CA2291260A1 - 207 human secreted proteins - Google Patents
207 human secreted proteins Download PDFInfo
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- CA2291260A1 CA2291260A1 CA002291260A CA2291260A CA2291260A1 CA 2291260 A1 CA2291260 A1 CA 2291260A1 CA 002291260 A CA002291260 A CA 002291260A CA 2291260 A CA2291260 A CA 2291260A CA 2291260 A1 CA2291260 A1 CA 2291260A1
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- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
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Abstract
The present invention relates to 207 novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human secreted proteins.
Description
DEMANDES OU BREVETS VOLUMINEUX
LA PRESE1NTE PART1E DE C~TTE DEMANDE OU C~ BREVET
COMPREND PLUS D'UN TOME.
CECt EST LE TOME . ~ DE
NOTE: Pour tes tomes additionels, veuitlez contacter le Bureau canadien des brevets 'JUMBO APP1.lCATIONS/PATENTS -THIS SECT10N OF THE APPUCAT10N/PATENT CONTAINS MORE' THAN ONE VOLUME ~ , , THfS tS VOLUME _ 01=
' NOTE: Eor additional volumes-piease~contact the Canadian Patent Office .
207 Human Secreted Proteins Field of the Invention This invention relates to newly identified polynucleotides and the polypeptides encoded by these polynucleotides, uses of such polynucleotides and polypeptides, and their production.
Background of the Invention Unlike bacterium, which exist as a single compartment surrounded by a membrane, human cells and other eucaryotes are subdivided by membranes into many functionally distinct compartments. Each membrane-bounded compartment, or organelle, contains different proteins essential for the function of the organelle. The cell uses "sorting signals," which are amino acid motifs located within the protein, to target proteins to particular cellular organelles.
One type of sorting signal, called a signal sequence, a signal peptide, or a leader sequence, directs a class of proteins to an organelle called the endoplasmic reticulum (ER). The ER separates the membrane-bounded proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus. Here, the Golgi distributes the proteins to vesicles, including secretory vesicles, the cell membrane, lysosomes, and the other organelles.
Proteins targeted to the ER by a signal sequence can be released into the extracellular space as a secreted protein. For example, vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space - a process called exocytosis. Exocytosis can occur constitutively or after receipt of a triggering signal. In the latter case, the proteins are stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins residing on the cell membrane can also be secreted into the extracellular space by proteolytic cleavage of a "linker" holding the protein to the membrane.
Despite the great progress made in recent years, only a small number of genes encoding human secreted proteins have been identified. These secreted proteins include the commercially valuable human insulin, interferon, Factor VIII, human growth hormone, tissue plasminogen activator, and erythropoeitin. Thus, in light of the pervasive role of secreted proteins in human physiology, a need exists for identifying and characterizing novel human secreted proteins and the genes that encode them. This knowledge will allow one to detect, to treat, and to prevent medical disorders by using secreted proteins or the genes that encode them.
Summary of the Invention The present invention relates to novel polynucleotides and the encoded polypeptides. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides.
Also provided are diagnostic methods for detecting disorders related to the polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of the polypeptides.
Detailed Description Definitions The following definitions are provided to facilitate understanding of certain terms used throughout this specification.
In the present invention, "isolated" refers to material removed from its original environment (e.g., the natural environment if it is naturally occurring), and thus is altered "by the hand of man" from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be "isolated" because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide.
In the present invention, a "secreted" protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a "mature" protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage.
As used herein , a "polynucleotide" refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X or the cDNA contained within the clone deposited with the ATCC. For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5' and 3' untranslated sequences, the coding region, with or without the signal sequence, the secreted protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence.
Moreover, as used herein, a "polypeptide" refers to a molecule having the translated amino acid sequence generated from the polynucleotide as broadly defined.
In the present invention, the full length sequence identified as SEQ ID NO:X
was often generated by overlapping sequences contained in multiple clones (contig analysis). A representative clone containing all or most of the sequence for SEQ ID
NO:X was deposited with the American Type Culture Collection ("ATCC"). As shown in Table l, each clone is identified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number. The ATCC is located at 10801 University Boulevard, Manassas, Virginia 20110-2209, USA. The ATCC deposit was made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for purposes of patent procedure.
A "polynucleotide" of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, the complement thereof, or the eDNA within the clone deposited with the ATCC. "Stringent hybridization conditions" refers to an overnight incubation at 42°
C in a solution comprising 50% formamide, Sx SSC (750 mM NaCI, 75 mM sodium citrate), 50 mM sodium phosphate {pH 7.6), Sx Denhardt's solution, 10% dextran sulfate, and 20 pg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in O.lx SSC at about 65°C.
Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions.
Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature.
For example, lower stringency conditions include an overnight incubation at 37°C in a solution comprising 6X SSPE (20X SSPE = 3M NaCI; 0.2M NaH~P04; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 ug/ml salmon sperm blocking DNA;
followed by washes at 50°C with 1XSSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5X SSC}.
Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations. The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.
Of course, a polynucleotide which hybridizes only to polyA+ sequences (such as any 3' terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of "polynucleotide," since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone).
The polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified-RNA or DNA
or modified RNA or DNA. For example, polynucleotides can be composed of single-and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single-and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single-and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability I S or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA
and RNA; thus, "polynucleotide" embraces chemically, enzymatically, or metabolically modified forms.
The polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art.
Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched , for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods.
Modifications include acetylation, acyiation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links. formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI
anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, . selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins 5 such as arginylation, and ubiquitination. (See, for instance, PROTEINS -p STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E. Creighton, W.
H. Freeman and Company, New York ( 1993); POSTTRANSLATIONAL
COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York, pgs. 1-12 (1983); Seifter et al., Meth Enzymol 182:626-646 (1990);
Rattan et al., Ann NY Acad Sci 663:48-62 ( 1992).) "SEQ ID NO:X" refers to a polynucleotide sequence while "SEQ ID NO:Y"
refers to a polypeptide sequence, both sequences identified by an integer specified in Table 1.
"A polypeptide having biological activity" refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention.) Polvnucleotides and Poly~eptides of the Invention FEATURES OF PROTEIN ENCODED BY GENE NO: 1 This gene is expressed primarily in melanocytes and, to a lesser extent, in testes, ovary, kidney and other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer, disorders of neural crest derived cells including pigmentation defects, melanoma, reproductive organ defects, and defects of the kidney.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skin, reproductive, and renal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders that arise from alterations in the number or fate of neural crest derived cells including cancers such as melanoma and defects of the developing reproductive system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 2 This gene is expressed primarily in infant brain and fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental disorders of the brain or lung. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous and pulmonary systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression Ievel in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating or diagnosing disorders associated with abnormal proliferation of cells in the Central nervous system and developing lung.
FEATURES OF PROTEIN ENCODED BY GENE NO: 3 This gene is expressed primarily in breast lymph node and to a lesser extent in ovarian cancer and chondrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune responses such as inflammation or immune surveillance for tumors. This gene may be important for inflammatory responses associated with tumors. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 236 as residues: Lys-45 to Val-50, Lys-69 to Arg-76.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment or diagnosis of immune responses including those associated with tumor-induced inflammation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 4 This gene is expressed primarily in T-cells and T-cell lymphomas.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunilogical diseases involving T-cells such as inflammation, autoimmunity, and cancers including T-cell lymphomas. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of T-cells and other cells of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids {e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing and treating T-cell based disorders such as inflammatory diseases, autoimmune disease and tumors including T-cell lymphomas.
WO 98!54963 PCT/US98/11422 FEATURES OF PROTEIN ENCODED BY GENE NO: 5 This gene is expressed primarily in activated monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation, autoimmunity, infection, or disorders involving activation of monocytes. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synoviai fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 238 as residues: Asp-19 to Arg-31.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing or treating diseases that result in activation of monocytes including infections, inflammatory responses or autoimmune diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 6 The translation product of this gene shares sequence homology with terminal deoxynucleotidyltransferase which is thought to be important in catalyzing the elongation of oligo- or polydeoxynucleotide chains.
This gene is expressed primarily in activated human neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer, particularly those of the blood such as leukemia and deficiencies in neutrophils such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to terminal deoxynucleotidyltransferase indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and differential diagnosis of acute leukemia's. Alternatively, this gene may function in the proliferation of neutrophils and be useful as a treatment for neutropenia, for example, following neutropenia as a result of chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 7 The contig exhibits a reasonable homology to the human chorionic gonadotropic (HCG) analogue-GT beta-subunit as disclosed in U.S. Patent No. 5,508,261 and PCT
Publication No. WO 92/22568. There is a high degree of conservation of the structurally important cysteine residues in these identities.
This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the immune system, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of diseases of the immune system since expression is primarily in neutrophils, and may be useful as a growth factor for the differentiation or proliferation of neutrophils for the treatment of neutropenia following chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 8 This gene is expressed primarily in IL-1- and LPS-induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include,but are not limited to, diseases of the immune system, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) 5 or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard 10 gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 241 as residues: Ser-14 to Pro-22, Leu-43 to Val-53.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases of the immune system since expression is primarily in neutrophils, and may be useful as a growth factor for the differentiation or proliferation of neutrophils for the treatment of neutropenia following chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 9 This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the immune system, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 242 as residues: Tyr-22 to His-35.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of diseases of the immune system since expression is primarily in neutrophils, and may be useful as a growth factor for the differentiation or proliferation of neutrophils for the treatment of neutropenia following chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 10 This gene is expressed primarily in activated T-cells and to a lesser extent in endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune dysfunctions including cancer of the T lymphocytes and autoimmune disorders and inflammation. Similarly, polypeptides and antibodies . directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of immune disorders particularly of T-cell origin and may act as a growth factor for particular subsets of T-cells such as CD4 positive cells which would make this a useful therapeutic for the treatment of HIV and other immune compromising illnesses.
FEATURES OF PROTEIN ENCODED BY GENE NO: 11 This gene is expressed primarily in fetal tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of many developmental abnormalities.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing fetus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucIeotides and polypeptides corresponding to this gene are useful as a growth factor or differentiation factor for particular cell types in the developing fetus and may be useful in replacement or other types of therapy in cases where the gene is expressed aberrantly.
FEATURES OF PROTEIN ENCODED BY GENE NO: 12 This gene is expressed primarily in T-cells and to a lesser extent in tumor tissue including glioblastoma, meningioma, and Wilm's tumor.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the immune system including autoimmune conditions such as I S rheumatoid arthritis, inflammatory disorders and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 245 as residues:
Thr-9 to Ser-14.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis/ modulation of immune function disorders, including rheumatoid arthritis and inflammatory responses.
FEATURES OF PROTEIN ENCODED BY GENE NO: 13 This gene is expressed primarily in placenta and to a lesser extent in fetal liver and bone marrow.
Therefore, polynucIeotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of hematological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematological and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a growth factor for hematapoietic stem cells or progenitor cells in the treatment of chemotherapy patients or kidney disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 14 This gene is expressed primarily in stromal cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of hematapoietic disorders including cancer, neutropenia, anemia, and thrombocytopenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematapoietic and immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a growth factor for hematapoietic stem cells or progenitor cells, in particular following chemotherapy treatment.
FEATURES OF PROTEIN ENCODED BY GENE NO: 15 The translation product of this gene shares sequence homology with epsilon-COP from Bos taurus which is thought to be important as a component of coatomer, a complex of seven proteins, that is the major component of the non-clathrin membrane coat. Preferred polypeptides encoded by this gene comprise the following amino acid sequences:
MAPPAPGPASGGSGEVDELFDVKNAFYIGSYQQCINEAXXVKLSSPERDVERD
VFLYRAYLAQRKFGVVLDEIKPSSAPELQAVRMFADYLAHESRRDSIVAELDRE
MSRSXDVTNTTFLLMAASIYLHDQNPDAALRALHQGDSLECTAMTVQILLKLD
RLDLARKELKRMQDLDEDATLTQLATAWVSLATGGEKLQDAYYIFQEMADKCS
PTLLLLNGQAACHMAQGRWEAAEGLLQEALDKDSGYPETLVNLIVLSQHLGKP
PEVTNRYLSQLKDAHRSHPFIKEYQAKENDFDRLVLQYAPSAEAGPELSGP
(SEQ ID N0:458); or RDVERDVFLYRAYLAQRKFGVVLDEIKPSSAPELQAVRMF
ADYLAHESRRDSIVAELDREMSRSXDVTNTTFLLMAASIYLHDQNPDAALRALH
QGDSLECTAMTVQILLKLDRLDLARKELKRMQDLDEDATLTQLATAVW SLATG
GEKLQDAYYIFQEMADKCSPTLLLLNGQAACHMAQGRWEAAEGLLQEALDKD
SGYPETLVNLIVLSQHLGKPPEVTNRYLSQLKDAHRSHPFIKEYQAKENDFDRL
VLQYAPSA (SEQ ID N0:459).
This gene is expressed primarily in activated monocytes and T-cells, and to a lesser extent in multiple other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunomodulation, specifically relating to transport problems in these cells. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to epsilon-COP indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating /diagnosing problems with the cellular transport of proteins that may result in immunologic dysfunction.
FEATURES OF PROTEIN ENCODED BY GENE NO: 16 The translation product of this gene shares sequence homology with an RNA
helicase which is thought to be important in polynucleotide metabolism. The translation product of this contig exhibits good homology to the LbeIF4A antigen of Leishmania braziliensis. The LbeIF4A antigen, or immunogenic portions of it, can be used to induce protective immunity against leishmaniasis, specifically L. donovani, L.
chagasi, L. infantum, L. major, L. braziliensis, L. panamensis, L. tropics and L.
guyanensis. It can also be used diagnostically to detect Leishmania infection or to stimulate a cellular and/or humoral immune response or to stimulate the production of interleukin-12.
This gene is expressed primarily in colon cancer and to a lesser extent in pituitary.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of cancers particularly of the colon.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing 10 immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample 15 taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 249 as residues: Glu-93 to Ala-98, Gln-150 to Leu-156, Leu-220 to Leu-231, Leu-268 to Arg-273, Val-324 to Pro-341, Arg-372 to Asn-380, Ser-405 to Gly-410, Phe-426 to Ala-433, Glu-458 to Asp-470, Arg-S06 to Ser-547.
The tissue distribution and homology to RNA helicase indicates that polynucleotides and polypeptides corresponding to this gene are useful for development of diagnostic tests for colon cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 17 The translation product of this contig has sequence homology to a cytoplasmic protein that binds specifically to JNK designated the JNK interacting protein-1 or JIP-1 in mice. JIP-1 caused cytoplasmic retention of JNK and inhibition of JNK-regulated gene expression.
This gene is expressed primarily in brain including pituitary cerebellum frontal cortex, fetal brain and to a lesser extent in the kidney cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of the central nervous system disorders including ischemia, epilepsy, Parkinson's disease, and schizophrenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Furthermore, the translation product of this contig may suppress the effects of the JNK signaling pathway on cellular proliferation, including transformation by the Bcr-Abl oncogene. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 250 as residues: Pro-6 to Ser-26, Ala-30 to Asp-41, GIy-55 to Ser-61, Gly-74 to Thr-80, Tyr-I 17 to AIa-123, Tyr-167 to Asp-172, Ala-212 to Cys-223, Pro-239 to Tyr-244.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for enhanced survival and/or differentiation of neurons as a treatment for neurodegenerative disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 18 The translation product of this gene shares sequence homology with a liver stage antigen from a protozoan parasite.
This gene is expressed primarily in fetal tissue and to a lesser extent in activated T-cells and other immune cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, bui are not limited to, developmental abnormalities and diseases of immune function.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to a protozoan antigen indicates that polynucleotides and polypeptides corresponding to this gene are useful' for treatment/immune modulation of parasitic infections.
FEATURES OF PROTEIN ENCODED BY GENE NO: 19 Preferred polypeptide encoded by this gene comprise the foilowing polypeptide sequences:
MKAIGIEPSLATYHHIIRLFDQPGDPLKRSSFIIYDIMNELMGKRFSPKD
DLICLMEQIDVTLKWYEDLIPSAYFPHSQTMIHLLQALDVANRLEVIPKIWER
(SEQ ID N0:460); and/or KDSKEYGHTFRSDLREEILMLMARDKHPPELQVAF
ADCAADIKSAYESQPIRQTAQDWPATSLNCIATLFLRAGRTQEAWKMLGLFRKH
NKIPRSELLNELMDSAKVSNSPSQAIEVVELASAFSLPICEGLTQRVMSDFAINQ
EQKEALSNLTALTSDSDTDSSSDSDSDTSEGK (SEQ ID N0:461 ). Polynucleotides encoding such polypeptides are also provided.
This gene is expressed primarily in stromal and CD34 depleted bone marrow cells and to a lesser extent in tissues of embryonic origin.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of hematologic origin including cancers and immune dysfunction. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunologicai probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematapoietic and immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 252 as residues: Ser-28 to Gln-34.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a growth factor for hematopoietic stem cells or progenitor cells which may be useful in the treatment of chemotherapy patients suffering from neutropenia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 20 Preferred polypeptide fragments can be found in an alternative open reading frame. These preferred polypeptides comprise the amino acid sequence:
MSSDNESDIEDEDLKLELRRLRDKHLKEIQDLQSRQKHEIESLYTKLGKVPPAVI
IPPAAPLSGRRRRPTKSKGSKSSRSSSLGNKSPQLSGNLSGQSAASVLHPQQTL
HPPGNIPESGQNQLLQPLKPSPSSDNLYSAFTSDGAISVPSLSAPGQGTSSTNTV
GATVNSQAAQAQPPAMTSSRKGTFTDDLHKLVDNWARDAMNLSGRRGSKGH
MNYEGPGMARKFSAPGQLCISMTSNLGGSAPISAASATSLGHFTKSMCPPQQY
GFPATPFGAQWSGTGGPAPQPLGQFQPVGTASLQNFNISNLQKSISNPPGSNL
RTT (SEQ ID N0:462); IQDLQSRQKHEIESLYTKLGKVPPAVIIPPAAPLSGRRRR
PTKSKGSKSSRSSSLGNKSPQLSGNLSGQSAASVLHPQQTLHPPGNIPESGQN
QLLQPLKPSPSSDNLYSAFTSDGAISVPSLSAPGQGTSST (SEQ ID N0:463);
TSDGAISVPSLSAPGQGTSSTNTVGATVNSQAAQAQPPAMTSSRKGTFTDDLH
(SEQ ID N0:464); KGHMNYEGPGMARKFSAPGQLCISMTSNLGGSAPISAAS
ATSLGHFTK (SEQ ID N0:465); QPLKPSPSSDNLYSAFTSDGAISVPSLSAPG
(SEQ ID N0:466). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in fetal liver and tissues associated with the CNS.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver and CNS diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the liver and CNS, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 253 as residues:
Gln-26 to Lys-34.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for liver diseases such as hepatocellular carcinomas and diseases of the CNS.
FEATURES OF PROTEIN ENCODED BY GENE NO: 21 In an alternative reading frame, this gene shows sequence homology to two recently cloned genes, karyopherin beta 3 and Ran GTP binding protein 5. (See Accession Nos. gi12102696 and gnIIPIDle328731.) The Ran GTP binding protein is related to importin-beta, the key mediator of nuclear localization signal (NLS)-dependent nuclear transport. Based on homology, it is likely that this gene may activity similar to the RAN GTP binding protein. Preferred polypeptide fragments comprise the amino acid sequence: VRVAAAESMXLLLECAXVRGPEYLTQMWI-~MCDALIKA
IGTEPDSDVLSEIMHSFAK (SEQ ID N0:467). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in thymus tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 22 This gene is expressed primarily in prostate and osteoclastoma tissues.
Preferred polypeptide fragments also comprise the amino acid sequence:
MEINNQNCFIVIDLVRTVMENGVEGLLIFGAFLPESWLIGVRCSSEPPKALLLIL
AHSQKRRLDGWSFIRHLRVHYCVSLTIHFS (SEQ ID N0:468). Also preferred are polynucleotide sequences encoding this polypeptide fragment.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, bone and prostate diseases, and cancers, particularly of the bone and prostate. Similarly. polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the_tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bone and prostate systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded 5 tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 255 as residues: Met-1 to Ser-1 I.
10 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for bone and prostate disorders, especially cancers of those systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 23 15 This gene shares sequence homology with the FK506-binding protein (FKBP-i 3) family, a known cytosolic receptor for the immunosuppressants. Recently, another group has cloned a very similar gene, recognizing the homology to FK506-binding protein family, calling their gene FKBP23. (See Accession No. 2827255.) This gene is expressed primarily in lymphoid tissues.
20 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample, especially for those susceptible to immune suppressant therapies and for diagnosis of diseases and conditions, which include, but are not limited to, immune suppressant disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 256 as residues: Ala-19 to Val-31, Arg-38 to Gly-49, Ala-61 to Lys-66, Tyr-68 to Pro-78, Gly-116 to Ala-121, Asp-154 to Ser-162, Glu-173 to Gln-186, Phe-194 to Gly-203, Pro-207 to Val-212.
The tissue distribution and homology to FKBP-12 and -13 indicates that polynucleotides and polypepiides corresponding to this gene are useful for diagnosis and treatment for immune suppressant disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 24 This gene is expressed primarily in the brain and in the retina. This gene maps to chromosome 8, and therefore can be used in linkage analysis as a marker for chromosome 8.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological and ocular associated disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 257 as residues: Cys-34 to Asp-40.
The tissue distribution in retina indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of eye disorders including blindness, color blindness, impaired vision, short and long sightedness, retinitis pigmentosa, retinitis proliferans, and retinoblastoma. Expression in the brain indicates a role in the is useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 25 This gene shows sequence homology to a newly identified class of proteins expressed in the nervous system, called stathmin family. (See Accession No.
2585991;
see also Eur. J. Biochem. 248 (3), 794-806 ( 1997).) The stathmin family appears to be an ubiquitous phosphoprotein involved as a relay integrating various intracellular signaling pathways. These pathways affect cell proliferation and differentiation.
Preferred polypeptide fragments comprise the amino acid sequence:
QDKHAEEVRKNKELKEEASR (SEQ ID N0:469); QQDLSPWAAPVGCPLXXASX
TCHXLPLSGCLRRQSXSLPV VAXLCFWFSCPLASLFVPGQPCVTCPFPSLPFQD
KHAEEVRKNKELKEEASR (SEQ ID N0:470). Also preferred are the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates. that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 26 The polynucleotide sequence of this gene contains a domain similar to a Flt3 ligand peptide. Preferred polypeptide fragments comprise the amino acid sequence:
PTRCCTTQPCRSSARRPCWVPMVPSPEGREXQPTCPS (SEQ ID N0:471). Thus, this gene may have activity as binding to Flt3 receptors, a process known to promote angiogenesis and/or lymphangiogenesis.
This gene is expressed in human tonsil, and to a lesser extent in teratocarcinoma, placenta, colon carcinoma, and fetal kidney.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the tonsil, as well as cancers, such as colon, reproductive, and kidney cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tonsils, colon, reproductive organs, and kidneys, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 259 as residues:
Pro-22 to Glu-33.
The tissue distribution in tonsil and several cancers and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases of the tonsil or colon, such as tonsillitis, inflammatory diseases involving nose and paranasal sinuses, especially during the infection of influenza, adenoviruses, parainfluenza, rhinoviruses. The gene may also be useful in the diagnosis and treatment of neoplasms of nasopharynx or colon origins.
FEATURES OF PROTEIN ENCODED BY GENE NO: 27 In an alternative reading frame exists a large open reading frame that encodes a preferred polypeptide. Preferred polypeptide fragments comprise the amino acid sequence:
MKRSLNENSARSTAGCLPVPLFNQKKRNRQPLTSNPLKDDSGISTPSDNYDFP
PLPTDWAWEAVNPEXAPVMKTVDTGQIPHSVSRPLRSQDSVFNSIQSNTGRSQ
GGWSYRDGNKNTSLKTWXKNDFKPQCKRTNLVANDGKNSCPMSSGAQQQK
QLRTPEPPNLSRNKETELLRQTHSSKISGCTMRGLDKNSALQTLKPNFQQNQY
KXQMLDDIPEDNTLKETSLYQLQFKEKASSLRIISAVIESMKYWREHAQKTVLL
FEVLAVLDSAVTPGPYYSKTFLMRDGKNTLPCVFYEIDRELPRLIRGRVHRCVG
NYDQKKNIFQCVSVRPASVSEQKTFQAFVKIADVEMQYYINVMNET (SEQ ID
N0:472); SQDSVFNSIQSNTGRSQGGWSYRDGNKNTSLKTWXKNDFKPQCKR
(SEQ ID N0:473); NKETELLRQTHSSKISGCTMRGLDKNSALQTLKPNF (SEQ ID
NO:474);SSLRIISAVIESMKYWREHAQKTVLLFEVLAVLDSAVTPGPYYSKTFLM
(SEQ ID N0:475); and PRLIRGRVHRCVGNYDQKKNIFQCVSVRPASVSEQKT
FQAFV (SEQ ID N0:476).
This gene is expressed primarily in human testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include.
but are not limited to, male reproductive disorders, including cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a hormone with reproductive or other systemic functions; contraceptive development; male infertility of testicular causes, such as Kleinfelteris syndrome, varicocele, orchitis; male sexual dysfunctions;
testicular neoplasms; and inflammatory disorders such as epididymitis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 28 This gene is expressed primarily in apoptotic T-cell.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases relating to T cells, as well as cancer in general.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders. Moreover, since the gene was isolated from an apoptotic cell and based on the understanding of the relationship of apoptosis and cancer, it is likely that this gene may play a role in the genesis of cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 29 This gene is expressed primarily in human tonsils.
Therefore, polynucleotides and polypeptides of the invention are useful as 5 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, gastrointestinal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above 10 tissues or cells, particularly of the gastrointestinal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level 15 in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of gastrointestinal diseases.
20 FEATURES OF PROTEIN ENCODED BY GENE NO: 30 The translation product of this gene shares sequence homology with C44C 1.2 gene product of Caenorhabditis elegans with unknown function. Preferred polypeptide fragments comprise the amino acid sequence:
GVFRPCVCGRPASLTCSPLDPEVGPYCDTPTMRTLFNLLWLALACSPVHTTLSK
FAGDVLGYVTPWNSHGYDVTKVFGSKFTQISPVWLQLKRRGREMFEVTGLHD
VDQGWMRAVRKHAKGLHIVPRLLFEDWTYDDFRNVLDSEDEIEELSKTVVQVA
KNQHFDGFWEVWNQLLSQKRVGLIHMLTHLAEALHQARLLALLVIPPATTPGT
DQLGMFTHKEFEQLAPVLDGFSLMTYDYSTAHQPGPNAPLSW VRACVQVLDP
KXKWRTKSSWGSTSMXWTXRXPXDARXPVVGXRXIQXLKDHXPRMVLDSK
PQ (SEQ ID N0:477); TCSPLDPEVGPYCDTPTMRTLFNLLWLALACSPVHTTLS
(SEQ ID N0:478); LVVTDLKAESWLEHRSYCSAKARDRHFAGDVLGYVTPW
NSHGYDVTKVFGSKF (SEQ ID N0:479); REMFEVTGLHDVDQGWMRAVRK
HAKGLHIVPRLLFEDWTYDDFRNVLDSEDE (SEQ ID N0:480); HFDGFVVEVW
NQLLSQKRVGLIf~IML,THLAEALHQARLLALLVIPPAITPGTDQLGM (SEQ ID
N0:481); DGFSLMTYDYSTAHQPGPNAPLSWVRACVQVLDPKXKWRTKSSW
GST (SEQ ID N0:482). Also preferred are polynucleotide fragments encoding these polypeptide fragments. This gene maps to human chromosome 11, and therefore is useful in linkage analysis as a marker for chromosome 11.
This gene is expressed primarily in human T cells and to a lesser extent in human colon carcinoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and gastrointestinal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 263 as residues: Leu-21 to Ala-30, Ser-38 to Asp-47, Pro-87 to Asp-94, Leu-to Thr-204, Pro-256 to Ser-262, Thr-277 to Arg-282, Thr-293 to Trp-303.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders and gastrointestinal diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 3I
The translation product of this gene shares sequence homology with Ribosomal protein L11 of Caenorhabditis elegans. (See Accession No. 156201.) Preferred polypeptide fragments comprise the amino acid sequence:
ERGVSINQFCKEFNERTKDIKEGIPLPTKILVKPDRTFEIKIGQPTVSYFLKAAAG
IEKGARQTGKEVAGLVTLKHVYEIARIKAQDEAFALQDVPLSS V VRSIIGSARSL
GIRVVKDLSSEELAAF QKERAIFLAAQKEADLAAQEEAAKK (SEQ ID N0:483).
Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in human embryo tissue and to a lesser extent in human epithelioid sarcoma and other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, development disorders and epithelial cell cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryonic and epithelial cell systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 264 as residues: Lys-34 to Gly-40.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of developmental disorders and epithelial cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 32 This gene is expressed primarily in resting T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory and general immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders of immune system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 33 This gene is believed to reside on chromosome 1. Accordingly, polynucleotides derived from this gene are useful in linkage analysis as chromosome 1 markers.
This gene is expressed primarily in prostate and to a lesser extent in snares adult brain, human umbilical vein endothelial cells, and amniotic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate-related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the urinary system and nervous system expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for the diagnosis and treatment of disorders of the urinary and nervous systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 34 This gene shares sequence homology with ROSG6.4 gene product. (See Accession No.
gi11326338.) This gene also shares sequence homology with the cyclophihn-like protein CyP-60. (See Accession No. 1199598, see also Biochem. J. 314 ( 1 ), 313-319 ( 1996).) Preferred polypeptide fragments comprise the amino acid sequence:
AVYTYHEKKKDTAASGYGTQNIRLSRDAVKDFDCCCLSLQPCHDPVVTPDGYL
YEREAILEYILHQKKEIARQMKAYEKQRGTRREEQKELQRAASQDHVRGFLEKE
SAIVSRP LNPFTAKALSGTSPDDVQPGPSVGPPSKDKDKVLPSFWIPSLTPEAK
ATKLEKPSRTVTCPMSGKPLRMSDLTPVHFTPLDSSVDRVGLITRSERYVCAVT
RDSLSNATPCA VLRPSGAWTLECVEKLIRKDMVDPVTGDKLTDRDIIVLQRGT
(SEQ ID N0:484); YLYEREAILEYILHQKKEIARQMKAYEKQRGTRREEQKELQ
RAASQDHVRGFLE (SEQ ID N0:485); and FTAKALSGTSPDDVQPGPSVGPP
SKDKDKVLPSFWIPSLTPEAKATKLEKPSRTVTCPMSGKPL (SEQ ID N0:486).
Also preferred are polynucleotide fragments that encode these polypeptide fragments.
This gene is expressed primarily in human testis and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive disorders and in particular testicular cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system.
Expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders of the male reproductive system and in particular of testicular cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 35 The translation product of this gene shares sequence homology with LpeSp of Saccharomyces cerevisiae which is thought to be important in the metabolism of phospholipids.
This gene is expressed primarily in liver and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, metabolic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful m providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the metabolic and nervous systems expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 268 as residues: Pro-14 to Leu-20, Lys-28 to Asn-38, Arg-109 to Arg-114, Lys-119 to Asn-124, Glu-152 to Leu-157, Pro-172 to Val-180.
The tissue distribution and homology to LpeSp of Saccharomyces cerevisiae indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of metabolic and nervous disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 36 This gene shares sequence homology with the nuclear ribonucleoprotein U (HNRNP
U), encoded by C. elegans (See Accession gi11703576.) Preferred polypeptide fragments comprise the amino acid sequence:
SATKGVPAGNSDTEGGQPGRKRRWGASTATTQKKPSISITTESLKSLIPDIKPL
AGQEAVVDLHADDSRISEDETERNGDDGTHDKGLKICRTVTQVVPAEGQENGQ
REEEEEEKEPEAEPPVPPQVSVEVALPPPAEHEVKKVTLGDTLTRRSISQQKSGV
SITIDDPVRTAQVPSPPRGKISNIVHISNLVRPFTLGQLKELLGRTGTLVEEAFWI
LVDRPSETKTEEQGIPRPLHPPPPPPVQPPQHPRAEQREQERAVREQWAERERE
MERRERTRSEREWDRDKVREGPRSRSRSRXRRRKERAKSKEKKSEKKEKAQE
EPPAKLLDDLFRKTKAAPCIYWLPLTDSQIVQKEAERAERAKEREKRRKEQEEE
EQKEREKEAERERNRQLEREKRREHSRERDRERERERERDRGDRDRDRERDRE
15 RGRERDRRDTKRHSRSRSRSTPVRDRGGR (SEQ ID N0:488). Also preferred are the polynucleotide fragments encoding this polypeptide fragments.
This gene is expressed primarily in epididymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 20 biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the male reproductive system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of 25 this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the 30 disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of male reproductive disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 37 This gene is expressed primarily in amygdala.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory diseases and reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the amygdala, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of inflammatory diseases and reproductive disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 38 This gene shares sequence homology with human opsonin protein P35 fragment. (See Accession No. 894181.) The opsonin protein activates the phagocytosis of pathogenic microbes by phagocytic cells. Preferred polypeptide fragments comprise the amino acid sequence: GCDSCPPHLPREAFAQDTQAEGECSSRAERADMCPDAP
PSQEVPEGPGAAP (SEQ ID N0:489). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in immune-related tissues such as thymus, macrophage, T cells and to a lesser extent in many other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders and infectious disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and infectious disease, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 271 as residues: Lys-9 to Arg-14, Met-38 to Asp-51.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders, as well as the treatment and/or diagnosis of infectious disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 39 The translation product of this gene shares sequence homology with alpha-2 type I collagen which is thought to be important in tissue repair. (See, e.g., 211607.) Preferred polypeptide fragments comprise the amino acid sequence: PQLPSCGRPW
PGTASVFQSHTQGPREDPDPCRAQGSAGTHCPISLSPPRQ (SEQ ID N0:490).
Also preferred are the polynucleotide sequences encoding these polypeptide sequences.
This gene is expressed primarily in the brain and to a lesser extent in the kidney and thymus Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain, kidney, and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain, kidney, and immune disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to alpha-2 type I collagen indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of tissue repair, and brain, kidney, immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 40 The translation product of this gene shares sequence homology with mini-collagen which is thought to be important in tissue repair tumor metastasis.
(See Accession No. gnlIPIDId1006976.) Preferred polypeptide fragments comprise the amino acid sequence: PGFRGPSGSLGCSFFPRSLGRVLPPGCQRPGAHAD
SSPPPTP (SEQ ID N0:491 ). Also preferred are polynucleotides encoding this polypeptide fragment.
This gene is expressed in ovarian cancer and to a Lesser extent in dedritic cells and smooth muscle.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumor metastasis and tissue repair. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tumor metastasis and tissue repair, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 273 as residues: Asn-2 to His-11.
The tissue distribution and homology to mini-collegen gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of tumor metastasis and tissue repair.
FEATURES OF PROTEIN ENCODED BY GENE NO: 41 This gene shares sequence homology with the HIV TAT protein. (See Accession No. 328416.) Preferred polypeptide fragments comprise the amino acid sequence: EDLKKPDPASLRAASCGEGKKRKACKNCTCGLAEELEKEK
SREQMSSQPKSACGNCYLGDAFRCASCPYLGMPAFKPGEKVLLS (SEQ ID
N0:492); EDLKKPDPASLRAASCGEGKKRKACKNCTCGLAEELEKEK
SREQMSSQPKSACGNCYLGDAFRCASCPYLGMPAFKPGEKVLLSDSNLHD
(SEQ ID N0:493); CGNCYLGDAFRCASCPYLGMPAFKPGEKVLLSDS
(SEQ ID N0:494); SCGEGKKRKACKNCTCGLAEELEKE (SEQ ID N0:495);
SQPKSAC GNCYLGDAFRCASC (SEQ ID N0:496); and REAGQNSERQYVS
LSRD (SEQ ID N0:497). Also preferred are polynucleotide fragments encoding these poIypeptide fragments.
This gene is expressed primarily in the infant brain and to a lesser extent in the breast and testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain, testes and breast disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of-disorders of the above tissues or cells, particularly of the brain, testes and breast disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 274 as residues: Pro-7 to Val-15.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of brain, testes and breast, and other related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 42 This gene is expressed primarily in the infant brain, human cerebellum, and to a lesser extent in medulloblastoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain related disorders and medulloblastoma and other brain cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain related disorders and brain cancers, including medulloblastoma, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 275 as residues: Thr-41 to Glu-47.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of human brain related disorders, brain cancers, and medulloblastoma.
5 FEATURES OF PROTEIN ENCODED BY GENE NO: 43 The translation product of this gene shares sequence homology with a phosphotyrosine-independent ligand for the lck SH2 domain which is thought to be important in signal transduction related to phosphotyrosine-independent ligand for the lck SH2 domain. (See Accession No. gil l 184951.) Preferred polypeptide fragments 10 comprise the amino acid sequence: ESSGQARTLADPGPGWPRQQGMCFGSLT
GLSTTPHGFLTVSAEADPRLIESLSQMLSMGFSDEGGWLTRLLQTKNYDIGAAL
DTIQYSKH (SEQ ID N0:498). Also preferred are polynucleotide fragments encoding this polypeptide fragment. It is likely that this gene is a new member of a family of phosphotyrosine-independent ligands for the lck SH2 domains.
15 This gene is expressed primarily in the placenta and to a lesser extent in endothelial cells and neutrophil.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 20 not limited to, reproductive, cardiovascular, immune, and infectious diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular, reproductive, and immune system, and infectious diseases, expression 25 of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the 30 disorder.
The tissue distribution and homology to a phosphotyrosine-independent ligand for the lck SH2 domain indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of cardiovascular, reproductive, and immune system diseases, as well as infectious diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 44 This gene is expressed primarily in the fetal brain, cerebellum and to a lesser extent in the placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal cell related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal cell related disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 277 as residues: Thr-20 to Gly-28.
The tissue distribution and homology to proline-rich protein genes indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal cell related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 45 The translation product of this gene shares sequence homology with precerebellin of human, which is thought to be important in synaptic physiology. (See Accession No. gi1180251.) It has been observed that cerebellin-like immunoreactivity is associated with Purkinje cell postsynaptic structures. Thus, it is likely that this gene also have synaptic activity. Preferred polypeptide fragments comprise the amino acid sequence: QEGSEPVLLEGECLVVCEPGRAAAGGPGGAALGEAPPGRVAFXAV
RSHHHEPAGETGNGTSGAIYFDQVLVNEGGGFDRASGSFVAPVRGVYSFRFH
VVKVYNRQTVQVSLMLNTWPVISAFANDPDVTREAATSSVLLPLDPGDRVSLR
LRRGXSTGW (SEQ ID N0:499). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in cerebellum and infant brain. By Northern analysis, a single transcript of 2.4 kb was observed in brain tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions. which include.
but are not limited to, neuronal cell signal transduction and synaptic physiology.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal cell signal transduction and synaptic physiology expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to gene or gene family indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal cell related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 46 This gene is expressed in fetal liver and spleen, and to a lesser extent in bone marrow, umbilical vein, and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders of the immune system, particularly hematopoiesis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoiesis and immune disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 279 as residues: Asp-30 to Glu-57.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of hematopieotic and immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 47 The translation product of this gene shares sequence homology with a 12 kD
nucleic acid binding protein of Feline calcivirus which is thought to be important in viral replication. (See Accession No. 59264) This gene is expressed primarily in human cardiomyopathy and to a lesser extent in T helper cells, fetal brain and synovial sarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cardiomyopathy as well as viral infection. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 280 as residues: Trp-20 to Cys-26.
The tissue distribution in cardiomyopathy and homology to viral 12 kD nucleic acid binding protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of cardiomyopathy, including those caused by ischemic, hypertensive, congenital, valvular, or pericardial abnormalities.
The gene expression pattern may be the consequence or the cause for these conditions.
FEATURES OF PROTEIN ENCODED BY GENE NO: 48 The translation product of this gene shares sequence homology with tumor necrosis factor related gene product which is thought to be important in tumor necrosis, bacterial and viral infection, immune diseases and immunoreactions.
This gene is expressed primarily in colon and to a lesser extent in ovarian and breast cancers.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors of colon, ovary or breast origins. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the colon, ovary and breast, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to Tumor necrosis factors indicates that polynucleotides and polypeptides corresponding to this gene are useful for intervention of cancers of colon, ovary and breast origins, because TNF family members are known to be involved in the tumor development.
FEATURES OF PROTEIN ENCODED BY GENE NO: 49 The translation product of this gene shares sequence homology with mucins, such as epithelial mucin, which is thought to be important in extracellular matrix functions such as protection, lubrication and cell adhesion (See for example Accession No. R68002). Preferred polypeptide fragments comprise the following amino acid sequence: PRSRPALRPGRQRPPSHSATSGVLRPRKKPDP (SEQ ID NO:500).
Also preferred are polynucleotide fragments encoding these polypeptide fragments.
Moreover, this gene maps to chromosome 22q 11.2-qter, and therefore, can be used as a marker in linkage analysis for chromosome 22.
This gene is expressed primarily in corpus colosum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors, especially of corpus colosum, as well as metastatic lesions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunologicai probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the corpus colosum and other solid tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to mucins indicates that polynucleotides and polypeptides corresponding to this gene are useful for serum tumor markers or immunotherapy targets because tumor cells have greatly elevated level of mucin expression and shed the molecules into the epithelial tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: SO
This gene is expressed primarily in CD34 depleted huffy coat cord blood and primary dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as 10 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic disorders and immunological disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For 15 a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard 20 gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in CD34 depleted huffy coat cord blood and primary dendritic cells indicates that polynucleotides and polypeptides con esponding to this gene are useful for diagnosis and treatment of hematopoietic and immune disorders.
25 Secreted or cell surface proteins in the above tissue distribution often are involved in cell activation (e.g. cytokines) or molecules involved in cell surface activation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 51 The translation product of this gene shares sequence homology with Interferon 30 induced 1-8 gene encoded polypeptide which is thought to be important in binding to retroviral rev responsive element. Preferred polypeptide fragment comprise the following amino acid sequences: MTLITPSXKLTFXKGNKSWSSRACSSTLVDP
(SEQ ID NO:SOI). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
35 This gene is expressed primarily in CD34 positive cells and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, retroviral infection, such as AIDS, and other immune disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 284 as residues: Gln-51 to Trp-62.
The tissue distribution and homology to interferon induced gene 1-8 indicates that polynucleotides and polypeptides corresponding to this gene are useful for intervention of retroviral infection including HIV. The factor may be involved in viral stability or viral entry into the cells. Alternatively, the virus/factor complex may elicit the cellular immune reaction.
FEATURES OF PROTEIN ENCODED BY GENE NO: 52 This gene shares sequence homology to immunoglobulin lambda chain (See Accession No. 2865484). Therefore it is likely that this gene has activity similar to an immunoglobulin lambda chain. Preferred polypeptide fragments comprise the following amino acid sequence: GHPSPALSIAPSDGSQLPCDEVPYGEAHVTRYCKKPLTNS
HLETEAQSSSL (SEQ ID N0:502). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in Hodgkin's lymphoma.
Therefore, polynucleotides and poIypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, Hodgkin's lymphoma and other immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 285 as residues: Pro-27 to Thr-32.
The tissue distribution in Hodgkin's lymphoma and the sequence homology indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of Hodgkin's lymphoma, since the elevated expression and secretion by the tumor mass may be indicative of tumors of this type. Additionally the gene product may be used as a target in the immunotherapy of the cancer.Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunoIogical disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 53 This gene has extensive homology to cDNA for Homo Sapiens mRNA for the ISLR gene(See Accession No. AB003184). This protein is considered to be a new member of the Ig superfamily and contains a leucine-rich repeat (LRR) with conserved flanking sequences and a C2-type immunoglobulin (Ig}-like domain. These domains are important for protein-protein interaction or cell adhesion, and therefore it is possible that the novel protein ISLR may also interact with other proteins or cells. The ISLR gene was mapped on human chromosome 15q23-q24 by fluorescence in situ hybridization (See Medline Article No. 97468140). Homology to the ISLR gene has been confirmed by another independent group as well (See Accession No. Hs.102171 ) This gene is expressed in a number of tissues including human retina, heart, skeletal muscle, prostate, ovary, small intestine, thyroid, adrenal cortex, testis, stomach, spinal cord, fetal lung and fetal kidney tissues, colon, tonsil and stomach cancer, and to a lesser extent in endometrial stromal cells treated with estradiol, breast tissue, synovium, lymphoma, and number of other tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors of colon, ovary and breast origins. However, due to the wide range of expression in various tissues, protein may play a vital role in the development of cancer in other tissues as well, not just those mentioned above. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the colon, ovary and breast, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues {e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Additionally, this gene maps to chromosome 15q23-q24, and therefore, can be used as a marker in linkage analysis for chromosome 15.
The tissue distribution in tumors of colon, ovary, and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 54 Gene has homology to multidrug resistance gene 1 (See Accession No.
P06795). Preferred polynucleotide fragments comprise the following sequence:
GCTTCGTGTCCAACCCTCTTGCCCTTCGCCTGTGTGCCTGGAGCCAGTCCCA
CCACGCTCGCGTTTCCTCCTGTAGTGCTCACAGGTCCCAGCACCGATGGCA
TTCCCTTTGCCCTGAGTCTGCAGCGGGTCCCTTTTGTGCTTCCTTCCCCTCA
GGTAGCCTCTCTCCCCCTGGGCCACTCCCGGGGGTGAGGGGGTTACCCCTT
CCCAGTGTTTT)-TATTCCTGTGGGGCTCACCCCAAAGTATTAAAAGTAGCTTT
GTAA (SEQ ID N0:503). Also preferred are polypeptide fragments encoded by these polynucleotide fragments.
This gene is expressed primarily in lung, esophagus, leukemia (Jurkat cells) and breast cancers and to a lesser extent in macrophages treated with GM-CSF fetal tissues and wide range of tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer of wide range of origins. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the solid tumors, lung and leukemia, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Furthermore, due to the high expression level in lung tissue and the proposed function of the multidrug resistance protein 1 gene as the efflux pump responsible for low-drug accumulation in multidrug-resistant cells, protein as well mutants thereof, may also be beneficial as a target for gene therapy, particularly for the chronic patient.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 287 as residues: Met-1 to Lys-16.
The tissue distribution in wide range of cancers and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection of cells in active proliferation, such as cancers. The gene products may be used for cancer markers or immunotherapy target.
FEATURES OF PROTEIN ENCODED BY GENE NO: 55 This gene maps to the X chromosome.
This gene is expressed primarily in the brain and to a lesser extent in the developing embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative disease states and developmental disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders, including sex-linked disorders, of the above tissues or cells, particularly of the neurological, developmental systems, and cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Moreover, this gene maps to the X chromosome, and therefore, may be used as a marker in linkage analysis for this chromosome.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Klinefelter's, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 56 5 The translation product of this gene shares sequence homology with paxillin which is thought to be important in mediating signal transduction from growth factor receptors to the cytoskeleton. Preferred polynucleotide fragments comprise the following sequence: TGGCTCACTGTCTTACAATCACTGCTGTGGAATCATGA
TACCACTTTTAGCTCTTTGCATCTTCCTTCAGTGTATTTTTGTTTTTCAAGAGG
GGCTTGTGGTTTCAA (SEQ ID N0:506). Also preferred are polypeptide fragments encoded by these polynucleotide fragments. More preferably, polypeptide fragments comprise the amino acid sequence: LDELMAHLTEMQAKVAVRAD
AGKKHLPDKQDHKASLDSMLGGLEQELQDLGIATVPKGHCASCQKPIAGKVI
ILDKVLTAMNQTWHPEHFFCSHCGEVFGAEGFHEKDKKPYCRKDFLAMFSPK
CGGCNRPVLENYLSAMDTVWHPECFVCGDCFTSFSTGSFFELDGRPFCELHYH
HRRGTLCHGCGQPITGRCISAMGYKFHPEHFVCAFCLTQLSKGIFREQNDKTY
CQPCFNKLF {SEQ ID N0:507); KASLDSMLGGLEQELQDLGIATVPKGHC
20 ASCQKPIAGKVIHAL (SEQ ID N0:508); CPNDYHQLFSPRCAYCAAPILDKVL
TAMNQTWHPEHFFCSHCGEVFGAEG (SEQ ID N0:509); DKKPYCRKDFLAM
FSPKCGGCNRPVLENYLSAMDTVWHPECFVCGDCFTSFSTGSFFELDGRPFCE
L (SEQ ID NO:510); CGQPITGRCISAMGYKFHPEHFVCAFCLTQLSKGIFRE
QNDKTYCQ (SEQ ID NO:511 ). Polynucleotide fragments encoding these preferred 25 polypeptide fragments are also contemplated.
This gene is expressed primarily in brain, and to a lesser extent in the developing embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 30 biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disease states and developmental abnormalities.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the immune and 35 nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Moreover, since this gene shares homology with a gene that maps to chromosome 11, (See Accession No.T87404), gene as well as its translated product may be used for linkage analysis on chromosome 11.
The tissue distribution and homology to paxillin indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and or detection of disease states associated with abnormal signal transduction in brain and/or the developing embryo. This would include treatment or detection of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder and also in the treatment and or detection of embryonic development defects.
FEATURES OF PROTEIN ENCODED BY GENE NO: 57 This gene is expressed primarily in fetal spleen, brain, and to a lesser extent in six week old embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders, neurological disorders, and developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and developmental systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 290 as residues: Arg-28 to Gly-34.
The expression of this gene in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/detection of immune disorders such as arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. In addition the expression of this gene in the early embryo, indicates a key role in embryo development and hence the gene or gene product could be used in the treatment and or detection of embryonic development defects. This would include treatment or detection of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder and also in the treatment and or detection of embryonic development defects.
