidate molecule and monitoring an activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01124 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01159 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1159 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01159 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 92 or about 137 and about 361, inclusive, of Figure 271 (SEQ ID N0:376).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203092 (DNA60627-1508) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203092 (DNAfi0627-1508).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377), or (b) the complement of the DNA of (a).
In a further aspect, the invention concerns an isolated nucleic acid molecule having at least 10 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01159 polypeptide having the sequence of amino acid residues from 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID N0:377), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01159 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 15 in the sequence of Figure 272 (SEQ
ID N0:377).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80 % positives, preferably at least about 8S % positives, more preferably at least about 90% positives, most preferably at least about 9S%
positives when compared with the amino acid sequence of residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID N0:377), or (b) the complement of the DNA of (a).
Another embodiment is directed to fragments of a PRO11S9 polypeptide coding sequence that may find use as hybridization probes. Such nucleic acid fragments are from about 20 to about 80 nucleotides in length, preferably from about 20 to about 60 nucleotides in length, more preferably from about 20 to about SO
nucleotides in length and most preferably from about 20 to about 40 nucleotides in length and may be derived from the nucleotide sequence shown in Figure 271 (SEQ ID N0:376).
In another embodiment, the invention provides isolated PRO11S9 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified.
In a specific aspect, the invention provides isolated native sequence PR01159 polypeptide, which in certain embodiments, includes an amino acid sequence comprising residues 1 or about 16 to about 90 of Figure 272 (SEQ ID N0:377).
In another aspect, the invention concerns an isolated PRO11S9 polypeptide, comprising an amino acid sequence having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 9S% sequence identity to the sequence of amino acid residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID N0:377).
In a further aspect, the invention concerns an isolated PRO 1159 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 8S%
positives, more preferably at least about 90 % positives, most preferably at least about 95 % positives when compared with the amino acid sequence of residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377).
In yet another aspect, the invention concerns an isolated PRO 11 S9 polypeptide, comprising the sequence of amino acid residues 1 or about 16 to about 90, inclusive of Figure 272 (SEQ
ID N0:377), or a fragment thereof sufficient to provide a binding site for an anti-PRO11S9 antibody.
Preferably, the PROlIS9 fragment retains a qualitative biological activity of a native PRO11S9 polypeptide.
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PRO11S9 polypeptide having the sequence of amino acid residues from about 1 or about 16 to about 90, inclusive of Figure 272 (SEQ ID
N0:377), or (b) the complement of the DNA molecule of (a), and if the test DNA
molecule has at least about an 80% sequence identity, preferably at least about an 8S% sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
WO 99/b3088 PCT/US99/12252 119. )PR01124 A cDNA clone (DNA60629-1481) has been identified, having sequence identity with a chloride channel protein and lung-endothelial cell adhesion molecule-1 (EAM-1) that encodes a novel polypeptide, designated in the present application as "PR01124."
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01124 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PR01124 polypeptide having the sequence of amino acid residues from about 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379), or (b) the complement of the DNA molecule of (a): As used herein, "or°, i.e., 1 or 22 and 25 or 88, is used to describe two alternative embodiments. For example, the invention includes amino acids 1 through 919 and in an alternative embodiment, provides amino acids 22 through 919, etc.
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01124 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about residues 25 or 88 and about 2781, inclusive, of Figure 273 (SEQ ID N0:378). In another aspect, the invention concerns an isolated nucleic acid molecule hybridizing to the complement of the nucleic acid of SEQ ID N0:378. Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209979 (DNA60629-1481), or (b) the complement of the DNA molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 209979 (DNA60629-1481).
In a still further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues from about 1 or 22 to about 919, inclusive of Figure 274 (SEQ
ID N0:379), or the complement of the DNA of (a).
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01124 polypeptide, with or without the N-terminal signal sequence and/or the initiating methionine, and its soluble, i.e. transmembrane domain deleted or inactivated variants, or is complementary to such encoding nucleic acid molecule. The cytoplasmic end can be excluded as well. The signal peptide has been tentatively identified as extending from amino acid position 1 to about amino acid position 21 in the sequence of Figure 274 (SEQ ID NO: 379). The transmembrane domains have been tentatively identified as extending from about amino acid position 284 to about amino acid position 300 and from about amino acid position 617 to about amino acid position 633 in the amino acid sequence (Figure 274, SEQ ID N0:379).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90% positives, most preferably at least about 95%
positives when compared with the amino acid sequence of residues 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379), or (b) the complement of the DNA of (a).
In another embodiment, the invention provides isolated PR01124 polypeptide encoded by any of the isolated nucleic acid sequences hereinabove defined.
In a specific aspect, the invention provides isolated native sequence PRO 1124 polypeptide, which in one embodiment, includes an amino acid sequence comprising residues 1 or 22 through 919 of Figure 274 (SEQ ID
N0:379).
In another aspect, the invention concerns an isolated PR01124 polypeptide, comprising an amino acid sequence having at least about 80 % sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95 % sequence identity to the sequence of amino acid residues 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379).
In a further aspect, the invention concerns an isolated PRO 1124 polypeptide, comprising an amino acid sequence scoring at least about 80% positives, preferably at least about 85%
positives, more preferably at least about 90% positives, most preferably at least about 95% positives when compared with the amino acid sequence of residues 1 or 22 to 919 of Figure 274 (SEQ ID N0:379).
In a still further aspect, the invention provides a polypeptide produced by (i) hybridizing a test DNA
molecule under stringent conditions with (a) a DNA molecule encoding a PR01124 polypeptide having the sequence of amino acid residues from about 1 or 22 to about 919, inclusive of Figure 274 (SEQ ID N0:379), or (b) the complement of the DNA molecule of (a), and if the test DNA molecule has at least about an 80%
sequence identity, preferably at least about an 85% sequence identity, more preferably at least about a 90%
sequence identity, most preferably at least about a 95 % sequence identity to (a) or (b), (ii) culturing a host cell comprising the test DNA molecule under conditions suitable for expression of the polypeptide, and (iii) recovering the polypeptide from the cell culture.
In yet another embodiment, the invention concerns agonists and antagonists of the a native PR01124 polypeptide. In a particular embodiment, the agonist or antagonist is an anti-PR01124 antibody.
In a further embodiment, the invention concerns a method of identifying agonists or antagonists of a native PR01124 polypeptide, by contacting the native PR01124 polypeptide with a candidate molecule and monitoring an activity mediated by said polypeptide.
In a still further embodiment, the invention concerns a composition comprising a PR01124 polypeptide, or an agonist or antagonist as hereinabove defined, in combination with a pharmaceutically acceptable carrier.
120. PR01287 A cDNA clone (DNA61755-1554) has been identified, having homology to nucleic acid encoding fringe protein, that encodes a novel polypeptide, designated in the present application as "PR01287".
In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01287 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1287 polypeptide having S the sequence of amino acid residues from about 1 or about 28 to about 532, inclusive of Figure 276 (SEQ ID
N0:381), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01287 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 655 or about 736 and about 2250, inclusive, of Figure 275 (SEQ ID N0:380).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95°.6 sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203112 (DNA61755-1554) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203112 (DNA61755-1554).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about $0% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 28 to about 532, inclusive of Figure 276 (SEQ ID
N0:381), or (b) the complement of the DNA of (a).
In a further aspect, the invention concet~tts an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01287 polypeptide having the sequence of amino acid residues from 1 or about 28 to about 532, inclusive of Figure 276 (SEQ ID N0:381), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01287 polypeptide, with or without the N-terminal signal sequence and/or the initiating methiottine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 27 in the sequence of Figure 276 (SEQ
ID N0:381).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90%a positives, most preferably at least about 95%
positives when compared with the CA 02328895 2000-11-23 .
