EP1064297A1 - 95 proteines humaines secretees - Google Patents

95 proteines humaines secretees

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Publication number
EP1064297A1
EP1064297A1 EP99916140A EP99916140A EP1064297A1 EP 1064297 A1 EP1064297 A1 EP 1064297A1 EP 99916140 A EP99916140 A EP 99916140A EP 99916140 A EP99916140 A EP 99916140A EP 1064297 A1 EP1064297 A1 EP 1064297A1
Authority
EP
European Patent Office
Prior art keywords
seq
gene
tissue
protein
tissues
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Withdrawn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
EP99916140A
Other languages
German (de)
English (en)
Other versions
EP1064297A4 (fr
Inventor
Steven M. Ruben
Jian Ni
Craig A. Rosen
Guo-Liang Yu
Paul E. Young
Ping Feng
Daniel R. Soppet
Ying-Fei Wei
Gregory A. Endress
Roxanne D. Duan
Hla Kyaw
Reinhard Ebner
David W. Lafleur
Henrik S. Olsen
Yanggu Shi
Paul A. Moore
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Human Genome Sciences Inc
Original Assignee
Human Genome Sciences Inc
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Filing date
Publication date
Application filed by Human Genome Sciences Inc filed Critical Human Genome Sciences Inc
Publication of EP1064297A1 publication Critical patent/EP1064297A1/fr
Publication of EP1064297A4 publication Critical patent/EP1064297A4/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Withdrawn legal-status Critical Current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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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 stringency hybridization conditions.
  • Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature.
  • washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5X SSC).
  • blocking reagents include Denhardt's reagent, BLOTTO, heparin, denatured salmon sperm DNA, and commercially available proprietary formulations.
  • the inclusion of specific blocking reagents may require modification of the hybridization conditions described above, due to problems with compatibility.
  • polynucleotide which hybridizes only to polyA+ sequences (such as any 3' terminal polyA-i- tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of "polynucleotide,” since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone).
  • polynucleotide of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA.
  • polynucleotides can be composed of single- and double-stranded DNA, DNA that is a mixture of single- and double- stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions.
  • polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA.
  • a polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability or for other reasons.
  • Modified bases include, for example, tritylated bases and unusual bases such as inosine.
  • a variety of modifications can be made to DNA and RNA; thus, "polynucleotide” embraces chemically, enzymatically, or metabolically modified forms.
  • the polypeptide of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids.
  • the polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini.
  • 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-ribosylation, amidation, covalent attachment of flavin, covalent attachment of a heme moiety, covalent attachment of a nucleotide or nucleotide derivative, covalent attachment of a lipid or lipid derivative, covalent attachment of phosphotidylinositol, cross-linking, cyclization, disulfide bond formation, demethylation, formation of covalent cross-links, formation of cysteine, formation of pyroglutamate, formylation, gamma-carboxylation, glycosylation, GPI anchor formation, hydroxylation, iodination, methylation, myristoylation, oxidation, pegylation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer-RNA mediated addition of amino acids to proteins 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.)
  • This gene is expressed primarily in anergic T cells and merkel 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 disorders and inflammatory 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., 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 epitopes include those comprising a sequence shown in SEQ ID NO:
  • T-cells and merkel cells indicate that the protein products of this gene are useful for the diagnosis and/or treatment of immune system diseases. Furthermore, 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 may be 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 may be 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.