FEATURES OF PROTEIN ENCODED BY GENE NO: 58 The translation product of this gene shares sequence homology with the gene disrupted in the neurodegenerative disease dentatorubal-palIidoluysian atrophy. Moreover a long open reading fame exists in an alternative frame. Preferred polypeptide fragments comprise the following:
MGSSQS VEIPGGGTEGYHVLRVQENSPGHRAGLEPFFDFIVSINGSRLNKDND
TLKDLLKXNVEKPV KMLIYSSKTLELRETS VTPSNLWGGQGLLG V SIRFCSFD
GANENVWHVLEVESNSPAALAGLRPHSDYIIGADTVMNESEDLFSLIETHEAKP
LKLYVYNTDTDNCREVIITPNSAWGGEGSLGCGIGYGYLHRIPTRPFEEGKKIS
LPGQMAGTPITPLKDGFTEVQLSSVNPPSLSPPGTTGIEQSLTGLSISSTPPAVSS
VLSTGVPTVPLLPPQVNQSLTSVPPMNPATTLPGLMPLPAGLPNLPNLNLNLPA
PHIMPGVGLPELVNPGLPPLPSMPPRNLPGIAPLPLPSEFLPSFPLVPESSSAASS
GELLSSLPPTSNAPSDPATTTAKADAASSLTVDVTPPTAKAPTTVEDRVGDSTPV
SEKPVSAAVDANASESP (SEQ ID N0:512); SVEIPGGGTEGYHVLRVQENSPGH
RAGLEPFFDFIVSINGSRLNKDNDTLKDLLKXNVEKPVKMLIYSSKTLELRETS
VTPSNLWGGQGLLGVSIRFCSFDGANENVWH (SEQ ID N0:513); ESNSPAA
LAGLRPHSDYIIGADTVMNESEDLFSLIETHEAKPLKLYVYNTDTDNCREVIITP
NSAWGGEGSLGCGIGYGYLHRIPTRPFEEGKKISLPGQMAGTPITPLKDGFTEV
QLSSVNPPSLSPPGTTGIEQSLTG LSISS (SEQ ID N0:514); RIPTRPFEEGKKI
SLPGQMAGTPITPLKDGFTEVQLSSVNPPSLSPPGTTGIEQSLTGLSISSTPPAVS
S VLSTGVPTVPLLPPQVNQSLTS VPPMNPATTLPGLMPLPAGLPNLPNLNLNLP
APH1MPGVGLPELVNPGLPPLPSMPPRN (SEQ ID N0:516); PGLPPLPSMPPRN
LPGIAPLPLPSEFLPSFPLVPESSSAASSGELLSSLPPTSNAPSDPATTTAKADAA
SSLTVDVTPPTAKAPTTVEDRVGDSTPVSEKPVSAAVDAN (SEQ ID N0:517).
This gene is expressed primarily in prostate cancer, and to a lesser extent in the pineal glands and in fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are . 35 not limited to, neurological conditions and pulmonary disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous, pulmonary, and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 291 as residues: Asn-9 to Leu-14.
The abundance of this gene in the pineal gland and its homology to a gene disrupted in the neurodegenerative disease state Dentatorubral-pallidoluysian atrophy indicates that this gene may be useful in the treatment and/or detection of other neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. The abundance of this gene in fetal lung would suggest that nusregulation of the expression of this protein product in the adult could lead to lymphoma or sarcoma formation, particularly in the lung;
that it may also be involved in predisposition to certain pulmonary defects such as pulmonary edema and embolism, bronchitis and cystic fibrosis; and thus the gen or the gene protein encoded by the gene could be used in the detection and/or treatment of these pulmonary disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 59 This gene is expressed primarily in the developing embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developmental system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The expression of this gene primarily in the embryo, indicates the gene plays a key role in embryo development and that the gene or the protein encoded by the gene could be used in the treatment and or detection of developmental defects in the embryo or in infants.
FEATURES OF PROTEIN ENCODED BY GENE NO: 60 This gene displays homology to nestin, an intermediate filament protein, the expression of which correlates with the proliferation of Central Nervous System progenitor cells and that is useful in the identification of brain tumors.
This gene maps to chromosome l, and therefore, may be used as a marker in linkage analysis for chromosome 1 (See Accession No. AA527348).
This gene is expressed primarily in kidney and to a lesser extent in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, renal disorders and neurodegenerative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the excretory and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 293 as residues: Thr-128 to Asn-135.
The tissue distribution and homology to nestin indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and/or treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, its abundance in kidney indicates that it is useful in the treatment and detection of acute renal failure and other disease states associated with the kidney.
FEATURES OF PROTEIN ENCODED BY GENE NO: 61 Gene shares homology with the latrophilin-related protein 1 precursor as well as the calcium-independent alpha-latrotoxin receptor. Preferred polypeptide fragments comprise the following amino acid sequence:
IYKVFRHTAGLKPEVSCFENIRSCARXXXXXXXXXXXXWIFGVLHVVHAS VV
TAYLFTVSNAFQGMFIFLFLCVLSRKIQEEYYRLFKNVPCC (SEQ ID N0:518);
WIFGVLHVVHAS VVTAYLFTVSNAFQGMFIFLFLCVLSRKIQEEYYRLFKNVPC
5 C (SEQ ID N0:519). Also preferred are polynucleotide fragments encoding these polypeptide fragments. (See Accession No. 2213659) The translation product of this gene shares sequence homology with CD 97, a seven transmembrane bound receptor.
This gene is expressed primarily in infant brain and in endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as i0 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders and hematopoeitic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For 15 a number of disorders of the above tissues or cells, particularly of the neurological and hematopoeitic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the 20 standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 294 as residues: Lys-13 to Leu-21.
The tissue distribution of this gene suggest that it may be useful in the detection and/or treatment of neurodegenerative disease states and behavioral disorders such as 25 Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder, while its expression in hematopoietic cell types indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma and immunodeficiency diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 62 This gene is expressed primarily in fetal liver and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematological and immunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunoiogical probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoetic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 295 as residues: Ser-91 to Lys-98.
The tissue distribution of this gene fetal liver and spleen indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, leukemia, asthma and immunodeficiency diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 63 Gene shares homology with human serum amyloid protein. Preferred polypeptide fragments comprise the following amino acid sequence:
ALTRIPPGDWVINVTAVSFAGKTTARFFHSSPPSLGDQARTDPGHQRRD (SEQ
ID N0:520) (See Accession No. W 13671 ). Also preferred are polynucleotide fragments encoding these polypeptide fragments This gene maps to chromosome 9, and therefore, may be used as a marker in linkage analysis for chromosome 9 (See Accession No. AA004342).
This gene is expressed primarily in fetal liver and spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in fetal liver-spleen indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, leukemia, asthma, and immunodeficiency diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 64 This gene maps to chromosome 3, and therefore, may be used as a marker in linkage analysis for chromosome 3 (See Accession No. AA219669).
This gene is expressed specifically in the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neurological systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 65 Gene shares homology with a yeast protein. Preferred polypeptide fragments comprise the following amino acid sequence: LQEVNITLPENSVWYERYKFDIP
VFHL (SEQ ID N0:521 ). Also preferred are polynucleotide fragments encoding these polypeptide fragments. (See Accession No. 1332638) This gene is expressed primarily in fetal tissue (fetus and fetal liver).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver disorders and cancers (e.g. hepatoblastoma). Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunologicai probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic system, expression of this gene at significantly higher or lower levels may be routinely detected S in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 298 as residues: Asn-59 to Glu-64.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). In addition the expression in fetus would suggest a useful role for the protein product in developmental abnormalities, fetal deficiencies, pre-natal disorders and various would-healing models and/or tissue trauma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 66 Gene has homology with a B-cell surface antigen which may indicate gene plays a role in the immune response, including, but not limited to disorders and infections of the immune system. Preferred polynucleotide fragments comprise the following sequence: TAGCATGTAGCCAGTCGAATAACNTATAAGGACAAAGTGGAGTC
CACGCGTGCGGCCGTCTAGACTAGTGGATCCCCCGGCTGCAGGATTCGGC
ACGAG (SEQ ID N0:523). Also preferred are polypeptide fragments encoded by these polynucleotide fragments (See Accession No.T94535). Additionally, this gene shares homology with an interferon-gamma receptor. Preferred polypeptide fragments also comprise the following amino acid sequence: MQGSGSQFRACLLCLCFSCPC
SPGGPRWNSRQGGRRFPKTCRAISQNLVFKYKTFCPVRYMQPHRSSLCLHFTS
YVFILSTWGSLRTYSTDLKKKKKNSRGGPVPIRPKS (SEQ ID N0:522);
MQGSGSQFRACLLCLCFSCPCSPGGPRWNSRQGGRRFPKTCRAISQNLVFK
(SEQ ID N0:524); PVRYMQPHRSSLCLHFTSYVFILSTWGSLRTYSTDLKKKKK
NSRGGPVPIRPKS (SEQ ID N0:525); and GEEQRDCSLGWRGVGMRATHCQAA
RMFVLFSLPKYAGL (SEQ ID N0:526). Also preferred are polynucleotide fragments encoding these polypeptide fragments This gene is expressed primarily in T-cells and gall bladder.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological disorders and conditions (immunodeficiencies, cancer, leukemia, hematopoeisis). Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and digestive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 299 as residues:
Thr-41 to Gly-52.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune disorders including: leukemias, lymphomas, auto-immune disorders, immuno-supressive (transplantation) and immunodeficiencies (e.g. AIDS), inflammation and hematopoeitic disorders. The expression of this gene in gall bladder would suggest a possible role for this gene product in digestive disorders, particularly of the pancreas.
FEATURES OF PROTEIN ENCODED BY GENE NO: 67 This gene maps to chromosome 11, and therefore, may be used as a marker in linkage analysis for chromosome 11 (See Accession No. AA011622).
This gene is expressed primarily in a variety of fetal and developmental tissues (e.g. fetal spleen, infant brain).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental, immune or neurological abnormalities.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing immune and central nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 300 as residues: Ser-38 to Ser-43.
5 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for developmental abnormalities or fetal deficiencies. The detection in infant brain would suggest a role in neurological disorders (both developmental and neurodegenerative conditions of the brain and nervous system, behavioral disorders, depression, schizophrenia, Alzheimer's disease, Parkinson's 10 disease, Huntington's disease, mania, dementia). In addition, the detection in spleen would similarly suggest a role in detection and treatment of immunologically mediated disorders (e.g. immunodeficiency, inflammation, cancer, wound healing, tissue repair, hematopoeisis).
15 FEATURES OF PROTEIN ENCODED BY GENE NO: 68 This gene is expressed primarily in spleen, T-cells, and fetal heart.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type.(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 20 not limited to, immunological deficiencies, including AIDSand cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and cardiovascular systems, expression of this gene at significantly higher 25 or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
30 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders including: leukemias, lymphomas, autoimmune disorders, immunodeficiencies (e.g. AIDS), immuno-suppressive conditions (transplantation) and hematopoeitic disorders. The expression in fetal heart indicates that polynucleotides and 35 polypeptides corresponding to this gene are useful for the treatment and diagnosis of cadiovascular disorders (e.g. heart disease, restenosis, atherosclerosis, stoke, angina, thrombosis).
FEATURES OF PROTEIN ENCODED BY GENE NO: G9 Gene shares homology with a human collagen protein. Preferred polypeptide fragments comprise the following amino acid sequence:
MPRKTSKCRQLLCSGASRNADTAARQSTCSSHRPPGKIPSLGPRRXPGCXSVP
SSRGEQSTGSPAAPRCGRRDAHRGLPGGAAMTPGDTWASFNPRAGHSKSQGE
GQESSGASRQDRHPVSHWVERQREAWGAPRSSSAGGVKVAATTEREPEFKIK
TGKA (SEQ ID N0:527); CSGASRNADTAARQSTCSSHRPPGKIPSLGPRRXPG
CXS VPSSRGEQSTGSPAAPRCGRRDAHRGLPGGAAMTPGDTWASFNPRAGHS
(SEQ ID N0:528); QGEGQESSGASRQDRHPVSHWVERQREAWGAPRSSSAGG
VKVAATTEREPEFKIKTGKA (SEQ ID N0:529) (See Accession No. 124886). Also preferred are polynucleotide fragments encoding these polypeptide fragments This gene is expressed primarily in fetal heart.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 302 as residues:
Pro-32 to Ser-39.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of cadiovascular disorders (e.g. heart disease, restenosis, atherosclerosis, stroke, angina, thrombosis).
FEATURES OF PROTEIN ENCODED BY GENE NO: 70 The translation product of this gene shares sequence homology with a chicken single-strand DNA-binding protein. Preferred polypeptide fragments comprise the following amino acid sequence:
MSPRYPGGPRPPLRIPNQALGGVPGSQPLLPSGMDPTRQQGHPNMGGPMQRM
TPPRGMVPLGPQNYGGAMRPPLNALGGPGMPGMNMGPGGGRPWPNPTNAN
SIPYSSASPGNYVGPPGGGGPPGTPIMPSPADSTNSGDNMYTLMNAVPPGPNR
PNFPMGPGSDGPMGGLGGMESHHMNGSLGSGDMDSISKNSPNNMSLSNQP
GTPRDDGEMGGNFLNPFQSESYSPSMTMSV (SEQ ID N0:530); MSPRYPGG
PRPPLRIPNQALGGVPGSQPLLPSGMDPTRQQGHPNMGGPMQRMTPPRGMVP
LGPQNYGGAMRPPLNALGGPGMPGMNMGPGGGRPWPNPTNANSIPYSSASP
GNY (SEQ ID. N0:531); LNALGGPGMPGMNMGPGGGRPWPNPTNANSIPYSS
ASPGNYVGPPGGGGPPGTPIMPSPADSTNSGDNMYTLMNAVPPGPN (SEQ ID
N0:532); GPMGGLGGMESHHMNGSLGSGDMDSISKNSPNNMSLSNQPGTPR
DDGEMGGNFLNPFQSESYSPSMTMSV (SEQ ID N0:533); TCEHSSEAKAFHDY
(SEQ ID N0:534). Also preferred are polynucleotide fragments encoding these polypeptide fragments. (See Accession No. 1562534) This gene is expressed primarily in placenta and to a lesser extent in the fetal heart and a variety of other tissues and cell types.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities, fetal deficiencies, and particularly of the cardiovascular system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of developmental abnormalities or fetal deficiencies, ovarian and other endometrial cancers, reproductive dysfunction, cardiovascular disorders, and pre-natal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 71 This gene is expressed primarily in fetal liver and to a lesser extent in the breast and testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver disorders (including hepatoblastomas) and reproductive disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic and reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression Level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and treatment of liver disorders and cancers (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). The expression in testes and breast indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of endocrine and reproductive disorders (e.g. sperm maturation, milk production, testicular and breast cancers).
FEATURES OF PROTEIN ENCODED BY GENE NO: 72 This gene maps to chromosome 1, and therefore, may be used as a marker in linkage analysis for chromosome 1 (See Accession No. W93595).
This gene is expressed primarily in smooth muscle and to a lesser extent in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cardiovascular and neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular and central nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of restenosis, atheroscIerosis, stroke, angina, thrombosis, wound healing and other conditions of heart disease. In addition, the expression in brain would suggest that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of developmental, degenerative and behavioral conditions of the brain and nervous system (e.g. schizophrenia, depression, Alzheimer's disease, Parkinson's disease, Huntington's disease, mania, dementia, paranoia, addictive behavior and sleep disorders).
FEATURES OF PROTEIN ENCODED BY GENE NO: 73 Gene shares homology with human stromalin-2. Preferred polypeptide fragments comprise the following amino acid sequence:
QAFVLLSDLLLIFSPQMIVGGRDFLRPLVFFPEATLQSELASFLMDHVFIQPGDL
GSGA (SEQ ID N0:535); ACSYLLCNPEFTFFSRADFARSQLVDLLTDRFQQE
LEELLQVG (SEQ ID NO:536),QKQLSSLRDRMVAFCELCQSCLSDVDTEIQEQV
ST (SEQ ID N0:537); QVILPALTLVYFSILWTLTHISKSDAS (SEQ ID N0:538);
STHDLTRWELYEPCCQLLQKAVDTGXVPHQV (SEQ ID N0:539). Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No.R65208 ) This gene maps to chromosome 7, and therefore, may be used as a marker in linkage analysis for chromosome 7 (See Accession No. D52585).
This gene is expressed primarily in the brain (infant brain, adult brain, pituitary, cerebellum, hippocampus, schizophrenic hypothalmus, amygdala).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental and neurodegenerative diseases of the brain and nervous system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those WO 98!54963 PCT/US98/11422 comprising a sequence shown in SEQ ID NO: 30b as residues: Thr-25 to Lys-3b, Lys-55 to Ser-63.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and treatment of developmental, 5 degenerative and behavioral conditions of the brain and nervous system (e.g.
schizophrenia, depression, Alzheimer's disease, Parkinson's disease, Huntington's disease, mania, dementia, paranoia, addictive behavior and sleep disorders).
FEATURES OF PROTEIN ENCODED BY GENE NO: 74 10 This gene is expressed primarily in the hypothalamus of a human suffering from schizophrenia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 15 not limited to, disorders of the CNS particularly schizophrenia. Sinularly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS, such as schizophrenia expression of this gene at significantly higher or lower levels may be routinely detected 20 in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
25 NO: 307 as residues: Gly-38 to Ala-44.
The tissue distribution indicates that the protein products of this gene are useful for the study, diagnosis and treatment of schizophrenia and other disorders involving the CNS.
30 FEATURES OF PROTEIN ENCODED BY GENE NO: 75 Preferred polypeptides of the invention comprise the following amino acid sequence encoded by this gene:
LAVSTSFICCADISTALPLGSSRPAPAPRHREHEHGHQARPPRLLXTSLMPLSTP
AAAQLLWTQLTPMGGRPGGRHSPPTLHTGPRALPPGPPHPSLHVAALSLLR
35 (SEQ ID N0:540). Polynucleotides encoding such polypeptides are also provided.
This gene is expressed primarily in endometrial tumor and to a lesser extent in amniotic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, reproductive and immune disorders particularly cancers of those systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 308 as residues: Ser-3 to Arg-9.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of immune and reproductive disorders particularly cancers of those systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 76 This gene is expressed primarily in kidney cortex and to a lesser extent in early stage human brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, renal disorders such as renal cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the kidney expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 309 as residues:
Gly-38 to Gly-45, Gly-47 to Gly-52, Pro-92 to Lys-110.
The tissue distribution indicates that the protein products of this gene are useful for study, treatment and diagnosis of renal diseases such as cancer of the kidney.
FEATURES OF PROTEIN ENCODED BY GENE NO: 77 This gene is expressed primarily in kidney medulla.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, metabolic and renal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the metabolic and renal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for study, treatment and diagnosis of metabolic and renal diseases and disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 78 This gene is expressed in chronic synovitis and microvascular endothelium.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, arthritis and atherosclerosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular and skeletal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for study, diagnosis and treatment of arthritic and other inflammatory diseases as well as cardiovascular diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 79 This gene is expressed in resting T-cells and activated monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for the study and treatment of immune diseases such as inflammatory conditions.
FEATURES OF PROTEIN ENCODED BY GENE NO: 80 This gene is expressed in a variety of immune system tissues, e.g., neutrophils, T-cells, and TNF induced epithelial and endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infectious and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and vascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 313 as residues: Met-1 to Trp-6.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of infectious diseases, immune and vascular disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 81 This gene is expressed in activated neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and other immune conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 82 This gene is expressed in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory and other immune conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 315 as residues:
Ala-83 to Thr-91.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 83 This gene is expressed in human neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as 5 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders 10 of the above tissues or cells, particularly of the immune and inflammatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., 15 the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of disorders of the inflammatory and immune systems.
20 FEATURES OF PROTEIN ENCODED BY GENE NO: 84 This gene is expressed in human neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 25 not limited to, disorders of the inflammatory and immune systems.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the inflammatory and immune systems, expression of this gene at significantly higher or lower levels may be 30 routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
35 The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of disorders of the immune and inflammatory systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 85 This gene is expressed in activated neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and immune system diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and inflammatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of diseases of the inflammatory and immune systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 86 This gene is expressed in activated neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and immune system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the inflammatory and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 319 as residues: Met-1 to Gly-6, Gly-32 to Pro-43, Leu-55 to Gln-60.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of disorders of the immune and inflammatory system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 87 In specific embodiments, polypeptides of the invention comprise the sequence:
EQVLALLWPRFELILEMNVQSVRSTDPQRLGGLDTRPHYITRRYAEFSSALVSIN
QTIPNERTMQLLGQLQVEVENFVLRVAAEFSSRKEQLVFLINNYDMMLGVLME
RAADDSKEVESFQQLLNARTQEFIEELLSPPFGGLVAFVKEAEALIERGQAERLR
GEEARVTQLIRGFGSSWKSSVESLSQDVMRSFTNFRNGTSIIQG (SEQ ID
N0:54I ),ALLKYRFFYQFLLGNERATAKEIRDEYVETLSKIYLSYYRSYLGRLMK
VQYEEVAEKDDLMGVEDTAKKGFXSKPSRSRNTIFTLGTRGSVISPTELEAPILV
PHTAQR (SEQ ID NO: 542); EQRYPFEALFRSQHYXLLDNSCREYLFICEFFVVS
GPXAHDLFHAVMGRTLSMTLKHLDSYLADCYDAIAVFLCIHIVLRFRNIAAKRD
VPALDRYW (SEQ ID NO:543),GGLDTRPHYITRRYAEFSSALVSINQ (SEQ ID
N0:544); SRKEQLVFLINNYDMMLGVL (SEQ ID NO: 545) and/or ALLKYRFFY
QFLLGNERATAKEIRDEYVETLSKIYLSYYRSYLGRLMKVQYEEVAEKDDLMG
VEDTAKKGFXSKPSLRSRNTIFTLGTRGSVISPTELEAPILVPHTAQRXEQRYPF
EALFRSQHYXLLDNSCREYLFICEF'FVVSGPXAHDLFHAVMGRTLSMTLKHLD
S YLADCYDAIA VFLCIHIVLRFRNIAAKRDV PALDRYWEQ VLALLWPRFELILEM
NVQSVRSTDPQRLGGLDTRPHYITRRYAEFSSALVSINQTIPNERTMQLLGQLQV
EVENFVLRVAAEFSSRKEQLVFLINNYDMMLGVLMERAADDSKEVESFQQLLN
ARTQEFIEELLSPPFGGLVAFVKEAEALIERGQAERLRGEEARVTQLIRGFGSSW
KSSVESLSQDVMRSFTNFRNGTS (SEQ ID N0:546). Polynucleotides encoding these polypeptides are also encompassed by the invention. The translation product of this gene shares sequence homology with suppressor of actin mutation which is thought to be important in mutation suppression.
This gene is expressed primarily in fetal liver and to a lesser extent in a variety of other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver and mutations. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the liver or cancer, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 320 as residues:
Val-53 to Arg-60, Thr-88 to Thr-94, Ala-142 to Ser-150, Gly-188 to Glu-196, Gly-208 to Ser-214, Thr-227 to Gly-232, Lys-279 to Phe-285.
The tissue distribution and homology to suppressor of actin mutation suggest that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and of liver disorder or cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 88 This gene maps to chromosome 9, and therefore can be used in linkage analysis as a marker for chromosome 9. In specific embodiments, polypeptides of the invention comprise the sequence:
YEGKEFDYVFSIDVNEGGPSYKLPYNTSDDPWLTAYNFLQKNDLNPMFLDQVA
KFIIDNTKGQMLGLGNPSFSDPFTGGGRYVPGSSGSSNTLPTADPFTGAGRYV
PGSASMGTTMAGVDPFTGNSAYRSAASKTMNIYFPKKEAVTFDQANPTQILGK
LKELNGTAPEEKKLTEDDLILLEKILSLICNSSSEKPTVQQLQILWKAINCPEDIV
FPALDILRLSIKHPSVNENFCNEKEGAQFSSHLINLLNPKGKPANQLLALRTFC
NCFVGQAGQKLMMSQRESLMSHAIELKSGSNKNI (SEQ ID NO: 547);
HIALATLALNYSVCFHKD (SEQ ID NO: 548); HNIEGKAQCLSLISTILEVVQ
DLEATFRLLVALGTLISDDSNAVQLAKS (SEQ ID N0:549); LGVDSQIKKYSS
VSEPAKVSECCRFILNLL (SEQ ID NO:550); and/or YEGKEFDYVFSIDVNEGGPS
YKLPYNTSDDPWLTAYNFLQKNDLNPMFLDQVAKFIIDNTKGQMLGLGNPSFS
DPFTGGGRYVPGSSGSSNTLPTADPFTGAGRYVPGSASMGTTMAGVDPFTGN
SAYRS AAS KTMNIYFPKKEA VTFDQANPTQILGKLKELNGTAPEEKKLTEDDLI
LLEKILSLICNSSSEKPTVQQLQILWKAINCPEDIVFPALDILRLSIKHPSVNENFC
NEKEGAQFSSHLINLLNPKGKPANQLLALRTFCNCFVGQAGQKLMMSQRESL
MSHAIELKSGSNKNIHIALATLALNYS VCFHKDHNIEGKAQCLSLISTILEV VQD
LEATFRLLVALGTLISDDSNAVQLAKSLGVDSQIKKYSS VSEPAKVSECCRFILN
LL (SEQ ID NO:551 ). Polynucleotides encoding these polypeptides are also encompassed by the invention. These polypeptides share significant homology with phospholipase A2 activating protein which is thought to be important in signal transduction (see, e.g., Wang et al., Gene 161 (2):237-241 ( 1995)).
This gene is expressed primarily in endothelial cells, to a less extent in placenta, endometrial stromal cells, osteosarcoma, testis tumor, muscle, and infant brain that are likely to be rich in blood vessles.
Therefore, polynucleotides and poIypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders in vascular system, aberrent angiogenesis, tumor angiogenesis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system or tumors, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in endothelial cells and several potential highly vascularized tissues and its homology to phospholipase A2 activating protein suggest that this gene may be involved in transducing signals for endothelial cells in angiogenesis or vasculogenesis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 89 In specific embodiments, polypeptides of the invention comprise the sequence:
YPNQDGDILRDQVLHEHIQRLSKWTANHRALQIPEVYLREAPWPSAQSEIRTIS
AYKTPRDKVQCILRMCSTIMNLLSLANEDSVPGADDFVPVLVFVLIKANPPCLL
STVQYISSFYASCLSGEESYWWMQFTAAVE (SEQ ID N0:552); YPNQDGDILR
DQVLHEHIQRLSKV VTANHRALQIPEVYLREAPWPSAQSEIRTISAYKTPRDKVQ
CILRMCSTIMNLLSLANEDSVPGADDFVPVLVFVLIKANPPCLLSTVQYISSFYA
SCLSGEESYWVVMQFTAAVEFIKTI (SEQ ID N0:553); YPNQDGDILRDQVL (SEQ
ID N0:554); EAPWPSAQSEI (SEQ ID N0:555); PVLVFVLIKANP (SEQ ID
N0:560); SGEESYWWMQFTAAVEFIKTI (SEQ ID N0:556); ADDFVPVLVF
VLIKANPP (SEQ ID N0:557); YKTPRDKVQCIL (SEQ ID N0:558); andlor GADDFVPVLVFVLIK (SEQ ID N0:559). The translation product of this gene shares sequence homology with human ras inhibitor and yeast VPS9p which is thought to be important in golgi vacuole transport.
This gene is expressed primarily in T cells and melanocytes and to a lesser extent in a variety of other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, dysfunction and disorders involving T cells and melanocytes.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression Ievel, i.e., the expression IeveI in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to ras inhibitor indicates that 10 polynucleotides and polypeptides corresponding to this gene are useful for regulating signal transduction; diagnosis and treatment of disorders involving T cells and melanocytes.
FEATURES OF PROTEIN ENCODED BY GENE NO: 90 15 This gene maps to chromosome 9 and therefore polypeptides of the invention can be used in linkage analysis as a marker for chromosome 9. The translation product of this gene shares sequence homology with neuronal olfactomedin-related ER
localized protein which is thought to be important in influence the maintenance, growth, or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. In 20 specific embodiments, polypeptides of the invention comprise the sequence:
SARASTQPPAGQHPGPC (SEQ ID N0:561); MPGRWRWQRDMHPARKLLSLL
FLILMGTELTQD (SEQ ID N0:562); SAAPDSLLRSSKGSTRGSL (SEQ ID
N0:563); AAIVIWRGKSESRIAKTPGI (SEQ ID N0:564); FRGGGTLVLPPTHT
PEWLIL (SEQ ID N0:567); PLGITLPLGAPETGGGD (SEQ ID N0:565); and/or 25 CAAETWKGSQRAGQLCALLA (SEQ ID N0:566).
This gene is expressed in pineal gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 30 not limited to, neurological and endocrinological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neurological or endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected 35 in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 323 as residues: Leu-20 to Ala-26, Arg-32 to Arg-39, Thr-104 to Gly-112.
The tissue distribution and homology to olfactomedin-related protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for maintenance, growth, or differentiation of neuron cells in pineal gland, therefore, may be useful for diagnosis and treatment of neurological disorders in pineal gland.
FEATURES OF PROTEIN ENCODED BY GENE NO: 91 This gene is expressed primarily in prostate and apoptotic T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate disease and T cell dysfunction. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing irnmunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate cancer, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detect abnormal activity in prostate and T cells or probably treatment of this abnormality.
FEATURES OF PROTEIN ENCODED BY GENE NO: 92 This gene is expressed primarily in prostate and to a lesser extent in smooth muscle cells, fibroblasts, and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders in prostate or vascular system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prosate or vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for regulating function of prostate or highly vascularized tissues, e.g. placenta.
FEATURES OF PROTEIN ENCODED BY GENE NO: 93 This gene is expressed primarily in embryos and fetal tissues stage human and to a lesser extent in a wide variety of other proliferative tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders in embryonic development and cell proliferation.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryonic tissues and proliferative cells, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis or treatment of abnormalities in developing and proliferative cells and organs.
FEATURES OF PROTEIN ENCODED BY GENE NO: 94 The translation product of this gene shares sequence homology with transformation related protein which is thought to be important in transformation.
This gene is expressed primarily in female reproductive tissues, i.e., breast cancer cells, placenta, and ovary and to a lesser extent in fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer or dysfunction of reproductive tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproduction system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids-(e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 327 as residues: Ser-50 to Pro-61.
The tissue distribution and homology to transformation related protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of conditions caused by transformation, i.e.
tumorigenesis in reproductive organs, e.g. breast, placenta, and ovary.
FEATURES OF PROTEIN ENCODED BY GENE NO: 95 This gene is expressed primarily in testes, rhabdomyosarcoma, infant brain and to a lesser extent in some tumors and highly vascularized tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumorigenesis, abnormal angiogenesis, and/or neurological disorders. , Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tumor tissues or vascular tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 328 as residues: Arg-46 to Trp-54, Pro-60 to Ile-69, Asn-116 to Ala-122, Arg-147 to Lys-153, Ser-158 to Glu-170, IIe-399 to Ser-405, Pro-486 to Met-499, Pro-502 to Asp-508.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for a range of disease states including treatment of tumor or vascular disorders and the treatment of neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 96 This gene maps to chromosome 7 and therefore polynucleotides of the present invention can be used in linkage analysis as a marker for chromosome 7. The translation product of this gene is homologous to the Clostridium perfringens enterotoxin (CPE} receptor gene product and shares sequence homology with a human ORF specific to prostate and a glycoprotein specific to oligodendrocytes both of which are tissue specific proteins.(See e.g., Katahira et al., J Cell Biol.
136(6):1239-1247 ( 1997). PMID: 9087440; UI: 97242441.
This gene is expressed primarily in pancreas tumor and ulcerative colitis and to a lesser extent in several tumors and normal tissues.
i 5 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, pancreatic disorder, ulcerative colitis, tumors and food poisoning.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system or tumorigenic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 329 as residues: Gly-147 to Met-152, Cys-I77 to Lys-188.
The tissue distribution and homology to prostate and oligodendrocyte-specific protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for marker of diagnosis or treatment of disorder in pancreas, ulcerative colitis, a.nd tumors. Furthermore, identity to the human receptor for Clostridium perfringenes entertoxin indicates that the soluble portion of this receptor could be used in the treatment of food poisoning associated with Clostridia perfringens by blocking the activity of perfringens enterotoxin.
FEATURES OF PROTEIN ENCODED BY GENE NO: 97 The translation product of this gene shares sequence homology with ATPase which is thought to be important in metabolism.
5 This gene is expressed primarily in testes and several hematopoietic cells and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 10 not limited to, leukemia and hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues 15 (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
20 NO: 330 as residues: Leu-37 to Ala-42.
The tissue distribution and homology to ATPase indicates that polynucleotides and polypeptides corresponding to this gene are useful for marker of diagnosis and treatment of leukemia and other hematopoietic disorders.
25 FEATURES OF PROTEIN ENCODED BY GENE NO: 98 In specific embodiments, polypeptides of the invention comprise the sequence:
MRSARPSLGCLPSWAFSQALNI (SEQ ID N0:568); LLGLKGLAPAEISAVCE
KGNFN (SEQ ID N0:569); VAHGLAWSYYIGYLRLILPELQARIR (SEQ ID
N0:570); TYNQHYNNLLRGAVSQRC (SEQ ID N0:571); ILLPLDCGVPDNLSM
30 ADPNIRFLDKLPQQTGDRAGIKDRVYSN (SEQ ID N0:572); SIYELLENGQRAGT
CVLEYATPLQTLFAMSQYSQAGFSGEDRLEQ (SEQ ID N0:573); AKLFCRTLE
DILADAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAV
PSTSTMSQEPELLISGMEKPLPLRTDFS (SEQ ID N0:574); andlor LLGLKGLA
PAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPEL (SEQ ID N0:575).
35 Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in prostate BPH and to a lesser extent in bone marrow.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, benign prostatic hypertrophy or prostate cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male urinary system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 331 as residues: Ile-60 to Asn-69, Leu-106 to Asp-112, Glu-130 to Gly-136, Phe-160 to Glu-167, Pro-184 to Cys-190, Glu-197 to Ser-202, Arg-215 to Glu-221, Thr-237 to Pro-242.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis or treatment of benign prostatic hypertrophy or prostate cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 99 This gene is expressed primarily in salivary gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders or injuries of the salivary gland. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of glandular tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides.
corresponding to this gene are useful for treatment of disorders of, or injuries to the salivary gland or other glandular tissue.
FEATURES OF PROTEIN ENCODED BY GENE NO: 100 This gene maps to chromosome 15, accordingly, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 15. The translation product of this gene shares sequence homology with a C.elegans gene of unknown function. In specific embodiments, polypeptides of the invention comprise the sequence: DPRVRLNSLTCKHIFISLTQ (SEQ ID N0:583); TMKLLKLRRNIV
KLSLYRHFTN (SEQ ID N0:576); TLILAVAASIVFIIWTTMKFRI (SEQ ID
N0:577); VTCQSDWRELWVDDAIWRLLFSMILFVI (SEQ ID N0:578); MVLWR
PSANNQRFAFSPLSEEEEEDEQ {SEQ ID N0:580); KEPMLKESFEGMKMRS
TKQEPNGNSKVNKAQEDDL (SEQ ID N0:584); and/or KWVEENVPSSVTDVALP
ALLDSDEERMITHFERSKME (SEQ ID N0:582). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in thyroid and to a lesser extent in osteoclastoma, kidney medulla, and lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, thyroid dysfunction or cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 333 as residues:
Lys-107 to Leu-124, Glu-150 to Thr-159, Pro-173 to Asp-179, Ser-192 to Ser-201.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of thyroid dysfunction or cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 101 This gene maps to chromosome 16, therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 16. In specific embodiments, polypeptides of the invention comprise the sequence:
IRHELTVLRDTRPACA (SEQ ID N0:585); and/or MDFXMALIYD (SEQ ID
N0:586). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in kidney cortex and to a lesser extent in adult brain, corpus colosum, hippocampus, and frontal cortex.
Therefore, polynucleotides and poIypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment or diagnosis of neurological disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 102 In specific embodiments, poIypeptides of the invention comprise the sequence:
MQEMMRNQDRALSNLESIPGGYNA (SEQ ID N0:587); LRRMYTDIQEPMLSA
AQEQF GGNPF (SEQ ID N0:588); ASLVSNTSSGEGSQPSRTENRDPLPNPWAP
QT (SEQ ID N0:589); SQSSSASSGTASTVGGTTGSTASGTSGQSTTAPNLVPGV
GASMFNTPG MQSLLQQITENPQLMQNMLSAPY (SEQ ID N0:590);
MRSMMQSLSQNPDLAAQMMLNNPLFAGNPQLQEQMRQQLPTFLQQ (SEQ ID
N0:591 ); MQNPDTLSAMSNPRAMQALLQIQQGLQTLATEAPGLIPGFTPGLG
ALGSTGGSSGTNGSNATPSENTSPTAGT (SEQ ID N0:592); TEPGHQQFI
QQMLQALAGVNPQLQNPEVRFQQQLEQLSAMGFLNREANLQALIATGGDINAA
IERLLGSQPS (SEQ ID N0:593); RNPAMMQEMMRNQDRALSNLESIPGGY
NALRRMYTDIQEPMLSAA (SEQ ID N0:594); GNPFASLVSNTSS (SEQ ID
N0:595); ENRDPLPNPWA (SEQ ID N0:595); GKILKDQDTLSQHGIHD (SEQ ID
N0:597); GLTVHLVIKTQNRP (SEQ ID N0:598); SELQSQMQRQLLSNPEMM
(SEQ ID N0:599); PEISHMLNNPDIMR (SEQ ID N0:600); and/or RQLIMANPQMQQLIQRNP (SEQ ID N0:601 ). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in breast.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, breast cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of tumor systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of some types of breast cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 103 The translation product of this gene shares sequence homology with secreted serine proteases and lysozyme C precursor, which is thought to be important in bacteriolytic function. In specific embodiments, polypeptides of the invention comprise the sequence: NLCHVDCQDLLNPNLLAGIHCAKRIVS (SEQ ID N0:602);
LDGFEGYSLSDWLCLAFVESKFN (SEQ ID N0:603);
NENADGSFDYGLFQINSHYWCN (SEQ ID N0:604); and/or NLCHVDCQDLLNPNLLAGIHCAKRIVS {SEQ ID N0:605). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infection. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 336 as residues: Ile-62 to Phe-70, Asn-5 78 to Asn-84.
The tissue distribution and homology to Iysozyme C precursor indicates that polynucleotides and polypeptides corresponding to this gene are useful for boosting the moncyte-macrophage system and enhance the activity of immunoagents.
10 FEATURES OF PROTEIN ENCODED BY GENE NO: 104 This gene is expressed primarily in apoptotic T-cell.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 15 not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues {e.g., 20 cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides 25 corresponding to this gene are useful for treatment and diagnosis of some immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 105 The translation product of this gene shares sequence homology with ARI
30 protein of Drosophila (accession 2058299; EMBL: locus DMARIADNE, accession X98309), which is thought to be important in axonal path-finding in the central nervous system. In specific embodiments, polypeptides of the invention comprise the sequence IREVNEVIQNPAT (SEQ ID N0:606); ITRILLSHFNWDKEKLMERYF
DGNLEKLFA (SEQ ID N0:607); NTRSSAQDMPCQICYLNYPNSYF (SEQ ID
35 N0:608); TGLECGHKFCMQCWSEYLTTKIMEEGMGQTISCPAHG (SEQ ID
N0:614); CDILVDDNTVMRLFTDSKVKLKYQHLITNSFVECNRLLKWCPAPD
CHHVVKVQYPDAKPV (SEQ 117 N0:609); CDILVDDNTVMRLITDSK
VKLKYQHLITNSFVECNRLLKWCPAPDCHHVVKV (SEQ ID N0:610);
GCNHMVCRNQNCKAEFCWVCLGPWEPHGSAWYNCNRYNEDDAKAARDAQE
RSRAALQRYL (SEQ ID N0:611); FYCNRYMNHMQSLRFEHKLYAQVKQ
KMEEMQQHNMSWIEVQFLKKAVDVLCQCRATLMYT (SEQ ID NO: 612);
YVFAFYLKKNNQS>TFENNQADLENATEVLSGYLERDISQDSLQDIKQKVQDKY
RYCESR (SEQ ID N0:613) Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adult brain, and to a lesser extent in endometrial tumor, melanocytes, and infant brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases or injuries involving axonal path development.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to ARI protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of disease states or injuries involving axonal path development, including neurodegenerative diseases and nerve injury.
FEATURES OF PROTEIN ENCODED BY GENE NO: 106 The translation product of this gene shares sequence homology with cytochrome b561 [Sus scrofa) which is thought to be an integral membrane protein of neuroendocrine storage vesicles of neurotransmitters and peptide hormones.
This gene is expressed primarily in frontal cortex and to a lesser extent in rhabdomyosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 339 as residues:
Ser-18 to Pro-24.
The tissue distribution and homology to cytochrome b561 [Sus scrofaJ indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of neurological disorders. This gene may also be important in regulation of some types of cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 107 In specific embodiments, polypeptides of the invention comprise the sequence:
MWGYLFVDAAWNFLGCLICGW (SEQ ID N0:615); MHFISSGNVSAIRSSILLL
RXSLSYLGNCLRVSAIFVYFLLFLLLS (SEQ ID N0:616); and/or MDQALRGSPSE
GFSTDPSPPQVGRQIPSFPPWRRLVLPKASGCFLEREWWLCVFKLRTRPGAEA
HAYNSSILGGRGKGIT (SEQ ID N0:617). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in pancreas tumor and to a lesser extent in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, pancreatic tumors. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred WO 98!54963 PCT/US98/11422 epitopes include those comprising a sequence shown in SEQ ID NO: 340 as residues:
Pro-22 to Phe-33.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of pancreatic tumors.
FEATURES OF PROTEIN ENCODED BY GENE NO: 108 This gene maps to chromosome 17 and therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 17. In specific embodiments, polypeptides of the invention comprise the sequence:
MLPALASCCHFSPPEQAARLKKLQEQEKQQKVEFRKRMEKEVSDFIQDSGQIK
KKFQPMNKIERSILHDV VEVAGLTSFSFGEDDDCRYVMIFKKEFAPSDEELDS Y
RRGEEWDPQKAEEKRNXKELAQRQ (SEQ ID N0:618); EEEAAQQGPV V V
SPASDYKDKYSHLIGKGAAKDAAHMLQANKTYGCXPVANKRDTRSIEEAMNE
IRAKKRLRQSGE (SEQ ID N0:619); PPRRPAQLPLTPGAGQGAGRDKAAAIRA
HPGAPPLNHLLP (SEQ IDN0:620); AVPQAGGKQVFDLSPLELGYVRGMCVCV
(SEQ ID N0:621) and/or MLPALASCCHFSPPEQAARLKKLQEQEKQQKVEFRK
RMEKEVSDFIQDSGQIKKKFQPMNKIERSILHDV VEVAGLTSFSFGEDDDCRYV
MIFKKEFAPSDEELDSYRRGEEWDPQKAEEKRNXKELAQRQEEEAAQQGPV V V
SPASDYKDKYSHLIGKGAAKDAAHMLQANKTYGCXPVANKRDTRSIEEAMNE
IRAKKRLRQSGE (SEQ ID N0:622). Polynucleotides encoding these polypeptides are also encompassed by the invention. The translation product of this gene shares sequence homology with FSA-1 which may play a role as a structural protein component of the acrosome.
This gene is expressed primarily in fetal kidney and sperm.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive disorders, especially involving acrosomal disfunction.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 341 as residues: Glu-8 to Asn-35.
The tissue distribution and homology to FSA-1 indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of infertility due to acrosomal disfunction of sperm.
FEATURES OF PROTEIN ENCODED BY GENE NO: 109 This gene is expressed primarily in pituitary and to a lesser extent in epididymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 342 as residues: Met-1 to Trp-6.
Because the gene is found in both pituitary and epididymus, this indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of male reproductive disorders. This may involve a secreted peptide produced in the pituitary targeting the epididymus.
FEATURES OF PROTEIN ENCODED BY GENE NO: 110 In specific embodiments, polypeptides of the invention comprise the sequence:
LLCPVLNSGXSWNFPHPSQPEYSFHGFHSTRLWI (SEQ ID N0:623); and/or PSTPWFLFLLGLTCPFSTSHPRWDSIPP (SEQ ID N0:624). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in resting T-cells. .
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are WO 98/54963 PCT/iJS98/11422 not limited to, T-cell disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or 5 lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
10 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of certain immune disorders, especially those involving T-cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 111 15 This gene is expressed primarily in cerebellum and whole brain and to a lesser extent in infant brain and fetal kidney.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 20 not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., 25 cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 344 as residues:
30 Asp-48 to Gly-55.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neurological disorders.
35 FEATURES OF PROTEIN ENCODED BY GENE NO: 112 The translation product of this gene shares sequence homology with yeast mitochondrial ribosomal protein homologous to ribosomal protein s 15 of E.coli which is thought to be important in the early assembly of ribosomes (See Accession No.
M38016). This gene maps to chromosome l, and therefore, may be used as a marker in linkage analysis for chromosome 1.
This gene is expressed primarily in developmental tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not linuted to, development of cancers and tumors in addition to healing wounds.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and developmental expression of this gene at signif cantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to ribosomalprotein s15 of E. coli indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases related to the assembly of ribosomes in the mitochondria which is important in the translation of RNA into protein. Therefore, this indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of multiple tumors as well as in healing wounds which are thought to be under similar regulation as developmental tissues. Protein, as well as, antibodies directed against the protein have utility as tumor markers, in addition to immunotherapy targets, for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 113 The translation product of this gene shares sequence homology with human poliovirus receptor precursors which are thought to be important in viral binding and uptake. Preferred polypeptide fragments comprise the following amino acid sequence:
ELSISISNVALADEGEYTCSIFTMPVRTAKSLVTVLGIPQKPIITGYKSSLREKDT
ATLNCQSSGSKPAARLTWRKGDQELHGEPTRIQEDPNGKTFTVSSSVTFQVTR
EDDGASIVCSVNHESLKGADRSTSQRIEVLYTPTAMIRPDPPHPREGQKLLLHC
EGRGNPVPQQYLWEKEGSVPPLKMTQESALIFPFLNKSDSGTYGCTATSNMGS
YKAYYTLNVND (SEQ ID N0:625). Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No. gnIIPIDId1002627).
This gene is expressed almost exclusively in human brain tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, susceptibility to viral disease and diseases of the CNS
especially cancers of that system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues} or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 346 as residues: Leu-26 to Asp-37, Lys-53 to Ser-59.
The tissue distribution and homology to poliovirus receptor precursors indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and prevention of diseases that involve the binding and uptake of virus particles for infection. It might also be helpful in genetic therapy where the goal is to insert foreign DNA into infected cells. With the help of this protein, the binding and uptake of this foreign DNA might be aided. In addition, it is expected that over expression of this gene will indicate abnormalities involving, the CNS, particularly cancers of that system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 114 The translation product of this gene shares sequence homology with Y087_CREEL hypothetical 28.5 KD protein ZK1236.7 in chromosome III of Caenorhabditis elegans in addition to alpha-1 collagen type III (See Accession No.
gi1537432). One embodiment for this gene is the polypeptide fragments) comprising the following amino acid sequence: VPELPDRVHQLHQAVQGCALGRPGFPGGPTH
SGHHKSHPGPAGGDYNRCDRPGQVHLHNPRGTGRRGQLHPTAGPGVHRRA
CPSQQLPHRLGPGVPCPSPSLTPVLPSWTQSWCG LPGYTSSS (SEQ ID
N0:630). An additional embodiment is the polynucleotide fragments) encoding these polypeptide fragments This gene is expressed primarily in brain cells and to a lesser extent in activated B and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegeneration and imunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 347 as residues: Glu-34 to Glu-39, Gly-51 to Ser-72, Ala-88 to Glu-93, Gln-to Val-105.
The tissue distribution and homology to Y087_CAEEL hypothetical 28.5 KD
protein ZK1236.7 in chromosome III of Caenorhabditis elegans as well as to a conserved alpha-1 collagen type III protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons' Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorders. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 115 The translation product of this gene shares sequence homology with alpha 3 type IX collagen which is thought to be important in hyaline cartilage formation via its ability to uptake inorganic sulfate by cells (See Accession No. gi1975657).
One embodiment of this gene is the polypeptide fragment comprising the following amino acid sequence: SLRRPRSAAXQTLTTFLSSVSSASSSALPGSREPCDPRAPPPPR
SGSAASCCSCCCSCPRRRAPLRSPRGSKRRIRQREVVDLYNGMCLQGPAGVPG
RDGSPGANGIPGTPGIPGRDGFKGEKGECLRESFEESWTPNYKQCSWSSLNY
GIDLGKIAECTFTKMRSNSALRVLFSGSLRLKCRNACCQRWYFTFNGAECSGP
LPIEAIIYLDQGSPEMNSTINIHRTSSVEGLCEGIGAGLVDVAIWVGTCSDYPKG
DASTGWNSVSRIIIEELPK (SEQ ID N0:634). An additional embodiment are the polynucleotide fragments encoding this polypeptide fragment.
This gene is expressed primarily in smooth muscle and to a lesser extent in synovial tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias i.e., spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid and autoimmune disorders . Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to alpha 3 type IX collagen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of diseases associated with the mutation in this gene which leads to the many different types of chondrodysplasias. By the use of this product, the abnormal growth and development of bones of the limbs and spine could be routinely detected or treated in utero since the protein or muteins thereof could affect epithelial cells early in development and later the chondrocytes of the developing craniofacial structure.
FEATURES OF PROTEIN ENCODED BY GENE NO: 116 The translation product of this gene shares sequence homology with retrovirus-related reverse transcriptase which is thought to be important in viral replication. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: TKKENCRPASLMNIDTKILNKIL.MNQ (SEQ ID N0:640). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments (See Accession No. pirIA253131GNHUL1).
This gene is expressed primarily in human meningima.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include.
but are not limited to, retroviral diseases such as AIDS, and possibly certain cancers due to transactivation of latent cell division genes. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of 5 the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level 10 in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to retrovirus-related reverse transcriptase indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of diseases and maladies associated with retroviral infection since a functional reverse transcriptase (RT) or RT-like molecule is an integral I S component of the retroviral life cycle.
FEATURES OF PROTEIN ENCODED BY GENE NO: 117 The translation product of this gene shares sequence homology with an unknown gene from C. elegans, as well as weak homolog with mammalian metaxin, a 20 gene contiguous to both thrombospondin 3 and glucocerebrosidase, is known to be required for embryonic development. Preferred polypeptide fragments comprise the following amino acid sequence: MCNLPIKVVCRANAEYMSPSGKVPXXHVGNQ
VVSELGPIVQFVKAKGHSLSDGLEEVQKAEMKAYMELVNNMLLTAELYLQWC
DEATVGXITHXRYGSPYPWPLXHILAYQKQWEVKRKXKAIGWGKKTLDQVLE
YSNLLAFCRRI EQHYFEDRGKGRLS (SEQ ID N0:641); MCNLPIKVVCRANAE
YMSPSGKVPXXHVGNQVVSELGPIVQFVK (SEQ ID N0:642),. Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No.
gi11326108).
30 This gene is expressed primarily in fetal tissues and to a lesser extent in hematopoietic cells and tissues, including spleen, monocytes, and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 35 not limited to, cancer; lymphoproliferative disorders; inflammation;
chondrosarcoma, and Gaucher disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and embryonic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other proliferative disorders. Expression in embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation or cellular division. Additionally, the expression in hematopoietic cells and tissues indicates that this protein may play a role in the proliferation, differentiation, and survival of hematopoietic cell lineages. Thus, this gene may be useful in the treatment of lymphoproliferative disorders, and in the maintenance and differentiation of various hematopoietic lineages from early hematopoietic stem and committed progenitor cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 118 The translation product of this gene shares sequence homology with reverse transcriptase which is important in the synthesis of a cDNA chain from an RNA
molecule, and is a method whereby the infecting RNA chains of retroviruses are transcribed into their DNA complements. One embodiment for this gene is the polypeptide fragment comprising the following amino acid sequence:
MXXXNSHITIFTLNVNGLNAPNERHRLANWIQSQDQVCCIQETHLTGRDTHRL
KIKGWRKIYQANGKQKK (SEQ ID NO:b47). An additional embodiment is the polynucleotide fragments comprising polynucleotides encoding these polypeptide fragments (See Accession No. gi12072964).