C
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In one embodiment, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01287 polypeptide.
In one aspect, the isolated nucleic acid comprises DNA having at least about 80% sequence identity, preferably at least about 85 % sequence identity, more preferably at least about 90 % sequence identity, most preferably at least about 95 % sequence identity to (a) a DNA molecule encoding a PRO 1287 polypeptide having S the sequence of amino acid residues from about 1 or about 28 to about 532, inclusive of Figure 276 (SEQ ID
N0:381), or (b) the complement of the DNA molecule of (a).
In another aspect, the invention concerns an isolated nucleic acid molecule encoding a PR01287 polypeptide comprising DNA hybridizing to the complement of the nucleic acid between about nucleotides 655 or about 736 and about 2250, inclusive, of Figure 275 (SEQ ID N0:380).
Preferably, hybridization occurs under stringent hybridization and wash conditions.
In a further aspect, the invention concerns an isolated nucleic acid molecule comprising DNA having at least about 80% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95°.6 sequence identity to (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA in ATCC
Deposit No. 203112 (DNA61755-1554) or (b) the complement of the nucleic acid molecule of (a). In a preferred embodiment, the nucleic acid comprises a DNA encoding the same mature polypeptide encoded by the human protein cDNA in ATCC Deposit No. 203112 (DNA61755-1554).
In still a further aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide having at least about $0% sequence identity, preferably at least about 85% sequence identity, more preferably at least about 90% sequence identity, most preferably at least about 95% sequence identity to the sequence of amino acid residues 1 or about 28 to about 532, inclusive of Figure 276 (SEQ ID
N0:381), or (b) the complement of the DNA of (a).
In a further aspect, the invention concet~tts an isolated nucleic acid molecule having at least 100 nucleotides and produced by hybridizing a test DNA molecule under stringent conditions with (a) a DNA
molecule encoding a PR01287 polypeptide having the sequence of amino acid residues from 1 or about 28 to about 532, inclusive of Figure 276 (SEQ ID N0:381), or (b) the complement of the DNA molecule of (a), and, if the DNA molecule has at least about an 80 % sequence identity, prefereably at least about an 85 % sequence identity, more preferably at least about a 90% sequence identity, most preferably at least about a 95% sequence identity to (a) or (b), isolating the test DNA molecule.
In a specific aspect, the invention provides an isolated nucleic acid molecule comprising DNA encoding a PR01287 polypeptide, with or without the N-terminal signal sequence and/or the initiating methiottine, or is complementary to such encoding nucleic acid molecule. The signal peptide has been tentatively identified as extending from about amino acid position 1 to about amino acid position 27 in the sequence of Figure 276 (SEQ
ID N0:381).
In another aspect, the invention concerns an isolated nucleic acid molecule comprising (a) DNA
encoding a polypeptide scoring at least about 80% positives, preferably at least about 85% positives, more preferably at least about 90%a positives, most preferably at least about 95%
positives when compared with the CA 02328895 2000-11-23 .
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Claims (26)
1. Isolated nucleic acid having at least 80% sequence identity to a nucleotide sequence that encodes a polypeptide comprising an amino acid sequence selected from the group consisting of the amino acid sequence shown in Figure 2 (SEQ ID NO:2), Figure 4 (SEQ ID NO:6), Figure 6 (SEQ ID NO:8), Figure 9 (SEQ ID NO:14), Figure 12 (SEQ ID NO:20), Figure 15 (SEQ ID NO:23), Figure 18 (SEQ ID NO:28), Figure 20 (SEQ ID NO:30), Figure 23 (SEQ ID NO:33), Figure 25 (SEQ ID NO:36), Figure 27 (SEQ ID NO:41), Figure 30 (SEQ ID NO:47), Figure 32 (SEQ ID NO:52), Figure 34 (SEQ 1D NO:57), Figure 36 (SEQ ID
NO:62), Figure 38 (SEQ ID NO:67), Figure 41 (SEQ ID NO:73), Figure 47 (SEQ ID
NO:84), Figure 49 (SEQ
ID NO:95), Figure 51 (SEQ ID NO:97), Figure 53 (SEQ ID NO:99), Figure 57 (SEQ
ID NO:103), Figure 64 (SEQ ID NO:113), Figure 66 (SEQ ID NO:115), Figure 68 (SEQ ID NO: 117), Figure 70 (SEQ ID NO:119), Figure 72 (SEQ ID NO:124), Figure 74 (SEQ ID NO:129), Figure 76 (SEQ ID
NO:135), Figure 79 (SEQ ID
NO:138), Figure 83 (SEQ ID NO:146), Figure 85 (SEQ ID NO:148), Figure 88 (SEQ
ID NO:151), Figure 90 (SEQ ID NO:153), Figure 93 (SEQ ID NO:156), Figure 95 (SEQ ID NO:158), Figure 97 (SEQ ID NO:160), Figure 99 (SEQ ID NO:165), Figure 101 (SEQ ID NO:167), Figure 103 (SEQ ID
NO:169), Figure 105 (SEQ
ID NO:171), Figure 109 (SEQ ID NO:175), Figure 111 (SEQ ID NO:177), Figure 113 (SEQ ID NO:179), Figure 115 (SEQ ID NO:181), Figure 117 (SEQ ID NO:183), Figure 120 (SEQ ID
NO:189), Figure 122 (SEQ
ID NO:194), Figure 125 (SEQ ID NO:197), Figure 127 (SEQ ID NO:199), Figure 129 (SEQ ID NO:201), Figure 131 (SEQ ID NO:203), Figure 133 (SEQ ID NO:205), Figure 135 (SEQ ID
NO:207), Figure 137 (SEQ
ID NO:209), Figure 139 (SEQ ID NO:211), Figure 141 (SEQ ID NO:213), Figure 144 (SEQ ID NO:216), Figure 147 (SEQ ID NO:219), Figure 149 (SEQ ID NO:221), Figure 151 (SEQ ID
NO:223), Figure 153 (SEQ
ID NO:225), Figure 155 (SEQ ID NO:227), Figure 157 (SEQ ID NO:229), Figure 159 (SEQ ID NO:231), Figure 161 (SEQ ID NO:236), Figure 163 (SEQ ID NO:241), Figure 165 (SEQ ID
NO:246), Figure 167 (SEQ
ID NO:248), Figure 169 (SEQ ID NO:250), Figure 171 (SEQ ID NO:253), Figure 174 (SEQ ID NO:256), Figure 176 (SEQ ID NO:258), Figure 178 (SEQ ID NO:260), Figure 180 (SEQ ID
NO:262), Figure 182 (SEQ
ID NO:264), Figure 184 (SEQ ID NO:266), Figure 186 (SEQ ID NO:268), Figure 188 (SEQ ID NO:270), Figure 190 (SEQ ID NO:272), Figure 192 (SEQ ID NO:274), Figure 194 (SEQ ID
NO:276), Figure 196 (SEQ
ID NO:278), Figure 198 (SEQ ID NO:281), Figure 200 (SEQ ID NO:283), Figure 202 (SEQ ID NO:285), Figure 204 (SEQ ID NO:287), Figure 206 (SEQ ID NO:289), Figure 208 (SEQ ID
NO:291), Figure 210 (SEQ
ID NO:293), Figure 212 (SEQ ID NO:295), Figure 214 (SEQ ID NO:297), Figure 216 (SEQ ID NO:299), Figure 218 (SEQ ID NO:301), Figure 220 (SEQ ID NO:303), Figure 226 (SEQ ID
NO:309), Figure 228 (SEQ
ID NO:314), Figure 230 (SEQ ID NO:319), Figure 233 (SEQ ID NO:326), Figure 235 (SEQ ID NO:334), Figure 238 (SEQ ID NO:340), Figure 240 (SEQ ID NO:345), Figure 242 (SEQ ID
NO:347), Figure 244 (SEQ
ID NO:349), Figure 246 (SEQ ID NO:351), Figure 248 (SEQ ID NO:353), Figure 250 (SEQ ID NO:355), Figure 252 (SEQ ID NO:357), Figure 254 (SEQ ID NO:359), Figure 256 (SEQ ID
NO:361), Figure 258 (SEQ
ID NO:363), Figure 260 (SEQ ID NO:365), Figure 262 (SEQ ID NO:367), Figure 264 (SEQ ID NO:369), Figure 266 (SEQ ID NO:371), Figure 268 (SEQ ID NO:373), Figure 270 (SEQ ID
NO:375), Figure 272 (SEQ
ID NO:377), Figure 274 (SEQ ID NO:379), Figure 276 (SEQ ID NO:381), Figure 278 (SEQ ID NO:387), Figure 280 (SEQ ID NO:389), Figure 282 (SEQ ID NO:394), Figure 284 (SEQ ID
NO:399), Figure 286 (SEQ
ID NO:401), Figure 288 (SEQ ID NO:403), Figure 290 (SEQ ID NO:408), Figure 292 (SEQ ID NO:410), Figure 294 (SEQ ID NO:412), Figure 296 (SEQ ID NO:414), Figure 298 (SEQ ID
NO:416), Figure 300 (SEQ
ID NO:418), Figure 302 (SEQ ID NO:420), Figure 304 (SEQ ID NO:422) and Figure 306 (SEQ ID NO:424).