  • 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 2329 of SEQ ID NO: 11, b is an integer of 15 to 2343, 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 of the invention comprise the following amino acid sequences: IPENRRPASXCTWSMWTSRTTTRRPPWGRFSSVSSASV SSTRKTWRTRSTSCCRSSRRRV AAPFCTPS ASTEPS ARMEPPLELPVVHTFSFL TFVFTYRCSAGDGSITQINCAYEMGEEMPKRQMKAIKFLLFHFYL (SEQ ID NO:205), IPENRRPASXCTWSMWTSRTTTRRPPWGRFSSVSSASVSST (SEQ ID NO:206), RKTWRTRSTSCCRSSRRRVAAPFCTPSASTEPSARMEPPLELP (SEQ ID NO:207), and/or VVHTFSFLTFVFTYRCSAGDGSITQINCAYEMGEEMPKRQ MKAIKFLLFHFYL (SEQ ID NO:208).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • This gene is expressed primarily in placental, brain and breast tissues, and to a lesser extent in T cells and 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, neurodegenerative and/or endocrine disorders and neoplasias, or 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., brain, endocrine, immune, 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 epitopes include those comprising a sequence shown in SEQ ID NO: 109 as residues: Ala-55 to Asn-60, Lys-65 to Met-71, Leu-75 to Asn-86, Asp-93 to Asp-110, Leu-130 to Cys-138, Gln-149 to Glu-154, Thr-172 to Ile-179, Glu-185 to Arg- 192.
  • tissue distribution in breast and brain tissues indicates that the protein products of this gene are useful for the diagnosis and/or treatment of endocrine disorders, neurodegenerative disorders, developmental disorders, immune system diseases and neoplasias.
  • tissue distribution in placental tissue 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 may be 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.
  • this gene product may be 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. It may serve to promote the proliferation, survival, activation, and/or differentiation of hematopoietic cells, as well as other cells throughout the body. Likewise,
  • 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 may be 10
  • cytokine production 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 may be 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. In addition, 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. Alternatively, the tissue distribution in brain tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons Disease, Huntingtons Disease, Tourette
  • 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.
  • 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: 12 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 a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1163 of SEQ ID NO: 12, b is an 11
  • polypeptides of the invention comprise the following amino acid sequences: HPSIIIWSGNNENEEALMMNWYHISFTDRPIYIKDYVTL YVKNIRELVLAGDKSRPFITSSPTNGAETVAEAWVSQNPNSNYFGDVHFYDYI SDCWNWKVFPKARFASEYGYQSWPSFSTLEKVSSTEDWSFNSKFSLHRQHH EGGNKQMLYQAGLHFKLPQSTDPLRTFKDTIYLTQVMQAQCVKTETEFYRRS RSEIVDQQGHTMGALYWQLNDIWQAPSW (SEQ ID NO:209), and/or VRVHTWS
  • SLEPVCSRVTERFVMKGGEAVCLYEEPVSELLRRCGNCTRESCVVSFYLSAD HELLSPTNYHFLSSPKEAVGLCKAQITAIISQQGDIFVFDLETSAVAPFVWLDV GSIPGRFSDNGFLMTEKTRTILFYPWEPTSKNELEQSFHVTSLTDIY SEQ ID NO:210.
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is thought to reside on chromosome 4. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 4.
  • polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a 12
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the chondro and immune system.
  • tissue or cell types e.g., immune, 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.
  • bovine beta-mannosidase The tissue distribution and homology to bovine beta-mannosidase indicates that the protein products of this gene are useful for the diagnosis and/or treatment of chondroma and mannosidosis.
  • Human beta-mannosidosis is an autosomal recessive, lysosomal storage disease caused by a deficiency of the enzyme beta-mannosidase.
  • the homology of the translation product of this gene to beta- mannosidase indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis, prevention, and/or treatment of various metabolic disorders such as lysosomal storage deficiencies, Tay-Sachs disease, phenylkenonuria, galactosemia, hyperlipidemias, porphyrias, and Hurler's syndrome.