This gene is expressed primarily in skin and to a lesser extent in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer, hematopoietic disorders; inflammation; disorders of immune surveillance. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the epidermis and/or hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to reverse transcriptase indicates that polynucleotides and polypeptides corresponding to this gene are useful for cancer therapy. Expression in the skin also indicates that this gene is useful in wound healing and fibrosis. Expression by neutrophils also indicates that this gene product plays a role in inflammation and the control of immune surveillance (i.e. recognition of viral pathogens). Reverse transcriptase family members are also useful in the detection and treatment of AIDS.
FEATURES OF PROTEIN ENCODED BY GENE NO: 119 The translation product of this gene shares sequence homology with reverse I S transcriptase which is important in the synthesis of a cDNA copy of an RNA
molecule, and is a method whereby a retrovirus reverse-transcribes its genome into an inheritable DNA copy.
This gene is expressed primarily in the frontal cortex of brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer and neurodegenerative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS and peripheral nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to reverse transcriptase suggest that this is useful in the treatment of cancer and AIDS. The expression in brain indicates that it plays a role in neurodegenerative disorders and in neural degeneration.
FEATURES OF PROTEIN ENCODED BY GENE NO: 120 One embodiment of this gene has homology to a hypothetical protein in Schizosaccharomyces pombe (See Accession No. 2281980). Another embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
IYHLHS WIFFHFKRAFCMCFITMKVIHAHCSKLRKCXNAQIS VFCTTLTASYPT
(SEQ ID N0:651}. An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments. This gene maps to chromosome 18, and therefore, may be used as a marker in linkage analysis for chromosome 18.
This gene is expressed primarily in adult hypothalamus and to a lesser extent in infant brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative disorders; endocrine function; and vertigo.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain, CNS and peripheral nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of neurodegenerative disorders; diagnosis of tumors of a brain or neuronal origin;
treatments involving hormonal control of the entire body and of homeostasis, behavioral disorders, such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo.
FEATURES OF PROTEIN ENCODED BY GENE NO: 121 The translation product of this gene shares sequence homology with the human IRLB protein which is thought to be important in binding to a c-myc promoter element and thus regulating its transcription (See Accession No. gi133969). This gene maps to chromosome 1, and therefore, may be used as a marker in linkage analysis for chromosome 1.
This gene is expressed primarily in brain and breast and to a lesser extent in a variety of hematopoietic tissues and cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer of the brain and breast; lymphoproliferative disorders;
neurodegenerative diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS, breast, and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial i 5 fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of cancer of the brain, breast, and hematopoietic system. In addition, it may be useful for the treatment of neurodegenerative disorders, as well as disorders of the hematopoietic system, including defects in immune competency and inflammation. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 122 The translation product of this gene shares sequence homology with an ATP
synthase, a key component of the proton channel that is thought to be important in the translocation of protons across the membrane.
This gene is expressed primarily in T cell lymphoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, T cell lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system. expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily 5 fluid from an individual not having the disorder.
The tissue distribution and homology to ATP synthase indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of defects in proton transport, homeostasis, and metabolism, as well as the diagnosis and treatment of lymphoma. Because the gene is expressed in cells of lymphoid origin, 10 the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for imununological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia FEATURES OF PROTEIN ENCODED BY GENE NO: 123 15 This gene maps to chromosome 1 S, and therefore, may be used as a marker in linkage analysis for chromosome 15.
This gene is expressed primarily in a variety of fetal tissues, including fetal liver, lung, and spleen, and to a lesser extent in a variety of blood cells, including eosinophils and T cells.
20 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer (abnormal cell proliferation); T cell lymphomas; and hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are 25 useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the fetus and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or 30 another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of conditions 35 involving cell proliferation. Expression of this gene in fetal tissues, as well as in a variety of blood cell lineages indicates that it may play a role in either cellular proliferation; apoptosis; or cell survival. Thus it may be useful in the management and treatment of a variety of cancers and malignancies. In addition, its expression in blood cells suggest that it may play additional roles in hematopoietic disorders and conditions, and could be useful in treating diseases involving autoimmunity, immune modulation, immune surveillance, and inflammation..
FEATURES OF PROTEIN ENCODED BY GENE NO: 124 -This gene is expressed primarily in placenta and to a lesser extent in pineal gland and rhabdomyosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental, endocrine, and female reproductive disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For I5 a number of disorders of the above tissues or cells, particularly of the [insert system where a related disease state is likely, e.g., immune], expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 357 as residues:
Leu-69 to Val-76.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders in development. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 125 This gene is expressed primarily in benign prostatic hyperplasia Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of benign prostatic hyperplasia.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of benign prostatic hyperplasia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 126 This gene is expressed primarily in apoptotic T-cells and to a lesser extent in suppressor T cells and ulcerative colitis.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases involving premature apoptosis, and immunological and gastrointestinal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders involving inappropriate levels of apoptosis, especially in immune cell lineages. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases (such as AIDS), and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: I27 This gene is expressed primarily in Raji cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and T cell autoimmune disorders. Similarly;
polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 360 as residues: Asp-23 to Gly-29.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of inflammation and T
cell autoimmune disorders. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases (such as AIDS), and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 128 The translation product of this gene shares sequence homology with an C.
elegans coding region C47D12.2 of unknown function (See Accession No.
gnIIPIDle348986). One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: EDDGFNRSIHEVILKNITWY
SERVLTEISLGSLLILV V IRTIQYNMTRTRDKYLHTNCLAALANMSAQFRSLHQY
AAQRIISLFSLLSKKHNKVLEQATQSLRGSLSSNDVPLPDYAQDLNVIEEVIRMM
LEIINSCLTNSLHHNPNLVALLYKRDLFEQFRTHPSFQDIMQNIDLVISFFSSRLL
QAGS (SEQ ID N0:657); EDDGFNRSIHEVILKNITWYSERVLTEISLGSLLILVV
(SEQ ID N0:658); RTIQYNMTRTRDKYLHTNCLAALANMSAQFRSLHQYAAQ
RIISLFSLLSKKHN (SEQ ID N0:659); KKHNKVLEQATQSLRGSLSSNDVPLPDY
AQD (SEQ ID N0:661); SCLTNSLHHNPNLVYALLYKRDLFEQFRTHPSFQD
IMQNIDLVISFFSSRLLQAGS (SEQ ID N0:660). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments. This gene maps to WO 98!54963 PCTNS98/11422 chromosome 18, and therefore, may be used as a marker in linkage analysis for chromosome 18.
This gene is expressed primarily in smooth muscle and to a lesser extent in fetal liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, atherosclerosis and other cardiovascular and hepatic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the circulatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of circulatory system disorders such as atherosclerosis, hypertension, and thrombosis . In addition, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers {e.g.
hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). In addition the expression in fetus would suggest a useful role for the protein product in developmental abnormalities, fetal deficiencies, pre-natal disorders and various would-healing models and/or tissue trauma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 129 The translation product of this gene shares sequence homology with a ribosomal protein which is thought to be important in cellular metabolism, in addition to the C.elegans protein F40F11.1 which does not have a known function at the current time (See Accession No. gnlIPIDIe244552 ). Preferred polypeptide fragments comprise the following amino acid sequence:
MADIQTERAYQKQPTIFQNKKRVLLGETGKEKLPRVTNKNIGLGFKDT
PRRLLRGTYIDKKCPFTGN V SIRGRILSG V V TQDEDAEDHCHPPRLSALHPQV Q
PLREAPQEHVCTPVPL LQGRPDR (SEQ ID N0:662); MKMQRTIVIRRDYLH
YIRKYNRFEKRHKNMSVHLSPCFRDVQIGDIVTVGECRPLSKTVRFNVLKVTK
AAGTKKQFQKF (SEQ ID N0:663); MADIQTERAYQKQPTIFQNKKRVLLGET
GK (SEQ ID N0:664); HCHPPRLSALHPQVQPLREAPQEHVCTPVPL LQGRPDR
(SEQ ID N0:666); NIGLGFKDTPRRLLRGTYIDKKCPFTGNVSIRGRILSGVVTQ
(SEQ ID N0:669); MKMQRTIVIRRDYLHYIRKYNRFEKRHKNMSVHLSP (SEQ
ID N0:667); CFRDVQIGDIVTVGECRPLSKTVRFNVLKVTKAAGTKKQFQKF
(SEQ ID N0:668). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in Wilm's tumor and to a lesser extent in thymus and stromal cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases affecting RNA translation. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the Wilm's tumors, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 362 as residues:
Thr-11 to Asp-20.
The tissue distribution and homology to a ribosomal protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases affecting RNA translation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 130 The translation product of this gene shares sequence homology with a yeast DNA helicase which is thought to be important in global transcriptional regulation (See Accession No. gnllPIDle243594). One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: IFYDSDWNPTVDQQA
MDRAHRLGQTKQVTVYRLICKGTIEERILQRAKEKSEIQRMVISG (SEQ ID
N0:670); TRMIDLLEEYMVYRKHTYXRLDGSSKISERRDMVADFQNRNDI
FVFLLSTRAGGLGINLTAXDTVHF (SEQ ID N0:671); TRMIDLLEEYMVYRK
HTYXRLDGSSKISERRDM (SEQ ID N0:674); RRDMVADFQNRNDIFVFLL
STRAGGLGINLTAXDTVHF (SEQ ID N0:675) , IFYDSDWNPTVDQQAMD
RAHRLGQTKQVTVYRLICKG (SEQ ID N0:676); RLICKGTIEERILQRAK
EKSEIQRMVISG (SEQ ID N0:678). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in amygdala.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases and disorders of the brain. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to a DNA helicase indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases affecting RNA transcription, particularly developmental disorders and healing wounds since the later are though to approximate developmental transcriptional regulation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 131 This gene is expressed primarily in prostate and to a lesser extent in arnygdala and pancreatic tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate enlargement and gastrointestinal disorders, particularly of the pancreas and gall bladder. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of prostate diseases, including benign prostatic hyperplasia and prostate cancer. In addition, the tissue distribution in tumors of the pancreas indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tissues where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 132 This gene is expressed primarily in adult lung and to a lesser extent in hypothalamus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, pulmonary diseases and neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the pulmonary and respiratory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid] or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of pulmonary and respiratory disorders such as emphysema, pneumonia, and pulmonary edema and emboli. In addition, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 133 This gene is expressed primarily in human liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cirrhosis of the liver and other hepatic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids {e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of liver disorders such as cirrhosis, jaundice, and Hepatitus. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 134 This gene is expressed primarily in fetal kidney and to a lesser extent in fetal liver and spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, development and regeneration of liver and kidney and immunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive and excretory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 367 as residues: Pro-70 to Arg-77, Tyr-102 to Thr-107.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases of the kidney and liver, such as cirrhosis, kidney failure, kidney stones, and liver failure, hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells. In addition the expression in fetus would suggest a useful role for the protein product in developmental abnormalities, fetal deficiencies, pre-natal disorders and various would-healing models and/or tissue trauma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 135 This gene is expressed primarily in brain, bone marrow, and to a lesser extent in placenta, T cell, testis and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative and immunological diseases and cancer.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid} or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 368 as residues: Met-I to His-6.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 136 Translatation product of this gene is homologous to the human WD repeat protein HAN 11. Preferred polypeptide fragments comprise the following amino acid sequence:
MSLHGKRKEIYKYEAPWTVYAMNWSVRPDKRFRLALGSFVEEYNNKVQLVG
LDEESSEFICRNTFDHPYPTTKLMWIPDTKGVYPDLLATSGDYLRVWRVGETET
RLECLLNNNKNSDFCAPLTSFDWNEVDPYLLGTSSIDTTCTIWGLETGQVLGRV
NLVSGHVKTQLIAHDKEVYDIAFSRAGGGRDMFAS VGADGS VRMFDLRHLEH
STIIYEDPQHHPLLRLCWNKQDPNYLATMAMDGMEVVILDVRVPAHLXPGTTIE
HV SMALLGPHIHPATSALQRMTTRLSSGTSSKCPEPLRTLS WPTQLXGEINNVQ
WASTQPELSPSATTTAWRYSECSVGGAVPTRQGLLYFLPLPHPQS (SEQ ID
N0:679); MSLHGKRKEIYKYEAPWTVYAMNWSVRPDKRFRLALGSFV
EEYNNKVQLVGLDEESSEFICRNTFDHPYPTTKLMWIPDTKGVYPDLLATSGDY
LRVWRVGETETRLECLLNNNKNSDFCAPLTSFDWNEVDPYLL (SEQ ID
N0:680); SFDWNEVDPYLLGTSSIDTTCTIWGLETGQVLGRVNLVSGHVK
HPLLRLCWNKQDPNYLATMAMDGMEVVILDVRVPAHLXPGTTI (SEQ m N0:681); VGADGSVRMFDLRHLEHSTIIYEDPQHHPLLRLCWNKQDPNYLA
TMAMDGMEVVILDVRVPAHLXPGTTIEHVSMALLGPHIHPATSALQRMTTRLS
SGTSSKCPEPLRTLSWPTQLXGEINNVQWASTQPELSPSATTTAWRYSECSVG
GAVPTRQGLLYFLPLPHPQS (SEQ ID N0:682). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in placenta, embryo, T cell and fetal lung and to a lesser extent in endothelial, tonsil and bone marrow.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological and developmental diseases in addition to cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 369 as residues: Gly-19 to Gln-28, Pro-36 to Phe-42.
The tissue distribution in tumors of colon, ovary, and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 137 This gene is expressed primarily in TNF and INF induced epithelial cells, T
cells and kidney.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory conditions particularly inflammatory reactions in the kidney. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 370 as residues: Thr-67 to Gly-72, Gln-132 to Ala-145, Arg-150 to Pro-157.
The tissue distribution indicates that the protein products of this gene are useful for treating the damage caused by inflammation of the kidney.
FEATURES OF PROTEIN ENCODED BY GENE NO: 138 This gene maps to chromosome l, and therefore, may be used as a marker in linkage analysis for chromosome 1 (See Accession No. D63485).
This gene is expressed primarily in breast cancer and colon cancer and to a lesser extent in thymus and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers, especially of the breast and colon tissues.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of colon and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 139 This gene maps to chromosome 17, and therefore, can be used as a marker for linkage analysis from chromosome 17.
This gene is expressed primarily in CD34 positive cells, and to lesser extent in activated T-cells and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(sj or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunologically related diseases and hematopoietic disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in CD34, T-cell and neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of hematopoietic disorders and immunologically related diseases, such as anemia, leukemia, inflammation, infection, allergy, immunodeficiency disorders, arthritis, asthma, immune deficiency diseases such as AIDS.
FEATURES OF PROTEIN ENCODED BY GENE NO: 140 This gene was recently cloned by another group, who called the gene KIAA0313 gene. (See Accession No. d1021609.) Preferred polypeptide fragments comprise the amino acid sequence:
LYATATVISSPSTEXLSQDQGDRASLDAADSGRGSWTSCSSGSHDNIQTIQ
HQRSWETLPFGHTHFDYSGDPAGLWASSSHMDQIMFSDHSTKYNRQNQSRES
LEQAQSRASWASSTGYWGEDSEGDTGTIKRRGGKDVSIEAESSSLTSVTTEETK
PVPMPAHIAVASSTTKGLIARKEGRYREPPPTPPGYIGIPITDFPEGHSHPARKP
PDYNVALQRSRMVARSSDTAGPSSVQQPHGHPTSSRPVNKPQWHKXNESDPR
LAPYQSQGFSTEEDEDEQVSAV (SEQ 117 N0:683); HMDQIMFSDHSTKYNRQ
NQSRESLEQAQSRASWASSTGYWGE (SEQ ID N0:684); SVTTEETKPVPMP
AHIAVASSTTKGLIARKEGRYREPPPTPPGYIGIPITD (SEQ ID N0:685); and VALQRSRMVARSSDTAGPSSVQQPHGHPTSSRPVNKPQW
HKXNESDPRLAPYQSQGF (SEQ ID N0:686). Also preferred are polynucleotide fragments encoding these polypeptide fragments. This gene maps to chromosome 4, and therefore, may be used as a marker in linkage analysis for chromosome 4 (See Accession No. AB0023I 1 ) This gene is expressed primarily in ovarian cancer, tumors of the Testis, brain, and colon.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, ovarian, testicle, brain and colon cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells. particularly of the male and female reproductive systems.
expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of colon, ovary, testis, and brain origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 141 This gene is expressed primarily in spleen and colon cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, colon cancer and immunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal trace and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of colon, ovary, and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 142 Translation product is homologous to T cell translocation protein, a putative zinc finger factor (See Accession No. 340454), as well as to the G-protein coupled receptor TMS consensus polypeptide (See Accession No. R50734). Preferred polypeptide fragments comprise the following amino acid sequence:
CLLFVFVSLGMRCLFWTIVYNVLYLKHKCNTVLLCYHLCSI (SEQ-ID N0:687);
ACSKLIPAFEMVMRAKDNVYHLDCFACQLCNQRXCVGDKFFLKNNXXLCQT
DYEEGLMKEGYAPXVR (SEQ ID N0:688). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in fetal brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types}
present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders including brain cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the Central Nervous System, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo.
FEATURES OF PROTEIN ENCODED BY GENE NO: 143 Translation product for this gene has significant homology to the Fas ligand, which is a cysteine-rich type II transmembrane protein/tumor necrosis factor receptor homolog. Mutations within this protein have been shown to result in generalized lymphoproliferative disease leading to the development of Iymphadenopathy and autoimmune disease (See Medline Article No. 94185175). Preferred polypeptide fragments comprise the following amino acid sequence:
SALSEPGAPDRRRPCPESVPRRPDDEQWPPPTALCLDVAPLPPSS (SEQ ID
N0:689). Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No. 473565).
This gene is expressed primarily in osteoblasts, lung, and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoblast-related, pulmonary, neurological, and immunological diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 376 as residues: Trp-33 to Thr-40, Lys-45 to Ile-63.
The tissue distribution in osteoblasts, lung, and brain combined with its homology to the Fas ligand indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. Because the Fas ligand gene is known to be expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including asthma, immune deficiency diseases such as AIDS
and leukemia, and various autoimmune disorders including lupus and arthritis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 144 This gene shares sequence homology with a 21.5 KD transmembrane protein in the SEC15-SAP4 intergenic region of yeast. (See Accession No. 1723971.) Preferred polypeptide fragments comprise the amino acid sequence:
AHASESGERWWACCGVRFGLRSIEAIGRSCCHDGPGGLVANRGRRFKWAIEL
SGPGGGSRGRSDRGSGQGDSLYPVGYLDKQVPDTSVQETDRILVEKRCWDIAL
GPLKQIPMNLFIMYMAGNTISIFPTMMVCMMAWRPIQALMAISATFKMLESSSQ
KFLQGLVYLIGNLMGLALAVYKCQSMGLLPTHASDWLAFIEPPERMEFSGG
GLLL (SEQ ID N0:691); PVGYLDKQVPDTSVQETDRILVEKRCWDIALGPLKQ
IPMNLFI (SEQ ID N0:693); and ATFKMLESSSQKFLQGLVYLIGNLMGLALAV
YKCQSMGLLPTHASD (SEQ ID N0:692). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in osteoclastoma, hemangiopericytoma, liver, lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoclastoma, hemangiopericytoma, liver and lung tumors.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the above tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the lung and liver systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing osteoclastoma, hemangiopericytoma, liver and lung tumors.
FEATURES OF PROTEIN ENCODED BY GENE NO: 145 Translation product of this gene shares homology with the glucagon-69 gene which may indicate this gene plays a role in regulating metabolism. (See Accession No.
A60318) One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
PTTKLDIMEKKKHIQIRFPSFYHKLVDSGRMRSKRETRREDSDTKHNL (SEQ ID
N0:694). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in brain, kidney, colon, and testis.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain, kidney, colon, and testicular cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, neurological, S circulatory, and gastrointestinal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of brain, kidney, colon, and testis origins, indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 146 The translation product of this gene shares sequence homology with goliath protein which is thought to be important in the regulation of gene expression during development. Protein may serve as a transcription factor. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
TEHIIAVMITELRGKDILSYLEKNISVQMTIAVGTRMPPKNFSRGSLVFVSISFIV
LMIISSAWLIFYFIQKIRYTNARDRNQRRLGDAAKKAISKLTTRTVKKGDKETD
PDFDHCAVCIESYKQNDVVRLLPCKHVFHKSCVDPWLSEHCTCPMCKLNILKA
LGIV (SEQ ID N0:695); TEHIIAVMITELRGKDILSYLEKNISVQMTIAVGTRMP
PKNFSRGSLVFVSISFIVLM IISSAWLIFYF (SEQ ID N0:697); SISFIVLMIISSA
WLIFYFIQKIRYTNARDRNQRRLGDAAKKAISKLTTRTVKKGDKE (SEQ ID
N0:698); VKKGDKETDPDFDHCAVCIESYKQNDVVRILPCKHVFHKSCVDP
WLSEHCTCPMCKLNILKALGIV (SEQ ID N0:699). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments (See Accession No.
157535). Moreover, another embodiment is the polynucleotide fragments encoding these polypeptide fragments:
MTHPGTEHIIAVMITELRGKDILSYLEKNISVQMTIAVGTRMPPKNFSRGS
LVFVSISFIVLMIISSAWLIFYFIQKIRYTNARDRNQRRLGDAAKKAISKLTTRTV
KKGDKETDPDFDHCAVCIESYKQNDV VRILPCKHVFHKSCVDPWLSEHCTCP
MCKLNILKALGIVPNLPCTDNVAFDMERLTRTQAVNRRSALGDLAGDNSLGLE
PLRTSGISPLPQDGELTPRTGEINIAVTKEWFIIASFGLLSALTLCYMIIRATASLN
ANEVEWF (SEQ ID NO:696);MTHPGTEHIIAVMIT'ELRGKDILSYLEKNISVQM
TIAVGTRMPPKNFSRGSLVFVSISFIVLMIISSAWLIFYFIQKIRYTNARDRNQRR
LGDAAKKAISKLTTRT (SEQ ID N0:700); AAKKAISKLTTRTVKKGDKE
TDPDFDHCAVCIESYKQNDV VRILPCKHVFHKSCVDPWLSEHCTCPMCKLNIL
KALGIVPNLPC (SEQ ID N0:701); TQAVNRRSALGDLAGDNSLGLEPLRTSGI
SPLPQDGELTPRTGEINIAVTKEWFIIASFGLLSALTLCYMIIRATASLNANEVEW
F (SEQ ID N0:702); PLHGVADHLGCDPQTRFFVPPNIKQWIALLQRGNCTF
KEKISRAAFHNAVAV VIYNNKS KEEPVTMTHPGTEHIIAVMITELRGKDILSYLE
KNISVQMTIAVGTRMPPKNFSRGSLVFVSISFIVLMIISSAWLIFYFIQKIRYTNA
RDRNQRRLGDAAKKAISKLTTRTVKKGDKETDPDFDHCA VCIESYKQNDV VRI
LPCKHVFHKSCVDPWLSEHCTCPMCKLNILKALGIVPNLPCTDNVAFDMERLT
RTQAVNRRSALGDLAGDNSLGLEPLRTSGISPLPQDGELTPRTGEINIAVTKEW
FIIASFGLLSALTLCYMIIRATASLNANEVEWF(SEQ ID N0:703); and HGVADHLGCDPQTRFFVPPNIKQWIALLQRGNCTFKEKISRAAFHNAVAVVIY
NNKSKEE (SEQ ID N0:704). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments. When tested against Jurkat cell lines, supernatants removed from cells containing this gene activated the GAS
pathway.
Thus, it is likely that this gene activates immune cells through the JAKS/STAT
signal transduction pathway.
This gene is expressed primarily in macrophage, breast, kidney and to a lesser extent in synovium, hypothalamus and rhabdomyosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, schizophrenia and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and neural system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to zinc finger protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of schizophrenia, kidney disease and other cancers. The tissue distribution in macrophage, breast, and kidney origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of tumors within these tissues, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 147 The translation product of this gene shares sequence homology with HNP36 protein, an equilibrative nucleoside transporter, which is thought to be important in gene transcription as well as serving as an important component of the nucleoside transport apparatus (See Accession No. 1845345). One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
MSGQGLAGFFASVAMICAIASGSELSESAFGYFITACAVIILTIICYLGLPRLEFYR
YYQQLKLEGPGEQETKLDLISKGEEPRAGKEESGVSVSNSQPTNESHSIKAILK
NISVLAFSVCFIFTITIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLG
RSLTAVFMWPGKDSRWLPSWXLARLVFVPLLLLCNIKPRRYLTV VFEHDAWFI
FFMAAFAFSNGYLASLCMCFGPKKVKPAEAETAEPSWPSSCVWVWHWGLFS
PSCSGQLCDKGWTEGLPASLPVCLLPLPSARGDPEWSGGFFF (SEQ ID
N0:705); MSGQGLAGFFASVAMICAIASGSELSESAFGYFTTACAVIILTIIC
YLGLPRLEFYRYYQQLKLE GPGEQETKLDLISKGEEPRAGKEESGVSVSNSQ
PTNESHSI (SEQ ID N0:706); SGVSVSNSQPTNESHSIKAILKNISVLAFSVCFI
FTITIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLGRS (SEQ ID
NO:707),TIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLGRSLTAVF
MWPGKDSRWLPSWXLARLVFVPLLLLCNIK PRRYLTVVFEHDA (SEQ ID
N0:708); FGPKKVKPAEAETAEPSWPSSCVWVWHWGLFSPSCSGQLCDK
GWTEGLPASLPVCLLPLPSARGDPEWSGGFFF (SEQ ID N0:709). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in eosinophils and aortic endothelium and to a lesser extent in umbilical vein endothelial cell and thymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the circular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to HNP36 protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of blood neoplasias and other hematopoietic disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 148 This gene is expressed primarily in breast cancer cell lines, thymus stromal cells, and ovary.
Therefore, polynucIeotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, endocrine and female reproductive system diseases including breast cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
WO 98/54963 PCT/tJS98/11422 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of endocrine disorders. In addition, the tissue distribution in tumors of thymus, ovary, and breast origins indicates that polynucIeotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues FEATURES OF PROTEIN ENCODED BY GENE NO: 149 Translation product of this gene has homology to pmt 1 and pmt 2, two conserved schizosaccharomyces pombe genes. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
DDDGFEIVPIEDPAKHRILDPEGLALGAVIASSKKAKRDLIDNSFNRYTFNEDEG
ELPEWFVQEEKQHRIRQLPVGKKEVEHYRKRWREINARPIXXXXXXXXXXX
XXXXXXLEQTRKKAEAVVNTVDIXRTRES (SEQ ID N0:710);
DDDGFEIVPIEDPAKHRILDPEGLALGAVIASSKKAKRDLIDNSFNRYTF (SEQ
ID N0:711 ); KRWREINARPIXXXXXXXXXXXXXXXXXLEQTRKKAE
AVVNTVDIXRTRES (SEQ ID N0:712). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments (See Accession No.
a 1216734).
This gene is expressed primarily in retina and ovary and to a lesser extent in brreast cancer cell, epididymus and osteosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal growth disorders, cancer and reproductive system disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural and reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 382 as residues: Met-1 to Gly-7.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or treatment of reproductive system disease and cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 150 One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
MIKDKGRARTALTSSQPAHLCPENPLLHLKAAVKEKKRNKKKKTIGSPKRIQS
PLNNKLLNSPAKTLPGACGSPQKLIDGFLKHEGPPAEKPLEELSASTSGVPGLS
SLQSDPAGCVRPPAPNLAGAVEFNDVKTLLREWITTISDPMEEDILQVVKYCTD
LIEEKDLEKLDLVIKYMKRLMQQS VES V WNMAFDFILDN V Q V VLQQTYGSTLK
VT (SEQ ID N0:713}; MIKDKGRARTALTSSQPAHLCPENPLLHLKAAVKE
KKRNKKKKTIGSPKRIQ (SEQ ID N0:714); KRIQSPLNNKLLNSPAKT
LPGACGSPQKLIDGFLKHEGPPAEKPLEELSASTSGVPGLSSLQSDPAGCVRPP
APNLAGAVEFNDVKTLLREWITTISDPM (SEQ ID N0:715);
TISDPMEEDILQWKYCTDLIEEKDLEKLDLVIKYMKRLMQQS VE
SVWNMAFDFILDNVQVVLQQTYGSTLKVT (SEQ ID N0:716). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in 12 week embryo and to a lesser extent in hemangiopericytoma and frontal cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, growth disorders and hemangiopericytoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the circular and neural system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 383 as residues: Leu-4 to Lys-11.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of growth disorders, hemangiopericytoma and other soft tissue tumors.
FEATURES OF PROTEIN ENCODED BY GENE NO: 151 The translation product of this gene has been found to have homology to a human DNA mismatch repair protein PMS3. Preferred polypeptide fragments comprise the following amino acid sequence: FCHDCKFPEASPAMNCEP {SEQ ID N0:717).
Also preferred are polynucleotide fragments encoding these polypeptide-fragments (See Accession No. 895250).
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not linuted to, lymphoma, immunodeficiency diseases, and cancers resulting from genetic instability. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 384 as residues: Met-1 to Lys-6.
The tissue distribution in neutrophils and the sequence homology indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of Hodgkin's lymphoma, since the elevated expression and secretion by the tumor mass may be indicative of tumors of this type. Additionally the gene product may be used as a target in the immunotherapy of the cancer. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
Furthermore, its homology to a known DNA repair protein would suggest gene may be useful in establishing cancer predisposition and prevention in gene therapy applications.
FEATURES OF PROTEIN ENCODED BY GENE NO: 152 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a l20 biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infectious diseases and lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of inflammation and infectious diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 153 One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
MASS VPAGGHTRAGGIFLIGKLDLEASLFKSFQWLPFVLRKKC
NFFCWDSSAHSLPLHPLSASCSAPACHASDTHLLYPSTRALCPSIFAWLVAPHS
VFRTNAPGPTPSSQSSPVFPVFPVSFMALIVCXLVCC (SEQ ID N0:720);
MASSVPAGGHTRAGGIFLIGKLDLEASLFKSFQWLPFVLRKKCNFFCWDSSAH
SLPLHPLSASCSAPACHA (SEQ ID N0:721);FAWLVAPHSVFRTNAPGPTPS
SQSSPVFPVFPVSFMALIVCXLVCC (SEQ ID N0:722). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited lo, inflammation and infectious disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 386 as residues:
Ser-1 i to Pro-17.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of infectious diseases and inflammation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 154 This gene is expressed in multiple tissues including ovary, uterus, adipose tissue, brain, and the liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, uterine, ovarian, brain, and liver cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the female reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnostic or therapeutic uses in the treatment of the female reproductive system, obesity, and liver disorders, particularly cancer in the above tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 155 This gene maps to chromosome 3, and therefore, may be used as a marker in linkage analysis for chromosome 3 (See Accession No. D87452).
This gene is expressed in multiple tissues including brain, aortic endothelial cells, smooth muscle, pituitary, testis, melancytes, spleen, nertrophils, and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological disorders including immunodeficiencies, cancers of the brain and the female reproductive system, as well as cardiovascular disorders, such as atherosclerosis and stroke. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution suggest that polynucleotides and poIypeptides coczesponding to this gene are useful in treatment/detection of disorders in the nervous system, including schizophrenia, neurodegeneration, neoplasia, brain cancer as well as cardiovascular and female reproductive disorders including cancer within the above tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 156 The translation product of this gene shares sequence homology with the human gene encoding cytochrome b561 (See Accession No. P10897). Cytochrome b561 is a transmembrane electron transport protein that is specific to a subset of secretory vesicles containing catecholamines and amidated peptides. This protein is thought to supply reducing equivalents to the intravesicular enzymes dopamine-beta-hydroxylase and alpha-peptide amidase. Preferred polypeptides of the invention comprise the amino acid sequence:
MAMEGYWRFLALLGSALLVGFLSVIFALVWVLHYREGLGWDGSALEFNWHP
VLMVTGFVFIQGIAIIVYRLPWTWKCSKLLMKSIHAGLNAVAAILAIISVVAVFE
NHNVNNIANMYSLHSWVGLIAVICYLLQLLSGFSVFLLPWAPLSLRAFLMPIHV
YSGIVIFGTVIATALMGLTEKLIFSLRDPAYSTFPPEGVFVNTLGLLILVFGALIF
WIVTRPQWKRPKEPNSTILHPNGGTEQGARGSMPAYSGNNMDKSDSEL
NSEVAARKRNLALDEAGQRSTM (SEQ ID N0:724); as well as antigenic fragments of at least 20 amino acids of this gene and/or biologically active fragments.
Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in anergic T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune system and metabolism related diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein product or RNA of this gene is useful for treatment or diagnosis of immune system and metabolic diseases or conditions including Tay-Sachs disease, phenylketonuria, galactosemia, various porphyrias, and Hurler's syndrome.
FEATURES OF PROTEIN ENCODED BY GENE NO: 157 The translation product of this gene shares sequence homology with collagen which is important in mammalian development. This gene also shows sequence homology with bcl-2. (See Accession No. P80988.) Preferred polypeptide fragments comprise the amino acid sequence: PGRAGPSPGLSLQLPAEPGHPAGNLAPL
TSRPQPLCRIPAVPG (SEQ ID N0:725). Also preferred are polynucleotide sequences encoding this polypeptide fragment.
This gene is expressed primarily in HL-60 tissue culture cells and to a lesser extent in liver, breast, and uterus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological diseases, hereditary disorders involving the MHC
class of immune molecules, as well as developmental disorders and reproductive disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and reproductive system expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 390 as residues: Ser-39 to Gly-46, Leu-49 to Ala-62.
The tissue distribution and homology to collagen indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of hereditary MHC disorders and particularly autoimmune disorders including rheumatoid arthritis, lupus, scleroderma, and dermatomyositis, as well as many reproductive disorders, including cancer of the uterus, and breast tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 158 This gene is expressed primarily in the amygdala region of the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, a variety of brain disorders, particularly those effecting mood and personality. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and/or diagnosis of a variety of brain disorders, particularly bipolar disorder, unipolar depression, and dementia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 159 This gene is expressed in a variety of tissues and cell types including brain, smooth muscle, kidney, salivary gland and T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers of a variety of organs including brain, smooth muscle, kidney, salivary gland and T-cells and cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous, urinary, salivary, digestive, and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain, smooth muscle, and T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of various neurological, and cardiovascular disorders, but not limited to cancer within the above tissues. Additionally the gene product may be used as a target in the immunotherapy of the cancer. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 160 The translation product of this gene shares sequence homology with collagen which is thought to be important in cellular interactions, extracellular matrix formation, and has been found to be an identifying determinant in autoimmune disorders.
Moreover, this gene shows sequence homology with the yeast protein, Slslp, an endoplasmic reticulum component, involved in the protein translocation process in Yeast Yarrowia lipolytica. (See Accession No. 1052828; see also J. Biol. Chem.
271, 11668-11675 (1996).) With mouse, this same region shows sequence homology with the heavy chain of kinesin. (See Accession No. 2062607.) Recently, suppression of the heavy chain of kinesin was shown to inhibits insulin secretion from primary cultures of mouse beta-cells. (See Endocrinology 138 (5), 1979-1987 (1997).) Moreover, kinesin was found associated with drug resistance and cell immortalization. (See 468355.) Thus, it is likely that this gene also act as a genetic suppressor elements.
This gene is expressed primarily in the greater omentum and to a lesser extent in a variety of organs and cell types including gall bladder, stromal bone marrow cells, lymph node, liver, testes, pituitary, and thymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders of the endocrine, gastrointestinal, and immunological systems, including autoimmune disorders and cancers in a variety of organs and cell types.
WO 98/54963 PCTlUS98/11422 Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and gastrointestinal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 393 as residues: Asn-27 to Leu-47, Gln-81 to Lys-88, Asp-93 to Lys-102, Asn-107 to Leu-116, Met-129 to Glu-141, Glu-to Asp-157, Lys-176 to Glu-185, Glu-333 to Tyr-349, Cys-393 to Leu-403, Gln-to Gly-429.
The tissue distribution in within various endocrine and immunological tissues combined with the sequence homology to a conserved collagen motif indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis of various autoimmune disorders including, but not limited to, rheumatoid arthritis, lupus erthyematosus, scleroderma, dermatomyositis Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 161 This gene has homology to the tissue inhibitor of metalloproteinase 2. Such inhibitors are vital to proper regulation of metalloproteins such as collagenases (See Accession No. P16368). In addition, this gene maps to chromosome 17, and therefore, may be used as a marker in linkage analysis for chromosome 17 (See Accession No. P16368).
This gene is expressed primarily in several types of cancer including osteoclastoma, chondrosarcoma, and rhabdomyosarcoma and to a lesser extent in several non-malignant tissues including synovium, amygdala, testes, placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a ~ biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, various types of cancer, particularly cancers of bone and cartilage, as well as various autoimmune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the musculoskeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in various cancers and the sequence homology to a collagenase inhibitor indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 162 This gene is homologous to the mitochondria) ATP6 gene and therefore is likely a homolog of this gene family (See Accession No. X76197).
This gene is expressed primarily in brain tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, a variety of brain disorders, including Down's syndrome, depression, Schizophrenia, and epilepsy. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain tissue indicates this gene is useful for diagnosis of various neurological disorders including, but not limited to, brain cancer.
Additionally the gene product may be used as a target in the immunotherapy of cancer in the brain as well as for the diagnosis of metabolic disorders such as obesity Tay-Sachs disease, phenylketonuria and Hurler's Syndrome.
FEATURES OF PROTEIN ENCODED BY GENE NO: lb3 This gene is expressed primarily in placenta, neutrophils, and microvascular endothelial cells and to a lesser extent in multiple tissues including brain, prostate, spleen, thymus, and bone.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neutropenea and other diseases of the immune system.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in placenta indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis various female reproductive disorders. Additionally the gene product may be used as a target in the immunotherapy of various cancers. Because the gene is expressed in some cells of lymphoid and endocrine origin, the natural gene product may be involved in immune functions and metabolism regulation, respectively. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 164 This gene is expressed primarily in neutrophils, monocytes, bone marrow, and fetal liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune system disorders including, but not limited to, autoimmune disorders such as lupus, and immunodeficiency disorders . Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in various immune system tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis of various immunological disorders such as Hodgkin's lymphoma, arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 165 The translation product of this gene shares sequence homology with dystrophin which is thought to be defective in both Duchene and Becker Muscular Dystrophy.
Preferred polypeptide fragments comprise the following amino acid sequence:
MKLLGECSSSIDSVKRLEHKLKEEEESLPGFVNLHSTETQTAGVIDRWELLQAQ
ALSKELRMKQNLQKWQQFNSDLNSIWAWLGDTEEELEQLQRLELSTDIQTIELQ
IKKLKELQKAVDHRKAIILSINLCSPEFTQADSKESRDLQDRLXQMNGRWDRV
CSLLEEWRGLLQDALMQCQGFHEMSHGLLLMLENIDRRKNEIVPIDSNLDAEIL
QDHHKQLMQIKHELLESQLRVASLQDMSCQLLVNAEGTDCLEAKEKVHVIGNR
LKLLLKEVSRHIKELEKLLDVSSSQQDLSSWSSADELDTSGSVSPXSGRSTPNR
QKTPRGKCSLSQPGPS VSSPHSRSTKGGSDSSLSEPXPGRSGRGFLFRVLRAA
LPLQLLLLLLIGLACLVPMSEEDYSCALSNNFARSFHPMLRYTNGPPPL (SEQ ID
N0:726); MKLLGECSSSIDSVKRLEHKLKEEEESLPGFVNLHSTETQTAGVIDR
WELLQAQALSKELRMKQNLQKWQQFNSDLNSIWAWLGDTEEELEQLQRLELS
TDIQTIELQIK (SEQ ID N0:727); KLKELQKAVDHRKAIILS1NLCSPEFTQADSK
ESRDLQDRLXQMNGRWDRVCSLLEEWRGLLQDALMQCQGFHEMSHGLLLML
ENIDRRKNEIVPIDSNLDAEILQDHHKQLMQIKHELLESQLRVASLQDMSCQL
(SEQ ID N0:728); QDMSCQLLVNAEGTDCLEAKEKVHVIGNRLKLLLKEVS
RHIKELEKLLDVSSSQQDLSSWSSADELDTSGSVSPXSGRSTPNRQKTPRGKCS
LSQPGPSVSSPHS (SEQ ID N0:729); DSSLSEPXPGRSGRGFLFRVLRAAL
PLQLLLLLLIGLACLVPMSEEDYSCALSNNFARSFHPMLRYTNGPPPL {SEQ ID
N0:730). Also preferred are polynucleotide fragments encoding these polypeptide fragments. Furthermore, this gene maps to chromosome 6, and therefore, may be used as a marker in linkage analysis for chromosome 6 (See Accession No. N62896).
This gene is expressed in numerous tissues including the heart, kidney, and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, musculoskeletal disorders including Muscular Dystrophy and cardiovascular diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the muscle tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to dystrophin indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of Muscular Dystrophy and other muscle disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 166 This gene is expressed primarily in human cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the central nervous system, including Alzheimer's Disease, Parkinson's Disease, ALS, and mental illnesses. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 399 as residues: Pro-20 to Gly-26, Leu-37 to Pro-42, His-57 to Gly-63.
The tissue distribution indicates that the protein products of this gene are useful for treatment/diagnosis of diseases of the central nervous system and may protect or enhance survival of neuronal cells by slowing progression of neurodegenerative diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 167 Preferred polypeptides encoded by this gene comprise the following amino acid sequence:
MKLLICGNYLAPSHSESSRRCCLLCFYPLCLEINFGMKVFLSMPFLVLFQ
SLIQED (SEQ ID N0:731). Polynucleotides encoding such polypeptides are also provided. This gene is believed to reside on chromosome 15. Therefore polynucleotides derived from this gene are useful in linkage analysis as chromosome 15 markers.
This gene is expressed primarily in human testes tumor and to a lesser extent in normal human testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the testes, particularly cancer, and other reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for treatment/diagnosis of testicular diseases including cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 168 This gene is expressed primarily in fetal liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, conditions affecting hematopoietic development and metabolic diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the i32 hepatic system, and fetal hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 401 as residues: His-7 to Trp-17, Leu-19 to Lys-27, Pro-33 to Gly-44, Lys-68 to Gly-74, Lys-85 to Cys-95.
The tissue distribution indicates that the protein products of this gene are useful for treatment/diagnosis of diseases of the developing liver and hematopoietic system, and act as a growth differentiation factor for hematopoietic stem cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 169 The polypeptide encoded by this gene is believed to be a membrane bound receptor. The extracellular domain of which is expected to consist of the following amino acid sequence:
RILLVKYSANEENKYDYLPTTVNVCSELVKLVFCVLVSFCVIKKDHQSRNLKY
ASWKEFSDFMKWSIPAFLYFLDNLIVFYVLSYLQPAMAVIFSNFSIITTALLFRIV
LKXRLNWIQWASLLTLFLSIVALTAGTKTLQHNLAGRGFHHDAFFSPSNSCLL
FRNECPRKDNCTAKEWTFPEAKWNTTARVFSHIRLGMGHVLIIVQCFISSMANI
YNEKILKEGNQLTEXIFIQNSKLYFFGILFNGLTLGLQRSNRDQIKNCGFFYGH
S (SEQ ID N0:732). Thus, preferred polypeptides encoded by this gene comprise the extracellular domain as shown above. It will be recognized, however, that deletions of either end of the extracellular domain up to the first cysteine from the N-terminus and the first cysteine of the C-terminus, is expected to retain the biological functions of the full-length extracellular domain because the cysteines are thought to be responsible for providing secondary structure to the molecule. Thus, deletions of one or more amino acids from either end (or both ends) of the extracellular domain are contemplated. Of course, further deletions including the cysteines are also contemplated as useful as such polypeptides is expected to have immunological properties such as the ability to evoke and immune response. Polynucleotides encoding all of the foregoing polypeptides are provided.
This gene is expressed primarily in human osteoclastoma and to a lesser extent in hippocampus and chondrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers, particularly those of the bone and connective tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 402 as residues: Met-1 to Cys-6, Ala-41 to Tyr-49, Lys-76 to Lys-84.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis of cancers of the bone and connective tissues, and may act as growth - factors for cells involved in bone or connective tissue growth.
FEATURES OF PROTEIN ENCODED BY GENE NO: 170 Preferred polypeptides encoded by this gene comprising the following amino acid sequence:
NSVPNLQTLAVLTEAIGPEPAIPRXPREPPVATSTPATPSAGPQPLPTGTV
LVPGGPAPPCLGEAWALLLPPCRPSLTSCFWSPRPSPWKETGV (SEQ ID
N0:733). Polynucleotides encoding such polypeptides are also provided herein.
This gene is expressed primarily in hematopoietic progenitor cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the blood including cancer and autoimmune disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the blood/circulatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 403 as residues: Gln-4 to His-10, Pro-25 to His-32.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis of diseases involving growth differentiation of hematopoietic cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 171 Preferred polypeptides encoded by this gene comprise the following amino acid sequences: ALQLAFYPDAVEEWLEENVHPSLQRLQXLLQDLSEVSAPP (SEQ ID
N0:734); and/or CHPPALAGTLLRTPEGRAHARGLLLEAGGA (SEQ ID N0:735).
Polynucleotides encoding such polypeptides are also provided. The protein product of this gene shares sequence homology with metallothionines. Thus, polypeptide encoded by this gene are expected to have metallothionine activity, such activities are known in the art and described elsewhere herein.
This gene is expressed primarily in kidney cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the kidney including cancer and renal dysfunction.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 404 as residues: Ser-47 to Gln-52.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of diseases of the kidney including kidney failure.
FEATURES OF PROTEIN ENCODED BY GENE NO: 172 This gene is expressed primarily in 12 week old early stage human.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing embryo, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i:e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 405 as residues: Gln-31 to Thr-43, Gly-51 to Ser-58, Pro-65 to Pro-72.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of developmental problems with fetal tissue. The gene may be involved in vital organ development in the early stage, especially hematopoiesis, cardiovascular system, and neural development.
FEATURES OF PROTEIN ENCODED BY GENE NO: 173 The translation product of this gene shares sequence homology with TGN38, an integral membrane protein previously shown to be predominantly localized to the trans-Golgi network (TGN) of cells.
This gene is expressed primarily in developing embryo and to a lesser extent in cancer tissues including lymphoma, endometrial, protate and colon.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing fetus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 406 as residues: His-65 to Ser-72, Pro-82 to Gly-91, Pro-98 to Glu-118, Ser-126 to Gly-166, Pro-180 to Asp-188, Tyr-209 to Lys-214, Gln-220 to Leu-228.
The tissue distribution and homology to an integral membrane protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of cancers and developmental abnormalities where aberrant expression relates to an abnormality.
FEATURES OF PROTEIN ENCODED BY GENE NO: 174 The translation product of this gene shares sequence homology with a dnaJ heat shock protein from E. coli which is allelic to sec63, a gene that affects transit of nascent secretory proteins across the endoplasmic reticulum in yeast.
This gene is expressed primarily in Hodgkin's lymphoma and to a lesser extent m testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 407 as residues: Thr-13 to Trp-21, Arg-74 to Asp-81.
The tissue distribution and homology to dnaJ indicates that polynucleotides and polypeptides corresponding to this gene are useful as a diagnostic for cancer including Hodgkin's lymphoma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 175 This gene is expressed primarily in endothelial cells and to a lesser extent in bone marrow stromal cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases involving angiogenic abnormalities including diabetic retinopathy, macular degeneration, and other diseases including arteriosclerosis and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for treating diseases where an increase or decrease in angiogenesis is indicated and as a factor in the wound healing process.
FEATURES OF PROTEIN ENCODED BY GENE NO: 176 The translation product of this gene shares sequence homology with MAT8 (mouse) which is thought to be important in regulating chloride conductance in cells (particularly in the breast) by modulating the response mediated by cAMP and protein kinase C to extracellular signals.
This gene is expressed primarily in amniotic cells and hematopoeitic cells including macrophages, Neutrophils, T cells, TNF induced aortic endothelium and to a lesser extent in testes, TNF induced epithelial cells, and smooth muscle.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory responses mediated by T cells, macrophages, and/or neutrophils particularly those involving TNF, and also cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 409 as residues: Thr-19 to Ala-33, Leu-54 to Asp-82, Pro-89 to Ala-97, Pro-to Lys-125, Ser-127 to Phe-135, Gly-164 to Leu-169, Cys-173 to Arg-178.
The tissue distribution and homology to mat-8 indicates that polynucleotides and polypeptides corresponding to this gene are useful for modifying inflammatory responses to cytokines such as TNF and thus modifying the duration and/or severity of inflammation. Polynucleotides and polypeptides derived from this gene are thought to be useful in the diagnosis and treatment of cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 177 This gene is expressed primarily in endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, vascular restenosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating diseases associated with vascular response to injury such as vascular restenosis following angioplasty..
FEATURES OF PROTEIN ENCODED BY GENE NO: 178 One embodiment of the claimed invention comprises:
MRPDWKAGAGPGGPPQKPAPSSQRKPPARPSAAAAAIAVAAAEEERRLRQRN
RLRLEEDKPAVERCLEELVFGDVENDEDALLRRLRGPRVQEHEDSGDSEVENEA
KGNFPPQKKPV W VDEEDEDEEM V DMMNNRFRKDMMKNASES KLS KDNLKK
RLKEEFQHAMGGVPAWAETTKRKTSSDDESEEDEDDLLQRTGNFISTSTSLPRG
ILKMKNCQHANAERPTVARISICAVPSRCTDCDGCWD (SEQ ID N0:737); or CLEELVFGDVENDEDALLRRLRGPRVQEHEDSGDSEVENEAKGNFPPQKKPV
WVDEEDEDEEMVDMMNNRFRKDMMKNASESKLSKDNLKKRLKEEFQHAMG
GVPAWAETTKRKTSSDDESEEDEDDLLQRTGNFISTSTSLPRGILKMKNCQHA
NAERPTVARISICAVPSRCTDCDGC (SEQ ID NO: 738). LKEKIVRSFEVSPDGS
FLLINGIAGYLHLLAMKTKELIGSMKINGRVAASTFSSDSKKVYASSGDGEVYV
WDVNSRKCLNRFVDEGSLYGLSIATSRNGQYVACGSNCGVVNIYNQDSCLQE
TNPKPIKAIMNLVTGVTSLTFNPTTEILAIASEKMKEAVRLVHLPSCTVFSNFPVI
KNKNISHVHTMDFSPRSGYFALGNEKGKALMYRLHHYSDF (SEQ ID N0:739);
and/or KINGRVAASTFSSDSKKVYASSGDGEVYVWDVNSRKCLNRFVDEGSL
YGLSIATSRNGQYVACGSNCGVVNIYNQDSCLQETNPKPIKAIMNLVTGVTSLT
FNPTTEILAIASEKMKEAVRLVHLPSCTVFSNFPVIKNKNISHVHTMDFSPRSG
YFALGNEKGKAL (SEQ ID N0:740).
