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WO2002081517A2 - Nouveaux polypeptides et acides nucleiques codant pour ces derniers - Google Patents

Nouveaux polypeptides et acides nucleiques codant pour ces derniers Download PDF

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Publication number
WO2002081517A2
WO2002081517A2 PCT/US2002/002064 US0202064W WO02081517A2 WO 2002081517 A2 WO2002081517 A2 WO 2002081517A2 US 0202064 W US0202064 W US 0202064W WO 02081517 A2 WO02081517 A2 WO 02081517A2
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Prior art keywords
polypeptide
amino acid
nucleic acid
seq
protein
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PCT/US2002/002064
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WO2002081517A3 (fr
Inventor
Marc F. Decristofaro
Muralidhara Padigaru
Charles Miller
Velizar Tchernev
Haihong Zhong
Mei Zhong
David Anderson
Robert Ballinger
Valerie Gerlach
Kimberly A. Spytek
Luca Rastelli
Ramesh Kekuda
Xiaojia Guo
Bryan Zerhusen
David Andrew
Peter Mezes
Meera Patturajan
Catherine E. Burgess
Andrew Eisen
Adam Wolenc
Jason Baumgartner
Richard A. Shimkets
Vladimir Gusev
Corine A. M. Vernet
Raymond J. Taupier
Carol Pena
Suresh Shenoy
Li Li
Stacie Casman
Ferenc Boldog
Elma Fernandes
Glennda Smithson
Uriel Malyankar
Bruce Taillon
Xiaohong Liu
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CuraGen Corp
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CuraGen Corp
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Priority to EP02736481A priority Critical patent/EP1360198A2/fr
Priority to CA002435528A priority patent/CA2435528A1/fr
Priority claimed from US10/055,877 external-priority patent/US7112668B2/en
Publication of WO2002081517A2 publication Critical patent/WO2002081517A2/fr
Priority claimed from US10/453,372 external-priority patent/US20060003323A1/en
Anticipated expiration legal-status Critical
Publication of WO2002081517A3 publication Critical patent/WO2002081517A3/fr
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the invention relates to polynucleotides and the polypeptides encoded by such polynucleotides, as well as vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using the same.
  • the invention is based in part upon the discovery of nucleic acid sequences encoding novel polypeptides.
  • the novel nucleic acids and polypeptides are referred to herein as NONX, or ⁇ OV1, ⁇ ON2, ⁇ ON3, ⁇ ON4, ⁇ OV5, NON6, ⁇ ON7, ⁇ OV8, NON9, ⁇ ON10, ⁇ ON11, ⁇ ON12, ⁇ ON13, ⁇ ON14, ⁇ ON15, ⁇ ON16, ⁇ ON17, ⁇ ON18, ⁇ OV19, NOV20, NOV21, NOV22, NOV23, NQN24, ⁇ ON25, ⁇ ON26, ⁇ ON27, ⁇ ON28, ⁇ OV29, NON30, ⁇ OV31, NOV32, and NOV33 nucleic acids and polypeptides.
  • NONX nucleic acid or ⁇ OV1, ⁇ ON2, ⁇ ON3, ⁇ ON4, ⁇ OV5, NON6, ⁇ ON7, ⁇ OV8, NON
  • the invention provides an isolated ⁇ ONX nucleic acid molecule encoding a ⁇ ONX polypeptide that includes a nucleic acid sequence that has identity to the nucleic acids disclosed in SEQ ID ⁇ OS:l, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122.
  • the ⁇ ONX nucleic acid molecule will hybridize under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule that includes a protein-coding sequence of a ⁇ OVX nucleic acid sequence.
  • the invention also includes an isolated nucleic acid that encodes a ⁇ ONX polypeptide, or a fragment, homolog, analog or derivative thereof.
  • the nucleic acid can encode a polypeptide at least 80% identical to a polypeptide comprising the amino acid sequences of SEQ ID ⁇ OS:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, and 123.
  • the nucleic acid can be, for example, a genomic DNA fragment or a cDNA molecule that includes the nucleic acid sequence of any of SEQ ID NOS:l, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, and 122.
  • an oligonucleotide e.g., an oligonucleotide which includes at least 6 contiguous nucleotides of a NONX nucleic acid (e.g., SEQ ID ⁇ OS:l, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59,
  • a NONX nucleic acid e.g., SEQ ID ⁇ OS:l, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59,
  • NONX polypeptides SEQ ID ⁇ OS:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60,
  • the NONX polypeptides include an amino acid sequence that is substantially identical to the amino acid sequence of a human ⁇ ONX polypeptide.
  • the invention also features antibodies that immunoselectively bind to ⁇ OVX polypeptides, or fragments, homologs, analogs or derivatives thereof.
  • the invention includes pharmaceutical compositions that include therapeutically- or prophylactically-effective amounts of a therapeutic and a pharmaceutically- acceptable carrier.
  • the therapeutic can be, e.g., a ⁇ ONX nucleic acid, a ⁇ ONX polypeptide, or an antibody specific for a ⁇ ONX polypeptide.
  • the invention includes, in one or more containers, a therapeutically- or prophylactically-effective amount of this pharmaceutical composition.
  • the invention includes a method of producing a polypeptide by culturing a cell that includes a ⁇ ONX nucleic acid, under conditions allowing for expression of the ⁇ ONX polypeptide encoded by the D ⁇ A. If desired, the ⁇ ONX polypeptide can then be recovered.
  • the invention includes a method of detecting the presence of a ⁇ ONX polypeptide in a sample.
  • a sample is contacted with a compound that selectively binds to the polypeptide under conditions allowing for formation of a complex between the polypeptide and the compound.
  • the complex is detected, if present, thereby identifying the NONX polypeptide within the sample.
  • the invention also includes methods to identify specific cell or tissue types based on their expression of a ⁇ ONX. Also included in the invention is a method of detecting the presence of a ⁇ OVX nucleic acid molecule in a sample by contacting the sample with a ⁇ ONX nucleic acid probe or primer, and detecting whether the nucleic acid probe or primer bound to a ⁇ ONX nucleic acid molecule in the sample.
  • the invention provides a method for modulating the activity of a ⁇ ONX polypeptide by contacting a cell sample that includes the ⁇ ONX polypeptide with a compound that binds to the ⁇ ONX polypeptide in an amount sufficient to modulate the activity of said polypeptide.
  • the compound can be, e.g., a small molecule, such as a nucleic acid, peptide, polypeptide, peptidomimetic, carbohydrate, lipid or other organic (carbon containing) or inorganic molecule, as further described herein.
  • a therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e.g., trauma, regeneration (in vitro and in vivo), viral/bacterial/parasitic infections, Non Hippel-Lindau (NHL) syndrome, Alzheimer's disease, stroke, tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, cerebral palsy, epilepsy, Lesch- ⁇ yhan syndrome, multiple sclerosis, ataxia- telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, actinic keratosis, acne, hair growth diseases, allopecia, pigmentation disorders, endocrine disorders, connective tissue disorders, such as severe neonatal Marfan syndrome, dominant ectopia lentis, familial ascending aortic aneurysm, inflammatory disorders such as osteo- and rheumatoid-arthritis, inflammatory bowel disease, Crohn's
  • the therapeutic can be, e.g., a ⁇ ONX nucleic acid, a ⁇ ONX polypeptide, or a ⁇ ONX- specific antibody, or biologically-active derivatives or fragments thereof.
  • the compositions of the present invention will have efficacy for treatment of patients suffering from the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the polypeptides can be used as immunogens to produce antibodies specific for the invention, and as vaccines. They can also be used to screen for potential agonist and antagonist compounds.
  • a cD ⁇ A encoding ⁇ ONX may be useful in gene therapy, and ⁇ ONX may be useful when administered to a subject in need thereof.
  • the compositions of the present invention will have efficacy for treatment of patients suffering from the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the invention further includes ⁇ a method for screening for a modulator of disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the method includes contacting a test compound with a ⁇ ONX polypeptide and determining if the test compound binds to said ⁇ ONX polypeptide. Binding of the test compound to the ⁇ ONX polypeptide indicates the test compound is a modulator of activity, or of latency or predisposition to the aforementioned disorders or syndromes.
  • Also within the scope of the invention is a method for screening for a modulator of activity, or of latency or predisposition to disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like by administering a test compound to a test animal at increased risk for the aforementioned disorders or syndromes.
  • the test animal expresses a recombinant polypeptide encoded by a NONX nucleic acid.
  • Expression or activity of ⁇ ONX polypeptide is then measured in the test animal, as is expression or activity of the protein in a control animal which recombinantly-expresses ⁇ ONX polypeptide and is not at increased risk for the disorder or syndrome.
  • the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a ⁇ ONX polypeptide, a ⁇ ONX nucleic acid, or both, in a subject (e.g., a human subject). The method includes measuring the amount of the ⁇ ONX polypeptide in a test sample from the subject and comparing the amount of the polypeptide in the test sample to the amount of the ⁇ ONX polypeptide present in a control sample.
  • an alteration in the level of the ⁇ OVX polypeptide in the test sample as compared to the control sample indicates the presence of or predisposition to a disease in the subject.
  • the predisposition includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the expression levels of the new polypeptides of the invention can be used in a method to screen for various cancers as well as to determine the stage of cancers.
  • the invention includes a method of treating or preventing a pathological condition associated with a disorder in a mammal by administering to the subject a ⁇ ONX polypeptide, a ⁇ ONX nucleic acid, or a ⁇ OVX-specific antibody to a subject (e.g., a human subject), in an amount sufficient to alleviate or prevent the pathological condition
  • a subject e.g., a human subject
  • the disorder includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.
  • the invention can be used in a method to identity the cellular receptors and downstream effectors of the invention by any one of a number of techniques commonly employed in the art. These include but are not limited to the two-hybrid system, affinity purification, co-precipitation with antibodies or other specific-interacting molecules.
  • NONX nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel ⁇ ONX substances for use in therapeutic or diagnostic methods.
  • These ⁇ ONX antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the "Anti- ⁇ OVX Antibodies" section below.
  • the disclosed ⁇ ONX proteins have multiple hydrophilic regions, each of which can be used as an immunogen. These ⁇ ONX proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.
  • the ⁇ ONX nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below.
  • the potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.
  • the present invention provides novel nucleotides and polypeptides encoded thereby.
  • NONX nucleic acids or “ ⁇ ONX polynucleotides” and the corresponding encoded polypeptides are referred to as “ ⁇ ONX polypeptides” or “ ⁇ ONX proteins.” Unless indicated otherwise, “ ⁇ ONX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NONX nucleic acids and their encoded polypeptides.
  • NONX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts.
  • the various ⁇ ONX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, ⁇ ONX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the ⁇ ONX polypeptides belong.
  • ⁇ ON1 is homologous to members of the neurotrophin-6 alpha family of proteins.
  • the ⁇ ON1 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat immune and nervous system disorders, e.g., proinflammatory disorder, immune disorder, inflammatory disease, septic shock, arthritis, bone pain, or bone deformity.
  • ⁇ ON2 is homologous to members of the guanylate kinase family of proteins.
  • the ⁇ ON2 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of biosynthesis and nucleotide metabolism.
  • the ⁇ ON2 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat genetic conditions, e.g.,Non Hippel- Lindau (NHL) syndrome, diabetes, or tuberous sclerosis.
  • NPL Non Hippel- Lindau
  • ⁇ ON3 is homologous to members of a family of the 85.6 kDa-like proteins that contain ankyrin domains.