NO:62), Figure 38 (SEQ ID NO:67), Figure 41 (SEQ ID NO:73), Figure 47 (SEQ ID
NO:84), Figure 49 (SEQ
ID NO:95), Figure 51 (SEQ ID NO:97), Figure 53 (SEQ ID NO:99), Figure 57 (SEQ
ID NO:103), Figure 64 (SEQ ID NO:113), Figure 66 (SEQ ID NO:115), Figure 68 (SEQ ID NO: 117), Figure 70 (SEQ ID NO:119), Figure 72 (SEQ ID NO:124), Figure 74 (SEQ ID NO:129), Figure 76 (SEQ ID
NO:135), Figure 79 (SEQ ID
NO:138), Figure 83 (SEQ ID NO:146), Figure 85 (SEQ ID NO:148), Figure 88 (SEQ
ID NO:151), Figure 90 (SEQ ID NO:153), Figure 93 (SEQ ID NO:156), Figure 95 (SEQ ID NO:158), Figure 97 (SEQ ID NO:160), Figure 99 (SEQ ID NO:165), Figure 101 (SEQ ID NO:167), Figure 103 (SEQ ID
NO:169), Figure 105 (SEQ
ID NO:171), Figure 109 (SEQ ID NO:175), Figure 111 (SEQ ID NO:177), Figure 113 (SEQ ID NO:179), Figure 115 (SEQ ID NO:181), Figure 117 (SEQ ID NO:183), Figure 120 (SEQ ID
NO:189), Figure 122 (SEQ
ID NO:194), Figure 125 (SEQ ID NO:197), Figure 127 (SEQ ID NO:199), Figure 129 (SEQ ID NO:201), Figure 131 (SEQ ID NO:203), Figure 133 (SEQ ID NO:205), Figure 135 (SEQ ID
NO:207), Figure 137 (SEQ
ID NO:209), Figure 139 (SEQ ID NO:211), Figure 141 (SEQ ID NO:213), Figure 144 (SEQ ID NO:216), Figure 147 (SEQ ID NO:219), Figure 149 (SEQ ID NO:221), Figure 151 (SEQ ID
NO:223), Figure 153 (SEQ
ID NO:225), Figure 155 (SEQ ID NO:227), Figure 157 (SEQ ID NO:229), Figure 159 (SEQ ID NO:231), Figure 161 (SEQ ID NO:236), Figure 163 (SEQ ID NO:241), Figure 165 (SEQ ID
NO:246), Figure 167 (SEQ
ID NO:248), Figure 169 (SEQ ID NO:250), Figure 171 (SEQ ID NO:253), Figure 174 (SEQ ID NO:256), Figure 176 (SEQ ID NO:258), Figure 178 (SEQ ID NO:260), Figure 180 (SEQ ID
NO:262), Figure 182 (SEQ
ID NO:264), Figure 184 (SEQ ID NO:266), Figure 186 (SEQ ID NO:268), Figure 188 (SEQ ID NO:270), Figure 190 (SEQ ID NO:272), Figure 192 (SEQ ID NO:274), Figure 194 (SEQ ID
NO:276), Figure 196 (SEQ
ID NO:278), Figure 198 (SEQ ID NO:281), Figure 200 (SEQ ID NO:283), Figure 202 (SEQ ID NO:285), Figure 204 (SEQ ID NO:287), Figure 206 (SEQ ID NO:289), Figure 208 (SEQ ID
NO:291), Figure 210 (SEQ
ID NO:293), Figure 212 (SEQ ID NO:295), Figure 214 (SEQ ID NO:297), Figure 216 (SEQ ID NO:299), Figure 218 (SEQ ID NO:301), Figure 220 (SEQ ID NO:303), Figure 226 (SEQ ID
NO:309), Figure 228 (SEQ
ID NO:314), Figure 230 (SEQ ID NO:319), Figure 233 (SEQ ID NO:326), Figure 235 (SEQ ID NO:334), Figure 238 (SEQ ID NO:340), Figure 240 (SEQ ID NO:345), Figure 242 (SEQ ID
NO:347), Figure 244 (SEQ
ID NO:349), Figure 246 (SEQ ID NO:351), Figure 248 (SEQ ID NO:353), Figure 250 (SEQ ID NO:355), Figure 252 (SEQ ID NO:357), Figure 254 (SEQ ID NO:359), Figure 256 (SEQ ID
NO:361), Figure 258 (SEQ
ID NO:363), Figure 260 (SEQ ID NO:365), Figure 262 (SEQ ID NO:367), Figure 264 (SEQ ID NO:369), Figure 266 (SEQ ID NO:371), Figure 268 (SEQ ID NO:373), Figure 270 (SEQ ID
NO:375), Figure 272 (SEQ
ID NO:377), Figure 274 (SEQ ID NO:379), Figure 276 (SEQ ID NO:381), Figure 278 (SEQ ID NO:387), Figure 280 (SEQ ID NO:389), Figure 282 (SEQ ID NO:394), Figure 284 (SEQ ID
NO:399), Figure 286 (SEQ
ID NO:401), Figure 288 (SEQ ID NO:403), Figure 290 (SEQ ID NO:408), Figure 292 (SEQ ID NO:410), Figure 294 (SEQ ID NO:412), Figure 296 (SEQ ID NO:414), Figure 298 (SEQ ID
NO:416), Figure 300 (SEQ
ID NO:418), Figure 302 (SEQ ID NO:420), Figure 304 (SEQ ID NO:422) and Figure 306 (SEQ ID NO:424).
2. The nucleic acid sequence of Claim 1, wherein said nucleotide sequence comprises a nucleotide sequence selected from the group consisting of the sequence shown in Figure 1 (SEQ ID NO:1), Figure 3 (SEQ
ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ
ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure S2 (SEQ ID
NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID NO:112), Figure 65 (SEQ
ID NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ ID NO:123), Figure 73 (SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID
NO:14S), Figure 84 (SEQ ID
NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID NO:152), Figure 92 (SEQ
ID NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ
ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ
ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ
ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ
ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ
ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ
ID NO:267), Figure 187 (SEQ ID NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ
ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ
ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ
ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ
ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 2S3 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ
ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ
ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ
ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ
ID NO:421) and Figure 305 (SEQ ID NO:423).
ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ
ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure S2 (SEQ ID
NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID NO:112), Figure 65 (SEQ
ID NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ ID NO:123), Figure 73 (SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID
NO:14S), Figure 84 (SEQ ID
NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID NO:152), Figure 92 (SEQ
ID NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ
ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ
ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ
ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ
ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ
ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ
ID NO:267), Figure 187 (SEQ ID NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ
ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ
ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ
ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ
ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 2S3 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ
ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ
ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ
ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ
ID NO:421) and Figure 305 (SEQ ID NO:423).
3. The nucleic acid of Claim 1, wherein said nucleotide sequence comprises a nucleotide sequence selected from the group consisting of the full-length coding sequence of the sequence shown in Figure 1 (SEQ
ID NO:1), Figure 3 (SEQ ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID
NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID
NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ
ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure 52 (SEQ ID NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID
NO:112), Figure 65 (SEQ ID
NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ
ID NO:123), Figure 73 (SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID NO:145), Figure 84 (SEQ ID NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID
NO:152), Figure 92 (SEQ ID
NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ
ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ ID NO:267), Figure 187 (SEQ ID NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 253 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ ID NO:421) or Figure 305 (SEQ ID NO:423).
ID NO:1), Figure 3 (SEQ ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID
NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID
NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ
ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure 52 (SEQ ID NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID
NO:112), Figure 65 (SEQ ID
NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ
ID NO:123), Figure 73 (SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID NO:145), Figure 84 (SEQ ID NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID
NO:152), Figure 92 (SEQ ID
NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ
ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ ID NO:267), Figure 187 (SEQ ID NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 253 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ ID NO:421) or Figure 305 (SEQ ID NO:423).
4. Isolated nucleic acid which comprises the full-length coding sequence of the DNA deposited under any ATCC accession number shown in Table 2.
5. A vector comprising the nucleic acid of Claim 1.
6. The vector of Claim 5 operably linked to control sequences recognized by a host cell transformed with the vector.
7. A host cell comprising the vector of Claim 5.
8. The host cell of Claim 7 wherein said cell is a CHO cell.
9. The host cell of Claim 7 wherein said cell is an E. coli.
10. The host cell of Claim 7 wherein said cell is a yeast cell.
11. A process for producing a PRO polypeptides comprising culturing the host cell of Claim 7 under conditions suitable for expression of said PRO polypeptide and recovering said PRO polypeptide from the cell culture.
12. Isolated PRO polypeptide having at least 80% sequence identity to an amino acid sequence selected from the group consisting of the amino acid sequence shown in Figure 2 (SEQ ID NO:2), Figure 4 (SEQ
ID NO:6), Figure 6 (SEQ ID NO:8), Figure 9 (SEQ ID NO:14), Figure 12 (SEQ ID
NO:20), Figure 15 (SEQ
ID NO:23), Figure 18 (SEQ ID NO:28), Figure 20 (SEQ ID NO:30), Figure 23 (SEQ
ID NO:33), Figure 25 (SEQ ID NO:36), Figure 27 (SEQ ID NO:41), Figure 30 (SEQ ID NO:47), Figure 32 (SEQ ID NO:52), Figure 34 (SEQ ID NO:57), Figure 36 (SEQ ID NO:62), Figure 38 (SEQ ID NO:67), Figure 41 (SEQ ID NO:73), Figure 47 (SEQ ID NO:84), Figure 49 (SEQ ID NO:95), Figure 51 (SEQ ID NO:97), Figure 53 (SEQ ID
NO:99), Figure 57 (SEQ ID NO:103), Figure 64 (SEQ ID NO:113), Figure 66 (SEQ
ID NO:115), Figure 68 (SEQ ID NO:117), Figure 70 (SEQ ID NO:119), Figure 72 (SEQ ID NO:124), Figure 74 (SEQ ID NO:129), Figure 76 (SEQ ID NO:135), Figure 79 (SEQ ID NO:138), Figure 83 (SEQ ID
NO:146), Figure 85 (SEQ ID
NO:148), Figure 88 (SEQ ID NO:151), Figure 90 (SEQ 1D NO:153), Figure 93 (SEQ
ID NO:156), Figure 95 (SEQ ID NO:158), Figure 97 (SEQ ID NO:160), Figure 99 (SEQ ID NO:165), Figure 101 (SEQ ID NO:167), Figure 103 (SEQ ID NO:169), Figure 105 (SEQ ID NO:171), Figure 109 (SEQ ID
NO:175), Figure 111 (SEQ
ID NO:177), Figure 113 (SEQ ID NO:I79), Figure 115 (SEQ ID NO:181), Figure 117 (SEQ ID NO:183), Figure 120 (SEQ ID NO:189), Figure 122 (SEQ ID NO:194), Figure 125 (SEQ ID
NO:197), Figure 127 (SEQ
ID NO:199), Figure 129 (SEQ ID NO:201), Figure 131 (SEQ ID NO:203), Figure 133 (SEQ ID NO:205), Figure 135 (SEQ ID NO:207), Figure 137 (SEQ ID NO:209), Figure 139 (SEQ ID
NO:211), Figure 141 (SEQ
ID NO:213), Figure 144 (SEQ ID NO:216), Figure 147 (SEQ ID NO:219), Figure 149 (SEQ ID NO:221), Figure 151 (SEQ ID NO:223), Figure 153 (SEQ ID NO:225), Figure 155 (SEQ ID
NO:227), Figure 157 (SEQ
ID NO:229), Figure 159 (SEQ ID NO:231), Figure 161 (SEQ ID NO:236), Figure 163 (SEQ ID NO:241), Figure 165 (SEQ ID NO:246), Figure 167 (SEQ ID NO:248), Figure 169 (SEQ ID
NO:250), Figure 171 (SEQ
ID NO:253), Figure 174 (SEQ ID NO:256), Figure 176 (SEQ ID NO:258), Figure 178 (SEQ ID NO:260), Figure 180 (SEQ ID NO:262), Figure 182 (SEQ ID NO:264), Figure 184 (SEQ ID
NO:266), Figure 186 (SEQ
ID NO:268), Figure 188 (SEQ ID NO:270), Figure 190 (SEQ ID NO:272), Figure 192 (SEQ ID NO:274), Figure 194 (SEQ ID NO:276), Figure 196 (SEQ ID NO:278), Figure 198 (SEQ ID
NO:281), Figure 200 (SEQ
ID NO:283), Figure 202 (SEQ ID NO:285), Figure 204 (SEQ ID NO:287), Figure 206 (SEQ ID NO:289), Figure 208 (SEQ ID NO:291), Figure 210 (SEQ ID NO:293), Figure 212 (SEQ ID
NO:295), Figure 214 (SEQ
ID NO:297), Figure 216 (SEQ ID NO:299), Figure 218 (SEQ ID NO:301), Figure 220 (SEQ ID NO:303), Figure 226 (SEQ ID NO:309), Figure 228 (SEQ ID NO:314), Figure 230 (SEQ ID
NO:319), Figure 233 (SEQ
ID NO:326), Figure 235 (SEQ ID NO:334), Figure 238 (SEQ ID NO:340), Figure 240 (SEQ ID NO:345), Figure 242 (SEQ ID NO:347), Figure 244 (SEQ ID NO:349), Figure 246 (SEQ ID
NO:351), Figure 248 (SEQ
ID NO:353), Figure 250 (SEQ ID NO:355), Figure 252 (SEQ ID NO:357), Figure 254 (SEQ ID NO:359), Figure 256 (SEQ ID NO:361), Figure 258 (SEQ ID NO:363), Figure 260 (SEQ ID
NO:365), Figure 262 (SEQ
ID NO:367), Figure 264 (SEQ ID NO:369), Figure 266 (SEQ ID NO:371), Figure 268 (SEQ ID NO:373), Figure 270 (SEQ ID NO:375), Figure 272 (SEQ ID NO:377), Figure 274 (SEQ ID
NO:379), Figure 276 (SEQ
ID NO:381), Figure 278 (SEQ ID NO:387), Figure 280 (SEQ ID NO:389), Figure 282 (SEQ ID NO:394), Figure 284 (SEQ ID NO:399), Figure 286 (SEQ ID NO:401), Figure 288 (SEQ ID
NO:403), Figure 290 (SEQ
ID NO:408), Figure 292 (SEQ ID NO:410), Figure 294 (SEQ ID NO:412), Figure 296 (SEQ ID NO:414), Figure 298 (SEQ ID NO:416), Figure 300 (SEQ ID NO:418), Figure 302 (SEQ ID
NO:420), Figure 304 (SEQ
ID NO:422) and Figure 306 (SEQ ID NO:424).
