EP1097199A1 - 71 proteines humaines secretees - Google Patents

71 proteines humaines secretees

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Publication number
EP1097199A1
EP1097199A1 EP99937247A EP99937247A EP1097199A1 EP 1097199 A1 EP1097199 A1 EP 1097199A1 EP 99937247 A EP99937247 A EP 99937247A EP 99937247 A EP99937247 A EP 99937247A EP 1097199 A1 EP1097199 A1 EP 1097199A1
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EP
European Patent Office
Prior art keywords
seq
gene
polypeptides
tissue
protein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99937247A
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German (de)
English (en)
Other versions
EP1097199A4 (fr
Inventor
Steven M. Ruben
George Komatsoulis
Roxanne D. Duan
Craig A. Rosen
Paul A. Moore
Yang-Gu Shi
David W. Lafleur
Reinhard Ebner
Henrik S. Olsen
Laurie A. Brewer
Kimberly A. Florence
Paul E. Young
Michael Human Genome Sciences Inc. MUCENSKI
Gregory A. Endress
Daniel R. Soppet
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Human Genome Sciences Inc
Original Assignee
Human Genome Sciences Inc
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Publication date
Application filed by Human Genome Sciences Inc filed Critical Human Genome Sciences Inc
Publication of EP1097199A1 publication Critical patent/EP1097199A1/fr
Publication of EP1097199A4 publication Critical patent/EP1097199A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/20—Screening for compounds of potential therapeutic value cell-free systems

Definitions

  • This invention relates to newly identified polynucleotides and the polypeptides encoded by these polynucleotides. uses of such polynucleotides and polypeptides, and their production.
  • One type of sorting signal directs a class of proteins to an organelle called the endoplasmic reticulum (ER).
  • ER endoplasmic reticulum
  • the ER separates the membrane-bounded proteins from all other types of proteins. Once localized to the ER, both groups of proteins can be further directed to another organelle called the Golgi apparatus.
  • the Golgi distributes the proteins to vesicles, including secretory vesicles, the cell membrane, lysosomes, and the other organelles. Proteins targeted to the ER by a signal sequence can be released into the extracellular space as a secreted protein.
  • vesicles containing secreted proteins can fuse with the cell membrane and release their contents into the extracellular space - a process called exocytosis. Exocytosis can occur constitutively or after receipt of a triggering signal. In the latter case, the proteins are stored in secretory vesicles (or secretory granules) until exocytosis is triggered. Similarly, proteins residing on the cell membrane can also be secreted into the extracellular space by proteolytic cleavage of a "linker" holding the protein to the membrane.
  • the present invention relates to novel polynucleotides and the encoded polypeptides. Moreover, the present invention relates to vectors, host cells, antibodies, and recombinant methods for producing the polypeptides and polynucleotides. Also provided are diagnostic methods for detecting disorders related to the polypeptides, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying binding partners of the polypeptides.
  • isolated refers to material removed from its original environment (e.g., the natural environment if it is naturally occurring), and thus is altered “by the hand of man” from its natural state.
  • an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be “isolated” because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide.
  • a "secreted" protein refers to those proteins capable of being directed to the ER, secretory vesicles, or the extracellular space as a result of a signal sequence, as well as those proteins released into the extracellular space without necessarily containing a signal sequence. If the secreted protein is released into the extracellular space, the secreted protein can undergo extracellular processing to produce a "mature" protein. Release into the extracellular space can occur by many mechanisms, including exocytosis and proteolytic cleavage.
  • the polynucleotides of the invention are less than 300 kb, 200 kb, 100 kb, 50 kb, 15 kb, 10 kb, or 7.5 kb in length.
  • polynucleotides of the invention comprise at least 15 contiguous nucleotides of the coding sequence, but do not comprise all or a portion of any intron.
  • the nucleic acid comprising the coding sequence does not contain coding sequences of a genomic flanking gene (i.e., 5' or 3' to the gene in the genome).
  • a "polynucleotide” refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X or the cDNA contained within the clone deposited with the ATCC.
  • the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5' and 3' untranslated sequences, the coding region, with or without the signal sequence, the secreted protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence.
  • a "polypeptide” refers to a molecule having the translated amino acid sequence generated from the polynucleotide as broadly defined.
  • the full length sequence identified as SEQ ID NO:X was often generated by overlapping sequences contained in multiple clones (contig analysis).
  • a representative clone containing all or most of the sequence for SEQ ID NO:X was deposited with the American Type Culture Collection ("ATCC"). As shown in Table 1, each clone is identified by a cDNA Clone ID (Identifier) and the ATCC Deposit Number.
  • the ATCC is located at 10801 University Boulevard, Manassas, Virginia 20110-2209, USA.
  • the ATCC deposit was made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for purposes of patent procedure.
  • a "polynucleotide” of the present invention also includes those polynucleotides capable of hybridizing, under stringent hybridization conditions, to sequences contained in SEQ ID NO:X, the complement thereof, or the cDNA within the clone deposited with the ATCC.
  • “Stringent hybridization conditions” refers to an overnight incubation at 42° C in a solution comprising 50% formamide, 5x SSC (750 mM NaCl, 75 mM sodium citrate), 50 mM sodium phosphate (pH 7.6), 5x Denhardt's solution, 10% dextran sulfate, and 20 ⁇ g/ml denatured, sheared salmon sperm DNA, followed by washing the filters in O.lx SSC at about 65°C Also contemplated are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower st ⁇ ngency hybridization conditions.
  • Changes in the st ⁇ ngency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered st ⁇ ngency); salt conditions, or temperature.
  • washes performed following st ⁇ ngent hyb ⁇ dization can be done at higher salt concentrations (e.g 5X SSC).
  • va ⁇ ations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hyb ⁇ dization expenments.
  • Typical blocking reagents include Denhardt's reagent, BLOTTO, hepa ⁇ n, denatured salmon sperm DNA, and commercially available prop ⁇ etary formulations.
  • the inclusion of specific blocking reagents may require modification of the hyb ⁇ dization conditions desc ⁇ bed above, due to problems with compatibility.
  • polynucleotide which hyb ⁇ dizes only to polyA+ sequences (such as any 3' terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of "polynucleotide,” since such a polynucleotide would hyb ⁇ dize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone).
  • polynucleotide of the present invention can be composed of any poly ⁇ bonucleotide or polydeox ⁇ bonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA.
  • polynucleotides can be composed of single- and double-stranded DNA, DNA that is a mixture of single- and double- stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hyb ⁇ d molecules compnsmg DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions.
  • polynucleotide can be composed of t ⁇ ple-stranded regions compnsmg RNA or DNA or both RNA and DNA.
  • a polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons "Modified" bases include, for example, t ⁇ tylated bases and unusual bases such as mos e.
  • Modified bases include, for example, t ⁇ tylated bases and unusual bases such as mos e.
  • a va ⁇ ety of modifications can be made to DNA and RNA; thus, "polynucleotide” embraces chemically, enzymatically, or metabo cally modified forms.
  • the polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids.
  • the polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art. Such modifications are well desc ⁇ bed in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the ammo acid side-chams and the am o or carboxyl termini.
  • polypeptides may be branched , for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods.
  • Modifications include acetylation, acylation, ADP-nbosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide de ⁇ vative, covalent attachment of a lipid or lipid denvative, covalent attachment of phosphotidy nositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins such as arginylation, and ubiquitination.
  • SEQ ID NO:X refers to a polynucleotide sequence while “SEQ ID NO:Y” refers to a polypeptide sequence, both sequences identified by an integer specified in Table 1.
  • a polypeptide having biological activity refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the present invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. In the case where dose dependency does exist, it need not be identical to that of the polypeptide, but rather substantially similar to the dose-dependence in a given activity as compared to the polypeptide of the present invention (i.e., the candidate polypeptide will exhibit greater activity or not more than about 25-fold less and, preferably, not more than about tenfold less activity, and most preferably, not more than about three-fold less activity relative to the polypeptide of the present invention.)
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence: PFCSGFFPSLWIYLPFIFNVSDLWMGSLSGCALPFCLXVFFLTVSPSAVGLLXF AGGPLQTLFAWVSPVEAAEQQRLLPVLSSGSFVSEGTCQMPARALLYEVSVG PYWEIPPSQDTRRSGTYLRRQSDP (SEQ ID NO: 195) .
  • Polynucleotides encoding these polypeptides are also provided.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the pancreas, including cancer and diabetes.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., endocrine, cancerous, or wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in tumors of pancreatic islet cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis, treatment and intervention of such tumors, in addition to other endocrine or gastrointestinal tumors where expression has been indicated.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 11 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 11 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1099 of SEQ ID NO: 11, b is an integer of 15 to 1113, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 11, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • HEGSCRAPGFSAHKGRGCPSPRMTLPSRALASLGVGVWGMLRLNQVTVSCG GSRWSSRVALGAFSWVCGVALVLQPSGGGLGLTSPSEGCWEGELALAVLRA PGGSPS (SEQ ID NO: 196) .
  • Polynucleotides encoding these polypeptides are also provided. This gene is expressed equally in in .
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoietic disorders, particularly leukemia.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 104 as residues: Gly-29 to Ser-35, Ser-63 to Cys-68. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in hemangiopericytoma, breast lymph node, and bone marrow indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages.
  • Representative uses are described in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • the uses include bone marrow cell ex vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia.
  • the gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 12 amino acid sequences
  • amino acid sequences are related to SEQ ID NO: 12 and may have been publicly available prior to conception of the present invention.
  • such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 969 of SEQ ID NO: 12, b is an integer of 15 to 983, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 12, and where b is greater than or equal to a + 14.
  • Drosophila melanogaster slit protein a secreted protein that contains both an EGF domain and Leucine Rich Repeat domains. It is thought to be important in the development of midline glia and commissural axon pathways (See e.g., Rothberg et al. Genes Dev. 4:2169-87 (1990); which is hereby incorporated by reference herein). This gene is expressed primarily in human hippocampus.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological, and developmental disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neurological, cancerous, or wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution within human hippocampus combined with the homology to the Drosophila slit protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions. Representative uses are described in the "Regeneration” and “Hyperproliferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, pe ⁇ pheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and preception.
  • the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved m synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nut ⁇ tional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 13 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 13 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 959 of SEQ ID NO: 13, b is an integer of 15 to 973, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO: 13, and where b is greater than or equal to a + 14
  • polypeptides compnsmg the ammo acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention compnse the following amino acid sequence:
  • polynucleotides encoding these polypeptides are also provided.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 16. Accordingly, polynucleotides related to this invention are useful as a marker m linkage analysis for chromosome 16.
  • This gene is expressed in KMH2 cells, osteoblasts, fetal spleen, Jurkat membrane bound polysomes, breast, and cerebellum
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer, immune, and skeletal disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • tissue or cell types e.g., immune, skeletal, cancerous, or wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, u ⁇ ne, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder
  • tissue distribution in KMH2 cells, osteoblasts, and fetal spleen indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a va ⁇ ety of immune system disorders.
  • Representative uses are desc ⁇ bed in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • Expression of this gene product in fetal spleen and T-cells indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e g., by boosting immune responses)
  • the gene Since the gene is expressed in cells of lymphoid ongin, the natural gene product is involved in immune functions. Therefore it is also used as an agent for immunological disorders including arth ⁇ tis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arth ⁇ tis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropema, neutrophiha, pso ⁇ asis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arth ⁇ tis, Sjogren's Disease, scleroderma and tissues.
  • immunological disorders
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of va ⁇ ous blood lineages, and in the differentiation and/or proliferation of vanous cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nut ⁇ tional supplement. Protein, as well as, antibodies directed against the protem may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 14 Some of these sequences are related to SEQ ID NO: 14 and may have been publicly available pnor to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b is any integer between 1 to 1444 of SEQ ID NO: 14
  • b is an integer of 15 to 1458, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO 14, and where b is greater than or equal to a + 14
  • PA2's are small and ⁇ gid proteins of 120 amino-acid residues that have four to seven disulfide bonds. PA2 binds a calcium ion which is required for activity.
  • Two different signature patterns for PA2's were developed. The first is centered on the active site histidine and contains three cysteines involved in disulfide bonds. The consensus pattern is as follows: C-C-x(2)-H-x(2)-C [H is the active site residue].
  • Preferred polypeptides of the invention compnse a Phospholipase A2 histidine active site domain selected from the following amino acid sequences: CCNQHDRC (SEQ ID NO: 199), SLTKCCNQHDRCYET (SEQ ID NO: 200) , and/or LTKCCNQHDRCYETCG (SEQ ID NO: 201) .
  • Polynucleotides encoding these polypeptides are also provided. Further prefe ⁇ ed are polypeptides compnsmg the Phospholipase A2 histidine active site domain of the sequence listed in Table 1 for this gene, and at least 5, 10, 15, 20, 25, 30, 50, or 75 additional contiguous amino acid residues of this referenced sequence.
  • the additional contiguous am o acid residues is N-terminal or C- terminal to the Phospholipase A2 histidine active site domain
  • the additional contiguous amino acid residues is both N-terminal and C-terminal to the Phospholipase A2 histidine active site domain, wherein the total N- and C-terminal contiguous amino acid residues equal the specified number.
  • the above preferred polypeptide domain is characte ⁇ stic of a signature specific to Phospholipase A2 proteins. Based on the sequence simila ⁇ ty, the translation product of this gene is expected to share at least some biological activities with Phospholipase A2 proteins.
  • polypeptides compnsmg the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention compnse the following amino acid sequence:
  • Polynucleotides encoding these polypeptides are also provided.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 4. Accordingly, polynucleotides related to this invention are useful as a marker m linkage analysis for chromosome 4 This gene is expressed in a va ⁇ ety of cell types with no single type predominating.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological disorders, or metabolism disorders, specifically phospholipase A2 deficiencies.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • tissue or cell types e.g., pancreas, cancerous and wounded tissues
  • bodily fluids e.g., bile, lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 107 as residues: Gln-23 to Asp-30, Lys-66 to Cys-87.
  • Polynucleotides encoding said polypeptides are also provided.
  • the ubiquitous tissue distribution and homology to phospholipase A2 indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosis and treatment of neuromuscular disorders.
  • polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and preception.
  • the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
  • the homology to Phospholipase A2 proteins may indicate a potential use for the protein product of this gene in diagnosis, treatment and/or prevention of metabolism disorders, specifically deficiencies in Phospholipase A2.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 15 Some of these sequences are related to SEQ ID NO: 15 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1991 of SEQ ID NO: 15, b is an integer of 15 to 2005, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO: 15, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence:
  • polypeptides of the invention comprise the following amino acid sequence:
  • ARAPPGPEGLSPEAQPPLLPMGNCQAGHNLFfLCLAHHPPLVCATLILLLLGLS GLGLGSFLLTHRTGLRT LTSPRTGSLF SEQ ID NO: 203 .
  • Polynucleotides encoding these polypeptides are also provided. This gene is expressed in a wide variety of tissue types including testes, cerebellum, dendritic cells, breast cancer, umbilical vein endothelial cells, epididymus, corpus colosum, chronic synovitis, liver hepatome, normal breast, osteoblasts, melanocytes, B cell lymphomas, and to a lesser extent in other tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to. cancer, particularly of endothelial tissues.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • tissue or cell types e.g., endothelial, cancerous, or wounded tissues
  • bodily fluids e.g., lymph, seminal fluid, serum, plasma, unne, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level m healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise lmmunogenic epitopes shown in SEQ ID NO: 108 as residues: Thr-52 to Gly-57. Polynucleotides encoding said polypeptides are also provided.
  • Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that the protein product of this gene may play a role in the regulation of cellular division and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, cancer, and other pro ferative conditions. Representative uses are desc ⁇ bed in the "Hyperprohferative Disorders" and "Regeneration" sections below and elsewhere herein. Additionally, the expression in hematopoietic cells and tissues indicates that this protein may play a role in the proliferation, differentiation, and/or survival of hematopoietic cell lineages.
  • this gene is useful in the treatment of lymphopro ferative disorders, and m the maintenance and differentiation of vanous hematopoietic lineages from early hematopoietic stem and committed progenitor cells.
  • embryonic development also relies on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inapprop ⁇ ate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult foi tissue regeneration and the treatment of cancers. It may also act as a morphogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful m treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to aberrant polypeptides, as may exist m proliferating and cancerous cells and tissues.
  • the protem can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutntional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 16 may have been publicly available pnor to conception of the present invention
  • related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 929 of SEQ ID NO: 16, b is an integer of 15 to 943, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 16, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention compnse the following amino acid sequence RFLSVXPQXEVPFLLHPCVCFXGGHPSLLPDPCRAVGGGWEAPRCCLHEALC QSLGCKAEEIVSVSESSSAQRCWYLLRGRKAGGRGPASPVLFALMRLESLCH LCLACLFFRLPATRTVYCMNEAEIVDVALGILIESRKQXKACEQPALAGADNP EHSPPCSVSPHTSSGSSSEEEDSGKQALXPGLSPSQRPGGSSSACSRSPEEEEEE EEDVLKYVREIFFS (SEQ ID NO: 204) Polynucleotides encoding these polypeptides are also provided. Polynucleotides of the invention do not consist of the nucleic acid sequences shown as GeneSeq Accession Nos: V59595 and V59744, which are hereby
  • This gene is expressed pnma ⁇ ly in a vanety of immune cell types, including stromal cells, dend ⁇ tic cells, leukocytes, activated T-cells, macrophages, monoctyes, neutrophils and to a lesser extent in a vanety of other adult and fetal tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer and other prohferative disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels is routinely detected in certain tissues or cell types (e.g., immune, cancerous, or wounded tissues) or bodily fluids
  • tissue dist ⁇ bution in immune cells indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Representative uses are desc ⁇ bed in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • This gene product in fetal tissue and vanous hematopoietic cancers indicates a role in the regulation of the proliferation; survival, differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses). Since the gene is expressed in cells of lymphoid ongin, the natural gene product is involved in immune functions.
  • immunological disorders including arth ⁇ tis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arth ⁇ tis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psonasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demye nation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthntis, Sjogren's Disease, scleroderma and tissues.
  • immunodeficiency diseases such as AIDS, leukemia, rheumatoid arth ⁇ tis, granulomatou's Disease, inflammatory bowel disease, se
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of va ⁇ ous blood lineages, and in the differentiation and/or proliferation of va ⁇ ous cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nut ⁇ tional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO.17 sequences are related to SEQ ID NO.17 and may have been publicly available prior to conception of the present invention.
  • related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 1489 of SEQ ID NO- 17, b is an integer of 15 to 1503, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NOT7, and where b is greater than or equal to a + 14.
  • NF-kB Nuclear Factor kB
  • NF-kB is a transc ⁇ ption factor activated by a wide va ⁇ ety of agents, leading to cell activation, differentiation, or apoptosis. Reporter constructs utilizing the NF-kB promoter element are used to screen supernatants for such activity.
  • polypeptides of the invention compnse the following amino acid sequence VPGWPRACSPCQADSPRAFfPPKLRGILRWAPVPLXCAALCPPLDSG MSMAACPEAPEPSFLREVPSSPASTQWHRPCNFRQVEANPRKEPKNLVWRD VSLGQXSRTPRGSGLELVRVCGGGMQRDKTVVEERVGEERERERERESLGG AGKHGEMRCVYVRESVGAPGRAGGGGNGVNSVGCVRTVHSGSXPPPSAGV S (SEQ ID NO: 205) . Polynucleotides encoding these polypeptides are also provided.
  • This gene is expressed pnma ⁇ ly in parts of the brain such as cerebellum and frontal lobe.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurodegenerative disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • tissue or cell types e.g., neural, cancerous, or wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue dist ⁇ bution in cerebellum and frontal lobe indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection, prevention and/or treatment of neurodegenerative disease states and behavioural disorders, or inflammatory conditions
  • Representative uses are descnbed in the "Regeneration” and "Hyperprohferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, pe ⁇ pheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception
  • elevated expression of this gene product m regions of the brain indicates it plays a role m normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutntional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 1498 of SEQ ID NOT 8
  • b is an integer of 15 to 1512, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO: 18, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence: TRPGKELNLVFGLQLSMARIGSTVNMNLMGWLYSKIEALLGSAGHTTLGITL MIGGITCILSLIC ALAL A YLDQRAERILHKEQGKTGEVIKLTD VKDFSLPLWLIF IICVCYYVAVFPFIGLGKVFFTEKFGFSSQAASAINSVVYVISAPMSPVFGLLV DKTGKNIIWVLCA (SEQ ID NO: 206) . Polynucleotides encoding these polypeptides are also provided.
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3.
  • This gene is expressed primarily in fetal tissue, and to a lesser extent in a variety of adult human tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, fetal abnormalities, particularly developmental disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developing, or cancerous and wounded tissues
  • bodily fluids e.g., amniotic fluid, lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention compnse lmmunogenic epitopes shown in SEQ ID NO 111 as residues Lys-30 to Thr-35. Polynucleotides encoding said polypeptides are also provided
  • tissue dist ⁇ bution in fetal tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other prohferative disorders. Representative uses are descnbed in the "Hyperprohferative Disorders" and "Regeneration” sections below and elsewhere herein.
  • developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation. Dysregulation of apoptosis can result in inapprop ⁇ ate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA). Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division.
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a morphogen to control cell and tissue type specification Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions Thus this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protem is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation Additionally, the expression in hematopoietic cells and tissues indicates that this prote may play a role in the proliferation, differentiation, and/or survival of hematopoietic cell lineages. In such an event, this gene is useful in the treatment of lymphoprohferative disorders, and in the maintenance and differentiation of va ⁇ ous hematopoietic lineages from early hematopoietic stem and committed progenitor cells Furthermore, the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 19 Some of these sequences are related to SEQ ID NO: 19 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1641 of SEQ ID NO: 19, b is an integer of 15 to 1655, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO: 19, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with human histiocyte-secreted factor (HSF) which is a novel cytokine that shows in vivo antitumour activity without the cytotoxicity associated with tumour necrosis factor. Furthermore, The translation product of this gene also shares sequence homology with the human endogenous virus S71 gag polyprotein, the sequence of which is believed to represent a transformation locus for several cancers (See Genebank Accession No. pir
  • polypeptides of the invention comprise the following amino acid sequence: CKDLCSRVYLLTLSPLLSYDPATSHSPRNTQ (SEQ ID NO: 207) . Also prefe ⁇ ed are the polynucleotides encoding these polypeptides.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hematopoietic, and gastrointestinal disorders, particularly tumors of the colon and tonsil.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, gastrointestinal, or cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 112 as residues: Met-1 to Cys-6. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in tonsil and colon combined with the homology to human histiocyte growth factor, the human endogenous viral protein, and B219 strongly indicate that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis, treatment and/or prevention, of a variety of hematopoietic and immune system disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia. Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • This gene product indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g., by boosting immune responses) Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions.