  • ⁇ ON3 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of signal transduction or cell activation.
  • antibodies and related compounds according to the invention may be used to treat genetic conditions, e.g., endometriosis, fertility, adrenoleukodystrophy, congenital adrenal hyperplasia, diabetes, Non Hippel-Lindau (vhl) syndrome , pancreatitis, obesity, hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypothyroidism, SIDS, xerostomia, scleroderma, hypercalceimia, ulcers, cinhosis, transplantation, inflammatory bowel disease, diverticular disease, hirschsprung's disease, crohn's disease, appendicitis, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, graft vesus host, anemia, ataxia-telangiectasia, lymphedema, tonsilitis
  • genetic conditions e.g., endometrios
  • ⁇ ON4 is homologous to members of the mytonic dystrophy kinase-related CDC42- binding kinase family of proteins.
  • the ⁇ ON4 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat muscle, or cell migration disorders, e.g., myotonic dystrophy, myotonic dystrophy type 2, proximal myotonic myopathy, proximal myotomc dystrophy, neuromuscular diseases associated with cardiomyopathy, multiple endocrine neoplasia type 1(ME ⁇ 1), insulin dependent diabetes mellitus, familial paraganglioma type 2, spinocerebellar ataxia type 5, Bardet-Biedl syndrome, non-hodgkins lymphoma, cancers such as breast cancer, liver, lung, pancrease, and prostate cancers.
  • myotonic dystrophy myotonic dystrophy type 2
  • proximal myotonic myopathy proxi
  • NON5 is homologous tomembers of the SI 00 Calcium binding protein family.
  • the ⁇ ON5 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat genetic conditions, e.g., various cancers like breast, lung, and colorectal, as well as heart disease such as myocardial ischemia.
  • ⁇ ON6, ⁇ ON16, ⁇ ON18, ⁇ ON31, and ⁇ ON33 are homologous to the olfactory receptor/GPCR-like family of proteins.
  • G-Protein Coupled Receptor GPCRs
  • GPCRs G-Protein Coupled Receptor
  • antibodies and related compounds according to the invention may be used to treat, e.g., developmental diseases, MHC II and III diseases (immune diseases), taste and scent detectability disorders, Burkitt's lymphoma, corticoneurogenic disease, signal transduction pathway disorders, retinal diseases including those involving photoreception, cell growth rate disorders, cell shape disorders, feeding disorders, control of feeding, potential obesity due to over-eating, potential disorders due to starvation (lack of apetite), noninsulin-dependent diabetes mellitus ( ⁇ TDDM1), bacterial, fungal, protozoal and viral infections (particularly infections caused by HIV-1 or HIN-2), pain, cancer (including but not limited to neoplasm, adenocarcinoma, lymphoma, prostate cancer, uterus cancer), anorexia, bulimia, asthma, parkinson's disease, acute heart failure, hypotension, hypertension, urinary retention, osteoporosis, crohn's disease
  • ⁇ ON7 is homologous to members of the carbonate dehydratase/anhydrase family of proteins.
  • the ⁇ ON7 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat respiratory or CO2 transport disorders, e.g., lung cancer, hypertension, asthma, emphysema, or diabetes.
  • NON8 is homologous to members of the carboxypeptidase family of proteins.
  • the ⁇ ON8 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat digestive disorders, e.g., xerostomia, hypercalceimia, ulcers, Von Hippel-Lindau (NHL) syndrome, cirrhosis, transplantation, inflammatory bowel disease, diverticular disease, hirschsprung's disease, crohn's disease, appendicitis, stroke, tuberous sclerosis, anxiety, pain, endocrine dysfunctions, nueroprotection, diabetes, obesity, growth and reproductive disorders, myasthenia gravis.
  • digestive disorders e.g., xerostomia, hypercalceimia, ulcers, Von Hippel-Lindau (NHL) syndrome, cirrhosis, transplantation, inflammatory bowel disease, diverticular disease, hirschsprung's disease, crohn's disease, appendicitis, stroke, tuberous sclerosis, anxiety, pain, endocrine dysfunctions, nueroprotection,
  • ⁇ ON9 is homologous to members of the neurotransmitter receptor family of proteins.
  • the ⁇ ON9 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat, e.g., leukemia, acute nonlymphocytic, spinocerebellar ataxia-1, or neurological disorders.
  • ⁇ ON10 is homologous to members of the proto-oncogene MAF-like family of proteins.
  • the ⁇ ON10 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat, e.g., anemia, ataxia-telangiectasia, autoimmume disease, cancer, immunodeficiencies, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, allergies, transplantation, graft versus host disease (GNHD), lymphaedema, systemic lupus erythematosus, asthma, emphysema, scleroderma, ARDS, diabetes, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, hypercalceimia, or Lesch- ⁇
  • ⁇ ON11 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat digestive disorders, e.g., diabetes, Non Hippel-Lindau (NHL) syndrome, pancreatitis, obesity, endometriosis, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, transplantation, graft versus host disease (GNHD), lymphaedema, osteoporosis, hypercalceimia, arthritis, ankylosing spondylitis, scoliosis, systemic lupus erythematosus, asthma, emphysema, scleroderma, allergy, ARDS, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidos
  • NON12 is homologous to members of the phosphatase family of proteins.
  • the ⁇ ON12 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat, e.g., hyperthyroidism, hypothyroidism, endometriosis, fertility, Non Hippel-Lindau (NHL) syndrome, cirrhosis, transplantation, hypogonadism, Alzheimer's disease, stroke, tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, cerebral palsy, epilepsy, Lesch- ⁇ yhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, neurodegeneration, endocrine dysfunctions, diabetes, obesity, growth and reproductive disorders, systemic lupus erythematosus, autoimmune disease, asthma, emphysema, scleroderma, allergy, ARDS, renal artery sten
  • ⁇ ON13 is homologous to members of the chloride channel CLC-KA family of proteins.
  • the ⁇ ON13 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat, e.g., diabetes, autoimmune disease, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, hypercalceimia, or Lesch- ⁇ yhan syndrome.
  • ⁇ ON14 is homologous to members of the mast cell function-associated antigen (MAF A) family of proteins.
  • MAF A mast cell function-associated antigen
  • the ⁇ ON14 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat, e.g., cancer, autoimmune disease, allergies, immunodeficiencies, transplantation, graft versus host disease (GNHD), or lymphaedema.
  • ⁇ ON15 is homologous to members of the murine epithelial growth factor (MEGF) family of proteins.
  • MEGF murine epithelial growth factor
  • the ⁇ ON15 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat, e.g., cancer, trauma, bacterial and viral infections, regeneration (in vitro and in vivo), fertility, endometriosis, cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-N) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (NSD), valve diseases, tuberous sclerosis, scleroderma, obesity, transplantation, anemia, bleeding disorders, transplantation, diabetes, autoimmune disease, renal artery stenosis, interstitial nephritis, glomeruloneph
  • NON17 is homologous to members of the monocarboxylate transporter (MCT)-like family of proteins.
  • MCT monocarboxylate transporter
  • the ⁇ ON17 nucleic acids and polypeptides, antibodies and related compounds according to the invention maybe used to treat, e.g., Salla disease, infantile sialic acid storage disease, cystinosis, or streptozotocin-induced diabetes.
  • ⁇ OV19 is homologous to members of the major Duchenne muscular dystrophy (DP71) family of proteins.
  • the NON 19 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat muscle and nervous system disorders, e.g., Duchenne muscular dystrophy, Becker muscular dystroph, cardiomyopathy, dilated, X- linked, McLeod phenotype, Lesch- ⁇ yhan syndrome, myasthenia gravis.
  • ⁇ ON20 is homologous to members of the GPCR RTA family of proteins.
  • the ⁇ ON20 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat a wide range of disorders such as cancer, immune disorders, endocrine disorders and other diseases, e.g., developmental diseases; MHCII and III diseases (immune diseases); taste and scent detectability disorders; Burkitt's lymphoma; corticoneurogenic disease; signal transduction pathway disorders; metabolic pathway disorders; retinal diseases including those involving photoreception; cell growth rate disorders; cell shape disorders; metabolic disorders; feeding disorders; control of feeding; the metabolic syndrome X; wasting disorders associated with chronic diseases; obesity; potential obesity due to over-eating or metabolic disturbances; potential disorders due to starvation (lack of appetite); diabetes; noninsulin-dependent diabetes mellitus ( ⁇ IDDM); infectious disease; bacterial, fungal, protozoal and viral infections (particularly infections caused by HIN-1 or HIN-2); pain; cancer (including but not limited
  • hypophosphatemic rickets autosomal dominant (2) Acrocallosal syndrome and dyskinesias, such as Huntington's disease or Gilles de la Tourette syndrome; immune disorders;
  • Adrenoleukodyst ophy Congenital Adrenal Hype ⁇ lasia; Hemophilia; Hypercoagulation;
  • Non Hippel-Lindau (NHL) syndrome Stroke; Tuberous sclerosis; hypercalceimia; Cerebral palsy;
  • Emphysema Scleroderma; ARDS; Renal artery stenosis; Interstitial nephritis;
  • Glomerulonephritis Polycystic kidney disease; Systemic lupus erythematosus; Renal tubular acidosis; IgA nephropathy; Cardiomyopathy; Atherosclerosis; Congenital heart defects; Aortic stenosis ; Atrial septal defect (ASD); Atrioventricular (A-N) canal defect; Ductus arteriosus; Pulmonary stenosis ; Subaortic stenosis; Ventricular septal defect (NSD); valve diseases;
  • Inflammatory bowel disease Diverticular disease; Leukodystrophies; Graft vesus host;
  • Hyperthyroidism Endometriosis; and hematopoietic disorders.
  • ⁇ ON21 is homologous to members of the TFIIIC box B-binding subunit family of proteins.
  • the ⁇ ON21 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat cancer and viral infections, e.g., TFIIIC box B- binding subunit protein is cleaved and inactivated by the polio virus-encoded 3C protease during poliovirus infection (Shen et al., Mol. Cell. Biol, 16: 4163-71 (1996)).
  • ⁇ ON22 is homologous to members of the nucleoside diphosphate kinase B family of proteins.
  • the ⁇ ON22 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat cancer, e.g., atherosclerosis, aneurysm, hypertension, fibromuscular dysplasia, stroke, scleroderma, obesity, transplantation, myocardial infarction, embolism, cardiovascular disorders, bypass surgery, fertility disorders, myasthenia gravis, leukodystrophies, pain, neuroprotection, systemic lupus erythematosus, autoimmune disease, asthma, emphysema, scleroderma, allergy, ARDS and other diseases, disorders and conditions of the like.
  • cancer e.g., atherosclerosis, aneurysm, hypertension, fibromuscular dysplasia, stroke, scleroderma, obesity, transplantation, myocardial infarction, emb
  • NON23 is homologous to members of the T-cell family of proteins.
  • the ⁇ ON23 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to immune disorders, e.g., inflammation, allergies, autoimmune disease, and asthma.
  • ⁇ ON24 is homologous to members of the organic anion transporter (OAT) 3 family of proteins.
  • the ⁇ ON24 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat a wide range of disorders such as cancer, kidney disorders, immune disorders and other diseases, e.g., Non Hippel-Lindau (NHL) syndrome, Cu ⁇ hosis,Transplantation, Osteoporosis, Hypercalceimia, Artliritis, Ahkylosing spondylitis, Scoliosis, Diabetes, Autoimmune disease, Renal artery stenosis, Interstitial nephritis, Glomerulonephritis, Polycystic kidney disease, Systemic lupus erythematosus, Renal tubular acidosis, IgA nephropathy, Lesch- ⁇ yhan syndrome renal malfunction, nephrotoxicity, disease associated with cytotoxic drug, osteoporosis, osteopetrosis resistance,
  • ⁇ ON25 and ⁇ ON26 are homologous to members of the ficolin family of proteins.