  • 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 is related to SEQ ID NO: 13 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence is cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2093 of SEQ ID NO: 13, b is an 13
  • polypeptides of the invention comprise the following amino acid sequences: PRLTPRMKWPTAALASRLLGWTVLRPPYPRVPSLPQVT LHPTDGLMAVLYTGGEGRTLGEQHFFHETFVTRWLLGPVPVRFGACSPLSFL APRRGQGAPAGXFCACPRPASRQLCPWPALPGTPYSNSAPLCTGMGHSNTPQ GPPS PQYALS PTEPTSLS GNS HLPAILVL (SEQ ID NO:211), PRLTPRMKWPTAAL ASRLLGWTVLRPPYPRVPSLPQVTLHP (SEQ ID NO:212), TDGLMAVLYTGGE GRTLGEQHFFHETFVTRWLLGPVPVRFG (SEQ ID NO:213), ACSPLSFLAPRRGQGAPAGXFCACPRPAS RQLCPWPALPGTP ( S E Q I D N O : 2 1 4 ) , a
  • YSNSAPLCTGMGHSNTPQGPPSPQYALSPTEPTSLSGNS HLPAILVL SEQ ID NO:215.
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • This gene is expressed primarily in human lung (adult and fetal), and to a lesser extent in liver and brain 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, pulmonary disorders and hemostasis.
  • 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., pulmonary, 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 epitopes include those comprising a sequence shown in SEQ ID NO: 111 as residues: Arg-28 to Gln-36.
  • tissue distribution in lung and liver tissues indicates that the protein products of this gene are useful for the diagnosis and/or treatment of pulmonary disorders and hematopoietic disorders.
  • the tissue distribution in adult and fetal lung tissues indicates that polynucleotides and polypeptides corresponding to this gene are useful for the detection and treatment of disorders associated with developing lungs, particularly in premature infants where the lungs are the last tissues to develop.
  • the tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and intervention of lung tumors, since the gene may be involved in the regulation of cell division, particularly since it is expressed in fetal tissue.
  • 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 may be 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 may be 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 are specifically excluded from the scope of the present invention.
  • a-b is any integer between 1 to 1248 of SEQ ID NO: 14
  • b is an integer of 15 to 1262
  • 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.
  • polypeptides of the invention comprise the following amino acid sequences: HLLEVTPCRLPVPEFPGRTPRGSRTPD (SEQ ID NO:216). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • This gene is expressed primarily in rapidly dividing liver tissue, (e.g., hepatoma, hepatocellular carcinoma, and fetal liver tissue), and to a lesser extent in normal liver tissue, and other tumors such as colon cancer and uterine cancer.
  • 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, cancers, particularly hepatomas, colon cancer, and uterine 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., liver, colon, uterus, 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 epitopes include those comprising a sequence shown in SEQ ID NO: 112 as residues: Trp-35 to Trp-45, Pro-52 to Asp-57, Thr-73 to Arg-82, Pro-105 to Leu- 112, Pro-115 to Arg-127, Pro-140 to Gln-151.
  • liver tissues and cancers thereof, as well as other cancerous tissues indicates that the protein products of this gene are useful for the diagnosis and/or treatment of cancers, particularly, hepatoma, colon cancer and uterine cancer, as well as cancers of other tissues where expression has been observed.
  • expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
  • 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 745 of SEQ ID NO: 15, b is an integer of 15 to 759, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 15, 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, hepatomas. Similarly, polypeptides and antibodies directed to these 17
  • polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue(s) or cell type(s) For a number of disorders of the above tissues or cells, particularly of the liver, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., liver, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, 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.
  • tissue or cell types e.g., liver, 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
  • tissue distribution in hepatocellular tumors indicates that the protein products of this gene are useful for the diagnosis and/or treatment of hepatomas, as well as cancers of other tissues where expression has been observed.
  • expression within cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
  • 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 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 16 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 is any integer between 1 to 1796 of SEQ ID NO: 16
  • b is an integer of 15 to 1810, 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.
  • 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, malignant neoplasms and reproductive 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, 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 epitopes include those comprising a sequence shown in SEQ ID NO: 114 as residues: Arg-23 to Trp-28, Phe-93 to Lys-98, Arg-199 to Trp-206, Gly-208 to Met-213.