ID NO:6), Figure 6 (SEQ ID NO:8), Figure 9 (SEQ ID NO:14), Figure 12 (SEQ ID
NO:20), Figure 15 (SEQ
ID NO:23), Figure 18 (SEQ ID NO:28), Figure 20 (SEQ ID NO:30), Figure 23 (SEQ
ID NO:33), Figure 25 (SEQ ID NO:36), Figure 27 (SEQ ID NO:41), Figure 30 (SEQ ID NO:47), Figure 32 (SEQ ID NO:52), Figure 34 (SEQ ID NO:57), Figure 36 (SEQ ID NO:62), Figure 38 (SEQ ID NO:67), Figure 41 (SEQ ID NO:73), Figure 47 (SEQ ID NO:84), Figure 49 (SEQ ID NO:95), Figure 51 (SEQ ID NO:97), Figure 53 (SEQ ID
NO:99), Figure 57 (SEQ ID NO:103), Figure 64 (SEQ ID NO:113), Figure 66 (SEQ
ID NO:115), Figure 68 (SEQ ID NO:117), Figure 70 (SEQ ID NO:119), Figure 72 (SEQ ID NO:124), Figure 74 (SEQ ID NO:129), Figure 76 (SEQ ID NO:135), Figure 79 (SEQ ID NO:138), Figure 83 (SEQ ID
NO:146), Figure 85 (SEQ ID
NO:148), Figure 88 (SEQ ID NO:151), Figure 90 (SEQ 1D NO:153), Figure 93 (SEQ
ID NO:156), Figure 95 (SEQ ID NO:158), Figure 97 (SEQ ID NO:160), Figure 99 (SEQ ID NO:165), Figure 101 (SEQ ID NO:167), Figure 103 (SEQ ID NO:169), Figure 105 (SEQ ID NO:171), Figure 109 (SEQ ID
NO:175), Figure 111 (SEQ
ID NO:177), Figure 113 (SEQ ID NO:I79), Figure 115 (SEQ ID NO:181), Figure 117 (SEQ ID NO:183), Figure 120 (SEQ ID NO:189), Figure 122 (SEQ ID NO:194), Figure 125 (SEQ ID
NO:197), Figure 127 (SEQ
ID NO:199), Figure 129 (SEQ ID NO:201), Figure 131 (SEQ ID NO:203), Figure 133 (SEQ ID NO:205), Figure 135 (SEQ ID NO:207), Figure 137 (SEQ ID NO:209), Figure 139 (SEQ ID
NO:211), Figure 141 (SEQ
ID NO:213), Figure 144 (SEQ ID NO:216), Figure 147 (SEQ ID NO:219), Figure 149 (SEQ ID NO:221), Figure 151 (SEQ ID NO:223), Figure 153 (SEQ ID NO:225), Figure 155 (SEQ ID
NO:227), Figure 157 (SEQ
ID NO:229), Figure 159 (SEQ ID NO:231), Figure 161 (SEQ ID NO:236), Figure 163 (SEQ ID NO:241), Figure 165 (SEQ ID NO:246), Figure 167 (SEQ ID NO:248), Figure 169 (SEQ ID
NO:250), Figure 171 (SEQ
ID NO:253), Figure 174 (SEQ ID NO:256), Figure 176 (SEQ ID NO:258), Figure 178 (SEQ ID NO:260), Figure 180 (SEQ ID NO:262), Figure 182 (SEQ ID NO:264), Figure 184 (SEQ ID
NO:266), Figure 186 (SEQ
ID NO:268), Figure 188 (SEQ ID NO:270), Figure 190 (SEQ ID NO:272), Figure 192 (SEQ ID NO:274), Figure 194 (SEQ ID NO:276), Figure 196 (SEQ ID NO:278), Figure 198 (SEQ ID
NO:281), Figure 200 (SEQ
ID NO:283), Figure 202 (SEQ ID NO:285), Figure 204 (SEQ ID NO:287), Figure 206 (SEQ ID NO:289), Figure 208 (SEQ ID NO:291), Figure 210 (SEQ ID NO:293), Figure 212 (SEQ ID
NO:295), Figure 214 (SEQ
ID NO:297), Figure 216 (SEQ ID NO:299), Figure 218 (SEQ ID NO:301), Figure 220 (SEQ ID NO:303), Figure 226 (SEQ ID NO:309), Figure 228 (SEQ ID NO:314), Figure 230 (SEQ ID
NO:319), Figure 233 (SEQ
ID NO:326), Figure 235 (SEQ ID NO:334), Figure 238 (SEQ ID NO:340), Figure 240 (SEQ ID NO:345), Figure 242 (SEQ ID NO:347), Figure 244 (SEQ ID NO:349), Figure 246 (SEQ ID
NO:351), Figure 248 (SEQ
ID NO:353), Figure 250 (SEQ ID NO:355), Figure 252 (SEQ ID NO:357), Figure 254 (SEQ ID NO:359), Figure 256 (SEQ ID NO:361), Figure 258 (SEQ ID NO:363), Figure 260 (SEQ ID
NO:365), Figure 262 (SEQ
ID NO:367), Figure 264 (SEQ ID NO:369), Figure 266 (SEQ ID NO:371), Figure 268 (SEQ ID NO:373), Figure 270 (SEQ ID NO:375), Figure 272 (SEQ ID NO:377), Figure 274 (SEQ ID
NO:379), Figure 276 (SEQ
ID NO:381), Figure 278 (SEQ ID NO:387), Figure 280 (SEQ ID NO:389), Figure 282 (SEQ ID NO:394), Figure 284 (SEQ ID NO:399), Figure 286 (SEQ ID NO:401), Figure 288 (SEQ ID
NO:403), Figure 290 (SEQ
ID NO:408), Figure 292 (SEQ ID NO:410), Figure 294 (SEQ ID NO:412), Figure 296 (SEQ ID NO:414), Figure 298 (SEQ ID NO:416), Figure 300 (SEQ ID NO:418), Figure 302 (SEQ ID
NO:420), Figure 304 (SEQ
ID NO:422) and Figure 306 (SEQ ID NO:424).
13. Isolated PRO polypeptide having at least 80 % sequence identity to the amino acid sequence encoded by a nucleic acid molecule deposited under any ATCC accession number shown in Table 2.