  • immunological disorders including arthntis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psonasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthntis, Sjogren's Disease, scleroderma and tissues.
  • immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne,
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and m the differentiation and/or proliferation of va ⁇ ous cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nut ⁇ tional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:20 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:20 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 2511 of SEQ ID NO.20, b is an integer of 15 to 2525, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:20, and where b is greater than or equal to a + 14.
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological and digestive disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neurological, gastrointestinal, or cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • the tissue distribution in brain indicates polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • this gene product in regions of the brain indicates it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Alternatively, expression of this gene in colon may indicate a role in the detection, prevention and/or treatment of colon diorders such as colon cancer, Crohn's Disease, ulcers, and digestive tract disorders in general.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:21 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:21 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention To list every related sequence is cumbersome.
  • a-b a nucleotide sequence descnbed by the general formula of a-b, where a is any integer between 1 to 1382 of SEQ ID NO:21, b is an integer of 15 to 1396, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO.21, and where b is greater than or equal to a + 14.
  • GAS gamma activation site
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological, behavioral, immune, and developmental disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • tissue or cell types e.g., neural, developing, immune, or cancerous and wounded tissues
  • bodily fluids e.g , lymph, amniotic fluid, serum, plasma, unne, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, I e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO. 114 as residues. Lys-60 to Asn-67. Polynucleotides encoding said polypeptides are also provided.
  • tissue distnbution in brain indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions.
  • Representative uses are descnbed in the "Regeneration” and "Hype ⁇ ro ferative
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, penpheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord inju ⁇ es, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • tissue distnbution in developing embryo indicates that the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system.
  • the biological activity within B-cells indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of a va ⁇ ety of immune system disorders.
  • Activation of genes wit B-cells indicates a role for this protein in the regulation of the proliferation, survival, differentiation, and/or activation of potentially all hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e g., by boosting immune responses) Since the gene is expressed in cells of lymphoid ongin, the natural gene product is involved in immune functions Therefore it is also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arth ⁇ tis, inflammatory bowel disease, sepsis, acne, and psonasis.
  • immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arth ⁇ tis, inflammatory bowel disease, sepsis, acne, and psonasis.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutntional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:22 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 1055 of SEQ ID NO:22, b is an integer of 15 to 1069, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO.22, and where b is greater than or equal to a + 14.
  • polypeptides related to this invention are useful as a marker in linkage analysis for chromosome 6.
  • polypeptides compnsmg the ammo acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention compnse the following amino acid sequence: LLSFKIRGLRTEDAGWAQSSSGGLCVRGDAFWMPSSSSGLGSPSRPPSSFLCL LLLLLPPAALALLLFFLDFFPPRAAVSPFLPDHCSARQPRVWRRETLNRSASGL GCWARSTEQGAVGVATGTVLDI SLPASCLSLWPPGPSGGI (SEQ ID NO: 209) .
  • Polynucleotides encoding these polypeptides are also provided.
  • polypeptides of the invention comprise the following amino acid sequence: QLGLCLTSASLPPASRCGHQAPLGASDLSAHHSAPGFSDSYFTMSCQSSLSRA EILQCPLVPSVSPPTHLPQGRANKSSRASLPLLPQTHWCLFPSARGWRRGIQSG LPPGGSCTSPRSPPQTLHQHITLVNHNTSYWQSPST (SEQ ID NO: 210) , HQPPCLLPLAVATRPLWGHLTCLPIILHLVSVTLTSPCLANQAFQGQRSYNAL WCPLFLLLPTSPKGEQTNHPEPACPCFPKLTGVFSLQHVVGAEEFSQVFLLVD PVPVLDHLLKLFTSTSHLLIIIPHIGKAPAPDSLL EELSLSLATHCKVAVARFT (SEQ ID NO: 211) .
  • polynucleotides encoding these polypeptides are also prefe ⁇ ed.
  • Polynucleotides of the invention do not consist of the nucleic acid sequence shown as GeneSeq Accession No. X04377, which is hereby inco ⁇ orated herein by reference. This gene is expressed primarily in brain.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, behavioral and neurological disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, or cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 115 as residues: Pro-2 to Gly-7, Ser-10 to Ser-16, Pro-52 to Val-62, Arg-64 to Ser-73. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions. Representative uses are described in the "Regeneration” and “Hype ⁇ roliferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences, such as EST sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:23 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention.
  • a-b is any integer between 1 to 1644 of SEQ ID NO:23
  • b is an integer of 15 to 1658, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO.23, and where b is greater than or equal to a + 14
  • RLVSPWGRHGLRILQIGHHHGRDGQHEATHHLL RVLRA SEQ ID NO. 213.
  • An additional embodiment is the polynucleotides encoding these polypeptides. This gene maps to chromosome 19, and therefore, is used as a marker in linkage analysis for chromosome 19.
  • This gene is expressed p ⁇ ma ⁇ ly in brain, placenta, fetal liver, and to a lesser extent in most tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological, reproductive, and hepatic disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s)
  • expression of this gene at significantly higher or lower levels is routinely detected in certain tissues or cell types (e.g., neural, hepatic, or cancerous and wounded tissues) or bodily fluids (e g., bile, amniotic fluid, serum, plasma, u ⁇ ne, synovial fluid and spinal fluid) or another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e , the expression level in healthy tissue or bodily fluid from an individual not having the disorder
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO- 116 as residues: Asn-34 to Lys-42, Leu-60 to T ⁇ -70.
  • tissue distnbution predominantly in brain indicates a role in the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntinton's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
  • tissue dist ⁇ bution in liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g , hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are att ⁇ butable to the differentiation of hepatocyte progenitor cells).
  • telomere sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:24 and may have been publicly available pnor to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence descnbed by the general formula of a-b, where a is any integer between 1 to 1063 of SEQ ID NO:24, b is an integer of 15 to 1077, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO.24, and where b is greater than or equal to a + 14.
  • This gene is expressed p ⁇ manly in spinal cord, Merkel cells, and adipose tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the nervous and immune systems, particularly those disorders relating to the CNS involving lipid metabolism disorders.
  • diseases and conditions which include, but are not limited to, disorders of the nervous and immune systems, particularly those disorders relating to the CNS involving lipid metabolism disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, immune, or cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in spinal cord, Merkel cells and adipose tissue indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment and/or diagnosis of diseases the nervous systems, such as spinal cord injury, neurodegenerative diseases, muscular dystrophy or obesity.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:25 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:25 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1191 of SEQ ID NO:25, b is an integer of 15 to 1205, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:25, and where b is greater than or equal to a + 14.
  • FEATURES OF PROTEIN ENCODED BY GENE NO: 16 The translation product of this gene shares sequence homology with the human uncoupling protein-2 which is thought to be important in energy metabolism, obesity, and the predisposition of hyperinsulinemia (See Genebank Accesion No. gi
  • One embodiment of this gene comprises polypeptides of the following amino acid sequence: PTDVLKIRMQAQ (SEQ ID NO: 214) , and/or TYEQLKR (SEQ ID NO: 215) .
  • An additional embodiment is the polynucleotides encoding these polypeptides. This gene maps to the X chromosome, and therefore, is used as a marker in linkage analysis for the X chromosome.
  • This gene is expressed primarily in manic depression brain tissue, epileptic frontal cortex, human erythroleukemia cell line, T-helper cells, and to a lesser extent in endothelial and amygdala cells.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the central nervous system or hematopoietic/immune disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, hemolymphoid, or cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 118 as residues: Ser-34 to Thr-39, Gln-198 to Leu- 205. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution in neural tissues combined with the homology to the human uncoupling protein indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and/or treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses , autism, and altered bahaviors, including disorders in feeding, sleep patterns, balance, and preception.
  • the gene or gene product may also play a role in the treatment and or detection of developmental disorders associated with the developing embryo, sexually-linked disorders, or disorders of the cardiovascular system. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the gene and/or its translation product may also be used in the diagnosis, treatment, and/or prevention of thermogenesis disorders such as obesity, cachexia, and hyperinsulinemia.
  • Uncoupling proteins dissipate the proton gradient created from the oxidation of fuels by the electron transport chain, thus releasing stored energy as heat. Dysfunction of thermogenesis can induce disorders such as obesity and cachexia. It is thought that obesity may result from decreased thermogenesis in humans.
  • cachexia is a metabolic state in which energy expenditure exceeds food intake, for example in anorexia nervosa.
  • Uncoupling proteins is useful for the treatment and/or prevention of diseases and or disorders involved with abe ⁇ ant metabolic and thermogenic pathways. The following method provides for the determination of respiration uncoupling activity of the polypeptides of the present invention, including fragments and variants of the full length proteins.
  • yeast are transfected with an expression vector expressing polypeptide of the present invention as previously described by Bouillaud et al., EMBO J., 13:1990 (1994) (inco ⁇ orated by reference herein in its entirety). Rates of growth in liquid medium of transformed yeast are measured in the presence of galactose, which induces expression, as described in Intemational Publication No. WO 98/31396 (inco ⁇ orated by reference herein in its entirety). Instanteous generation times are compared between the polypeptide of the present invention and appropnate controls.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:26 Some of these sequences are related to SEQ ID NO:26 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 1660 of SEQ ID NO:26, b is an integer of 15 to 1674, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:26, and where b is greater than or equal to a + 14.
  • Prefe ⁇ ed polypeptides of the invention compnse the following ammo acid sequence: RPRPSASSLARSASLLPAAHGXGVGGAGGGSSXLRSRYQQLQNEEESGEPEQ AAGDAPPPYSSISAESAHXFDYKDESGFPKPPSYNVATTLPSYDEAERTKAEA TIPLVPGRDEDFVGRDDFDDADQLRIGNDGIF (SEQ ID NO: 216) , RYQQLQNEEESGEPEQAAGD (SEQ ID NO: 217) , and/or PGRDEDFVGRDDFDDADQLRIG (SEQ ID NO: 218) .
  • Polynucleotides encoding these polypeptides are also provided.
  • Prefe ⁇ ed polypeptide fragments of the invention comprise the following amino acid sequence: MLTFFMAFLFNWIGFFLSFCLTTSAAGRYG AISGFGLSLIKWILIVRFSTYFPGYFDGQY
  • WLWWVFLVLGFLLFLRGFINYAKVRKMPET FSNLPRTRVLFIY SEQ ID NO: 219.
  • Polynucleotides encoding these polypeptides are also provided.
  • polypeptide varients of the invention comprise the following amino acid sequence:
  • GAS gamma activating sequence
  • This gene is expressed primarily in adult kidney, colon adenocarcinoma, and fetal brain, and to a lesser extent, ubiquitously expression in many tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of kidney, colon cancers, and central nervous system.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., renal, neural, urogenital, or cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 119 as residues: Cys-15 to Gly-36. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution adult kidney, colon adenocarcinoma, and fetal brain indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosis and treatment of kidney diseases, colon cancers, and disorders of the central nervous system. Additionally, the homology to the zona pellucida protein indicates that the gene product is used for male contraceptive development, and infertility diagnosis etc. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:27 Some of these sequences are related to SEQ ID NO:27 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1951 of SEQ ID NO:27, b is an integer of 15 to 1965, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:27, and where b is greater than or equal to a + 14.
  • FEATURES OF PROTEIN ENCODED BY GENE NO: 18 The translation product of this gene shares sequence homology with the chicken transferrin receptor in addition to a human prostate-specific protein homolog (See Genebank Accession Nos.pir
  • a prefe ⁇ ed polypeptide fragment of the invention comprises the following amino acid sequence: MTVMDPKQMNVAAAVWAVVSYVVADMEEML PRS (SEQ ID NO: 224). Polynucleotides encoding these polypeptides are also provided. This gene is expressed primarily in fetal tissues, such as liver/spleen and brain.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, pre-natal disorders, anomalies, deficiencies.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developing, cancerous and wounded tissues
  • bodily fluids e.g., amniotic fluid, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 120 as residues: Arg-31 to Lys-37, Lys-58 to Glu-65, Asp-157 to Gly-168, Ile-219 to Gly-225, Ala-260 to Ser-268, Thr-276 to Glu-282. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for treatment and diagnosis of pre-natal disorders, anomalies and deficiencies.
  • the homology to the hematopoietic lineage switch 2 proteins indicates that The translation product of this gene is useful for the detection and/or treatment of immune system disorders.
  • the homology to the transferrin receptor indicates that the translation product of the present invention may have utility in the regulation of iron metabolism as well as the numerous genes under the stringent control of physiologic iron levels. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:28 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:28 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1849 of SEQ ID NO:28, b is an integer of 15 to 1863, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:28, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence: PRVRSREPVAGAPGCGTAGPPAMATLWGGLLRLGSLLSLSCLALSVLLLAHC QTPPSDCLHVVEPMPVRGPDVEAYCLRCECKYEERSSVTIKVTIIIYLSILGLLL LYMVYLTLVEPILKRRLFGHAQLIQSDDDIGDHQPFANAHDVLARSRSRANV LNKVEYAQQRWKLQVQEQRKSVFDRHVVLS (SEQ ID NO: 225). Polynucleotides encoding these polypeptides are also provided.
  • the polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 72 - 88 of the amino acid sequence referenced in Table 1 for this gene. Moreover, a cytoplasmic tail encompassing amino acids 89 to 167 of this protein has also been determined. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type la membrane proteins.
  • a prefe ⁇ ed polypeptide varient of the invention comprise the following amino acid sequence:
  • This gene is expressed primarily in infant brain tissue, and to a lesser extent in other cell types and tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, developmental and neurodegenerative diseases of the brain and nervous system, such as depression, schizophrenia, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, mania, dementia, paranoia, addictive behavior, sleep disorders, epilepsy, transmissible spongiform encephalopathy (TSE), Creutzfeldt- Jakob disease (CJD).
  • TSE transmissible spongiform encephalopathy
  • CJD Creutzfeldt- Jakob disease
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 121 as residues: Gln-110 to Pro-120, Val-152 to Val- 159. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in infant brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or diagnosis of developmental, degenerative and behavioral conditions of the brain and nervous system.
  • Representative uses are described in the "Regeneration” and "Hype ⁇ roliferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein. Briefly, the uses include, but are not limited to the detection, treatment, and/or prevention of schizophrenia, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, transmissible spongiform encephalopathy (TSE), Creutzfeldt-Jakob disease (CJD), mania, depression, dementia, paranoia, addictive behavior, obsessive-compulsisve disorder and sleep disorders.
  • TSE transmissible spongiform encephalopathy
  • CJD Creutzfeldt-Jakob disease
  • mania depression
  • dementia dementia
  • paranoia addictive behavior
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:29 Some of these sequences are related to SEQ ID NO:29 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1612 of SEQ ID NO:29, b is an integer of 15 to 1626, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:29, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immunodeficiency, tumor necrosis, lymphomas, auto-immunities, cancer, inflammation, anemias (leukemia) and liver disorders, vascular disorders, and cancers (e.g., hepatoblastoma, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells).
  • diseases and conditions include, but are not limited to, immunodeficiency, tumor necrosis, lymphomas, auto-immunities, cancer, inflammation, anemias (leukemia) and liver disorders, vascular disorders, and cancers (e.g., hepatoblastoma, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells).
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., hepatic, developmental, vascular, or cancerous and wounded tissues
  • bodily fluids e.g., amniotic fluid, bile, lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of immune disorders including: leukemias, lymphomas, auto-immunities, immunodeficiencies (e.g., AIDS), immuno-supressive conditions (transplantation) and hematopoeitic disorders.
  • this gene product is applicable in conditions of general
  • PZ030PCT microbial infection, inflammation or cancer expression in liver may suggest a role for this gene product in the treatment and detection of liver disorders and cancers (e.g., hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells).
  • liver disorders and cancers e.g., hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells.
  • the tissue distribution in fetal heart tissue indicates that the protein product of this gene is useful for the diagnosis and treatment of conditions and pathologies of the cardiovascular system, such as heart disease, restenosis, atherosclerosis, stoke, angina, thrombosis, and wound healing.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the homology to the dysferlin gene indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diseases related to degenerative myopathies that are characterized by the weakness and atrophy of muscles without neural degradation; such as Duchenne and Becker's muscular dystropies.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:30 Some of these sequences are related to SEQ ID NO:30 and may have been publicly available prior to conception of the present invention.
  • related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 591 of SEQ ID NO:30, b is an integer of 15 to 605, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:30, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, haemopoietic disorders, diseases of the renal and pancreatic systems, and cancer.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., pancreas, renal, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or diagnosis of disorders of the renal, pancreatic and haemopoietic systems, and cancers thereof.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:31 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 917 of SEQ ID NO:31, b is an integer of 15 to 931, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:31, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, metabolic disorders, diseases of developing systems and cancers.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developing, metabolic, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 124 as residues: His-44 to Gly-49.
  • Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment and/or diagnosis of disorders of the fetus, metabolic systems and cancers.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection and treatment of liver disorders and cancers (e.g.
  • hepatoblastoma hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells).
  • expression in fetus would suggest a useful role for the protein product in developmental abnormalities, fetal deficiencies, pre-natal disorders and various would-healing models and/or tissue trauma.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences, such as EST sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:32 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention.
  • a-b is any integer between 1 to 1393 of SEQ ID NO:32
  • b is an integer of 15 to 1407, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:32, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the CNS and cancers.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 125 as residues: Tyr- 16 to Ser-22, Asp-209 to Leu- 215. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution in central nervous system tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment and/or diagnosis of diseases of the central nervous system, as well as cancers of tissues where expression of this gene has been observed, such as in endometrial tumors.
  • the tissue distribution in central nervous system tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:33 Some of these sequences are related to SEQ ID NO:33 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1512 of SEQ ID NO:33, b is an integer of 15 to 1526, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:33, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with low- density lipoprotein receptor (See Genbank Accession No. >dbj
  • the translation product of this gene also shares sequence homology with a rat homolog of the human CD94 (See Genbank Accession No. gb
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the immune and haemopoietic systems and diseases of the endothelial and vascular system.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 126 as residues: Lys-9 to Ala-17, Met-55 to Leu-61, Tyr-105 to Cys-127, Asp-132 to Lys-141, Ser-165 to Tyr-172, Pro-178 to Met-186, His-222 to Gln-227. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution and homology to LDL receptor and rat CD94 homolog indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment and/or diagnosis of disorders of the immune, haemopoietic and vascular systems.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and/or treatment of hematopoietic disorders.
  • This gene product is primarily expressed in hematopoietic cells and tissues, suggesting that it plays a role in the survival, proliferation, and/or differentiation of hematopoieitic lineages.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:34 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:34 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1723 of SEQ ID NO:34, b is an integer of 15 to 1737, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:34, and where b is greater than or equal to a + 14.
  • a preferred polypeptide fragment of the invention comprises the following amino acid sequence:
  • Polynucleotides encoding these polypeptides are also provided.
  • GAS gamma activating sequence
  • This gene is expressed primarily in infant brain and placental tissues, and to a lesser extent in several other tissues including cancers.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, brain disorders and diseases of developing systems and cancers.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, developing, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 127 as residues: Leu-56 to Thr-62, Gln-80 to Pro-87, Gly-106 to Gln-113, Pro-122 to Lys-127, Gln-138 to Asn-146. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution in neural tissues and developing tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment and/or diagnosis of disorders of the central nervous system, disorders of developing systems, and cancers.
  • the tissue distribution in infant brain tissue indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually- linked disorders.
  • tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of disorders of the placenta.
  • Specific expression within the placenta indicates that this gene product may play a role in the proper establishment and maintenance of placental function. Alternately, this gene product is produced by the placenta and then transported to the embryo, where it may play a crucial role in the development and/or survival of the developing embryo or fetus.
  • Expression of this gene product in a vascular-rich tissue such as the placenta also indicates that this gene product is produced more generally in endothelial cells or within the circulation. In such instances, it may play more generalized roles in vascular function, such as in angiogenesis.
  • hematopoietic cells may also be produced in the vasculature and have effects on other cells within the circulation, such as hematopoietic cells. It may serve to promote the proliferation, survival, activation, and/or differentiation of hematopoietic cells, as well as other cells throughout the body. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:35 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2228 of SEQ ID NO:35, b is an integer of 15 to 2242, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:35, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence:
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7.
  • the gamma activating sequence is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway.
  • the Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the reproductive and developing systems and cancers.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, testicular, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, seminal fluid, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in testes tissue, synovial sarcoma, and fetal tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and or diagnosis of disorders of the reproductive and developing systems, and cancers.
  • the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of conditions concerning proper testicular function (e.g: endocrine function, sperm maturation), as well as cancer. Therefore, this gene product is useful in the treatment of male infertility and/or impotence.
  • This gene product is also useful in assays designed to identify binding agents, as such agents (antagonists) are useful as male contraceptive agents.
  • testes are also a site of active gene expression of transcripts that is expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product is expressed in other specific tissues or organs where it may play related functional roles in other processes, such as hematopoiesis, inflammation, bone formation, and kidney function, to name a few possible target indications.
  • tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of cancer and other prohferative disorders.
  • Expression within embryonic tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division.
  • the expression in hematopoietic cells and tissues indicates that this protein may play a role in the proliferation, differentiation, and/or survival of hematopoietic cell lineages. In such an event, this gene is useful in the treatment of lymphoprohferative disorders, and in the maintenance and differentiation of various hematopoietic lineages from early hematopoietic stem and committed progenitor cells.
  • embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation.
  • this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
  • This protein is useful for the treatment, detection, and/or prevention of William's Disease.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:36 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:36 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2221 of SEQ ID NO:36, b is an integer of 15 to 2235, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:36, and where b is greater than or equal to a + 14.