  • nucleic acid or protein therapeutics designed with the protein encoded for by ⁇ ON26 could function as an opsinin to target and eliminate bacteria by complement -mediated destruction.
  • These proteins could be important for the treatment of bacterial septicemia.
  • Ficolins may also have the ability to bind to elastins. Elastins are functionally important for lung alveolar development and inactivation of these proteins can lead to emphysema-like disease.
  • Antibodies against ⁇ ON25 and ⁇ ON26 may prevent tissue destruction mediated by ficolin activity during emphysema, asthma and arthritis.
  • ⁇ ON27 is homologous to members of the peroxisomal Ca + -dependent solute carrier family of proteins.
  • the ⁇ ON27 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat metabolic disorders, e.g., cancer, trauma, regeneration (in vitro and in vivo), viral/bacterial/parasitic infections, atherosclerosis, aneurysm, hypertension, fibromuscular dysplasia, stroke, scleroderma, obesity, Non Hippel- Lindau (NHL) syndrome, Alzheimer's disease, stroke, tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, cerebral palsy, epilepsy, Lesch- ⁇ yhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, diabetes, autoimmune disease, renal artery stenosis, interstitial nephritis, glomerulonephritis, polyc
  • NON28, ⁇ ON29, and ⁇ ON30 are homologous to members of the ⁇ a+/glucose cotransporter family of proteins.
  • the NOV28 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat metabolic, immune and renal disorders, e.g., metabolic diseases such as diabetes and hypertension, or cancer, trauma, regeneration (in vitro and in vivo), viral/bacterial/parasitic infections, diabetes, autoimmune disease, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, hypercalceimia, Lesch- Nyhan syndrome, cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, duct
  • ⁇ ON32 is homologous to members of the phosphoenolpyruvate carboxykinase family of proteins.
  • the ⁇ ON32 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat metabolic disorders, e.g., hypoglycemia.
  • ⁇ ONX nucleic acids and proteins of the invention are useful in potential therapeutic applications implicated, for example but not limited to, in various pathologies /disorders as described herein and/or other pathologies/disorders.
  • Potential therapeutic uses for the invention(s) are, for example but not limited to, the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), (v) an agent promoting tissue regeneration in vitro and in vivo, and (vi) a biological defense weapon.
  • the disclosed ⁇ ON1 nucleic acid (alternatively referred to herein as CG56181-01) encodes a novel neutrophin-6 alpha-like protein and includes the 796 nucleotide sequence (SEQ ID NO:
  • the novel NOV1 nucleic acid of the invention maps to chromosome 19.
  • the NOVl protein (SEQ ID NO:2) encoded by SEQ TD NO: 1 is 258 amino acid residues in length and is presented using the one-letter amino acid code in Table IB.
  • the SignalP, Psort and/or Hydropathy results indicate that NOVl has a signal peptide and is likely to be localized in the microbody (peroxisome) with a certainty of 0.5952.
  • a NOVl polypeptide is located to the cytoplasm with a certainty of 0.4500, the lysosome (lumen) with a certainty of 0.2100, or the mitochondrial matrix space with a certainty of 0.1000.
  • NOVl nucleic acid sequence of this invention has 762 of 796 bases (95%) identical to a gb:GENBANK-ID:HUMNT4PSG
  • full amino acid sequence of the disclosed protein of the invention has 239 of 258 amino acid residues (92%) identical to, and 244 of 258 amino acid residues (94%) similar to, the 257 amino acid residue ptnr:SWISSPROT-ACC:P34132 protein from Human (NEUROTROPHIN-6 ALPHA (NT-6 ALPHA)).
  • the "E-value” or “Expect” value is a numeric indication of the probability that the aligned sequences could have achieved their similarity to the BLAST query sequence by chance alone, within the database that was searched.
  • the probability that the subject ("Sbjct") retrieved from the IIT BLAST analysis, matched the Query IIT sequence purely by chance is the E value.
  • the Expect value (E) is a parameter that describes the number of hits one can "expect" to see just by chance when searching a database of a particular size. It decreases exponentially with the Score (S) that is assigned to a match between two sequences. Essentially, the E value describes the random background noise that exists for matches between sequences.
  • Blasting is performed against public nucleotide databases such as GenBank databases and the GeneSeq patent database. For example, BLASTX searching is performed against public protein databases, which include GenBank databases, SwissProt, PDB and PIR.
  • the Expect value is used as a convenient way to create a significance threshold for reporting results.
  • the default value used for blasting is typically set to 0.0001.
  • the Expect value is also used instead of the P value (probability) to report the significance of matches.
  • an E value of one assigned to a hit can be interpreted as meaning that in a database of the current size one might expect to see one match with a similar score simply by chance.
  • An E value of zero means that one would not expect to see any matches with a similar score simply by chance. See, e.g., http://www.ncbi.nlm.nih.gov/Education/BLASTinfo/. Occasionally, a string of X's or N's will result from a BLAST search.
  • the NOVl protein of the invention also has homolgy to the proteins shown in the BLASTP data in Table ID.
  • NGF domain 1 of 2 , from 133 to 184 70 . 6 1. 5e-19
  • NGF domain 2 of 2, from 213 to 258 100 . 5 2 . 5e-28
  • NGF HWnSeCkttqtYVRALTmdnnklVgWRflRIDTACVCtLsrKtGrt (SEQ ID NO : 130 )
  • NOVl contains nerve growth factor domains as illustrated in Table IF.
  • the NOVl nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • NOVl nucleic acids and polypeptides can be used to identify proteins that are members of the neurotrophin family of proteins.
  • the NOVl nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVl activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., development and survival of certain sympathetic and sensory neurons in both the central and peripheral nervous systems. These molecules can be used to treat, e.g., proinflammatory disorder, immune disorder, and inflammatory disease.
  • NOVl nucleic acid and polypeptide according to the invention are useful, inter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the NOVl nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of nerve growth factors such as the neurotrophin proteins.
  • Nerve growth factor is the prototype for the neurotrophin family of polypeptides which are essential in the developments and survival of certain sympathetic and sensory neurons in both the central and peripheral nervous systems. NGF was discovered when mouse sarcoma tissue transplants in chicken embryos caused an increase in the size of spinal ganglia.
  • NOVl nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of the peripheral and central nervous system.
  • the NOVl nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat immune and nervous system disorders, e.g., proinflammatory disorder, immune disorder, inflammatory disease, septic shock, arthritis, bone pain, or bone deformity.
  • the NOVl nucleic acid and polypeptide are useful for detecting specific cell types. For example, expression analysis has demonstrated that a NOVl nucleic acid is expressed in placenta and uterus.
  • the disclosed NOV2 nucleic acid encodes a novel Guanylate kinase-like protein and includes the 1336 nucleotide sequence (SEQ ID NO:3) shown in Table 2A.
  • the novel NOV2 nucleic acid of the invention maps to chromosome 2. An open reading frame for the mature protein was identified beginning with an ATG initiation codon at nucleotides 3-5, and ending with a TGA stop codon at nucleotides 1326-1328. Putative untranslated regions, if any, are found upstream from the initiation codon and downstream from the termination codon. The start and stop codons are in bold letters.
  • the NOV2 protein (SEQ ID NO:4) encoded by SEQ ID NO:3 is 441 amino acid residues in length and is presented using the one-letter amino acid code in Table 2B.
  • the SignalP, Psort and/or Hydropathy results indicates that NOV2 has a signal peptide and is likely to be localized in the microbody (peroxisome) with a certainty of 0.3000.
  • a NOV2 polypeptide is located to the nucleus with a certainty of 0.3000, the mitochondrial matrix space with a certainty of 0.1000, or the lysosome (lumen) with a certainty of 0.1000.
  • SNP Small nucleotide polymo ⁇ hisms
  • the full amino acid sequence of the disclosed NOV2 protein of the invention has 346 of 441 amino acid residues (78%) identical to, and 380 of 441 amino acid residues (86%) similar to, the 441 amino acid residue ⁇ tnr:SPTREMBL-ACC:Q9QYHl protein from Rattus norvegicus (Rat) (DLG6 ALPHA).
  • the NOV2 protein of the invention also has homolgy to the proteins shown in the BLASTP data in Table 2D.
  • NOV2 contains guanylate kinase domains as illustrated in Table 2F.
  • NOV2 nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • NOV2 nucleic acids and polypeptides can be used to identify proteins that are members of the guanylate kinase family of proteins.
  • the NOV2 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOV2 activity or function.
  • the nucleic acids and polypeptides according to the invention maybe used as targets for the identification of small molecules that modulate or inhibit, e.g., cell signaling pathways, cell junction organization, or transmembrane regulation.. These molecules can be used to treat, e.g., Von Hippel-Lindau (VHL) syndrome, diabetes, and tuberous sclerosis.
  • VHL Von Hippel-Lindau
  • the NOV2 nucleic acid and polypeptide according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the NOV2 nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of kinases such as the guanylate kinase proteins.
  • Guanylate kinase is a critical enzyme for biosynthesis of GTP and dGTP, and its role in nucleotide metabolism makes it a target for cancer chemotherapy.
  • the structure of mouse guanylate kinase (gmk) includes an N-terminal ATP binding motif and a neighboring guanylate kinase signature sequence (GKSS).
  • the low molecular mass cytosolic forms of guanylate kinase are implicated in the regulation of the supply of guanine nucleotides to cell signaling pathways, while the related families of high molecular mass and membrane-associated forms of guanylate kinase, such as MAGUK, CASK, SAP102, ZO-1, and MAGI-1, have roles in cell junction organization and transmembrane regulation.
  • the NOV2 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of biosynthesis and nucleotide metabolism. As such the NOV2 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat genetic conditions, e.g., Von Hippel-Lindau (VHL) syndrome, diabetes, or tuberous sclerosis.
  • VHL Von Hippel-Lindau
  • the NOV2 nucleic acid and polypeptide are useful for detecting specific cell types. For example, expression analysis has demonstrated that a NOV2 nucleic acid is expressed in synovium/synovial membrane.
  • the disclosed NOV3 nucleic acid (alternatively referred to herein as CG53400-01) encodes a novel hypothetical 85.6 kDa-like protem and includes the 3089 nucleotide sequence (SEQ ID NO: 5) shown in Table 3 A.
  • the novel NOV3 nucleic acid of the invention maps to chromosome 12.
  • the NOV3 protein (SEQ ID NO:6) encoded by SEQ ID NO:5 is 993 amino acid residues in length and is presented using the one-letter amino acid code in Table 3B.
  • the SignalP, Psort and/or Hydropathy results indicate that NOV3 has no known signal peptide and is likely to be localized in the mitochondrial matrix space with a certainty of 0.5083.
  • a NOV3 polypeptide is located to the nucleus with a certainty of 0.3000, the mitochondrial inner membrane with a certainty of 0.2317, or the mitochondrial intermembrane space with a certainty of 0.2217.
  • variants of the parent clone NOV3 as shown below in Table 3C. These novel variants were derived by laboratory cloning of cDNA fragments coding for a domain of the full length form of NOV3 (CG53400-01), between residues 596 and 968.