14. A chimeric molecule comprising a polypeptide according to Claim 12 fused to a heterologous amino acid sequence.
15. The chimeric molecule of Claim 14 wherein said heterologous amino acid sequence is an epitope tag sequence.
16. The chimeric molecule of Claim 14 wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin.
17. An antibody which specifically binds to a PRO polypeptide according to Claim 12.
18. The antibody of Claim 17 wherein said antibody is a monoclonal antibody.
19. The antibody of Claim 17 wherein said antibody is a humanized antibody.
20. The antibody of Claim 17 wherein said antibody is an antibody fragment.
21. An isolated nucleic acid molecule which has at least 80% sequence identity to a nucleic acid which comprises a nucleotide sequence selected from the group consisting of that shown in Figure 1 (SEQ ID
NO:1), Figure 3 (SEQ ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID
NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID
NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ
ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure 52 (SEQ ID NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID
NO:112), Figure 65 (SEQ ID
NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ
ID NO:123), Figure 73 {SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID NO:145), Figure 84 (SEQ ID NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID
NO:152), Figure 92 (SEQ ID
NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ
ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ ID NO:267), Figure 187 (SEQ ID NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 253 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ ID NO:421) and Figure 305 (SEQ ID NO:423).
NO:1), Figure 3 (SEQ ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID
NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID
NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ
ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure 52 (SEQ ID NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID
NO:112), Figure 65 (SEQ ID
NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ
ID NO:123), Figure 73 {SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID NO:145), Figure 84 (SEQ ID NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID
NO:152), Figure 92 (SEQ ID
NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ
ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ ID NO:267), Figure 187 (SEQ ID NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 253 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ ID NO:421) and Figure 305 (SEQ ID NO:423).
22. An isolated nucleic acid molecule which has at least 80% sequence identity to the full-length coding sequence of a nucleotide sequence selected from the group consisting of that shown in Figure 1 (SEQ ID
NO:1), Figure 3 (SEQ ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID
NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID
NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ
ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure 52 (SEQ ID NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID
NO:112), Figure 65 (SEQ ID
NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ
ID NO:123), Figure 73 (SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID NO:145), Figure 84 (SEQ ID NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID
NO:152), Figure 92 (SEQ ID
NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ
ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ ID NO:267), Figure 187 (SEQ 1D NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 253 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ ID NO:421) and Figure 305 (SEQ ID NO:423).
NO:1), Figure 3 (SEQ ID NO:5), Figure 5 (SEQ ID NO:7), Figure 8 (SEQ ID
NO:13), Figure 11 (SEQ ID
NO:19), Figure 14 (SEQ ID NO:22), Figure 17 (SEQ ID NO:27), Figure 19 (SEQ ID
NO:29), Figure 22 (SEQ
ID NO:32), Figure 24 (SEQ ID NO:35), Figure 26 (SEQ ID NO:40), Figure 29 (SEQ
ID NO:46), Figure 31 (SEQ ID NO:51), Figure 33 (SEQ ID NO:56), Figure 35 (SEQ ID NO:61), Figure 37 (SEQ ID NO:66), Figure 40 (SEQ ID NO:72), Figure 46 (SEQ ID NO:83), Figure 48 (SEQ ID NO:94), Figure 50 (SEQ ID NO:96), Figure 52 (SEQ ID NO:98), Figure 56 (SEQ ID NO:102), Figure 63 (SEQ ID
NO:112), Figure 65 (SEQ ID
NO:114), Figure 67 (SEQ ID NO:116), Figure 69 (SEQ ID NO:118), Figure 71 (SEQ
ID NO:123), Figure 73 (SEQ ID NO:128), Figure 75 (SEQ ID NO:134), Figure 78 (SEQ ID NO:137), Figure 82 (SEQ ID NO:145), Figure 84 (SEQ ID NO:147), Figure 87 (SEQ ID NO:150), Figure 89 (SEQ ID
NO:152), Figure 92 (SEQ ID
NO:155), Figure 94 (SEQ ID NO:157), Figure 96 (SEQ ID NO:159), Figure 98 (SEQ
ID NO:164), Figure 100 (SEQ ID NO:166), Figure 102 (SEQ ID NO:168), Figure 104 (SEQ ID NO:170), Figure 108 (SEQ ID
NO:174), Figure 110 (SEQ ID NO:176), Figure 112 (SEQ ID NO:178), Figure 114 (SEQ ID NO:180), Figure 116 (SEQ ID NO:182), Figure 119 (SEQ ID NO:188), Figure 121 (SEQ ID NO:193), Figure 124 (SEQ ID
NO:196), Figure 126 (SEQ ID NO:198), Figure 128 (SEQ ID NO:200), Figure 130 (SEQ ID NO:202), Figure 132 (SEQ ID NO:204), Figure 134 (SEQ ID NO:206), Figure 136 (SEQ ID NO:208), Figure 138 (SEQ ID
NO:210), Figure 140 (SEQ ID NO:212), Figure 143 (SEQ ID NO:215), Figure 146 (SEQ ID NO:218), Figure 148 (SEQ ID NO:220), Figure 150 (SEQ ID NO:222), Figure 152 (SEQ ID NO:224), Figure 154 (SEQ ID
NO:226), Figure 156 (SEQ ID NO:228), Figure 158 (SEQ ID NO:230), Figure 160 (SEQ ID NO:235), Figure 162 (SEQ ID NO:240), Figure 164 (SEQ ID NO:245), Figure 166 (SEQ ID NO:247), Figure 168 (SEQ ID
NO:249), Figure 170 (SEQ ID NO:252), Figure 173 (SEQ ID NO:255), Figure 175 (SEQ ID NO:257), Figure 177 (SEQ ID NO:259), Figure 179 (SEQ ID NO:261), Figure 181 (SEQ ID NO:263), Figure 183 (SEQ ID
NO:265), Figure 185 (SEQ ID NO:267), Figure 187 (SEQ 1D NO:269), Figure 189 (SEQ ID NO:271), Figure 191 (SEQ ID NO:273), Figure 193 (SEQ ID NO:275), Figure 195 (SEQ ID NO:277), Figure 197 (SEQ ID
NO:280), Figure 199 (SEQ ID NO:282), Figure 201 (SEQ ID NO:284), Figure 203 (SEQ ID NO:286), Figure 205 (SEQ ID NO:288), Figure 207 (SEQ ID NO:290), Figure 209 (SEQ ID NO:292), Figure 211 (SEQ ID
NO:294), Figure 213 (SEQ ID NO:296), Figure 215 (SEQ ID NO:298), Figure 217 (SEQ ID NO:300), Figure 219 (SEQ ID NO:302), Figure 225 (SEQ ID NO:308), Figure 227 (SEQ ID NO:313), Figure 229 (SEQ ID
NO:318), Figure 232 (SEQ ID NO:325), Figure 234 (SEQ ID NO:333), Figure 237 (SEQ ID NO:339), Figure 239 (SEQ ID NO:344), Figure 241 (SEQ ID NO:346), Figure 243 (SEQ ID NO:348), Figure 245 (SEQ ID
NO:350), Figure 247 (SEQ ID NO:352), Figure 249 (SEQ ID NO:354), Figure 251 (SEQ ID NO:356), Figure 253 (SEQ ID NO:358), Figure 255 (SEQ ID NO:360), Figure 257 (SEQ ID NO:362), Figure 259 (SEQ ID
NO:364), Figure 261 (SEQ ID NO:366), Figure 263 (SEQ ID NO:368), Figure 265 (SEQ ID NO:370), Figure 267 (SEQ ID NO:372), Figure 269 (SEQ ID NO:374), Figure 271 (SEQ ID NO:376), Figure 273 (SEQ ID
NO:378), Figure 275 (SEQ ID NO:380), Figure 277 (SEQ ID NO:386), Figure 279 (SEQ ID NO:388), Figure 281 (SEQ ID NO:393), Figure 283 (SEQ ID NO:398), Figure 285 (SEQ ID NO:400), Figure 287 (SEQ ID
NO:402), Figure 289 (SEQ ID NO:407), Figure 291 (SEQ ID NO:409), Figure 293 (SEQ ID NO:411), Figure 295 (SEQ ID NO:413), Figure 297 (SEQ ID NO:415), Figure 299 (SEQ ID NO:417), Figure 301 (SEQ ID
NO:419), Figure 303 (SEQ ID NO:421) and Figure 305 (SEQ ID NO:423).