This gene is expressed primarily in epidydimus and endometrial tumors and to a lesser extent in T cell lymphoma and cell lines derived from colon cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors of the reproductive organs including testis and endometrial cells.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 411 as residues: Ser-67 to Lys-72, Val-87 to Leu-93, Tyr-128 to Pro-141, Asp-204 to Gly-210.
The tissue distribution indicates that the protein products of this gene are useful for treating tumors of the endometrium or epithelial tumors of the reproductive system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 179 Preferred polypeptides encoded by this gene comprise the following amino acid sequence:
MRILQLILLALATGLVGGETRIIKGFECKLHSQPWQAALFEKTRLLCGATLIAPR
WLLTAAHCLKPRYIVHLGQHNLQKEEGCEQTRTATESFPHPGFNNSLPNKDH
RNDIMLVKMASPVSITWAVRPLTLSSRCVTAGTSCSFPAGAARPDPSYACLTPC
DAPTSPSLSTRSVRTPTPATSQTPWCVPACRKGARTPARVTPGALWSVTSLFKA
LSPGARIRVRSPESLVSTRKSANMWTGSRRR (SEQ ID N0:741); ETRIIKGFEC
KLHSQPWQAALFEKTRLLCGATLIAPRWLLTAAHCLKPRYIVHLGQHNLQKEE
GCEQTRTATESFPHPGFNNSLPNKDHRNDIMLVKMASPVSITWAVRPLTLSSR
CVTAGTSCSFPAGAARPDPSYACLTPCDAPTSPSLSTRSVRTPTPATSQTPWCVP
ACRKGARTPARVTPGALWS VTSLFKALSPGARIRVRSPESLVSTRKSANMWTG
SRRR (SEQ ID N0:742); or CKLHSQPWQAALFEKTRLLCGATLIAPRWLLT
AAHCLKPRYIVHLGQHNLQKEEGCEQTRTATESFPHPGFNS
(SEQ ID N0:743). The translation product of this gene shares sequence homology with neuropsin a novel serine protease which is thought to be important in modulating extracellular signaling pathways in the brain. Owing to the structural similarity to other serine proteases the protein products of this gene are expected to have serine protease activity which may be assayed by methods known in the art and described elsewhere herein.
This gene is expressed primarily in endometrial tumor and to a lesser extent in colon cancer, benign hypertrophic prostate, and thymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers of the endometrium or colon and benign hypertrophy of the prostate. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the urogenital or reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 412 as residues: Gly-12 to Ser-22, Pro-34 to Ser-53.
The tissue distribution and homology to serine proteases indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing or treating hperproliferative disorders such as cancer of the endometrium or colon and hyperplasia of the prostate.
FEATURES OF PROTEIN ENCODED BY GENE NO: 180 Preferred polypeptide encoded by this gene comprise the following amino acid sequence: VLQGRYFSPILEMRRLRPEGXXNLPGGSRAQKEPRQDLTLVLWPHC
PHFAMTRSYVPTKQCMVQGSFYCIFIFKGPVQNWC (SEQ ID N0:744).
Polynucleotides encoding such polypeptide are also provided.
This gene is expressed primarily in fetal brain Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, identifying and expanding stem cells in the CNS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for detecting and expanding stem cell populations in the (or of the) central nervous system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 181 This gene is expressed primarily in early stage human brain and a stromal cell line.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities of the CNS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 414 as residues: Gln-42 to Gln-47, Gln-54 to Pro-60.
The tissue distribution indicates that the protein products of this gene play a role in the development of the central nervous system. Therefore this gene and its products are useful for diagnosing or treating developmental abnormalities of the central nervous system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 182 Preferred polypeptides encoded by this gene comprise the following amino acid sequence:
MPIIDQVNPELHDFMQSAEVGTIFALSWLITWFGHVLSDFRHV VRLYDF
FLACHPLMPIYFAAVIVLYREQEVLDCDCDMASVHHLLSQIPQDLPYETLISRXE
TFLFSFPHPNLLGRPLPNSKLRGRQPLLSKTLSWHQPSRGLIWCCGSGXRGLL
RPEDRTKDVLTKPRTNRFVKLAVMGLTVALGAAALAVVKSALEWAPKFQLQL
FP (SEQ ID N0:745); or CPEFFIPATLPCPFVFAFTSEASSRAYLTQRGPGGLAQ
NLMPLPVGFWMGSLPPPWCWRKWVSEACSCFC (SEQ ID N0:746) These polypeptides are structurally similar to various TGF-beta family members.
Thus, this polypeptide is expected to have a variety of activities in the modulation of cell growth and proliferation.
This gene is expressed primarily in osteoclastoma, microvascular endothelium, and bone marrow derived cell lines.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematological diseases particularly involving aberrant proliferation of stem cells. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 415 as residues: Ser-33 to Ala-39.
The tissue distribution indicates that the protein products of this gene is useful for treating disorders of the progenitors of the immune system. Applications include in vivo expansion of progenitor cells, ex vivo expansion of progenitor cells, or the treatment of tumors of the circulatory system, such as lymphomas.
FEATURES OF PROTEIN ENCODED BY GENE NO: 183 This gene maps to chromosome 17 and therefore, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 17. In specific embodiments, polypeptides of the invention comprise the sequence:
GFGSVSAAGRRSGGTWQPVQ (SEQ ID N0:747); PGGLAVGSRWWSRSLT
(SEQ ID N0:748); LEPSRQRRPRRRGGTSRPETDQRAKCWRQL (SEQ ID
N0:749); and/or VCLRCQNRMEN (SEQ ID N0:750}. In further specific embodiments, polypeptides of the invention comprise the sequence: MAACTARRPGR
GQPLVVPVADXGPVAKAALCAAXAGAFSPASTTTTRRHLSSRNRPEGKVLETV
GVFEVPKQNGKYETGQLFLHSIFGYRGVVLFPWQARLXDRDVASAAPEKAEN
PAGHGSKEVKGKTHTYYQVLIDARDCPHISQRSQTEAVTFLANHDDSRALYAIP
GLDYVSHEDILPYTSTDQVPIQHELFERFLLYDQTKAPPFVARETLRAWQEKNH
PWLELSDVHRETTENIRVTVIPFYMGMREAQNSHVYWWRYCIRLENLDSDV VQ
LRERHWRIFSLSGTLETVRGRGVVGREPVLSKEQPAFQYSSHVSLQASSGHMW
GTFRFERPDGSHFDVRIPPFSLESNKDEKTPPSGLHW (SEQ ID N0:751 );
MAACTARRPGRGQPLVVPVADXGPVAKAALCAA (SEQ >D N0:752};
VLETVGVFEVPKQNGKYETGQLFLHSIFGYRGVVL (SEQ ID N0:757);
GLDYVSHEDILPYTST (SEQ ID N0:758); DVHRETTENIRVTVIPFYM (SEQ ID
N0:759); WWRYCIRLENLDSDVVQLRER (SEQ ID N0:760); and/or PAFQYSS
HVSLQASSGHMWGTFRFER (SEQ ID N0:761). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in gall bladder, prostate, and fetal brain, and to a lesser extent in a few tumor and fetal tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, growth related disorders such as cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate, gall bladder, and fetal brain, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of growth-related disorders, such cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 184 In specific embodiments, polypeptides of the invention comprise the sequence:SLCCPEGAEGC (SEQ ID N0:762) andlor QLKKTHYDRPCP (SEQ ID
N0:763). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in stromal cell, tonsil, and glioblastoma and to a lesser extent in some other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune and inflammatory disorders and glioblastoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the stromal cells, tonsil, and glioblastoma expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Additionally, it is believed that the product of this gene regulates pancreatic cell differentiation into beta cells. Accordingly, polynucleotides and polypeptides of the invention are useful in the treatment of insulin-dependent diabetes mellitus and associated conditions e.g. pancreatic hypofunction and the prevention, as well as the treatment of undifferentiated type pancreatic cancers.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 417 as residues: Pro-27 to Ala-32.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune and inflammatory disorders and glioblastoma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 185 This gene is expressed primarily in hepatocellular carcinoma and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above rissues or cells, particularly of the liver, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 418 as residues: Gly-32 to Lys-39.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of liver diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 186 This gene is expressed primarily in hippocampus and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neutronal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hippocampus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 187 This gene is expressed primarily in bone cancer and hippocampus and to a lesser extent in osteoclastoma and other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, bone-related disorders and neuronal diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bone, ostoeclast, and hippocampus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of bone-related disorders and neuronal diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 188 This gene maps to chromosome 4 and therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 4.
This gene is expressed primarily in neuronal tissues such as hippocampus, spinal cord, and hypothalamus and to a lesser extent in a few other tissues such as ovary.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 189 This gene maps to chromosome 10, therefore, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 10.
This gene is expressed primarily in neuronal tissues and immune tissues, and to a lesser extent in a few other tissues such as skin tumor, lung etc.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal and immune-related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal and immune-related tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 422 as residues: Pro-19 to Asp-25.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal and immune-related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 190 The translation product of this gene shares sequence homology with human N33, a gene located in a homozygously deleted region of human metastatic prostate cancer which is thought to be important in prevention of prostate cancer. In specific embodiments, polypeptides of the invention comprise the sequence:
AQRKKEMVLSEKVSQLMEWTNKRPVIRMNGDKFRRLVKAPPRNYSVIVMFTA
LQLHRQCVVCKQADEEFQILANSWRYSSAFTNRIFFAMVDFDEGSDVFQMLNM
NSAPTFINFPAKGKPKRGDTYELQVRGFSAEQIARWIADRTDVNIRVIRPPNMA
ARWRFWCVSVT (SEQ ID N0:765); MVVALLIVCDVPSAS (SEQ ID N0:766);
AQRKKEMVLSEKVSQL (SEQ ID N0:767); MEWTNKRPVIRMNGDKF (SEQ
ID:768); RRLVKAPPRNYSVIVMFTALQLHRQCVVCKQADEEFQILANSWRY
SSAF'TNRIFFA (SEQ ID N0:769); MVDFDEGSDVFQMLNMNSAPTFINFPAK
GKP (SEQ ID N0:770); KRGDTYELQVRGFSAEQIARWIADRTDVNIRVIRPPN
(SEQ ID N0:771); and/or YAGPLMLGLLLAVIGGLVYLRRVIWNFSLIKLDGLLQL
CVLCLL (SEQ ID N0:772). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in infant adrenal gland prostate cell line and to a lesser extent in a few other tissues Iike liver, smooth muscle etc.
Therefore, polynucleotides and polypeptides of the invention are-useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate cancer and endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate and adrenal gland, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 423 as residues: Pro-34 to Gly-43, Arg-113 to Pro-120.
The tissue distribution and homology to N33 indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for prostate cancer and endocrine disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 191 This gene is expressed primarily in T cell and to a lesser extent in fetal lung.
Therefore, poIynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 424 as residues: Trp-3 to Phe-9.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 192 This gene maps to chromosome 6, therefore, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 6. Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression.
This gene is believed to be a glycosylphoshatidylinositol-anchored protein encoded by a hippocampal gene and to possess neural activity. This molecule is believed to be expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Message of this gene is believed to be induced by neuronal activity and by the activity-regulated neurotrophins BDNF and NT-3. The product of this gene is believed to stimulate neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures and to act as a downstream effector of activity-induced neurite outgrowth. In specific embodiments, polypeptides of the invention comprise the sequence: DAVFKGFSDCLLKLGDS (SEQ
ID N0:773); CQEGAKDMWDKLRKESKNLN (SEQ ID N0:774);
VLLVSLSAALATWLSF (SEQ ll~ N0:775); MGLKLNGRYISLILAVQIAYLVQAVR
AAGKCDAVFKGFSDCLLKLGDS (SEQ ID N0:776); PAAWDDKTNIKTVCTYW
EDFHSCTVTALTDCQEGAKDMWDKLRKESKNLNIQGSLFELCGSGNGAAGSL
LPAFPVLLVSLSAALATWLSF (SEQ ID N0:777); and/or MGLKLNGRYISLILA
VQIAYLVQAVRAAGKCDAVFKGFSDCLLKLGDSXXXXXPAAWDDKTNIKTVC
TYWEDFHSCTVTALTDCQEGAKDMWDKLRKESKNLNIQGSLFELCGSGNGAA
GSLLPAFPVLLVSLSAALATWLSF (SEQ ID N0:778). Polynucleotides encoding this polypeptide are also encompassed by the invention.
This gene is expressed primarily in human placenta, endometrial tumor and tissues of the central nervous system (CNS).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, relating to reproductive disorders, cancers and neurological diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and neurological disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 425 as residues: Asp-47 to Asp-63, His-75 to Tyr-80, Pro-83 to Tyr-89.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of reproductive disorders such as endometrial tumors. Expression of this gene in tissues of the CNS
and its strong homology to Neuritin suggest that the protein product from this gene may also be used in the treatment and diagnosis of neurological disorders and in the regeneration of neural tissues, e.g., following injury.
FEATURES OF PROTEIN ENCODED BY GENE NO: 193 The translation product of this gene shares sequence homology with tenascin which is thought to be important in development. The translation product of this gene is believed to be a ligand of the fibroblast growth factor family. FGF ligand activity is known in the art and can be assayed by methods known in the art and disclosed elsewhere herein.
This gene is expressed primarily in endometrial tumors, and other types of tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 426 as residues: Gly-29 to Glu-34, Arg-71 to Arg-76, Thr-176 to Cys-182, Gly-184 to Glu-199.
The tissue distribution and homology to tenascin indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 194 In specific embodiments, polypeptides of the invention comprise the sequence:
MNSAAGFSHLDRRERVLKLGESFEKQPRCASTLC (SEQ ID N0:779).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in fetal human lung and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, lung development and respiratory disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing irnmunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the respiratory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal lung and neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of lung and immunity related diseases, for example, lung cancer, viral, fungal or bacterial infections (e.g. lesions caused by tuberculosis), inflammation (e.g.
pneumonia), metabolic lesions etc.
FEATURES OF PROTEIN ENCODED BY GENE NO: 195 This gene is expressed primarily in breast lymph node.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immunal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 196 This gene maps to chromosome 5 and accordingly, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 5. The translation product of this gene shares sequence homology with human M-phase phosphoprotein 4 which is thought to be important in phosphorylation and signal transduction processes.
In specific embodiments, polypeptides of the invention comprise the sequence:
TIYPTEEELQAVQKIVSITERALKLVSD (SEQ ID N0:780}; RALKGVLRV
GVLAKGLLLRGDRNVNLVLLC (SEQ ID N0:781 ); ALAALRHAKWFQARAN
GLQSCVIIIRILRDLCQRVPTWS (SEQ ID N0:782); GDALRRVFECISSGIIL (SEQ
ID N0:783); LAFRQIHKVLGMDPLP (SEQ ID N0:784); and/or TIYPTEEELQAVQ
KIVSITERALKLVSDSLSEHEKNKNKEGDDKKEGGKDRALKGVLRVGVLAKG
LLLRGDRNVNLVLLCSEKPSKTLLSRIAENLPKQLAVISPEKYDIKCAVSEAAIIL
NSCVEPKMQVTITLTSPIIREENMREGDVTSGMVKDPPDVLDRQKCLDALAALR
HAKWFQARANGLQSCVIIIRILRDLCQRVPT'WSDFPSWAMELLVEKAISSASSP
QSPGDALRRVFECISSGITLKGSPGLLDPCEKDPFDTLATMTDQQREDITSSAQFA
LRLLAFRQIHKVLGMDPLPQMSQRFNIHNNRKRRRDSDGVDGFEAEGKKDKK
DYDNF (SEQ ID N0:785). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in Human Hippocampus and to a lesser extent in Prostate, Human Frontal Cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders related to reproductive system and nervous system.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system and nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to human M-phase phosphoprotein 4 indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of reproductive and nervous system disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 197 In specific embodiments, polypeptides of the invention comprise the sequence:
MGSQHSAAARPSSCRRKQEDDRDG (SEQ ID N0:786);
LLAEREQEEAIAQFPYVEFTGRDSITCLTC (SEQ ID N0:787); and/or QGTGYIPTEQVNELVALIPHSDQRLRPQRTKQYV (SEQ ID N0:788).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in Human Primary Breast Cancer and to a lesser extent in Human Adult Spleen, Hodgkin's Lymphoma I, Salivary Gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer and immunal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 430 as residues: Ser-126 to Gly-138.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and immunal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 198 This gene is expressed primarily in monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, blood cell disorders. Similarly, polypeptides and antibodies-directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of blood cell disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 199 This gene is expressed primarily in Human Ovary and Synovia and to a lesser extent in Human 8 Week Whole Embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, reproductive and developmental disorders. Sinularly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and developmental system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of reproductive and developmental disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 200 This gene maps to chromosome 8 and therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 8. The translation product of this gene shares limited sequence homology with collagen proline rich domain.
This gene is expressed primarily in CNS.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 433 as residues:
Pro-35 to Asp-41.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neurological diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 201 Translation product of this gene shares homology with a mammalian histone Hla protein. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: ARLNVGRESLKREMLKSQGVKVSESPMGAR
HSSWPEGAAFCKKVQGAQMQFPPRR (SEQ ID N0:789); ARLNVGRESLKR
EML (SEQ ID N0:790); LKSQGVKVSESPMGARHSSW (SEQ ID N0:791 );
AFCKKVQGAQMQFPPRR (SEQ ID N0:792). An additional embodiment is the polynucleotide fragments encoding these polypeptide (See Accession No.
pirfS24178) fragments.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are WO 98!54963 PCT/US98/11422 not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders.
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in vital immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such I S as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 202 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders.
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 203 ' This gene is expressed primarily in Neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infectious disorders, immune disorders, and cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 436 as residues: Thr-31 to Lys-36.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of infectious disorders, immune disorders, and cancers. Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 204 This gene maps to chromosome 16 and therefore polynucleotides of the invention can be used in linkage analysis as markers for chromosome 16. The translation product of this gene shares sequence homology with lactate dehydrogenase which is thought to be important in lactate metabolism.
This gene is expressed primarily in human tonsils and to a lesser extent in Spleen, and Neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders, infectious disorders, and cancers.
Similarly.
polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune disorders, infectious disorders, and cancers, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 437 as residues: Gly-7 to Ser-12.
The tissue distribution and homology to lactate dehydrogenase gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders, infectious disorders, and cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 205 The translation product of this gene shares sequence homology with Gcap 1 protein which is developmentally regulated in brain.
This gene is expressed primarily in placenta and endometrial tumor and to a lesser extent in several other tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, vasculogenesis/angiogenesis and tumorigenesis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system and tumors, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to Gcap 1 protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorder or dysfunction of vascular system of tumorigenesis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 206 In specific embodiments, polypeptides of the invention comprise the sequence MPYAQWLAENDRFEEAQKAFHKAGRQREA (SEQ ID N0:799);
VQVLEQLTNNAVAESRFNDAAYYYWMLSMQCLDIAQD (SEQ ID N0:794);
PAQKDTMLGKFYHFQRLAELYHGYHAIHRHTEDP (SEQ ID NO: 795);
FSVHRPETLFNISRFLLHSLPKDTPSGISKVKILFT (SEQ ID N0:800);
LAKQSKALGAYRLARHAYDKLRGLYIP (SEQ ID N0:796); ARFQKSIELG
TLTIRAKPFHDSEELVPLCYRCSTNN (SEQ ID NO: 797); andlor PLLNNLGNVC
INCRQPFIF'SASSYDVLHLVEFYLEEGITDEEAISLIDLEVLRPKRDDRQLEICKQQ
LPDSCG (SEQ ID N0:798). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive and endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of male reproductive and endocrine disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 207 This gene is expressed in fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, lung diseases such as cystic fibrosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the respiratory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 440 as residues: Tyr-49 to Cys-54.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and treatment of disorders associated with developing lungs particularly in premature infants where the lungs are the last tissues to develop. The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of lung tumors since the gene may be involved in the regulation of cell division, particularly since it is expressed in fetal tissue. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
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Table 1 summarizes the information corresponding to each "Gene No." described above. The nucleotide sequence identified as "NT SEQ ID NO:X" was assembled from partially homologous ("overlapping") sequences obtained from the "cDNA clone ID"
identified in Table 1 and, in some cases, from additional related DNA clones.
The overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X.
The cDNA Clone ID was deposited on the date and given the corresponding deposit number listed in "ATCC Deposit No:Z and Date." Some of the deposits contain multiple different clones corresponding to the same gene. "Vector" refers to the type of vector contained in the cDNA Clone ID.
"Total NT Seq." refers to the total number of nucleotides in the contig identified by "Gene No." The deposited clone may contain all or most of these sequences, reflected by the nucleotide position indicated as "5' NT of Clone Seq." and the "3' NT
of Clone Seq." of SEQ ID NO:X. The nucleotide position of SEQ ID NO:X of the putative start codon (rnethionine) is identified as "5' NT of Start Codon."
Similarly , the nucleotide position of SEQ ID NO:X of the predicted signal sequence is identified as "5' NT of First AA of Signal Pep."
The translated amino acid sequence, beginning with the methionine, is identified as "AA SEQ ID NO:Y," although other reading frames can also be easily translated using known molecular biology techniques. The polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.
The first and last amino acid position of SEQ ID NO:Y of the predicted signal peptide is identified as "First AA of Sig Pep" and "Last AA of Sig Pep." The predicted first amino acid position of SEQ ID NO:Y of the secreted portion is identified as "Predicted First AA of Secreted Portion." Finally, the amino acid position of SEQ ID
NO:Y of the last amino acid in the open reading frame is identified as "Last AA of ORF."
SEQ ID NO:X and the translated SEQ ID NO:Y are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, SEQ ID NO:X is useful for designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA
contained in the deposited clone. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling a variety of forensic and diagnostic ' 35 methods of the invention. Similarly, polypeptides identified from SEQ ID
NO:Y may be used to generate antibodies which bind specifically to the secreted proteins encoded by the cDNA clones identified in Table 1.
Nevertheless, DNA sequences generated by sequencing reactions can contain sequencing errors. The errors exist as misidentified nucleotides, or as insertions or deletions of nucleotides in the generated DNA sequence. The erroneously inserted or deleted nucleotides cause frame shifts in the reading frames of the predicted amino acid sequence. In these cases, the predicted amino acid sequence diverges from the actual amino acid sequence, even though the generated DNA sequence may be greater than 99.9% identical to the actual DNA sequence (for example, one base insertion or deletion in an open reading frame of over 1000 bases).
Accordingly, for those applications requiring precision in the nucleotide sequence or the amino acid sequence, the present invention provides not only the generated nucleotide sequence identified as SEQ ID NO:X and the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA
containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1. The nucleotide sequence of each deposited clone can readily be determined by sequencing the deposited clone in accordance with known methods. The predicted amino acid sequence can then be verified from such deposits. Moreover, the amino acid sequence of the protein encoded by a particular clone can also be directly determined by peptide sequencing or by expressing the protein in a suitable host cell containing the deposited human cDNA, collecting the protein, and determining its sequence.
The present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, or the deposited clone. The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein.
Such methods include preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.
Also provided in the present invention are species homologs. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source for the desired homologue.
The polypeptides of the invention can be prepared in any suitable manner. Such polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or polypeptides produced by a combination of these methods. Means for preparing such polypeptides are well understood in the art.
The polypeptides may be in the form of the secreted protein, including the mature form, or may be a part of a larger protein, such as a fusion protein (see below).
It is often advantageous to include an additional amino acid sequence which contains secretory or leader sequences, pro-sequences, sequences which aid in purification , such as multiple histidine residues, or an additional sequence for stability during recombinant production.
The polypeptides of the present invention are preferably provided in an isolated form, and preferably are substantially purified. A recombinantly produced version of a polypeptide, including the secreted polypeptide, can be substantially purified by the one-step method described in Smith and Johnson, Gene 67:31-40 (1988).
Polypeptides of the invention also can be purified from natural or recombinant sources using antibodies of the invention raised against the secreted protein in methods which are well known in the art.
Signal Seauences Methods for predicting whether a protein has a signal sequence, as well as the cleavage point for that sequence, are available. For instance, the method of McGeoch, Virus Res. 3:271-286 ( 1985), uses the information from a short N-terminal charged region and a subsequent uncharged region of the complete (uncleaved) protein.
The method of von Heinje, Nucleic Acids Res. 14:4683-4690 ( 1986) uses the information from the residues surrounding the cleavage site, typically residues -13 to +2, where +1 indicates the amino terminus of the secreted protein. The accuracy of predicting the cleavage points of known mammalian secretory proteins for each of these methods is in the range of 75-80%. (von Heinje, supra.) However, the two methods do not always produce the same predicted cleavage points) for a given protein.
In the present case, the deduced amino acid sequence of the secreted polypeptide was analyzed by a computer program called SignalP (Henrik Nielsen et al., Protein Engineering 10:1-6 (1997)), which predicts the cellular location of a protein based on the amino acid sequence. As part of this computational prediction of localization, the methods of McGeoch and von Heinje are incorporated. The analysis of the amino acid sequences of the secreted proteins described herein by this program provided the results shown in Table 1.
As one of ordinary skill would appreciate, however, cleavage sites sometimes vary from organism to organism and cannot be predicted with absolute certainty.
Accordingly, the present invention provides secreted polypeptides having a sequence shown in SEQ ID NO:Y which have an N-terminus beginning within 5 residues (i.e., +
or - 5 residues) of the predicted cleavage point. Similarly, it is also recognized that in some cases, cleavage of the signal sequence from a secreted protein is not entirely uniform, resulting in more than one secreted species. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention.
Moreover, the signal sequence identified by the above analysis may not necessarily predict the naturally occurring signal sequence. For example, the naturally occurring signal sequence may be further upstream from the predicted signal sequence.
However, it is likely that the predicted signal sequence will be capable ofdirecting the secreted protein to the ER. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention.
PolYnucleotide and Polypeptide Variants "Variant" refers to a polynucleotide or polypeptide differing from the polynucleotide or polypeptide of the present invention, but retaining essential properties thereof. Generally, variants are overall closely similar, and, in many regions, identical to the polynucleotide or polypeptide of the present invention.
By a polynucleotide having a nucleotide sequence at least, for example, 95%
"identical" to a reference nucleotide sequence of the present invention, it is intended that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence encoding the polypeptide.
In other words, to obtain a polynucleotide having a nucleotide sequence at least 95%
identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. The query sequence may be an entire sequence shown inTable l, the ORF
(open reading frame), or any fragement specified as described herein.
As a practical matter, whether any particular nucleic acid molecule or polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to a nucleotide sequence of the presence invention can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB
computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci.
( 1990) b:237-245). In a sequence alignment the query and subject sequences are both DNA
sequences. An RNA sequence can be compared by converting U's to T's. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB alignment of DNA sequences to calculate percent identiy are:
Matrix=Unitary, k-tuple=4, Mismatch Penalty=1, Joining Penalty=30, Randomization Group Length=0, Cutoff Score=1, Gap Penalty=5, Gap Size Penalty 0.05, Window Size=500 or the lenght of the subject nucleotide sequence, whichever is shorter.
If the subject sequence is shorter than the query sequence because of 5' or 3' deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for 5' and 3' truncations of the subject sequence when calculating percent identity. For subject sequences truncated at the 5' or 3' ends, relative to the the query sequence, the percent identity is corrected by calculating the number of bases of the query sequence that are 5' and 3' of the subject sequence, which are not matched/aligned, as a percent of the total bases of the query sequence. Whether a nucleotide is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This corrected score is what is used for the purposes of the present invention. Only bases outside the 5' and 3' bases of the subject sequence, as displayed by the FASTDB alignment, which are not matched/aligned with the query sequence, are calculated for the purposes of manually adjusting the percent identity score.
For example, a 90 base subject sequence is aligned to a 100 base query sequence to determine percent identity. The deletions occur at the 5' end of the subject sequence and therefore, the FASTDB alignment does not show a matched/alignement of the first 10 bases at 5' end. The 10 unpaired bases represent 10% of the sequence (number of bases at the 5' and 3' ends not matched/total number of bases in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 bases were perfectly matched the final percent identity would be 90%. In another example, a 90 base subject sequence is compared with a 100 base query sequence. This time the deletions are internal deletions so that there are no bases on the S' or 3' of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only bases 5' and 3' of the subject sequence which are not matched/aligned with the query sequnce are manually corrected for. No other manual - corrections are to made for the purposes of the present invention.
By a polypeptide having an amino acid sequence at least, for example, 95%
"identical" to a query amino acid sequence of the present invention, it is intended that the amino acid sequence of the subject polypeptide is identical to the query sequence except that the subject polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a query WO 98/54963 PCT/(JS98/11422 amino acid sequence, up to 5% of the amino acid residues in the subject sequence may be inserted, deleted, (indels) or substituted with another amino acid. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the reference sequence.
As a practical matter, whether any particular polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, the anuno acid sequences shown in Table 1 or to the amino acid sequence encoded by deposited DNA clone can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. ( 1990) 6:237-245). In a sequence alignment the query and subject sequences are either both nucleotide sequences or both amino acid sequences.
The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2, Mismatch Penalty=l, Joining Penalty=20, Randomization Group Length=0, Cutoff Score=1, Window Size=sequence length, Gap Penalty=S, Gap Size Penalty=0.05, Window Size=500 or the length of the subject amino acid sequence, whichever is shorter.
If the subject sequence is shorter than the query sequence due to N- or C-terminal deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity.
For subject sequences truncated at the N- and C-termini, relative to the the query sequence, the percent identity is corrected by calculating the number of residues of the query sequence that are N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence. Whether a residue is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score is what is used for the purposes of the present invention. Only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score.
That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence.
For example, a 90 amino acid residue subject sequence is aligned with a 100 residue query sequence to determine percent identity. The deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining residues were perfectly matched the final percent identity would be 90%. In another example, a 90 residue subject sequence is compared with a 100 residue query sequence.
This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query.
In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only residue positions outside the N- and C-terminal ends of the subject sequence, as displayed in the FASTDB alignment, which are not matched/aligned with the query sequnce are manually corrected for. No other manual corrections are to made for the purposes of the present invention.
The variants may contain alterations in the coding regions, non-coding regions, or both. Especially preferred are polynucleotide variants containing alterations which produce silent substitutions, additions, or deletions, but do not alter the properties or activities of the encoded polypeptide. Nucleotide variants produced by silent substitutions due to the degeneracy of the genetic code are preferred.
Moreover, variants in which 5-10, 1-5, or 1-2 amino acids are substituted, deleted, or added in any combination are also preferred. Polynucleotide variants can be produced for a variety of reasons, e.g., to optimize codon expression for a particular host (change codons in the human mRNA to those preferred by a bacterial host such as E. coli).
Naturally occurring variants are called "allelic variants," and refer to one of several alternate forms of a gene occupying a given locus on a chromosome of an organism. (Genes II, Lewin, B., ed., John Wiley & Sons, New York (1985).) These allelic variants can vary at either the polynucleotide and/or polypeptide level.
Alternatively, non-naturally occurring variants may be produced by mutagenesis techniques or by direct synthesis.
Using known methods of protein engineering and recombinant DNA
technology, variants may be generated to improve or alter the characteristics of the polypeptides of the present invention. For instance, one or more amino acids can be deleted from the N-terminus or C-terminus of the secreted protein without substantial loss of biological function. The authors of Ron et al., J. Biol. Chem. 268:
(1993), reported variant KGF proteins having heparin binding activity even after deleting 3, 8, or 27 amino-terminal amino acid residues. Similarly, Interferon gamma exhibited up to ten times higher activity after deleting 8-10 amino acid residues from the carboxy terminus of this protein. (Dobeli et al., J. Biotechnology 7:199-216 (1988).) Moreover, ample evidence demonstrates that variants often retain a biological activity similar to that of the naturally occurring protein. For example, Gayle and coworkers (J. Biol. Chem 268:22105-22111 (1993)) conducted extensive mutational analysis of human cytokine IL-la. They used random mutagenesis to generate over 3,500 individual IL-la mutants that averaged 2.5 amino acid changes per variant over the entire length of the molecule. Multiple mutations were examined at every possible amino acid position. The investigators found that "[m]ost of the molecule could be altered with little effect on either [binding or biological activity]." (See, Abstract.) In fact, only 23 unique amino acid sequences, out of more than 3,500 nucleotide sequences examined, produced a protein that significantly differed in activity from wild-type.
Furthermore, even if deleting one or more amino acids from the N-terminus or C-terminus of a polypeptide results in modification or loss of one or more biological functions, other biological activities may still be retained. For example, the ability of a deletion variant to induce and/or to bind antibodies which recognize the secreted form wilt likely be retained when less than the majority of the residues of the secreted form are removed from the N-terminus or C-terminus. Whether a particular polypeptide lacking N- or C-terminal residues of a protein retains such immunogenic activities can readily be determined by routine methods described herein and otherwise known in the art.
Thus, the invention further includes polypeptide variants which show substantial biological activity. Such variants include deletions, insertions, inversions, repeats, and substitutions selected according to general rules known in the art so as have little effect on activity. For example, guidance concerning how to make phenotypically silent amino acid substitutions is provided in Bowie, J. U. et al., Science 247:1306-1310 (1990), wherein the authors indicate that there are two main strategies for studying the tolerance of an amino acid sequence to change.
The first strategy exploits the tolerance of amino acid substitutions by natural selection during the process of evolution. By comparing amino acid sequences in different species, conserved amino acids can be identified. These conserved amino acids are likely important for protein function. In contrast, the amino acid positions where substitutions have been tolerated by natural selection indicates that these positions are not critical for protein function. Thus, positions tolerating amino acid substitution could be modified while still maintaining biological activity of the protein.
The second strategy uses genetic engineering to introduce amino acid changes at specific positions of a cloned gene to identify regions critical for protein function. For example, site directed mutagenesis or alanine-scanning mutagenesis (introduction of single alanine mutations at every residue in the molecule) can be used.
{Cunningham and Wells, Science 244:1081-1085 (1989).) The resulting mutant molecules can then be tested for biological activity.
As the authors state, these two strategies have revealed that proteins are surprisingly tolerant of amino acid substitutions. The authors further indicate which amino acid changes are likely to be permissive at certain amino acid positions in the protein. For example, most buried (within the tertiary structure of the protein) amino acid residues require nonpolar side chains, whereas few features of surface side chains are generally conserved. Moreover, tolerated conservative amino acid substitutions involve replacement of the aliphatic or hydrophobic amino acids Ala, Val, Leu and Ile;
replacement of the hydroxyl residues Ser and Thr; replacement of the acidic residues i 5 Asp and Glu; replacement of the amide residues Asn and Gln, replacement of the basic residues Lys, Arg, and His; replacement of the aromatic residues Phe, Tyr, and Trp, and replacement of the small-sized amino acids Ala, Ser, Thr, Met, and Gly.
Besides conservative amino acid substitution, variants of the present invention include (i) substitutions with one or more of the non-conserved amino acid residues, where the substituted amino acid residues may or may not be one encoded by the genetic code, or (ii) substitution with one or more of amino acid residues having a substituent group, or (iii) fusion of the mature polypeptide with another compound, such as a compound to increase the stability and/or solubility of the polypeptide (for example, polyethylene glycol), or (iv) fusion of the polypeptide with additional amino acids, such as an IgG Fc fusion region peptide, or leader or secretory sequence, or a sequence facilitating purification. Such variant polypeptides are deemed to be within the scope of those skilled in the art from the teachings herein.
For example, polypeptide variants containing amino acid substitutions of charged amino acids with other charged or neutral amino acids may produce proteins with improved characteristics, such as less aggregation. Aggregation of pharmaceutical formulations both reduces activity and increases clearance due to the aggregate's immunogenic activity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967);
Robbins et al., Diabetes 36: 838-845 ( 1987); Cleland et al., Crit. Rev.
Therapeutic Drug Carrier Systems 10:307-377 (1993).) Polynucleotide and Polypeptide Fr~ments In the present invention, a "polynucleotide fragment" refers to a short polynucleotide having a nucleic acid sequence contained in the deposited clone or shown in SEQ ID NO:X. The short nucleotide fragments are preferably at least about 15 nt, and more preferably at least about 20 nt, still more preferably at least about 30 nt, and even more preferably, at least about 40 nt in length. A fragment "at Ieast 20 nt in length," for example, is intended to include 20 or more contiguous bases from the cDNA sequence contained in the deposited clone or the nucleotide sequence shown in SEQ ID NO:X. These nucleotide fragments are useful as diagnostic probes and primers as discussed herein. Of course, larger fragments (e.g., 50, 150, 500, 600, nucleotides) are preferred.
Moreover, representative examples of polynucleotide fragments of the invention, include, for example, fragments having a sequence from about nucleotide - number 1-50, 51-100, 101-150, 151-200, 201-250, 25I-300, 301-350, 351-400, 450, 451-500, 501-550, 551-600, 651-700, 701-750, 751-800, 800-850, 851-900, 901-950, 951-1000, 1001-1050, 1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951-2000, or 2001 to the end of SEQ ID NO:X or the cDNA contained in the deposited clone. In this context "about" includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1 ) nucleotides, at either terminus or at both termini.
Preferably, these fragments encode a polypeptide which has biological activity. More preferably, these polynucleotides can be used as probes or primers as discussed herein.
In the present invention, a "polypeptide fragment" refers to a short amino acid sequence contained in SEQ ID NO:Y or encoded by the cDNA contained in the deposited clone. Protein fragments may be "free-standing," or comprised within a larger polypeptide of which the fragment forms a part or region, most preferably as a single continuous region. Representative examples of polypeptide fragments of the invention, include, for example, fragments from about amino acid number 1-20, 2I-40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, or 161 to the end of the coding region. Moreover, polypeptide fragments can be about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 amino acids in length. In this context "about"
includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1 ) amino acids, at either extreme or at both extremes.
Preferred polypeptide fragments include the secreted protein as well as the mature form. Further preferred polypeptide fragments include the secreted protein or the mature form having a continuous series of deleted residues from the amino or the carboxy terminus, or both. For example, any number of amino acids, ranging from 1-60, can be deleted from the amino terminus of either the secreted polypeptide or the mature form. Similarly, any number of amino acids, ranging from 1-30, can be deleted from the carboxy terminus of the secreted protein or mature form. Furthermore, any combination of the above amino and carboxy terminus deletions are preferred.
Similarly, polynucleotide fragments encoding these polypeptide fragments are also preferred.
Particularly, N-terminal deletions of the polypeptide of the present invention can be described by the general formula m-p, where p is the total number of amino acids in the polypeptide and m is an integer from 2 to (p-1), and where both of these integers (m & p) correspond to the position of the amino acid residue identified in SEQ ID
NO:Y.
Moreover, C-terminal deletions of the polypeptide of the present invention can also be described by the general formula 1-n, where n is an integer from 2 to (p-1), and again where these integers (n & p) correspond to the position of the amino acid residue identified in SEQ ID NO:Y.
The invention also provides polypeptides having one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m-n of SEQ ID NO:Y, where m and n are integers as described above.
Also preferred are polypeptide and polynucleotide fragments characterized by structural or functional domains, such as fragments that comprise alpha-helix and alpha-helix forming regions, beta-sheet and beta-sheet-forming regions, turn and turn-forming regions, coil and coil-forming regions, hydrophilic regions, hydrophobic regions, alpha amphipathic regions, beta amphipathic regions, flexible regions, surface-forming regions, substrate binding region, and high antigenic index regions.
Polypeptide fragments of SEQ ID NO: Y falling within conserved domains are specifically contemplated by the present invention. Moreover, polynucleotide fragments encoding these domains are also contemplated.
Other preferred fragments are biologically active fragments. Biologically active fragments are those exhibiting activity similar, but not necessarily identical, to an activity of the polypeptide of the present invention. The biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity.
E hopes & Antibodies In the present invention, "epitopes" refer to polypeptide fragments having antigenic or immunogenic activity in an animal, especially in a human. A
preferred embodiment of the present invention relates to a polypeptide fragment comprising an W O 98!54963 PCT/US98/i 1422 epitope, as well as the polynucleotide encoding this fragment. A region of a protein molecule to which an antibody can bind is defined as an "antigenic epitope."
In contrast, an "immunogenic epitope" is defined as a part of a protein that elicits an antibody response. (See, for instance, Geysen et al., Proc. Natl. Acad. Sci.
USA
81:3998- 4002 (1983).) Fragments which function as epitopes may be produced by any conventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985) further described in U.S. Patent No. 4,631,211.) In the present invention, antigenic epitopes preferably contain a sequence of at least seven, more preferably at least nine, and most preferably between about 15 to about 30 amino acids. Antigenic epitopes are useful to raise antibodies, including monoclonal antibodies, that specifically bind the epitope. (See, for instance, Wilson et al., Cell 37:767-778 ( 1984); Sutcliffe, J. G. et al., Science 219:660-666 ( 1983).) Similarly, immunogenic epitopes can be used to induce antibodies according to methods well known in the art. (See, for instance, SutcIiffe et al., supra;
Wilson et al., supra; Chow, M. et al., Proc. Natl. Acad. Sci. USA 82:910-914; and Bittle, F.
J. et al., J. Gen. Virol. 66:2347-2354 ( 1985).) A preferred immunogenic epitope includes the secreted protein. The immunogenic epitopes may be presented together with a carrier protein, such as an albumin, to an animal system (such as rabbit or mouse) or, if it is long enough (at least about 25 amino acids), without a carrier. However, immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to raise antibodies capable of binding to, at the very least, linear epitopes in a denatured polypeptide (e.g., in Western blotting.) As used herein, the term "antibody" (Ab) or "monoclonal antibody" (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab')2 fragments) which are capable of specifically binding to protein. Fab and F(ab')2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody.
(Wahl et al., J. Nucl. Med. 24:316-325 (1983).) Thus, these fragments are preferred, as well as the products of a FAB or other immunoglobulin expression library.
Moreover, antibodies of the present invention include chimeric, single chain, and humanized antibodies.
Fusion Proteins Any polypeptide of the present invention can be used to generate fusion proteins. For example, the polypeptide of the present invention, when fused to a second protein, can be used as an antigenic tag. Antibodies raised against the DEMANDES OU BREVETS VOLUMINEUX
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207 Human Secreted Proteins Field of the Invention This invention relates to newly identified polynucleotides and the polypeptides encoded by these polynucleotides, uses of such polynucleotides and polypeptides, and their production.
Background of the Invention Unlike bacterium, which exist as a single compartment surrounded by a membrane, human cells and other eucaryotes are subdivided by membranes into many functionally distinct compartments. Each membrane-bounded compartment, or organelle, contains different proteins essential for the function of the organelle. The cell uses "sorting signals," which are amino acid motifs located within the protein, to target proteins to particular cellular organelles.
One type of sorting signal, called a signal sequence, a signal peptide, or a leader sequence, directs a class of proteins to an organelle called the endoplasmic reticulum (ER). The ER separates the membrane-bounded proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus. Here, the Golgi distributes the proteins to vesicles, including secretory vesicles, the cell membrane, lysosomes, and the other organelles.
Proteins targeted to the ER by a signal sequence can be released into the extracellular space as a secreted protein. For example, vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space - a process called exocytosis. Exocytosis can occur constitutively or after receipt of a triggering signal. In the latter case, the proteins are stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins residing on the cell membrane can also be secreted into the extracellular space by proteolytic cleavage of a "linker" holding the protein to the membrane.
Despite the great progress made in recent years, only a small number of genes encoding human secreted proteins have been identified. These secreted proteins include the commercially valuable human insulin, interferon, Factor VIII, human growth hormone, tissue plasminogen activator, and erythropoeitin. Thus, in light of the pervasive role of secreted proteins in human physiology, a need exists for identifying and characterizing novel human secreted proteins and the genes that encode them. This knowledge will allow one to detect, to treat, and to prevent medical disorders by using secreted proteins or the genes that encode them.
Summary of the Invention The present invention relates to novel polynucleotides and the encoded polypeptides. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides.
Also provided are diagnostic methods for detecting disorders related to the polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of the polypeptides.
Detailed Description Definitions The following definitions are provided to facilitate understanding of certain terms used throughout this specification.
In the present invention, "isolated" refers to material removed from its original environment (e.g., the natural environment if it is naturally occurring), and thus is altered "by the hand of man" from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be "isolated" because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide.
In the present invention, a "secreted" protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a "mature" protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage.
As used herein , a "polynucleotide" refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X or the cDNA contained within the clone deposited with the ATCC. For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5' and 3' untranslated sequences, the coding region, with or without the signal sequence, the secreted protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence.
Moreover, as used herein, a "polypeptide" refers to a molecule having the translated amino acid sequence generated from the polynucleotide as broadly defined.
In the present invention, the full length sequence identified as SEQ ID NO:X
was often generated by overlapping sequences contained in multiple clones (contig analysis). A representative clone containing all or most of the sequence for SEQ ID
NO:X was deposited with the American Type Culture Collection ("ATCC"). As shown in Table l, each clone is identified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number. The ATCC is located at 10801 University Boulevard, Manassas, Virginia 20110-2209, USA. The ATCC deposit was made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for purposes of patent procedure.
A "polynucleotide" of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, the complement thereof, or the eDNA within the clone deposited with the ATCC. "Stringent hybridization conditions" refers to an overnight incubation at 42°
C in a solution comprising 50% formamide, Sx SSC (750 mM NaCI, 75 mM sodium citrate), 50 mM sodium phosphate {pH 7.6), Sx Denhardt's solution, 10% dextran sulfate, and 20 pg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in O.lx SSC at about 65°C.
Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions.
Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature.
For example, lower stringency conditions include an overnight incubation at 37°C in a solution comprising 6X SSPE (20X SSPE = 3M NaCI; 0.2M NaH~P04; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 ug/ml salmon sperm blocking DNA;
followed by washes at 50°C with 1XSSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5X SSC}.
Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations. The inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.
Of course, a polynucleotide which hybridizes only to polyA+ sequences (such as any 3' terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of "polynucleotide," since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone).
The polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified-RNA or DNA
or modified RNA or DNA. For example, polynucleotides can be composed of single-and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single-and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single-and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability I S or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications can be made to DNA
and RNA; thus, "polynucleotide" embraces chemically, enzymatically, or metabolically modified forms.
The polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art.
Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched , for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods.
Modifications include acetylation, acyiation, ADP-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links. formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI
anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, . selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins 5 such as arginylation, and ubiquitination. (See, for instance, PROTEINS -p STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E. Creighton, W.
H. Freeman and Company, New York ( 1993); POSTTRANSLATIONAL
COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York, pgs. 1-12 (1983); Seifter et al., Meth Enzymol 182:626-646 (1990);
Rattan et al., Ann NY Acad Sci 663:48-62 ( 1992).) "SEQ ID NO:X" refers to a polynucleotide sequence while "SEQ ID NO:Y"
refers to a polypeptide sequence, both sequences identified by an integer specified in Table 1.
"A polypeptide having biological activity" refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention.) Polvnucleotides and Poly~eptides of the Invention FEATURES OF PROTEIN ENCODED BY GENE NO: 1 This gene is expressed primarily in melanocytes and, to a lesser extent, in testes, ovary, kidney and other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer, disorders of neural crest derived cells including pigmentation defects, melanoma, reproductive organ defects, and defects of the kidney.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skin, reproductive, and renal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating disorders that arise from alterations in the number or fate of neural crest derived cells including cancers such as melanoma and defects of the developing reproductive system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 2 This gene is expressed primarily in infant brain and fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental disorders of the brain or lung. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous and pulmonary systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression Ievel in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating or diagnosing disorders associated with abnormal proliferation of cells in the Central nervous system and developing lung.
FEATURES OF PROTEIN ENCODED BY GENE NO: 3 This gene is expressed primarily in breast lymph node and to a lesser extent in ovarian cancer and chondrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune responses such as inflammation or immune surveillance for tumors. This gene may be important for inflammatory responses associated with tumors. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 236 as residues: Lys-45 to Val-50, Lys-69 to Arg-76.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment or diagnosis of immune responses including those associated with tumor-induced inflammation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 4 This gene is expressed primarily in T-cells and T-cell lymphomas.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunilogical diseases involving T-cells such as inflammation, autoimmunity, and cancers including T-cell lymphomas. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of T-cells and other cells of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids {e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing and treating T-cell based disorders such as inflammatory diseases, autoimmune disease and tumors including T-cell lymphomas.
WO 98!54963 PCT/US98/11422 FEATURES OF PROTEIN ENCODED BY GENE NO: 5 This gene is expressed primarily in activated monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation, autoimmunity, infection, or disorders involving activation of monocytes. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synoviai fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 238 as residues: Asp-19 to Arg-31.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing or treating diseases that result in activation of monocytes including infections, inflammatory responses or autoimmune diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 6 The translation product of this gene shares sequence homology with terminal deoxynucleotidyltransferase which is thought to be important in catalyzing the elongation of oligo- or polydeoxynucleotide chains.
This gene is expressed primarily in activated human neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer, particularly those of the blood such as leukemia and deficiencies in neutrophils such as neutropenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to terminal deoxynucleotidyltransferase indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and differential diagnosis of acute leukemia's. Alternatively, this gene may function in the proliferation of neutrophils and be useful as a treatment for neutropenia, for example, following neutropenia as a result of chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 7 The contig exhibits a reasonable homology to the human chorionic gonadotropic (HCG) analogue-GT beta-subunit as disclosed in U.S. Patent No. 5,508,261 and PCT
Publication No. WO 92/22568. There is a high degree of conservation of the structurally important cysteine residues in these identities.
This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the immune system, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of diseases of the immune system since expression is primarily in neutrophils, and may be useful as a growth factor for the differentiation or proliferation of neutrophils for the treatment of neutropenia following chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 8 This gene is expressed primarily in IL-1- and LPS-induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include,but are not limited to, diseases of the immune system, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) 5 or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard 10 gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 241 as residues: Ser-14 to Pro-22, Leu-43 to Val-53.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of diseases of the immune system since expression is primarily in neutrophils, and may be useful as a growth factor for the differentiation or proliferation of neutrophils for the treatment of neutropenia following chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 9 This gene is expressed primarily in IL-1 and LPS induced neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the immune system, including inflammatory diseases and allergies. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 242 as residues: Tyr-22 to His-35.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of diseases of the immune system since expression is primarily in neutrophils, and may be useful as a growth factor for the differentiation or proliferation of neutrophils for the treatment of neutropenia following chemotherapy.
FEATURES OF PROTEIN ENCODED BY GENE NO: 10 This gene is expressed primarily in activated T-cells and to a lesser extent in endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune dysfunctions including cancer of the T lymphocytes and autoimmune disorders and inflammation. Similarly, polypeptides and antibodies . directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of immune disorders particularly of T-cell origin and may act as a growth factor for particular subsets of T-cells such as CD4 positive cells which would make this a useful therapeutic for the treatment of HIV and other immune compromising illnesses.
FEATURES OF PROTEIN ENCODED BY GENE NO: 11 This gene is expressed primarily in fetal tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of many developmental abnormalities.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing fetus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucIeotides and polypeptides corresponding to this gene are useful as a growth factor or differentiation factor for particular cell types in the developing fetus and may be useful in replacement or other types of therapy in cases where the gene is expressed aberrantly.
FEATURES OF PROTEIN ENCODED BY GENE NO: 12 This gene is expressed primarily in T-cells and to a lesser extent in tumor tissue including glioblastoma, meningioma, and Wilm's tumor.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the immune system including autoimmune conditions such as I S rheumatoid arthritis, inflammatory disorders and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 245 as residues:
Thr-9 to Ser-14.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis/ modulation of immune function disorders, including rheumatoid arthritis and inflammatory responses.