  • NOV3 nucleic acid sequence of this invention has 1552 of 2369 bases (65%) identical to a gb:GENBANK-H):HSM801363
  • the full amino acid sequence of the disclosed NOV3 protein of the invention has 498 of 791 amino acid residues (62%) identical to, and 600 of 791 amino acid residues (75%) similar to, the 791 amino acid residue ptnr:SPTREMBL-ACC:Q9UFA4 protein from Human (HYPOTHETICAL 85.6 KDA PROTEIN).
  • the NOV3 protein of the invention also has homolgy to the proteins shown in the BLASTP data in Table 3E.
  • NOV3 contains ankyrin domains as illustrated in Table 3G.
  • NOV3 nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • NOV3 nucleic acids and polypeptides can be used to identify proteins that are members of the ankyrin family of proteins.
  • the NOV3 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOV3 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., red blood cell formation/organization, or signal transduction/cell activation. These molecules can be used to treat, e.g., spherocytosis.
  • the NOV3 nucleic acid and polypeptide according to the invention are useful, inter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the NOV3 nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of transmembrane proteins/membrane skeleton proteins such as the ankyrin proteins.
  • Ankyrin is a globular protein (200 kD) that links spectrin and an integral membrane protein (Band III) in the erythrocyte plasma membrane.
  • Ankyrin belongs to a family of closely related polypeptides associated with the plasma membrane of cells in a variety of cell types (e.g.
  • Ankyrin has been shown to underlie membrane proteins including CD44, the voltage-dependent sodium channel, NA+/K+ ATPase and the anion exchanger protein. Functional diversity between members of the ankyrin family is generated by the expression of multiple genes as well as alternative splicing of pre-mRna's. The formation of a direct connection between ankyrin and functionally important transmembrane proteins/membrane skeleton may be one of the earliest events to occur during signal transduction and cell activation.
  • NOV3 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of signal transduction or cell activation.
  • the NOV3 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat genetic conditions, e.g., endometriosis, fertility, adrenoleukodystrophy, congenital adrenal hyperplasia, diabetes, Von Hippel-Lindau (vhl) syndrome , pancreatitis, obesity, hype ⁇ arathyroidism, hypoparathyroidism, hyperthyroidism, hypothyroidism, SIDS, xerostomia, scleroderma, hypercalceimia, ulcers, cirrhosis, transplantation, inflammatory bowel disease, diverticular disease, hirschsprung's disease, crohn's disease, appendicitis, hemophilia, hypercoagulation, idiopathic thrombocytopenic pu ⁇ ura, autoimmume
  • the NOV3 nucleic acid and polypeptide are useful for detecting specific cell types. For example, expression analysis has demonstrated that a NOV3 nucleic acid is expressed in adrenal gland/suprarenal gland, bone, brain, cartilage, cervix, coronary artery, platelets, kidney, kidney cortex, liver, mammary gland/breast, pancreas, placenta, salivary glands, spleen, synovium/synovial membrane, thymus, cerebral medulla/cerebral white matter, and left cerebellum. Additional utilities for the NOV3 nucleic acid and polypeptide according to the invention are disclosed herein.
  • the NOV4 proteins descibed herein are novel myotonic dystrophy kinase-related CDC-42 binding kinase (MRCK)-like proteins.
  • the NOV4 nucleic acids disclosed herein map to chromosome 1 lql3.
  • Two alternative novel NOV4 nucleic acids and polypeptides are disclosed herein, namely NO V4a andNOV4b.
  • a NOV4 variant is NOV4a (alternatively referred to herein as CG56209-01), which encodes the 3835 nucleotide sequence (SEQ ID NO:7) shown in Table 4A.
  • SEQ ID NO:7 An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 98-100 and ending with a TAG codon at nucleotides 3689-3691. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NOV4a protein (SEQ ID NO:8) encoded by SEQ ID NO:7 is 1197 amino acid residues in length and is presented using the one-letter amino acid code in Table 4B.
  • the SignalP, Psort and/or Hydropathy results indicate that NOV4a has no known signal peptide and is likely to be localized in the nucleus with a certainty of 0.7600.
  • a NOV4a polypeptide is located to the microbody (peroxisome) with a certainty of 0.3114, the lysosome (lumen) with a certainty of 0.1772, or the mitochondrial matrix space with a certainty of 0.1000.
  • NOV4b (alternatively referred to herein as CG56209-02), which includes the 3985 nucleotide sequence (SEQ ID NO:9) shown in Table 4C.
  • SEQ ID NO:9 3985 nucleotide sequence shown in Table 4C.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 98- 100 and ending with a TAG codon at nucleotides 3839-3841. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NOV4b protein (SEQ ID NO:10) encoded by SEQ ID NO:9 is 1247 amino acid residues in length and is presented using the one-letter amino acid code in Table 4D.
  • the SignalP, Psort and/or Hydropathy results indicate that NOV4b has no known signal peptide and is likely to be localized in the nucleus with a certainty of 0.8800.
  • a NOV4b polypeptide is located to the microbody (peroxisome) with a certainty of 0.3226, the lysosome (lumen) with a certainty of 0.1925, or the mitochondrial matrix space with a certainty of 0.1000.
  • NOV4a or NOV4b any reference to NOV4 is assumed to encompass all variants.
  • a search against the Patp database a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4E.
  • NOV4a nucleic acid sequence of this invention has 865 of 865 bases (100%) identical to a gb:GENBANK-ro:HSMDPKJN
  • the full amino acid sequence of the disclosed NOV4a protein of the invention has 314 of 572 amino acid residues (54%) identical to, and 418 of 572 amino acid residues (73%) similar to, the 1732 amino acid residue ptnr:SPTREMBL- ACC:O54874 protein from Rattus norvegicus (Rat) (MYTONIC DYSTROPHY KINASE- RELATED CDC42-BINDING KINASE).
  • NOV4 contains protein kinase domains as illustrated in Table 4H.
  • NON4 nucleic acids, and the encoded polypeptides, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON4 nucleic acids and polypeptides can be used to identify proteins that are members of the protein kinase family of proteins.
  • the ⁇ ON4 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON4 activity or function.
  • nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., cytoskeletal reorganization or molecular switch mechanisms. These molecules can be used to treat, e.g., myotonic dystrophy, myotonic dystrophy type 2, proximal myotonic myopathy, or proximal myotonic dystrophy.
  • various ⁇ OV4 nucleic acids and polypeptides according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the NOV4 nucleic acids and their encoded polypeptides include structural motifs that are characteristic of proteins belonging to the family of protein kinases such as the MRCK protein.
  • MRCK is a Ser/Thr kinase that is highly related to myotonic dystrophy kinase and ROKs.
  • MRCK contains an N-terminal kinase domain, a coiled-coil region, a cysteine-rich domain (CR), a pleckstrin-like domain (PH), and a C-terminal p21 GTPase-binding domain (GBD). Two different MRCK genes are expressed in rat.
  • MRCKa mRNA is enriched in brain and lung, while MRCKb mRNA is expressed in lung and kidney.
  • MRCKa phosphorylates Ser/Thr residues in myelin basic protein, histone HI, and non-muscle myosin regulatory light chain.
  • expression of kinase-dead MRCKa blocks Cdc42-dependent formation of focal complexes and peripheral microspikes, while in PC 12 cells MRCKa may act downstream of Cdc42 and Racl to promote neurite outgrowth.
  • the NOV4 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of cell migration and differentiation.
  • the NOV4 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat muscle, or cell migration disorders, e.g., myotonic dystrophy, myotonic dystrophy type 2, proximal myotonic myopathy, proximal myotonic dystrophy, neuromuscular diseases associated with cardiomyopathy, multiple endocrine neoplasia type 1(MEN1), insulin dependent diabetes mellitus, familial paraganglioma type 2, spinocerebellar ataxia type 5, Bardet-Biedl syndrome, non-hodgkins lymphoma, cancers such as breast cancer, liver, lung, pancrease, and prostate cancers.
  • myotonic dystrophy myotonic dystrophy type 2
  • proximal myotonic myopathy proximal myo
  • the NON4 nucleic acids and polypeptides are useful for detecting specific cell types.
  • expression analysis has demonstrated that a ⁇ ON4 nucleic acid is expressed in adrenal gland, bone marrow, brain - amygdala, brain - cerebellum, brain - hippocampus, brain - substantia nigra, brain - thalamus, brain -whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma - Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, and uterus.
  • the disclosed NOV5 nucleic acid encodes a novel SI 00 calcium binding-like protein and includes the 332 nucleotide sequence (SEQ ID NO: 11) shown in Table 5 A.
  • SEQ ID NO: 11 the 332 nucleotide sequence shown in Table 5 A.
  • SignalP, Psort and/or hydropathy suggest that the SI 00 Calcium Binding Protein-like protein may be localized in the cytoplasm, the protein predicted here is similar to the SI 00 Calcium Binding Protein family, some members of which are secreted. Therefore it is likely that this novel SI 00 Calcium Binding Protein-like protein is available at the same sub-cellular localization and hence accessible to a diagnostic probe and for various therapeutic applications.
  • the NOV5 protein (SEQ ID NO: 12) encoded by SEQ ID NO: 11 is 104 amino acid residues in length and is presented using the one-letter amino acid code in Table 5B.
  • the SignalP, Psort and/or Hydropathy results indicate that NON5 has no known signal peptide and is likely to be localized in the mitochondrial matrix space with a certainty of 0.5964.
  • a ⁇ ON5 polypeptide is located to the mitochondrial inner membrane with a certainty of 0.3037, the mitochondrial intermembrane space with a certainty of 0.3037, or the mitochondrial outer membrane with a certainty of 0.3037.
  • the NOV5 nucleic acid sequence of this invention has 305 of 335 bases (91%) identical to a gb:GENBANK-ID:HUMS100CPl
  • the full amino acid sequence of the disclosed NON5 protein of the invention has 102 of 103 amino acid residues (99%) identical to, and 102 of 103 amino acid residues (99%) similar to, the 104 amino acid residue ptnr:SPTREMBL-ACC:Q9UDP3 protein from Human (WUGSC:H_ ⁇ H0456 ⁇ 16.1 PROTEIN).
  • the NON5 protein of the invention also has homolgy to the proteins shown in the
  • NON5 contains S100 calcium binding domains as illustrated in Table 5F.
  • ⁇ ON5 nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON5 nucleic acids and polypeptides can be used to identify proteins that are members of the S100 family of proteins.
  • the ⁇ OV5 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOV5 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., calcium regulation. These molecules can be used to treat, e.g., various cancers hke breast, lung, or colorectal.
  • the NOV5 nucleic acid and polypeptide according to the invention are useful, inter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the NOV5 nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of S100 proteins. S100 proteins are expressed in a cell-type specific manner in higher organisms, including humans, and are involved in the calcium-regulated control of very diverse cellular processes. Proteins of the S100 family belong to the large group of EF-hand calcium-binding proteins.
  • the NON5 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of calcium regulation.
  • ⁇ ON5 nucleic acid and polypeptide antibodies and related compounds according to the invention may be used to treat genetic conditions, e.g., various cancers like breast, lung, and colorectal, as well as heart disease such as myocardial ischemia.
  • the ⁇ ON5 nucleic acid and polypeptide are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON5 nucleic acid is expressed in elevated levels in colorectal cancers compared with that of normal colorectal mucosa, as well as in breast cancer-derived metastatic axillary lymph nodes, but not in normal lymph nodes or breast fibroadenomas.
  • the ⁇ ON5 nucleic acids and polypeptides, antibodies and related compounds accoring to the invention will have diagnostic and therapeutic applications in the detection of cancer, e.g., breast or colorectal cancer.