  • tissue distribution in placental tissue and human rhabdomyosarcoma tissue indicates that the protein products of this gene are useful for the diagnosis and/or treatment of skeletal and reproductive disorders. Furthermore, the tissue distribution in placental tissue 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 may be 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. 19
  • this gene product may be 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. 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.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 17 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 17 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 1038 of SEQ ID NO: 17, b is an integer of 15 to 1052, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 17, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in fetal liver/spleen and fetal skin tissues, and to a lesser extent in breast cancer tissue.
  • 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 disorders and neoplasias.
  • polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the fetal tissue and adult immune system, expression of this gene at significantly higher or lower levels may be 20
  • tissue or cell types e.g., developing, 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.
  • tissue distribution in fetal liver/spleen and skin tissues indicates that the protein products of this gene are useful for the diagnosis and/or treatment of developmental disorders and malignant neoplasias.
  • expression within fetal tissue and other cellular sources marked by proliferating cells indicates that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • fetal development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus, this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
  • tissue distribution in fetal skin tissue indicates that polynucleotides and polypeptides corresponding to this gene are useful for the treatment, diagnosis, and/or prevention of various skin disorders including 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
  • injuries and inflammation of the skin i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis
  • atherosclerosis i.e. rashes, prickly heat disorder, psoriasis, dermatitis
  • atherosclerosis uticaria, eczema
  • photosensitivity autoimmune disorders
  • lupus erythematosus vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus
  • keloids striae, erythema, petechiae, purpura, and xanthelasma.
  • disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm).
  • 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. 21
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 18 Some of these sequences are related to SEQ ID NO: 18 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 1 116 of SEQ ID NO: 18, b is an integer of 15 to 1130, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 18, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequences: MIPGSDSQTALNFGSTLMKKKSDPEGPALLFPESELSIRI GRAGLLSDKSENGEAYQRKKAAATGLPEGPAVPVPSRGNLAQPGGSSWRRI ALLILAITIHNVPEGLAVGVGFGAIEKTASATFESARNLAIGIGIQNFPEGLAVS LPLRGAGFSTWRAFWYGQLSGMVEPLAGVFGAFAVVLAEPILPYALAFAAG AMVYVVMDDIIPEAQISGNGKLASWASILGFVVMMSLDVGLG (SEQ ID NO:217), MIPGSDSQTALNFGSTLMKKKSDPEGPALLFPESELSIRIGRA (SEQ ID NO:218), GLLSDKSENGEAYQRKKAAATGLPEGPAVPVPSRGNLAQPG ( S E Q I D
  • GSSWRRIALLILAITIHNVPEGLAVGVGFGAIEKTASATFESAR SEQ ID NO:220
  • NLAIGIGIQNFPEGLAVSLPLRGAGFSTWRAFWYGQLS GMVEP SEQ ID NO:221
  • LAGVFGAFAVVLAEPILPYALAFAAGAMVYVVM DDIIPEAQIS SEQ ID NO:222
  • GNGKLASWASILGFVVMMSLDVGLG SEQ ID NO:223
  • 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 system, such as AIDS, as well as inflammatory 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, 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.
  • tissue distribution indicates that polynucleotides and polypeptides corresponding to this gene are useful for the diagnosis and treatment of a variety of immune system disorders.
  • This gene product in immune cells such as macrophage 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 may be 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 may be 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. Expression of this gene product in macrophage also strongly indicates a role 23
  • 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 869 of SEQ ID NO: 19, b is an integer of 15 to 883, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 19, and where b is greater than or equal to a + 14.
  • This gene is expressed primarily in the spleen metastic melanoma tissue as well as in embryonic 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 affecting the spleen or immune system, developmental disorders, 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., spleen, 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 epitopes include those comprising a sequence shown in SEQ ID NO: 117 as residues: Asn-37 to Lys-44, Ser-73 to Glu-78, Ala- 103 to Ser-111.