FEATURES OF PROTEIN ENCODED BY GENE NO: 13 This gene is expressed primarily in placenta and to a lesser extent in fetal liver and bone marrow.
Therefore, polynucIeotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of hematological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematological and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a growth factor for hematapoietic stem cells or progenitor cells in the treatment of chemotherapy patients or kidney disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 14 This gene is expressed primarily in stromal cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of hematapoietic disorders including cancer, neutropenia, anemia, and thrombocytopenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematapoietic and immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a growth factor for hematapoietic stem cells or progenitor cells, in particular following chemotherapy treatment.
FEATURES OF PROTEIN ENCODED BY GENE NO: 15 The translation product of this gene shares sequence homology with epsilon-COP from Bos taurus which is thought to be important as a component of coatomer, a complex of seven proteins, that is the major component of the non-clathrin membrane coat. Preferred polypeptides encoded by this gene comprise the following amino acid sequences:
MAPPAPGPASGGSGEVDELFDVKNAFYIGSYQQCINEAXXVKLSSPERDVERD
VFLYRAYLAQRKFGVVLDEIKPSSAPELQAVRMFADYLAHESRRDSIVAELDRE
MSRSXDVTNTTFLLMAASIYLHDQNPDAALRALHQGDSLECTAMTVQILLKLD
RLDLARKELKRMQDLDEDATLTQLATAWVSLATGGEKLQDAYYIFQEMADKCS
PTLLLLNGQAACHMAQGRWEAAEGLLQEALDKDSGYPETLVNLIVLSQHLGKP
PEVTNRYLSQLKDAHRSHPFIKEYQAKENDFDRLVLQYAPSAEAGPELSGP
(SEQ ID N0:458); or RDVERDVFLYRAYLAQRKFGVVLDEIKPSSAPELQAVRMF
ADYLAHESRRDSIVAELDREMSRSXDVTNTTFLLMAASIYLHDQNPDAALRALH
QGDSLECTAMTVQILLKLDRLDLARKELKRMQDLDEDATLTQLATAVW SLATG
GEKLQDAYYIFQEMADKCSPTLLLLNGQAACHMAQGRWEAAEGLLQEALDKD
SGYPETLVNLIVLSQHLGKPPEVTNRYLSQLKDAHRSHPFIKEYQAKENDFDRL
VLQYAPSA (SEQ ID N0:459).
This gene is expressed primarily in activated monocytes and T-cells, and to a lesser extent in multiple other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunomodulation, specifically relating to transport problems in these cells. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to epsilon-COP indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating /diagnosing problems with the cellular transport of proteins that may result in immunologic dysfunction.
FEATURES OF PROTEIN ENCODED BY GENE NO: 16 The translation product of this gene shares sequence homology with an RNA
helicase which is thought to be important in polynucleotide metabolism. The translation product of this contig exhibits good homology to the LbeIF4A antigen of Leishmania braziliensis. The LbeIF4A antigen, or immunogenic portions of it, can be used to induce protective immunity against leishmaniasis, specifically L. donovani, L.
chagasi, L. infantum, L. major, L. braziliensis, L. panamensis, L. tropics and L.
guyanensis. It can also be used diagnostically to detect Leishmania infection or to stimulate a cellular and/or humoral immune response or to stimulate the production of interleukin-12.
This gene is expressed primarily in colon cancer and to a lesser extent in pituitary.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of cancers particularly of the colon.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing 10 immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample 15 taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 249 as residues: Glu-93 to Ala-98, Gln-150 to Leu-156, Leu-220 to Leu-231, Leu-268 to Arg-273, Val-324 to Pro-341, Arg-372 to Asn-380, Ser-405 to Gly-410, Phe-426 to Ala-433, Glu-458 to Asp-470, Arg-S06 to Ser-547.
The tissue distribution and homology to RNA helicase indicates that polynucleotides and polypeptides corresponding to this gene are useful for development of diagnostic tests for colon cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 17 The translation product of this contig has sequence homology to a cytoplasmic protein that binds specifically to JNK designated the JNK interacting protein-1 or JIP-1 in mice. JIP-1 caused cytoplasmic retention of JNK and inhibition of JNK-regulated gene expression.
This gene is expressed primarily in brain including pituitary cerebellum frontal cortex, fetal brain and to a lesser extent in the kidney cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of the central nervous system disorders including ischemia, epilepsy, Parkinson's disease, and schizophrenia. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Furthermore, the translation product of this contig may suppress the effects of the JNK signaling pathway on cellular proliferation, including transformation by the Bcr-Abl oncogene. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 250 as residues: Pro-6 to Ser-26, Ala-30 to Asp-41, GIy-55 to Ser-61, Gly-74 to Thr-80, Tyr-I 17 to AIa-123, Tyr-167 to Asp-172, Ala-212 to Cys-223, Pro-239 to Tyr-244.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for enhanced survival and/or differentiation of neurons as a treatment for neurodegenerative disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 18 The translation product of this gene shares sequence homology with a liver stage antigen from a protozoan parasite.
This gene is expressed primarily in fetal tissue and to a lesser extent in activated T-cells and other immune cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, bui are not limited to, developmental abnormalities and diseases of immune function.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to a protozoan antigen indicates that polynucleotides and polypeptides corresponding to this gene are useful' for treatment/immune modulation of parasitic infections.
FEATURES OF PROTEIN ENCODED BY GENE NO: 19 Preferred polypeptide encoded by this gene comprise the foilowing polypeptide sequences:
MKAIGIEPSLATYHHIIRLFDQPGDPLKRSSFIIYDIMNELMGKRFSPKD
DLICLMEQIDVTLKWYEDLIPSAYFPHSQTMIHLLQALDVANRLEVIPKIWER
(SEQ ID N0:460); and/or KDSKEYGHTFRSDLREEILMLMARDKHPPELQVAF
ADCAADIKSAYESQPIRQTAQDWPATSLNCIATLFLRAGRTQEAWKMLGLFRKH
NKIPRSELLNELMDSAKVSNSPSQAIEVVELASAFSLPICEGLTQRVMSDFAINQ
EQKEALSNLTALTSDSDTDSSSDSDSDTSEGK (SEQ ID N0:461 ). Polynucleotides encoding such polypeptides are also provided.
This gene is expressed primarily in stromal and CD34 depleted bone marrow cells and to a lesser extent in tissues of embryonic origin.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of hematologic origin including cancers and immune dysfunction. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunologicai probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematapoietic and immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 252 as residues: Ser-28 to Gln-34.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a growth factor for hematopoietic stem cells or progenitor cells which may be useful in the treatment of chemotherapy patients suffering from neutropenia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 20 Preferred polypeptide fragments can be found in an alternative open reading frame. These preferred polypeptides comprise the amino acid sequence:
MSSDNESDIEDEDLKLELRRLRDKHLKEIQDLQSRQKHEIESLYTKLGKVPPAVI
IPPAAPLSGRRRRPTKSKGSKSSRSSSLGNKSPQLSGNLSGQSAASVLHPQQTL
HPPGNIPESGQNQLLQPLKPSPSSDNLYSAFTSDGAISVPSLSAPGQGTSSTNTV
GATVNSQAAQAQPPAMTSSRKGTFTDDLHKLVDNWARDAMNLSGRRGSKGH
MNYEGPGMARKFSAPGQLCISMTSNLGGSAPISAASATSLGHFTKSMCPPQQY
GFPATPFGAQWSGTGGPAPQPLGQFQPVGTASLQNFNISNLQKSISNPPGSNL
RTT (SEQ ID N0:462); IQDLQSRQKHEIESLYTKLGKVPPAVIIPPAAPLSGRRRR
PTKSKGSKSSRSSSLGNKSPQLSGNLSGQSAASVLHPQQTLHPPGNIPESGQN
QLLQPLKPSPSSDNLYSAFTSDGAISVPSLSAPGQGTSST (SEQ ID N0:463);
TSDGAISVPSLSAPGQGTSSTNTVGATVNSQAAQAQPPAMTSSRKGTFTDDLH
(SEQ ID N0:464); KGHMNYEGPGMARKFSAPGQLCISMTSNLGGSAPISAAS
ATSLGHFTK (SEQ ID N0:465); QPLKPSPSSDNLYSAFTSDGAISVPSLSAPG
(SEQ ID N0:466). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in fetal liver and tissues associated with the CNS.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver and CNS diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the liver and CNS, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 253 as residues:
Gln-26 to Lys-34.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for liver diseases such as hepatocellular carcinomas and diseases of the CNS.
FEATURES OF PROTEIN ENCODED BY GENE NO: 21 In an alternative reading frame, this gene shows sequence homology to two recently cloned genes, karyopherin beta 3 and Ran GTP binding protein 5. (See Accession Nos. gi12102696 and gnIIPIDle328731.) The Ran GTP binding protein is related to importin-beta, the key mediator of nuclear localization signal (NLS)-dependent nuclear transport. Based on homology, it is likely that this gene may activity similar to the RAN GTP binding protein. Preferred polypeptide fragments comprise the amino acid sequence: VRVAAAESMXLLLECAXVRGPEYLTQMWI-~MCDALIKA
IGTEPDSDVLSEIMHSFAK (SEQ ID N0:467). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in thymus tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 22 This gene is expressed primarily in prostate and osteoclastoma tissues.
Preferred polypeptide fragments also comprise the amino acid sequence:
MEINNQNCFIVIDLVRTVMENGVEGLLIFGAFLPESWLIGVRCSSEPPKALLLIL
AHSQKRRLDGWSFIRHLRVHYCVSLTIHFS (SEQ ID N0:468). Also preferred are polynucleotide sequences encoding this polypeptide fragment.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, bone and prostate diseases, and cancers, particularly of the bone and prostate. Similarly. polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the_tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bone and prostate systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded 5 tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 255 as residues: Met-1 to Ser-1 I.
10 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for bone and prostate disorders, especially cancers of those systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 23 15 This gene shares sequence homology with the FK506-binding protein (FKBP-i 3) family, a known cytosolic receptor for the immunosuppressants. Recently, another group has cloned a very similar gene, recognizing the homology to FK506-binding protein family, calling their gene FKBP23. (See Accession No. 2827255.) This gene is expressed primarily in lymphoid tissues.
20 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample, especially for those susceptible to immune suppressant therapies and for diagnosis of diseases and conditions, which include, but are not limited to, immune suppressant disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 256 as residues: Ala-19 to Val-31, Arg-38 to Gly-49, Ala-61 to Lys-66, Tyr-68 to Pro-78, Gly-116 to Ala-121, Asp-154 to Ser-162, Glu-173 to Gln-186, Phe-194 to Gly-203, Pro-207 to Val-212.
The tissue distribution and homology to FKBP-12 and -13 indicates that polynucleotides and polypepiides corresponding to this gene are useful for diagnosis and treatment for immune suppressant disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 24 This gene is expressed primarily in the brain and in the retina. This gene maps to chromosome 8, and therefore can be used in linkage analysis as a marker for chromosome 8.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological and ocular associated disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 257 as residues: Cys-34 to Asp-40.
The tissue distribution in retina indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or detection of eye disorders including blindness, color blindness, impaired vision, short and long sightedness, retinitis pigmentosa, retinitis proliferans, and retinoblastoma. Expression in the brain indicates a role in the is useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 25 This gene shows sequence homology to a newly identified class of proteins expressed in the nervous system, called stathmin family. (See Accession No.
2585991;
see also Eur. J. Biochem. 248 (3), 794-806 ( 1997).) The stathmin family appears to be an ubiquitous phosphoprotein involved as a relay integrating various intracellular signaling pathways. These pathways affect cell proliferation and differentiation.
Preferred polypeptide fragments comprise the amino acid sequence:
QDKHAEEVRKNKELKEEASR (SEQ ID N0:469); QQDLSPWAAPVGCPLXXASX
TCHXLPLSGCLRRQSXSLPV VAXLCFWFSCPLASLFVPGQPCVTCPFPSLPFQD
KHAEEVRKNKELKEEASR (SEQ ID N0:470). Also preferred are the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates. that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 26 The polynucleotide sequence of this gene contains a domain similar to a Flt3 ligand peptide. Preferred polypeptide fragments comprise the amino acid sequence:
PTRCCTTQPCRSSARRPCWVPMVPSPEGREXQPTCPS (SEQ ID N0:471). Thus, this gene may have activity as binding to Flt3 receptors, a process known to promote angiogenesis and/or lymphangiogenesis.
This gene is expressed in human tonsil, and to a lesser extent in teratocarcinoma, placenta, colon carcinoma, and fetal kidney.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the tonsil, as well as cancers, such as colon, reproductive, and kidney cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tonsils, colon, reproductive organs, and kidneys, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 259 as residues:
Pro-22 to Glu-33.
The tissue distribution in tonsil and several cancers and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases of the tonsil or colon, such as tonsillitis, inflammatory diseases involving nose and paranasal sinuses, especially during the infection of influenza, adenoviruses, parainfluenza, rhinoviruses. The gene may also be useful in the diagnosis and treatment of neoplasms of nasopharynx or colon origins.
FEATURES OF PROTEIN ENCODED BY GENE NO: 27 In an alternative reading frame exists a large open reading frame that encodes a preferred polypeptide. Preferred polypeptide fragments comprise the amino acid sequence:
MKRSLNENSARSTAGCLPVPLFNQKKRNRQPLTSNPLKDDSGISTPSDNYDFP
PLPTDWAWEAVNPEXAPVMKTVDTGQIPHSVSRPLRSQDSVFNSIQSNTGRSQ
GGWSYRDGNKNTSLKTWXKNDFKPQCKRTNLVANDGKNSCPMSSGAQQQK
QLRTPEPPNLSRNKETELLRQTHSSKISGCTMRGLDKNSALQTLKPNFQQNQY
KXQMLDDIPEDNTLKETSLYQLQFKEKASSLRIISAVIESMKYWREHAQKTVLL
FEVLAVLDSAVTPGPYYSKTFLMRDGKNTLPCVFYEIDRELPRLIRGRVHRCVG
NYDQKKNIFQCVSVRPASVSEQKTFQAFVKIADVEMQYYINVMNET (SEQ ID
N0:472); SQDSVFNSIQSNTGRSQGGWSYRDGNKNTSLKTWXKNDFKPQCKR
(SEQ ID N0:473); NKETELLRQTHSSKISGCTMRGLDKNSALQTLKPNF (SEQ ID
NO:474);SSLRIISAVIESMKYWREHAQKTVLLFEVLAVLDSAVTPGPYYSKTFLM
(SEQ ID N0:475); and PRLIRGRVHRCVGNYDQKKNIFQCVSVRPASVSEQKT
FQAFV (SEQ ID N0:476).
This gene is expressed primarily in human testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include.
but are not limited to, male reproductive disorders, including cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful as a hormone with reproductive or other systemic functions; contraceptive development; male infertility of testicular causes, such as Kleinfelteris syndrome, varicocele, orchitis; male sexual dysfunctions;
testicular neoplasms; and inflammatory disorders such as epididymitis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 28 This gene is expressed primarily in apoptotic T-cell.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases relating to T cells, as well as cancer in general.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the disorders of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for immune disorders. Moreover, since the gene was isolated from an apoptotic cell and based on the understanding of the relationship of apoptosis and cancer, it is likely that this gene may play a role in the genesis of cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 29 This gene is expressed primarily in human tonsils.
Therefore, polynucleotides and polypeptides of the invention are useful as 5 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, gastrointestinal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above 10 tissues or cells, particularly of the gastrointestinal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level 15 in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of gastrointestinal diseases.
20 FEATURES OF PROTEIN ENCODED BY GENE NO: 30 The translation product of this gene shares sequence homology with C44C 1.2 gene product of Caenorhabditis elegans with unknown function. Preferred polypeptide fragments comprise the amino acid sequence:
GVFRPCVCGRPASLTCSPLDPEVGPYCDTPTMRTLFNLLWLALACSPVHTTLSK
FAGDVLGYVTPWNSHGYDVTKVFGSKFTQISPVWLQLKRRGREMFEVTGLHD
VDQGWMRAVRKHAKGLHIVPRLLFEDWTYDDFRNVLDSEDEIEELSKTVVQVA
KNQHFDGFWEVWNQLLSQKRVGLIHMLTHLAEALHQARLLALLVIPPATTPGT
DQLGMFTHKEFEQLAPVLDGFSLMTYDYSTAHQPGPNAPLSW VRACVQVLDP
KXKWRTKSSWGSTSMXWTXRXPXDARXPVVGXRXIQXLKDHXPRMVLDSK
PQ (SEQ ID N0:477); TCSPLDPEVGPYCDTPTMRTLFNLLWLALACSPVHTTLS
(SEQ ID N0:478); LVVTDLKAESWLEHRSYCSAKARDRHFAGDVLGYVTPW
NSHGYDVTKVFGSKF (SEQ ID N0:479); REMFEVTGLHDVDQGWMRAVRK
HAKGLHIVPRLLFEDWTYDDFRNVLDSEDE (SEQ ID N0:480); HFDGFVVEVW
NQLLSQKRVGLIf~IML,THLAEALHQARLLALLVIPPAITPGTDQLGM (SEQ ID
N0:481); DGFSLMTYDYSTAHQPGPNAPLSWVRACVQVLDPKXKWRTKSSW
GST (SEQ ID N0:482). Also preferred are polynucleotide fragments encoding these polypeptide fragments. This gene maps to human chromosome 11, and therefore is useful in linkage analysis as a marker for chromosome 11.
This gene is expressed primarily in human T cells and to a lesser extent in human colon carcinoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and gastrointestinal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 263 as residues: Leu-21 to Ala-30, Ser-38 to Asp-47, Pro-87 to Asp-94, Leu-to Thr-204, Pro-256 to Ser-262, Thr-277 to Arg-282, Thr-293 to Trp-303.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders and gastrointestinal diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 3I
The translation product of this gene shares sequence homology with Ribosomal protein L11 of Caenorhabditis elegans. (See Accession No. 156201.) Preferred polypeptide fragments comprise the amino acid sequence:
ERGVSINQFCKEFNERTKDIKEGIPLPTKILVKPDRTFEIKIGQPTVSYFLKAAAG
IEKGARQTGKEVAGLVTLKHVYEIARIKAQDEAFALQDVPLSS V VRSIIGSARSL
GIRVVKDLSSEELAAF QKERAIFLAAQKEADLAAQEEAAKK (SEQ ID N0:483).
Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in human embryo tissue and to a lesser extent in human epithelioid sarcoma and other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, development disorders and epithelial cell cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryonic and epithelial cell systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 264 as residues: Lys-34 to Gly-40.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of developmental disorders and epithelial cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 32 This gene is expressed primarily in resting T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory and general immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders of immune system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 33 This gene is believed to reside on chromosome 1. Accordingly, polynucleotides derived from this gene are useful in linkage analysis as chromosome 1 markers.
This gene is expressed primarily in prostate and to a lesser extent in snares adult brain, human umbilical vein endothelial cells, and amniotic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate-related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the urinary system and nervous system expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for the diagnosis and treatment of disorders of the urinary and nervous systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 34 This gene shares sequence homology with ROSG6.4 gene product. (See Accession No.
gi11326338.) This gene also shares sequence homology with the cyclophihn-like protein CyP-60. (See Accession No. 1199598, see also Biochem. J. 314 ( 1 ), 313-319 ( 1996).) Preferred polypeptide fragments comprise the amino acid sequence:
AVYTYHEKKKDTAASGYGTQNIRLSRDAVKDFDCCCLSLQPCHDPVVTPDGYL
YEREAILEYILHQKKEIARQMKAYEKQRGTRREEQKELQRAASQDHVRGFLEKE
SAIVSRP LNPFTAKALSGTSPDDVQPGPSVGPPSKDKDKVLPSFWIPSLTPEAK
ATKLEKPSRTVTCPMSGKPLRMSDLTPVHFTPLDSSVDRVGLITRSERYVCAVT
RDSLSNATPCA VLRPSGAWTLECVEKLIRKDMVDPVTGDKLTDRDIIVLQRGT
(SEQ ID N0:484); YLYEREAILEYILHQKKEIARQMKAYEKQRGTRREEQKELQ
RAASQDHVRGFLE (SEQ ID N0:485); and FTAKALSGTSPDDVQPGPSVGPP
SKDKDKVLPSFWIPSLTPEAKATKLEKPSRTVTCPMSGKPL (SEQ ID N0:486).
Also preferred are polynucleotide fragments that encode these polypeptide fragments.
This gene is expressed primarily in human testis and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive disorders and in particular testicular cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system.
Expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders of the male reproductive system and in particular of testicular cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 35 The translation product of this gene shares sequence homology with LpeSp of Saccharomyces cerevisiae which is thought to be important in the metabolism of phospholipids.
This gene is expressed primarily in liver and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, metabolic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful m providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the metabolic and nervous systems expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 268 as residues: Pro-14 to Leu-20, Lys-28 to Asn-38, Arg-109 to Arg-114, Lys-119 to Asn-124, Glu-152 to Leu-157, Pro-172 to Val-180.
The tissue distribution and homology to LpeSp of Saccharomyces cerevisiae indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of metabolic and nervous disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 36 This gene shares sequence homology with the nuclear ribonucleoprotein U (HNRNP
U), encoded by C. elegans (See Accession gi11703576.) Preferred polypeptide fragments comprise the amino acid sequence:
SATKGVPAGNSDTEGGQPGRKRRWGASTATTQKKPSISITTESLKSLIPDIKPL
AGQEAVVDLHADDSRISEDETERNGDDGTHDKGLKICRTVTQVVPAEGQENGQ
REEEEEEKEPEAEPPVPPQVSVEVALPPPAEHEVKKVTLGDTLTRRSISQQKSGV
SITIDDPVRTAQVPSPPRGKISNIVHISNLVRPFTLGQLKELLGRTGTLVEEAFWI
LVDRPSETKTEEQGIPRPLHPPPPPPVQPPQHPRAEQREQERAVREQWAERERE
MERRERTRSEREWDRDKVREGPRSRSRSRXRRRKERAKSKEKKSEKKEKAQE
EPPAKLLDDLFRKTKAAPCIYWLPLTDSQIVQKEAERAERAKEREKRRKEQEEE
EQKEREKEAERERNRQLEREKRREHSRERDRERERERERDRGDRDRDRERDRE
15 RGRERDRRDTKRHSRSRSRSTPVRDRGGR (SEQ ID N0:488). Also preferred are the polynucleotide fragments encoding this polypeptide fragments.
This gene is expressed primarily in epididymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 20 biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the male reproductive system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of 25 this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the 30 disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of male reproductive disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 37 This gene is expressed primarily in amygdala.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory diseases and reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the amygdala, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of inflammatory diseases and reproductive disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 38 This gene shares sequence homology with human opsonin protein P35 fragment. (See Accession No. 894181.) The opsonin protein activates the phagocytosis of pathogenic microbes by phagocytic cells. Preferred polypeptide fragments comprise the amino acid sequence: GCDSCPPHLPREAFAQDTQAEGECSSRAERADMCPDAP
PSQEVPEGPGAAP (SEQ ID N0:489). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed in immune-related tissues such as thymus, macrophage, T cells and to a lesser extent in many other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders and infectious disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and infectious disease, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 271 as residues: Lys-9 to Arg-14, Met-38 to Asp-51.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders, as well as the treatment and/or diagnosis of infectious disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 39 The translation product of this gene shares sequence homology with alpha-2 type I collagen which is thought to be important in tissue repair. (See, e.g., 211607.) Preferred polypeptide fragments comprise the amino acid sequence: PQLPSCGRPW
PGTASVFQSHTQGPREDPDPCRAQGSAGTHCPISLSPPRQ (SEQ ID N0:490).
Also preferred are the polynucleotide sequences encoding these polypeptide sequences.
This gene is expressed primarily in the brain and to a lesser extent in the kidney and thymus Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain, kidney, and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain, kidney, and immune disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to alpha-2 type I collagen indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of tissue repair, and brain, kidney, immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 40 The translation product of this gene shares sequence homology with mini-collagen which is thought to be important in tissue repair tumor metastasis.
(See Accession No. gnlIPIDId1006976.) Preferred polypeptide fragments comprise the amino acid sequence: PGFRGPSGSLGCSFFPRSLGRVLPPGCQRPGAHAD
SSPPPTP (SEQ ID N0:491 ). Also preferred are polynucleotides encoding this polypeptide fragment.
This gene is expressed in ovarian cancer and to a Lesser extent in dedritic cells and smooth muscle.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumor metastasis and tissue repair. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tumor metastasis and tissue repair, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 273 as residues: Asn-2 to His-11.
The tissue distribution and homology to mini-collegen gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of tumor metastasis and tissue repair.
FEATURES OF PROTEIN ENCODED BY GENE NO: 41 This gene shares sequence homology with the HIV TAT protein. (See Accession No. 328416.) Preferred polypeptide fragments comprise the amino acid sequence: EDLKKPDPASLRAASCGEGKKRKACKNCTCGLAEELEKEK
SREQMSSQPKSACGNCYLGDAFRCASCPYLGMPAFKPGEKVLLS (SEQ ID
N0:492); EDLKKPDPASLRAASCGEGKKRKACKNCTCGLAEELEKEK
SREQMSSQPKSACGNCYLGDAFRCASCPYLGMPAFKPGEKVLLSDSNLHD
(SEQ ID N0:493); CGNCYLGDAFRCASCPYLGMPAFKPGEKVLLSDS
(SEQ ID N0:494); SCGEGKKRKACKNCTCGLAEELEKE (SEQ ID N0:495);
SQPKSAC GNCYLGDAFRCASC (SEQ ID N0:496); and REAGQNSERQYVS
LSRD (SEQ ID N0:497). Also preferred are polynucleotide fragments encoding these poIypeptide fragments.
This gene is expressed primarily in the infant brain and to a lesser extent in the breast and testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain, testes and breast disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of-disorders of the above tissues or cells, particularly of the brain, testes and breast disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 274 as residues: Pro-7 to Val-15.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of brain, testes and breast, and other related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 42 This gene is expressed primarily in the infant brain, human cerebellum, and to a lesser extent in medulloblastoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain related disorders and medulloblastoma and other brain cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain related disorders and brain cancers, including medulloblastoma, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 275 as residues: Thr-41 to Glu-47.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of human brain related disorders, brain cancers, and medulloblastoma.
5 FEATURES OF PROTEIN ENCODED BY GENE NO: 43 The translation product of this gene shares sequence homology with a phosphotyrosine-independent ligand for the lck SH2 domain which is thought to be important in signal transduction related to phosphotyrosine-independent ligand for the lck SH2 domain. (See Accession No. gil l 184951.) Preferred polypeptide fragments 10 comprise the amino acid sequence: ESSGQARTLADPGPGWPRQQGMCFGSLT
GLSTTPHGFLTVSAEADPRLIESLSQMLSMGFSDEGGWLTRLLQTKNYDIGAAL
DTIQYSKH (SEQ ID N0:498). Also preferred are polynucleotide fragments encoding this polypeptide fragment. It is likely that this gene is a new member of a family of phosphotyrosine-independent ligands for the lck SH2 domains.
15 This gene is expressed primarily in the placenta and to a lesser extent in endothelial cells and neutrophil.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 20 not limited to, reproductive, cardiovascular, immune, and infectious diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular, reproductive, and immune system, and infectious diseases, expression 25 of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the 30 disorder.
The tissue distribution and homology to a phosphotyrosine-independent ligand for the lck SH2 domain indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of cardiovascular, reproductive, and immune system diseases, as well as infectious diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 44 This gene is expressed primarily in the fetal brain, cerebellum and to a lesser extent in the placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal cell related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal cell related disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 277 as residues: Thr-20 to Gly-28.
The tissue distribution and homology to proline-rich protein genes indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal cell related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 45 The translation product of this gene shares sequence homology with precerebellin of human, which is thought to be important in synaptic physiology. (See Accession No. gi1180251.) It has been observed that cerebellin-like immunoreactivity is associated with Purkinje cell postsynaptic structures. Thus, it is likely that this gene also have synaptic activity. Preferred polypeptide fragments comprise the amino acid sequence: QEGSEPVLLEGECLVVCEPGRAAAGGPGGAALGEAPPGRVAFXAV
RSHHHEPAGETGNGTSGAIYFDQVLVNEGGGFDRASGSFVAPVRGVYSFRFH
VVKVYNRQTVQVSLMLNTWPVISAFANDPDVTREAATSSVLLPLDPGDRVSLR
LRRGXSTGW (SEQ ID N0:499). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in cerebellum and infant brain. By Northern analysis, a single transcript of 2.4 kb was observed in brain tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions. which include.
but are not limited to, neuronal cell signal transduction and synaptic physiology.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal cell signal transduction and synaptic physiology expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to gene or gene family indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal cell related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 46 This gene is expressed in fetal liver and spleen, and to a lesser extent in bone marrow, umbilical vein, and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders of the immune system, particularly hematopoiesis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoiesis and immune disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 279 as residues: Asp-30 to Glu-57.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of hematopieotic and immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 47 The translation product of this gene shares sequence homology with a 12 kD
nucleic acid binding protein of Feline calcivirus which is thought to be important in viral replication. (See Accession No. 59264) This gene is expressed primarily in human cardiomyopathy and to a lesser extent in T helper cells, fetal brain and synovial sarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cardiomyopathy as well as viral infection. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 280 as residues: Trp-20 to Cys-26.
The tissue distribution in cardiomyopathy and homology to viral 12 kD nucleic acid binding protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of cardiomyopathy, including those caused by ischemic, hypertensive, congenital, valvular, or pericardial abnormalities.
The gene expression pattern may be the consequence or the cause for these conditions.
FEATURES OF PROTEIN ENCODED BY GENE NO: 48 The translation product of this gene shares sequence homology with tumor necrosis factor related gene product which is thought to be important in tumor necrosis, bacterial and viral infection, immune diseases and immunoreactions.
This gene is expressed primarily in colon and to a lesser extent in ovarian and breast cancers.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors of colon, ovary or breast origins. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the colon, ovary and breast, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to Tumor necrosis factors indicates that polynucleotides and polypeptides corresponding to this gene are useful for intervention of cancers of colon, ovary and breast origins, because TNF family members are known to be involved in the tumor development.
FEATURES OF PROTEIN ENCODED BY GENE NO: 49 The translation product of this gene shares sequence homology with mucins, such as epithelial mucin, which is thought to be important in extracellular matrix functions such as protection, lubrication and cell adhesion (See for example Accession No. R68002). Preferred polypeptide fragments comprise the following amino acid sequence: PRSRPALRPGRQRPPSHSATSGVLRPRKKPDP (SEQ ID NO:500).
Also preferred are polynucleotide fragments encoding these polypeptide fragments.
Moreover, this gene maps to chromosome 22q 11.2-qter, and therefore, can be used as a marker in linkage analysis for chromosome 22.
This gene is expressed primarily in corpus colosum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors, especially of corpus colosum, as well as metastatic lesions.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunologicai probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the corpus colosum and other solid tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to mucins indicates that polynucleotides and polypeptides corresponding to this gene are useful for serum tumor markers or immunotherapy targets because tumor cells have greatly elevated level of mucin expression and shed the molecules into the epithelial tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: SO
This gene is expressed primarily in CD34 depleted huffy coat cord blood and primary dendritic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as 10 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic disorders and immunological disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For 15 a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard 20 gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in CD34 depleted huffy coat cord blood and primary dendritic cells indicates that polynucleotides and polypeptides con esponding to this gene are useful for diagnosis and treatment of hematopoietic and immune disorders.
25 Secreted or cell surface proteins in the above tissue distribution often are involved in cell activation (e.g. cytokines) or molecules involved in cell surface activation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 51 The translation product of this gene shares sequence homology with Interferon 30 induced 1-8 gene encoded polypeptide which is thought to be important in binding to retroviral rev responsive element. Preferred polypeptide fragment comprise the following amino acid sequences: MTLITPSXKLTFXKGNKSWSSRACSSTLVDP
(SEQ ID NO:SOI). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
35 This gene is expressed primarily in CD34 positive cells and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, retroviral infection, such as AIDS, and other immune disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 284 as residues: Gln-51 to Trp-62.
The tissue distribution and homology to interferon induced gene 1-8 indicates that polynucleotides and polypeptides corresponding to this gene are useful for intervention of retroviral infection including HIV. The factor may be involved in viral stability or viral entry into the cells. Alternatively, the virus/factor complex may elicit the cellular immune reaction.
FEATURES OF PROTEIN ENCODED BY GENE NO: 52 This gene shares sequence homology to immunoglobulin lambda chain (See Accession No. 2865484). Therefore it is likely that this gene has activity similar to an immunoglobulin lambda chain. Preferred polypeptide fragments comprise the following amino acid sequence: GHPSPALSIAPSDGSQLPCDEVPYGEAHVTRYCKKPLTNS
HLETEAQSSSL (SEQ ID N0:502). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in Hodgkin's lymphoma.
Therefore, polynucleotides and poIypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, Hodgkin's lymphoma and other immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 285 as residues: Pro-27 to Thr-32.
The tissue distribution in Hodgkin's lymphoma and the sequence homology indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of Hodgkin's lymphoma, since the elevated expression and secretion by the tumor mass may be indicative of tumors of this type. Additionally the gene product may be used as a target in the immunotherapy of the cancer.Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunoIogical disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 53 This gene has extensive homology to cDNA for Homo Sapiens mRNA for the ISLR gene(See Accession No. AB003184). This protein is considered to be a new member of the Ig superfamily and contains a leucine-rich repeat (LRR) with conserved flanking sequences and a C2-type immunoglobulin (Ig}-like domain. These domains are important for protein-protein interaction or cell adhesion, and therefore it is possible that the novel protein ISLR may also interact with other proteins or cells. The ISLR gene was mapped on human chromosome 15q23-q24 by fluorescence in situ hybridization (See Medline Article No. 97468140). Homology to the ISLR gene has been confirmed by another independent group as well (See Accession No. Hs.102171 ) This gene is expressed in a number of tissues including human retina, heart, skeletal muscle, prostate, ovary, small intestine, thyroid, adrenal cortex, testis, stomach, spinal cord, fetal lung and fetal kidney tissues, colon, tonsil and stomach cancer, and to a lesser extent in endometrial stromal cells treated with estradiol, breast tissue, synovium, lymphoma, and number of other tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors of colon, ovary and breast origins. However, due to the wide range of expression in various tissues, protein may play a vital role in the development of cancer in other tissues as well, not just those mentioned above. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the colon, ovary and breast, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues {e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Additionally, this gene maps to chromosome 15q23-q24, and therefore, can be used as a marker in linkage analysis for chromosome 15.
The tissue distribution in tumors of colon, ovary, and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 54 Gene has homology to multidrug resistance gene 1 (See Accession No.
P06795). Preferred polynucleotide fragments comprise the following sequence:
GCTTCGTGTCCAACCCTCTTGCCCTTCGCCTGTGTGCCTGGAGCCAGTCCCA
CCACGCTCGCGTTTCCTCCTGTAGTGCTCACAGGTCCCAGCACCGATGGCA
TTCCCTTTGCCCTGAGTCTGCAGCGGGTCCCTTTTGTGCTTCCTTCCCCTCA
GGTAGCCTCTCTCCCCCTGGGCCACTCCCGGGGGTGAGGGGGTTACCCCTT
CCCAGTGTTTT)-TATTCCTGTGGGGCTCACCCCAAAGTATTAAAAGTAGCTTT
GTAA (SEQ ID N0:503). Also preferred are polypeptide fragments encoded by these polynucleotide fragments.
This gene is expressed primarily in lung, esophagus, leukemia (Jurkat cells) and breast cancers and to a lesser extent in macrophages treated with GM-CSF fetal tissues and wide range of tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer of wide range of origins. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the solid tumors, lung and leukemia, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Furthermore, due to the high expression level in lung tissue and the proposed function of the multidrug resistance protein 1 gene as the efflux pump responsible for low-drug accumulation in multidrug-resistant cells, protein as well mutants thereof, may also be beneficial as a target for gene therapy, particularly for the chronic patient.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 287 as residues: Met-1 to Lys-16.
The tissue distribution in wide range of cancers and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection of cells in active proliferation, such as cancers. The gene products may be used for cancer markers or immunotherapy target.
FEATURES OF PROTEIN ENCODED BY GENE NO: 55 This gene maps to the X chromosome.
This gene is expressed primarily in the brain and to a lesser extent in the developing embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative disease states and developmental disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders, including sex-linked disorders, of the above tissues or cells, particularly of the neurological, developmental systems, and cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Moreover, this gene maps to the X chromosome, and therefore, may be used as a marker in linkage analysis for this chromosome.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Klinefelter's, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 56 5 The translation product of this gene shares sequence homology with paxillin which is thought to be important in mediating signal transduction from growth factor receptors to the cytoskeleton. Preferred polynucleotide fragments comprise the following sequence: TGGCTCACTGTCTTACAATCACTGCTGTGGAATCATGA
TACCACTTTTAGCTCTTTGCATCTTCCTTCAGTGTATTTTTGTTTTTCAAGAGG
GGCTTGTGGTTTCAA (SEQ ID N0:506). Also preferred are polypeptide fragments encoded by these polynucleotide fragments. More preferably, polypeptide fragments comprise the amino acid sequence: LDELMAHLTEMQAKVAVRAD
AGKKHLPDKQDHKASLDSMLGGLEQELQDLGIATVPKGHCASCQKPIAGKVI
ILDKVLTAMNQTWHPEHFFCSHCGEVFGAEGFHEKDKKPYCRKDFLAMFSPK
CGGCNRPVLENYLSAMDTVWHPECFVCGDCFTSFSTGSFFELDGRPFCELHYH
HRRGTLCHGCGQPITGRCISAMGYKFHPEHFVCAFCLTQLSKGIFREQNDKTY
CQPCFNKLF {SEQ ID N0:507); KASLDSMLGGLEQELQDLGIATVPKGHC
20 ASCQKPIAGKVIHAL (SEQ ID N0:508); CPNDYHQLFSPRCAYCAAPILDKVL
TAMNQTWHPEHFFCSHCGEVFGAEG (SEQ ID N0:509); DKKPYCRKDFLAM
FSPKCGGCNRPVLENYLSAMDTVWHPECFVCGDCFTSFSTGSFFELDGRPFCE
L (SEQ ID NO:510); CGQPITGRCISAMGYKFHPEHFVCAFCLTQLSKGIFRE
QNDKTYCQ (SEQ ID NO:511 ). Polynucleotide fragments encoding these preferred 25 polypeptide fragments are also contemplated.
This gene is expressed primarily in brain, and to a lesser extent in the developing embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a 30 biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disease states and developmental abnormalities.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the immune and 35 nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Moreover, since this gene shares homology with a gene that maps to chromosome 11, (See Accession No.T87404), gene as well as its translated product may be used for linkage analysis on chromosome 11.
The tissue distribution and homology to paxillin indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and or detection of disease states associated with abnormal signal transduction in brain and/or the developing embryo. This would include treatment or detection of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder and also in the treatment and or detection of embryonic development defects.
FEATURES OF PROTEIN ENCODED BY GENE NO: 57 This gene is expressed primarily in fetal spleen, brain, and to a lesser extent in six week old embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders, neurological disorders, and developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and developmental systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 290 as residues: Arg-28 to Gly-34.
The expression of this gene in fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/detection of immune disorders such as arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia. In addition the expression of this gene in the early embryo, indicates a key role in embryo development and hence the gene or gene product could be used in the treatment and or detection of embryonic development defects. This would include treatment or detection of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder and also in the treatment and or detection of embryonic development defects.
FEATURES OF PROTEIN ENCODED BY GENE NO: 58 The translation product of this gene shares sequence homology with the gene disrupted in the neurodegenerative disease dentatorubal-palIidoluysian atrophy. Moreover a long open reading fame exists in an alternative frame. Preferred polypeptide fragments comprise the following:
MGSSQS VEIPGGGTEGYHVLRVQENSPGHRAGLEPFFDFIVSINGSRLNKDND
TLKDLLKXNVEKPV KMLIYSSKTLELRETS VTPSNLWGGQGLLG V SIRFCSFD
GANENVWHVLEVESNSPAALAGLRPHSDYIIGADTVMNESEDLFSLIETHEAKP
LKLYVYNTDTDNCREVIITPNSAWGGEGSLGCGIGYGYLHRIPTRPFEEGKKIS
LPGQMAGTPITPLKDGFTEVQLSSVNPPSLSPPGTTGIEQSLTGLSISSTPPAVSS
VLSTGVPTVPLLPPQVNQSLTSVPPMNPATTLPGLMPLPAGLPNLPNLNLNLPA
PHIMPGVGLPELVNPGLPPLPSMPPRNLPGIAPLPLPSEFLPSFPLVPESSSAASS
GELLSSLPPTSNAPSDPATTTAKADAASSLTVDVTPPTAKAPTTVEDRVGDSTPV
SEKPVSAAVDANASESP (SEQ ID N0:512); SVEIPGGGTEGYHVLRVQENSPGH
RAGLEPFFDFIVSINGSRLNKDNDTLKDLLKXNVEKPVKMLIYSSKTLELRETS
VTPSNLWGGQGLLGVSIRFCSFDGANENVWH (SEQ ID N0:513); ESNSPAA
LAGLRPHSDYIIGADTVMNESEDLFSLIETHEAKPLKLYVYNTDTDNCREVIITP
NSAWGGEGSLGCGIGYGYLHRIPTRPFEEGKKISLPGQMAGTPITPLKDGFTEV
QLSSVNPPSLSPPGTTGIEQSLTG LSISS (SEQ ID N0:514); RIPTRPFEEGKKI
SLPGQMAGTPITPLKDGFTEVQLSSVNPPSLSPPGTTGIEQSLTGLSISSTPPAVS
S VLSTGVPTVPLLPPQVNQSLTS VPPMNPATTLPGLMPLPAGLPNLPNLNLNLP
APH1MPGVGLPELVNPGLPPLPSMPPRN (SEQ ID N0:516); PGLPPLPSMPPRN
LPGIAPLPLPSEFLPSFPLVPESSSAASSGELLSSLPPTSNAPSDPATTTAKADAA
SSLTVDVTPPTAKAPTTVEDRVGDSTPVSEKPVSAAVDAN (SEQ ID N0:517).
This gene is expressed primarily in prostate cancer, and to a lesser extent in the pineal glands and in fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are . 35 not limited to, neurological conditions and pulmonary disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous, pulmonary, and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 291 as residues: Asn-9 to Leu-14.
The abundance of this gene in the pineal gland and its homology to a gene disrupted in the neurodegenerative disease state Dentatorubral-pallidoluysian atrophy indicates that this gene may be useful in the treatment and/or detection of other neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. The abundance of this gene in fetal lung would suggest that nusregulation of the expression of this protein product in the adult could lead to lymphoma or sarcoma formation, particularly in the lung;
that it may also be involved in predisposition to certain pulmonary defects such as pulmonary edema and embolism, bronchitis and cystic fibrosis; and thus the gen or the gene protein encoded by the gene could be used in the detection and/or treatment of these pulmonary disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 59 This gene is expressed primarily in the developing embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developmental system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The expression of this gene primarily in the embryo, indicates the gene plays a key role in embryo development and that the gene or the protein encoded by the gene could be used in the treatment and or detection of developmental defects in the embryo or in infants.
FEATURES OF PROTEIN ENCODED BY GENE NO: 60 This gene displays homology to nestin, an intermediate filament protein, the expression of which correlates with the proliferation of Central Nervous System progenitor cells and that is useful in the identification of brain tumors.
This gene maps to chromosome l, and therefore, may be used as a marker in linkage analysis for chromosome 1 (See Accession No. AA527348).
This gene is expressed primarily in kidney and to a lesser extent in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, renal disorders and neurodegenerative conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the excretory and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 293 as residues: Thr-128 to Asn-135.
The tissue distribution and homology to nestin indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and/or treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, its abundance in kidney indicates that it is useful in the treatment and detection of acute renal failure and other disease states associated with the kidney.
FEATURES OF PROTEIN ENCODED BY GENE NO: 61 Gene shares homology with the latrophilin-related protein 1 precursor as well as the calcium-independent alpha-latrotoxin receptor. Preferred polypeptide fragments comprise the following amino acid sequence:
IYKVFRHTAGLKPEVSCFENIRSCARXXXXXXXXXXXXWIFGVLHVVHAS VV
TAYLFTVSNAFQGMFIFLFLCVLSRKIQEEYYRLFKNVPCC (SEQ ID N0:518);
WIFGVLHVVHAS VVTAYLFTVSNAFQGMFIFLFLCVLSRKIQEEYYRLFKNVPC
5 C (SEQ ID N0:519). Also preferred are polynucleotide fragments encoding these polypeptide fragments. (See Accession No. 2213659) The translation product of this gene shares sequence homology with CD 97, a seven transmembrane bound receptor.
This gene is expressed primarily in infant brain and in endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as i0 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders and hematopoeitic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For 15 a number of disorders of the above tissues or cells, particularly of the neurological and hematopoeitic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the 20 standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 294 as residues: Lys-13 to Leu-21.
The tissue distribution of this gene suggest that it may be useful in the detection and/or treatment of neurodegenerative disease states and behavioral disorders such as 25 Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder, while its expression in hematopoietic cell types indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, asthma and immunodeficiency diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 62 This gene is expressed primarily in fetal liver and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematological and immunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunoiogical probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and hematopoetic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 295 as residues: Ser-91 to Lys-98.
The tissue distribution of this gene fetal liver and spleen indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, leukemia, asthma and immunodeficiency diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 63 Gene shares homology with human serum amyloid protein. Preferred polypeptide fragments comprise the following amino acid sequence:
ALTRIPPGDWVINVTAVSFAGKTTARFFHSSPPSLGDQARTDPGHQRRD (SEQ
ID N0:520) (See Accession No. W 13671 ). Also preferred are polynucleotide fragments encoding these polypeptide fragments This gene maps to chromosome 9, and therefore, may be used as a marker in linkage analysis for chromosome 9 (See Accession No. AA004342).
This gene is expressed primarily in fetal liver and spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in fetal liver-spleen indicates that the gene could be important for the treatment or detection of immune or hematopoietic disorders including arthritis, leukemia, asthma, and immunodeficiency diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 64 This gene maps to chromosome 3, and therefore, may be used as a marker in linkage analysis for chromosome 3 (See Accession No. AA219669).
This gene is expressed specifically in the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative disease states. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neurological systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntintons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 65 Gene shares homology with a yeast protein. Preferred polypeptide fragments comprise the following amino acid sequence: LQEVNITLPENSVWYERYKFDIP
VFHL (SEQ ID N0:521 ). Also preferred are polynucleotide fragments encoding these polypeptide fragments. (See Accession No. 1332638) This gene is expressed primarily in fetal tissue (fetus and fetal liver).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver disorders and cancers (e.g. hepatoblastoma). Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunologicai probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic system, expression of this gene at significantly higher or lower levels may be routinely detected S in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 298 as residues: Asn-59 to Glu-64.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). In addition the expression in fetus would suggest a useful role for the protein product in developmental abnormalities, fetal deficiencies, pre-natal disorders and various would-healing models and/or tissue trauma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 66 Gene has homology with a B-cell surface antigen which may indicate gene plays a role in the immune response, including, but not limited to disorders and infections of the immune system. Preferred polynucleotide fragments comprise the following sequence: TAGCATGTAGCCAGTCGAATAACNTATAAGGACAAAGTGGAGTC
CACGCGTGCGGCCGTCTAGACTAGTGGATCCCCCGGCTGCAGGATTCGGC
ACGAG (SEQ ID N0:523). Also preferred are polypeptide fragments encoded by these polynucleotide fragments (See Accession No.T94535). Additionally, this gene shares homology with an interferon-gamma receptor. Preferred polypeptide fragments also comprise the following amino acid sequence: MQGSGSQFRACLLCLCFSCPC
SPGGPRWNSRQGGRRFPKTCRAISQNLVFKYKTFCPVRYMQPHRSSLCLHFTS
YVFILSTWGSLRTYSTDLKKKKKNSRGGPVPIRPKS (SEQ ID N0:522);
MQGSGSQFRACLLCLCFSCPCSPGGPRWNSRQGGRRFPKTCRAISQNLVFK
(SEQ ID N0:524); PVRYMQPHRSSLCLHFTSYVFILSTWGSLRTYSTDLKKKKK
NSRGGPVPIRPKS (SEQ ID N0:525); and GEEQRDCSLGWRGVGMRATHCQAA
RMFVLFSLPKYAGL (SEQ ID N0:526). Also preferred are polynucleotide fragments encoding these polypeptide fragments This gene is expressed primarily in T-cells and gall bladder.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological disorders and conditions (immunodeficiencies, cancer, leukemia, hematopoeisis). Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and digestive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 299 as residues:
Thr-41 to Gly-52.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of immune disorders including: leukemias, lymphomas, auto-immune disorders, immuno-supressive (transplantation) and immunodeficiencies (e.g. AIDS), inflammation and hematopoeitic disorders. The expression of this gene in gall bladder would suggest a possible role for this gene product in digestive disorders, particularly of the pancreas.
FEATURES OF PROTEIN ENCODED BY GENE NO: 67 This gene maps to chromosome 11, and therefore, may be used as a marker in linkage analysis for chromosome 11 (See Accession No. AA011622).
This gene is expressed primarily in a variety of fetal and developmental tissues (e.g. fetal spleen, infant brain).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental, immune or neurological abnormalities.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing immune and central nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 300 as residues: Ser-38 to Ser-43.
5 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for developmental abnormalities or fetal deficiencies. The detection in infant brain would suggest a role in neurological disorders (both developmental and neurodegenerative conditions of the brain and nervous system, behavioral disorders, depression, schizophrenia, Alzheimer's disease, Parkinson's 10 disease, Huntington's disease, mania, dementia). In addition, the detection in spleen would similarly suggest a role in detection and treatment of immunologically mediated disorders (e.g. immunodeficiency, inflammation, cancer, wound healing, tissue repair, hematopoeisis).
15 FEATURES OF PROTEIN ENCODED BY GENE NO: 68 This gene is expressed primarily in spleen, T-cells, and fetal heart.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type.(s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 20 not limited to, immunological deficiencies, including AIDSand cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and cardiovascular systems, expression of this gene at significantly higher 25 or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
30 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immune disorders including: leukemias, lymphomas, autoimmune disorders, immunodeficiencies (e.g. AIDS), immuno-suppressive conditions (transplantation) and hematopoeitic disorders. The expression in fetal heart indicates that polynucleotides and 35 polypeptides corresponding to this gene are useful for the treatment and diagnosis of cadiovascular disorders (e.g. heart disease, restenosis, atherosclerosis, stoke, angina, thrombosis).