23. An isolated extracellular domain of of PRO polypeptide.
24. An isolated PRO polypeptide lacking its associated signal peptide.
25. An isolated polypeptide having at least about 80% amino acid sequence identity to an extracellular domain of of PRO polypeptide.
26. An isolated polypeptide having at least about 80 % amino acid sequence identity to a PRO
polypeptide lacking its associated signal peptide.
polypeptide lacking its associated signal peptide.
Applications Claiming Priority (235)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8760998P | 1998-06-02 | 1998-06-02 | |
| US8760798P | 1998-06-02 | 1998-06-02 | |
| US8775998P | 1998-06-02 | 1998-06-02 | |
| US60/087,607 | 1998-06-02 | ||
| US60/087,609 | 1998-06-02 | ||
| US60/087,759 | 1998-06-02 | ||
| US8782798P | 1998-06-03 | 1998-06-03 | |
| US60/087,827 | 1998-06-03 | ||
| US8802598P | 1998-06-04 | 1998-06-04 | |
| US8802198P | 1998-06-04 | 1998-06-04 | |
| US8803398P | 1998-06-04 | 1998-06-04 | |
| US8802998P | 1998-06-04 | 1998-06-04 | |
| US8802898P | 1998-06-04 | 1998-06-04 | |
| US8832698P | 1998-06-04 | 1998-06-04 | |
| US8803098P | 1998-06-04 | 1998-06-04 | |
| US60/088,326 | 1998-06-04 | ||
| US60/088,025 | 1998-06-04 | ||
| US60/088,021 | 1998-06-04 | ||
| US60/088,030 | 1998-06-04 | ||
| US60/088,033 | 1998-06-04 | ||
| US60/088,029 | 1998-06-04 | ||
| US60/088,028 | 1998-06-04 | ||
| US8820298P | 1998-06-05 | 1998-06-05 | |
| US8816798P | 1998-06-05 | 1998-06-05 | |
| US8821298P | 1998-06-05 | 1998-06-05 | |
| US8821798P | 1998-06-05 | 1998-06-05 | |
| US60/088,167 | 1998-06-05 | ||
| US60/088,217 | 1998-06-05 | ||
| US60/088,212 | 1998-06-05 | ||
| US60/088,202 | 1998-06-05 | ||
| US8865598P | 1998-06-09 | 1998-06-09 | |
| US60/088,655 | 1998-06-09 | ||
| US8872298P | 1998-06-10 | 1998-06-10 | |
| US8874298P | 1998-06-10 | 1998-06-10 | |
| US8873498P | 1998-06-10 | 1998-06-10 | |
| US8873898P | 1998-06-10 | 1998-06-10 | |
| US8881098P | 1998-06-10 | 1998-06-10 | |
| US8882598P | 1998-06-10 | 1998-06-10 | |
| US8874198P | 1998-06-10 | 1998-06-10 | |
| US8881198P | 1998-06-10 | 1998-06-10 | |
| US8882498P | 1998-06-10 | 1998-06-10 | |
| US8882698P | 1998-06-10 | 1998-06-10 | |
| US8874098P | 1998-06-10 | 1998-06-10 | |
| US8873098P | 1998-06-10 | 1998-06-10 | |
| US60/088,738 | 1998-06-10 | ||
| US60/088,730 | 1998-06-10 | ||
| US60/088,722 | 1998-06-10 | ||
| US60/088,741 | 1998-06-10 | ||
| US60/088,811 | 1998-06-10 | ||
| US60/088,742 | 1998-06-10 | ||
| US60/088,810 | 1998-06-10 | ||
| US60/088,824 | 1998-06-10 | ||
| US60/088,740 | 1998-06-10 | ||
| US60/088,825 | 1998-06-10 | ||
| US60/088,734 | 1998-06-10 | ||
| US60/088,826 | 1998-06-10 | ||
| US8885898P | 1998-06-11 | 1998-06-11 | |
| US8886398P | 1998-06-11 | 1998-06-11 | |
| US8887698P | 1998-06-11 | 1998-06-11 | |
| US8886198P | 1998-06-11 | 1998-06-11 | |
| US60/088,861 | 1998-06-11 | ||
| US60/088,858 | 1998-06-11 | ||
| US60/088,863 | 1998-06-11 | ||
| US60/088,876 | 1998-06-11 | ||
| US8909098P | 1998-06-12 | 1998-06-12 | |
| US8910598P | 1998-06-12 | 1998-06-12 | |
| US60/089,105 | 1998-06-12 | ||
| US60/089,090 | 1998-06-12 | ||
| US8951298P | 1998-06-16 | 1998-06-16 | |
| US8944098P | 1998-06-16 | 1998-06-16 | |
| US8951498P | 1998-06-16 | 1998-06-16 | |
| US60/089,512 | 1998-06-16 | ||
| US60/089,514 | 1998-06-16 | ||
| US60/089,440 | 1998-06-16 | ||
| US8960098P | 1998-06-17 | 1998-06-17 | |
| US8953298P | 1998-06-17 | 1998-06-17 | |
| US8959998P | 1998-06-17 | 1998-06-17 | |
| US8959898P | 1998-06-17 | 1998-06-17 | |
| US8953898P | 1998-06-17 | 1998-06-17 | |
| US8965398P | 1998-06-17 | 1998-06-17 | |
| US60/089,653 | 1998-06-17 | ||
| US60/089,600 | 1998-06-17 | ||
| US60/089,599 | 1998-06-17 | ||
| US60/089,598 | 1998-06-17 | ||
| US60/089,538 | 1998-06-17 | ||
| US60/089,532 | 1998-06-17 | ||
| US8990898P | 1998-06-18 | 1998-06-18 | |
| US8990798P | 1998-06-18 | 1998-06-18 | |
| US8980198P | 1998-06-18 | 1998-06-18 | |
| US60/089,801 | 1998-06-18 | ||
| US60/089,907 | 1998-06-18 | ||
| US60/089,908 | 1998-06-18 | ||
| US8994898P | 1998-06-19 | 1998-06-19 | |
| US8994798P | 1998-06-19 | 1998-06-19 | |
| US8995298P | 1998-06-19 | 1998-06-19 | |
| US60/089,948 | 1998-06-19 | ||
| US60/089,947 | 1998-06-19 | ||
| US60/089,952 | 1998-06-19 | ||
| US9025298P | 1998-06-22 | 1998-06-22 | |
| US9025498P | 1998-06-22 | 1998-06-22 | |
| US9024698P | 1998-06-22 | 1998-06-22 | |
| US60/090,254 | 1998-06-22 | ||
| US60/090,246 | 1998-06-22 | ||
| US60/090,252 | 1998-06-22 | ||
| US9034998P | 1998-06-23 | 1998-06-23 | |
| US9035598P | 1998-06-23 | 1998-06-23 | |
| US60/090,349 | 1998-06-23 | ||
| US60/090,355 | 1998-06-23 | ||
| US9047298P | 1998-06-24 | 1998-06-24 | |
| US9044598P | 1998-06-24 | 1998-06-24 | |
| US9044498P | 1998-06-24 | 1998-06-24 | |
| US9046198P | 1998-06-24 | 1998-06-24 | |
| US9043598P | 1998-06-24 | 1998-06-24 | |
| US9053898P | 1998-06-24 | 1998-06-24 | |
| US9053598P | 1998-06-24 | 1998-06-24 | |
| US9055798P | 1998-06-24 | 1998-06-24 | |
| US9054098P | 1998-06-24 | 1998-06-24 | |
| US9042998P | 1998-06-24 | 1998-06-24 | |
| US9043198P | 1998-06-24 | 1998-06-24 | |
| US60/090,538 | 1998-06-24 | ||
| US60/090,557 | 1998-06-24 | ||
| US60/090,535 | 1998-06-24 | ||