  • tissue distribution in spleen metastic melanoma and embryonic tissues indicates that the protein products of this gene are useful for the diagnosis and/or treatment of disorders affecting the spleen, including cancers of the spleen, as well as cancers of other tissues where expression has been observed.
  • 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, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • embryonic development also involves decisions involving cell differentiation and/or apoptosis in pattern formation. Thus, this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
  • 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: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.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 975 of SEQ ID NO:20, b is an integer of 15 to 989, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:20, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: disorders affecting the immune 25
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue(s) or cell type(s) e.g., immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • the tissue distribution in monocytes and neutrophils indicates that the protein products of this clone are useful for the diagnosis and/or treatment of immune system disorders, including AIDS. Furthermore, expression of this gene product in monocytes and neutrophils suggests 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 may be 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 may be 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. Expression of this gene product in monocytes and neutrophils also strongly suggests a role for this protein in immune function and immune surveillance. Protein, 26
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 481 of SEQ ID NO:21, b is an integer of 15 to 495, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:21, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: disorders affecting the immune system.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution suggests that the protein product of this clone is useful for the diagnosis and treatment of a variety of immune system disorders.
  • Expression of this gene product in monocytes suggests 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 may be 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 may be 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. Expression of this gene product in monocytes also strongly suggests a role for this protein in immune function and immune surveillance. 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:22 amino acid sequences
  • amino acid 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 would be cumbersome.
  • a-b a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2303 of SEQ ID NO:22, b is an integer of 15 to 2317, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:22, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: disorders of the immune system.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • the tissue distribution in monocytes indicates that the protein products of this clone are useful for the diagnosis and/or treatment of disorders of the immune system.
  • Expression of this gene product in monocytes suggests 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 may be 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.
  • this gene product may have commercial utility in the expansion of stem cells and committed progenitors of 29
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:23 amino acid sequences
  • amino acid 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. Preferably, such related polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1712 of SEQ ID NO:23, b is an integer of 15 to 1726, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:23, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with a gene from C. elegans of unknown function.
  • polypeptides of the invention comprise the following amino acid sequences: TRPITYVLLAG (SEQ ID NO:224).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is thought to reside on chromosome 11. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 11.
  • this gene is expressed primarily in fetal lung, liver, spleen and heart tissues, as well as adult liver, bladder, endometrial stromal cells, synovium, colon cancer, smooth muscle, keratinocytes, and the bone marrow derived cell line RS4;11.
  • nucleic acids 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 the following diseases and conditions: disorders of the musculo-skeletal system, and cancers of the immune system.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, musculo-skeletal, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • tissue distribution in tissues of the immune system indicates that the protein products of this clone are useful for treating proliferative disorders of immune system precursor cells.
  • tissue distribution in smooth muscle and 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.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:24 Some of these sequences are related to SEQ ID NO:24 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 515 of SEQ ID NO:24, b is an integer of 15 to 529, where both a and b correspond to the positions of 31
  • polypeptides of the invention comprise the following amino acid sequences: GTSLTAPLLEFLLALYFLFADAMQLNDKWQGLCWP (SEQ ID NO:225). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • this gene is expressed primarily in T-cells, fetal spleen and infant brain tissues, and to a lesser extent in many other tissues including melanocytes, lung cancer, macrophages, dendritic cells, stromal cells, adrenal gland and others.
  • nucleic acids 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 the following diseases and conditions: inflammation and autoimmunity, developing tissues.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, developing, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution in T-cells and other immune cells indicates that the protein products of this clone are useful for treating diseases involving the activation of T-cells, including inflammation and autoimmune diseases.
  • tissue distribution in a wide range of fetal tissues suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and 32
  • this protein may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy. 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1741 of SEQ ID NO:25, b is an integer of 15 to 1755, 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.
  • polypeptides of the invention comprise the following amino acid sequences: LANFZCSDCAQTVLFVLZFZILVFTYEIPF (SEQ ID NO:226).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is thought to reside on chromosome 13. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 13. Recently another group published this gene, referring to it as CLN5 (See Genbank Accession No.: 3342386).