FEATURES OF PROTEIN ENCODED BY GENE NO: G9 Gene shares homology with a human collagen protein. Preferred polypeptide fragments comprise the following amino acid sequence:
MPRKTSKCRQLLCSGASRNADTAARQSTCSSHRPPGKIPSLGPRRXPGCXSVP
SSRGEQSTGSPAAPRCGRRDAHRGLPGGAAMTPGDTWASFNPRAGHSKSQGE
GQESSGASRQDRHPVSHWVERQREAWGAPRSSSAGGVKVAATTEREPEFKIK
TGKA (SEQ ID N0:527); CSGASRNADTAARQSTCSSHRPPGKIPSLGPRRXPG
CXS VPSSRGEQSTGSPAAPRCGRRDAHRGLPGGAAMTPGDTWASFNPRAGHS
(SEQ ID N0:528); QGEGQESSGASRQDRHPVSHWVERQREAWGAPRSSSAGG
VKVAATTEREPEFKIKTGKA (SEQ ID N0:529) (See Accession No. 124886). Also preferred are polynucleotide fragments encoding these polypeptide fragments This gene is expressed primarily in fetal heart.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 302 as residues:
Pro-32 to Ser-39.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of cadiovascular disorders (e.g. heart disease, restenosis, atherosclerosis, stroke, angina, thrombosis).
FEATURES OF PROTEIN ENCODED BY GENE NO: 70 The translation product of this gene shares sequence homology with a chicken single-strand DNA-binding protein. Preferred polypeptide fragments comprise the following amino acid sequence:
MSPRYPGGPRPPLRIPNQALGGVPGSQPLLPSGMDPTRQQGHPNMGGPMQRM
TPPRGMVPLGPQNYGGAMRPPLNALGGPGMPGMNMGPGGGRPWPNPTNAN
SIPYSSASPGNYVGPPGGGGPPGTPIMPSPADSTNSGDNMYTLMNAVPPGPNR
PNFPMGPGSDGPMGGLGGMESHHMNGSLGSGDMDSISKNSPNNMSLSNQP
GTPRDDGEMGGNFLNPFQSESYSPSMTMSV (SEQ ID N0:530); MSPRYPGG
PRPPLRIPNQALGGVPGSQPLLPSGMDPTRQQGHPNMGGPMQRMTPPRGMVP
LGPQNYGGAMRPPLNALGGPGMPGMNMGPGGGRPWPNPTNANSIPYSSASP
GNY (SEQ ID. N0:531); LNALGGPGMPGMNMGPGGGRPWPNPTNANSIPYSS
ASPGNYVGPPGGGGPPGTPIMPSPADSTNSGDNMYTLMNAVPPGPN (SEQ ID
N0:532); GPMGGLGGMESHHMNGSLGSGDMDSISKNSPNNMSLSNQPGTPR
DDGEMGGNFLNPFQSESYSPSMTMSV (SEQ ID N0:533); TCEHSSEAKAFHDY
(SEQ ID N0:534). Also preferred are polynucleotide fragments encoding these polypeptide fragments. (See Accession No. 1562534) This gene is expressed primarily in placenta and to a lesser extent in the fetal heart and a variety of other tissues and cell types.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities, fetal deficiencies, and particularly of the cardiovascular system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of developmental abnormalities or fetal deficiencies, ovarian and other endometrial cancers, reproductive dysfunction, cardiovascular disorders, and pre-natal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 71 This gene is expressed primarily in fetal liver and to a lesser extent in the breast and testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver disorders (including hepatoblastomas) and reproductive disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hepatic and reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression Level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and treatment of liver disorders and cancers (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). The expression in testes and breast indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of endocrine and reproductive disorders (e.g. sperm maturation, milk production, testicular and breast cancers).
FEATURES OF PROTEIN ENCODED BY GENE NO: 72 This gene maps to chromosome 1, and therefore, may be used as a marker in linkage analysis for chromosome 1 (See Accession No. W93595).
This gene is expressed primarily in smooth muscle and to a lesser extent in brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cardiovascular and neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cardiovascular and central nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of restenosis, atheroscIerosis, stroke, angina, thrombosis, wound healing and other conditions of heart disease. In addition, the expression in brain would suggest that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of developmental, degenerative and behavioral conditions of the brain and nervous system (e.g. schizophrenia, depression, Alzheimer's disease, Parkinson's disease, Huntington's disease, mania, dementia, paranoia, addictive behavior and sleep disorders).
FEATURES OF PROTEIN ENCODED BY GENE NO: 73 Gene shares homology with human stromalin-2. Preferred polypeptide fragments comprise the following amino acid sequence:
QAFVLLSDLLLIFSPQMIVGGRDFLRPLVFFPEATLQSELASFLMDHVFIQPGDL
GSGA (SEQ ID N0:535); ACSYLLCNPEFTFFSRADFARSQLVDLLTDRFQQE
LEELLQVG (SEQ ID NO:536),QKQLSSLRDRMVAFCELCQSCLSDVDTEIQEQV
ST (SEQ ID N0:537); QVILPALTLVYFSILWTLTHISKSDAS (SEQ ID N0:538);
STHDLTRWELYEPCCQLLQKAVDTGXVPHQV (SEQ ID N0:539). Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No.R65208 ) This gene maps to chromosome 7, and therefore, may be used as a marker in linkage analysis for chromosome 7 (See Accession No. D52585).
This gene is expressed primarily in the brain (infant brain, adult brain, pituitary, cerebellum, hippocampus, schizophrenic hypothalmus, amygdala).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental and neurodegenerative diseases of the brain and nervous system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those WO 98!54963 PCT/US98/11422 comprising a sequence shown in SEQ ID NO: 30b as residues: Thr-25 to Lys-3b, Lys-55 to Ser-63.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and treatment of developmental, 5 degenerative and behavioral conditions of the brain and nervous system (e.g.
schizophrenia, depression, Alzheimer's disease, Parkinson's disease, Huntington's disease, mania, dementia, paranoia, addictive behavior and sleep disorders).
FEATURES OF PROTEIN ENCODED BY GENE NO: 74 10 This gene is expressed primarily in the hypothalamus of a human suffering from schizophrenia.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 15 not limited to, disorders of the CNS particularly schizophrenia. Sinularly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS, such as schizophrenia expression of this gene at significantly higher or lower levels may be routinely detected 20 in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
25 NO: 307 as residues: Gly-38 to Ala-44.
The tissue distribution indicates that the protein products of this gene are useful for the study, diagnosis and treatment of schizophrenia and other disorders involving the CNS.
30 FEATURES OF PROTEIN ENCODED BY GENE NO: 75 Preferred polypeptides of the invention comprise the following amino acid sequence encoded by this gene:
LAVSTSFICCADISTALPLGSSRPAPAPRHREHEHGHQARPPRLLXTSLMPLSTP
AAAQLLWTQLTPMGGRPGGRHSPPTLHTGPRALPPGPPHPSLHVAALSLLR
35 (SEQ ID N0:540). Polynucleotides encoding such polypeptides are also provided.
This gene is expressed primarily in endometrial tumor and to a lesser extent in amniotic cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, reproductive and immune disorders particularly cancers of those systems. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 308 as residues: Ser-3 to Arg-9.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of immune and reproductive disorders particularly cancers of those systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 76 This gene is expressed primarily in kidney cortex and to a lesser extent in early stage human brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, renal disorders such as renal cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the kidney expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 309 as residues:
Gly-38 to Gly-45, Gly-47 to Gly-52, Pro-92 to Lys-110.
The tissue distribution indicates that the protein products of this gene are useful for study, treatment and diagnosis of renal diseases such as cancer of the kidney.
FEATURES OF PROTEIN ENCODED BY GENE NO: 77 This gene is expressed primarily in kidney medulla.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, metabolic and renal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the metabolic and renal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for study, treatment and diagnosis of metabolic and renal diseases and disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 78 This gene is expressed in chronic synovitis and microvascular endothelium.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, arthritis and atherosclerosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular and skeletal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for study, diagnosis and treatment of arthritic and other inflammatory diseases as well as cardiovascular diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 79 This gene is expressed in resting T-cells and activated monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for the study and treatment of immune diseases such as inflammatory conditions.
FEATURES OF PROTEIN ENCODED BY GENE NO: 80 This gene is expressed in a variety of immune system tissues, e.g., neutrophils, T-cells, and TNF induced epithelial and endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infectious and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and vascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 313 as residues: Met-1 to Trp-6.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of infectious diseases, immune and vascular disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 81 This gene is expressed in activated neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and other immune conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 82 This gene is expressed in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory and other immune conditions. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 315 as residues:
Ala-83 to Thr-91.
The tissue distribution indicates that the protein products of this gene are useful for study and treatment of immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 83 This gene is expressed in human neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as 5 reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders 10 of the above tissues or cells, particularly of the immune and inflammatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., 15 the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of disorders of the inflammatory and immune systems.
20 FEATURES OF PROTEIN ENCODED BY GENE NO: 84 This gene is expressed in human neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 25 not limited to, disorders of the inflammatory and immune systems.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the inflammatory and immune systems, expression of this gene at significantly higher or lower levels may be 30 routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
35 The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of disorders of the immune and inflammatory systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 85 This gene is expressed in activated neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and immune system diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and inflammatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of diseases of the inflammatory and immune systems.
FEATURES OF PROTEIN ENCODED BY GENE NO: 86 This gene is expressed in activated neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and immune system disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the inflammatory and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 319 as residues: Met-1 to Gly-6, Gly-32 to Pro-43, Leu-55 to Gln-60.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis and treatment of disorders of the immune and inflammatory system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 87 In specific embodiments, polypeptides of the invention comprise the sequence:
EQVLALLWPRFELILEMNVQSVRSTDPQRLGGLDTRPHYITRRYAEFSSALVSIN
QTIPNERTMQLLGQLQVEVENFVLRVAAEFSSRKEQLVFLINNYDMMLGVLME
RAADDSKEVESFQQLLNARTQEFIEELLSPPFGGLVAFVKEAEALIERGQAERLR
GEEARVTQLIRGFGSSWKSSVESLSQDVMRSFTNFRNGTSIIQG (SEQ ID
N0:54I ),ALLKYRFFYQFLLGNERATAKEIRDEYVETLSKIYLSYYRSYLGRLMK
VQYEEVAEKDDLMGVEDTAKKGFXSKPSRSRNTIFTLGTRGSVISPTELEAPILV
PHTAQR (SEQ ID NO: 542); EQRYPFEALFRSQHYXLLDNSCREYLFICEFFVVS
GPXAHDLFHAVMGRTLSMTLKHLDSYLADCYDAIAVFLCIHIVLRFRNIAAKRD
VPALDRYW (SEQ ID NO:543),GGLDTRPHYITRRYAEFSSALVSINQ (SEQ ID
N0:544); SRKEQLVFLINNYDMMLGVL (SEQ ID NO: 545) and/or ALLKYRFFY
QFLLGNERATAKEIRDEYVETLSKIYLSYYRSYLGRLMKVQYEEVAEKDDLMG
VEDTAKKGFXSKPSLRSRNTIFTLGTRGSVISPTELEAPILVPHTAQRXEQRYPF
EALFRSQHYXLLDNSCREYLFICEF'FVVSGPXAHDLFHAVMGRTLSMTLKHLD
S YLADCYDAIA VFLCIHIVLRFRNIAAKRDV PALDRYWEQ VLALLWPRFELILEM
NVQSVRSTDPQRLGGLDTRPHYITRRYAEFSSALVSINQTIPNERTMQLLGQLQV
EVENFVLRVAAEFSSRKEQLVFLINNYDMMLGVLMERAADDSKEVESFQQLLN
ARTQEFIEELLSPPFGGLVAFVKEAEALIERGQAERLRGEEARVTQLIRGFGSSW
KSSVESLSQDVMRSFTNFRNGTS (SEQ ID N0:546). Polynucleotides encoding these polypeptides are also encompassed by the invention. The translation product of this gene shares sequence homology with suppressor of actin mutation which is thought to be important in mutation suppression.
This gene is expressed primarily in fetal liver and to a lesser extent in a variety of other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver and mutations. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the liver or cancer, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder. relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 320 as residues:
Val-53 to Arg-60, Thr-88 to Thr-94, Ala-142 to Ser-150, Gly-188 to Glu-196, Gly-208 to Ser-214, Thr-227 to Gly-232, Lys-279 to Phe-285.
The tissue distribution and homology to suppressor of actin mutation suggest that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and of liver disorder or cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 88 This gene maps to chromosome 9, and therefore can be used in linkage analysis as a marker for chromosome 9. In specific embodiments, polypeptides of the invention comprise the sequence:
YEGKEFDYVFSIDVNEGGPSYKLPYNTSDDPWLTAYNFLQKNDLNPMFLDQVA
KFIIDNTKGQMLGLGNPSFSDPFTGGGRYVPGSSGSSNTLPTADPFTGAGRYV
PGSASMGTTMAGVDPFTGNSAYRSAASKTMNIYFPKKEAVTFDQANPTQILGK
LKELNGTAPEEKKLTEDDLILLEKILSLICNSSSEKPTVQQLQILWKAINCPEDIV
FPALDILRLSIKHPSVNENFCNEKEGAQFSSHLINLLNPKGKPANQLLALRTFC
NCFVGQAGQKLMMSQRESLMSHAIELKSGSNKNI (SEQ ID NO: 547);
HIALATLALNYSVCFHKD (SEQ ID NO: 548); HNIEGKAQCLSLISTILEVVQ
DLEATFRLLVALGTLISDDSNAVQLAKS (SEQ ID N0:549); LGVDSQIKKYSS
VSEPAKVSECCRFILNLL (SEQ ID NO:550); and/or YEGKEFDYVFSIDVNEGGPS
YKLPYNTSDDPWLTAYNFLQKNDLNPMFLDQVAKFIIDNTKGQMLGLGNPSFS
DPFTGGGRYVPGSSGSSNTLPTADPFTGAGRYVPGSASMGTTMAGVDPFTGN
SAYRS AAS KTMNIYFPKKEA VTFDQANPTQILGKLKELNGTAPEEKKLTEDDLI
LLEKILSLICNSSSEKPTVQQLQILWKAINCPEDIVFPALDILRLSIKHPSVNENFC
NEKEGAQFSSHLINLLNPKGKPANQLLALRTFCNCFVGQAGQKLMMSQRESL
MSHAIELKSGSNKNIHIALATLALNYS VCFHKDHNIEGKAQCLSLISTILEV VQD
LEATFRLLVALGTLISDDSNAVQLAKSLGVDSQIKKYSS VSEPAKVSECCRFILN
LL (SEQ ID NO:551 ). Polynucleotides encoding these polypeptides are also encompassed by the invention. These polypeptides share significant homology with phospholipase A2 activating protein which is thought to be important in signal transduction (see, e.g., Wang et al., Gene 161 (2):237-241 ( 1995)).
This gene is expressed primarily in endothelial cells, to a less extent in placenta, endometrial stromal cells, osteosarcoma, testis tumor, muscle, and infant brain that are likely to be rich in blood vessles.
Therefore, polynucleotides and poIypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders in vascular system, aberrent angiogenesis, tumor angiogenesis.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system or tumors, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene in endothelial cells and several potential highly vascularized tissues and its homology to phospholipase A2 activating protein suggest that this gene may be involved in transducing signals for endothelial cells in angiogenesis or vasculogenesis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 89 In specific embodiments, polypeptides of the invention comprise the sequence:
YPNQDGDILRDQVLHEHIQRLSKWTANHRALQIPEVYLREAPWPSAQSEIRTIS
AYKTPRDKVQCILRMCSTIMNLLSLANEDSVPGADDFVPVLVFVLIKANPPCLL
STVQYISSFYASCLSGEESYWWMQFTAAVE (SEQ ID N0:552); YPNQDGDILR
DQVLHEHIQRLSKV VTANHRALQIPEVYLREAPWPSAQSEIRTISAYKTPRDKVQ
CILRMCSTIMNLLSLANEDSVPGADDFVPVLVFVLIKANPPCLLSTVQYISSFYA
SCLSGEESYWVVMQFTAAVEFIKTI (SEQ ID N0:553); YPNQDGDILRDQVL (SEQ
ID N0:554); EAPWPSAQSEI (SEQ ID N0:555); PVLVFVLIKANP (SEQ ID
N0:560); SGEESYWWMQFTAAVEFIKTI (SEQ ID N0:556); ADDFVPVLVF
VLIKANPP (SEQ ID N0:557); YKTPRDKVQCIL (SEQ ID N0:558); andlor GADDFVPVLVFVLIK (SEQ ID N0:559). The translation product of this gene shares sequence homology with human ras inhibitor and yeast VPS9p which is thought to be important in golgi vacuole transport.
This gene is expressed primarily in T cells and melanocytes and to a lesser extent in a variety of other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, dysfunction and disorders involving T cells and melanocytes.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression Ievel, i.e., the expression IeveI in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to ras inhibitor indicates that 10 polynucleotides and polypeptides corresponding to this gene are useful for regulating signal transduction; diagnosis and treatment of disorders involving T cells and melanocytes.
FEATURES OF PROTEIN ENCODED BY GENE NO: 90 15 This gene maps to chromosome 9 and therefore polypeptides of the invention can be used in linkage analysis as a marker for chromosome 9. The translation product of this gene shares sequence homology with neuronal olfactomedin-related ER
localized protein which is thought to be important in influence the maintenance, growth, or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons. In 20 specific embodiments, polypeptides of the invention comprise the sequence:
SARASTQPPAGQHPGPC (SEQ ID N0:561); MPGRWRWQRDMHPARKLLSLL
FLILMGTELTQD (SEQ ID N0:562); SAAPDSLLRSSKGSTRGSL (SEQ ID
N0:563); AAIVIWRGKSESRIAKTPGI (SEQ ID N0:564); FRGGGTLVLPPTHT
PEWLIL (SEQ ID N0:567); PLGITLPLGAPETGGGD (SEQ ID N0:565); and/or 25 CAAETWKGSQRAGQLCALLA (SEQ ID N0:566).
This gene is expressed in pineal gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 30 not limited to, neurological and endocrinological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neurological or endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected 35 in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 323 as residues: Leu-20 to Ala-26, Arg-32 to Arg-39, Thr-104 to Gly-112.
The tissue distribution and homology to olfactomedin-related protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for maintenance, growth, or differentiation of neuron cells in pineal gland, therefore, may be useful for diagnosis and treatment of neurological disorders in pineal gland.
FEATURES OF PROTEIN ENCODED BY GENE NO: 91 This gene is expressed primarily in prostate and apoptotic T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate disease and T cell dysfunction. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing irnmunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate cancer, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detect abnormal activity in prostate and T cells or probably treatment of this abnormality.
FEATURES OF PROTEIN ENCODED BY GENE NO: 92 This gene is expressed primarily in prostate and to a lesser extent in smooth muscle cells, fibroblasts, and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders in prostate or vascular system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prosate or vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for regulating function of prostate or highly vascularized tissues, e.g. placenta.
FEATURES OF PROTEIN ENCODED BY GENE NO: 93 This gene is expressed primarily in embryos and fetal tissues stage human and to a lesser extent in a wide variety of other proliferative tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders in embryonic development and cell proliferation.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the embryonic tissues and proliferative cells, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis or treatment of abnormalities in developing and proliferative cells and organs.
FEATURES OF PROTEIN ENCODED BY GENE NO: 94 The translation product of this gene shares sequence homology with transformation related protein which is thought to be important in transformation.
This gene is expressed primarily in female reproductive tissues, i.e., breast cancer cells, placenta, and ovary and to a lesser extent in fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer or dysfunction of reproductive tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproduction system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids-(e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 327 as residues: Ser-50 to Pro-61.
The tissue distribution and homology to transformation related protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of conditions caused by transformation, i.e.
tumorigenesis in reproductive organs, e.g. breast, placenta, and ovary.
FEATURES OF PROTEIN ENCODED BY GENE NO: 95 This gene is expressed primarily in testes, rhabdomyosarcoma, infant brain and to a lesser extent in some tumors and highly vascularized tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumorigenesis, abnormal angiogenesis, and/or neurological disorders. , Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the tumor tissues or vascular tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 328 as residues: Arg-46 to Trp-54, Pro-60 to Ile-69, Asn-116 to Ala-122, Arg-147 to Lys-153, Ser-158 to Glu-170, IIe-399 to Ser-405, Pro-486 to Met-499, Pro-502 to Asp-508.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for a range of disease states including treatment of tumor or vascular disorders and the treatment of neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
FEATURES OF PROTEIN ENCODED BY GENE NO: 96 This gene maps to chromosome 7 and therefore polynucleotides of the present invention can be used in linkage analysis as a marker for chromosome 7. The translation product of this gene is homologous to the Clostridium perfringens enterotoxin (CPE} receptor gene product and shares sequence homology with a human ORF specific to prostate and a glycoprotein specific to oligodendrocytes both of which are tissue specific proteins.(See e.g., Katahira et al., J Cell Biol.
136(6):1239-1247 ( 1997). PMID: 9087440; UI: 97242441.
This gene is expressed primarily in pancreas tumor and ulcerative colitis and to a lesser extent in several tumors and normal tissues.
i 5 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, pancreatic disorder, ulcerative colitis, tumors and food poisoning.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system or tumorigenic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 329 as residues: Gly-147 to Met-152, Cys-I77 to Lys-188.
The tissue distribution and homology to prostate and oligodendrocyte-specific protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for marker of diagnosis or treatment of disorder in pancreas, ulcerative colitis, a.nd tumors. Furthermore, identity to the human receptor for Clostridium perfringenes entertoxin indicates that the soluble portion of this receptor could be used in the treatment of food poisoning associated with Clostridia perfringens by blocking the activity of perfringens enterotoxin.
FEATURES OF PROTEIN ENCODED BY GENE NO: 97 The translation product of this gene shares sequence homology with ATPase which is thought to be important in metabolism.
5 This gene is expressed primarily in testes and several hematopoietic cells and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 10 not limited to, leukemia and hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues 15 (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
20 NO: 330 as residues: Leu-37 to Ala-42.
The tissue distribution and homology to ATPase indicates that polynucleotides and polypeptides corresponding to this gene are useful for marker of diagnosis and treatment of leukemia and other hematopoietic disorders.
25 FEATURES OF PROTEIN ENCODED BY GENE NO: 98 In specific embodiments, polypeptides of the invention comprise the sequence:
MRSARPSLGCLPSWAFSQALNI (SEQ ID N0:568); LLGLKGLAPAEISAVCE
KGNFN (SEQ ID N0:569); VAHGLAWSYYIGYLRLILPELQARIR (SEQ ID
N0:570); TYNQHYNNLLRGAVSQRC (SEQ ID N0:571); ILLPLDCGVPDNLSM
30 ADPNIRFLDKLPQQTGDRAGIKDRVYSN (SEQ ID N0:572); SIYELLENGQRAGT
CVLEYATPLQTLFAMSQYSQAGFSGEDRLEQ (SEQ ID N0:573); AKLFCRTLE
DILADAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAV
PSTSTMSQEPELLISGMEKPLPLRTDFS (SEQ ID N0:574); andlor LLGLKGLA
PAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPEL (SEQ ID N0:575).
35 Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in prostate BPH and to a lesser extent in bone marrow.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, benign prostatic hypertrophy or prostate cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male urinary system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 331 as residues: Ile-60 to Asn-69, Leu-106 to Asp-112, Glu-130 to Gly-136, Phe-160 to Glu-167, Pro-184 to Cys-190, Glu-197 to Ser-202, Arg-215 to Glu-221, Thr-237 to Pro-242.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis or treatment of benign prostatic hypertrophy or prostate cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 99 This gene is expressed primarily in salivary gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders or injuries of the salivary gland. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of glandular tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides.
corresponding to this gene are useful for treatment of disorders of, or injuries to the salivary gland or other glandular tissue.
FEATURES OF PROTEIN ENCODED BY GENE NO: 100 This gene maps to chromosome 15, accordingly, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 15. The translation product of this gene shares sequence homology with a C.elegans gene of unknown function. In specific embodiments, polypeptides of the invention comprise the sequence: DPRVRLNSLTCKHIFISLTQ (SEQ ID N0:583); TMKLLKLRRNIV
KLSLYRHFTN (SEQ ID N0:576); TLILAVAASIVFIIWTTMKFRI (SEQ ID
N0:577); VTCQSDWRELWVDDAIWRLLFSMILFVI (SEQ ID N0:578); MVLWR
PSANNQRFAFSPLSEEEEEDEQ {SEQ ID N0:580); KEPMLKESFEGMKMRS
TKQEPNGNSKVNKAQEDDL (SEQ ID N0:584); and/or KWVEENVPSSVTDVALP
ALLDSDEERMITHFERSKME (SEQ ID N0:582). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in thyroid and to a lesser extent in osteoclastoma, kidney medulla, and lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, thyroid dysfunction or cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 333 as residues:
Lys-107 to Leu-124, Glu-150 to Thr-159, Pro-173 to Asp-179, Ser-192 to Ser-201.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of thyroid dysfunction or cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 101 This gene maps to chromosome 16, therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 16. In specific embodiments, polypeptides of the invention comprise the sequence:
IRHELTVLRDTRPACA (SEQ ID N0:585); and/or MDFXMALIYD (SEQ ID
N0:586). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in kidney cortex and to a lesser extent in adult brain, corpus colosum, hippocampus, and frontal cortex.
Therefore, polynucleotides and poIypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment or diagnosis of neurological disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 102 In specific embodiments, poIypeptides of the invention comprise the sequence:
MQEMMRNQDRALSNLESIPGGYNA (SEQ ID N0:587); LRRMYTDIQEPMLSA
AQEQF GGNPF (SEQ ID N0:588); ASLVSNTSSGEGSQPSRTENRDPLPNPWAP
QT (SEQ ID N0:589); SQSSSASSGTASTVGGTTGSTASGTSGQSTTAPNLVPGV
GASMFNTPG MQSLLQQITENPQLMQNMLSAPY (SEQ ID N0:590);
MRSMMQSLSQNPDLAAQMMLNNPLFAGNPQLQEQMRQQLPTFLQQ (SEQ ID
N0:591 ); MQNPDTLSAMSNPRAMQALLQIQQGLQTLATEAPGLIPGFTPGLG
ALGSTGGSSGTNGSNATPSENTSPTAGT (SEQ ID N0:592); TEPGHQQFI
QQMLQALAGVNPQLQNPEVRFQQQLEQLSAMGFLNREANLQALIATGGDINAA
IERLLGSQPS (SEQ ID N0:593); RNPAMMQEMMRNQDRALSNLESIPGGY
NALRRMYTDIQEPMLSAA (SEQ ID N0:594); GNPFASLVSNTSS (SEQ ID
N0:595); ENRDPLPNPWA (SEQ ID N0:595); GKILKDQDTLSQHGIHD (SEQ ID
N0:597); GLTVHLVIKTQNRP (SEQ ID N0:598); SELQSQMQRQLLSNPEMM
(SEQ ID N0:599); PEISHMLNNPDIMR (SEQ ID N0:600); and/or RQLIMANPQMQQLIQRNP (SEQ ID N0:601 ). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in breast.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, breast cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of tumor systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of some types of breast cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 103 The translation product of this gene shares sequence homology with secreted serine proteases and lysozyme C precursor, which is thought to be important in bacteriolytic function. In specific embodiments, polypeptides of the invention comprise the sequence: NLCHVDCQDLLNPNLLAGIHCAKRIVS (SEQ ID N0:602);
LDGFEGYSLSDWLCLAFVESKFN (SEQ ID N0:603);
NENADGSFDYGLFQINSHYWCN (SEQ ID N0:604); and/or NLCHVDCQDLLNPNLLAGIHCAKRIVS {SEQ ID N0:605). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infection. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 336 as residues: Ile-62 to Phe-70, Asn-5 78 to Asn-84.
The tissue distribution and homology to Iysozyme C precursor indicates that polynucleotides and polypeptides corresponding to this gene are useful for boosting the moncyte-macrophage system and enhance the activity of immunoagents.
10 FEATURES OF PROTEIN ENCODED BY GENE NO: 104 This gene is expressed primarily in apoptotic T-cell.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 15 not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues {e.g., 20 cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides 25 corresponding to this gene are useful for treatment and diagnosis of some immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 105 The translation product of this gene shares sequence homology with ARI
30 protein of Drosophila (accession 2058299; EMBL: locus DMARIADNE, accession X98309), which is thought to be important in axonal path-finding in the central nervous system. In specific embodiments, polypeptides of the invention comprise the sequence IREVNEVIQNPAT (SEQ ID N0:606); ITRILLSHFNWDKEKLMERYF
DGNLEKLFA (SEQ ID N0:607); NTRSSAQDMPCQICYLNYPNSYF (SEQ ID
35 N0:608); TGLECGHKFCMQCWSEYLTTKIMEEGMGQTISCPAHG (SEQ ID
N0:614); CDILVDDNTVMRLFTDSKVKLKYQHLITNSFVECNRLLKWCPAPD
CHHVVKVQYPDAKPV (SEQ 117 N0:609); CDILVDDNTVMRLITDSK
VKLKYQHLITNSFVECNRLLKWCPAPDCHHVVKV (SEQ ID N0:610);
GCNHMVCRNQNCKAEFCWVCLGPWEPHGSAWYNCNRYNEDDAKAARDAQE
RSRAALQRYL (SEQ ID N0:611); FYCNRYMNHMQSLRFEHKLYAQVKQ
KMEEMQQHNMSWIEVQFLKKAVDVLCQCRATLMYT (SEQ ID NO: 612);
YVFAFYLKKNNQS>TFENNQADLENATEVLSGYLERDISQDSLQDIKQKVQDKY
RYCESR (SEQ ID N0:613) Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in adult brain, and to a lesser extent in endometrial tumor, melanocytes, and infant brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases or injuries involving axonal path development.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type{s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to ARI protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of disease states or injuries involving axonal path development, including neurodegenerative diseases and nerve injury.
FEATURES OF PROTEIN ENCODED BY GENE NO: 106 The translation product of this gene shares sequence homology with cytochrome b561 [Sus scrofa) which is thought to be an integral membrane protein of neuroendocrine storage vesicles of neurotransmitters and peptide hormones.
This gene is expressed primarily in frontal cortex and to a lesser extent in rhabdomyosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues} or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 339 as residues:
Ser-18 to Pro-24.
The tissue distribution and homology to cytochrome b561 [Sus scrofaJ indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of neurological disorders. This gene may also be important in regulation of some types of cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 107 In specific embodiments, polypeptides of the invention comprise the sequence:
MWGYLFVDAAWNFLGCLICGW (SEQ ID N0:615); MHFISSGNVSAIRSSILLL
RXSLSYLGNCLRVSAIFVYFLLFLLLS (SEQ ID N0:616); and/or MDQALRGSPSE
GFSTDPSPPQVGRQIPSFPPWRRLVLPKASGCFLEREWWLCVFKLRTRPGAEA
HAYNSSILGGRGKGIT (SEQ ID N0:617). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in pancreas tumor and to a lesser extent in cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, pancreatic tumors. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred WO 98!54963 PCT/US98/11422 epitopes include those comprising a sequence shown in SEQ ID NO: 340 as residues:
Pro-22 to Phe-33.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of pancreatic tumors.
FEATURES OF PROTEIN ENCODED BY GENE NO: 108 This gene maps to chromosome 17 and therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 17. In specific embodiments, polypeptides of the invention comprise the sequence:
MLPALASCCHFSPPEQAARLKKLQEQEKQQKVEFRKRMEKEVSDFIQDSGQIK
KKFQPMNKIERSILHDV VEVAGLTSFSFGEDDDCRYVMIFKKEFAPSDEELDS Y
RRGEEWDPQKAEEKRNXKELAQRQ (SEQ ID N0:618); EEEAAQQGPV V V
SPASDYKDKYSHLIGKGAAKDAAHMLQANKTYGCXPVANKRDTRSIEEAMNE
IRAKKRLRQSGE (SEQ ID N0:619); PPRRPAQLPLTPGAGQGAGRDKAAAIRA
HPGAPPLNHLLP (SEQ IDN0:620); AVPQAGGKQVFDLSPLELGYVRGMCVCV
(SEQ ID N0:621) and/or MLPALASCCHFSPPEQAARLKKLQEQEKQQKVEFRK
RMEKEVSDFIQDSGQIKKKFQPMNKIERSILHDV VEVAGLTSFSFGEDDDCRYV
MIFKKEFAPSDEELDSYRRGEEWDPQKAEEKRNXKELAQRQEEEAAQQGPV V V
SPASDYKDKYSHLIGKGAAKDAAHMLQANKTYGCXPVANKRDTRSIEEAMNE
IRAKKRLRQSGE (SEQ ID N0:622). Polynucleotides encoding these polypeptides are also encompassed by the invention. The translation product of this gene shares sequence homology with FSA-1 which may play a role as a structural protein component of the acrosome.
This gene is expressed primarily in fetal kidney and sperm.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive disorders, especially involving acrosomal disfunction.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 341 as residues: Glu-8 to Asn-35.
The tissue distribution and homology to FSA-1 indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of infertility due to acrosomal disfunction of sperm.
FEATURES OF PROTEIN ENCODED BY GENE NO: 109 This gene is expressed primarily in pituitary and to a lesser extent in epididymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 342 as residues: Met-1 to Trp-6.
Because the gene is found in both pituitary and epididymus, this indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of male reproductive disorders. This may involve a secreted peptide produced in the pituitary targeting the epididymus.
FEATURES OF PROTEIN ENCODED BY GENE NO: 110 In specific embodiments, polypeptides of the invention comprise the sequence:
LLCPVLNSGXSWNFPHPSQPEYSFHGFHSTRLWI (SEQ ID N0:623); and/or PSTPWFLFLLGLTCPFSTSHPRWDSIPP (SEQ ID N0:624). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in resting T-cells. .
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are WO 98/54963 PCT/iJS98/11422 not limited to, T-cell disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or 5 lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
10 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of certain immune disorders, especially those involving T-cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 111 15 This gene is expressed primarily in cerebellum and whole brain and to a lesser extent in infant brain and fetal kidney.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 20 not limited to, neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., 25 cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 344 as residues:
30 Asp-48 to Gly-55.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neurological disorders.
35 FEATURES OF PROTEIN ENCODED BY GENE NO: 112 The translation product of this gene shares sequence homology with yeast mitochondrial ribosomal protein homologous to ribosomal protein s 15 of E.coli which is thought to be important in the early assembly of ribosomes (See Accession No.
M38016). This gene maps to chromosome l, and therefore, may be used as a marker in linkage analysis for chromosome 1.
This gene is expressed primarily in developmental tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not linuted to, development of cancers and tumors in addition to healing wounds.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and developmental expression of this gene at signif cantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to ribosomalprotein s15 of E. coli indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases related to the assembly of ribosomes in the mitochondria which is important in the translation of RNA into protein. Therefore, this indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of multiple tumors as well as in healing wounds which are thought to be under similar regulation as developmental tissues. Protein, as well as, antibodies directed against the protein have utility as tumor markers, in addition to immunotherapy targets, for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 113 The translation product of this gene shares sequence homology with human poliovirus receptor precursors which are thought to be important in viral binding and uptake. Preferred polypeptide fragments comprise the following amino acid sequence:
ELSISISNVALADEGEYTCSIFTMPVRTAKSLVTVLGIPQKPIITGYKSSLREKDT
ATLNCQSSGSKPAARLTWRKGDQELHGEPTRIQEDPNGKTFTVSSSVTFQVTR
EDDGASIVCSVNHESLKGADRSTSQRIEVLYTPTAMIRPDPPHPREGQKLLLHC
EGRGNPVPQQYLWEKEGSVPPLKMTQESALIFPFLNKSDSGTYGCTATSNMGS
YKAYYTLNVND (SEQ ID N0:625). Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No. gnIIPIDId1002627).
This gene is expressed almost exclusively in human brain tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, susceptibility to viral disease and diseases of the CNS
especially cancers of that system. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues} or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 346 as residues: Leu-26 to Asp-37, Lys-53 to Ser-59.
The tissue distribution and homology to poliovirus receptor precursors indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and prevention of diseases that involve the binding and uptake of virus particles for infection. It might also be helpful in genetic therapy where the goal is to insert foreign DNA into infected cells. With the help of this protein, the binding and uptake of this foreign DNA might be aided. In addition, it is expected that over expression of this gene will indicate abnormalities involving, the CNS, particularly cancers of that system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 114 The translation product of this gene shares sequence homology with Y087_CREEL hypothetical 28.5 KD protein ZK1236.7 in chromosome III of Caenorhabditis elegans in addition to alpha-1 collagen type III (See Accession No.
gi1537432). One embodiment for this gene is the polypeptide fragments) comprising the following amino acid sequence: VPELPDRVHQLHQAVQGCALGRPGFPGGPTH
SGHHKSHPGPAGGDYNRCDRPGQVHLHNPRGTGRRGQLHPTAGPGVHRRA
CPSQQLPHRLGPGVPCPSPSLTPVLPSWTQSWCG LPGYTSSS (SEQ ID
N0:630). An additional embodiment is the polynucleotide fragments) encoding these polypeptide fragments This gene is expressed primarily in brain cells and to a lesser extent in activated B and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegeneration and imunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 347 as residues: Glu-34 to Glu-39, Gly-51 to Ser-72, Ala-88 to Glu-93, Gln-to Val-105.
The tissue distribution and homology to Y087_CAEEL hypothetical 28.5 KD
protein ZK1236.7 in chromosome III of Caenorhabditis elegans as well as to a conserved alpha-1 collagen type III protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons' Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorders. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 115 The translation product of this gene shares sequence homology with alpha 3 type IX collagen which is thought to be important in hyaline cartilage formation via its ability to uptake inorganic sulfate by cells (See Accession No. gi1975657).
One embodiment of this gene is the polypeptide fragment comprising the following amino acid sequence: SLRRPRSAAXQTLTTFLSSVSSASSSALPGSREPCDPRAPPPPR
SGSAASCCSCCCSCPRRRAPLRSPRGSKRRIRQREVVDLYNGMCLQGPAGVPG
RDGSPGANGIPGTPGIPGRDGFKGEKGECLRESFEESWTPNYKQCSWSSLNY
GIDLGKIAECTFTKMRSNSALRVLFSGSLRLKCRNACCQRWYFTFNGAECSGP
LPIEAIIYLDQGSPEMNSTINIHRTSSVEGLCEGIGAGLVDVAIWVGTCSDYPKG
DASTGWNSVSRIIIEELPK (SEQ ID N0:634). An additional embodiment are the polynucleotide fragments encoding this polypeptide fragment.
This gene is expressed primarily in smooth muscle and to a lesser extent in synovial tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias i.e., spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid and autoimmune disorders . Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to alpha 3 type IX collagen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of diseases associated with the mutation in this gene which leads to the many different types of chondrodysplasias. By the use of this product, the abnormal growth and development of bones of the limbs and spine could be routinely detected or treated in utero since the protein or muteins thereof could affect epithelial cells early in development and later the chondrocytes of the developing craniofacial structure.
FEATURES OF PROTEIN ENCODED BY GENE NO: 116 The translation product of this gene shares sequence homology with retrovirus-related reverse transcriptase which is thought to be important in viral replication. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: TKKENCRPASLMNIDTKILNKIL.MNQ (SEQ ID N0:640). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments (See Accession No. pirIA253131GNHUL1).
This gene is expressed primarily in human meningima.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include.
but are not limited to, retroviral diseases such as AIDS, and possibly certain cancers due to transactivation of latent cell division genes. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of 5 the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level 10 in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to retrovirus-related reverse transcriptase indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of diseases and maladies associated with retroviral infection since a functional reverse transcriptase (RT) or RT-like molecule is an integral I S component of the retroviral life cycle.
FEATURES OF PROTEIN ENCODED BY GENE NO: 117 The translation product of this gene shares sequence homology with an unknown gene from C. elegans, as well as weak homolog with mammalian metaxin, a 20 gene contiguous to both thrombospondin 3 and glucocerebrosidase, is known to be required for embryonic development. Preferred polypeptide fragments comprise the following amino acid sequence: MCNLPIKVVCRANAEYMSPSGKVPXXHVGNQ
VVSELGPIVQFVKAKGHSLSDGLEEVQKAEMKAYMELVNNMLLTAELYLQWC
DEATVGXITHXRYGSPYPWPLXHILAYQKQWEVKRKXKAIGWGKKTLDQVLE
YSNLLAFCRRI EQHYFEDRGKGRLS (SEQ ID N0:641); MCNLPIKVVCRANAE
YMSPSGKVPXXHVGNQVVSELGPIVQFVK (SEQ ID N0:642),. Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No.
gi11326108).
30 This gene is expressed primarily in fetal tissues and to a lesser extent in hematopoietic cells and tissues, including spleen, monocytes, and T cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are 35 not limited to, cancer; lymphoproliferative disorders; inflammation;
chondrosarcoma, and Gaucher disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hematopoietic and embryonic systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other proliferative disorders. Expression in embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation or cellular division. Additionally, the expression in hematopoietic cells and tissues indicates that this protein may play a role in the proliferation, differentiation, and survival of hematopoietic cell lineages. Thus, this gene may be useful in the treatment of lymphoproliferative disorders, and in the maintenance and differentiation of various hematopoietic lineages from early hematopoietic stem and committed progenitor cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 118 The translation product of this gene shares sequence homology with reverse transcriptase which is important in the synthesis of a cDNA chain from an RNA
molecule, and is a method whereby the infecting RNA chains of retroviruses are transcribed into their DNA complements. One embodiment for this gene is the polypeptide fragment comprising the following amino acid sequence:
MXXXNSHITIFTLNVNGLNAPNERHRLANWIQSQDQVCCIQETHLTGRDTHRL
KIKGWRKIYQANGKQKK (SEQ ID NO:b47). An additional embodiment is the polynucleotide fragments comprising polynucleotides encoding these polypeptide fragments (See Accession No. gi12072964).
This gene is expressed primarily in skin and to a lesser extent in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer, hematopoietic disorders; inflammation; disorders of immune surveillance. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the epidermis and/or hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to reverse transcriptase indicates that polynucleotides and polypeptides corresponding to this gene are useful for cancer therapy. Expression in the skin also indicates that this gene is useful in wound healing and fibrosis. Expression by neutrophils also indicates that this gene product plays a role in inflammation and the control of immune surveillance (i.e. recognition of viral pathogens). Reverse transcriptase family members are also useful in the detection and treatment of AIDS.
FEATURES OF PROTEIN ENCODED BY GENE NO: 119 The translation product of this gene shares sequence homology with reverse I S transcriptase which is important in the synthesis of a cDNA copy of an RNA
molecule, and is a method whereby a retrovirus reverse-transcribes its genome into an inheritable DNA copy.
This gene is expressed primarily in the frontal cortex of brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types}
present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer and neurodegenerative disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS and peripheral nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to reverse transcriptase suggest that this is useful in the treatment of cancer and AIDS. The expression in brain indicates that it plays a role in neurodegenerative disorders and in neural degeneration.
FEATURES OF PROTEIN ENCODED BY GENE NO: 120 One embodiment of this gene has homology to a hypothetical protein in Schizosaccharomyces pombe (See Accession No. 2281980). Another embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
IYHLHS WIFFHFKRAFCMCFITMKVIHAHCSKLRKCXNAQIS VFCTTLTASYPT
(SEQ ID N0:651}. An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments. This gene maps to chromosome 18, and therefore, may be used as a marker in linkage analysis for chromosome 18.
This gene is expressed primarily in adult hypothalamus and to a lesser extent in infant brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative disorders; endocrine function; and vertigo.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain, CNS and peripheral nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of neurodegenerative disorders; diagnosis of tumors of a brain or neuronal origin;
treatments involving hormonal control of the entire body and of homeostasis, behavioral disorders, such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo.
FEATURES OF PROTEIN ENCODED BY GENE NO: 121 The translation product of this gene shares sequence homology with the human IRLB protein which is thought to be important in binding to a c-myc promoter element and thus regulating its transcription (See Accession No. gi133969). This gene maps to chromosome 1, and therefore, may be used as a marker in linkage analysis for chromosome 1.
This gene is expressed primarily in brain and breast and to a lesser extent in a variety of hematopoietic tissues and cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer of the brain and breast; lymphoproliferative disorders;
neurodegenerative diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS, breast, and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial i 5 fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of cancer of the brain, breast, and hematopoietic system. In addition, it may be useful for the treatment of neurodegenerative disorders, as well as disorders of the hematopoietic system, including defects in immune competency and inflammation. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 122 The translation product of this gene shares sequence homology with an ATP
synthase, a key component of the proton channel that is thought to be important in the translocation of protons across the membrane.
This gene is expressed primarily in T cell lymphoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, T cell lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell types}. For a number of disorders of the above tissues or cells, particularly of the immune system. expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily 5 fluid from an individual not having the disorder.
The tissue distribution and homology to ATP synthase indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of defects in proton transport, homeostasis, and metabolism, as well as the diagnosis and treatment of lymphoma. Because the gene is expressed in cells of lymphoid origin, 10 the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for imununological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia FEATURES OF PROTEIN ENCODED BY GENE NO: 123 15 This gene maps to chromosome 1 S, and therefore, may be used as a marker in linkage analysis for chromosome 15.
This gene is expressed primarily in a variety of fetal tissues, including fetal liver, lung, and spleen, and to a lesser extent in a variety of blood cells, including eosinophils and T cells.
20 Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer (abnormal cell proliferation); T cell lymphomas; and hematopoietic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are 25 useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the fetus and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or 30 another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of conditions 35 involving cell proliferation. Expression of this gene in fetal tissues, as well as in a variety of blood cell lineages indicates that it may play a role in either cellular proliferation; apoptosis; or cell survival. Thus it may be useful in the management and treatment of a variety of cancers and malignancies. In addition, its expression in blood cells suggest that it may play additional roles in hematopoietic disorders and conditions, and could be useful in treating diseases involving autoimmunity, immune modulation, immune surveillance, and inflammation..
FEATURES OF PROTEIN ENCODED BY GENE NO: 124 -This gene is expressed primarily in placenta and to a lesser extent in pineal gland and rhabdomyosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental, endocrine, and female reproductive disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For I5 a number of disorders of the above tissues or cells, particularly of the [insert system where a related disease state is likely, e.g., immune], expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 357 as residues:
Leu-69 to Val-76.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorders in development. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 125 This gene is expressed primarily in benign prostatic hyperplasia Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of benign prostatic hyperplasia.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of benign prostatic hyperplasia. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 126 This gene is expressed primarily in apoptotic T-cells and to a lesser extent in suppressor T cells and ulcerative colitis.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases involving premature apoptosis, and immunological and gastrointestinal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders involving inappropriate levels of apoptosis, especially in immune cell lineages. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases (such as AIDS), and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: I27 This gene is expressed primarily in Raji cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammation and T cell autoimmune disorders. Similarly;
polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 360 as residues: Asp-23 to Gly-29.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of inflammation and T
cell autoimmune disorders. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases (such as AIDS), and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 128 The translation product of this gene shares sequence homology with an C.
elegans coding region C47D12.2 of unknown function (See Accession No.
gnIIPIDle348986). One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: EDDGFNRSIHEVILKNITWY
SERVLTEISLGSLLILV V IRTIQYNMTRTRDKYLHTNCLAALANMSAQFRSLHQY
AAQRIISLFSLLSKKHNKVLEQATQSLRGSLSSNDVPLPDYAQDLNVIEEVIRMM
LEIINSCLTNSLHHNPNLVALLYKRDLFEQFRTHPSFQDIMQNIDLVISFFSSRLL
QAGS (SEQ ID N0:657); EDDGFNRSIHEVILKNITWYSERVLTEISLGSLLILVV
(SEQ ID N0:658); RTIQYNMTRTRDKYLHTNCLAALANMSAQFRSLHQYAAQ
RIISLFSLLSKKHN (SEQ ID N0:659); KKHNKVLEQATQSLRGSLSSNDVPLPDY
AQD (SEQ ID N0:661); SCLTNSLHHNPNLVYALLYKRDLFEQFRTHPSFQD
IMQNIDLVISFFSSRLLQAGS (SEQ ID N0:660). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments. This gene maps to WO 98!54963 PCTNS98/11422 chromosome 18, and therefore, may be used as a marker in linkage analysis for chromosome 18.
This gene is expressed primarily in smooth muscle and to a lesser extent in fetal liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, atherosclerosis and other cardiovascular and hepatic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the circulatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of circulatory system disorders such as atherosclerosis, hypertension, and thrombosis . In addition, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers {e.g.
hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells). In addition the expression in fetus would suggest a useful role for the protein product in developmental abnormalities, fetal deficiencies, pre-natal disorders and various would-healing models and/or tissue trauma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 129 The translation product of this gene shares sequence homology with a ribosomal protein which is thought to be important in cellular metabolism, in addition to the C.elegans protein F40F11.1 which does not have a known function at the current time (See Accession No. gnlIPIDIe244552 ). Preferred polypeptide fragments comprise the following amino acid sequence:
MADIQTERAYQKQPTIFQNKKRVLLGETGKEKLPRVTNKNIGLGFKDT
PRRLLRGTYIDKKCPFTGN V SIRGRILSG V V TQDEDAEDHCHPPRLSALHPQV Q
PLREAPQEHVCTPVPL LQGRPDR (SEQ ID N0:662); MKMQRTIVIRRDYLH
YIRKYNRFEKRHKNMSVHLSPCFRDVQIGDIVTVGECRPLSKTVRFNVLKVTK
AAGTKKQFQKF (SEQ ID N0:663); MADIQTERAYQKQPTIFQNKKRVLLGET
GK (SEQ ID N0:664); HCHPPRLSALHPQVQPLREAPQEHVCTPVPL LQGRPDR
(SEQ ID N0:666); NIGLGFKDTPRRLLRGTYIDKKCPFTGNVSIRGRILSGVVTQ
(SEQ ID N0:669); MKMQRTIVIRRDYLHYIRKYNRFEKRHKNMSVHLSP (SEQ
ID N0:667); CFRDVQIGDIVTVGECRPLSKTVRFNVLKVTKAAGTKKQFQKF
(SEQ ID N0:668). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in Wilm's tumor and to a lesser extent in thymus and stromal cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases affecting RNA translation. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the Wilm's tumors, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 362 as residues:
Thr-11 to Asp-20.