| US60/090,435 | 1998-06-24 | ||
| US60/090,444 | 1998-06-24 | ||
| US60/090,431 | 1998-06-24 | ||
| US60/090,429 | 1998-06-24 | ||
| US60/090,445 | 1998-06-24 | ||
| US60/090,472 | 1998-06-24 | ||
| US60/090,540 | 1998-06-24 | ||
| US60/090,461 | 1998-06-24 | ||
| US9068898P | 1998-06-25 | 1998-06-25 | |
| US9069698P | 1998-06-25 | 1998-06-25 | |
| US9069198P | 1998-06-25 | 1998-06-25 | |
| US9067698P | 1998-06-25 | 1998-06-25 | |
| US9069598P | 1998-06-25 | 1998-06-25 | |
| US9069498P | 1998-06-25 | 1998-06-25 | |
| US9069098P | 1998-06-25 | 1998-06-25 | |
| US9067898P | 1998-06-25 | 1998-06-25 | |
| US60/090,690 | 1998-06-25 | ||
| US60/090,694 | 1998-06-25 | ||
| US60/090,688 | 1998-06-25 | ||
| US60/090,695 | 1998-06-25 | ||
| US60/090,691 | 1998-06-25 | ||
| US60/090,676 | 1998-06-25 | ||
| US60/090,678 | 1998-06-25 | ||
| US60/090,696 | 1998-06-25 | ||
| US9086398P | 1998-06-26 | 1998-06-26 | |
| US9086298P | 1998-06-26 | 1998-06-26 | |
| US60/090,862 | 1998-06-26 | ||
| US60/090,863 | 1998-06-26 | ||
| US9135898P | 1998-07-01 | 1998-07-01 | |
| US9136098P | 1998-07-01 | 1998-07-01 | |
| US9154498P | 1998-07-01 | 1998-07-01 | |
| US60/091,544 | 1998-07-01 | ||
| US60/091,358 | 1998-07-01 | ||
| US60/091,360 | 1998-07-01 | ||
| US9163398P | 1998-07-02 | 1998-07-02 | |
| US9167398P | 1998-07-02 | 1998-07-02 | |
| US9162698P | 1998-07-02 | 1998-07-02 | |
| US9147898P | 1998-07-02 | 1998-07-02 | |
| US9162898P | 1998-07-02 | 1998-07-02 | |
| US9148698P | 1998-07-02 | 1998-07-02 | |
| US9164698P | 1998-07-02 | 1998-07-02 | |
| US9151998P | 1998-07-02 | 1998-07-02 | |
| US60/091,478 | 1998-07-02 | ||
| US60/091,628 | 1998-07-02 | ||
| US60/091,646 | 1998-07-02 | ||
| US60/091,519 | 1998-07-02 | ||
| US60/091,673 | 1998-07-02 | ||
| US60/091,486 | 1998-07-02 | ||
| US60/091,633 | 1998-07-02 | ||
| US60/091,626 | 1998-07-02 | ||
| US9198298P | 1998-07-07 | 1998-07-07 | |
| US9197898P | 1998-07-07 | 1998-07-07 | |
| US60/091,978 | 1998-07-07 | ||
| US60/091,982 | 1998-07-07 | ||
| US9218298P | 1998-07-09 | 1998-07-09 | |
| US60/092,182 | 1998-07-09 | ||
| US9247298P | 1998-07-10 | 1998-07-10 | |
| US60/092,472 | 1998-07-10 | ||
| US9333998P | 1998-07-20 | 1998-07-20 | |
| US60/093,339 | 1998-07-20 | ||
| US9465198P | 1998-07-30 | 1998-07-30 | |
| US60/094,651 | 1998-07-30 | ||
| US9532598P | 1998-08-04 | 1998-08-04 | |
| US9531898P | 1998-08-04 | 1998-08-04 | |
| US9530298P | 1998-08-04 | 1998-08-04 | |
| US9532198P | 1998-08-04 | 1998-08-04 | |
| US9528598P | 1998-08-04 | 1998-08-04 | |
| US9528298P | 1998-08-04 | 1998-08-04 | |
| US9530198P | 1998-08-04 | 1998-08-04 | |
| US60/095,302 | 1998-08-04 | ||
| US60/095,282 | 1998-08-04 | ||
| US60/095,285 | 1998-08-04 | ||
| US60/095,318 | 1998-08-04 | ||
| US60/095,301 | 1998-08-04 | ||
| US60/095,325 | 1998-08-04 | ||
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| US60/095,916 | 1998-08-10 | ||
| US60/096,012 | 1998-08-10 | ||
| US60/096,143 | 1998-08-11 | ||
| US60/096,146 | 1998-08-11 | ||
| US60/096,329 | 1998-08-12 | ||
| US60/096,791 | 1998-08-17 | ||
| US60/096,897 | 1998-08-17 | ||
| US60/096,895 | 1998-08-17 | ||
| US60/096,766 | 1998-08-17 | ||
| US60/096,757 | 1998-08-17 | ||
| US60/096,891 | 1998-08-17 | ||
| US60/096,768 | 1998-08-17 | ||
| US60/096,867 | 1998-08-17 | ||
| US60/096,773 | 1998-08-17 | ||
| US60/096,894 | 1998-08-17 | ||
| US60/096,949 | 1998-08-18 | ||
| US60/096,959 | 1998-08-18 | ||
| US60/096,960 | 1998-08-18 | ||
| US60/096,950 | 1998-08-18 | ||
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| US60/097,218 | 1998-08-20 | ||
| US60/097,661 | 1998-08-24 | ||
| US60/098,014 | 1998-08-26 | ||
| US60/097,978 | 1998-08-26 | ||
| US60/097,952 | 1998-08-26 | ||
| US60/097,986 | 1998-08-26 | ||
| US60/097,955 | 1998-08-26 | ||
| US60/097,979 | 1998-08-26 | ||
| US60/097,954 | 1998-08-26 | ||
| US60/097,971 | 1998-08-26 | ||
| US60/097,974 | 1998-08-26 | ||
| US60/097,951 | 1998-08-26 | ||
| US60/098,525 | 1998-08-31 | ||
| US60/100,634 | 1998-09-16 | ||
| US60/115,565 | 1999-01-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2328895A1 true CA2328895A1 (en) | 1999-12-09 |
Family
ID=27587108
Family Applications (1)
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| CA002328895A Abandoned CA2328895A1 (en) | 1998-06-02 | 1999-06-02 | Secreted and transmembrane polypeptides and nucleic acids encoding the same |
Country Status (3)
| Country | Link |
|---|---|
| CA (1) | CA2328895A1 (en) |
| IL (1) | IL139686A0 (en) |
| WO (1) | WO1999063088A2 (en) |
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| JP2879303B2 (en) * | 1993-01-14 | 1999-04-05 | 佑 本庶 | Method for preparing cDNA library, novel polypeptide and DNA encoding the same |
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-
1999
- 1999-06-02 IL IL13968699A patent/IL139686A0/en not_active IP Right Cessation
- 1999-06-02 WO PCT/US1999/012252 patent/WO1999063088A2/en not_active Ceased
- 1999-06-02 CA CA002328895A patent/CA2328895A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999063088A3 (en) | 2001-03-29 |
| IL139686A0 (en) | 2002-02-10 |
| WO1999063088A8 (en) | 2000-10-19 |
| WO1999063088A2 (en) | 1999-12-09 |
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| FZDE | Discontinued |