  • a ⁇ ON5 nucleic acid is also expressed in brain, lung, smooth muscle and keratinocyte tissue.
  • the disclosed NOV6 nucleic acid encodes a novel olfactory receptor-like protein/G-protein coupled receptor (GPCR) protein and includes the 1121 nucleotide sequence (SEQ ID NO: 13) shown in Table 6A.
  • GPCR G-protein coupled receptor
  • An open reading frame for the mature protein was identified beginning with an ATG initiation codon at nucleotides 30-32, and ending with a TAG stop codon at nucleotides 1119- 1121. Putative untranslated regions, if any, are found upstream from the initiation codon and downstream from the termination codon. The start and stop codons are in bold letters.
  • Table 6A NOV6 Nucleotide Sequence (SEQ ID NO:13)
  • the NOV6 protein (SEQ ID NO: 14) encoded by SEQ ID NO: 13 is 363 amino acid residues in length and is presented using the one-letter amino acid code in Table 6B.
  • the SignalP, Psort and/or Hydropathy results indicate that NON6 has a signal peptide and is likely to be localized in the plasma membrane with a certainty of 0.6000.
  • a ⁇ ON6 polypeptide is located to the Golgi body with a certainty of 0.4000, the endoplasmic reticulum (membrane) with a certainty of 0.3000, or the mitochondrial inner membrane with a certainty of 0.0300.
  • the SignalP indicates a likely cleavage site for a ⁇ ON6 polypeptide is between positions 41 and 42, i.e., at the dash in the sequence CFG- ⁇ L.
  • NOV6 nucleic acid sequence of this invention has 723 of 1057 bases (68%) identical to a gb:GENBANK-ID:AF190500
  • LGR7 G protein-coupled receptor 7
  • the full amino acid sequence of the disclosed NOV6 protein of the invention has 203 of 339 amino acid residues (59%) identical to, and 271 of 339 amino acid residues (79%) similar to, the 757 amino acid residue ptnr:TREMBLNEW-ACC:AAG17167 protein from Human (LEUCINE-RICH REPEAT-
  • the NOV6 protein of the invention also has homolgy to the proteins shown in the BLASTP data in Table 6D.
  • SEQ ID NO. 14 NOV6 4. SEQ ID NO. 158 CAC38938
  • NON6 contains 7-transmembrane domains as illustrated in Table 6F.
  • ⁇ ON6 nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON6 nucleic acids and polypeptides can be used to identify proteins that are members of the olfactory receptor family of proteins.
  • the ⁇ ON6 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON6 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., cellular recognition, or G-protein-mediated transduction of odorant signals. These molecules can be used to treat, e.g., taste and scent detectability disorders, immune diseases, or signal transduction pathways.
  • the ⁇ ON6 nucleic acid and polypeptide according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the ⁇ ON6 nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of olfactory receptor proteins. Olfactory receptors have great variety, extraordinar specificity, high sensitivity and fast response.
  • the human olfactory epithelium contains two to three thousand distinct olfactory receptors, a class of G-protein coupled receptors.
  • the receptors consist of seven hydrophobic segments that span the cell membrane (trans-membrane domains I-NII), separated by hydrophilic segments that project into the intra- or extra-cellular space.
  • Trans-membrane domains II-NII comprise a hypervariable segment that defines the ligand specificity of the receptor.
  • the ⁇ ON6 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of signal transduction.
  • the ⁇ ON6 nucleic acid and polypeptide, antibodies and related compounds according to the invention may be used to treat, e.g., developmental diseases, MHC II and III diseases (immune diseases), taste and scent detectability disorders, Burkitt's lymphoma, corticoneurogenic disease, signal transduction pathway disorders, retinal diseases including those involving photoreception, cell growth rate disorders, cell shape disorders, feeding disorders, control of feeding, potential obesity due to over-eating, potential disorders due to starvation (lack of apetite), noninsulin-dependent diabetes mellitus ( ⁇ TDDMl), bacterial, fungal, protozoal and viral infections (particularly infections caused by HIN-1 or HIN-2), pain, cancer (including but not limited to neoplasm, adenocarcinoma, lymphoma, prostate cancer, uterus cancer), anorexia
  • the NON6 nucleic acid and polypeptide are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON6 nucleic acid is predominantly expressed in olfactory epithelium and taste receptor cells of the tongue.
  • the ⁇ ON7 proteins descibed herein are novel carbonate dehydratase-like proteins.
  • the ⁇ ON7 nucleic acids disclosed herein map to chromosome 15.
  • Two alternative novel ⁇ ON7 nucleic acids and polypeptides are disclosed herein, namely ⁇ ON7a and ⁇ ON7b.
  • ⁇ OV7a A NON7 variant is ⁇ ON7a (alternatively referred to herein as CG50365-01 ), which encodes the 828 nucleotide sequence (SEQ ID NO: 15) shown in Table 7A.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 16-18 and ending with a TAA codon at nucleotides 802-804. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NON7a protein (SEQ ID NO: 16) encoded by SEQ TD NO: 15 is 262 amino acid residues in length and is presented using the one-letter amino acid code in Table 7B.
  • the SignalP, Psort and/or Hydropathy results indicate that NOV7a has no known signal peptide and is likely to be localized in the microbody (peroxisome) with a certainty of 0.7480.
  • a NOV7a polypeptide is located to the mitochondrial matrix space with a certainty of 0.1000, the lysosome (lumen) with a certainty of 0.1000, or the endoplasmic reticulum (membrane) with a certainty of 0.1000.
  • a NON7 variant is ⁇ ON7b (alternatively referred to herein as CG50365-02), which includes the 833 nucleotide sequence (SEQ ID NO: 17) shown in Table 7C.
  • SEQ ID NO: 17 An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 21-23 and ending with a TAA codon at nucleotides 807-809. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NON7b protein (SEQ ID ⁇ O:18) encoded by SEQ ID NO:17 is 262 amino acid residues in length and is presented using the one-letter amino acid code in Table 7D.
  • the SignalP, Psort and/or Hydropathy results indicate that NOV7b has no known signal peptide and is likely to be localized in the microbody (peroxisome) with a certainty of 0.7480.
  • a NON7b polypeptide is located to the mitochondrial matrix space with a certainty of 0.1000, the lysosome (lumen) with a certainty of 0.1000, or the endoplasmic reticulum (membrane) with a certainty of 0.1000.
  • any reference to ⁇ ON7 is assumed to encompass all variants.
  • the full amino acid sequence of the disclosed NOV7a protein of the invention has 160 of 257 amino acid residues (62%) identical to, and 197 of 257 amino acid residues (76%) similar to, the 260 amino acid residue ptnr:SWISSPROT-ACC:Q92051 protein from Brachydanio rerio (Zebrafish) (Zebra danio) (CARBONIC ANHYDRASE (EC 4.2.1.1) (CARBONATE DEHYDRATASE)).
  • NOV7b nucleic acid sequence of this invention has 549 of 789 bases (69%) identical to a gb:GENBANK-ID:HSCAIR
  • the full amino acid sequence of the disclosed NOV7b protein of the invention has 156 of 261 amino acid residues (59%) identical to, and 202 of 261 amino acid residues (77%) similar to, the 261 amino acid residue ptnr:pir-id:CRHUl protein from human (carbonate dehydratase (EC 4.2.1.1) I [validated]).
  • NOV7 contains carbonic anhydrase domains as illustrated in Table 7H.
  • NON7 nucleic acids, and the encoded polypeptides, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON7 nucleic acids and polypeptides can be used to identify proteins that are members of the carbonate dehydratase family of proteins.
  • the ⁇ ON7 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON7 activity or function.
  • nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., a variety of biological processes such as respiration, calcification, acid-base balance, bone resorption and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. These molecules can be used to treat, e.g., hypertension, asthma, or emphysema.
  • ⁇ ON7 nucleic acids and polypeptides according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the ⁇ ON7 nucleic acids and their encoded polypeptides include structural motifs that are characteristic of proteins belonging to the lyase family such as the carbonic dehydratase protein.
  • Carbonic dehydratase is an enzyme that catalyzes the equilibration of dissolved carbon dioxide and carbonic acid, speeding the movement of carbon dioxide from tissues to blood to alveolar air. It is a zinc metalloenzyme of great physiological importance.
  • ⁇ ON7 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of CO2 transport.
  • the ⁇ ON7 nucleic acids and polypeptides, antibodies and related compounds according to the invention may be used to treat respiratory or CO2 transport disorders, e.g., lung cancer, hypertension, asthma, emphysema, or diabetes.
  • the ⁇ ON7 nucleic acids and polypeptides are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON7 nucleic acid is expressed in lung.
  • the ⁇ ON8 proteins descibed herein are novel carboxypeptidase-like proteins.
  • the ⁇ ON8 nucleic acids disclosed herein map to chromosome 2.
  • Four alternative novel ⁇ OV8 nucleic acids and polypeptides are disclosed herein, namely NON8a, ⁇ ON8b, ⁇ ON8c and ⁇ ON8d.
  • a NOV8 variant is NOV8a (alternatively referred to herein as CG55794-01), which encodes the 1196 nucleotide sequence (SEQ ID NO: 19) shown in Table 8 A.
  • SEQ ID NO: 19 1196 nucleotide sequence shown in Table 8 A.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 16-18 and ending with a TAA codon at nucleotides 1138-1140. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NOV8a protein (SEQ ID NO:20) encoded by SEQ ID NO: 19 is 374 amino acid residues in length and is presented using the one-letter amino acid code in Table 8B.
  • the SignalP, Psort and/or Hydropathy results indicate that NOV8a has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.9190.
  • a NON8a polypeptide is located to the lysosome (membrane) with a certainty of 0.2000, the microbody (peroxisome) with a certainty of 0.1292, or the endoplasmic reticulum (membrane) with a certainty of 0.1000.
  • the SignalP indicates a likely cleavage site for a ⁇ ON8a peptide is between positions 20 and 21, i.e., at the dash in the sequence GLG-YD.
  • Table 8B Encoded NOV8a Protein Sequence (SEQ ID NO:20)
  • a ⁇ ON8 variant is ⁇ ON8b (alternatively referred to herein as CG55794-03), which includes the 1222 nucleotide sequence (SEQ ID ⁇ O:21) shown in Table 8C.
  • SEQ ID ⁇ O:21 1222 nucleotide sequence shown in Table 8C.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 41-43 and ending with a TAA codon at nucleotides 1163-1165. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NON8b protein (SEQ ID ⁇ O:22) encoded by SEQ ID NO:21 is 347 amino acid residues in length and is presented using the one-letter amino acid code in Table 8D.
  • NON8b has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.9190.
  • a NON8b polypeptide is located to the lysosome (membrane) with a certainty of 0.2000, the microbody (peroxisome) with a certainty of 0.1345, or the endoplasmic reticulum (membrane) with a certainty of 0.1000.
  • the SignalP indicates a likely cleavage site for a ⁇ ON8b peptide is between positions 20 and 21, i.e., at the dash in the sequence GLG-YD.
  • aNOV8 variant is NON8c (alternatively referred to herein as CG55794-06), which includes the 977 nucleotide sequence (SEQ ID ⁇ O:23) shown in Table 8E.
  • SEQ ID ⁇ O:23 977 nucleotide sequence shown in Table 8E.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 41-43 and ending with a TAG codon at nucleotides 671-673. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NOV8c protein (SEQ ID NO:24) encoded by SEQ ID NO:23 is 210 amino acid residues in length and is presented using the one-letter amino acid code in Table 8F.