The tissue distribution and homology to a ribosomal protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases affecting RNA translation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 130 The translation product of this gene shares sequence homology with a yeast DNA helicase which is thought to be important in global transcriptional regulation (See Accession No. gnllPIDle243594). One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: IFYDSDWNPTVDQQA
MDRAHRLGQTKQVTVYRLICKGTIEERILQRAKEKSEIQRMVISG (SEQ ID
N0:670); TRMIDLLEEYMVYRKHTYXRLDGSSKISERRDMVADFQNRNDI
FVFLLSTRAGGLGINLTAXDTVHF (SEQ ID N0:671); TRMIDLLEEYMVYRK
HTYXRLDGSSKISERRDM (SEQ ID N0:674); RRDMVADFQNRNDIFVFLL
STRAGGLGINLTAXDTVHF (SEQ ID N0:675) , IFYDSDWNPTVDQQAMD
RAHRLGQTKQVTVYRLICKG (SEQ ID N0:676); RLICKGTIEERILQRAK
EKSEIQRMVISG (SEQ ID N0:678). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in amygdala.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases and disorders of the brain. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to a DNA helicase indicates that polynucleotides and polypeptides corresponding to this gene are useful for diseases affecting RNA transcription, particularly developmental disorders and healing wounds since the later are though to approximate developmental transcriptional regulation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 131 This gene is expressed primarily in prostate and to a lesser extent in arnygdala and pancreatic tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate enlargement and gastrointestinal disorders, particularly of the pancreas and gall bladder. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of prostate diseases, including benign prostatic hyperplasia and prostate cancer. In addition, the tissue distribution in tumors of the pancreas indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tissues where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 132 This gene is expressed primarily in adult lung and to a lesser extent in hypothalamus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue{s) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, pulmonary diseases and neurological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the pulmonary and respiratory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid] or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of pulmonary and respiratory disorders such as emphysema, pneumonia, and pulmonary edema and emboli. In addition, the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 133 This gene is expressed primarily in human liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cirrhosis of the liver and other hepatic disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids {e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of liver disorders such as cirrhosis, jaundice, and Hepatitus. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 134 This gene is expressed primarily in fetal kidney and to a lesser extent in fetal liver and spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, development and regeneration of liver and kidney and immunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the digestive and excretory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 367 as residues: Pro-70 to Arg-77, Tyr-102 to Thr-107.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of diseases of the kidney and liver, such as cirrhosis, kidney failure, kidney stones, and liver failure, hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells. In addition the expression in fetus would suggest a useful role for the protein product in developmental abnormalities, fetal deficiencies, pre-natal disorders and various would-healing models and/or tissue trauma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 135 This gene is expressed primarily in brain, bone marrow, and to a lesser extent in placenta, T cell, testis and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurodegenerative and immunological diseases and cancer.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid} or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 368 as residues: Met-I to His-6.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 136 Translatation product of this gene is homologous to the human WD repeat protein HAN 11. Preferred polypeptide fragments comprise the following amino acid sequence:
MSLHGKRKEIYKYEAPWTVYAMNWSVRPDKRFRLALGSFVEEYNNKVQLVG
LDEESSEFICRNTFDHPYPTTKLMWIPDTKGVYPDLLATSGDYLRVWRVGETET
RLECLLNNNKNSDFCAPLTSFDWNEVDPYLLGTSSIDTTCTIWGLETGQVLGRV
NLVSGHVKTQLIAHDKEVYDIAFSRAGGGRDMFAS VGADGS VRMFDLRHLEH
STIIYEDPQHHPLLRLCWNKQDPNYLATMAMDGMEVVILDVRVPAHLXPGTTIE
HV SMALLGPHIHPATSALQRMTTRLSSGTSSKCPEPLRTLS WPTQLXGEINNVQ
WASTQPELSPSATTTAWRYSECSVGGAVPTRQGLLYFLPLPHPQS (SEQ ID
N0:679); MSLHGKRKEIYKYEAPWTVYAMNWSVRPDKRFRLALGSFV
EEYNNKVQLVGLDEESSEFICRNTFDHPYPTTKLMWIPDTKGVYPDLLATSGDY
LRVWRVGETETRLECLLNNNKNSDFCAPLTSFDWNEVDPYLL (SEQ ID
N0:680); SFDWNEVDPYLLGTSSIDTTCTIWGLETGQVLGRVNLVSGHVK
HPLLRLCWNKQDPNYLATMAMDGMEVVILDVRVPAHLXPGTTI (SEQ m N0:681); VGADGSVRMFDLRHLEHSTIIYEDPQHHPLLRLCWNKQDPNYLA
TMAMDGMEVVILDVRVPAHLXPGTTIEHVSMALLGPHIHPATSALQRMTTRLS
SGTSSKCPEPLRTLSWPTQLXGEINNVQWASTQPELSPSATTTAWRYSECSVG
GAVPTRQGLLYFLPLPHPQS (SEQ ID N0:682). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in placenta, embryo, T cell and fetal lung and to a lesser extent in endothelial, tonsil and bone marrow.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological and developmental diseases in addition to cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 369 as residues: Gly-19 to Gln-28, Pro-36 to Phe-42.
The tissue distribution in tumors of colon, ovary, and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 137 This gene is expressed primarily in TNF and INF induced epithelial cells, T
cells and kidney.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory conditions particularly inflammatory reactions in the kidney. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 370 as residues: Thr-67 to Gly-72, Gln-132 to Ala-145, Arg-150 to Pro-157.
The tissue distribution indicates that the protein products of this gene are useful for treating the damage caused by inflammation of the kidney.
FEATURES OF PROTEIN ENCODED BY GENE NO: 138 This gene maps to chromosome l, and therefore, may be used as a marker in linkage analysis for chromosome 1 (See Accession No. D63485).
This gene is expressed primarily in breast cancer and colon cancer and to a lesser extent in thymus and fetal spleen.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers, especially of the breast and colon tissues.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of colon and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 139 This gene maps to chromosome 17, and therefore, can be used as a marker for linkage analysis from chromosome 17.
This gene is expressed primarily in CD34 positive cells, and to lesser extent in activated T-cells and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(sj or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunologically related diseases and hematopoietic disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system and hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in CD34, T-cell and neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of hematopoietic disorders and immunologically related diseases, such as anemia, leukemia, inflammation, infection, allergy, immunodeficiency disorders, arthritis, asthma, immune deficiency diseases such as AIDS.
FEATURES OF PROTEIN ENCODED BY GENE NO: 140 This gene was recently cloned by another group, who called the gene KIAA0313 gene. (See Accession No. d1021609.) Preferred polypeptide fragments comprise the amino acid sequence:
LYATATVISSPSTEXLSQDQGDRASLDAADSGRGSWTSCSSGSHDNIQTIQ
HQRSWETLPFGHTHFDYSGDPAGLWASSSHMDQIMFSDHSTKYNRQNQSRES
LEQAQSRASWASSTGYWGEDSEGDTGTIKRRGGKDVSIEAESSSLTSVTTEETK
PVPMPAHIAVASSTTKGLIARKEGRYREPPPTPPGYIGIPITDFPEGHSHPARKP
PDYNVALQRSRMVARSSDTAGPSSVQQPHGHPTSSRPVNKPQWHKXNESDPR
LAPYQSQGFSTEEDEDEQVSAV (SEQ 117 N0:683); HMDQIMFSDHSTKYNRQ
NQSRESLEQAQSRASWASSTGYWGE (SEQ ID N0:684); SVTTEETKPVPMP
AHIAVASSTTKGLIARKEGRYREPPPTPPGYIGIPITD (SEQ ID N0:685); and VALQRSRMVARSSDTAGPSSVQQPHGHPTSSRPVNKPQW
HKXNESDPRLAPYQSQGF (SEQ ID N0:686). Also preferred are polynucleotide fragments encoding these polypeptide fragments. This gene maps to chromosome 4, and therefore, may be used as a marker in linkage analysis for chromosome 4 (See Accession No. AB0023I 1 ) This gene is expressed primarily in ovarian cancer, tumors of the Testis, brain, and colon.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, ovarian, testicle, brain and colon cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells. particularly of the male and female reproductive systems.
expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of colon, ovary, testis, and brain origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 141 This gene is expressed primarily in spleen and colon cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, colon cancer and immunological disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the gastrointestinal trace and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of colon, ovary, and breast origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 142 Translation product is homologous to T cell translocation protein, a putative zinc finger factor (See Accession No. 340454), as well as to the G-protein coupled receptor TMS consensus polypeptide (See Accession No. R50734). Preferred polypeptide fragments comprise the following amino acid sequence:
CLLFVFVSLGMRCLFWTIVYNVLYLKHKCNTVLLCYHLCSI (SEQ-ID N0:687);
ACSKLIPAFEMVMRAKDNVYHLDCFACQLCNQRXCVGDKFFLKNNXXLCQT
DYEEGLMKEGYAPXVR (SEQ ID N0:688). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in fetal brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types}
present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological disorders including brain cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the Central Nervous System, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo.
FEATURES OF PROTEIN ENCODED BY GENE NO: 143 Translation product for this gene has significant homology to the Fas ligand, which is a cysteine-rich type II transmembrane protein/tumor necrosis factor receptor homolog. Mutations within this protein have been shown to result in generalized lymphoproliferative disease leading to the development of Iymphadenopathy and autoimmune disease (See Medline Article No. 94185175). Preferred polypeptide fragments comprise the following amino acid sequence:
SALSEPGAPDRRRPCPESVPRRPDDEQWPPPTALCLDVAPLPPSS (SEQ ID
N0:689). Also preferred are polynucleotide fragments encoding these polypeptide fragments (See Accession No. 473565).
This gene is expressed primarily in osteoblasts, lung, and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoblast-related, pulmonary, neurological, and immunological diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 376 as residues: Trp-33 to Thr-40, Lys-45 to Ile-63.
The tissue distribution in osteoblasts, lung, and brain combined with its homology to the Fas ligand indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. Because the Fas ligand gene is known to be expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including asthma, immune deficiency diseases such as AIDS
and leukemia, and various autoimmune disorders including lupus and arthritis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 144 This gene shares sequence homology with a 21.5 KD transmembrane protein in the SEC15-SAP4 intergenic region of yeast. (See Accession No. 1723971.) Preferred polypeptide fragments comprise the amino acid sequence:
AHASESGERWWACCGVRFGLRSIEAIGRSCCHDGPGGLVANRGRRFKWAIEL
SGPGGGSRGRSDRGSGQGDSLYPVGYLDKQVPDTSVQETDRILVEKRCWDIAL
GPLKQIPMNLFIMYMAGNTISIFPTMMVCMMAWRPIQALMAISATFKMLESSSQ
KFLQGLVYLIGNLMGLALAVYKCQSMGLLPTHASDWLAFIEPPERMEFSGG
GLLL (SEQ ID N0:691); PVGYLDKQVPDTSVQETDRILVEKRCWDIALGPLKQ
IPMNLFI (SEQ ID N0:693); and ATFKMLESSSQKFLQGLVYLIGNLMGLALAV
YKCQSMGLLPTHASD (SEQ ID N0:692). Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in osteoclastoma, hemangiopericytoma, liver, lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, osteoclastoma, hemangiopericytoma, liver and lung tumors.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the above tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the lung and liver systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing osteoclastoma, hemangiopericytoma, liver and lung tumors.
FEATURES OF PROTEIN ENCODED BY GENE NO: 145 Translation product of this gene shares homology with the glucagon-69 gene which may indicate this gene plays a role in regulating metabolism. (See Accession No.
A60318) One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
PTTKLDIMEKKKHIQIRFPSFYHKLVDSGRMRSKRETRREDSDTKHNL (SEQ ID
N0:694). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in brain, kidney, colon, and testis.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, brain, kidney, colon, and testicular cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive system, neurological, S circulatory, and gastrointestinal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in tumors of brain, kidney, colon, and testis origins, indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntingtons Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder. In addition, the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 146 The translation product of this gene shares sequence homology with goliath protein which is thought to be important in the regulation of gene expression during development. Protein may serve as a transcription factor. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
TEHIIAVMITELRGKDILSYLEKNISVQMTIAVGTRMPPKNFSRGSLVFVSISFIV
LMIISSAWLIFYFIQKIRYTNARDRNQRRLGDAAKKAISKLTTRTVKKGDKETD
PDFDHCAVCIESYKQNDVVRLLPCKHVFHKSCVDPWLSEHCTCPMCKLNILKA
LGIV (SEQ ID N0:695); TEHIIAVMITELRGKDILSYLEKNISVQMTIAVGTRMP
PKNFSRGSLVFVSISFIVLM IISSAWLIFYF (SEQ ID N0:697); SISFIVLMIISSA
WLIFYFIQKIRYTNARDRNQRRLGDAAKKAISKLTTRTVKKGDKE (SEQ ID
N0:698); VKKGDKETDPDFDHCAVCIESYKQNDVVRILPCKHVFHKSCVDP
WLSEHCTCPMCKLNILKALGIV (SEQ ID N0:699). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments (See Accession No.
157535). Moreover, another embodiment is the polynucleotide fragments encoding these polypeptide fragments:
MTHPGTEHIIAVMITELRGKDILSYLEKNISVQMTIAVGTRMPPKNFSRGS
LVFVSISFIVLMIISSAWLIFYFIQKIRYTNARDRNQRRLGDAAKKAISKLTTRTV
KKGDKETDPDFDHCAVCIESYKQNDV VRILPCKHVFHKSCVDPWLSEHCTCP
MCKLNILKALGIVPNLPCTDNVAFDMERLTRTQAVNRRSALGDLAGDNSLGLE
PLRTSGISPLPQDGELTPRTGEINIAVTKEWFIIASFGLLSALTLCYMIIRATASLN
ANEVEWF (SEQ ID NO:696);MTHPGTEHIIAVMIT'ELRGKDILSYLEKNISVQM
TIAVGTRMPPKNFSRGSLVFVSISFIVLMIISSAWLIFYFIQKIRYTNARDRNQRR
LGDAAKKAISKLTTRT (SEQ ID N0:700); AAKKAISKLTTRTVKKGDKE
TDPDFDHCAVCIESYKQNDV VRILPCKHVFHKSCVDPWLSEHCTCPMCKLNIL
KALGIVPNLPC (SEQ ID N0:701); TQAVNRRSALGDLAGDNSLGLEPLRTSGI
SPLPQDGELTPRTGEINIAVTKEWFIIASFGLLSALTLCYMIIRATASLNANEVEW
F (SEQ ID N0:702); PLHGVADHLGCDPQTRFFVPPNIKQWIALLQRGNCTF
KEKISRAAFHNAVAV VIYNNKS KEEPVTMTHPGTEHIIAVMITELRGKDILSYLE
KNISVQMTIAVGTRMPPKNFSRGSLVFVSISFIVLMIISSAWLIFYFIQKIRYTNA
RDRNQRRLGDAAKKAISKLTTRTVKKGDKETDPDFDHCA VCIESYKQNDV VRI
LPCKHVFHKSCVDPWLSEHCTCPMCKLNILKALGIVPNLPCTDNVAFDMERLT
RTQAVNRRSALGDLAGDNSLGLEPLRTSGISPLPQDGELTPRTGEINIAVTKEW
FIIASFGLLSALTLCYMIIRATASLNANEVEWF(SEQ ID N0:703); and HGVADHLGCDPQTRFFVPPNIKQWIALLQRGNCTFKEKISRAAFHNAVAVVIY
NNKSKEE (SEQ ID N0:704). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments. When tested against Jurkat cell lines, supernatants removed from cells containing this gene activated the GAS
pathway.
Thus, it is likely that this gene activates immune cells through the JAKS/STAT
signal transduction pathway.
This gene is expressed primarily in macrophage, breast, kidney and to a lesser extent in synovium, hypothalamus and rhabdomyosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues} or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, schizophrenia and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and neural system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to zinc finger protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of schizophrenia, kidney disease and other cancers. The tissue distribution in macrophage, breast, and kidney origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of tumors within these tissues, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 147 The translation product of this gene shares sequence homology with HNP36 protein, an equilibrative nucleoside transporter, which is thought to be important in gene transcription as well as serving as an important component of the nucleoside transport apparatus (See Accession No. 1845345). One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
MSGQGLAGFFASVAMICAIASGSELSESAFGYFITACAVIILTIICYLGLPRLEFYR
YYQQLKLEGPGEQETKLDLISKGEEPRAGKEESGVSVSNSQPTNESHSIKAILK
NISVLAFSVCFIFTITIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLG
RSLTAVFMWPGKDSRWLPSWXLARLVFVPLLLLCNIKPRRYLTV VFEHDAWFI
FFMAAFAFSNGYLASLCMCFGPKKVKPAEAETAEPSWPSSCVWVWHWGLFS
PSCSGQLCDKGWTEGLPASLPVCLLPLPSARGDPEWSGGFFF (SEQ ID
N0:705); MSGQGLAGFFASVAMICAIASGSELSESAFGYFTTACAVIILTIIC
YLGLPRLEFYRYYQQLKLE GPGEQETKLDLISKGEEPRAGKEESGVSVSNSQ
PTNESHSI (SEQ ID N0:706); SGVSVSNSQPTNESHSIKAILKNISVLAFSVCFI
FTITIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLGRS (SEQ ID
NO:707),TIGMFPAVTVEVKSSIAGSSTWERYFIPVSCFLTFNIFDWLGRSLTAVF
MWPGKDSRWLPSWXLARLVFVPLLLLCNIK PRRYLTVVFEHDA (SEQ ID
N0:708); FGPKKVKPAEAETAEPSWPSSCVWVWHWGLFSPSCSGQLCDK
GWTEGLPASLPVCLLPLPSARGDPEWSGGFFF (SEQ ID N0:709). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in eosinophils and aortic endothelium and to a lesser extent in umbilical vein endothelial cell and thymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematopoietic disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the circular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to HNP36 protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of blood neoplasias and other hematopoietic disease.
FEATURES OF PROTEIN ENCODED BY GENE NO: 148 This gene is expressed primarily in breast cancer cell lines, thymus stromal cells, and ovary.
Therefore, polynucIeotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, endocrine and female reproductive system diseases including breast cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
WO 98/54963 PCT/tJS98/11422 The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of endocrine disorders. In addition, the tissue distribution in tumors of thymus, ovary, and breast origins indicates that polynucIeotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues FEATURES OF PROTEIN ENCODED BY GENE NO: 149 Translation product of this gene has homology to pmt 1 and pmt 2, two conserved schizosaccharomyces pombe genes. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
DDDGFEIVPIEDPAKHRILDPEGLALGAVIASSKKAKRDLIDNSFNRYTFNEDEG
ELPEWFVQEEKQHRIRQLPVGKKEVEHYRKRWREINARPIXXXXXXXXXXX
XXXXXXLEQTRKKAEAVVNTVDIXRTRES (SEQ ID N0:710);
DDDGFEIVPIEDPAKHRILDPEGLALGAVIASSKKAKRDLIDNSFNRYTF (SEQ
ID N0:711 ); KRWREINARPIXXXXXXXXXXXXXXXXXLEQTRKKAE
AVVNTVDIXRTRES (SEQ ID N0:712). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments (See Accession No.
a 1216734).
This gene is expressed primarily in retina and ovary and to a lesser extent in brreast cancer cell, epididymus and osteosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal growth disorders, cancer and reproductive system disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neural and reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 382 as residues: Met-1 to Gly-7.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis or treatment of reproductive system disease and cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 150 One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
MIKDKGRARTALTSSQPAHLCPENPLLHLKAAVKEKKRNKKKKTIGSPKRIQS
PLNNKLLNSPAKTLPGACGSPQKLIDGFLKHEGPPAEKPLEELSASTSGVPGLS
SLQSDPAGCVRPPAPNLAGAVEFNDVKTLLREWITTISDPMEEDILQVVKYCTD
LIEEKDLEKLDLVIKYMKRLMQQS VES V WNMAFDFILDN V Q V VLQQTYGSTLK
VT (SEQ ID N0:713}; MIKDKGRARTALTSSQPAHLCPENPLLHLKAAVKE
KKRNKKKKTIGSPKRIQ (SEQ ID N0:714); KRIQSPLNNKLLNSPAKT
LPGACGSPQKLIDGFLKHEGPPAEKPLEELSASTSGVPGLSSLQSDPAGCVRPP
APNLAGAVEFNDVKTLLREWITTISDPM (SEQ ID N0:715);
TISDPMEEDILQWKYCTDLIEEKDLEKLDLVIKYMKRLMQQS VE
SVWNMAFDFILDNVQVVLQQTYGSTLKVT (SEQ ID N0:716). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in 12 week embryo and to a lesser extent in hemangiopericytoma and frontal cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, growth disorders and hemangiopericytoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the circular and neural system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 383 as residues: Leu-4 to Lys-11.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of growth disorders, hemangiopericytoma and other soft tissue tumors.
FEATURES OF PROTEIN ENCODED BY GENE NO: 151 The translation product of this gene has been found to have homology to a human DNA mismatch repair protein PMS3. Preferred polypeptide fragments comprise the following amino acid sequence: FCHDCKFPEASPAMNCEP {SEQ ID N0:717).
Also preferred are polynucleotide fragments encoding these polypeptide-fragments (See Accession No. 895250).
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not linuted to, lymphoma, immunodeficiency diseases, and cancers resulting from genetic instability. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 384 as residues: Met-1 to Lys-6.
The tissue distribution in neutrophils and the sequence homology indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of Hodgkin's lymphoma, since the elevated expression and secretion by the tumor mass may be indicative of tumors of this type. Additionally the gene product may be used as a target in the immunotherapy of the cancer. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
Furthermore, its homology to a known DNA repair protein would suggest gene may be useful in establishing cancer predisposition and prevention in gene therapy applications.
FEATURES OF PROTEIN ENCODED BY GENE NO: 152 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a l20 biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infectious diseases and lymphoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of inflammation and infectious diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 153 One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence:
MASS VPAGGHTRAGGIFLIGKLDLEASLFKSFQWLPFVLRKKC
NFFCWDSSAHSLPLHPLSASCSAPACHASDTHLLYPSTRALCPSIFAWLVAPHS
VFRTNAPGPTPSSQSSPVFPVFPVSFMALIVCXLVCC (SEQ ID N0:720);
MASSVPAGGHTRAGGIFLIGKLDLEASLFKSFQWLPFVLRKKCNFFCWDSSAH
SLPLHPLSASCSAPACHA (SEQ ID N0:721);FAWLVAPHSVFRTNAPGPTPS
SQSSPVFPVFPVSFMALIVCXLVCC (SEQ ID N0:722). An additional embodiment is the polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited lo, inflammation and infectious disease. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 386 as residues:
Ser-1 i to Pro-17.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment of infectious diseases and inflammation.
FEATURES OF PROTEIN ENCODED BY GENE NO: 154 This gene is expressed in multiple tissues including ovary, uterus, adipose tissue, brain, and the liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, uterine, ovarian, brain, and liver cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the female reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution of this gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnostic or therapeutic uses in the treatment of the female reproductive system, obesity, and liver disorders, particularly cancer in the above tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 155 This gene maps to chromosome 3, and therefore, may be used as a marker in linkage analysis for chromosome 3 (See Accession No. D87452).
This gene is expressed in multiple tissues including brain, aortic endothelial cells, smooth muscle, pituitary, testis, melancytes, spleen, nertrophils, and placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological disorders including immunodeficiencies, cancers of the brain and the female reproductive system, as well as cardiovascular disorders, such as atherosclerosis and stroke. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution suggest that polynucleotides and poIypeptides coczesponding to this gene are useful in treatment/detection of disorders in the nervous system, including schizophrenia, neurodegeneration, neoplasia, brain cancer as well as cardiovascular and female reproductive disorders including cancer within the above tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 156 The translation product of this gene shares sequence homology with the human gene encoding cytochrome b561 (See Accession No. P10897). Cytochrome b561 is a transmembrane electron transport protein that is specific to a subset of secretory vesicles containing catecholamines and amidated peptides. This protein is thought to supply reducing equivalents to the intravesicular enzymes dopamine-beta-hydroxylase and alpha-peptide amidase. Preferred polypeptides of the invention comprise the amino acid sequence:
MAMEGYWRFLALLGSALLVGFLSVIFALVWVLHYREGLGWDGSALEFNWHP
VLMVTGFVFIQGIAIIVYRLPWTWKCSKLLMKSIHAGLNAVAAILAIISVVAVFE
NHNVNNIANMYSLHSWVGLIAVICYLLQLLSGFSVFLLPWAPLSLRAFLMPIHV
YSGIVIFGTVIATALMGLTEKLIFSLRDPAYSTFPPEGVFVNTLGLLILVFGALIF
WIVTRPQWKRPKEPNSTILHPNGGTEQGARGSMPAYSGNNMDKSDSEL
NSEVAARKRNLALDEAGQRSTM (SEQ ID N0:724); as well as antigenic fragments of at least 20 amino acids of this gene and/or biologically active fragments.
Also preferred are polynucleotide fragments encoding these polypeptide fragments.
This gene is expressed primarily in anergic T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune system and metabolism related diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein product or RNA of this gene is useful for treatment or diagnosis of immune system and metabolic diseases or conditions including Tay-Sachs disease, phenylketonuria, galactosemia, various porphyrias, and Hurler's syndrome.
FEATURES OF PROTEIN ENCODED BY GENE NO: 157 The translation product of this gene shares sequence homology with collagen which is important in mammalian development. This gene also shows sequence homology with bcl-2. (See Accession No. P80988.) Preferred polypeptide fragments comprise the amino acid sequence: PGRAGPSPGLSLQLPAEPGHPAGNLAPL
TSRPQPLCRIPAVPG (SEQ ID N0:725). Also preferred are polynucleotide sequences encoding this polypeptide fragment.
This gene is expressed primarily in HL-60 tissue culture cells and to a lesser extent in liver, breast, and uterus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunological diseases, hereditary disorders involving the MHC
class of immune molecules, as well as developmental disorders and reproductive disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and reproductive system expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 390 as residues: Ser-39 to Gly-46, Leu-49 to Ala-62.
The tissue distribution and homology to collagen indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of hereditary MHC disorders and particularly autoimmune disorders including rheumatoid arthritis, lupus, scleroderma, and dermatomyositis, as well as many reproductive disorders, including cancer of the uterus, and breast tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 158 This gene is expressed primarily in the amygdala region of the brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, a variety of brain disorders, particularly those effecting mood and personality. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the brain and central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and/or diagnosis of a variety of brain disorders, particularly bipolar disorder, unipolar depression, and dementia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 159 This gene is expressed in a variety of tissues and cell types including brain, smooth muscle, kidney, salivary gland and T-cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers of a variety of organs including brain, smooth muscle, kidney, salivary gland and T-cells and cardiovascular disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous, urinary, salivary, digestive, and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain, smooth muscle, and T-cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of various neurological, and cardiovascular disorders, but not limited to cancer within the above tissues. Additionally the gene product may be used as a target in the immunotherapy of the cancer. Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 160 The translation product of this gene shares sequence homology with collagen which is thought to be important in cellular interactions, extracellular matrix formation, and has been found to be an identifying determinant in autoimmune disorders.
Moreover, this gene shows sequence homology with the yeast protein, Slslp, an endoplasmic reticulum component, involved in the protein translocation process in Yeast Yarrowia lipolytica. (See Accession No. 1052828; see also J. Biol. Chem.
271, 11668-11675 (1996).) With mouse, this same region shows sequence homology with the heavy chain of kinesin. (See Accession No. 2062607.) Recently, suppression of the heavy chain of kinesin was shown to inhibits insulin secretion from primary cultures of mouse beta-cells. (See Endocrinology 138 (5), 1979-1987 (1997).) Moreover, kinesin was found associated with drug resistance and cell immortalization. (See 468355.) Thus, it is likely that this gene also act as a genetic suppressor elements.
This gene is expressed primarily in the greater omentum and to a lesser extent in a variety of organs and cell types including gall bladder, stromal bone marrow cells, lymph node, liver, testes, pituitary, and thymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders of the endocrine, gastrointestinal, and immunological systems, including autoimmune disorders and cancers in a variety of organs and cell types.
WO 98/54963 PCTlUS98/11422 Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune and gastrointestinal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 393 as residues: Asn-27 to Leu-47, Gln-81 to Lys-88, Asp-93 to Lys-102, Asn-107 to Leu-116, Met-129 to Glu-141, Glu-to Asp-157, Lys-176 to Glu-185, Glu-333 to Tyr-349, Cys-393 to Leu-403, Gln-to Gly-429.
The tissue distribution in within various endocrine and immunological tissues combined with the sequence homology to a conserved collagen motif indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis of various autoimmune disorders including, but not limited to, rheumatoid arthritis, lupus erthyematosus, scleroderma, dermatomyositis Because the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 161 This gene has homology to the tissue inhibitor of metalloproteinase 2. Such inhibitors are vital to proper regulation of metalloproteins such as collagenases (See Accession No. P16368). In addition, this gene maps to chromosome 17, and therefore, may be used as a marker in linkage analysis for chromosome 17 (See Accession No. P16368).
This gene is expressed primarily in several types of cancer including osteoclastoma, chondrosarcoma, and rhabdomyosarcoma and to a lesser extent in several non-malignant tissues including synovium, amygdala, testes, placenta.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a ~ biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, various types of cancer, particularly cancers of bone and cartilage, as well as various autoimmune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the musculoskeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in various cancers and the sequence homology to a collagenase inhibitor indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 162 This gene is homologous to the mitochondria) ATP6 gene and therefore is likely a homolog of this gene family (See Accession No. X76197).
This gene is expressed primarily in brain tissue.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, a variety of brain disorders, including Down's syndrome, depression, Schizophrenia, and epilepsy. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in brain tissue indicates this gene is useful for diagnosis of various neurological disorders including, but not limited to, brain cancer.
Additionally the gene product may be used as a target in the immunotherapy of cancer in the brain as well as for the diagnosis of metabolic disorders such as obesity Tay-Sachs disease, phenylketonuria and Hurler's Syndrome.
FEATURES OF PROTEIN ENCODED BY GENE NO: lb3 This gene is expressed primarily in placenta, neutrophils, and microvascular endothelial cells and to a lesser extent in multiple tissues including brain, prostate, spleen, thymus, and bone.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell type{s) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neutropenea and other diseases of the immune system.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in placenta indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis various female reproductive disorders. Additionally the gene product may be used as a target in the immunotherapy of various cancers. Because the gene is expressed in some cells of lymphoid and endocrine origin, the natural gene product may be involved in immune functions and metabolism regulation, respectively. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 164 This gene is expressed primarily in neutrophils, monocytes, bone marrow, and fetal liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune system disorders including, but not limited to, autoimmune disorders such as lupus, and immunodeficiency disorders . Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in various immune system tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis of various immunological disorders such as Hodgkin's lymphoma, arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 165 The translation product of this gene shares sequence homology with dystrophin which is thought to be defective in both Duchene and Becker Muscular Dystrophy.
Preferred polypeptide fragments comprise the following amino acid sequence:
MKLLGECSSSIDSVKRLEHKLKEEEESLPGFVNLHSTETQTAGVIDRWELLQAQ
ALSKELRMKQNLQKWQQFNSDLNSIWAWLGDTEEELEQLQRLELSTDIQTIELQ
IKKLKELQKAVDHRKAIILSINLCSPEFTQADSKESRDLQDRLXQMNGRWDRV
CSLLEEWRGLLQDALMQCQGFHEMSHGLLLMLENIDRRKNEIVPIDSNLDAEIL
QDHHKQLMQIKHELLESQLRVASLQDMSCQLLVNAEGTDCLEAKEKVHVIGNR
LKLLLKEVSRHIKELEKLLDVSSSQQDLSSWSSADELDTSGSVSPXSGRSTPNR
QKTPRGKCSLSQPGPS VSSPHSRSTKGGSDSSLSEPXPGRSGRGFLFRVLRAA
LPLQLLLLLLIGLACLVPMSEEDYSCALSNNFARSFHPMLRYTNGPPPL (SEQ ID
N0:726); MKLLGECSSSIDSVKRLEHKLKEEEESLPGFVNLHSTETQTAGVIDR
WELLQAQALSKELRMKQNLQKWQQFNSDLNSIWAWLGDTEEELEQLQRLELS
TDIQTIELQIK (SEQ ID N0:727); KLKELQKAVDHRKAIILS1NLCSPEFTQADSK
ESRDLQDRLXQMNGRWDRVCSLLEEWRGLLQDALMQCQGFHEMSHGLLLML
ENIDRRKNEIVPIDSNLDAEILQDHHKQLMQIKHELLESQLRVASLQDMSCQL
(SEQ ID N0:728); QDMSCQLLVNAEGTDCLEAKEKVHVIGNRLKLLLKEVS
RHIKELEKLLDVSSSQQDLSSWSSADELDTSGSVSPXSGRSTPNRQKTPRGKCS
LSQPGPSVSSPHS (SEQ ID N0:729); DSSLSEPXPGRSGRGFLFRVLRAAL
PLQLLLLLLIGLACLVPMSEEDYSCALSNNFARSFHPMLRYTNGPPPL {SEQ ID
N0:730). Also preferred are polynucleotide fragments encoding these polypeptide fragments. Furthermore, this gene maps to chromosome 6, and therefore, may be used as a marker in linkage analysis for chromosome 6 (See Accession No. N62896).
This gene is expressed in numerous tissues including the heart, kidney, and brain.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, musculoskeletal disorders including Muscular Dystrophy and cardiovascular diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the muscle tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to dystrophin indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of Muscular Dystrophy and other muscle disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 166 This gene is expressed primarily in human cerebellum.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the central nervous system, including Alzheimer's Disease, Parkinson's Disease, ALS, and mental illnesses. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 399 as residues: Pro-20 to Gly-26, Leu-37 to Pro-42, His-57 to Gly-63.
The tissue distribution indicates that the protein products of this gene are useful for treatment/diagnosis of diseases of the central nervous system and may protect or enhance survival of neuronal cells by slowing progression of neurodegenerative diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 167 Preferred polypeptides encoded by this gene comprise the following amino acid sequence:
MKLLICGNYLAPSHSESSRRCCLLCFYPLCLEINFGMKVFLSMPFLVLFQ
SLIQED (SEQ ID N0:731). Polynucleotides encoding such polypeptides are also provided. This gene is believed to reside on chromosome 15. Therefore polynucleotides derived from this gene are useful in linkage analysis as chromosome 15 markers.
This gene is expressed primarily in human testes tumor and to a lesser extent in normal human testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the testes, particularly cancer, and other reproductive disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the male reproductive tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for treatment/diagnosis of testicular diseases including cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 168 This gene is expressed primarily in fetal liver.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, conditions affecting hematopoietic development and metabolic diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the i32 hepatic system, and fetal hematopoietic system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 401 as residues: His-7 to Trp-17, Leu-19 to Lys-27, Pro-33 to Gly-44, Lys-68 to Gly-74, Lys-85 to Cys-95.
The tissue distribution indicates that the protein products of this gene are useful for treatment/diagnosis of diseases of the developing liver and hematopoietic system, and act as a growth differentiation factor for hematopoietic stem cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 169 The polypeptide encoded by this gene is believed to be a membrane bound receptor. The extracellular domain of which is expected to consist of the following amino acid sequence:
RILLVKYSANEENKYDYLPTTVNVCSELVKLVFCVLVSFCVIKKDHQSRNLKY
ASWKEFSDFMKWSIPAFLYFLDNLIVFYVLSYLQPAMAVIFSNFSIITTALLFRIV
LKXRLNWIQWASLLTLFLSIVALTAGTKTLQHNLAGRGFHHDAFFSPSNSCLL
FRNECPRKDNCTAKEWTFPEAKWNTTARVFSHIRLGMGHVLIIVQCFISSMANI
YNEKILKEGNQLTEXIFIQNSKLYFFGILFNGLTLGLQRSNRDQIKNCGFFYGH
S (SEQ ID N0:732). Thus, preferred polypeptides encoded by this gene comprise the extracellular domain as shown above. It will be recognized, however, that deletions of either end of the extracellular domain up to the first cysteine from the N-terminus and the first cysteine of the C-terminus, is expected to retain the biological functions of the full-length extracellular domain because the cysteines are thought to be responsible for providing secondary structure to the molecule. Thus, deletions of one or more amino acids from either end (or both ends) of the extracellular domain are contemplated. Of course, further deletions including the cysteines are also contemplated as useful as such polypeptides is expected to have immunological properties such as the ability to evoke and immune response. Polynucleotides encoding all of the foregoing polypeptides are provided.
This gene is expressed primarily in human osteoclastoma and to a lesser extent in hippocampus and chondrosarcoma.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers, particularly those of the bone and connective tissues. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the skeletal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 402 as residues: Met-1 to Cys-6, Ala-41 to Tyr-49, Lys-76 to Lys-84.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis of cancers of the bone and connective tissues, and may act as growth - factors for cells involved in bone or connective tissue growth.
FEATURES OF PROTEIN ENCODED BY GENE NO: 170 Preferred polypeptides encoded by this gene comprising the following amino acid sequence:
NSVPNLQTLAVLTEAIGPEPAIPRXPREPPVATSTPATPSAGPQPLPTGTV
LVPGGPAPPCLGEAWALLLPPCRPSLTSCFWSPRPSPWKETGV (SEQ ID
N0:733). Polynucleotides encoding such polypeptides are also provided herein.
This gene is expressed primarily in hematopoietic progenitor cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the blood including cancer and autoimmune disorders.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the blood/circulatory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 403 as residues: Gln-4 to His-10, Pro-25 to His-32.
The tissue distribution indicates that the protein products of this gene are useful for diagnosis of diseases involving growth differentiation of hematopoietic cells.
FEATURES OF PROTEIN ENCODED BY GENE NO: 171 Preferred polypeptides encoded by this gene comprise the following amino acid sequences: ALQLAFYPDAVEEWLEENVHPSLQRLQXLLQDLSEVSAPP (SEQ ID
N0:734); and/or CHPPALAGTLLRTPEGRAHARGLLLEAGGA (SEQ ID N0:735).
Polynucleotides encoding such polypeptides are also provided. The protein product of this gene shares sequence homology with metallothionines. Thus, polypeptide encoded by this gene are expected to have metallothionine activity, such activities are known in the art and described elsewhere herein.
This gene is expressed primarily in kidney cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases of the kidney including cancer and renal dysfunction.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the renal system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 404 as residues: Ser-47 to Gln-52.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of diseases of the kidney including kidney failure.
FEATURES OF PROTEIN ENCODED BY GENE NO: 172 This gene is expressed primarily in 12 week old early stage human.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing embryo, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i:e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 405 as residues: Gln-31 to Thr-43, Gly-51 to Ser-58, Pro-65 to Pro-72.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment/diagnosis of developmental problems with fetal tissue. The gene may be involved in vital organ development in the early stage, especially hematopoiesis, cardiovascular system, and neural development.
FEATURES OF PROTEIN ENCODED BY GENE NO: 173 The translation product of this gene shares sequence homology with TGN38, an integral membrane protein previously shown to be predominantly localized to the trans-Golgi network (TGN) of cells.
This gene is expressed primarily in developing embryo and to a lesser extent in cancer tissues including lymphoma, endometrial, protate and colon.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the developing fetus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 406 as residues: His-65 to Ser-72, Pro-82 to Gly-91, Pro-98 to Glu-118, Ser-126 to Gly-166, Pro-180 to Asp-188, Tyr-209 to Lys-214, Gln-220 to Leu-228.
The tissue distribution and homology to an integral membrane protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis of cancers and developmental abnormalities where aberrant expression relates to an abnormality.
FEATURES OF PROTEIN ENCODED BY GENE NO: 174 The translation product of this gene shares sequence homology with a dnaJ heat shock protein from E. coli which is allelic to sec63, a gene that affects transit of nascent secretory proteins across the endoplasmic reticulum in yeast.
This gene is expressed primarily in Hodgkin's lymphoma and to a lesser extent m testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 407 as residues: Thr-13 to Trp-21, Arg-74 to Asp-81.
The tissue distribution and homology to dnaJ indicates that polynucleotides and polypeptides corresponding to this gene are useful as a diagnostic for cancer including Hodgkin's lymphoma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 175 This gene is expressed primarily in endothelial cells and to a lesser extent in bone marrow stromal cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, diseases involving angiogenic abnormalities including diabetic retinopathy, macular degeneration, and other diseases including arteriosclerosis and cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for treating diseases where an increase or decrease in angiogenesis is indicated and as a factor in the wound healing process.
FEATURES OF PROTEIN ENCODED BY GENE NO: 176 The translation product of this gene shares sequence homology with MAT8 (mouse) which is thought to be important in regulating chloride conductance in cells (particularly in the breast) by modulating the response mediated by cAMP and protein kinase C to extracellular signals.
This gene is expressed primarily in amniotic cells and hematopoeitic cells including macrophages, Neutrophils, T cells, TNF induced aortic endothelium and to a lesser extent in testes, TNF induced epithelial cells, and smooth muscle.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, inflammatory responses mediated by T cells, macrophages, and/or neutrophils particularly those involving TNF, and also cancer. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 409 as residues: Thr-19 to Ala-33, Leu-54 to Asp-82, Pro-89 to Ala-97, Pro-to Lys-125, Ser-127 to Phe-135, Gly-164 to Leu-169, Cys-173 to Arg-178.
The tissue distribution and homology to mat-8 indicates that polynucleotides and polypeptides corresponding to this gene are useful for modifying inflammatory responses to cytokines such as TNF and thus modifying the duration and/or severity of inflammation. Polynucleotides and polypeptides derived from this gene are thought to be useful in the diagnosis and treatment of cancer.
FEATURES OF PROTEIN ENCODED BY GENE NO: 177 This gene is expressed primarily in endothelial cells.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, vascular restenosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating diseases associated with vascular response to injury such as vascular restenosis following angioplasty..
FEATURES OF PROTEIN ENCODED BY GENE NO: 178 One embodiment of the claimed invention comprises:
MRPDWKAGAGPGGPPQKPAPSSQRKPPARPSAAAAAIAVAAAEEERRLRQRN
RLRLEEDKPAVERCLEELVFGDVENDEDALLRRLRGPRVQEHEDSGDSEVENEA
KGNFPPQKKPV W VDEEDEDEEM V DMMNNRFRKDMMKNASES KLS KDNLKK
RLKEEFQHAMGGVPAWAETTKRKTSSDDESEEDEDDLLQRTGNFISTSTSLPRG
ILKMKNCQHANAERPTVARISICAVPSRCTDCDGCWD (SEQ ID N0:737); or CLEELVFGDVENDEDALLRRLRGPRVQEHEDSGDSEVENEAKGNFPPQKKPV
WVDEEDEDEEMVDMMNNRFRKDMMKNASESKLSKDNLKKRLKEEFQHAMG
GVPAWAETTKRKTSSDDESEEDEDDLLQRTGNFISTSTSLPRGILKMKNCQHA
NAERPTVARISICAVPSRCTDCDGC (SEQ ID NO: 738). LKEKIVRSFEVSPDGS
FLLINGIAGYLHLLAMKTKELIGSMKINGRVAASTFSSDSKKVYASSGDGEVYV
WDVNSRKCLNRFVDEGSLYGLSIATSRNGQYVACGSNCGVVNIYNQDSCLQE
TNPKPIKAIMNLVTGVTSLTFNPTTEILAIASEKMKEAVRLVHLPSCTVFSNFPVI
KNKNISHVHTMDFSPRSGYFALGNEKGKALMYRLHHYSDF (SEQ ID N0:739);
and/or KINGRVAASTFSSDSKKVYASSGDGEVYVWDVNSRKCLNRFVDEGSL
YGLSIATSRNGQYVACGSNCGVVNIYNQDSCLQETNPKPIKAIMNLVTGVTSLT
FNPTTEILAIASEKMKEAVRLVHLPSCTVFSNFPVIKNKNISHVHTMDFSPRSG
YFALGNEKGKAL (SEQ ID N0:740).
This gene is expressed primarily in epidydimus and endometrial tumors and to a lesser extent in T cell lymphoma and cell lines derived from colon cancer.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, tumors of the reproductive organs including testis and endometrial cells.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 411 as residues: Ser-67 to Lys-72, Val-87 to Leu-93, Tyr-128 to Pro-141, Asp-204 to Gly-210.
The tissue distribution indicates that the protein products of this gene are useful for treating tumors of the endometrium or epithelial tumors of the reproductive system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 179 Preferred polypeptides encoded by this gene comprise the following amino acid sequence:
MRILQLILLALATGLVGGETRIIKGFECKLHSQPWQAALFEKTRLLCGATLIAPR
WLLTAAHCLKPRYIVHLGQHNLQKEEGCEQTRTATESFPHPGFNNSLPNKDH
RNDIMLVKMASPVSITWAVRPLTLSSRCVTAGTSCSFPAGAARPDPSYACLTPC
DAPTSPSLSTRSVRTPTPATSQTPWCVPACRKGARTPARVTPGALWSVTSLFKA
LSPGARIRVRSPESLVSTRKSANMWTGSRRR (SEQ ID N0:741); ETRIIKGFEC
KLHSQPWQAALFEKTRLLCGATLIAPRWLLTAAHCLKPRYIVHLGQHNLQKEE
GCEQTRTATESFPHPGFNNSLPNKDHRNDIMLVKMASPVSITWAVRPLTLSSR
CVTAGTSCSFPAGAARPDPSYACLTPCDAPTSPSLSTRSVRTPTPATSQTPWCVP
ACRKGARTPARVTPGALWS VTSLFKALSPGARIRVRSPESLVSTRKSANMWTG
SRRR (SEQ ID N0:742); or CKLHSQPWQAALFEKTRLLCGATLIAPRWLLT
AAHCLKPRYIVHLGQHNLQKEEGCEQTRTATESFPHPGFNS
(SEQ ID N0:743). The translation product of this gene shares sequence homology with neuropsin a novel serine protease which is thought to be important in modulating extracellular signaling pathways in the brain. Owing to the structural similarity to other serine proteases the protein products of this gene are expected to have serine protease activity which may be assayed by methods known in the art and described elsewhere herein.
This gene is expressed primarily in endometrial tumor and to a lesser extent in colon cancer, benign hypertrophic prostate, and thymus.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers of the endometrium or colon and benign hypertrophy of the prostate. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the urogenital or reproductive systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 412 as residues: Gly-12 to Ser-22, Pro-34 to Ser-53.
The tissue distribution and homology to serine proteases indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosing or treating hperproliferative disorders such as cancer of the endometrium or colon and hyperplasia of the prostate.
FEATURES OF PROTEIN ENCODED BY GENE NO: 180 Preferred polypeptide encoded by this gene comprise the following amino acid sequence: VLQGRYFSPILEMRRLRPEGXXNLPGGSRAQKEPRQDLTLVLWPHC
PHFAMTRSYVPTKQCMVQGSFYCIFIFKGPVQNWC (SEQ ID N0:744).
Polynucleotides encoding such polypeptide are also provided.
This gene is expressed primarily in fetal brain Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, identifying and expanding stem cells in the CNS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that the protein products of this gene are useful for detecting and expanding stem cell populations in the (or of the) central nervous system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 181 This gene is expressed primarily in early stage human brain and a stromal cell line.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, developmental abnormalities of the CNS. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the central nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 414 as residues: Gln-42 to Gln-47, Gln-54 to Pro-60.
The tissue distribution indicates that the protein products of this gene play a role in the development of the central nervous system. Therefore this gene and its products are useful for diagnosing or treating developmental abnormalities of the central nervous system.
FEATURES OF PROTEIN ENCODED BY GENE NO: 182 Preferred polypeptides encoded by this gene comprise the following amino acid sequence:
MPIIDQVNPELHDFMQSAEVGTIFALSWLITWFGHVLSDFRHV VRLYDF
FLACHPLMPIYFAAVIVLYREQEVLDCDCDMASVHHLLSQIPQDLPYETLISRXE
TFLFSFPHPNLLGRPLPNSKLRGRQPLLSKTLSWHQPSRGLIWCCGSGXRGLL
RPEDRTKDVLTKPRTNRFVKLAVMGLTVALGAAALAVVKSALEWAPKFQLQL
FP (SEQ ID N0:745); or CPEFFIPATLPCPFVFAFTSEASSRAYLTQRGPGGLAQ
NLMPLPVGFWMGSLPPPWCWRKWVSEACSCFC (SEQ ID N0:746) These polypeptides are structurally similar to various TGF-beta family members.
Thus, this polypeptide is expected to have a variety of activities in the modulation of cell growth and proliferation.
This gene is expressed primarily in osteoclastoma, microvascular endothelium, and bone marrow derived cell lines.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, hematological diseases particularly involving aberrant proliferation of stem cells. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 415 as residues: Ser-33 to Ala-39.
The tissue distribution indicates that the protein products of this gene is useful for treating disorders of the progenitors of the immune system. Applications include in vivo expansion of progenitor cells, ex vivo expansion of progenitor cells, or the treatment of tumors of the circulatory system, such as lymphomas.
FEATURES OF PROTEIN ENCODED BY GENE NO: 183 This gene maps to chromosome 17 and therefore, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 17. In specific embodiments, polypeptides of the invention comprise the sequence:
GFGSVSAAGRRSGGTWQPVQ (SEQ ID N0:747); PGGLAVGSRWWSRSLT
(SEQ ID N0:748); LEPSRQRRPRRRGGTSRPETDQRAKCWRQL (SEQ ID
N0:749); and/or VCLRCQNRMEN (SEQ ID N0:750}. In further specific embodiments, polypeptides of the invention comprise the sequence: MAACTARRPGR
GQPLVVPVADXGPVAKAALCAAXAGAFSPASTTTTRRHLSSRNRPEGKVLETV
GVFEVPKQNGKYETGQLFLHSIFGYRGVVLFPWQARLXDRDVASAAPEKAEN
PAGHGSKEVKGKTHTYYQVLIDARDCPHISQRSQTEAVTFLANHDDSRALYAIP
GLDYVSHEDILPYTSTDQVPIQHELFERFLLYDQTKAPPFVARETLRAWQEKNH
PWLELSDVHRETTENIRVTVIPFYMGMREAQNSHVYWWRYCIRLENLDSDV VQ
LRERHWRIFSLSGTLETVRGRGVVGREPVLSKEQPAFQYSSHVSLQASSGHMW
GTFRFERPDGSHFDVRIPPFSLESNKDEKTPPSGLHW (SEQ ID N0:751 );
MAACTARRPGRGQPLVVPVADXGPVAKAALCAA (SEQ >D N0:752};
VLETVGVFEVPKQNGKYETGQLFLHSIFGYRGVVL (SEQ ID N0:757);
GLDYVSHEDILPYTST (SEQ ID N0:758); DVHRETTENIRVTVIPFYM (SEQ ID
N0:759); WWRYCIRLENLDSDVVQLRER (SEQ ID N0:760); and/or PAFQYSS
HVSLQASSGHMWGTFRFER (SEQ ID N0:761). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in gall bladder, prostate, and fetal brain, and to a lesser extent in a few tumor and fetal tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, growth related disorders such as cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate, gall bladder, and fetal brain, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of growth-related disorders, such cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 184 In specific embodiments, polypeptides of the invention comprise the sequence:SLCCPEGAEGC (SEQ ID N0:762) andlor QLKKTHYDRPCP (SEQ ID
N0:763). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in stromal cell, tonsil, and glioblastoma and to a lesser extent in some other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune and inflammatory disorders and glioblastoma. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the stromal cells, tonsil, and glioblastoma expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Additionally, it is believed that the product of this gene regulates pancreatic cell differentiation into beta cells. Accordingly, polynucleotides and polypeptides of the invention are useful in the treatment of insulin-dependent diabetes mellitus and associated conditions e.g. pancreatic hypofunction and the prevention, as well as the treatment of undifferentiated type pancreatic cancers.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 417 as residues: Pro-27 to Ala-32.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune and inflammatory disorders and glioblastoma.
FEATURES OF PROTEIN ENCODED BY GENE NO: 185 This gene is expressed primarily in hepatocellular carcinoma and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, liver diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above rissues or cells, particularly of the liver, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 418 as residues: Gly-32 to Lys-39.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of liver diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 186 This gene is expressed primarily in hippocampus and to a lesser extent in other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neutronal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the hippocampus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 187 This gene is expressed primarily in bone cancer and hippocampus and to a lesser extent in osteoclastoma and other tissues.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, bone-related disorders and neuronal diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the bone, ostoeclast, and hippocampus, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of bone-related disorders and neuronal diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 188 This gene maps to chromosome 4 and therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 4.