  • Preferred polypeptides of the invention comprise the following amino acid sequence positions 1-363, 2-363, 4-363, 5-363, 30-363, 31-363, 32-363, 75-363, 76- 363 and 82-363 of the following amino acid sequence:
  • a prefe ⁇ ed polypeptide varient of the invention comprises the following amino acid sequence: MLFLFSMATLLRTSFSDPGVIPRALPDEAA FIEMEIEATNGAVPQGQRPPPRIKNFQINNQIVKLKYCYTCKIFRPPRASHCSIC DNCVE RFDHHCPWVGNCVGKRNYRYFYLFILSLSLLTIYVFAFNIVYVALK SLKIGFLETLKGNS WNCSRSPHLLLYTLVRRGTDWISYFPRGSQ PDNQ (SEQ ID NO: 231). Polynucleotides encoding these polypeptides are also provided. This gene is expressed primarily in ovarian and endometrial tumors, fetal liver, spleen and brain tissues, and to a lesser extent in several other tissues and organs.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the developing systems, and cancers of the female reproductive system.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, developing, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 129 as residues: Pro-44 to Lys-54, Cys-88 to His-95, Val-103 to Tyr-108, Gln-181 to Ser-190, Thr-192 to Ile-206, Glu-233 to Ser-245, Ser- 252 to Ala-286. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution in developing systems indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or diagnosis of disorders of developing and fetal systems, and cancers. Furthermore, the tissue distribution in ovarian and endometrial tumor tissues indicates that the translation product of this gene is useful for the detection, diagnosis, and/or treatment of cancers of the female reproductive system. Accordingly, prefe ⁇ ed are antibodies which specifically bind a portion of The translation product of this gene. Also provided is a kit for detecting these tumors. Such a kit comprises in one embodiment an antibody specific for The translation product of this gene bound to a solid support.
  • Also provided is a method of detecting these tumors in an individual which comprises a step of contacting an antibody specific for The translation product of this gene to a bodily fluid from the individual, preferably serum, and ascertaining whether antibody binds to an antigen found in the bodily fluid.
  • a bodily fluid from the individual, preferably serum
  • the antibody is bound to a solid support and the bodily fluid is serum.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:37 Some of these sequences are related to SEQ ID NO:37 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2957 of SEQ ID NO:37, b is an integer of 15 to 2971, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:37, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in normal and cancerous colon tissue, macrophages, endothelial cells and placental tissue, and to a lesser extent in several other tissues and organs.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, colon cancer and gastrointestinal disorders, immune disorders, vascular diseases and disorders of developing systems.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 130 as residues: Thr- 27 to Ser-33. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in macrophage, endothelial and placental tissues, and normal and cancerous colon tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or diagnosis of immune, gastrointestinal and vascular disorders and diseases.
  • Expression of this gene product in colon tissue indicates involvement in digestion, processing, and elimination of food, as well as a potential role for this gene as a diagnostic marker or causative agent in the development of colon cancer, and cancer in general.
  • prefe ⁇ ed are antibodies which specifically bind a portion of the translation product of this gene.
  • kit for detecting colon cancer comprises in one embodiment an antibody specific for The translation product of this gene bound to a solid support.
  • a method of detecting colon cancer in an individual which comprises a step of contacting an antibody specific for The translation product of this gene to a bodily fluid from the individual, preferably serum, and ascertaining whether antibody binds to an antigen found in the bodily fluid.
  • a bodily fluid from the individual, preferably serum
  • the antibody is bound to a solid support and the bodily fluid is serum.
  • the tissue distribution in placental tissue indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and/or treatment of disorders of the placenta.
  • this gene product may play a role in the proper establishment and maintenance of placental function. Alternately, this gene product is produced by the placenta and then transported to the embryo, where it may play a crucial role in the development and/or survival of the developing embryo or fetus.
  • Expression of this gene product in a vascular-rich tissue such as the placenta and endothelial cells also indicates that this gene product is produced more generally in endothelial cells or within the circulation. In such instances, it may play more generalized roles in vascular function, such as in angiogenesis. It may also be produced in the vasculature and have effects on other cells within the circulation, such as hematopoietic cells.
  • this gene product may serve to promote the proliferation, survival, activation, and/or differentiation of hematopoietic cells, as well as other cells throughout the body. Additionally, expression of this gene product in macrophage also strongly indicates a role for this protein in immune function and immune surveillance. This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it is also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and or immunotherapy targets for the above listed tissues.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1149 of SEQ ID NO:38, b is an integer of 15 to 1163, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:38, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares homology with HNK- sulfotransferase, which directs glycan synthesis (see Genbank Accession no. AF033827).
  • This gene is expressed primarily in activated T cells, osteoclastoma, and glioblastoma, and to a lesser extent in various other normal and transformed cell types.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, inflammation, immune defects, cancer.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 131 as residues: Pro-32 to Gly-48, Gln-63 to Thr-69, Pro-77 to T ⁇ -84, Val-88 to Leu-94.
  • Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution in T-cells and various types of neoplasms indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection, study and/or treatment of inflammatory and general immune defects, and various types of neoplasms.
  • Expression of this gene product in T cells strongly indicates a role for this protein in immune function and immune surveillance. This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it is also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the tissue distribution in various cancerous tissues indicates that the translation product of the gene is useful for the detection, diagnosis, and/or treatment of these cancers, as well as cancers of other tissues where expression has been observed.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:39 Some of these sequences are related to SEQ ID NO:39 and may have been publicly available prior to conception of the present invention.
  • such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1918 of SEQ ID NO:39, b is an integer of 15 to 1932, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:39, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: LHECLPGSISYLHPRTPWLCLPPQHLSFSTFSPPWQPAMSPVPGTGGPPCGL (SEQ ID NO: 232), and or
  • This gene is expressed primarily in infant brain, testes and activated T cells, and to a lesser extent in various other normal and transformed cell types.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological, reproductive and inflammatory conditions.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, immune, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 132 as residues: Gly-41 to Leu-46, Asp-67 to Thr-75, Ile-114 to Ala-123. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution in infant brain tissue, testes tissue, and activated T- cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for the study, diagnosis, and/or treatment of neurological, reproductive and immune system disorders. Expression of this gene product in T-cells indicates a role in the regulation of the proliferation; survival; differentiation; and/or activation of potentially all hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the gene or protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues. Therefore it is also used as an agent for immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis.
  • immunological disorders including arthritis, asthma, immune deficiency diseases such as AIDS, leukemia, rheumatoid arthritis, inflammatory bowel disease, sepsis, acne, and psoriasis.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell type.
  • tissue distribution in testes tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of conditions concerning proper testicular function (e.g. endocrine function, sperm maturation), as well as cancer. Therefore, this gene product is useful in the treatment of male infertility and/or impotence.
  • This gene product is also useful in assays designed to identify binding agents, as such agents (antagonists) are useful as male contraceptive agents.
  • the protein is believed to be useful in the treatment and/or diagnosis of testicular cancer.
  • testes are also a site of active gene expression of transcripts that is expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product is expressed in other specific tissues or organs where it may play related functional roles in other processes, such as hematopoiesis, inflammation, bone formation, and kidney function, to name a few possible target indications.
  • tissue distribution in infant brain tissue indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:40 amino acid sequences
  • amino acid sequences are related to SEQ ID NO:40 and may have been publicly available prior to conception of the present invention.
  • related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 867 of SEQ ID NO:40, b is an integer of 15 to 881, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:40, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with some human and rodent melanoma and leukocyte specific antigens (see, for example, Genbank accession nos: gi
  • the translation product of this gene shares sequence homology with Tetraspan protein (see, for example, Genbank accession number: Gl 3152703). Therefore, it is likely that the polypeptide of this gene shares some biological functions, such as cell-to-cell signaling, adhesion, proliferation, and differentiation with Tetraspan.
  • polypeptide of this gene has been determined to have two transmembrane domains at about amino acid position 52-68 and 197 - 213 of the amino acid sequence referenced in Table 1 for this gene. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type Ilia membrane proteins.
  • the transmembrane 4 superfamily (TM4SF) or tetraspan superfamily has at least 16 members (including CD9, CD20, CD37, CD53, CD63, CD81, CD82, A15, CO-029, Sm23, RDS, Uro B, Uro A, SAS, Rom-1, PET A3, and YKK8), is the second biggest subfamily among CD antigen superfamily. and activation antigen of T- cells. All TM4SF member contains four putative transmembrane domains, two extracellular loops, and two short cytoplasmic tails.
  • CD9 cell surface protein is expressed by both hematopoietic and neural cells, and may play a role for CD9 in intercellular signaling in the immune and nervous system.
  • CD63 is a 53-Kd lysosomal membrane glycoprotein that has been identified as a platelet activation molecule, which play important role in cell adhesion of platelets and endothelial cells. Increased mRNA for CD63 antigen was found in atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits, suggesting a potential role of CD63 in progression of atherosclerosis. CD63 is also a mast cell marker.
  • CD82 was originally identified as the target of several mAbs inhibitory to syncytium formation induced by human T-cell leukemia virus type I (HTLV-I), the etiological agent of adult T-cell leukemia. Therefore, this gene could be a target for the development of a drug for this leukemia.
  • CD81 is the target of an antiproliferative antibody.
  • a diverse group of human cell lines, including hematolymphoid, neuroectodermal, and mesenchymal cells express the CD81 protein. Many of the lymphoid cell lines, in particular those derived from large cell lymphomas, were susceptible to the antiproliferative effects of the antibody. CD81 may therefore play an important role in the regulation of lymphoma cell growth.
  • CD9, CD20, CD37, CD63, CD81 and CD82 have been implicated in the regulation of cell growth, adhesion, and signal transduction of B, T lymphocytes and some other non-lymphoid cells. They associate with CD2, CD21, CD4, CD8, MHC Class II molecules, integrins, function as co-receptor for T, B and other lymphoid cells.
  • Some TM4SF are leukocyte antigens, highly expressed in activated leukocytes, lymphocytes, are highly specific surface marker for lymphoblastic leukemia, lymphoma, melanoma, and neuroblastoma.
  • CD9 has been show to be involved in cell motility and tumor metastasis.
  • C33 antigen CD82
  • TMSF transmembrane 4 superfamily
  • C33 Ag CD82 was originally identified as the target of several mAbs inhibitory to syncytium formation induced by human T-cell leukemia virus type I (HTLV-I), the etiological agent of adult T-cell leukemia. Therefore, this gene could be very important target for developing drug for leukemia.
  • CD63 is a 53-Kd lysosomal membrane glycoprotein that has been identified as a platelet activation molecule.
  • Pltgp40 a platelet membrane glycoprotein are the same molecule and that CD63/Pltgp40 is identical to the well-characterized, stage-specific melanoma-associated antigen ME491.
  • These antigen could be valuable immunogens or target to implement active and passive immunotherapy in patients with cancer.
  • This gene is expressed primarily in fetal tissue (kidney, heart, liver, spleen, brain), macrophages, dendritic cells, retina and to a lesser extent in various other tissues, mostly of lymphoid origin or epithelial cell types. In addition This gene is expressed in cancerous tissues (e.g. breast).
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoietic diseases and/or disorders and cancers in a variety of organs and cell types.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developmental, proliferating, immune, hematopoietic, integumentary, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid, spinal fluid, or amniotic fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 133 as residues: Tyr-123 to Tyr-131, Cys-134 to Ser- 145, Tyr-234 to Tyr-244. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution fetal cells and tissues and homology to tumor antigens indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, treatment and diagnosis of lymphoid and epithelial disorders and neoplasms. Additionally, tissue distribution in immune cells and other tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders affecting hematopoesis, including cancers. Representative uses are described in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses). Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions.
  • immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophi
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration” sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to aberrant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:41 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:41 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1918 of SEQ ID NO:41, b is an integer of 15 to 1932, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:41, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares limited sequence homology with VEGF which is thought to be important in regulation of endothelial cell growth. Therefore, it is likely that the protein encoded by this gene would share some similar biological functions.
  • the gamma activating sequence is a promoter element found upstream of many genes which are involved in the Jak-STAT pathway.
  • the Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the GAS element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
  • polypeptides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, nervous system disease and/or disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 134 as residues: Thr-25 to Pro-46. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in brain indicates polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions. Representative uses are described in the "Regeneration” and "Hype ⁇ roliferative
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • this gene product in regions of the brain indicates it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1150 of SEQ ID NO:42, b is an integer of 15 to 1164, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:42, and where b is greater than or equal to a + 14.
  • polypeptides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological and growth defects/disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for study and treatment of central nervous system, neurodevelopmental, cognitive, and memory disorders.
  • tissue distribution also indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions. Representative uses are described in the "Regeneration” and "Hype ⁇ roliferative Disorders" sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the expression within embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration" sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattem formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:43 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:43 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1091 of SEQ ID NO:43, b is an integer of 15 to 1105, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:43, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in PMA stimulated HL-60 cells and to a lesser extent in 6 week embryo.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders affecting cell differentiation, particulary hematopoietic disorders and or defects.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 136 as residues: Pro-61 to Asp-68. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the study of cellular differentiation and for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia.
  • the tissue distribution also indicates polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Representative uses are described in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types
  • the expression within embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration" sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:44 amino acid sequence sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:44 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1248 of SEQ ID NO:44, b is an integer of 15 to 1262, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:44, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in colon.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders and/or defects of the digestive tract including but not limited to cancers of the gastrointestinal tract.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., gastrointestinal, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the digestive system particulary disorders involving the colon. Further, expression of this gene product in colon tissue indicates involvement in digestion, processing, and elimination of food, as well as a potential role for this gene as a diagnostic marker or causative agent in the development of colon cancer, and cancer in general. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the colon and/or other gastrointestinal tissue including, but not limited to, stomach, small intestine, large intestine, and rectum. Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 503 of SEQ ID NO:45, b is an integer of 15 to 517, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:45, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in blood cells.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoietic diseases.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 138 as residues: Pro-19 to Cys-29, Thr-35 to Glu-44, Val-72 to Lys-78. Polynucleotides encoding said polypeptides are also provided. The tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis and or treatment of disorders of the immune and hematopoietic system. Representative uses are described in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:46 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:46 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 844 of SEQ ID NO:46, b is an integer of 15 to 858, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:46, and where b is greater than or equal to a + 14.
  • FEATURES OF PROTEIN ENCODED BY GENE NO: 37 This gene is expressed in multiple tissue systems such as brain, immune cells, prostate, uterus, testes, placenta, and fetal heart as well as in cancerous tissues such as ovarian tumors. .
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the immune, reproductive, urogenital, and central nervous system.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, reproductive, urogenital, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 139 as residues: Tyr-33 to Lys-38. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for treatment and diagnosis of disorders of the immune, urogenital, reproductive, and central nervous systems.
  • the tissue distribution in central nervous system tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or diagnosis of diseases of the central nervous system, as well as cancers of tissues where expression of this gene has been observed, such as in ovarian tumors.
  • tissue distribution in central nervous system tissues also indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • the gene or gene product may also play a role in the treatment and/or detection of developmental disorders associated with the developing embryo.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration” sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattem formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to aberrant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the tissue distribution in uterus indicates that polynucleotides and polypeptides corresponding to this gene are useful for treating female infertility.
  • the protein product is likely involved in preparation of the endometnum of implantation and could be administered either topically or orally.
  • this gene could be transfected in gene-replacement treatments into the cells of the endometrium and the protein products could be produced.
  • these treatments could be performed during artificial insemination for the pu ⁇ ose of increasing the likelyhood of implantation and development of a healthy embryo. In both cases this gene or its gene product could be administered at later stages of pregnancy to promote heathy development of the endometrium.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the tissue distribution in testes indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of conditions concerning proper testicular function (e.g. endocrine function, sperm maturation), as well as cancer. Therefore, this gene product is useful in the treatment of male infertility and/or impotence.
  • This gene product is also useful in assays designed to identify binding agents, as such agents (antagonists) are useful as male contraceptive agents.
  • the protein is believed to be useful in the treatment and/or diagnosis of testicular cancer.
  • testes are also a site of active gene expression of transcripts that is expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product is expressed in other specific tissues or organs where it may play related functional roles in other processes, such as hematopoiesis, inflammation, bone formation, and kidney function, to name a few possible target indications.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:47 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:47 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 6093 of SEQ ID NO:47, b is an integer of 15 to 6107, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:47, and where b is greater than or equal to a + 14.
  • FEATURES OFPROTEIN ENCODED BY GENE NO: 38 This gene is expressed in a wide range of tissue systems such as brain, immune cells, fetal liver, kidney, testes, breast, and pancreas as well as cancerous tissue such as ovarian tumors.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders of the central nervous system, immune system, urogenital, and reproductive system.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, CNS, urogenital, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 140 as residues: Met-1 to Ser-7, Asp-32 to Pro-43, Ser-96 to Arg-102.
  • Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune, reproductive, urogenital and central nervous systems.
  • the tissue distribution in central nervous system tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment and/or diagnosis of diseases of the central nervous system, as well as cancers of tissues where expression of this gene has been observed, such as in ovarian tumors.
  • the tissue distribution in central nervous system tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • the tissue distribution indicates polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders.
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration” sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to aberrant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 689 of SEQ ID NO:48, b is an integer of 15 to 703, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:48, and where b is greater than or equal to a + 14.
  • FEATURES OF PROTEIN ENCODED BY GENE NO: 39 This gene is expressed primarily in macrophages and fetal cells and to a lesser extent in cancerous ovarian tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune diseases, disorders of developing tissues, and cancer.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for treatment and diagnosis of developmental abnormalities and disorders of the immune systems.
  • the tissue distribution cancerous ovaries indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and intervention of these tumors.
  • Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and or immunotherapy target for the above listed tissues.
  • Expression of this gene product in macrophage cells strongly indicates a role for this protein in immune function and immune surveillance.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • This gene product may have clinical utility in the treatment of immune dysfunction; in the correction of autoimmunity; in immune modulation; and in the control of inflammation.
  • tissue distribution indicates polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Representative uses are described in the "Immune
  • Example 11 Activity and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration” sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the tissue distribution also indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders such as melanomas.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:49 Some of these sequences are related to SEQ ID NO:49 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 625 of SEQ ID NO:49, b is an integer of 15 to 639, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:49, and where b is greater than or equal to a + 14.
  • polypeptides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hematopoietic disorders, Limbic system disfunction/defects and disorders of the immune system and developing systems.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 142 as residues: Ala-84 to Gln-93. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for treatment and diagnosis of disorders of the immune, Limbic system, CNS and developing systems.
  • Expression of this gene product in bone marrow, eosinophils, and neutrophils strongly indicates a role for this protein in hematopoiesis and immune surveillance.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes that may also suggest a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • This gene product may have clinical utility in the treatment of immune dysfunction; in the correction of autoimmunity; in immune modulation; and in the control of inflammation.
  • Protein as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the tissue distribution indicates polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration” sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to aberrant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:50 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:50 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 853 of SEQ ID NO:50, b is an integer of 15 to 867, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:50, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, ovarian cancer, gastrointestinal and immune system disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, gastrointestinal, immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 143 as residues: Ile-23 to Ala-29. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for diagnosis and treatment of ovarian cancer and related metastases.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for treating female infertility.
  • the tissue distribution in colon tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and/or treatment of disorders involving the gastrointestinal tract.
  • This may include diseases associated with digestion and food abso ⁇ tion, as well as hematopoietic disorders involving the Peyer's patches of the small intestine, or other hematopoietic cells and tissues within the body Similarly, expression of this gene product in colon tissue indicates again involvement in digestion, processing, and elimination of food, as well as a potential role for this gene as a diagnostic marker or causative agent the development of colon cancer, and cancer in general. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions.
  • Representative uses are descnbed in the "Hype ⁇ rohferative Disorders" and "Regeneration" sections below and elsewhere herein. Bnefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result m inapprop ⁇ ate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications m the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist m proliferating and cancerous cells and tissues
  • the prote can also be used to gam new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:51 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:51 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1555 of SEQ ID NO:51, b is an integer of 15 to 1569, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:51, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with retrovirus-related reverse transcriptase pseudogene.
  • this gene shares homology with human interferon-beta (Genseq accession number T35524; all references available through this accession are hereby inco ⁇ orated herein by reference), therefore, it is likely that this gene and the protein encoded by this gene shares some similar biological functions with this protein.
  • This gene is expressed primarily in frontal cortex.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurodegenerative diseases and/or disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in frontal cortex and homology to retrovirus-related reverse transcriptase pseudogene and human interferon-beta indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosis and treatment of neurodegenerative diseases of the brain, particularly of the frontal cortex.
  • the tissue distribution indicates polynucleotides and polypeptides corresponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions.
  • Representative uses are described in the "Regeneration” and "Hype ⁇ roliferative Disorders" sections below, in Example 11, 15, and 18, and elsewhere herein. Briefly, the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, multiple schlerosis, cystic fibrosis,
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 1182 of SEQ ID NO:52, b is an integer of 15 to 1196, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO.52, and where b is greater than or equal to a + 14
  • This gene is expressed p ⁇ manly in immune cells, brain, fetal tissue, and cancerous tissues (such as testes, stomach, lung, pancreas, ova ⁇ es) and to a lesser extent in other numerous tissues including, but not limited to, testes and kidney.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurodegenerative diseases Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s)
  • tissues or cell types e g , cancerous and wounded tissues
  • bodily fluids e g., lymph, serum, plasma, unne, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, I e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder
  • Prefe ⁇ ed polypeptides of the present invention compnse immunogenic epitopes shown in SEQ ID NO 145 as residues Lys-23 to Lys-35, Met-46 to Tyr-52 Polynucleotides encoding said polypeptides are also provided The tissue distnbution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosis and treatment of neurodegenerative disorders of the frontal cortex, as well as, cancer or a number of tissues including but not limited to testes, stomach, lung, pancreas, and ova ⁇ es.
  • tissue dist ⁇ bution indicates polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions.
  • Representative uses are desc ⁇ bed in the "Regeneration” and "Hype ⁇ rohferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, penpheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord mjunes, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protem may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutntional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • the tissue dist ⁇ bution indicates polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of a va ⁇ ety of immune system disorders.