  • the SignalP, Psort and/or Hydropathy results indicate that NON ⁇ c has a signal peptide and is likely to be localized extracellularly at the plasma membrane with a certainty of 0.3700.
  • a ⁇ ON8c polypeptide is located to the microbody (peroxisome) with a certainty of 0.2242, the lysosome (lumen) with a certainty of 0.1900, or the endoplasmic reticulum (membrane) with a certainty of 0.1000.
  • the SignalP indicates a likely cleavage site for a ⁇ ON8c peptide is between positions 20 and 21, i.e., at the dash in the sequence GLG-YD.
  • NON8d a NON8 variant is ⁇ ON8d (alternatively referred to herein as CG55794-07), which includes the 1378 nucleotide sequence (SEQ ID ⁇ O:25) shown in Table 8G.
  • SEQ ID ⁇ O:25 the 1378 nucleotide sequence shown in Table 8G.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 259-261 and ending with a TAA codon at nucleotides 1225-1227. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • NOV8d has no known signal peptide and is likely to be localized in the cytoplasm at the endoplasmic reticulum (membrane) with a certainty of 0.8500.
  • a NON8d polypeptide is located to the microbody (peroxisome) with a certainty of 0.4781, the plasma membrane with a certainty of 0.4400, or the mitochondrial inner membrane with a certainty of 0.1000.
  • any reference to ⁇ ON8 is assumed to encompass all variants.
  • NOV8a nucleic acid sequence of this invention has 584 of 914 bases (63%) identical to a gb:GENBANK-ID:AF190274
  • the full amino acid sequence of the disclosed NON8 a protein of the invention has 151 of 325 amino acid residues (46%) identical to, and 219 of 325 amino acid residues (67%) similar to, the 416 amino acid residue ⁇ tnr:SPTREMBL-ACC:Q9PUF2 protein from Bothrops jararaca (Jararaca) (CARBOXYPEPTIDASE HOMOLOG).
  • ⁇ ON8b nucleic acid sequence of this invention has 586 of 914 bases (64%) identical to a gb:GE ⁇ BA ⁇ K-ID:AF190274
  • the full amino acid sequence of the disclosed NOV8b protein of the invention has 152 of 325 amino acid residues (46%) identical to, and 219 of 325 amino acid residues (67%) similar to, the 416 amino acid residue ⁇ tnr:SPTREMBL-ACC:Q9PUF2 protein from Bothrops jararaca (Jararaca) (CARBOXYPEPTIDASE HOMOLOG).
  • NON8c nucleic acid sequence of this invention has 621 of 672 bases (92%) identical to a gb:GE ⁇ BA ⁇ K-ID:AX083139
  • the full amino acid sequence of the disclosed NON8c protein of the invention has 83 of 176 amino acid residues (47%) identical to, and 122 of 176 amino acid residues (69%) similar to, the 422 amino acid residue ptnr:SPTREMBL-ACC:Q9EQN9 protein from Rattus norvegicus (Rat) (PRE-PROCARBOXYPEPTIDASE R).
  • the ⁇ ON8d nucleic acid sequence of this invention has 1073 of 1077 bases (99%) identical to a gb:GE ⁇ BA ⁇ K-ID:AX083139
  • the full amino acid sequence of the disclosed NOV8d protein of the invention has 142 of 283 amino acid residues (50%) identical to, and 199 of 283 amino acid residues (70%) similar to, the 416 amino acid residue ⁇ tnr:SPTREMBL-ACC:Q9PUF2 protein from Bothrops jararaca (Jararaca) (CARBOXYPEPTIDASE HOMOLOG). Additional BLAST results are shown in Table 8 J.
  • Zn_carbOpept domain 1 of 1 , from 50 to 332 384.8 8.7e-112
  • NOV8 contains a zinc carboxypeptidase domain as illustrated in Table 8L.
  • NON8 nucleic acids, and the encoded polypeptides, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON8 nucleic acids and polypeptides can be used to identify proteins that are members of the carboxypeptidase family of proteins.
  • the ⁇ ON8 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON8 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., digestion or hydrolysis of polypeptide chains. These molecules can be used to treat, , e.g., pancreatitis, ulcers, inflammatory bowel disease, diverticular disease, Crohn's disease, appendicitis, or obesity.
  • ⁇ ON8 nucleic acids and polypeptides according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the ⁇ ON8 nucleic acids and their encoded polypeptides include structural motifs that are characteristic of proteins belonging to the carboxypeptidase family.
  • Carboxypeptidase B, (CPB) like carboxypeptidase A is a pancreatic exopeptidase. Unlike carboxypeptidase A, however, carboxypeptidase B catalyzes the hydrolysis of the peptide bonds involving basic amino acids lysine, arginine and ornithine. This hydrolysis occurs at the C-terminal bond in these polypeptides.
  • the ⁇ ON8 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of hydrolysis.
  • the ⁇ ON8 nucleic acids and polypeptides, antibodies and related compounds according to the invention maybe used to treat digestive disorders, e.g., xerostomia, hypercalceimia, ulcers, Non Hippel-Lindau (NHL) syndrome, cirrhosis, transplantation, inflammatory bowel disease, diverticular disease, hirschsprung's disease, crohn's disease, appendicitis, stroke, tuberous sclerosis, anxiety, pain, endocrine dysfunctions, nueroprotection, diabetes, obesity, growth and reproductive disorders, myasthenia gravis.
  • digestive disorders e.g., xerostomia, hypercalceimia, ulcers, Non Hippel-Lindau (NHL) syndrome, cirrhosis, transplantation, inflammatory bowel disease, diverticular disease, hirschsprung's disease
  • the NON8 nucleic acids and polypeptides are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON8 nucleic acid is expressed in pooled mammalian tissue, small intestine, and spinal cord.
  • the disclosed ⁇ ON9 nucleic acid (alternatively referred to herein as CG56463-01) encodes a novel neurotransmitter receptor-like protein and includes the 1142 nucleotide sequence (SEQ ID ⁇ O:27) shown in Table 9A.
  • the NON9 nucleic acid disclosed herein maps to chromosome 6p23.
  • NON9 has a signal peptide and is likely to be localized in the plasma membrane with a certainty of 0.6000.
  • a ⁇ ON9 polypeptide is located to the Golgi body with a certainty of 0.4000, the endoplasmic reticulum (membrane) with a certainty of 0.3000, or the mitochondrial inner membrane with a certainty of 0.0300.
  • the SignalP indicates a likely cleavage site for a ⁇ ON9 polypeptide is between positions 47 and 48, i.e., at the dash in the sequence MIA-IL.
  • the ⁇ ON9 nucleic acid sequence of this invention has 601 of 1000 bases (60%) identical to a gb:GE ⁇ BA ⁇ K-ID:AR035954
  • the NOV9 protein of the invention also has homolgy to the proteins shown in the BLASTP data in Table 9D.
  • NOV9 contains 7-transmembrane domains as illustrated in Table 9F.
  • NOV9 nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • NOV9 nucleic acids and polypeptides can be used to identify proteins that are members of the neurotransmitter receptor family of proteins.
  • the NOV9 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOV9 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., cellular recognition, or G-protein-mediated transduction of neuromuscular/synaptic signals. These molecules can be used to treat, e.g., neurological disorders, immune diseases, or signal transduction pathways.
  • the NON9 nucleic acid and polypeptide according to the invention are useful, inter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the ⁇ ON9 nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of neurotransmitter receptor proteins.
  • Nerve cells are highly specialized for cell-to-cell communication.
  • a number of small molecules called neurofransmitters act as the actual signals, released from one nerve cell only to dock on another cell.
  • neurotransmitter molecule When a neurotransmitter molecule fits into a receptor, it typically opens the gate, allowing ions to travel through the cell's membrane. The ions, in turn, excite the cell. If the receiving cell is a nerve cell, this excitation can lead to release of its own neurofransmitters.
  • the vast majority of neurotransmitter receptors belong to a class of proteins known as the se ⁇ entine receptors. This class exhibits a characteristic transmembrane structure: spaning the cell membrane, seven times.
  • neurotransmitter receptors are subject to ligand-induced desensitization: such that they can become unresponsive upon prolonged exposure to their neurotransmitter.
  • the NOV9 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of signal transduction.
  • the NON9 nucleic acid and polypeptide, antibodies and related compounds according to the invention maybe used to treat, e.g., leukemia, acute nonlymphocytic, spinocerebellar ataxia-1, or neurological disorders.
  • the ⁇ ON9 nucleic acid and polypeptide are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON9 nucleic acid is predominantly expressed in skeletal muscle and selected areas of the brain. Additional utilities for the NON9 nucleic acid and polypeptide according to the invention are disclosed herein.
  • the disclosed ⁇ ON10 nucleic acid (alternatively referred to herein as CG56321-01) encodes a novel proto-oncogene MAF-like protein and includes the 1189 nucleotide sequence (SEQ ID ⁇ O:29) shown in Table 10A.
  • the NON10 nucleic acid disclosed herein maps to chromosome 8.
  • the NOV10 protein (SEQ ID NO:30) encoded by SEQ ID NO:29 is 353 amino acid residues in length and is presented using the one-letter amino acid code in Table 10B.
  • the SignalP, Psort and/or Hydropathy results indicate that NOV10 has no known signal peptide and is likely to be localized in the nucleus with a certainty of 0.7600.
  • a NONIO polypeptide is located to the microbody (peroxisome) with a certainty of 0.5418, the lysosome (lumen) with a certainty of 0.1882, or the mitochondrial matrix space with a certainty of 0.1000.
  • Table 10B Encoded NOV10 Protein Sequence (SEQ ID NO:30)
  • ⁇ ON10 nucleic acid sequence of this invention has 258 of 322 bases (80%) identical to a gb:GE ⁇ BA ⁇ K-ID:AF034693
  • the full amino acid sequence of the disclosed NONIO protein of the invention has 134 of 249 amino acid residues (53%) identical to, and 151 of 249 amino acid residues (60%) similar to, the 311 amino acid residue ptnr:SPTREMBL-ACC:Q90370 protein from Coturnix coturnix japonica (Japanese quail) (MAFB PROTEIN).
  • the NOVl 0 protein of the invention also has homolgy to the proteins shown in the
  • NONIO contains MAF domains as illustrated in Table 10F.
  • ⁇ ON10 nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON10 nucleic acids and polypeptides can be used to identify proteins that are members of the bZip transcription factor family of proteins.
  • the ⁇ ON10 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON10 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., gene regulation/expression. These molecules can be used to treat, e.g., autoimmune disorders or antioxidant induction of molecules such as ⁇ QO1, GST,
  • the ⁇ ON10 nucleic acid and polypeptide according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the ⁇ ON10 nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of bZip transcription factor proteins.
  • Transcription factors are proteins that bind to the enhancer or promoter regions and interact such that transcription occurs from only a small group of promoters in any cell. Most transcription factors can bind to specific D ⁇ A sequences, and these trans- regulatory proteins can be grouped together in families based on similarities in structure.
  • transcription factors contain a domain involved in activating the transcription of the gene whose promoter or enhancer it has bound. Usually, this trans-activating domain enables that transcription factor to interact with proteins involved in binding RNA polymerase. This interaction often enhances the efficiency with which the basal transcriptional complex can be built and bind RNA polymerase II.
  • transcription factors There are several families of transcription factors.