  • this gene is expressed primarily in placental tissue, 12 week embryos, and tumors including testes, tongue and pharynx, and to a lesser extent in adipose tissue, tonsils, melanocytes, fetal spleen, macrophages, T-cells, amniotic cells, and brain tissue. 33
  • nucleic acids 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 the following diseases and conditions: tumors, particularly of the tongue and throat, and neurodegenerative disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., tongue, throat, brain, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 123 as residues: Pro-44 to Ala-60, Val-187 to Thr-193, Lys-203 to Ala-210, Thr-212 to Cys-219.
  • tissue distribution in tongue and pharynx carcinoma tissue indicates that the protein products of this clone are useful for diagnosing and/or treating oral cancers, including tumors of the throat and tongue.
  • tissue distribution in brain tissue suggests that the protein product of this clone is useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as neuronal ceroid lipofuscinoses (NCLs), Alzheimers Disease, Parkinsons Disease, Huntingtons 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.
  • NCLs neuronal ceroid lipofuscinoses
  • Alzheimers Disease Parkinsons Disease
  • Huntingtons Disease Huntingtons 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
  • 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.
  • Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are 34
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1737 of SEQ ID NO:26, b is an integer of 15 to 1751, 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.
  • polypeptides of the invention comprise the following amino acid sequences: QAWHEVGGGVRRCWFVLGERRAGSLLSASYGTFAMPG MVLFGRRWAIASDDLVFPGFFELVVRVLWWIGILTLYL (SEQ ID NO:227), and/or PGMVLFGRRWAIASDDLVFPGFFELVVRVLWWIGILTLYLMHRGKLD CAGGALLSSYLIVLMILLAVVICTVSAIMCVSMRGTICNPGPRKSMSKLLYIRL ALFFPEMVWASLGAAWVADGVQCD (SEQ ID NO:228). Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed in activated neutrophils, infant brain tissue and primary dendritic cells.
  • nucleic acids 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 the following diseases and conditions: disorders of the immune system, and neurodegenerative disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, brain, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual 35
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 124 as residues: Pro-47 to Met-53, Ser-130 to Ser-138.
  • the tissue distribution in neutrophils and primary dendritic cells indicates that the protein products of this clone are useful for diagnosing and/or treating immune system disorders.
  • Expression of this gene product in neutrophils and primary dendritic cells suggests 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 may be 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 may be 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. Expression of this gene product in neutrophils and primary dendritic cells also strongly suggests a role for this protein in immune function and immune surveillance.
  • tissue distribution in brain tissue suggests that the protein product of this clone is useful for the detection/treatment of neurodegenerative disease states and behavioural disorders such as Alzheimers Disease, Parkinsons
  • 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 36
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1198 of SEQ ID NO:27, b is an integer of 15 to 1212, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:27, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: immune and inflammatory disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • the tissue distribution in neutrophils indicates that the protein products of this clone are useful for the diagnosis and/or treatment of immune and inflammatory disorders.
  • Expression of this gene product in neutrophils suggests 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 may be 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 may be 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. Expression of this gene product in neutrophils also strongly suggests a role for this protein in immune function and immune surveillance. 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 would be cumbersome.
  • a-b a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1098 of SEQ ID NO:28, b is an integer of 15 to 1112, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:28, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequences: HERNCFPMWLNHSAFPPV (SEQ ID NO:229). Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in neutrophils, and to a lesser extent in other tissues.
  • nucleic acids 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 the following diseases and conditions: immune and inflammatory disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • the tissue distribution in neutrophils indicates that the protein products of this clone are useful for the diagnosis and/or treatment of immune and inflammatory disorders.