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration” sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:53 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:53 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 931 of SEQ ID NO:53, b is an integer of 15 to 945, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:53, and where b is greater than or equal to a + 14.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., cancerous and wounded tissues
  • bodily fluids e.g., amniotic, lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 146 as residues: Tyr-39 to Arg-51. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosis and treatment of certain cancers, including epithelioid sarcoma and pancreatic carcinoma.
  • the tissue distribution in tumors of lung, ovary, and pancreas origins indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and intervention of these tumors, in addition to other tumors where expression has been indicated.
  • Protein, as well as, antibodies directed against the protein may show utility as a tissue-specific marker and/or immunotherapy target for the above listed tissues.
  • embryonic tissue and other cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration” sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • tissue distribution indicates polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders. Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:54 Some of these sequences are related to SEQ ID NO:54 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 474 of SEQ ID NO: 54, b is an integer of 15 to 488, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:54, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence: PPVPPWISLPLTGSPPRPGFVPVSPFCFSPMTNGHQVLLLLLLTSAVAAGPWPQ VHAGQWGWMCLPPGLPSVQARSGLGGLPGGPQWVPGGARGY (SEQ ID NO: 234).
  • Polynucleotides encoding these polypeptides are also provided.
  • This gene is expressed primarily in fetal and infant tissue, particularly infant brain and fetal liver/spleen libraries, and to a lesser extent in breast, ovary tumor, pharynx carcinoma, endometrial stromal cells, thymus, islet cell tumors, and adult cerebellum.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, cancer and other prohferative disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, developmental, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, amniotic fluid, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in developing cells and tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosis and treatment of cancer and other prohferative disorders.
  • the expression within cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to aberrant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:55 Some of these sequences are related to SEQ ID NO:55 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2846 of SEQ ID NO:55, b is an integer of 15 to 2860, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:55, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • Polynucleotides encoding these polypeptides are also provided.
  • This gene is expressed primarily in breast cancer, and to a lesser extent in a variety of other cancers, including uterine cancer, synovial sarcoma, and pharynx carcinoma.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, breast cancer; prohferative diseases and or disroders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, breast, prohferative, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, breast milk, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 148 as residues: Glu-35 to His-41, Ser-62 to Ala-67, Pro-145 to Leu-155, Glu-157 to Ser-163, Arg-190 to Val-197, Asp-208 to Pro-215, Ser-247 to Pro-252. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in breast cancer tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and/or treatment of cancer. Elevated expression of this gene product in cancers, such as breast cancer, suggest that it is involved in the abnormal proliferation of cells, dedifferentiation, angiogenesis, and other processes that accompany the development of cancer. Thus, therapeutics targeted against this gene product is useful therapeutic products in and of themselves. Alternately, expression of this gene product at elevated levels in breast tissue is reflective of expression within breast lymph nodes, and may suggest a hematopoietic role for this protein. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration" sections below and elsewhere herein.
  • apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to aberrant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:56 Some of these sequences are related to SEQ ID NO:56 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1545 of SEQ ID NO:56, b is an integer of 15 to 1559, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:56, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares limited sequence homology with cytochrome-c oxidase.
  • An alternative embodiment is the polypeptide comprising the following amino acid sequence:
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence: WARLRGPGAHARTSPQPWRGPSPAQAAMGFLQLLVVXVLXSEHRVAGAAE VFGNSSEGLIEFSVGKFRYF
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurodegenerative disorders; hematopoietic disorders; integumentary disroders; immune dysfunction; learning disabilities.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., integumentary, neural, developmental, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in brain and spinal cord cells and tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of a vanety of neurological and hematopoietic disorders.
  • elevated levels of expression of this gene product in brain and spinal cord indicates that it is involved in neurodegenerative disorders
  • Representative uses are desc ⁇ bed in the "Regeneration” and "Hype ⁇ ro ferative Disorders" sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, pe ⁇ pheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord inju ⁇ es, ischemia and infarction, aneurysms, hemorrhages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • this gene product in regions of the brain indicates it plays a role in normal neural function Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. Alternately, expression of this gene product in hematopoietic cells indicates that it is involved in the proliferation, differentiation, survival, and activation of all hematopoietic lineages, including stem and progenitor cells Expression of this gene product in keratinocytes indicates that it is involved m normal skin function, and could be involved m skin disorders, dermatitis, and fibrosis. The protein is useful in detecting, treating, and/or preventing congenital disorders (I e.
  • nevi moles, freckles, Mongolian spots, hemangiomas, port-wine syndrome
  • integumentary tumors i.e. keratoses, Bowen's Disease, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, Paget's Disease, mycosis fungoides, and Kaposi's sarcoma
  • inju ⁇ es and inflammation of the skin I e.wounds, rashes, pnckly heat disorder, psonasis, dermatitis
  • atherosclerosis utica ⁇ a, eczema, photosensitivity, autoimmune disorders (i.e.
  • lupus erythematosus vitihgo, dermatomyositis, mo ⁇ hea, scleroderma, pemphigoid, and pemphigus
  • keloids st ⁇ ae, erythema, petechiae, pu ⁇ ura, and xanthelasma.
  • disorders may predispose increased susceptibility to viral and bactenal infections of the skin (l e. cold sores, warts, chickenpox, molluscum contagiosum, he ⁇ es zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm).
  • the protein product of this gene may also be useful for the treatment or diagnosis of various connective tissue disorders (i.e., arthritis, trauma, tendonitis, chrondomalacia and inflammation, etc.), autoimmune disorders (i.e., rheumatoid arthritis, lupus, scleroderma, dermatomyositis, etc.), dwarfism, spinal deformation, joint abnormalities, amd chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).
  • connective tissue disorders i.e., arthritis, trauma, tendonitis, chrondomalacia and inflammation, etc.
  • autoimmune disorders i.e., rheumatoid arthritis, lupus, scleroderma, dermatomyositis, etc.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:57 Some of these sequences are related to SEQ ID NO:57 and may have been publicly available prior to conception of the present invention.
  • related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2050 of SEQ ID NO:57, b is an integer of 15 to 2064, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:57, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence: PRVRPASPPVRSPARWGSMAGSPLLWGPRAGGVGLLVLLLLGLFRPPPALCA RPVKEPRGLSAASPPLARLALLAASGGQCPEVRRRGRCRPGAGAGASAGAER QERARAEAQRLRISRRASWRSCCASGAPPATLIRLWAWTTTPTRLQRSSLALC SAPALTLPP (SEQ ID NO: 238).
  • Polynucleotides encoding these polypeptides are also provided.
  • This gene is expressed primarily in human pituitary and to a lesser extent in pineal gland, and other areas of the brain.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, pituitary dysfunction; abnormal growth; neurological defects; insufficient milk secretion; abnormal smooth muscle contraction.
  • diseases and conditions which include, but are not limited to, pituitary dysfunction; abnormal growth; neurological defects; insufficient milk secretion; abnormal smooth muscle contraction.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., endocrine, developmental, reproductive, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, amniotic fluid, breast milk, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 150 as residues: Pro-36 to Gly-42, Pro-64 to Ala-76, Gly-83 to Ala-90, Ser- 100 to Cys-108, Thr- 126 to Ser- 135.
  • Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution primarily in pituitary cells and tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and/or treatment of a variety of disorders.
  • Elevated expression of this gene product in the pituitary indicates that it is possibly a hormone-like substance that either controls pituitary development itself, or various processes controlled by the pituitary. These include growth, milk secretion, smooth muscle contraction, diuresis, blood pressure, and homeostasis. Thus, this gene product may have numerous clinical applications. Expression of this gene product in other regions of the brain also indicates that it is involved in normal neurological function, and is useful in the treatment of a variety of neurological disorders. Representative uses are described in the "Biological Activity”, “Hype ⁇ roliferative Disorders", and “Binding Activity” sections below, in Example 11, 17, 18, 19, 20 and 27, and elsewhere herein.
  • the protein can be used for the detection, treatment, and/or prevention of Addison's Disease, Cushing's Syndrome, and disorders and/or cancers of the pancrease (e.g. diabetes mellitus), adrenal cortex, ovaries, pituitary (e.g., hyper-, hypopituitarism), thyroid (e.g. hyper-, hypothyroidism), parathyroid (e.g. hyper-,hypoparathyroidism) , hypothallamus, and testes.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement.
  • Protein, as well as, antibodies directed against the protein may show utility
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:58 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1036 of SEQ ID NO:58, b is an integer of 15 to 1050, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:58, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • the polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 7 - 23 of the amino acid sequence referenced in Table 1 for this gene. Moreover, a cytoplasmic tail encompassing amino acids 24 to 390 of this protein has also been determined. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type lb membrane proteins. The gene encoding the disclosed cDNA is believed to reside on chromosome
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 12.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, prostate cancer; pancreatic cancer; prostate dysfunction; hematopoietic disorders; reproductive diseases and/or disorders, and pancreatitis.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, prostate, pancease, placental, vascular, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, seminal fluid, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 151 as residues: Pro-85 to Ser-94, Pro-127 to Thr- 136, Glu-154 to Glu-160, Phe-240 to Ser-250, Leu-255 to Leu-265, Leu-341 to Lys- 351, Thr-372 to Gly-384. Polynucleotides encoding said polypeptides are also provided.
  • tissue dist ⁇ bution in prostate and placental cells and tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and/or treatment of a vanety of reproductive disorders. Elevated expression of this gene product in the prostate indicates that it is involved in normal prostate function, and is a diagnostic marker for prostate cancer. Alternately, expression of this gene product in placenta indicates that it may play a role in normal vascular function, and is involved m such processes as angiogenesis and endothelial cell chemotaxis. Thus, this gene product is useful in the treatment of myocardial infarction, cancer, ischemia, and diabetic retmopathy. Expression of this gene product in placenta may also be indicative of fetal health and development.
  • expression of this gene product in hematopoietic cells indicates that it is involved in the proliferation, differentiation, survival, or activation of all hematopoietic cell lineages.
  • expression of this gene product in pancreatic cancers indicates that it may play a role in cancer in general, or in pancreatic function.
  • the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, and as nutritional supplements. It may also have a very wide range of biological activities. Representative uses are descnbed in the "Chemotaxis" and "Binding Activity" sections below, in Examples 11, 12, 13, 14, 15, 16, 18, 19, and 20, and elsewhere herein.
  • the protein may possess the following activities: cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines, immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:59 Some of these sequences are related to SEQ ID NO:59 and may have been publicly available pnor to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • a-b a nucleotide sequence desc ⁇ bed by the general formula of a-b, where a is any integer between 1 to 2519 of SEQ ID NO:59, b is an integer of 15 to 2533, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:59, and where b is greater than or equal to a + 14.
  • GAS gamma activating sequence
  • ISRE miterferon-sensitive responsive element
  • ISRE is also a promoter element found upstream in many genes which are involved in the Jak-STAT pathway.
  • the Jak-STAT pathway is a large, signal transduction pathway involved in the differentiation and proliferation of cells. Therefore, activation of the Jak-STAT pathway, reflected by the binding of the ISRE element, can be used to indicate proteins involved in the proliferation and differentiation of cells.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • polynucleotides encoding these polypeptides are also provided. This gene is expressed primarily in brain and placenta. Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, reproductive, vascular, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 152 as residues: Met-1 to Thr-7, Glu-36 to Ser-43, Pro-46 to Gly-63. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in brain and placental cells and tissues indicates that the protein products of this gene are useful for the diagnosis and/or treatment of a variety of neural, reproductive, and vascular diseases and/or disorders, neurodegenerative disease states, behavioral disorders, or inflammatory conditions.
  • Representative uses are described in the "Regeneration” and "Hype ⁇ roliferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • Expression of this gene product in placenta indicates that it may play a role in blood vessel development or function, as the placenta is a highly vascularized organ.
  • this gene product is involved in such processes as angiogenesis, endothelial cell chemotaxis, and vascular cord formation.
  • it is useful in the treatment of such conditions as myocardial infarction; ischemia; and cancer.
  • this gene product in the brain indicates that it may play a role in the survival, proliferation, or function of neurons, and thus is useful in the diagnosis and treatment of such neurological disorders as ALS, schizophrenia, and Alzheimer's Disease. It may likewise be involved in learning disorders as well.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:60 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:60 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 885 of SEQ ID NO:60, b is an integer of 15 to 899, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:60, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • the polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 40 - 56 of the amino acid sequence referenced in Table 1 for this gene. Moreover, a cytoplasmic tail encompassing amino acids 57 to 60 of this protein has also been determined. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type la membrane proteins. This gene is expressed primarily in spleen derived from patients with chronic lymphocytic leukemia.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, chronic lymphocytic leukemia; hematopoietic disorders; impaired immune function; cancer.
  • diseases and conditions which include, but are not limited to, chronic lymphocytic leukemia; hematopoietic disorders; impaired immune function; cancer.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in spleen cells and tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and/or treatment of a variety of hematopoietic disorders.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the uses include bone marrow cell ex-vivo culture, bone marrow transplantation, bone ma ⁇ ow reconstitution, radiotherapy or chemotherapy of neoplasia.
  • the gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types. Elevated expression of this protein in the spleens of patients with CLL indicates that it is a useful marker for thi's Disease. Alternately, it is associated with the development and/or progression of the disease, and is a useful target for therapeutic intervention.
  • this gene product may play more general roles in hematopoiesis, and may serve to control cellular decisions regarding proliferation, survival, activation, and/or differentiation of all hematopoietic cell lineages.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:61 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:61 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1065 of SEQ ID NO:61, b is an integer of 15 to 1079, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:61, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with a putative tyrosine protein kinase from the Chilo iridescent virus. See, for example, Genbank accession no. gi
  • This gene is expressed in a variety of tissues, including microvascular endothelial cells, dendritic cells, and fetal tissues, as well as several tumors.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, vascular, immune, and developmental diseases and/or disorders, particularly cancer.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., vascular, immune, developmental, prohferative, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, amniotic fluid, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 154 as residues: Ala-21 to Lys-31, Arg-41 to Cys-56, Thr-92 to Cys-102, Arg-132 to Val-137, Lys-152 to Ue-159, Pro-199 to Ser-205, Arg- 210 to Asp-219, Ser-225 to Lys-230, Tyr-236 to Ala-241, Lys-243 to Leu-249, Thr- 375 to Asp-381. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution and homology to a tyrosine kinase indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosis and treatment of cancer.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein is useful in the detection, treatment, and/or prevention of vascular conditions, which include, but are not limited to, microvascular disease, vascular leak syndrome, aneurysm, stroke, atherosclerosis, arteriosclerosis, or embolism.
  • this gene product may represent a soluble factor produced by smooth muscle that regulates the innervation of organs or regulates the survival of neighboring neurons.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:62 Some of these sequences are related to SEQ ID NO:62 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1914 of SEQ ID NO:62, b is an integer of 15 to 1928, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:62, and where b is greater than or equal to a + 14.
  • polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 2 - 18 of the amino acid sequence referenced in Table 1 for this gene. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type lb membrane proteins. This gene is expressed primarily in neutrophils. Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoietic diseases and/or disorders, particularly cancer and immune suppression.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 155 as residues: Gly-63 to Ser-72. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful as a marker for neutrophil monitoring in cancer and/or immune suppressed patients and/or during chemotherapy or radiation therapy.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:63 amino acid sequence sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:63 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 767 of SEQ ID NO:63, b is an integer of 15 to 781, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:63, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in IL-1 and LPS induced neutrophils, and to a lesser extent, in fetal brain.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune, hematopoietic, and neural diseases and/or disorders, particularly cancer and immune suppression.
  • diseases and conditions which include, but are not limited to, immune, hematopoietic, and neural diseases and/or disorders, particularly cancer and immune suppression.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, neural, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, amniotic fluid, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 156 as residues: Ile-28 to T ⁇ -37, Ser-68 to Lys-81. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in neutrophils indicates that polynucleotides and polypeptides corresponding to this gene are useful as a marker in neutrophils to monitor patients who are immune suppressed or cancer patients during chemotherapy or radiation therapy.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:64 Some of these sequences are related to SEQ ID NO:64 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1180 of SEQ ID NO:64, b is an integer of 15 to 1194, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:64, and where b is greater than or equal to a + 14.
  • polypeptides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, urogenital diseases and/or disorders, particularly prostate cancer.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., urogenital, prostate, renal, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 157 as residues: Arg-30 to Gln-36. Polynucleotides encoding said polypeptides are also provided.
  • the tissue distribution in prostate cancer cells indicates that polynucleotides and polypeptides corresponding to this gene are useful for study, treatment and diagnosis of prostate cancer and other urogenital disorders. Moreover, the expression within cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration" sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:65 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:65 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1663 of SEQ ID NO:65, b is an integer of 15 to 1677, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:65, and where b is greater than or equal to a + 14.
  • a preferred polypeptide of the invention comprises the following amino acid sequence: MVLVLRHPLCARERAFREPGRGLLTRTGQHDGAPAVTAVPGPLGAVAAAEG RRSAWGAGGSSPPRKVLWGDMRGRRAGVDVLGPALSSEAAGAEARGWGM PGMGVGVGASETRGALFLGREGVHGPCPMDGLGPWPWGPW (SEQ ID NO: 242). Polynucleotides encoding these polypeptides are also provided. This gene is expressed primarily in rejected kidney.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases and/or disorders affecting the kidney.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., urogenital, renal, kidney, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 158 as residues: Ala-30 to Gly-36, Asp-45 to T ⁇ -50, Lys-65 to Cys-71, Pro-80 to Cys-87. Polynucleotides encoding said polypeptides are also provided.
  • kidney distribution in kidney indicates the protein product of this gene could be used in the treatment and/or detection of kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome.
  • the protein is useful for modulating the immune response to abe ⁇ ant proteins, as may exist in proliferating cells and tissues.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:66 amino acid sequence sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:66 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1223 of SEQ ID NO:66, b is an integer of 15 to 1237, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:66, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with both human and mouse Fibulin-2 which is an extracellular matrix protein found in heart tissue (See Genbank Accession Nos. emb
  • polypeptides encoded by this gene comprise the following amino acid sequence: MGPAVKMWTNAWKGLDDCHYNQLCENTPGGHRCSCPRGYRMQGPSLPCL DVNECLQLPKACAYQCHNLQGSYRCLCPPGQTLLRDGKACTSLERNGQNVT TVSHRGPLLPWLRPWASIPGTSYHAWVSLRPGPMALSSVGRAWCPPGFIRQN GVCTDLDECRVRNLCQHACRNTEGSYQCLCPAGYRLLPSGKNCQDINECEEE SIECGPGQMCFNTRGSYQCVDTPCPATYRQGPSPGTCFRRCSQDCGTGGPSTL QYRLLPLPLGVRAHHDVARLTAFSEVGVPANRTELSMLEPDPRSPFALRPLRA GLGAVYTRRALTRAGLYRLTVRAAAPRHQSVFVLLIAVSPYPY (SEQ ID NO: 243). Polynucleotides encoding these polypeptides are also provided.
  • a prefe ⁇ ed polypeptide fragment of the invention comprises the following amino acid sequence:
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • GAS gamma activating sequence
  • polypeptides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases and/or disorders affecting the kidney and renal system.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., renal, urogenital, kidney, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 159 as residues: Lys-32 to Ser-37, His-89 to Gly-94, Asn-124 to Gln-130, Ala-163 to Val-168, Cys-196 to Arg-201. Gln-244 to Gln-264, His-288 to Tyr-294, Leu-314 to Gln-319, Ala-392 to Ser-399, Pro-412 to Asp-419, Ala-452 to Pro-460, Arg-466 to Thr-473. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in rejected kidney indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of disorders affecting kidneys, particularly prohferative disorders. Representative uses are described here and elsewhere herein.
  • kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi's syndrome.
  • kidney diseases including renal failure, nephritus, renal tubular acidosis, proteinuria, pyuria, edema, pyelonephritis, hydronephritis, nephrotic syndrome, crush syndrome, glomerulonephritis, hematuria, renal colic and kidney stones, in addition to Wilm's Tumor Disease, and congenital kidney abnormalities such as horseshoe kidney, polycystic kidney, and Falconi
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:67 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1920 of SEQ ID NO:67, b is an integer of 15 to 1934, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:67, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence:
  • a preferred polypeptide fragment of the invention comprises the following amino acid sequence:
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • the polypeptide of this gene has been determined to have two transmembrane domains at about amino acid position 144 - 160, and 462 - 478 of the amino acid sequence referenced in Table 1 for this gene. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type Ilia membrane proteins. Included in this invention as a preferred domain is the formate and nitrite transporters domain, which was identified using the ProSite analysis tool (Swiss Institute of Bioinformatics). A number of bacterial and archaebacterial proteins involved in transporting formate or nitrite have been shown [1] to be related: - focA and focB, from Escherichia coli, transporters involved in the bidirectional transport of formate.
  • - fdhC from Methanobacterium formicicum and thermoformicicum, a probable formate transporter.
  • - nirC from Escherichia coli and Salmonella typhimurium, a probable nitrite transporter.
  • Bacillus subtilis hypothetical protein yrhG. Bacillus subtilis hypothetical protein ywcJ (ipa-48R).
  • These transporters are proteins of about 280 residues and seem to contain six transmembrane regions. As signature patterns, we selected two conserved regions. The first one is located in what seems to be a cytoplasmic loop between the second and third transmembrane domains; the second is part of the fourth transmembrane region.
  • the 70 Kd yeast hypothetical protein YHL008c is highly similar, in its N- terminal section, to the prokaryotic members of this family.
  • the concensus pattern is as follows: [LIVMA]-[LIVMY]-x-G-[GSTA]-[DES]-L-[H]-[TN]-[GS].
  • polypeptides of the invention comprise the following amino acid sequence: IISGSELITG (SEQ ID NO: 249). Polynucleotides encoding these polypeptides are also provided. Further preferred are polypeptides comprising the formate and nitrite transporter domain of the sequence referenced in Table for this gene, and at least 5, 10, 15, 20, 25, 30, 50, or 75 additional contiguous amino acid residues of this referenced sequence. The additional contiguous amino acid residues is N-terminal or C- terminal to the formate and nitrite transporter domain.
  • the additional contiguous amino acid residues is both N-terminal and C-terminal to the formate and nitrite transporter domain, wherein the total N- and C-terminal contiguous amino acid residues equal the specified number.
  • the above prefe ⁇ ed polypeptide domain is characteristic of a signature specific to formate and nitrite transporter proteins.