  • the bZip transcription factor family of proteins are dimers, each of whose subunits contains a basic DNA-binding domain at the carboxyl end, followed closely by an a helix containing several leucine residues. These leucines are placed in the helix such that they interact with similarly spaced leucine residues on other bZip proteins to form a "leucine zipper" between them, causing dimers to form. This domain is followed by a regulatory domain that can interact with the promoter to stimulate or repress transcription.
  • the NONIO nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of gene transcription.
  • antibodies and related compounds according to the invention may be used to treat, e.g., anemia, ataxia-telangiectasia, autoimmume disease, cancer, immunodeficiencies, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, allergies, transplantation, graft versus host disease (GNHD), lymphaedema, systemic lupus erythematosus, asthma, emphysema, scleroderma, ARDS, diabetes, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, hypercalceimia, or Lesch- ⁇ yhan syndrome.
  • the ⁇ ON10 nucleic acid and polypeptide are useful for detecting specific cell types. For example, anemia, ataxia-telangiec
  • the NOVl 1 proteins descibed herein are novel lysyl oxidase-like proteins.
  • the NOVl 1 nucleic acids disclosed herein map to chromosome 10.
  • Two alternative novel NOVl 1 nucleic acids and polypeptides are disclosed herein, namely NON1 la and ⁇ ON1 lb.
  • a ⁇ ON11 variant is ⁇ ON1 la (alternatively referred to herein as CG56381-01), which encodes the 2599 nucleotide sequence (SEQ ID ⁇ O:31) shown in Table 1 IA.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 78-80 and ending with a TGA codon at nucleotides 2568-2570. Putative untranslated regions, if any, downstream from the termination codon and upstream from the imtiation codon are underlined. The start and stop codons are in bold letters.
  • the NONl la protein (SEQ ID ⁇ O:32) encoded by SEQ ID NO:31 is 830 amino acid residues in length and is presented using the one-letter amino acid code in Table 1 IB.
  • the SignalP, Psort and/or Hydropathy results indicate that NOVl la has a signal peptide and is likely to be localized in the lysosome (lumen) with a certainty of 0.4247.
  • a NOVl la polypeptide is located extracellularly with a certainty of 0.3700, the microbody (peroxisome) with a certainty of 0.1250, or the endoplasmic reticulum (membrane) with a certainty of 0.1000.
  • the SignalP indicates a likely cleavage site for a NOVl la peptide between positions 24 and 25, i.e., at the dash in the sequence SRP-QS.
  • a ⁇ ON11 variant is ⁇ ON1 lb (alternatively referred to herein as CG56381- 02), which includes the 2592 nucleotide sequence (SEQ ID ⁇ O:33) shown in Table 1 IC.
  • SEQ ID ⁇ O:33 2592 nucleotide sequence shown in Table 1 IC.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 46-48 and ending with a TGA codon at nucleotides 2314-2316. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • the NONl lb protein (SEQ ID ⁇ O:34) encoded by SEQ ID NO:33 is 756 amino acid residues in length and is presented using the one-letter amino acid code in Table 1 ID.
  • the SignalP, Psort and/or Hydropathy results indicate that NOVl lb has a signal peptide and is likely to be localized in the lysosome (lumen) with a certainty of 0.4302.
  • a NOVl lb polypeptide is located extracellularly with a certainty of 0.3700, the microbody (peroxisome) with a certainty of 0.1403, or the endoplasmic reticulum (membrane) with a certainty of 0.1000.
  • the SignalP indicates a likely cleavgae site for a NONl lb peptide between positions 24 and 25, i.e., at the dash in the sequence SRP-QS.
  • any reference to ⁇ OV11 is assumed to encompass all variants.
  • a search against the Patp database a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table HE.
  • NOVl la nucleic acid sequence of this invention has 1075 of 1078 bases (99%) identical to a gb:GENBANK-ID:AK025542
  • the full amino acid sequence of the disclosed NONl la protein of the invention has 404 of 705 amino acid residues (57%) identical to, and 523 of 705 amino acid residues (74%) similar to, the 774 amino acid residue ⁇ tnr:SPTREMBL-ACC:Q9Y4K0 protein from Human (LYSYL OXIDASE-RELATED PROTEIN).
  • NOVl lb nucleic acid sequence of this invention has 1070 of 1076 bases (99%) identical to a gb:GENBANK-ID:AK025542
  • the full amino acid sequence of the disclosed NONl lb protein of the invention has 360 of 616 amino acid residues (58%) identical to, and 456 of 616 amino acid residues (74%) similar to, the 895 amino acid residue ptnr:SPTREMBL-ACC:Q9W6Nl protein from Perca flavescens (Yellow perch) (LYSYL OXIDASE RELATED PROTEIN HOMOLOG). Additional BLAST results are shown in Table 1 IF.
  • NONl 1 contains a lysyl oxidase domain as illustrated in Table 1 IH.
  • ⁇ ON11 nucleic acids, and the encoded polypeptides, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON11 nucleic acids and polypeptides can be used to identify proteins that are members of the copper-dependent amine oxidase family of proteins.
  • the ⁇ ON11 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON11 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., crosslinking of extracellular matrix proteins. These molecules can be used to treat, e.g., autoimmune disease, allergies, immunodeficiencies, asthma, psoriasis, acne, or pigmentation disorders.
  • ⁇ ON11 nucleic acids and polypeptides according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the ⁇ ON11 nucleic acids and their encoded polypeptides include structural motifs that are characteristic of proteins belonging to the lysyl oxidase family.
  • Lysyl oxidase (LOX) is a secreted enzyme that cross-links collagen and elastin, and thus is critical for the integrity of the extracellular matrix, the breakdown of which contributes to cancer invasion and metastasis.
  • LOX is also important to the health of connective tissues and arteries.
  • Lysyl oxidase requires a copper co-factor and therefore its activity can be lowered by a dietary deficiency.
  • the NONl 1 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of crosslinking and biogenesis of connective tissue matrices.
  • ⁇ ON11 nucleic acids and polypeptides antibodies and related compounds according to the invention may be used to treat digestive disorders, e.g., diabetes, Non Hippel-Lindau (NHL) syndrome, pancreatitis, obesity, endometriosis, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmume disease, allergies, immunodeficiencies, transplantation, graft versus host disease (GNHD), lymphaedema, osteoporosis, hypercalceimia, arthritis, ankylosing spondylitis, scoliosis, systemic lupus erythematosus, asthma, emphysema, scleroderma, allergy, ARDS, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acid
  • the ⁇ ON11 nucleic acids and polypeptides are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON11 nucleic acid is expressed in kidney, lung, lymphoid tissue, mammary gland/breast, ovary, pancreas, testis, uterus, and bone.
  • the ⁇ ON12 proteins descibed herein are novel phosphatase-like proteins.
  • the ⁇ ON12 nucleic acids disclosed herein map to chromosome 17.
  • Two alternative novel ⁇ ON12 nucleic acids and polypeptides are disclosed herein, namely ⁇ ON12a and ⁇ ON12b.
  • ⁇ ON12a A ⁇ ON12 variant is ⁇ ON12a (alternatively referred to herein as CG56436-01), which encodes the 1002 nucleotide sequence (SEQ ID ⁇ O:35) shown in Table 12A.
  • SEQ ID ⁇ O:35 1002 nucleotide sequence
  • the NOV12a protein (SEQ TD NO:36) encoded by SEQ ID NO:35 is 267 amino acid residues in length and is presented using the one-letter amino acid code in Table 12B.
  • the SignalP, Psort and/or Hydropathy results indicate that NON 12a has no known signal peptide and is likely to be localized in the mitochondrial matrix space with a certainty of 0.4728.
  • a ⁇ ON12a polypeptide is located in the microbody (peroxisome) with a certainty of 0.2224, the lysosome (lumen) with a certainty of 0.1905, or the mitochondrial inner membrane with a certainty of 0.1762.
  • NOV12b (alternatively referred to herein as CG56436- 02), which includes the 903 nucleotide sequence (SEQ ID NO:37) shown in Table 12C.
  • SEQ ID NO:37 the 903 nucleotide sequence shown in Table 12C.
  • An open reading frame for the mature protein was identified beginning with an ATG codon at nucleotides 4-6 and ending with a TGA codon at nucleotides 805-807. Putative untranslated regions, if any, downstream from the termination codon and upstream from the initiation codon are underlined. The start and stop codons are in bold letters.
  • Table 12C NON12b Nucleotide Sequence (SEQ ID NO:37)
  • the NOV12b protem (SEQ ID NO:38) encoded by SEQ ID NO:37 is 267 amino acid residues in length and is presented using the one-letter amino acid code in Table 12D.
  • the SignalP, Psort and/or Hydropathy results predict that NOV12b has no known signal peptide and is likely to be localized in the mitochondrial matrix space with a certainty of 0.4728.
  • a NON 12b polypeptide is located in the microbody (peroxisome) with a certainty of 0.2224, the lysosome (lumen) with a certainty of 0.1905, or the mitochondrial inner membrane with a certainty of 0.1762.
  • NOV12a or NOV12b any reference to NOV12 is assumed to encompass all variants.
  • a search against the Patp database a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12E.
  • NOVl 2a nucleic acid sequence of this invention has 609 of 916 bases (66%) identical to a gb:GENBANK-ID:GGA6529
  • the full amino acid sequence of the disclosed NON12a protein of the invention has 159 of 265 amino acid residues (60%) identical to, and 199 of 265 amino acid residues (75%) similar to, the 268 amino acid residue ⁇ tnr:SPTREMBL-ACC:O73884 protein from Gallus gallus (Chicken) (PUTATIVE PHOSPHATASE).
  • the ⁇ ON12b nucleic acid sequence of this invention has 579 of 865 bases (66%) identical to a gb:GE ⁇ BA ⁇ K-ID:GGA6529
  • the full amino acid sequence of the disclosed NON12b protein of the invention has 159 of 265 amino acid residues (60%) identical to, and 199 of 265 amino acid residues (75%) similar to, the 268 amino acid residue ptnr:SPTREMBL-ACC:O73884 protein from Gallus gallus (Chicken) (PUTATIVE PHOSPHATASE).
  • NOVl2a 267 NOV12b 267 073884 268 Q9D9M5 241 Q9V F0 RASAVAGPTKSPN 306 Q9SU92 245 Q9FZ62 EPIQVPLNLVK- - 279
  • Hyd. nD. apalaaAGvgvamgngg (SEQ ID NO: 198)
  • NOV12 contains a hydrolase domain as illustrated in Table 12H.
  • NON12 nucleic acids, and the encoded polypeptides, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON12 nucleic acids and polypeptides can be used to identify proteins that are members of the protein phosphatase family of proteins.
  • the ⁇ ON12 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON12 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., biological processes that control cell growth and homeostasis.
  • these molecules can be used to treat, e.g., hyper/hypothyroidism, endometriosis, fertility, transplantation, hypogonadism, Alzheimer's disease, Parkinson's disease, neurodegeneration, or grwoth disorders.
  • various ⁇ OV12 nucleic acids and polypeptides according to the invention are useful, ter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the NON 12 nucleic acids and their encoded polypeptides include structural motifs that are characteristic of proteins belonging to the protein phosphatase family. The major protein phosphatases in all cells are highly conserved and widely distributed.
  • NON12 nucleic acids and polypeptides, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of cell signaling/signal transduction.