This gene is expressed primarily in neuronal tissues such as hippocampus, spinal cord, and hypothalamus and to a lesser extent in a few other tissues such as ovary.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 189 This gene maps to chromosome 10, therefore, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 10.
This gene is expressed primarily in neuronal tissues and immune tissues, and to a lesser extent in a few other tissues such as skin tumor, lung etc.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neuronal and immune-related disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the neuronal and immune-related tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 422 as residues: Pro-19 to Asp-25.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neuronal and immune-related disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 190 The translation product of this gene shares sequence homology with human N33, a gene located in a homozygously deleted region of human metastatic prostate cancer which is thought to be important in prevention of prostate cancer. In specific embodiments, polypeptides of the invention comprise the sequence:
AQRKKEMVLSEKVSQLMEWTNKRPVIRMNGDKFRRLVKAPPRNYSVIVMFTA
LQLHRQCVVCKQADEEFQILANSWRYSSAFTNRIFFAMVDFDEGSDVFQMLNM
NSAPTFINFPAKGKPKRGDTYELQVRGFSAEQIARWIADRTDVNIRVIRPPNMA
ARWRFWCVSVT (SEQ ID N0:765); MVVALLIVCDVPSAS (SEQ ID N0:766);
AQRKKEMVLSEKVSQL (SEQ ID N0:767); MEWTNKRPVIRMNGDKF (SEQ
ID:768); RRLVKAPPRNYSVIVMFTALQLHRQCVVCKQADEEFQILANSWRY
SSAF'TNRIFFA (SEQ ID N0:769); MVDFDEGSDVFQMLNMNSAPTFINFPAK
GKP (SEQ ID N0:770); KRGDTYELQVRGFSAEQIARWIADRTDVNIRVIRPPN
(SEQ ID N0:771); and/or YAGPLMLGLLLAVIGGLVYLRRVIWNFSLIKLDGLLQL
CVLCLL (SEQ ID N0:772). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in infant adrenal gland prostate cell line and to a lesser extent in a few other tissues Iike liver, smooth muscle etc.
Therefore, polynucleotides and polypeptides of the invention are-useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, prostate cancer and endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the prostate and adrenal gland, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 423 as residues: Pro-34 to Gly-43, Arg-113 to Pro-120.
The tissue distribution and homology to N33 indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment for prostate cancer and endocrine disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 191 This gene is expressed primarily in T cell and to a lesser extent in fetal lung.
Therefore, poIynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 424 as residues: Trp-3 to Phe-9.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 192 This gene maps to chromosome 6, therefore, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 6. Neural activity and neurotrophins induce synaptic remodeling in part by altering gene expression.
This gene is believed to be a glycosylphoshatidylinositol-anchored protein encoded by a hippocampal gene and to possess neural activity. This molecule is believed to be expressed in postmitotic-differentiating neurons of the developing nervous system and neuronal structures associated with plasticity in the adult. Message of this gene is believed to be induced by neuronal activity and by the activity-regulated neurotrophins BDNF and NT-3. The product of this gene is believed to stimulate neurite outgrowth and arborization in primary embryonic hippocampal and cortical cultures and to act as a downstream effector of activity-induced neurite outgrowth. In specific embodiments, polypeptides of the invention comprise the sequence: DAVFKGFSDCLLKLGDS (SEQ
ID N0:773); CQEGAKDMWDKLRKESKNLN (SEQ ID N0:774);
VLLVSLSAALATWLSF (SEQ ll~ N0:775); MGLKLNGRYISLILAVQIAYLVQAVR
AAGKCDAVFKGFSDCLLKLGDS (SEQ ID N0:776); PAAWDDKTNIKTVCTYW
EDFHSCTVTALTDCQEGAKDMWDKLRKESKNLNIQGSLFELCGSGNGAAGSL
LPAFPVLLVSLSAALATWLSF (SEQ ID N0:777); and/or MGLKLNGRYISLILA
VQIAYLVQAVRAAGKCDAVFKGFSDCLLKLGDSXXXXXPAAWDDKTNIKTVC
TYWEDFHSCTVTALTDCQEGAKDMWDKLRKESKNLNIQGSLFELCGSGNGAA
GSLLPAFPVLLVSLSAALATWLSF (SEQ ID N0:778). Polynucleotides encoding this polypeptide are also encompassed by the invention.
This gene is expressed primarily in human placenta, endometrial tumor and tissues of the central nervous system (CNS).
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, relating to reproductive disorders, cancers and neurological diseases.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and neurological disorders, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 425 as residues: Asp-47 to Asp-63, His-75 to Tyr-80, Pro-83 to Tyr-89.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of reproductive disorders such as endometrial tumors. Expression of this gene in tissues of the CNS
and its strong homology to Neuritin suggest that the protein product from this gene may also be used in the treatment and diagnosis of neurological disorders and in the regeneration of neural tissues, e.g., following injury.
FEATURES OF PROTEIN ENCODED BY GENE NO: 193 The translation product of this gene shares sequence homology with tenascin which is thought to be important in development. The translation product of this gene is believed to be a ligand of the fibroblast growth factor family. FGF ligand activity is known in the art and can be assayed by methods known in the art and disclosed elsewhere herein.
This gene is expressed primarily in endometrial tumors, and other types of tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancers. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer tissues, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 426 as residues: Gly-29 to Glu-34, Arg-71 to Arg-76, Thr-176 to Cys-182, Gly-184 to Glu-199.
The tissue distribution and homology to tenascin indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 194 In specific embodiments, polypeptides of the invention comprise the sequence:
MNSAAGFSHLDRRERVLKLGESFEKQPRCASTLC (SEQ ID N0:779).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in fetal human lung and neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, lung development and respiratory disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing irnmunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the respiratory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution in fetal lung and neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of lung and immunity related diseases, for example, lung cancer, viral, fungal or bacterial infections (e.g. lesions caused by tuberculosis), inflammation (e.g.
pneumonia), metabolic lesions etc.
FEATURES OF PROTEIN ENCODED BY GENE NO: 195 This gene is expressed primarily in breast lymph node.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immunal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of immunal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 196 This gene maps to chromosome 5 and accordingly, polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 5. The translation product of this gene shares sequence homology with human M-phase phosphoprotein 4 which is thought to be important in phosphorylation and signal transduction processes.
In specific embodiments, polypeptides of the invention comprise the sequence:
TIYPTEEELQAVQKIVSITERALKLVSD (SEQ ID N0:780}; RALKGVLRV
GVLAKGLLLRGDRNVNLVLLC (SEQ ID N0:781 ); ALAALRHAKWFQARAN
GLQSCVIIIRILRDLCQRVPTWS (SEQ ID N0:782); GDALRRVFECISSGIIL (SEQ
ID N0:783); LAFRQIHKVLGMDPLP (SEQ ID N0:784); and/or TIYPTEEELQAVQ
KIVSITERALKLVSDSLSEHEKNKNKEGDDKKEGGKDRALKGVLRVGVLAKG
LLLRGDRNVNLVLLCSEKPSKTLLSRIAENLPKQLAVISPEKYDIKCAVSEAAIIL
NSCVEPKMQVTITLTSPIIREENMREGDVTSGMVKDPPDVLDRQKCLDALAALR
HAKWFQARANGLQSCVIIIRILRDLCQRVPT'WSDFPSWAMELLVEKAISSASSP
QSPGDALRRVFECISSGITLKGSPGLLDPCEKDPFDTLATMTDQQREDITSSAQFA
LRLLAFRQIHKVLGMDPLPQMSQRFNIHNNRKRRRDSDGVDGFEAEGKKDKK
DYDNF (SEQ ID N0:785). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in Human Hippocampus and to a lesser extent in Prostate, Human Frontal Cortex.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, disorders related to reproductive system and nervous system.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive system and nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to human M-phase phosphoprotein 4 indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of reproductive and nervous system disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 197 In specific embodiments, polypeptides of the invention comprise the sequence:
MGSQHSAAARPSSCRRKQEDDRDG (SEQ ID N0:786);
LLAEREQEEAIAQFPYVEFTGRDSITCLTC (SEQ ID N0:787); and/or QGTGYIPTEQVNELVALIPHSDQRLRPQRTKQYV (SEQ ID N0:788).
Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in Human Primary Breast Cancer and to a lesser extent in Human Adult Spleen, Hodgkin's Lymphoma I, Salivary Gland.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, cancer and immunal disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the cancer and immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 430 as residues: Ser-126 to Gly-138.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and immunal disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 198 This gene is expressed primarily in monocytes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, blood cell disorders. Similarly, polypeptides and antibodies-directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue{s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of blood cell disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 199 This gene is expressed primarily in Human Ovary and Synovia and to a lesser extent in Human 8 Week Whole Embryo.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, reproductive and developmental disorders. Sinularly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and developmental system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of reproductive and developmental disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 200 This gene maps to chromosome 8 and therefore polynucleotides of the invention can be used in linkage analysis as a marker for chromosome 8. The translation product of this gene shares limited sequence homology with collagen proline rich domain.
This gene is expressed primarily in CNS.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, neurological diseases. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the nervous system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 433 as residues:
Pro-35 to Asp-41.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of neurological diseases.
FEATURES OF PROTEIN ENCODED BY GENE NO: 201 Translation product of this gene shares homology with a mammalian histone Hla protein. One embodiment for this gene is the polypeptide fragments comprising the following amino acid sequence: ARLNVGRESLKREMLKSQGVKVSESPMGAR
HSSWPEGAAFCKKVQGAQMQFPPRR (SEQ ID N0:789); ARLNVGRESLKR
EML (SEQ ID N0:790); LKSQGVKVSESPMGARHSSW (SEQ ID N0:791 );
AFCKKVQGAQMQFPPRR (SEQ ID N0:792). An additional embodiment is the polynucleotide fragments encoding these polypeptide (See Accession No.
pirfS24178) fragments.
This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are WO 98!54963 PCT/US98/11422 not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders.
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in vital immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such I S as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 202 This gene is expressed primarily in neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders.
Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
FEATURES OF PROTEIN ENCODED BY GENE NO: 203 ' This gene is expressed primarily in Neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, infectious disorders, immune disorders, and cancers.
Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 436 as residues: Thr-31 to Lys-36.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of infectious disorders, immune disorders, and cancers. Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions.
Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, and leukemia.
Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tumors and tissues.
FEATURES OF PROTEIN ENCODED BY GENE NO: 204 This gene maps to chromosome 16 and therefore polynucleotides of the invention can be used in linkage analysis as markers for chromosome 16. The translation product of this gene shares sequence homology with lactate dehydrogenase which is thought to be important in lactate metabolism.
This gene is expressed primarily in human tonsils and to a lesser extent in Spleen, and Neutrophils.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, immune disorders, infectious disorders, and cancers.
Similarly.
polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune disorders, infectious disorders, and cancers, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ ID NO: 437 as residues: Gly-7 to Ser-12.
The tissue distribution and homology to lactate dehydrogenase gene indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of immune disorders, infectious disorders, and cancers.
FEATURES OF PROTEIN ENCODED BY GENE NO: 205 The translation product of this gene shares sequence homology with Gcap 1 protein which is developmentally regulated in brain.
This gene is expressed primarily in placenta and endometrial tumor and to a lesser extent in several other tumors.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, vasculogenesis/angiogenesis and tumorigenesis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the vascular system and tumors, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution and homology to Gcap 1 protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of disorder or dysfunction of vascular system of tumorigenesis.
FEATURES OF PROTEIN ENCODED BY GENE NO: 206 In specific embodiments, polypeptides of the invention comprise the sequence MPYAQWLAENDRFEEAQKAFHKAGRQREA (SEQ ID N0:799);
VQVLEQLTNNAVAESRFNDAAYYYWMLSMQCLDIAQD (SEQ ID N0:794);
PAQKDTMLGKFYHFQRLAELYHGYHAIHRHTEDP (SEQ ID NO: 795);
FSVHRPETLFNISRFLLHSLPKDTPSGISKVKILFT (SEQ ID N0:800);
LAKQSKALGAYRLARHAYDKLRGLYIP (SEQ ID N0:796); ARFQKSIELG
TLTIRAKPFHDSEELVPLCYRCSTNN (SEQ ID NO: 797); andlor PLLNNLGNVC
INCRQPFIF'SASSYDVLHLVEFYLEEGITDEEAISLIDLEVLRPKRDDRQLEICKQQ
LPDSCG (SEQ ID N0:798). Polynucleotides encoding these polypeptides are also encompassed by the invention.
This gene is expressed primarily in testes.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, male reproductive and endocrine disorders. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the reproductive and endocrine systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment of male reproductive and endocrine disorders.
FEATURES OF PROTEIN ENCODED BY GENE NO: 207 This gene is expressed in fetal lung.
Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissues) or cell types) present in a biological sample and for diagnosis of diseases and conditions, which include, but are not limited to, lung diseases such as cystic fibrosis. Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissues) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the respiratory system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder. Preferred epitopes include those comprising a sequence shown in SEQ
ID
NO: 440 as residues: Tyr-49 to Cys-54.
The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for detection and treatment of disorders associated with developing lungs particularly in premature infants where the lungs are the last tissues to develop. The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and intervention of lung tumors since the gene may be involved in the regulation of cell division, particularly since it is expressed in fetal tissue. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
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Table 1 summarizes the information corresponding to each "Gene No." described above. The nucleotide sequence identified as "NT SEQ ID NO:X" was assembled from partially homologous ("overlapping") sequences obtained from the "cDNA clone ID"
identified in Table 1 and, in some cases, from additional related DNA clones.
The overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X.
The cDNA Clone ID was deposited on the date and given the corresponding deposit number listed in "ATCC Deposit No:Z and Date." Some of the deposits contain multiple different clones corresponding to the same gene. "Vector" refers to the type of vector contained in the cDNA Clone ID.
"Total NT Seq." refers to the total number of nucleotides in the contig identified by "Gene No." The deposited clone may contain all or most of these sequences, reflected by the nucleotide position indicated as "5' NT of Clone Seq." and the "3' NT
of Clone Seq." of SEQ ID NO:X. The nucleotide position of SEQ ID NO:X of the putative start codon (rnethionine) is identified as "5' NT of Start Codon."
Similarly , the nucleotide position of SEQ ID NO:X of the predicted signal sequence is identified as "5' NT of First AA of Signal Pep."
The translated amino acid sequence, beginning with the methionine, is identified as "AA SEQ ID NO:Y," although other reading frames can also be easily translated using known molecular biology techniques. The polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.
The first and last amino acid position of SEQ ID NO:Y of the predicted signal peptide is identified as "First AA of Sig Pep" and "Last AA of Sig Pep." The predicted first amino acid position of SEQ ID NO:Y of the secreted portion is identified as "Predicted First AA of Secreted Portion." Finally, the amino acid position of SEQ ID
NO:Y of the last amino acid in the open reading frame is identified as "Last AA of ORF."
SEQ ID NO:X and the translated SEQ ID NO:Y are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, SEQ ID NO:X is useful for designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA
contained in the deposited clone. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling a variety of forensic and diagnostic ' 35 methods of the invention. Similarly, polypeptides identified from SEQ ID
NO:Y may be used to generate antibodies which bind specifically to the secreted proteins encoded by the cDNA clones identified in Table 1.
Nevertheless, DNA sequences generated by sequencing reactions can contain sequencing errors. The errors exist as misidentified nucleotides, or as insertions or deletions of nucleotides in the generated DNA sequence. The erroneously inserted or deleted nucleotides cause frame shifts in the reading frames of the predicted amino acid sequence. In these cases, the predicted amino acid sequence diverges from the actual amino acid sequence, even though the generated DNA sequence may be greater than 99.9% identical to the actual DNA sequence (for example, one base insertion or deletion in an open reading frame of over 1000 bases).
Accordingly, for those applications requiring precision in the nucleotide sequence or the amino acid sequence, the present invention provides not only the generated nucleotide sequence identified as SEQ ID NO:X and the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA
containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1. The nucleotide sequence of each deposited clone can readily be determined by sequencing the deposited clone in accordance with known methods. The predicted amino acid sequence can then be verified from such deposits. Moreover, the amino acid sequence of the protein encoded by a particular clone can also be directly determined by peptide sequencing or by expressing the protein in a suitable host cell containing the deposited human cDNA, collecting the protein, and determining its sequence.
The present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, or the deposited clone. The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein.
Such methods include preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.
Also provided in the present invention are species homologs. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source for the desired homologue.
The polypeptides of the invention can be prepared in any suitable manner. Such polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or polypeptides produced by a combination of these methods. Means for preparing such polypeptides are well understood in the art.
The polypeptides may be in the form of the secreted protein, including the mature form, or may be a part of a larger protein, such as a fusion protein (see below).
It is often advantageous to include an additional amino acid sequence which contains secretory or leader sequences, pro-sequences, sequences which aid in purification , such as multiple histidine residues, or an additional sequence for stability during recombinant production.
The polypeptides of the present invention are preferably provided in an isolated form, and preferably are substantially purified. A recombinantly produced version of a polypeptide, including the secreted polypeptide, can be substantially purified by the one-step method described in Smith and Johnson, Gene 67:31-40 (1988).
Polypeptides of the invention also can be purified from natural or recombinant sources using antibodies of the invention raised against the secreted protein in methods which are well known in the art.
Signal Seauences Methods for predicting whether a protein has a signal sequence, as well as the cleavage point for that sequence, are available. For instance, the method of McGeoch, Virus Res. 3:271-286 ( 1985), uses the information from a short N-terminal charged region and a subsequent uncharged region of the complete (uncleaved) protein.
The method of von Heinje, Nucleic Acids Res. 14:4683-4690 ( 1986) uses the information from the residues surrounding the cleavage site, typically residues -13 to +2, where +1 indicates the amino terminus of the secreted protein. The accuracy of predicting the cleavage points of known mammalian secretory proteins for each of these methods is in the range of 75-80%. (von Heinje, supra.) However, the two methods do not always produce the same predicted cleavage points) for a given protein.
In the present case, the deduced amino acid sequence of the secreted polypeptide was analyzed by a computer program called SignalP (Henrik Nielsen et al., Protein Engineering 10:1-6 (1997)), which predicts the cellular location of a protein based on the amino acid sequence. As part of this computational prediction of localization, the methods of McGeoch and von Heinje are incorporated. The analysis of the amino acid sequences of the secreted proteins described herein by this program provided the results shown in Table 1.
As one of ordinary skill would appreciate, however, cleavage sites sometimes vary from organism to organism and cannot be predicted with absolute certainty.
Accordingly, the present invention provides secreted polypeptides having a sequence shown in SEQ ID NO:Y which have an N-terminus beginning within 5 residues (i.e., +
or - 5 residues) of the predicted cleavage point. Similarly, it is also recognized that in some cases, cleavage of the signal sequence from a secreted protein is not entirely uniform, resulting in more than one secreted species. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention.
Moreover, the signal sequence identified by the above analysis may not necessarily predict the naturally occurring signal sequence. For example, the naturally occurring signal sequence may be further upstream from the predicted signal sequence.
However, it is likely that the predicted signal sequence will be capable ofdirecting the secreted protein to the ER. These polypeptides, and the polynucleotides encoding such polypeptides, are contemplated by the present invention.
PolYnucleotide and Polypeptide Variants "Variant" refers to a polynucleotide or polypeptide differing from the polynucleotide or polypeptide of the present invention, but retaining essential properties thereof. Generally, variants are overall closely similar, and, in many regions, identical to the polynucleotide or polypeptide of the present invention.
By a polynucleotide having a nucleotide sequence at least, for example, 95%
"identical" to a reference nucleotide sequence of the present invention, it is intended that the nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence encoding the polypeptide.
In other words, to obtain a polynucleotide having a nucleotide sequence at least 95%
identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. The query sequence may be an entire sequence shown inTable l, the ORF
(open reading frame), or any fragement specified as described herein.
As a practical matter, whether any particular nucleic acid molecule or polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to a nucleotide sequence of the presence invention can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB
computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci.
( 1990) b:237-245). In a sequence alignment the query and subject sequences are both DNA
sequences. An RNA sequence can be compared by converting U's to T's. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB alignment of DNA sequences to calculate percent identiy are:
Matrix=Unitary, k-tuple=4, Mismatch Penalty=1, Joining Penalty=30, Randomization Group Length=0, Cutoff Score=1, Gap Penalty=5, Gap Size Penalty 0.05, Window Size=500 or the lenght of the subject nucleotide sequence, whichever is shorter.
If the subject sequence is shorter than the query sequence because of 5' or 3' deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for 5' and 3' truncations of the subject sequence when calculating percent identity. For subject sequences truncated at the 5' or 3' ends, relative to the the query sequence, the percent identity is corrected by calculating the number of bases of the query sequence that are 5' and 3' of the subject sequence, which are not matched/aligned, as a percent of the total bases of the query sequence. Whether a nucleotide is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This corrected score is what is used for the purposes of the present invention. Only bases outside the 5' and 3' bases of the subject sequence, as displayed by the FASTDB alignment, which are not matched/aligned with the query sequence, are calculated for the purposes of manually adjusting the percent identity score.
For example, a 90 base subject sequence is aligned to a 100 base query sequence to determine percent identity. The deletions occur at the 5' end of the subject sequence and therefore, the FASTDB alignment does not show a matched/alignement of the first 10 bases at 5' end. The 10 unpaired bases represent 10% of the sequence (number of bases at the 5' and 3' ends not matched/total number of bases in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 bases were perfectly matched the final percent identity would be 90%. In another example, a 90 base subject sequence is compared with a 100 base query sequence. This time the deletions are internal deletions so that there are no bases on the S' or 3' of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only bases 5' and 3' of the subject sequence which are not matched/aligned with the query sequnce are manually corrected for. No other manual - corrections are to made for the purposes of the present invention.
By a polypeptide having an amino acid sequence at least, for example, 95%
"identical" to a query amino acid sequence of the present invention, it is intended that the amino acid sequence of the subject polypeptide is identical to the query sequence except that the subject polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a query WO 98/54963 PCT/(JS98/11422 amino acid sequence, up to 5% of the amino acid residues in the subject sequence may be inserted, deleted, (indels) or substituted with another amino acid. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the reference sequence.
As a practical matter, whether any particular polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, the anuno acid sequences shown in Table 1 or to the amino acid sequence encoded by deposited DNA clone can be determined conventionally using known computer programs. A preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. ( 1990) 6:237-245). In a sequence alignment the query and subject sequences are either both nucleotide sequences or both amino acid sequences.
The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2, Mismatch Penalty=l, Joining Penalty=20, Randomization Group Length=0, Cutoff Score=1, Window Size=sequence length, Gap Penalty=S, Gap Size Penalty=0.05, Window Size=500 or the length of the subject amino acid sequence, whichever is shorter.
If the subject sequence is shorter than the query sequence due to N- or C-terminal deletions, not because of internal deletions, a manual correction must be made to the results. This is becuase the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity.
For subject sequences truncated at the N- and C-termini, relative to the the query sequence, the percent identity is corrected by calculating the number of residues of the query sequence that are N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence. Whether a residue is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score is what is used for the purposes of the present invention. Only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score.
That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence.
For example, a 90 amino acid residue subject sequence is aligned with a 100 residue query sequence to determine percent identity. The deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining residues were perfectly matched the final percent identity would be 90%. In another example, a 90 residue subject sequence is compared with a 100 residue query sequence.
This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query.
In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only residue positions outside the N- and C-terminal ends of the subject sequence, as displayed in the FASTDB alignment, which are not matched/aligned with the query sequnce are manually corrected for. No other manual corrections are to made for the purposes of the present invention.
The variants may contain alterations in the coding regions, non-coding regions, or both. Especially preferred are polynucleotide variants containing alterations which produce silent substitutions, additions, or deletions, but do not alter the properties or activities of the encoded polypeptide. Nucleotide variants produced by silent substitutions due to the degeneracy of the genetic code are preferred.
Moreover, variants in which 5-10, 1-5, or 1-2 amino acids are substituted, deleted, or added in any combination are also preferred. Polynucleotide variants can be produced for a variety of reasons, e.g., to optimize codon expression for a particular host (change codons in the human mRNA to those preferred by a bacterial host such as E. coli).
Naturally occurring variants are called "allelic variants," and refer to one of several alternate forms of a gene occupying a given locus on a chromosome of an organism. (Genes II, Lewin, B., ed., John Wiley & Sons, New York (1985).) These allelic variants can vary at either the polynucleotide and/or polypeptide level.
Alternatively, non-naturally occurring variants may be produced by mutagenesis techniques or by direct synthesis.
Using known methods of protein engineering and recombinant DNA
technology, variants may be generated to improve or alter the characteristics of the polypeptides of the present invention. For instance, one or more amino acids can be deleted from the N-terminus or C-terminus of the secreted protein without substantial loss of biological function. The authors of Ron et al., J. Biol. Chem. 268:
(1993), reported variant KGF proteins having heparin binding activity even after deleting 3, 8, or 27 amino-terminal amino acid residues. Similarly, Interferon gamma exhibited up to ten times higher activity after deleting 8-10 amino acid residues from the carboxy terminus of this protein. (Dobeli et al., J. Biotechnology 7:199-216 (1988).) Moreover, ample evidence demonstrates that variants often retain a biological activity similar to that of the naturally occurring protein. For example, Gayle and coworkers (J. Biol. Chem 268:22105-22111 (1993)) conducted extensive mutational analysis of human cytokine IL-la. They used random mutagenesis to generate over 3,500 individual IL-la mutants that averaged 2.5 amino acid changes per variant over the entire length of the molecule. Multiple mutations were examined at every possible amino acid position. The investigators found that "[m]ost of the molecule could be altered with little effect on either [binding or biological activity]." (See, Abstract.) In fact, only 23 unique amino acid sequences, out of more than 3,500 nucleotide sequences examined, produced a protein that significantly differed in activity from wild-type.
Furthermore, even if deleting one or more amino acids from the N-terminus or C-terminus of a polypeptide results in modification or loss of one or more biological functions, other biological activities may still be retained. For example, the ability of a deletion variant to induce and/or to bind antibodies which recognize the secreted form wilt likely be retained when less than the majority of the residues of the secreted form are removed from the N-terminus or C-terminus. Whether a particular polypeptide lacking N- or C-terminal residues of a protein retains such immunogenic activities can readily be determined by routine methods described herein and otherwise known in the art.
Thus, the invention further includes polypeptide variants which show substantial biological activity. Such variants include deletions, insertions, inversions, repeats, and substitutions selected according to general rules known in the art so as have little effect on activity. For example, guidance concerning how to make phenotypically silent amino acid substitutions is provided in Bowie, J. U. et al., Science 247:1306-1310 (1990), wherein the authors indicate that there are two main strategies for studying the tolerance of an amino acid sequence to change.
The first strategy exploits the tolerance of amino acid substitutions by natural selection during the process of evolution. By comparing amino acid sequences in different species, conserved amino acids can be identified. These conserved amino acids are likely important for protein function. In contrast, the amino acid positions where substitutions have been tolerated by natural selection indicates that these positions are not critical for protein function. Thus, positions tolerating amino acid substitution could be modified while still maintaining biological activity of the protein.
The second strategy uses genetic engineering to introduce amino acid changes at specific positions of a cloned gene to identify regions critical for protein function. For example, site directed mutagenesis or alanine-scanning mutagenesis (introduction of single alanine mutations at every residue in the molecule) can be used.
{Cunningham and Wells, Science 244:1081-1085 (1989).) The resulting mutant molecules can then be tested for biological activity.
As the authors state, these two strategies have revealed that proteins are surprisingly tolerant of amino acid substitutions. The authors further indicate which amino acid changes are likely to be permissive at certain amino acid positions in the protein. For example, most buried (within the tertiary structure of the protein) amino acid residues require nonpolar side chains, whereas few features of surface side chains are generally conserved. Moreover, tolerated conservative amino acid substitutions involve replacement of the aliphatic or hydrophobic amino acids Ala, Val, Leu and Ile;
replacement of the hydroxyl residues Ser and Thr; replacement of the acidic residues i 5 Asp and Glu; replacement of the amide residues Asn and Gln, replacement of the basic residues Lys, Arg, and His; replacement of the aromatic residues Phe, Tyr, and Trp, and replacement of the small-sized amino acids Ala, Ser, Thr, Met, and Gly.
Besides conservative amino acid substitution, variants of the present invention include (i) substitutions with one or more of the non-conserved amino acid residues, where the substituted amino acid residues may or may not be one encoded by the genetic code, or (ii) substitution with one or more of amino acid residues having a substituent group, or (iii) fusion of the mature polypeptide with another compound, such as a compound to increase the stability and/or solubility of the polypeptide (for example, polyethylene glycol), or (iv) fusion of the polypeptide with additional amino acids, such as an IgG Fc fusion region peptide, or leader or secretory sequence, or a sequence facilitating purification. Such variant polypeptides are deemed to be within the scope of those skilled in the art from the teachings herein.
For example, polypeptide variants containing amino acid substitutions of charged amino acids with other charged or neutral amino acids may produce proteins with improved characteristics, such as less aggregation. Aggregation of pharmaceutical formulations both reduces activity and increases clearance due to the aggregate's immunogenic activity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967);
Robbins et al., Diabetes 36: 838-845 ( 1987); Cleland et al., Crit. Rev.
Therapeutic Drug Carrier Systems 10:307-377 (1993).) Polynucleotide and Polypeptide Fr~ments In the present invention, a "polynucleotide fragment" refers to a short polynucleotide having a nucleic acid sequence contained in the deposited clone or shown in SEQ ID NO:X. The short nucleotide fragments are preferably at least about 15 nt, and more preferably at least about 20 nt, still more preferably at least about 30 nt, and even more preferably, at least about 40 nt in length. A fragment "at Ieast 20 nt in length," for example, is intended to include 20 or more contiguous bases from the cDNA sequence contained in the deposited clone or the nucleotide sequence shown in SEQ ID NO:X. These nucleotide fragments are useful as diagnostic probes and primers as discussed herein. Of course, larger fragments (e.g., 50, 150, 500, 600, nucleotides) are preferred.
Moreover, representative examples of polynucleotide fragments of the invention, include, for example, fragments having a sequence from about nucleotide - number 1-50, 51-100, 101-150, 151-200, 201-250, 25I-300, 301-350, 351-400, 450, 451-500, 501-550, 551-600, 651-700, 701-750, 751-800, 800-850, 851-900, 901-950, 951-1000, 1001-1050, 1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951-2000, or 2001 to the end of SEQ ID NO:X or the cDNA contained in the deposited clone. In this context "about" includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1 ) nucleotides, at either terminus or at both termini.
Preferably, these fragments encode a polypeptide which has biological activity. More preferably, these polynucleotides can be used as probes or primers as discussed herein.
In the present invention, a "polypeptide fragment" refers to a short amino acid sequence contained in SEQ ID NO:Y or encoded by the cDNA contained in the deposited clone. Protein fragments may be "free-standing," or comprised within a larger polypeptide of which the fragment forms a part or region, most preferably as a single continuous region. Representative examples of polypeptide fragments of the invention, include, for example, fragments from about amino acid number 1-20, 2I-40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, or 161 to the end of the coding region. Moreover, polypeptide fragments can be about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 amino acids in length. In this context "about"
includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1 ) amino acids, at either extreme or at both extremes.
Preferred polypeptide fragments include the secreted protein as well as the mature form. Further preferred polypeptide fragments include the secreted protein or the mature form having a continuous series of deleted residues from the amino or the carboxy terminus, or both. For example, any number of amino acids, ranging from 1-60, can be deleted from the amino terminus of either the secreted polypeptide or the mature form. Similarly, any number of amino acids, ranging from 1-30, can be deleted from the carboxy terminus of the secreted protein or mature form. Furthermore, any combination of the above amino and carboxy terminus deletions are preferred.
Similarly, polynucleotide fragments encoding these polypeptide fragments are also preferred.
Particularly, N-terminal deletions of the polypeptide of the present invention can be described by the general formula m-p, where p is the total number of amino acids in the polypeptide and m is an integer from 2 to (p-1), and where both of these integers (m & p) correspond to the position of the amino acid residue identified in SEQ ID
NO:Y.
Moreover, C-terminal deletions of the polypeptide of the present invention can also be described by the general formula 1-n, where n is an integer from 2 to (p-1), and again where these integers (n & p) correspond to the position of the amino acid residue identified in SEQ ID NO:Y.
The invention also provides polypeptides having one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m-n of SEQ ID NO:Y, where m and n are integers as described above.
Also preferred are polypeptide and polynucleotide fragments characterized by structural or functional domains, such as fragments that comprise alpha-helix and alpha-helix forming regions, beta-sheet and beta-sheet-forming regions, turn and turn-forming regions, coil and coil-forming regions, hydrophilic regions, hydrophobic regions, alpha amphipathic regions, beta amphipathic regions, flexible regions, surface-forming regions, substrate binding region, and high antigenic index regions.
Polypeptide fragments of SEQ ID NO: Y falling within conserved domains are specifically contemplated by the present invention. Moreover, polynucleotide fragments encoding these domains are also contemplated.
Other preferred fragments are biologically active fragments. Biologically active fragments are those exhibiting activity similar, but not necessarily identical, to an activity of the polypeptide of the present invention. The biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity.
E hopes & Antibodies In the present invention, "epitopes" refer to polypeptide fragments having antigenic or immunogenic activity in an animal, especially in a human. A
preferred embodiment of the present invention relates to a polypeptide fragment comprising an W O 98!54963 PCT/US98/i 1422 epitope, as well as the polynucleotide encoding this fragment. A region of a protein molecule to which an antibody can bind is defined as an "antigenic epitope."
In contrast, an "immunogenic epitope" is defined as a part of a protein that elicits an antibody response. (See, for instance, Geysen et al., Proc. Natl. Acad. Sci.
USA
81:3998- 4002 (1983).) Fragments which function as epitopes may be produced by any conventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985) further described in U.S. Patent No. 4,631,211.) In the present invention, antigenic epitopes preferably contain a sequence of at least seven, more preferably at least nine, and most preferably between about 15 to about 30 amino acids. Antigenic epitopes are useful to raise antibodies, including monoclonal antibodies, that specifically bind the epitope. (See, for instance, Wilson et al., Cell 37:767-778 ( 1984); Sutcliffe, J. G. et al., Science 219:660-666 ( 1983).) Similarly, immunogenic epitopes can be used to induce antibodies according to methods well known in the art. (See, for instance, SutcIiffe et al., supra;
Wilson et al., supra; Chow, M. et al., Proc. Natl. Acad. Sci. USA 82:910-914; and Bittle, F.
J. et al., J. Gen. Virol. 66:2347-2354 ( 1985).) A preferred immunogenic epitope includes the secreted protein. The immunogenic epitopes may be presented together with a carrier protein, such as an albumin, to an animal system (such as rabbit or mouse) or, if it is long enough (at least about 25 amino acids), without a carrier. However, immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to raise antibodies capable of binding to, at the very least, linear epitopes in a denatured polypeptide (e.g., in Western blotting.) As used herein, the term "antibody" (Ab) or "monoclonal antibody" (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab')2 fragments) which are capable of specifically binding to protein. Fab and F(ab')2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody.
(Wahl et al., J. Nucl. Med. 24:316-325 (1983).) Thus, these fragments are preferred, as well as the products of a FAB or other immunoglobulin expression library.
Moreover, antibodies of the present invention include chimeric, single chain, and humanized antibodies.
Fusion Proteins Any polypeptide of the present invention can be used to generate fusion proteins. For example, the polypeptide of the present invention, when fused to a second protein, can be used as an antigenic tag. Antibodies raised against the DEMANDES OU BREVETS VOLUMINEUX
LA PRESE1NTE PART1E DE C~TTE DEMANDE OU C~ BREVET
COMPREND PLUS D'UN TOME.
CECt EST LE TOME . ~ DE
NOTE: Pour tes tomes additionels, veuitlez contacter le Bureau canadien des brevets 'JUMBO APP1.lCATIONS/PATENTS -THIS SECT10N OF THE APPUCAT10N/PATENT CONTAINS MORE' THAN ONE VOLUME ~ , , THfS tS VOLUME _ 01=
' NOTE: Eor additional volumes-piease~contact the Canadian Patent Office .
Claims (23)
1. An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:
(a) a polynucleotide fragment of SEQ ID NO:X or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X;
(b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:Y or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(c) a polynucleotide encoding a polypeptide domain of SEQ ID NO:Y or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(d) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:Y or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(e) a polynucleotide encoding a polypeptide of SEQ ID NO:Y or the eDNA
sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X, having biological activity;
(f) a polynucleotide which is a variant of SEQ ID NO:X;
(g) a polynucleotide which is an allelic variant of SEQ ID NO:X;
(h) a polynucleotide which encodes a species homologue of the SEQ ID NO:Y;
(i) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(h), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or of only T residues.
(a) a polynucleotide fragment of SEQ ID NO:X or a polynucleotide fragment of the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X;
(b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO:Y or a polypeptide fragment encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(c) a polynucleotide encoding a polypeptide domain of SEQ ID NO:Y or a polypeptide domain encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(d) a polynucleotide encoding a polypeptide epitope of SEQ ID NO:Y or a polypeptide epitope encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X;
(e) a polynucleotide encoding a polypeptide of SEQ ID NO:Y or the eDNA
sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X, having biological activity;
(f) a polynucleotide which is a variant of SEQ ID NO:X;
(g) a polynucleotide which is an allelic variant of SEQ ID NO:X;
(h) a polynucleotide which encodes a species homologue of the SEQ ID NO:Y;
(i) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(h), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or of only T residues.
2. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding a secreted protein.
3. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding the sequence identified as SEQ ID NO:Y or the polypeptide encoded by the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ ID NO:X.
4. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises the entire nucleotide sequence of SEQ ID
NO:X or the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X.
NO:X or the cDNA sequence included in ATCC Deposit No:Z, which is hybridizable to SEQ
ID
NO:X.
. The isolated nucleic acid molecule of claim 2, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.
6. The isolated nucleic acid molecule of claim 3, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.
7. A recombinant vector comprising the isolated nucleic acid molecule of claim 1.
8. A method of making a recombinant host cell comprising the isolated nucleic acid molecule of claim 1.
9. A recombinant host cell produced by the method of claim 8.
10. The recombinant host cell of claim 9 comprising vector sequences.
11. An isolated polypeptide comprising an amino acid sequence at least 95%
identical to a sequence selected from the group consisting of:
(a) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(b) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z, having biological activity;
(c) a polypeptide domain of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(d) a polypeptide epitope of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(e) a secreted form of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(f) a full length protein of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(g) a variant of SEQ ID NO:Y;
(h) an allelic variant of SEQ ID NO:Y; or (i) a species homologue of the SEQ ID NO:Y.
identical to a sequence selected from the group consisting of:
(a) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(b) a polypeptide fragment of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z, having biological activity;
(c) a polypeptide domain of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(d) a polypeptide epitope of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(e) a secreted form of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(f) a full length protein of SEQ ID NO:Y or the encoded sequence included in ATCC Deposit No:Z;
(g) a variant of SEQ ID NO:Y;
(h) an allelic variant of SEQ ID NO:Y; or (i) a species homologue of the SEQ ID NO:Y.
12. The isolated polypeptide of claim 11, wherein the secreted form or the full length protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus.
13. An isolated antibody that binds specifically to the isolated polypeptide of claim 11.
14. A recombinant host cell that expresses the isolated polypeptide of claim 11.
15. A method of making an isolated polypeptide comprising:
(a) culturing the recombinant host cell of claim 14 under conditions such that said polypeptide is expressed; and (b) recovering said polypeptide.
(a) culturing the recombinant host cell of claim 14 under conditions such that said polypeptide is expressed; and (b) recovering said polypeptide.
16. The polypeptide produced by claim 15.
17. A method for preventing, treating, or ameliorating a medical condition, comprising administering to a mammalian subject a therapeutically effective amount of the polypeptide of claim 11 or the polynucleotide of claim 1.
18. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:
(a) determining the presence or absence of a mutation in the polynucleotide of claim 1; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.
(a) determining the presence or absence of a mutation in the polynucleotide of claim 1; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.
19. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:
(a) determining the presence or amount of expression of the polypeptide of claim 11 in a biological sample; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.
(a) determining the presence or amount of expression of the polypeptide of claim 11 in a biological sample; and (b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.
20. A method for identifying a binding partner to the polypeptide of claim 11 comprising:
(a) contacting the polypeptide of claim 11 with a binding partner; and (b) determining whether the binding partner effects an activity of the polypeptide.
(a) contacting the polypeptide of claim 11 with a binding partner; and (b) determining whether the binding partner effects an activity of the polypeptide.
21. The gene corresponding to the cDNA sequence of SEQ ID NO:Y.
22. A method of identifying an activity in a biological assay, wherein the method comprises:
(a) expressing SEQ ID NO:X in a cell;
(b) isolating the supernatant;
(c) detecting an activity in a biological assay; and (d) identifying the protein in the supernatant having the activity.
(a) expressing SEQ ID NO:X in a cell;
(b) isolating the supernatant;
(c) detecting an activity in a biological assay; and (d) identifying the protein in the supernatant having the activity.
23. The product produced by the method of claim 22.
Applications Claiming Priority (147)
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| US5776597P | 1997-09-05 | 1997-09-05 | |
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| US5765197P | 1997-09-05 | 1997-09-05 | |
| US5766897P | 1997-09-05 | 1997-09-05 | |
| US5776997P | 1997-09-05 | 1997-09-05 | |
| US5776497P | 1997-09-05 | 1997-09-05 | |
| US60/057,645 | 1997-09-05 | ||
| US60/057,770 | 1997-09-05 | ||
| US60/057,584 | 1997-09-05 | ||
| US60/057,648 | 1997-09-05 | ||
| US60/057,643 | 1997-09-05 | ||
| US60/057,771 | 1997-09-05 | ||
| US60/057,627 | 1997-09-05 | ||
| US60/057,646 | 1997-09-05 | ||
| US60/057,635 | 1997-09-05 | ||
| US60/057,778 | 1997-09-05 | ||
| US60/057,650 | 1997-09-05 | ||
| US60/057,644 | 1997-09-05 | ||
| US60/057,765 | 1997-09-05 | ||
| US60/057,666 | 1997-09-05 | ||
| US60/057,769 | 1997-09-05 | ||
| US60/057,763 | 1997-09-05 | ||
| US60/057,651 | 1997-09-05 | ||
| US60/057,642 | 1997-09-05 | ||
| US60/057,762 | 1997-09-05 | ||
| US60/057,654 | 1997-09-05 | ||
| US60/057,775 | 1997-09-05 | ||
| US60/057,661 | 1997-09-05 | ||
| US60/057,634 | 1997-09-05 | ||
| US60/057,760 | 1997-09-05 | ||
| US60/057,764 | 1997-09-05 | ||
| US60/057,647 | 1997-09-05 | ||
| US60/057,629 | 1997-09-05 | ||
| US60/057,776 | 1997-09-05 | ||
| US60/057,662 | 1997-09-05 | ||
| US60/057,668 | 1997-09-05 | ||
| US60/057,667 | 1997-09-05 | ||
| US60/057,774 | 1997-09-05 | ||
| US60/057,649 | 1997-09-05 | ||
| US60/057,761 | 1997-09-05 | ||
| US60/057,628 | 1997-09-05 | ||
| US60/057,777 | 1997-09-05 | ||
| US7092397P | 1997-12-18 | 1997-12-18 | |
| US60/070,923 | 1997-12-18 | ||
| PCT/US1998/011422 WO1998054963A2 (en) | 1997-06-06 | 1998-06-04 | 207 human secreted proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2291260A1 true CA2291260A1 (en) | 1998-12-10 |
Family
ID=27587074
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002291260A Abandoned CA2291260A1 (en) | 1997-06-06 | 1998-06-04 | 207 human secreted proteins |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1039801A4 (en) |
| CA (1) | CA2291260A1 (en) |
| WO (1) | WO1998054963A2 (en) |
Families Citing this family (66)
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| WO2001062891A2 (en) * | 2000-02-24 | 2001-08-30 | Human Genome Sciences, Inc. | 207 human secreted proteins |
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| JP2002506615A (en) * | 1998-02-27 | 2002-03-05 | 財団法人相模中央化学研究所 | Human protein having transmembrane domain and DNA encoding the same |
| WO1999047676A1 (en) * | 1998-03-18 | 1999-09-23 | Icos Corporation | Human leupaxin polypeptide and dna encoding it, their uses |
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| DE19818619A1 (en) * | 1998-04-21 | 1999-10-28 | Metagen Gesellschaft Fuer Genomforschung Mbh | New nucleic acid sequences expressed in bladder tumor tissue, and derived polypeptides, for treatment of bladder tumor and identification of therapeutic agents |
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| US6528297B1 (en) * | 1998-08-31 | 2003-03-04 | Institute Of Genetics Fudan University | Human lysozyme gene, its encoded polypeptide and the method for preparing them |
| AU2003204361B2 (en) * | 1998-09-01 | 2006-03-30 | Genentech, Inc. | Further pro polypeptides and sequences thereof |
| JP2005502301A (en) * | 1998-09-18 | 2005-01-27 | インサイト・ファーマスーティカルズ・インコーポレイテッド | Human ISRE binding protein |
| CA2344457A1 (en) * | 1998-09-30 | 2000-04-06 | Millennium Pharmaceuticals, Inc. | Slgp protein and nucleic acid molecule and uses therefor |
| US7414112B2 (en) | 1998-10-08 | 2008-08-19 | Genentech, Inc. | Antibodies to PRO1550 polypeptides |
| US6020164A (en) * | 1998-10-21 | 2000-02-01 | Incyte Pharmaceuticals, Inc. | Human RNA binding proteins |
| US6921658B1 (en) | 1998-11-20 | 2005-07-26 | Fuso Pharmacutical Industries, Ltd. | Serine protease BSSP6 |
| HK1041025A1 (en) * | 1998-12-23 | 2002-06-28 | Corixa Corporation | Compounds for immunotherapy and diagnosis of colon cancer and methods for their use |
| GB9828704D0 (en) | 1998-12-24 | 1999-02-17 | Nippon Glaxo Limited | Proteins |
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| EP1159284A4 (en) * | 1999-02-10 | 2003-10-29 | Human Genome Sciences Inc | 33 human secreted proteins |
| CA2361277A1 (en) * | 1999-03-12 | 2000-09-21 | Craig A. Rosen | 49 human secreted proteins |
| WO2000058356A1 (en) * | 1999-03-26 | 2000-10-05 | Human Genome Sciences, Inc. | 50 human secreted proteins |
| EP1181390A4 (en) * | 1999-03-18 | 2004-08-04 | Human Genome Sciences Inc | 27 human secreted proteins |
| AU3747000A (en) * | 1999-03-23 | 2000-10-09 | Human Genome Sciences, Inc. | 49 human secreted proteins |
| JP2002541804A (en) * | 1999-04-09 | 2002-12-10 | カイロン コーポレイション | Secreted human protein |
| CA2370039A1 (en) * | 1999-04-09 | 2000-10-19 | Shionogi & Co., Ltd. | Apoptosis-associated gene |
| CA2371172A1 (en) * | 1999-04-09 | 2000-10-19 | Human Genome Sciences, Inc. | 50 human secreted proteins |
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| EP1192247B9 (en) * | 1999-05-13 | 2007-10-31 | Johnson & Johnson Pharmaceutical Research and Development LLC | Sphingosine kinase enzyme |
| AU4778600A (en) * | 1999-05-20 | 2000-12-12 | Takeda Chemical Industries Ltd. | Novel polypeptide |
| AU5458300A (en) * | 1999-06-07 | 2000-12-28 | Human Genome Sciences, Inc. | 26 human secreted proteins |
| JP2003516114A (en) * | 1999-06-11 | 2003-05-13 | ヒューマン ジノーム サイエンシーズ, インコーポレイテッド | 50 human secreted proteins |
| AU5308200A (en) * | 1999-06-11 | 2001-01-02 | Human Genome Sciences, Inc. | 48 human secreted proteins |
| CA2383041A1 (en) * | 1999-06-11 | 2000-12-21 | Human Genome Sciences, Inc. | 49 human secreted proteins |
| EP1192171A4 (en) * | 1999-06-11 | 2003-05-07 | Human Genome Sciences Inc | 48 human secreted proteins |
| WO2001005969A2 (en) * | 1999-07-14 | 2001-01-25 | Incyte Genomics, Inc. | Electron transfer proteins |
| AU6181300A (en) * | 1999-07-29 | 2001-02-19 | Helix Research Institute | Liver cancer-associated genes |
| US6673570B1 (en) * | 1999-09-20 | 2004-01-06 | Ludwig Institute For Cancer Research | Smad associating polypeptides |
| EP1228204A2 (en) * | 1999-09-20 | 2002-08-07 | Ludwig Institute For Cancer Research | Smad associating polypeptides |
| WO2001021815A1 (en) * | 1999-09-23 | 2001-03-29 | Rigel Pharmaceuticals, Inc. | Checkpoint gene associated cell cycle proteins, compositions and methods of use |
| AU1020201A (en) * | 1999-10-28 | 2001-05-08 | Warner-Lambert Company | Human sphingosine kinase gene |
| EP1248800A2 (en) | 1999-11-30 | 2002-10-16 | Corixa Corporation | Compositions and methods for therapy and diagnosis of breast cancer |
| AU785055B2 (en) | 2000-01-13 | 2006-09-07 | Genentech Inc. | Novel stra6 polypeptides |
| AU2001238283C1 (en) * | 2000-02-14 | 2006-02-02 | Curagen Corporation | Sphingosine kinases |
| EP1313503A4 (en) * | 2000-07-24 | 2005-05-04 | Human Genome Sciences Inc | Human tumor necrosis factor receptors tr21 and tr22 |
| US20040132030A1 (en) * | 2000-09-27 | 2004-07-08 | Roy Frans Van | Identification of neuroblastoma tumor suppressor genes |
| US6630325B1 (en) * | 2000-10-19 | 2003-10-07 | Maine Medical Center Research Institute | Compositions, methods and kits relating to remodel |
| EP1397383A2 (en) * | 2001-06-20 | 2004-03-17 | Genentech, Inc. | Secreted polypeptide and their use in the treatment of bone disorders |
| AU2002362309A1 (en) * | 2001-09-14 | 2003-04-01 | Gene Logic, Inc. | Genes associated with malignant neoplasms |
| EP2305710A3 (en) | 2002-06-03 | 2013-05-29 | Genentech, Inc. | Synthetic antibody phage libraries |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2206488A1 (en) * | 1994-12-06 | 1996-06-13 | Immunex Corporation | Cytokine designated lerk-7 |
| EP0839196B1 (en) * | 1995-07-19 | 2005-05-11 | Genetics Institute, LLC | Human ctla-8 and uses of ctla-8-related proteins |
-
1998
- 1998-06-04 CA CA002291260A patent/CA2291260A1/en not_active Abandoned
- 1998-06-04 WO PCT/US1998/011422 patent/WO1998054963A2/en not_active Ceased
- 1998-06-04 EP EP98926237A patent/EP1039801A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998054963A2 (en) | 1998-12-10 |
| EP1039801A1 (en) | 2000-10-04 |
| EP1039801A4 (en) | 2003-03-26 |
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| EEER | Examination request | ||
| FZDE | Dead |