  • the translation product of this gene is expected to share at least some biological activities with formate and nitrite transporter proteins. Such activities are known in the art, some of which are described elsewhere herein. It is believed that this gene maps to chromosome 2. Accordingly, polynucleotides derived from this gene are useful in linkage analysis as markers for chromosome 2. This gene is expressed primarily in cells of the immune system, primarily T- cells and to a lesser extent in spleen, liver, thymus, tonsils, and testis.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoietic diseases and/or disorders, particularly disorders affecting hematopoesis.
  • diseases and conditions which include, but are not limited to, immune and hematopoietic diseases and/or disorders, particularly disorders affecting hematopoesis.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 160 as residues: Gly-2 to Pro-8, Ser-82 to His-92, Tyr-107 to Asp-117, Arg-162 to Pro-169, Ser-224 to Thr-229, Leu-310 to His-315, Ser-333 to Glu-338, Glu-381 to Ser-388, Gln-428 to Ala-433, Met-446 to Thr-455, Ser-548 to Ser-554, Gly-613 to Asp-618, Ser-627 to Gln-633. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in immune cells and tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of disorders affecting hematopoesis, including cancers.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences, such as EST sequences are publicly available and accessible through sequence databases.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 3286 of SEQ ID NO:68, b is an integer of 15 to 3300, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:68, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence: VDGIDKLDIEFLQQFLETHSRGPRLHSPGH ASQEATPG ANMSSGTELLWPGA A LLVLLGVAASLCVRCSRPGAKRSEKIYQQRSLREDQQSFTGSRTYSLVGQAW PGPLADMAPTRKDKLLQFYPSLEDPASSRYQNFSKGSRHGSEEAYIDPIAMEY YNWGRFSKPPEDDDANSYENVLICKQKTTETGAQQEGIGGLCRGDLSLSLAL KTGPTSGLCPSASPEEDEGI (SEQ ID NO: 250). Polynucleotides encoding these polypeptides are also provided.
  • the polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 10 - 26 of the amino acid sequence referenced in Table 1 for this gene. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type lb membrane proteins.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, disorders affecting the immune and hematopoietic systems, particularly hematopoesis.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 161 as residues: Ser-29 to Thr-57, Pro-74 to Lys-79, Pro-85 to Glu-107, Tyr-118 to Tyr-136, Gln-144 to Gln-152, Ala-182 to Glu-188. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in immune and hematopoietic cells and tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the diagnosis and treatment of disorders affecting the immune system and hematopoesis.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages.
  • the uses include bone marrow cell ex-vivo culture, bone ma ⁇ ow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia.
  • the secreted protein can also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, and as nutritional supplements. It may also have a very wide range of biological activities.
  • the protein may possess the following activities: cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g. for treating human immunodeficiency virus infection, cancer, autoimmune diseases and allergy); regulation of hematopoiesis (e.g. for treating anemia or as adjunct to chemotherapy); stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves (e.g.
  • follicle stimulating hormone for control of fertility
  • chemotactic and chemokinetic activities e.g. for treating infections, tumors
  • hemostatic or thrombolytic activity e.g. for treating hemophilia, cardiac infarction etc.
  • anti-inflammatory activity e.g. for treating septic shock, Crohn's Disease
  • antimicrobials for treating psoriasis or other hype ⁇ roliferative diseases; for regulation of metabolism, and behavior.
  • the use of the corresponding nucleic acid in gene therapy procedures are also contemplated.
  • the proteins immune cell specific message distribution it may be involved in many aspects of the immune response, especially its initial stages, inflammation, allograft rejection, infectious disease response etc.
  • the expression of this clone is frequently found in the hematopoietic cell cDNA libraries.
  • this factor could be involved in the control of hematopoietic cell proliferation, differentiation, and function. Based on this one can postulate its use in the management of anemias, leukemias, neutropenia, thrombocytopenia, autoimmune diseases, blood tissue engraftment, and poikilothromerythromatosis.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:69 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1783 of SEQ ID NO:69, b is an integer of 15 to 1797, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:69, and where b is greater than or equal to a + 14.
  • polypeptides compnsmg the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention Specifically, polypeptides of the invention compnse the following amino acid sequence VLWREASALVLSNRLSSGLLHDLLLQPAIHSRLFPRRSRGLSEGEGSSVSLQRS RVLSAMKHVLNLYLLGVVLTLLSIFVRVMESLEGLLESPSPGTSWTTRSQLAN TEPTKGLPDHPSRSM (SEQ ID NO: 251). Polynucleotides encoding these polypeptides are also provided.
  • This gene is expressed p ⁇ ma ⁇ ly in immune cells including activated T cells, macrophages, jurkat cells, bone marrow cells, and osteoblasts and to a lesser extent in kidney cortex, brain, placenta and lung.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which mclude, but are not limited to, immune and hematopoietic diseases and/or disorders, particularly inflammation and diseases related to inflammatory activity
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, u ⁇ ne, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • polypeptides of the present invention compnse immunogenic epitopes shown in SEQ ID NO. 162 as residues: Pro-34 to Met-63 Polynucleotides encoding said polypeptides are also provided.
  • tissue distnbution in immune cells and tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for treating or diagnosing disease related to the normal or abnormal activation of T cells
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:70 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:70 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1359 of SEQ ID NO:70, b is an integer of 15 to 1373, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:70, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • polypeptide of this gene has been determined to have two transmembrane domains at about amino acid position 2 - 18 and 22 - 38 of the amino acid sequence referenced in Table 1 for this gene. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type Ilia membrane proteins.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, tumors of various organs including the pancreas, colon, and bone.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, hepatic, metabolic, reproductive, testicular, skeletal, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in tumors and prohferative tissues indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for treating or diagnosing tumors of several major organs including the pancreas and large intestine.
  • This protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration" sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattem formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:71 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:71 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1565 of SEQ ID NO:71, b is an integer of 15 to 1579, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:71, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in dendritic cells and fetal liver/spleen and to a lesser extent in many tissues including tonsils, fetal lung, stromal cell lines, bone ma ⁇ ow cell lines, placenta and tumors including hepatocellular carcinoma, pancreas tumor and osteosarcoma.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases and/or disorders of the immune and hematopoietic system.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in dendritic cells and fetal liver/spleen indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnaosing and treating disorders of the immune system particularlly related to the control and generation of precursor cells, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages.
  • Representative uses are described in the "Immune Activity" and "infectious disease" sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the uses include bone ma ⁇ ow cell ex-vivo culture, bone ma ⁇ ow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia.
  • the gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and or proliferation of various cell types.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:72 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:72 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1014 of SEQ ID NO:72, b is an integer of 15 to 1028, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:72, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endocrine and vascular diseases and/or disorders, particularly diseases associated with the vascular endothelium.
  • diseases and conditions which include, but are not limited to, endocrine and vascular diseases and/or disorders, particularly diseases associated with the vascular endothelium.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., endocrine, vascular, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in endothelial cells indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for diagnosing and treating disorders that involve the vascular system including diseases such as atherschlerosis, neoangiogenesis associated with tumor growth and conditions associated with inflammation.
  • the protein is useful in the detection, treatment, and/or prevention of a variety of vascular disorders and conditions, which include, but are not limited to miscrovascular disease, vascular leak syndrome, aneurysm, stroke, embolism, thrombosis, coronary artery disease, arteriosclerosis, and/or atherosclerosis.
  • the protein is useful in the treatment, detection, and/or prevention of metabolic disorders, particularly lethargy and depression.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:73 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:73 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 3660 of SEQ ID NO:73, b is an integer of 15 to 3674, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:73, and where b is greater than or equal to a + 14.
  • the translation product of this gene is related to bovine PAM precursor. See Genbank record gi
  • PAM purified from bovine neurointermediate pituitary is generated by endoproteolytic cleavage at a subset of the 10 pairs of basic amino acids in the precursor.
  • High levels of PAM mRNA have been found in bovine pituitary and cerebral cortex.
  • levels of PAM mRNA and pro-ACTH/endo ⁇ hin mRNA are known to be regulated in parallel by glucocorticoids and CRF.
  • This gene is expressed primarily in endometrial tumors, dendritic cells, a multiple sclerosis library, kidney, hematopoietic cells, melanocytes, osteoblasts, the spleen, colon, ovary, stromal cells, fetal and adult brain, heart, and in tissues undergoing wound repair.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, endometriosis, endometrial cancer, multiple sclerosis, hematopoietic diseases, bone disease, and wound healing.
  • diseases and conditions which include, but are not limited to, endometriosis, endometrial cancer, multiple sclerosis, hematopoietic diseases, bone disease, and wound healing.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, immune, hematopoieticm integumentary, skeletal, gastrointestinal, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid
  • tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue distribution in dendritic and hematopoietic cells and tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful as a therapuetic or diagnostic agent i's Diseases of hematopoietic origin as well as the female reproductive track due to the gene's primary pattern of expression.
  • polynucleotides and polypeptides co ⁇ esponding to this gene are useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. Representative uses are described in the "Immune Activity" and "infectious disease” sections below, in
  • Example 11 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the uses include bone ma ⁇ ow cell ex-vivo culture, bone ma ⁇ ow transplantation, bone ma ⁇ ow reconstitution, radiotherapy or chemotherapy of neoplasia.
  • the gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also have a very wide range of biological activities. Representative uses are described in the "Chemotaxis" and "Binding Activity" sections below, in Examples 11, 12, 13, 14, 15, 16, 18, 19, and 20, and elsewhere herein. Briefly, the protein may possess the following activities: cytokine, cell proliferation/differentiation modulating activity or induction of other cytokines; immunostimulating/immunosuppressant activities (e.g.
  • hematopoiesis e.g. for treating anemia or as adjunct to chemotherapy
  • stimulation or growth of bone, cartilage, tendons, ligaments and/or nerves e.g. for treating wounds, stimulation of follicle stimulating hormone (for control of fertility); chemotactic and chemokinetic activities (e.g. for treating infections, tumors); hemostatic or thrombolytic activity (e.g. for treating hemophilia, cardiac infarction etc.); anti-inflammatory activity (e.g. for treating septic shock, Crohn's Disease); as antimicrobials; for treating psoriasis or other hype ⁇ roliferative diseases; for regulation of metabolism, and behavior.
  • nucleic acid in gene therapy procedures.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:74 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2783 of SEQ ID NO:74, b is an integer of 15 to 2797, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:74, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence similarity with several G- protein coupled receptors (See Genbank Accession No. gb
  • G-protein coupled receptors are well known in the are and affect a variety of functions.
  • the translation product of this gene shares similarity with Follical Stimulating Hormone Receptor.
  • polypeptides encoded by this gene comprise the following amino acid sequence: GTRFPTGETPSLGFTVTLVLLNSLAFLLMA VI YTKLYCNLEKEDLSENSQSSMI KHVAWLIFTNCIFFCPVAFFSFAPLITAISISPEIMKSVTLIFFP (SEQ ID NO: 253). Polynucleotides encoding such polypeptides are also provided.
  • a prefe ⁇ ed polypeptide fragment of the invention comprises the following amino acid sequence: MIKHVAWLIFTNCIFFCP VAFFSFAPLITAISISPEIMKSVTLIFFPCLLA (SEQ ID NO: 254). Polynucleotides encoding these polypeptides are also provided.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • the polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 43 - 59 of the amino acid sequence referenced in Table 1 for this gene. Moreover, a cytoplasmic tail encompassing amino acids 60 to 207 of this protein has also been determined. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type la membrane proteins. Included in this invention as prefe ⁇ ed domains are Zinc finger, C2H2 type domains, which were identified using the ProSite analysis tool (Swiss Institute of Bioinformatics). 'Zinc finger' domains [1-5] are nucleic acid-binding protein structures first identified in the Xenopus transcription factor TFTIIA.
  • a zinc finger domain is composed of 25 to 30 amino-acid residues. There are two cysteine or histidine residues at both extremities of the domain, which are involved in the tetrahedral coordination of a zinc atom. It has been proposed that such a domain interacts with about five nucleotides.
  • a schematic representation of a zinc finger domain is shown below:
  • C2H2 the first pair of zinc coordinating residues are cysteines, while the second pair are histidines.
  • Preferred polypeptides of the invention comprise the following amino acid sequence: CDCCESFLLTKPVSCKHLIKSH (SEQ ID NO: 256). Polynucleotides encoding these polypeptides are also provided. Further prefe ⁇ ed are polypeptides comprising the Zinc finger, C2H2 type domain of the sequence referenced in Table for this gene, and at least 5, 10, 15, 20, 25, 30, 50, or 75 additional contiguous amino acid residues of this referenced sequence. The additional contiguous amino acid residues is N-terminal or C- terminal to the Zinc finger, C2H2 type domain.
  • the additional contiguous amino acid residues is both N-terminal and C-terminal to the Zinc finger, C2H2 type domain, wherein the total N- and C-terminal contiguous amino acid residues equal the specified number.
  • the above preferred polypeptide domain is characteristic of a signature specific to zinc finger proteins. Based on the sequence similarity, the translation product of this gene is expected to share at least some biological activities with G-coupled proteins, their receptors, and zinc finger proteins. Such activities are known in the art, some of which are described elsewhere herein.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, diseases of the liver, developmental abnormalities, neurologic diseases, lung cancer, pancreatic cancer, and colon cancer.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue(s) or cell type(s) particularly of the neurological and hepatic origin, as well as the proliferation and/or differentiation of numerous types of tissues.
  • tissue or cell types e.g., hepatic, immune, hematopoietic, neural, gastrointestinal, reproductive, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, amniotic fluid, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 167 as residues: Pro-62 to Asp-67, Arg-74 to Gly-80, Gln-146 to Glu-168. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in fetal liver indicates that polynucleotides and polypeptides corresponding to this gene are useful for a diagnositic marker or therapeutic in a wide variety of disease states, polynucleotides and polypeptides corresponding to this gene are useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia since stromal cells are important in the production of cells of hematopoietic lineages. Representative uses are described in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein.
  • the uses include bone marrow cell ex-vivo culture, bone marrow transplantation, bone marrow reconstitution, radiotherapy or chemotherapy of neoplasia.
  • the gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein expression in placental and brain tissue indicates the protein is useful in the detection, treatment, and/or prevention of vascular conditions, which include, but are not limited to, microvascular disease, vascular leak syndrome, aneurysm, stroke, atherosclerosis, arteriosclerosis, or embolism.
  • this gene product may represent a soluble factor produced by smooth muscle that regulates the innervation of organs or regulates the survival of neighboring neurons. Likewise, it is involved in controlling the digestive process, and such actions as peristalsis. Similarly, it is involved in controlling the vasculature in areas where smooth muscle su ⁇ ounds the endothelium of blood vessels.
  • the protein is useful in the treatment, detection, and/or prevention of bacterial, fungal, protozoan and viral infections, particularly infections caused by HJV-1 or HTV-2; pain; cancers; anorexia; bulimia; asthma; Parkinson's Disease; acute heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; ulcers; allergies; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, severe mental retardation and dyskinesias, such as Huntington's Disease or Gilles de la Tourette's syndrome.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:75 Some of these sequences are related to SEQ ID NO:75 and may have been publicly available prior to conception of the present invention.
  • related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2689 of SEQ ID NO:75, b is an integer of 15 to 2703, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:75, and where b is greater than or equal to a + 14.
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hematopietic, vascular, and developmental diseases and/or disorders.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 168 as residues: Ser-30 to T ⁇ -37. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in hematopoietic cells indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful for therapeutic and/or diagnostic intervention in hematopoietic and developmental disorders.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the uses include bone marrow cell ex-vivo culture, bone ma ⁇ ow transplantation, bone ma ⁇ ow reconstitution, radiotherapy or chemotherapy of neoplasia.
  • the gene product may also be involved in lymphopoiesis, therefore, it can be used in immune disorders such as infection, inflammation, allergy, immunodeficiency etc.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein is useful in the detection, treatment, and/or prevention of vascular conditions, which include, but are not limited to, microvascular disease, vascular leak syndrome, aneurysm, stroke, atherosclerosis, arteriosclerosis, or embolism.
  • this gene product may represent a soluble factor produced by smooth muscle that regulates the innervation of organs or regulates the survival of neighboring neurons.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:76 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:76 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 728 of SEQ ID NO:76, b is an integer of 15 to 742, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:76, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, prostate cancer and diseases of hematopoietic origin, particularly of B- cells.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., prostate, reproductive, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, seminal fluid, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Prefe ⁇ ed polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 169 as residues: Asp-33 to Lys-42. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in prostate tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful as a therapeutic or diagnostic marker for prostate cancer and disorders involving hematopoietic cells, especially those of B-cell origin.
  • the expression within cellular sources marked by proliferating cells indicates this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis, treatment, and/or prevention of developmental diseases and disorders, including cancer, and other prohferative conditions. Representative uses are described in the "Hype ⁇ roliferative Disorders" and "Regeneration" sections below and elsewhere herein. Briefly, developmental tissues rely on decisions involving cell differentiation and/or apoptosis in pattern formation.
  • Dysregulation of apoptosis can result in inappropriate suppression of cell death, as occurs in the development of some cancers, or in failure to control the extent of cell death, as is believed to occur in acquired immunodeficiency and certain neurodegenerative disorders, such as spinal muscular atrophy (SMA).
  • SMA spinal muscular atrophy
  • this gene product may have applications in the adult for tissue regeneration and the treatment of cancers. It may also act as a mo ⁇ hogen to control cell and tissue type specification. Therefore, the polynucleotides and polypeptides of the present invention are useful in treating, detecting, and/or preventing said disorders and conditions, in addition to other types of degenerative conditions.
  • this protein may modulate apoptosis or tissue differentiation and is useful in the detection, treatment, and/or prevention of degenerative or prohferative conditions and diseases.
  • the protein is useful in modulating the immune response to abe ⁇ ant polypeptides, as may exist in proliferating and cancerous cells and tissues.
  • the protein can also be used to gain new insight into the regulation of cellular growth and proliferation.
  • the protein is useful in modulating the immune response to abe ⁇ ant proteins and polypeptides, as may exist in rapidly proliferating cells and tissues.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement.
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:77 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1811 of SEQ ID NO:77, b is an integer of 15 to 1825, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:77, and where b is greater than or equal to a + 14.
  • GAS gamma activating sequence
  • polypeptides comprising the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention comprise the following amino acid sequence:
  • GHESICGSCRSWIYFSIRCRRRMRPWWSLLLEACATCAQTGPTRSTSCTQEVS HSSSTAYPAPMRRRCCL PSPRSCT SEQ ID NO: 258.
  • Polynucleotides encoding these polypeptides are also provided.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 17. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17. This gene is expressed primarily in the brain and the developing embryo and to a lesser extent in the heart, colon, adipose tissue, kidney, mammary tissue, activated T-cells and dendritic cells.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, neurological diseases, developmental conditions, colon cancer, and hematopoietic diseases, especially of T-cell origin .
  • diseases and conditions which include, but are not limited to, neurological diseases, developmental conditions, colon cancer, and hematopoietic diseases, especially of T-cell origin .
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, developmental, cardiovascular, adipose, immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 170 as residues: Thr- 18 to Cys-26, Glu-29 to Thr-36, Ser-50 to Thr-55. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution in brain indicates that polynucleotides and polypeptides corresponding to this gene are useful for therapeutic and/or diagnostic agents in neurological diseases, developmental abnormalities, colon cancer, and hematopoietic diseases, especially those of T-cell origin.
  • Representative uses are described in the "Regeneration” and “Hype ⁇ roliferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception.
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • Many polynucleotide sequences, such as EST sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:78 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention.
  • a-b is any integer between 1 to 1660 of SEQ ID NO:78
  • b is an integer of 15 to 1674
  • both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO.78
  • b is greater than or equal to a + 14.
  • polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 2 - 18 of the amino acid sequence referenced in Table 1 for this gene. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type II membrane proteins.
  • polypeptides compnsmg the amino acid sequence of the open reading frame upstream of the predicted signal peptide are contemplated by the present invention.
  • polypeptides of the invention compnse the following amino acid sequence KRAGVEVGGLVMALAGSVFVLGGVLVLCVERNGEGEMGWPQHLPKSQPLS PPVAVRRCSFERSWIDLLVETSSSMVTCRQQVGTPNGMEGRGGGPKTTFPIRL QLSGACAVRPEIQWEV (SEQ ID NO: 259). Polynucleotides encoding these polypeptides are also provided.
  • This gene is expressed p ⁇ manly in activated monocytes, dend ⁇ tic cells, and in the tonsils.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the t ⁇ ssue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immune and hematopoietic diseases and/or disorders, particularly leukemia, lymphomas, tumors of hematopoietic ongin.
  • diseases and conditions which include, but are not limited to, immune and hematopoietic diseases and/or disorders, particularly leukemia, lymphomas, tumors of hematopoietic ongin.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the t ⁇ ssue(s) or cell type(s).
  • tissue or cell types e.g , immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, unne, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO 171 as residues Gln-30 to Leu-38, Asn-75 to Thr-86. Polynucleotides encoding said polypeptides are also provided.
  • tissue distnbution activated monocytes, dendritic cells, and tonsils indicates that polynucleotides and polypeptides co ⁇ esponding to this gene are useful as a therapeutic and/or diagnostic agent for leukemias, lymphomas, and other diseases associated with cells of hematopoietic ongin
  • Representative uses are descnbed in the "Immune Activity" and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:79 Some of these sequences are related to SEQ ID NO:79 and may have been publicly available prior to conception of the present invention.
  • such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2177 of SEQ ID NO:79, b is an integer of 15 to 2191, where both a and b co ⁇ espond to the positions of nucleotide residues shown in SEQ ID NO:79, and where b is greater than or equal to a + 14.
  • GAS gamma activating sequence
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 12.
  • This gene is expressed primarily in the placenta, brain, and liver and to a lesser extent in most other tissues.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, hematopoietic, neurological, vascular, and developmental diseases and/or disorders, particularly cancers.
  • diseases and conditions which include, but are not limited to, hematopoietic, neurological, vascular, and developmental diseases and/or disorders, particularly cancers.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., hematopoietic, neurological, vascular, developmental, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, amniotic fluid, bile, plasma, urine, synovial fluid and spinal fluid
  • tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, l e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • tissue dist ⁇ bution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful therapeutic and/or diagnostic agent in a multitude of disease states, particularly those involving the immune and neurologic systems.