  • antibodies and related compounds according to the invention may be used to treat, e.g., hyperthyroidism, hypothyroidism, endometriosis, fertility, Non Hippel-Lindau (NHL) syndrome, cirrhosis, transplantation, hypogonadism, Alzheimer's disease, stroke, tuberous sclerosis, hypercalceimia, Parkinson's disease, Huntington's disease, cerebral palsy, epilepsy, Lesch- ⁇ yhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, neurodegeneration, endocrine dysfunctions, diabetes, obesity, growth and reproductive disorders, systemic lupus erythematosus, autoimmune disease, asthma, emphysema, scleroderma, allergy, ARDS, renal artery stenosis, interstitial nephritis, glomeruloneph
  • the ⁇ ON12 nucleic acids and polypeptides are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON12 nucleic acid is expressed in bone marrow, brain, kidney, liver, lung, lung pleura, pituitary gland, placenta, and thyroid.
  • the disclosed ⁇ ON13 nucleic acid (alternatively referred to herein as CG56441-01) encodes a novel chloride channel protein CLC-KA-like protein and includes the 1991 nucleotide sequence (SEQ ID ⁇ O:39) shown in Table 13A.
  • the NON13 protein (SEQ ID ⁇ O:40) encoded by SEQ ID NO:39 is 655 amino acid residues in length and is presented using the one-letter amino acid code in Table 13B.
  • the SignalP, Psort and/or Hydropathy results indicate that NOVl 3 has a signal peptide and is likely to be localized at the plasma membrane with a certainty of 0.6000.
  • a NON13 polypeptide is located to the Golgi body with a certainty of 0.4000, the endoplasmic reticulum (membrane) with a certainty of 0.1882, or the microbody (peroxisome) with a certainty of 0.3000.
  • the SignalP indicates a likely cleavage site for a ⁇ ON13 peptide between positions 66 and 67, i.e., at the dash in the sequence SYA-M ⁇ .
  • NON 13 nucleic acid sequence of this invention has 1768 of 1779 bases (99%) identical to a gb:GE ⁇ BA ⁇ K-TD:HSCLCHPRA
  • the full amino acid sequence of the disclosed NON13 protein of the invention has 578 of 579 amino acid residues (99%) identical to, and 578 of 579 amino acid residues (99%) similar to, the 687 amino acid residue ⁇ tnr:SWISSPROT-ACC:P51800 protein from Human (CHLORIDE CHANNEL PROTEIN CLC-KA (CLC-K1)).
  • the NONl 3 protein of the invention also has homolgy to the proteins shown in the BLASTP data in Table 13D.
  • NON 13 contains CLC domains as illustrated in Table 13F.
  • ⁇ ON13 nucleic acid, and the encoded polypeptide, according to the invention are useful in a variety of applications and contexts.
  • ⁇ ON13 nucleic acids and polypeptides can be used to identify proteins that are members of the voltage-gated chloride chaimel family of proteins.
  • the ⁇ ON13 nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance ⁇ ON13 activity or function.
  • the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit, e.g., physiological functions such as cell volume regulation, membrane potential stabilization, signal transduction, or transepithelial transport. These molecules can be used to treat, e.g., diseases associated with the kidney such as renal artery stenosis, diabetes, or renal tubular acidosis.
  • the ⁇ ON13 nucleic acid and polypeptide according to the invention are useful, inter alia, as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins.
  • the ⁇ ON13 nucleic acid and polypeptide include structural motifs that are characteristic of proteins belonging to the family of voltage-gated chloride channel proteins. All functionally characterized members of the CLC family transport chloride, some in a voltage-regulated process. These channels serve a variety of physiological functions such as cell volume regulation, membrane potential stabilization, signal transduction, and transepithelial transport.
  • the NONl 3 nucleic acid and polypeptide, antibodies and related compounds according to the invention will be useful in therapeutic and diagnostic applications in the mediation of kidney diseases.
  • antibodies and related compounds according to the invention may be used to treat, e.g., diabetes, autoimmune disease, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, hypercalceimia, or Lesch- ⁇ yhan syndrome.
  • the ⁇ ON13 nucleic acid and polypeptide are useful for detecting specific cell types. For example, expression analysis has demonstrated that a ⁇ ON13 nucleic acid is expressed in the kidney.
  • NOV14 nucleic acid (alternatively referred to herein as CG56443-01) encodes a novel mast cell function-associated antigen (MAFA)-like protein and includes the 645 nucleotide sequence (SEQ ID NO:41) shown in Table 14A.
  • the NON14 nucleic acid disclosed herein maps to chromosome 19.
  • NOV14 has a signal peptide and is likely to be localized at the plasma membrane with a certainty of 0.7900.
  • a NOV14 polypeptide is located to the microbody (peroxisome) with a certainty of 0.5804, the Golgi body with a certainty of 0.3000, or the endoplasmic reticulum (membrane) with a certainty of 0.2000.
  • the SignalP indicates a likely cleavage site for a NON14 peptide between positions 57 and 58, i.e:, at the dash in the sequence SLA-LS.

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Abstract

La présente invention concerne de nouveaux polypeptides et des acides nucléiques codant pour ces derniers. Cette invention concerne aussi des vecteurs, des cellules hôtes, des anticorps et des techniques de recombinaison permettant de produire ces polypeptides et ces polynucléotides, ainsi que des techniques d'utilisation de ceux-ci.
PCT/US2002/002064 2001-01-19 2002-01-22 Nouveaux polypeptides et acides nucleiques codant pour ces derniers Ceased WO2002081517A2 (fr)

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WO2003090771A3 (fr) * 2002-04-25 2004-04-08 Bayer Healthcare Ag Diagnostique et therapeutique de maladies associees aux recepteurs 3 d'amine sous forme de traces (ta3)
EP1254265A4 (fr) * 2000-02-03 2004-06-30 Nuvelo Inc Methodes et materiaux concernant des polypeptides et des polynucleotides du type metallocarboxypeptidase
EP1406653A4 (fr) * 2001-06-29 2005-05-04 Univ Leland Stanford Junior Genes regulateurs de lymphocytes t et leurs methodes d'utilisation
WO2005040803A1 (fr) * 2003-10-21 2005-05-06 Bayer Healthcare Ag Diagnostics et therapeutique destines a des maladies associees a l'element 6 de type 2 de famille 22 de support de solute humain (slc22a6-type2)
WO2004050831A3 (fr) * 2002-11-27 2006-09-14 Wyeth Corp Compositions, organismes et procedes faisant appel a une nouvelle kinase humaine
EP1576169A4 (fr) * 2002-03-19 2008-07-16 Curagen Corp Polypeptides therapeutiques, acides nucleiques codant pour ceux-ci et methodes d'utilisation associees
US7741271B2 (en) 2004-03-12 2010-06-22 The Brigham And Women's Hospital, Inc. Methods of modulating immune responses by modulating tim-1, tim-2 and tim-4 function
EP2333112A2 (fr) 2004-02-20 2011-06-15 Veridex, LLC Pronostics de cancer du sein
US8008332B2 (en) 2006-05-31 2011-08-30 Takeda San Diego, Inc. Substituted indazoles as glucokinase activators
US8034822B2 (en) 2006-03-08 2011-10-11 Takeda San Diego, Inc. Glucokinase activators
US8124617B2 (en) 2005-09-01 2012-02-28 Takeda San Diego, Inc. Imidazopyridine compounds
US8163779B2 (en) 2006-12-20 2012-04-24 Takeda San Diego, Inc. Glucokinase activators
US8173645B2 (en) 2007-03-21 2012-05-08 Takeda San Diego, Inc. Glucokinase activators
US8329660B2 (en) 2003-10-03 2012-12-11 The Brigham And Women's Hospital, Inc. Tim-3 ligands and methods thereof
US8709412B2 (en) 2001-06-29 2014-04-29 The Board Of Trustees Of The Leland Stanford Junior University Modulation of TIM receptor activity in combination with cytoreductive therapy
US11547765B2 (en) 2016-06-21 2023-01-10 The University Of North Carolina At Chapel Hill Optimized mini-dystrophin genes and expression cassettes and their use

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ATE140966T1 (de) * 1990-09-25 1996-08-15 Genentech Inc Neuer neurotropischer faktor
US7122345B2 (en) * 2001-01-09 2006-10-17 Curagen Corporation Nucleic acid encoding a NOVX13 polypeptide

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EP1254265A4 (fr) * 2000-02-03 2004-06-30 Nuvelo Inc Methodes et materiaux concernant des polypeptides et des polynucleotides du type metallocarboxypeptidase
EP1406653A4 (fr) * 2001-06-29 2005-05-04 Univ Leland Stanford Junior Genes regulateurs de lymphocytes t et leurs methodes d'utilisation
US9683049B2 (en) 2001-06-29 2017-06-20 The Board Of Trustees Of The Leland Stanford Junior University Modulation of TIM receptor activity in combination with cytoreductive therapy
US7553939B2 (en) 2001-06-29 2009-06-30 The Board Of Trustees Of The Leland Stanford Junior University T cell regulatory genes and methods of use thereof
US8709412B2 (en) 2001-06-29 2014-04-29 The Board Of Trustees Of The Leland Stanford Junior University Modulation of TIM receptor activity in combination with cytoreductive therapy
EP1576169A4 (fr) * 2002-03-19 2008-07-16 Curagen Corp Polypeptides therapeutiques, acides nucleiques codant pour ceux-ci et methodes d'utilisation associees
WO2003090771A3 (fr) * 2002-04-25 2004-04-08 Bayer Healthcare Ag Diagnostique et therapeutique de maladies associees aux recepteurs 3 d'amine sous forme de traces (ta3)
WO2004050831A3 (fr) * 2002-11-27 2006-09-14 Wyeth Corp Compositions, organismes et procedes faisant appel a une nouvelle kinase humaine
US7297525B2 (en) * 2002-11-27 2007-11-20 Wyeth Composition employing a novel human kinase
US8329660B2 (en) 2003-10-03 2012-12-11 The Brigham And Women's Hospital, Inc. Tim-3 ligands and methods thereof
US9346876B2 (en) 2003-10-03 2016-05-24 The Brigham And Women's Hospital, Inc. TIM-3 ligands and methods of modulating immune responses
WO2005040803A1 (fr) * 2003-10-21 2005-05-06 Bayer Healthcare Ag Diagnostics et therapeutique destines a des maladies associees a l'element 6 de type 2 de famille 22 de support de solute humain (slc22a6-type2)
EP2333112A2 (fr) 2004-02-20 2011-06-15 Veridex, LLC Pronostics de cancer du sein
US7741271B2 (en) 2004-03-12 2010-06-22 The Brigham And Women's Hospital, Inc. Methods of modulating immune responses by modulating tim-1, tim-2 and tim-4 function
US8124617B2 (en) 2005-09-01 2012-02-28 Takeda San Diego, Inc. Imidazopyridine compounds
US8034822B2 (en) 2006-03-08 2011-10-11 Takeda San Diego, Inc. Glucokinase activators
US8008332B2 (en) 2006-05-31 2011-08-30 Takeda San Diego, Inc. Substituted indazoles as glucokinase activators
US8394843B2 (en) 2006-05-31 2013-03-12 Takeda California, Inc. Substituted isoindoles as glucokinase activators
US8163779B2 (en) 2006-12-20 2012-04-24 Takeda San Diego, Inc. Glucokinase activators
US8173645B2 (en) 2007-03-21 2012-05-08 Takeda San Diego, Inc. Glucokinase activators
US11547765B2 (en) 2016-06-21 2023-01-10 The University Of North Carolina At Chapel Hill Optimized mini-dystrophin genes and expression cassettes and their use
US12257321B2 (en) 2016-06-21 2025-03-25 The University Of North Carolina At Chapel Hill Optimized mini-dystrophin genes and expression cassettes and their use

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