  • Representative uses are desc ⁇ bed in the "Regeneration” and "Hype ⁇ rohferative Disorders” sections below, in Example 11, 15, and 18, and elsewhere herein.
  • the uses include, but are not limited to the detection, treatment, and/or prevention of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyehnating diseases, pe ⁇ pheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, ischemia and infarction, aneurysms, hemo ⁇ hages, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, depression, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception
  • elevated expression of this gene product in regions of the brain indicates it plays a role in normal neural function.
  • this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival.
  • the protein is useful in the detection, treatment, and/or prevention of a va ⁇ ety of vascular disorders and conditions, which include, but are not limited to miscrovascular disease, vascular leak syndrome, aneurysm, stroke, embolism, thrombosis, coronary artery disease, arte ⁇ osclerosis, and/or atherosclerosis
  • the protein may also be used to determine biological activity, to raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1321 of SEQ ID NO:80, b is an integer of 15 to 1335, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:80, and where b is greater than or equal to a + 14.
  • VVLLTASGPAVKRITFS (SEQ ID NO: 260), and/or LPRHMQEALRRLHYVPATKVFLSFRRPFWREEF ⁇ EGGHSNTDRPSRM ⁇ FYPPP REGALLLASYTWSDAAAAFAGLSREEALRLALDDVAALHGPVVRQLWDGT GVVKRWAEDQHSQGGFVVQXPALWQTEKDDWTVPYGRIYFAGEHTAYPHG WVETAVKSALRAAIKINSRKGPASDTASPEGHASDMEGQGHVHGVASSPSH
  • a preferred polypeptide fragment of the invention comprises the following amino acid sequence:
  • the translation product of this gene is expected to share at least some biological activities with monoamine oxidases, disintegrins, metalloproteinases, and apoptosis modulating proteins. Such activities are known in the art, some of which are described elsewhere herein. Polynucleotides encoding these polypeptides are also provided. The polypeptide of this gene has been determined to have a transmembrane domain at about amino acid position 235 - 251 of the amino acid sequence referenced in Table 1 for this gene. Moreover, a cytoplasmic tail encompassing amino acids 252 to 319 of this protein has also been determined. Based upon these characteristics, it is believed that the protein product of this gene shares structural features to type la membrane proteins.
  • This gene is expressed primarily in hematopoietic cells, particularly in dendritic cells, and activated monocytes and to a lesser extent in T-cells, endothelial cells, and cells associated with ulcerative colitis.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, leukemias, lymphomas, and diseases associated with antigen presenting cells, in addition to apoptosis dependant events.
  • diseases and conditions which include, but are not limited to, leukemias, lymphomas, and diseases associated with antigen presenting cells, in addition to apoptosis dependant events.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid and spinal fluid
  • another tissue or cell sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.
  • Preferred polypeptides of the present invention comprise immunogenic epitopes shown in SEQ ID NO: 173 as residues: Gln-22 to Gln-44, Ala-90 to Gly-95, Lys-137 to T ⁇ -146, Arg-171 to Asp-181, Glu-370 to Ser-380, Asp-447 to Gly-452, Gln-463 to T ⁇ -469, Asn-504 to Ala-510, Asp-512 to His-519, Ala-541 to Val-550, Asn-558 to His-566. Polynucleotides encoding said polypeptides are also provided.
  • tissue distribution immune and hematopoietic cells and tissues combined with the homology to the murine Fig 1 gene indicates that polynucleotides and polypeptides corresponding to this gene are useful as a therapeutic and/or diagnostic agent for hematopoietic diseases, especially those associated with antigen presenting cells.
  • Representative uses are described in the "Immune Activity” and "infectious disease” sections below, in Example 11, 13, 14, 16, 18, 19, 20, and 27, and elsewhere herein. Briefly, the expression of this gene product indicates a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product is involved in the regulation of cytokine production, antigen presentation, or other processes suggesting a usefulness in the treatment of cancer (e.g. by boosting immune responses).
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product is involved in immune functions. Therefore it is also useful as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatou's Disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophiha, psoriasis, hypersensitivities, such as T-cell mediated cytotoxicity; immune reactions to transplanted organs and tissues, such as host-versus-graft and graft-versus-host diseases, or autoimmunity disorders, such as autoimmune infertility, lense tissue injury, demyehnation, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's Disease, and scleroderma.
  • immunodeficiency diseases such as AIDS, leukemia, rheuma
  • the protein may represent a secreted factor that influences the differentiation or behavior of other blood cells, or that recruits hematopoietic cells to sites of injury.
  • this gene product is thought to be useful in the expansion of stem cells and committed progenitors of various blood lineages, and in the differentiation and/or proliferation of various cell types.
  • the protein may also be used to determine biological activity, raise antibodies, as tissue markers, to isolate cognate ligands or receptors, to identify agents that modulate their interactions, in addition to its use as a nutritional supplement. Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and/or immunotherapy targets for the above listed tissues.
  • polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ED NO: 81 and may have been publicly available prior to conception of the present invention. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1853 of SEQ ID NO:81, b is an integer of 15 to 1867, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:81, and where b is greater than or equal to a + 14.
  • Table 1 summarizes the information corresponding to each "Gene No.” described above.
  • the nucleotide sequence identified as “NT SEQ ID NO:X” was assembled from partially homologous ("overlapping") sequences obtained from the "cDNA clone ID” identified in Table 1 and, in some cases, from additional related DNA clones.
  • the overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X.
  • the cDNA Clone ID was deposited on the date and given the corresponding deposit number listed in "ATCC Deposit No:Z and Date.” Some of the deposits contain multiple different clones corresponding to the same gene. "Vector” refers to the type of vector contained in the cDNA Clone ID.
  • Total NT Seq refers to the total number of nucleotides in the contig identified by "Gene No.”
  • the deposited clone may contain all or most of these sequences, reflected by the nucleotide position indicated as “5' NT of Clone Seq.” and the "3' NT of Clone Seq.” of SEQ ID NO:X.
  • the nucleotide position of SEQ ID NO:X of the putative start codon (methionine) is identified as "5' NT of Start Codon.”
  • the nucleotide position of SEQ ID NO:X of the predicted signal sequence is identified as "5' NT of First AA of Signal Pep.”
  • the translated amino acid sequence beginning with the methionine, is identified as "AA SEQ ID NO:Y,” although other reading frames can also be easily translated using known molecular biology techniques.
  • the polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.
  • SEQ ID NO:Y of the predicted signal peptide is identified as "First AA of Sig Pep" and "Last AA of Sig Pep.”
  • the predicted first amino acid position of SEQ ID NO:Y of the secreted portion is identified as "Predicted First AA of Secreted Portion.”
  • the amino acid position of SEQ ID NO:Y of the last amino acid in the open reading frame is identified as "Last AA of ORF.”
  • SEQ ID NO:X and the translated SEQ ID NO:Y are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below For instance, SEQ ID NO-X is useful for designing nucleic acid hyb ⁇ dization probes that will detect nucleic acid sequences contained m SEQ ID NO.X or the cDNA contained in the deposited clone.
  • polypeptides identified from SEQ ID NO:Y may be used to generate antibodies which bind specifically to the secreted proteins encoded by the cDNA clones identified in Table 1.
  • DNA sequences generated by sequencing reactions can contain sequencing errors.
  • the errors exist as misidentified nucleotides, or as insertions or deletions of nucleotides in the generated DNA sequence.
  • the erroneously inserted or deleted nucleotides cause frame shifts in the reading frames of the predicted amino acid sequence.
  • the predicted ammo acid sequence diverges from the actual ammo acid sequence, even though the generated DNA sequence may be greater than 99.9% identical to the actual DNA sequence (for example, one base insertion or deletion in an open reading frame of over 1000 bases).
  • the present invention provides not only the generated nucleotide sequence identified as SEQ ID NO:X and the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1.
  • the nucleotide sequence of each deposited clone can readily be determined by sequencing the deposited clone in accordance with known methods. The predicted ammo acid sequence can then be verified from such deposits.
  • the amino acid sequence of the protein encoded by a particular clone can also be directly determined by peptide sequencing or by expressing the protein in a suitable host cell containing the deposited human cDNA, collecting the prote , and determining its sequence.
  • the present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, or the deposited clone.
  • the corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include preparing probes or p ⁇ mers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.
  • species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source for the desired homologue.
  • polypeptides of the invention can be prepared in any suitable manner.
  • polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or polypeptides produced by a combination of these methods. Means for preparing such polypeptides are well understood in the art.
  • polypeptides may be in the form of the secreted protein, including the mature form, or may be a part of a larger protein, such as a fusion protein (see below).
  • polypeptides of the present invention are preferably provided in an isolated form, and preferably are substantially purified.
  • a recombinantly produced version of a polypeptide, including the secreted polypeptide, can be substantially purified by the one-step method described in Smith and Johnson, Gene 67:31-40
  • Polypeptides of the invention also can be purified from natural or recombinant sources using antibodies of the invention raised against the secreted protein in methods which are well known in the art.
  • Methods for predicting whether a protein has a signal sequence, as well as the cleavage point for that sequence, are available. For instance, the method of
  • the deduced amino acid sequence of the secreted polypeptide was analyzed by a computer program called SignalP (Hen ⁇ k Nielsen et al., Protein Engmee ⁇ ng 10:1-6 (1997)), which predicts the cellular location of a protein based on the amino acid sequence.
  • SignalP Haten ⁇ k Nielsen et al., Protein Engmee ⁇ ng 10:1-6 (1997)
  • the analysis of the amino acid sequences of the secreted proteins desc ⁇ bed herein by this program provided the results shown in Table 1.
  • cleavage sites sometimes vary from organism to organism and cannot be predicted with absolute certainty.
  • the present invention provides secreted polypeptides having a sequence shown in SEQ ID NO:Y which have an N-termmus beginning withm 5 residues (i.e., + or - 5 residues) of the predicted cleavage point.
  • SEQ ID NO:Y which have an N-termmus beginning withm 5 residues (i.e., + or - 5 residues) of the predicted cleavage point.
  • cleavage of the signal sequence from a secreted protein is not entirely uniform, resulting m more than one secreted species.
  • the signal sequence identified by the above analysis may not necessarily predict the naturally occumng signal sequence.
  • the naturally occumng signal sequence may be further upstream from the predicted signal sequence.
  • the predicted signal sequence will be capable of directing the secreted protein to the ER.
  • Variants refers to a polynucleotide or polypeptide differing from the polynucleotide or polypeptide of the present invention, but retaining essential properties thereof. Generally, variants are overall closely similar, and, in many regions, identical to the polynucleotide or polypeptide of the present invention. By a polynucleotide having a nucleotide sequence at least, for example, 95%
  • nucleotide sequence of the polynucleotide is identical to the reference sequence except that the polynucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence encoding the polypeptide.
  • a polynucleotide having a nucleotide sequence at least 95% identical to a reference nucleotide sequence up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence.
  • the query sequence may be an entire sequence shown inTable 1, the ORF (open reading frame), or any fragement specified as described herein.
  • nucleic acid molecule or polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to a nucleotide sequence of the presence invention can be determined conventionally using known computer programs.
  • a preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:237-245).
  • the query and subject sequences are both DNA sequences.
  • An RNA sequence can be compared by converting U's to T's.
  • the result of said global sequence alignment is in percent identity.
  • the FASTDB program does not account for 5' and 3' truncations of the subject sequence when calculating percent identity.
  • the percent identity is corrected by calculating the number of bases of the query sequence that are 5' and 3' of the subject sequence, which are not matched/aligned, as a percent of the total bases of the query sequence. Whether a nucleotide is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This corrected score is what is used for the purposes of the present invention. Only bases outside the 5' and 3' bases of the subject sequence, as displayed by the FASTDB alignment, which are not matched/aligned with the query sequence, are calculated for the purposes of manually adjusting the percent identity score.
  • a 90 base subject sequence is aligned to a 100 base query sequence to determine percent identity.
  • the deletions occur at the 5' end of the subject sequence and therefore, the FASTDB alignment does not show a matched/aligmeld of the first 10 bases at 5' end.
  • the 10 unpaired bases represent 10% of the sequence (number of bases at the 5' and 3' ends not matched/total number of bases in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 bases were perfectly matched the final percent identity would be 90%.
  • a 90 base subject sequence is compared with a 100 base query sequence.
  • deletions are internal deletions so that there are no bases on the 5' or 3' of the subject sequence which are not matched/aligned with the query.
  • percent identity calculated by FASTDB is not manually corrected.
  • bases 5' and 3' of the subject sequence which are not matched/aligned with the query sequnce are manually corrected for. No other manual corrections are to made for the purposes of the present invention.
  • a polypeptide having an amino acid sequence at least, for example, 95% "identical" to a query amino acid sequence of the present invention it is intended that the amino acid sequence of the subject polypeptide is identical to the query sequence except that the subject polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence.
  • the amino acid sequence of the subject polypeptide may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence.
  • up to 5% of the amino acid residues in the subject sequence may be inserted, deleted, (indels) or substituted with another amino acid.
  • These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the reference sequence.
  • any particular polypeptide is at least 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, the amino acid sequences shown in Table 1 or to the amino acid sequence encoded by deposited DNA clone can be determined conventionally using known computer programs.
  • a preferred method for determing the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. (1990) 6:237-245).
  • the query and subject sequences are either both nucleotide sequences or both amino acid sequences.
  • the result of said global sequence alignment is in percent identity.
  • the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity.
  • the percent identity is corrected by calculating the number of residues of the query sequence that are N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence Whether a residue is matched/aligned is determined by results of the FASTDB sequence alignment.
  • This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to amve at a final percent identity score.
  • This final percent identity score is what is used for the purposes of the present invention. Only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence.
  • a 90 amino acid residue subject sequence is aligned with a 100 residue query sequence to determine percent identity.
  • the deletion occurs at the N- terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-termmus.
  • the 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C- termim not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program If the remaining 90 residues were perfectly matched the final percent identity would be 90%.
  • a 90 residue subject sequence is compared with a 100 residue query sequence.
  • deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query.
  • percent identity calculated by FASTDB is not manually corrected
  • residue positions outside the N- and C-terminal ends of the subject sequence, as displayed the FASTDB alignment, which are not matched/aligned with the query sequnce are manually corrected for No other manual corrections are to made for the purposes of the present invention
  • the va ⁇ ants may contain alterations in the coding regions, non-coding regions, or both Especially preferred are polynucleotide variants containing alterations which produce silent substitutions, additions, or deletions, but do not alter the properties or activities of the encoded polypeptide. Nucleotide variants produced by silent substitutions due to the degeneracy of the genetic code are preferred. Moreover, va ⁇ ants in which 5-10, 1-5, or 1-2 amino acids are substituted, deleted, or added in any combination are also preferred. Polynucleotide va ⁇ ants can be produced for a variety of reasons, e.g., to optimize codon expression for a particular host
  • Naturally occumng va ⁇ ants are called "allehc va ⁇ ants,” and refer to one of several alternate forms of a gene occupying a given locus on a chromosome of an organism. (Genes II, Lewin, B., ed., John Wiley & Sons, New York (1985).) These allehc va ⁇ ants can vary at either the polynucleotide and/or polypeptide level. Alternatively, non-naturally occumng va ⁇ ants may be produced by mutagenesis techniques or by direct synthesis.
  • va ⁇ ants may be generated to improve or alter the characte ⁇ stics of the polypeptides of the present invention.
  • one or more ammo acids can be deleted from the N-terminus or C-terminus of the secreted protein without substantial loss of biological function.
  • va ⁇ ants often retain a biological activity similar to that of the naturally occurring protein.
  • Gayle and coworkers J Biol. Chem 268:22105-22111 (1993) conducted extensive mutational analysis of human cytokine IL-la. They used random mutagenesis to generate over 3,500 individual IL-la mutants that averaged 2.5 amino acid changes per va ⁇ ant over the entire length of the molecule. Multiple mutations were examined at every possible amino acid position.
  • the invention further includes polypeptide va ⁇ ants which show substantial biological activity
  • va ⁇ ants include deletions, insertions, inversions, repeats, and substitutions selected according to general rules known in the art so as have little effect on activity.
  • the first strategy exploits the tolerance of amino acid substitutions by natural selection du ⁇ ng the process of evolution.
  • conserved amino acids By compa ⁇ ng amino acid sequences in different species, conserved amino acids can be identified These conserved amino acids are likely important for protein function.
  • the amino acid positions where substitutions have been tolerated by natural selection indicates that these positions are not critical for protem function. Thus, positions tolerating ammo acid substitution could be modified while still maintaining biological activity of the protein.
  • the second strategy uses genetic enginee ⁇ ng to introduce amino acid changes at specific positions of a cloned gene to identify regions c ⁇ tical for protein function.
  • site directed mutagenesis or alanine-scanning mutagenesis introduction of single alanine mutations at every residue in the molecule
  • the resulting mutant molecules can then be tested for biological activity
  • va ⁇ ants of the present invention include (l) substitutions with one or more of the non-conserved amino acid residues, where the substituted amino acid residues may or may not be one encoded by the genetic code, or (n) substitution with one or more of ammo acid residues having a substituent group, or (in) fusion of the mature polypeptide with another compound, such as a compound to increase the stability and/or solubility of the polypeptide (for example, polyethylene glycol), or (IV) fusion of the polypeptide with additional am o acids, such as an IgG Fc fusion region peptide, or leader or secretory sequence, or a sequence facilitating pu ⁇ fication.
  • additional am o acids such as an IgG Fc fusion region peptide, or leader or secretory sequence, or a sequence facilitating pu ⁇ fication.
  • va ⁇ ant polypeptides are deemed to be within the scope of those skilled in the art from the teachings herein.
  • polypeptide variants containing amino acid substitutions of charged amino acids with other charged or neutral amino acids may produce proteins with improved characte ⁇ stics, such as less aggregation.
  • Aggregation of pharmaceutical formulations both reduces activity and increases clearance due to the aggregate's immunogenic activity (Pmckard et al., Clin. Exp. Immunol. 2 331-340 (1967), Robbins et al., Diabetes 36- 838-845 (1987); Cleland et al., C ⁇ t. Rev.
  • a further embodiment of the invention relates to a polypeptide which comprises the amino acid sequence of the present invention having an amino acid sequence which contains at least one amino acid substitution, but not more than 50 amino acid substitutions, even more preferably, not more than 40 amino acid substitutions, still more preferably, not more than 30 amino acid substitutions, and still even more preferably, not more than 20 amino acid substitutions.
  • a polypeptide it is highly preferable for a polypeptide to have an amino acid sequence which comprises the amino acid sequence of the present invention, which contains at least one, but not more than 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid substitutions.
  • the number of additions, substitutions, and/or deletions in the amino acid sequence of the present invention or fragments thereof is 1-5, 5-10, 5-25, 5-50, 10-50 or 50-150, conservative amino acid substitutions are preferable.
  • a "polynucleotide fragment” refers to a short polynucleotide having a nucleic acid sequence contained in the deposited clone or shown in SEQ ID NO:X.
  • the short nucleotide fragments are preferably at least about 15 nt, and more preferably at least about 20 nt, still more preferably at least about 30 nt, and even more preferably, at least about 40 nt in length.
  • a fragment "at least 20 nt in length,” for example, is intended to include 20 or more contiguous bases from the cDNA sequence contained in the deposited clone or the nucleotide sequence shown in SEQ ID NO:X. These nucleotide fragments are useful as diagnostic probes and primers as discussed herein. Of course, larger fragments (e.g., 50, 150, 500, 600, 2000 nucleotides) are preferred.
  • polynucleotide fragments of the invention include, for example, fragments having a sequence from about nucleotide number 1-50, 51-100, 101-150, 151-200, 201-250, 251-300, 301-350, 351-400, 401- 450, 451-500, 501-550, 551-600, 651-700, 701-750, 751-800, 800-850, 851-900, 901- 950, 951-1000, 1001- 1050, 1051-1100, 1101-1 150, 1151-1200, 1201-1250, 1251- 1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601- 1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951- 2000, or 2001 to the end of SEQ ID NO:X or the cDNA contained in the deposited clone.
  • polypeptide fragment refers to a short amino acid sequence contained in SEQ ID NO:Y or encoded by the cDNA contained in the deposited clone. Protein fragments may be "free-standing,” or comprised within a larger polypeptide of which the fragment forms a part or region, most preferably as a single continuous region. Representative examples of polypeptide fragments of the invention, include, for example, fragments from about amino acid number 1-20, 21- 40, 41-60, 61-80, 81-100, 102-120, 121-140, 141-160, or 161 to the end of the coding region.
  • polypeptide fragments can be about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, or 150 amino acids in length. In this context "about” includes the particularly recited ranges, larger or smaller by several (5, 4, 3, 2, or 1) amino acids, at either extreme or at both extremes.
  • Preferred polypeptide fragments include the secreted protein as well as the mature form. Further preferred polypeptide fragments include the secreted protein or the mature form having a continuous series of deleted residues from the amino or the carboxy terminus, or both. For example, any number of amino acids, ranging from 1- 60, can be deleted from the amino terminus of either the secreted polypeptide or the mature form.
  • any number of amino acids can be deleted from the carboxy terminus of the secreted protein or mature form. Furthermore, any combination of the above amino and carboxy terminus deletions are preferred. Similarly, polynucleotide fragments encoding these polypeptide fragments are also preferred.
  • polypeptide and polynucleotide fragments characterized by structural or functional domains, such as fragments that comprise alpha-helix and alpha-helix forming regions, beta-sheet and beta-sheet-forming regions, turn and turn- forming regions, coil and coil-forming regions, hydrophilic regions, hydrophobic regions, alpha amphipathic regions, beta amphipathic regions, flexible regions, surface-forming regions, substrate binding region, and high antigenic index regions.
  • Polypeptide fragments of SEQ ID NO:Y falling within conserved domains are specifically contemplated by the present invention.
  • polynucleotide fragments encoding these domains are also contemplated.
  • Biologically active fragments are those exhibiting activity similar, but not necessarily identical, to an activity of the polypeptide of the present invention.
  • the biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity.
  • epitopes & Antibodies refer to polypeptide fragments having antigenic or immunogenic activity in an animal, especially in a human.
  • a preferred embodiment of the present invention relates to a polypeptide fragment comprising an epitope, as well as the polynucleotide encoding this fragment.
  • a region of a protein molecule to which an antibody can bind is defined as an "antigenic epitope.”
  • an "immunogenic epitope” is defined as a part of a protein that elicits an antibody response. (See, for instance, Geysen et al., Proc. Natl. Acad. Sci. USA 81:3998- 4002 (1983).)
  • Fragments which function as epitopes may be produced by any conventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985) further described in U.S. Patent No. 4,631,211.)
  • antigenic epitopes preferably contain a sequence of at least seven, more preferably at least nine, and most preferably between about 15 to about 30 amino acids.
  • Antigenic epitopes are useful to raise antibodies, including monoclonal antibodies, that specifically bind the epitope.
  • monoclonal antibodies that specifically bind the epitope.
  • immunogenic epitopes can be used to induce antibodies according to methods well known in the art. (See, for instance, Sutcliffe et al., supra; Wilson et al., supra; Chow, M. et al., Proc. Natl. Acad.
  • a preferred immunogenic epitope includes the secreted protein.
  • the immunogenic epitopes may be presented together with a carrier protein, such as an albumin, to an animal system (such as rabbit or mouse) or, if it is long enough (at least about 25 amino acids), without a carrier.
  • a carrier protein such as an albumin
  • immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to raise antibodies capable of binding to, at the very least, linear epitopes in a denatured polypeptide (e.g., in Western blotting.)
  • antibody As used herein, the term "antibody” (Ab) or “monoclonal antibody” (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab')2 fragments) which are capable of specifically binding to protein. Fab and F(ab')2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody. (Wahl et al., J. Nucl. Med. 24:316-325 (1983).) Thus, these fragments are preferred, as well as the products of a FAB or other immunoglobulin expression library. Moreover, antibodies of the present invention include chimeric, single chain, and humanized antibodies.
  • any polypeptide of the present invention can be used to generate fusion proteins.
  • the polypeptide of the present invention when fused to a second protein, can be used as an antigenic tag.
  • Antibodies raised against the polypeptide of the present invention can be used to indirectly detect the second protein by binding to the polypeptide.
  • secreted proteins target cellular locations based on trafficking signals, the polypeptides of the present invention can be used as targeting molecules once fused to other proteins.
  • domains that can be fused to polypeptides of the present invention include not only heterologous signal sequences, but also other heterologous functional regions.
  • the fusion does not necessarily need to be direct, but may occur through linker sequences.
  • fusion proteins may also be engineered to improve characteristics of the polypeptide of the present invention. For instance, a region of additional amino acids, particularly charged amino acids, may be added to the N-terminus of the polypeptide to improve stability and persistence during purification from the host cell or subsequent handling and storage. Also, peptide moieties may be added to the polypeptide to facilitate purification. Such regions may be removed prior to final preparation of the polypeptide. The addition of peptide moieties to facilitate handling of polypeptides are familiar and routine techniques in the art.
  • polypeptides of the present invention can be combined with parts of the constant domain of immunoglobulins (IgG), resulting in chimeric polypeptides.
  • IgG immunoglobulins
  • fusion proteins facilitate purification and show an increased half-life in vivo.
  • chimeric proteins consisting of the first two domains of the human CD4- polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins.
  • Fusion proteins having disulfide-linked dimeric structures can also be more efficient in binding and neutralizing other molecules, than the monomeric secreted protein or protein fragment alone.
  • EP-A-O 464 533 (Canadian counterpart 2045869) discloses fusion proteins comprising various portions of constant region of immunoglobulin molecules together with another human protein or part thereof.
  • the Fc part in a fusion protein is beneficial in therapy and diagnosis, and thus can result in, for example, improved pharmacokinetic properties.
  • EP-A 0232 262. Alternatively, deleting the Fc part after the fusion protein has been expressed, detected, and purified, would be desired. For example, the Fc portion may hinder therapy and diagnosis if the fusion protein is used as an antigen for immunizations.
  • human proteins such as hIL-5
  • Fc portions for the purpose of high-throughput screening assays to identify antagonists of hIL-5.
  • polypeptides of the present invention can be fused to marker sequences, such as a peptide which facilitates purification of the fused polypeptide.
  • the marker amino acid sequence is a hexa-histidine peptide, such as the tag provided in a pQE vector (QIAGEN, Inc., 9259 Eton Avenue,
  • hexa-histidine provides for convenient purification of the fusion protein.
  • Another peptide tag useful for purification, the "HA" tag corresponds to an epitope derived from the influenza hemagglutinin protein.
  • any of these above fusions can be engineered using the polynucleotides or the polypeptides of the present invention.
  • the present invention also relates to vectors containing the polynucleotide of the present invention, host cells, and the production of polypeptides by recombinant techniques.
  • the vector may be, for example, a phage, plasmid, viral, or retroviral vector.
  • Retroviral vectors may be replication competent or replication defective. In the latter case, viral propagation generally will occur only in complementing host cells.
  • the polynucleotides may be joined to a vector containing a selectable marker for propagation in a host.
  • a plasmid vector is introduced in a precipitate, such as a calcium phosphate precipitate, or in a complex with a charged lipid. If the vector is a virus, it may be packaged in vitro using an appropriate packaging cell line and then transduced into host cells.
  • the polynucleotide insert should be operatively linked to an appropriate promoter, such as the phage lambda PL promoter, the E. coli lac, tip, phoA and tac promoters, the SV40 early and late promoters and promoters of retroviral LTRs, to name a few. Other suitable promoters will be known to the skilled artisan.
  • the expression constructs will further contain sites for transcription initiation, termination, and, in the transcribed region, a ribosome binding site for translation.
  • the coding portion of the transcripts expressed by the constructs will preferably include a translation initiating codon at the beginning and a termination codon (UAA, UGA or UAG) appropriately positioned at the end of the polypeptide to be translated.
  • the expression vectors will preferably include at least one selectable marker.
  • markers include dihydrofolate reductase, G418 or neomycin resistance for eukaryotic cell culture and tetracycline, kanamycin or ampicillin resistance genes for culturing in E. coli and other bacteria.
  • appropriate hosts include, but are not limited to, bacterial cells, such as E. coli, Streptomyces and Salmonella typhimurium cells; fungal cells, such as yeast cells; insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS, 293, and Bowes melanoma cells; and plant cells. Appropriate culture mediums and conditions for the above-described host cells are known in the art.
  • vectors preferred for use in bacteria include pQE70, pQE60 and pQE-
  • pBluescript vectors Phagescript vectors, pNH8A, pNHl ⁇ a, pNH18A, pNH46A, available from Stratagene Cloning Systems, Inc.; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 available from Pharmacia Biotech, Inc.
  • preferred eukaryotic vectors are pWLNEO, pSV2CAT, pOG44, pXTl and pSG available from Stratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia.
  • Other suitable vectors will be readily apparent to the skilled artisan.
  • Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection, or other methods. Such methods are described in many standard laboratory manuals, such as Davis et al., Basic Methods In Molecular Biology (1986). It is specifically contemplated that the polypeptides of the present invention may in fact be expressed by a host cell lacking a recombinant vector.
  • a polypeptide of this invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography Most preferably, high performance liquid chromatography (“HPLC”) is employed for punfication.
  • HPLC high performance liquid chromatography
  • Polypeptides of the present invention can also be recovered from: products pu ⁇ fied from natural sources, including bodily fluids, tissues and cells, whether directly isolated or cultured; products of chemical synthetic procedures; and products produced by recombinant techniques from a prokaryotic or eukaryotic host, including, for example, bacte ⁇ al, yeast, higher plant, insect, and mammalian cells.
  • a prokaryotic or eukaryotic host including, for example, bacte ⁇ al, yeast, higher plant, insect, and mammalian cells.
  • the polypeptides of the present invention may be glycosylated or may be non-glycosylated.
  • polypeptides of the invention may also include an initial modified methionine residue, in some cases as a result of host- mediated processes.
  • the N-terminal methionine encoded by the translation initiation codon generally is removed with high efficiency from any protein after translation in all eukaryotic cells While the N-terminal methionine on most proteins also is efficiently removed in most prokaryotes, for some proteins, this prokaryotic removal process is inefficient, depending on the nature of the amino acid to which the N-termmal methionine is covalently linked
  • the invention also encompasses primary, secondary, and immortalized host cells of vertebrate ongin, particularly mammalian ongin, that have been engineered to delete or replace endogenous genetic material (e.g., coding sequence), and/or to include genetic material (e.g., heterologous polynucleotide sequences) that is operably associated with the polynucleotides of the invention, and which activates, alters, and/or amplifies endogenous polynucleotides
  • endogenous genetic material e.g., coding sequence
  • polynucleotides identified herein can be used in numerous ways as reagents. The following description should be considered exemplary and utilizes known techniques.
  • the polynucleotides of the present invention are useful for chromosome identification. There exists an ongoing need to identify new chromosome markers, since few chromosome marking reagents, based on actual sequence data (repeat polymorphisms), are presently available.
  • Each polynucleotide of the present invention can be used as a chromosome marker. Briefly, sequences can be mapped to chromosomes by preparing PCR primers
  • Primers can be selected using computer analysis so that primers do not span more than one predicted exon in the genomic DNA. These primers are then used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the SEQ ID NO:X will yield an amplified fragment.
  • somatic hybrids provide a rapid method of PCR mapping the polynucleotides to particular chromosomes. Three or more clones can be assigned per day using a single thermal cycler. Moreover, sublocalization of the polynucleotides can be achieved with panels of specific chromosome fragments.
  • Other gene mapping strategies that can be used include in situ hybridization, prescreening with labeled flow-sorted chromosomes, and preselection by hybridization to construct chromosome specific-cDNA libraries.
  • FISH fluorescence in situ hybridization
  • the polynucleotides can be used individually (to mark a single chromosome or a single site on that chromosome) or in panels (for marking multiple sites and/or multiple chromosomes). Preferred polynucleotides correspond to the noncoding regions of the cDNAs because the coding sequences are more likely conserved within gene families, thus increasing the chance of cross hybridization during chromosomal mapping.
  • the physical position of the polynucleotide can be used in linkage analysis. Linkage analysis establishes coinheritance between a chromosomal location and presentation of a particular disease.
  • a polynucleotide can be used to control gene expression through triple helix formation or antisense DNA or RNA. Both methods rely on binding of the polynucleotide to DNA or RNA. For these techniques, preferred polynucleotides are usually 20 to 40 bases in length and complementary to either the region of the gene involved in transcription (triple helix - see Lee et al., Nucl. Acids Res. 3:173 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991) ) or to the mRNA itself (antisense - Okano, J. Neurochem.
  • the polynucleotides are also useful for identifying individuals from minute biological samples.
  • the United States military for example, is considering the use of restriction fragment length polymorphism (RFLP) for identification of its personnel.
  • RFLP restriction fragment length polymorphism
  • an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identifying personnel.
  • This method does not suffer from the current limitations of "Dog Tags" which can be lost, switched, or stolen, making positive identification difficult.
  • the polynucleotides of the present invention can be used as additional DNA markers for RFLP.
  • the polynucleotides of the present invention can also be used as an alternative to RFLP, by determining the actual base-by-base DNA sequence of selected portions of an individual's genome These sequences can be used to prepare PCR p ⁇ mers for amplifying and isolating such selected DNA, which can then be sequenced. Using this technique, individuals can be identified because each individual will have a unique set of DNA sequences. Once an unique ID database is established for an individual, positive identification of that individual, living or dead, can be made from extremely small tissue samples.
  • DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, etc.
  • DNA sequences amplified from polymorphic loci such as DQa class II HLA gene, are used in forensic biology to identify individuals.
  • polynucleotides of the present invention can be used as polymo ⁇ hic markers for forensic pu ⁇ oses.
  • reagents capable of identifying the source of a particular tissue Such need arises, for example, in forensics when presented with tissue of unknown origin.
  • Approp ⁇ ate reagents can compnse, for example, DNA probes or p ⁇ mers specific to particular tissue prepared from the sequences of the present invention. Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue cultures for contamination.
  • the polynucleotides of the present invention can be used as molecular weight markers on Southern gels, as diagnostic probes for the presence of a specific mRNA m a particular cell type, as a probe to "subtract-out" known sequences in the process of discove ⁇ ng novel polynucleotides, for selecting and making oligomers for attachment to a "gene chip” or other support, to raise anti-DNA antibodies using DNA immunization techniques, and as an antigen to elicit an immune response.
  • polypeptides identified herein can be used in numerous ways. The following description should be considered exemplary and utilizes known techniques.
  • a polypeptide of the present invention can be used to assay protein levels in a biological sample using antibody-based techniques. For example, protein expression in tissues can be studied with classical immunohistological methods. (Jalkanen, M., et al., J. Cell. Biol. 101:976-985 (1985); Jalkanen, M., et al., J. Cell . Biol.
  • antibody-based methods useful for detecting protein gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA).
  • ELISA enzyme linked immunosorbent assay
  • RIA radioimmunoassay
  • Suitable antibody assay labels include enzyme labels, such as, glucose oxidase, and radioisotopes, such as iodine (1251, 1211), carbon (14C), sulfur (35S), tritium (3H), indium (112In), and technetium (99mTc), and fluorescent labels, such as fluorescein and rhodamine, and biotin.
  • proteins can also be detected in vivo by imaging.
  • Antibody labels or markers for in vivo imaging of protein include those detectable by X-radiography, NMR or ESR.
  • suitable labels include radioisotopes such as barium or cesium, which emit detectable radiation but are not overtly harmful to the subject.
  • Suitable markers for NMR and ESR include those with a detectable characteristic spin, such as deuterium, which may be inco ⁇ orated into the antibody by labeling of nutrients for the relevant hybridoma.
  • a protein-specific antibody or antibody fragment which has been labeled with an appropriate detectable imaging moiety such as a radioisotope (for example, 1311, 112In, 99mTc), a radio-opaque substance, or a material detectable by nuclear magnetic resonance, is introduced (for example, parenterally, subcutaneously, or intraperitoneally) into the mammal.
  • an appropriate detectable imaging moiety such as a radioisotope (for example, 1311, 112In, 99mTc), a radio-opaque substance, or a material detectable by nuclear magnetic resonance
  • the size of the subject and the imaging system used will determine the quantity of imaging moiety needed to produce diagnostic images
  • the quantity of radioactivity injected will normally range from about 5 to 20 mil cu ⁇ es of 99mTc
  • the labeled antibody or antibody fragment will then preferentially accumulate at the location of cells which contain the specific protein.
  • In vivo tumor imaging is desc ⁇ bed in S.W. Burchiel et al., "Immunopharmacokmetics of Radiolabeled Antibodies and Their Fragments.” (Chapter 13 in Tumor Imaging: The Radiochemical Detection of Cancer, S.W. Burchiel and B. A. Rhodes, eds., Masson Publishing Inc. (1982).)
  • the invention provides a diagnostic method of a disorder, which involves (a) assaying the expression of a polypeptide of the present invention in cells or body fluid of an individual; (b) compa ⁇ ng the level of gene expression with a standard gene expression level, whereby an increase or decrease in the assayed polypeptide gene expression level compared to the standard expression level is indicative of a disorder.
  • polypeptides of the present invention can be used to treat disease.
  • patients can be administered a polypeptide of the present invention in an effort to replace absent or decreased levels of the polypeptide (e.g., insulin), to supplement absent or decreased levels of a different polypeptide (e.g., hemoglobin S for hemoglobin B), to inhibit the activity of a polypeptide (e.g., an oncogene), to activate the activity of a polypeptide (e.g., by binding to a receptor), to reduce the activity of a membrane bound receptor by competing with it for free ligand (e.g., soluble TNF receptors used in reducing inflammation), or to b ⁇ ng about a desired response (e g., blood vessel growth).
  • a polypeptide of the present invention in an effort to replace absent or decreased levels of the polypeptide (e.g., insulin), to supplement absent or decreased levels of a different polypeptide (e.g., hemoglobin S for hemoglobin B), to inhibit the activity of a polypeptide (e.g., an oncogene), to activate the
  • antibodies directed to a polypeptide of the present invention can also be used to treat disease.
  • administration of an antibody directed to a polypeptide of the present invention can bind and reduce ove ⁇ roduction of the polypeptide.
  • administration of an antibody can activate the polypeptide, such as by binding to a polypeptide bound to a membrane (receptor).
  • polypeptides of the present invention can be used as molecular weight markers on SDS-PAGE gels or on molecular sieve gel filtration columns using methods well known to those of skill in the art. Polypeptides can also be used to raise antibodies, which in turn are used to measure protein expression from a recombinant cell, as a way of assessing transformation of the host cell Moreover, the polypeptides of the present invention can be used to test the following biological activities
  • polynucleotides and polypeptides of the present invention can be used in assays to test for one or more biological activities. If these polynucleotides and polypeptides do exhibit activity in a particular assay, it is likely that these molecules may be involved in the diseases associated with the biological activity Thus, the polynucleotides and polypeptides could be used to treat the associated disease
  • a polypeptide or polynucleotide of the present invention may be useful in treating deficiencies or disorders of the immune system, by activating or inhibiting the proliferation, differentiation, or mobilization (chemotaxis) of immune cells.
  • Immune cells develop through a process called hematopoiesis. producing myeloid (platelets, red blood cells, neutrophils, and macrophages) and lymphoid (B and T lymphocytes) cells from plu ⁇ potent stem cells
  • the etiology of these immune deficiencies or disorders may be genetic, somatic, such as cancer or some autoimmune disorders, acquired (e.g., by chemotherapy or toxins), or infectious.
  • a polynucleotide or polypeptide of the present invention can be used as a marker or detector of a particular immune system disease or disorder.
  • a polynucleotide or polypeptide of the present invention may be useful in treating or detecting deficiencies or disorders of hematopoietic cells.
  • a polypeptide or polynucleotide of the present invention could be used to increase differentiation and proliferation of hematopoietic cells, including the plu ⁇ potent stem cells, in an effort to treat those disorders associated with a decrease in certain (or many) types hematopoietic cells
  • Examples of lmmunologic deficiency syndromes include, but are not limited to blood protein disorders (e g agammaglobuhnemia, dysgammaglobuhnemia). ataxia telangiectasia.
  • a polypeptide or polynucleotide of the present invention could also be used to modulate hemostatic (the stopping of bleeding) or thrombolytic activity (clot formation).
  • a polynucleotide or polypeptide of the present invention could be used to treat blood coagulation disorders (e.g., afib ⁇ nogenemia, factor deficiencies), blood platelet disorders (e.g. thrombocytopenia). or wounds resulting from trauma, surgery, or other causes.
  • a polynucleotide or polypeptide of the present invention that can decrease hemostatic or thrombolytic activity could be used to inhibit or dissolve clotting. These molecules could be important in the treatment of heart attacks (infarction), strokes, or scamng
  • a polynucleotide or polypeptide of the present invention may also be useful in treating or detecting autoimmune disorders.
  • autoimmune disorders result from inapprop ⁇ ate recognition of self as foreign mate ⁇ al by immune cells. This inapprop ⁇ ate recognition results in an immune response leading to the destruction of the host tissue. Therefore, the administration of a polypeptide or polynucleotide of the present invention that inhibits an immune response, particularly the proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy preventing autoimmune disorders.
  • autoimmune disorders examples include, but are not limited to. Addison's Disease, hemolytic anemia, antiphosphohpid syndrome, rheumatoid arthritis, dermatitis, allergic encephalomyehtis, glomerulonephntis, Goodpasture's Syndrome, Graves' Disease, Multiple Sclerosis, Myasthenia Gravis.
  • allergic reactions and conditions such as asthma (particularly allergic asthma) or other respiratory pioblems, may also be treated by a polypeptide or polynucleotide of the present invention.
  • these molecules can be used to treat anaphylaxis, hypersensitivity to an antigenic molecule, or blood group incompatibility.
  • a polynucleotide or polypeptide of the present invention may also be used to treat and/or prevent organ rejection or graft-versus-host disease (GVHD).
  • Organ rejection occurs by host immune cell destruction of the transplanted tissue through an immune response.
  • an immune response is also involved in GVHD, but, in this case, the foreign transplanted immune cells destroy the host tissues.
  • the administration of a polypeptide or polynucleotide of the present invention that inhibits an immune response, particularly the proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing organ rejection or GVHD.
  • a polypeptide or polynucleotide of the present invention may also be used to modulate inflammation
  • the polypeptide or polynucleotide may inhibit the proliferation and differentiation of cells involved in an inflammatory response.
  • These molecules can be used to treat inflammatory conditions, both chronic and acute conditions, including inflammation associated with infection (e.g., septic shock, sepsis, or systemic inflammatory response syndrome (SIRS)), lschemia- reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine induced lung injury, inflammatory bowel disease, Crohn's disease, or resulting from over production of cytokines (e.g., TNF or IL-1.)
  • SIRS systemic inflammatory response syndrome
  • a polypeptide or polynucleotide can be used to treat or detect hype ⁇ ro ferative disorders, including neoplasms.
  • a polypeptide or polynucleotide of the present invention may inhibit the proliferation of the disorder through direct or indirect interactions.
  • a polypeptide or polynucleotide of the present invention may proliferate other cells which can inhibit the hype ⁇ ro ferative disorder.
  • hype ⁇ rohferative disorders can be treated.
  • This immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response.
  • decreasing an immune response may also be a method of treating hype ⁇ ro ferative disorders, such as a chemotherapeutic agent.
  • Examples of hype ⁇ ro ferative disorders that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but are not limited to neoplasms located in the: abdomen, bone, breast, digestive system, liver, pancreas, pe ⁇ toneum, endocrine glands (adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid), eye, head and neck, nervous (central and pe ⁇ pheral), lymphatic system, pelvic, sk , soft tissue, spleen, thoracic, and urogenital.
  • neoplasms located in the: abdomen, bone, breast, digestive system, liver, pancreas, pe ⁇ toneum, endocrine glands (adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid), eye, head and neck, nervous (central and pe ⁇ pheral), lymphatic system, pelvic, sk , soft tissue
  • hype ⁇ rohferative disorders can also be treated or detected by a polynucleotide or polypeptide of the present invention.
  • hype ⁇ ro ferative disorders include, but are not limited to: hypergammaglobuhnemia, lymphoprohferative disorders, paraproteinemias, pu ⁇ ura, sarcoidosis, Sezary Syndrome, Waldenstron's Macroglobuhnemia, Gaucher's Disease, histiocytosis, and any other hype ⁇ rohferative disease, besides neoplasia, located m an organ system listed above.
  • a polypeptide or polynucleotide of the present invention can be used to treat or detect infectious agents. For example, by increasing the immune response, particularly increasing the proliferation and differentiation of B and/or T cells, infectious diseases may be treated.
  • the immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response.
  • the polypeptide or polynucleotide of the present invention may also directly inhibit the infectious agent, without necessa ⁇ ly eliciting an immune response.
  • Viruses are one example of an infectious agent that can cause disease or symptoms that can be treated or detected by a polynucleotide or polypeptide of the present invention Examples of viruses, include, but are not limited to the following DNA and RNA viral families.
  • Arbovirus Adenovi ⁇ dae, Arenavi ⁇ dae, Arte ⁇ virus, Bimavi ⁇ dae, Bunyavi ⁇ dae, Cahcivi ⁇ dae. Circovindae, Coronavi ⁇ dae, Flavivi ⁇ dae, Hepadnavi ⁇ dae (Hepatitis), He ⁇ esvi ⁇ dae (such as, Cytomegalovirus, He ⁇ es Simplex, He ⁇ es Zoster), Mononegavirus (e.g., Paramyxovi ⁇ dae, Morbilhvirus, Rhabdovi ⁇ dae), Orthomyxovi ⁇ dae (e.g., Influenza), Papovavi ⁇ dae, Parvovi ⁇ dae, Picornavi ⁇ dae, Poxvi ⁇ dae (such as Smallpox or Vaccinia), Reovi ⁇ dae (e.g., Rotavirus), Retrovi ⁇ dae (HTLV-I, HTLV-II, Lentivirus), and
  • Viruses falling within these families can cause a va ⁇ ety of diseases or symptoms, including, but not limited to: arth ⁇ tis, bronchiolhtis, encephalitis, eye infections (e.g., conjunctivitis, keratitis), chronic fatigue syndrome, hepatitis (A, B, C, E, Chronic Active, Delta), meningitis, opportunistic infections (e.g., AIDS), pneumonia, Burkitt's Lymphoma, chickenpox , hemorrhagic fever, Measles, Mumps, Para fluenza, Rabies, the common cold, Polio, leukemia, Rubella, sexually transmitted diseases, sk diseases (e.g., Kaposi's, warts), and viremia.
  • a polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases.
  • Actinomycetales e.g., Corynebacte ⁇ um, Mycobacte ⁇ um, Norcardia
  • Aspergillosis e.g., Bacillaceae (e.g., Anthrax, Clost ⁇ dium), Bacteroidaceae, Blastomycosis.
  • Hehcobacter Legionellosis, Leptospirosis, Liste ⁇ a, Mycoplasmatales, Neisse ⁇ aceae (e.g., Acmetobacter, Gonorrhea, Memgococcal), Pasteurellacea Infections (e g., Actinobacillus, Heamophilus, Pasteurella), Pseudomonas, Rickettsiaceae, Chlamydiaceae, Syphilis, and Staphylococcal.
  • Neisse ⁇ aceae e.g., Acmetobacter, Gonorrhea, Memgococcal
  • Pasteurellacea Infections e g., Actinobacillus, Heamophilus, Pasteurella
  • Pseudomonas Rickettsiaceae
  • Chlamydiaceae Chlamydiaceae
  • Syphilis Staphylococcal.
  • bacterial or fungal families can cause the following diseases or symptoms, including, but not limited to bacteremia, endocarditis, eye infections (conjunctivitis, tuberculosis, uveitis), gingivitis, opportunistic infections (e.g., AIDS related infections), paronychia, prosthesis-related infections.
  • Reiter's Disease respiratory tract infections, such as Whooping Cough or Empyema. sepsis, Lyme Disease, Cat-Scratch Disease, Dysentery, Paratyphoid Fever, food poisoning, Typhoid, pneumonia, Gonorrhea, meningitis, Chlamydia, Syphilis, Diphthe ⁇ a.
  • a polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases.
  • parasitic agents causing disease or symptoms that can be treated or detected by a polynucleotide or polypeptide of the present invention include, but not limited to, the following families: Amebiasis, Babesiosis, Coccidiosis, Cryptospo ⁇ diosis, Dientamoebiasis, Dou ⁇ ne, Ectoparasitic, Giardiasis, Helmmthiasis, Leishmaniasis, Theile ⁇ asis, Toxoplasmosis, Trypanosomiasis, and T ⁇ chomonas.
  • These parasites can cause a va ⁇ ety of diseases or symptoms, including, but not limited to: Scabies, Trombicuhasis, eye infections, intestinal disease (e.g., dysentery, giardiasis), liver disease, lung disease, opportunistic infections (e.g., AIDS related), Mala ⁇ a, pregnancy complications, and toxoplasmosis.
  • a polypeptide or polynucleotide of the present invention can be used to treat or detect any of these symptoms or diseases.
  • treatment using a polypeptide or polynucleotide of the present invention could either be by adm iste ⁇ ng an effective amount of a polypeptide to the patient, or by removing cells from the patient, supplying the cells with a polynucleotide of the present invention, and returning the engineered cells to the patient (ex vivo therapy).
  • the polypeptide or polynucleotide of the present invention can be used as an antigen in a vaccine to raise an immune response against infectious disease.
  • a polynucleotide or polypeptide of the present invention can be used to differentiate, proliferate, and attract cells, leading to the regeneration of tissues.
  • the regeneration of tissues could be used to repair, replace, or protect tissue damaged by congenital defects, trauma (wounds, burns, incisions, or ulcers), age, disease (e.g. osteoporosis, osteocarth ⁇ tis, pe ⁇ odontal disease, liver failure), surgery, including cosmetic plastic surgery, fibrosis, reperfusion injury, or systemic cytokine damage.
  • Tissues that could be regenerated using the present invention include organs (e.g., pancreas, liver, intestine, kidney, skm, endothe um), muscle (smooth, skeletal or cardiac), vasculature (including vascular and lymphatics), nervous, hematopoietic, and skeletal (bone, cartilage, tendon, and ligament) tissue.
  • organs e.g., pancreas, liver, intestine, kidney, skm, endothe um
  • muscle smooth, skeletal or cardiac
  • vasculature including vascular and lymphatics
  • nervous hematopoietic
  • skeletal bone, cartilage, tendon, and ligament
  • skeletal tissue e.g., hematopoietic, and skeletal tissue.
  • regeneration occurs without or decreased scarnng.
  • Regeneration also may include angiogenesis.
  • a polynucleotide or polypeptide of the present invention may increase regeneration of tissues difficult to heal. For example, increased tendon
  • a polynucleotide or polypeptide of the present invention could also be used prophylactically in an effort to avoid damage.
  • Specific diseases that could be treated include of tendinitis, ca ⁇ al tunnel syndrome, and other tendon or ligament defects.
  • tissue regeneration of non-healing wounds includes pressure ulcers, ulcers associated with vascular insufficiency, surgical, and traumatic wounds.
  • nerve and brain tissue could also be regenerated by using a polynucleotide or polypeptide of the present invention to proliferate and differentiate nerve cells.
  • Diseases that could be treated using this method include central and pe ⁇ pheral nervous system diseases, neuropathies, or mechanical and traumatic disorders (e.g., spinal cord disorders, head trauma, cerebrovascular disease, and stoke).
  • diseases associated with pe ⁇ pheral nerve inju ⁇ es, pe ⁇ pheral neuropathy (e.g., resulting from chemotherapy or other medical therapies), localized neuropathies, and central nervous system diseases (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy- Drager syndrome) could all be treated using the polynucleotide or polypeptide of the present invention.
  • Chemotaxis A polynucleotide or polypeptide of the present invention may have chemotaxis activity.
  • a chemotaxic molecule attracts or mobilizes cells (e.g , monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells) to a particular site in the body, such as inflammation, infection, or site of hype ⁇ ro feration.
  • the mobilized cells can then fight off and/or heal the particular trauma or abnormality.
  • a polynucleotide or polypeptide of the present invention may increase chemotaxic activity of particular cells. These chemotactic molecules can then be used to treat inflammation, infection, hype ⁇ ro ferative disorders, or any immune system disorder by increasing the number of cells targeted to a particular location in the body. For example, chemotaxic molecules can be used to treat wounds and other trauma to tissues by attracting immune cells to the injured location Chemotactic molecules of the present invention can also attract fibroblasts, which can be used to treat wounds. It is also contemplated that a polynucleotide or polypeptide of the present invention may inhibit chemotactic activity. These molecules could also be used to treat disorders Thus, a polynucleotide or polypeptide of the present invention could be used as an inhibitor of chemotaxis.
  • a polypeptide of the present invention may be used to screen for molecules that bind to the polypeptide or for molecules to which the polypeptide binds.
  • the binding of the polypeptide and the molecule may activate (agonist), increase, inhibit (antagonist), or decrease activity of the polypeptide or the molecule bound
  • Examples of such molecules include antibodies, oligonucleotides, proteins (e.g., receptors),or small molecules.
  • the molecule is closely related to the natural ligand of the polypeptide, e.g., a fragment of the ligand, or a natural substrate, a ligand, a structural or functional mimetic.
  • the molecule can be closely related to the natural receptor to which the polypeptide binds, or at least, a fragment of the receptor capable of being bound by the polypeptide (e g., active site). In either case, the molecule can be rationally designed using known techniques
  • the screening for these molecules involves producing approp ⁇ ate cells which express the polypeptide, either as a secreted protein or on the cell membrane.
  • Preferred cells include cells from mammals, yeast, Drosophila, or E. coli.
  • Cells expressing the polypeptide (or cell membrane containing the expressed polypeptide) are then preferably contacted with a test compound potentially containing the molecule to observe binding, stimulation, or inhibition of activity of either the polypeptide or the molecule.
  • the assay may simply test binding of a candidate compound to the polypeptide, wherein binding is detected by a label, or in an assay involving competition with a labeled competitor.
  • the assay may test whether the candidate compound results in a signal generated by bmdmg to the polypeptide
  • the assay can be earned out using cell-free preparations, polypeptide/molecule affixed to a solid support, chemical libra ⁇ es, or natural product mixtures.
  • the assay may also simply compnse the steps of mixing a candidate compound with a solution containing a polypeptide, measunng polypeptide/molecule activity or binding, and compa ⁇ ng the polypeptide/molecule activity or binding to a standard.
  • an ELISA assay can measure polypeptide level or activity in a sample (e.g., biological sample) using a monoclonal or polyclonal antibody.
  • the antibody can measure polypeptide level or activity by either binding, directly or indirectly, to the polypeptide or by competing with the polypeptide for a substrate. All of these above assays can be used as diagnostic or prognostic markers. The molecules discovered using these assays can be used to treat disease or to bnng about a particular result in a patient (e.g., blood vessel growth) by activating or inhibiting the polypeptide/molecule Moreover, the assays can discover agents which may inhibit or enhance the production of the polypeptide from suitably manipulated cells or tissues. Therefore, the invention includes a method of identifying compounds which bind to a polypeptide of the invention comprising the steps of (a) incubating a 99?
  • the invention includes a method of identifying agonists/antagonists comprising the steps of: (a) incubating a candidate compound with a polypeptide of the invention, (b) assaying a biological activity , and (b) determining if a biological activity of the polypeptide has been altered.
  • a polypeptide or polynucleotide of the present invention may also increase or decrease the differentiation or proliferation of embryonic stem cells, besides, as discussed above, hematopoietic lineage.
  • a polypeptide or polynucleotide of the present invention may also be used to modulate mammalian characteristics, such as body height, weight, hair color, eye color, skin, percentage of adipose tissue, pigmentation, size, and shape (e.g., cosmetic surgery).
  • a polypeptide or polynucleotide of the present invention may be used to modulate mammalian metabolism affecting catabolism, anabolism, processing, utilization, and storage of energy.
  • a polypeptide or polynucleotide of the present invention may be used to change a mammal's mental state or physical state by influencing biorhythms, caricadic rhythms, depression (including depressive disorders), tendency for violence, tolerance for pain, reproductive capabilities (preferably by Activin or Inhibin-like activity), hormonal or endocrine levels, appetite, libido, memory, stress, or other cognitive qualities.
  • a polypeptide or polynucleotide of the present invention may also be used as a food additive or preservative, such as to increase or decrease storage capabilities, fat content, lipid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional components.
  • nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 50 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1.
  • nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5' Nucleotide of the Clone Sequence and ending with the nucleotide at about the position of the 3' Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.
  • nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5' Nucleotide of the Start Codon and ending with the nucleotide at about the position of the 3' Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.
  • nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions beginning with the nucleotide at about the position of the 5' Nucleotide of the First Amino Acid of the Signal Peptide and ending with the nucleotide at about the position of the 3' Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.
  • nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 150 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X.
  • an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 500 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X.
  • a further preferred embodiment is a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NO:X beginning with the nucleotide at about the position of the 5' Nucleotide of the First Amino Acid of the Signal Peptide and ending with the nucleotide at about the position of the 3' Nucleotide of the Clone Sequence as defined for SEQ ID NO:X in Table 1.
  • a further preferred embodiment is an isolated nucleic acid molecule compnsmg a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence of SEQ ID NO:X.
  • nucleic acid molecule which hyb ⁇ dizes under stnngent hyb ⁇ dization conditions to a nucleic acid molecule, wherein said nucleic acid molecule which hyb ⁇ dizes does not hybridize under stringent hybndization conditions to a nucleic acid molecule having a nucleotide sequence consisting of only A residues or of only T residues.
  • composition of matter compnsmg a DNA molecule which comp ⁇ ses a human cDNA clone identified by a cDNA Clone Identifier in Table 1, which DNA molecule is contained the material deposited with the Ame ⁇ can Type Culture Collection and given the ATCC Deposit Number shown in Table 1 for said cDNA Clone Identifier.
  • nucleic acid molecule compnsmg a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in the nucleotide sequence of a human cDNA clone identified by a cDNA Clone Identifier in Table 1, which DNA molecule is contained in the deposit given the ATCC Deposit Number shown in Table 1.
  • nucleic acid molecule wherein said sequence of at least 50 contiguous nucleotides is included the nucleotide sequence of the complete open reading frame sequence encoded by said human cDNA clone.
  • nucleic acid molecule compnsmg a nucleotide sequence which is at least 95% identical to sequence of at least 150 contiguous nucleotides in the nucleotide sequence encoded by said human cDNA clone.
  • a further preferred embodiment is an isolated nucleic acid molecule compnsmg a nucleotide sequence which is at least 95% identical to sequence of at least 500 contiguous nucleotides the nucleotide sequence encoded by said human cDNA clone.
  • a further preferred embodiment is an isolated nucleic acid molecule compnsmg a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence encoded by said human cDNA clone.
  • a further preferred embodiment is a method for detecting in a biological sample a nucleic acid molecule compnsmg a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of.
  • step of comparing sequences compnses determining the extent of nucleic acid hybndization between nucleic acid molecules in said sample and a nucleic acid molecule comprising said sequence selected from said group.
  • step of compa ⁇ ng sequences is performed by companng the nucleotide sequence determined from a nucleic acid molecule in said sample with said sequence selected from said group.
  • the nucleic acid molecules can compnse DNA molecules or RNA molecules.
  • a further preferred embodiment is a method for identifying the species, tissue or cell type of a biological sample which method comprises a step of detecting nucleic acid molecules in said sample, if any, compnsmg a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X wherein X is any integer as defined in Table 1; and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA Clone Identifier in Table 1 and contained in the deposit with the ATCC Deposit Number shown for said cDNA clone in Table 1.
  • the method for identifying the species, tissue or cell type of a biological sample can comprise a step of detecting nucleic acid molecules compnsmg a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence m said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from said group
  • a method for diagnosing in a subject a pathological condition associated with abnormal structure or expression of a gene encoding a secreted protein identified Table 1 comprises a step of detecting in a biological sample obtained from said subject nucleic acid molecules, if any, compnsmg a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO X wherem X is any integer as defined in Table 1 , and a nucleotide sequence encoded by a human cDNA clone identified by a cDNA
  • the method for diagnosing a pathological condition can compnse a step of detecting nucleic acid molecules compnsmg a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least
  • composition of matter compnsmg isolated nucleic acid molecules wherein the nucleotide sequences of said nucleic acid molecules compnse a panel of at least two nucleotide sequences, wherein at least one sequence m said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of a nucleotide sequence of SEQ ID NO: 1
  • nucleic acid molecules can comprise DNA molecules or RNA molecules
  • an isolated polypeptide compnsmg an amino acid sequence at least 90% identical to a sequence of at least about 10 contiguous amino acids in the amino acid sequence of SEQ ID NO Y wherein Y is any integer as defined in Table 1
  • a polypeptide wherein said sequence of contiguous amino acids is included in the amino acid sequence of SEQ ID NO: Y in the range of positions beginning with the residue at about the position of the First Amino Acid of the Secreted Portion and ending with the residue at about the Last Amino Acid of the Open Reading Frame as set forth for SEQ ID NO: Y in Table 1.
  • an isolated polypeptide compnsmg an amino acid sequence at least 95% identical to a sequence of at least about 30 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y.

Abstract

La présente invention concerne de nouvelles protéines humaines sécrétées ainsi que des acides nucléiques isolés contenant les régions codantes des gènes codant pour ces protéines. L'invention concerne également des vecteurs, des cellules hôtes, des anticorps et des techniques de recombinaison permettant de produire ces protéines humaines sécrétées. L'invention concerne enfin des méthodes diagnostiques et thérapeutiques permettant de diagnostiquer et de traiter les troubles liés à ces nouvelles protéines humaines sécrétées.
EP99937247A 1998-07-15 1999-07-14 71 proteines humaines secretees Withdrawn EP1097199A4 (fr)

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US9292298P 1998-07-15 1998-07-15
US9292198P 1998-07-15 1998-07-15
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US92922P 1998-07-15
US92956P 1998-07-15
US92921P 1998-07-15
PCT/US1999/015849 WO2000004140A1 (fr) 1998-07-15 1999-07-14 71 proteines humaines secretees

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Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030170864A1 (en) 2000-05-30 2003-09-11 Genentech, Inc. Secreted and transmembrane polypeptides and nucleic acids encoding the same
WO2002026931A2 (fr) * 2000-09-25 2002-04-04 Human Genome Sciences, Inc. 71 proteines humaines secretees
US6534631B1 (en) 1998-07-15 2003-03-18 Human Genome Sciences, Inc. Secreted protein HT5GJ57
US20020192752A1 (en) 1998-09-09 2002-12-19 Genentech, Inc. Compositions and methods for the treatment of immune related diseases
US6914130B2 (en) 1998-06-17 2005-07-05 Genentech, Inc. Compositions and methods for the diagnosis and treatment of tumor
US20070014787A1 (en) 1998-07-15 2007-01-18 Human Genome Sciences, Inc. 71 human secreted proteins
ES2248458T3 (es) * 1999-02-10 2006-03-16 Genentech, Inc. Polipeptido secretado y acidos nucleicos que lo codifican.
US7576182B1 (en) 1999-08-31 2009-08-18 Genentech, Inc. Compositions and methods for the treatment of immune related diseases
DE60041266D1 (de) * 1999-08-31 2009-02-12 Genentech Inc Zusammensetzung und verfahren zur behandlung von immunverwandten krankheiten
KR100543857B1 (ko) * 1999-09-01 2006-01-23 제넨테크, 인크. 혈관신생 및 심혈관형성의 촉진 또는 억제
US20020172996A1 (en) * 2000-06-23 2002-11-21 Glucksmann Maria Alexandra 58199, a novel membrane-associated protein and uses therefor
WO2002006312A2 (fr) * 2000-07-13 2002-01-24 Novartis Ag Gene associe a une maladie
WO2002008283A2 (fr) * 2000-07-20 2002-01-31 Eli Lilly And Company Polypeptides lp120 et leurs utilisations therapeutiques
EP1311662A2 (fr) * 2000-08-24 2003-05-21 Genentech, Inc. Compositions et methodes pour le diagnostic et le traitement de tumeurs
US20020119139A1 (en) * 2000-10-11 2002-08-29 Michel Lazdunski Cloning and recombinant expression of mammalian group XII secreted phospholipase A2
US7227007B2 (en) 2000-12-28 2007-06-05 Asahi Kasei Pharma Corporation NF-κB activating gene
CA2441702A1 (fr) * 2001-03-21 2002-12-27 Human Genome Sciences, Inc. Proteines secretees par l'homme
CA2559211A1 (fr) 2004-03-19 2005-09-29 Yale University Detection, isolement et utilisations de la renalase (monoamine oxydase de type c)
TW200738255A (en) 2005-11-21 2007-10-16 Univ Yale Methods of regulating renalase (Monoamine Oxidase C)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5536637A (en) * 1993-04-07 1996-07-16 Genetics Institute, Inc. Method of screening for cDNA encoding novel secreted mammalian proteins in yeast
WO1997004097A2 (fr) * 1995-07-19 1997-02-06 Genetics Institute, Inc. Proteines humaines ctla-8 et utilisation de proteines apparentees aux proteines ctla-8

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE253123T1 (de) * 1991-08-26 2003-11-15 Baxter Healthcare Sa Ein intaktes fpv-tk-gen enthaltender rekombinanter virus der vogelpocken
US5849498A (en) * 1997-05-16 1998-12-15 Incyte Pharmaceuticals, Inc. Human 3-hydroxyisobutyryl-coenzyme a hydrolase

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5536637A (en) * 1993-04-07 1996-07-16 Genetics Institute, Inc. Method of screening for cDNA encoding novel secreted mammalian proteins in yeast
WO1997004097A2 (fr) * 1995-07-19 1997-02-06 Genetics Institute, Inc. Proteines humaines ctla-8 et utilisation de proteines apparentees aux proteines ctla-8

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DATABASE EMBL 2 June 1996 (1996-06-02), XP002301323 Database accession no. Z73913 *
DATABASE EMBL 6 March 1997 (1997-03-06), "zr47h07.r1 Soares_NhHMPu_S1 Homo sapiens cDNA clone IMAGE:666589 5', mRNA sequence." XP002311843 retrieved from EBI accession no. EM_PRO:HS1151648 Database accession no. HS1151648 *
See also references of WO0004140A1 *

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EP1097199A4 (fr) 2005-02-23

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