  • This gene product in neutrophils suggests 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 may be 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 may be also used as an agent for immunological disorders including arthritis, asthma, immune 39
  • 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. Expression of this gene product in neutrophils also strongly suggests a role for this protein in immune function and immune surveillance. 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 734 of SEQ ID NO:29, b is an integer of 15 to 748, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:29, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequences: GWTRENDHRALSKAGIGSAEIQPSNLRVGSAKDLGKPW AGKLLLLSSCLLFFSLGVLYRGQMLAPPLQEDWKGGVKDSDLIDDSSASPIPP SYLEYKAALYPFSEHKSVRNATDSLTFFLVTDHFLDNQDSQ (SEQ ID NO:
  • SSCLLFFSLGVLYRGQMLAPPLQEDWKGGVKDSDLIDDSSASPIPP SEQ ID NO:232
  • SYLEYKAALYPFSEHKSVRNATDSLTFFLVTDHFL DNQDSQ SEQ ID NO:233.
  • nucleic acids 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 the following diseases and conditions: ovarian cancer.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution in ovarian cancer tissue indicates that the protein products of this clone are useful for the diagnosis and/or treatment of ovarian cancer, 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: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.
  • polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 764 of SEQ ID NO:30, b is an integer of 15 to 778, where both a and b correspond to the positions of 41
  • FEATURES OFPROTEINENCODEDBY GENE NO: 21 When tested against U937 Myeloid cell lines, supernatants removed from cells containing this gene activated the GAS assay. Thus, it is likely that this gene activates myeloid cells, and to a lesser extent other cells, through the Jak-STAT signal transduction pathway.
  • the gamma activating sequence (GAS) 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 of the invention comprise the following amino acid sequences: LKFHQESLSGD (SEQ ID NO:234). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: growth disorders, immune and inflammatory diseases, and tumorigenesis.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 128 as residues: Glu-60 to Arg-65.
  • tissue distribution in immune tissues indicates that the protein products of this clone are useful for the diagnosis and/or treatment of growth disorders, immune and inflammatory diseases, and tumorigenesis.
  • expression within embryonic tissue and other cellular sources marked by proliferating cells suggests that this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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.
  • 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:31 amino acid sequences
  • amino acid 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1310 of SEQ ID NO:31, b is an integer of 15 to 1324, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:31, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequences: EAKSRPVTQAGVQWHDLGSLQPLPP (SEQ ID NO:235). Polynucleotides encoding these polypeptides are also encompassed by the invention. 43
  • this gene is expressed primarily in ovarian cancer tissue, and to a lesser extent in fetal liver/spleen and retinal tissues.
  • nucleic acids 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 the following diseases and conditions: ovarian cancer, immune disorders, and retinal disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types
  • tissue distribution in ovarian cancer tissue indicates that the protein products of this clone are useful for the diagnosis and/or treatment of ovarian cancer, as well as cancers of other tissues where expression has been observed.
  • tissue distribution also suggests that the protein product of this clone is useful for the diagnosis and treatment of a variety of immune system disorders.
  • This gene product in fetal liver/spleen suggests 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 may be 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 may be 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. In addition, this gene product may have 44
  • the tissue distribution in retinal tissue suggests that the protein product of this clone is useful for the treatment and/or detection of eye disorders including blindness, color blindness, impaired vision, short and long sightedness, retinitis pigmentosa, retinitis proliferans, and retinoblastoma, retinochoroiditis, retinopathy and retinoschisis.
  • 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 725 of SEQ ID NO:32, b is an integer of 15 to 739, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:32, and where b is greater than or equal to a + 14.
  • EGR1 Early growth response 1
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 17.
  • polypeptides of the invention comprise the following amino acid sequences: EAKSRPVTQAGVQWHDLGSLQPLPP (SEQ ID NO:236), and/or ALVLVCRQRYCRPRDLLQRYDSKPIVDLIGAMETQSEPSELELDDVVIT NPHIEAILENEDWIEDASGLMSHCIAILKICHTLTEKLVAMTMGSGAKMKTSA SVSDIIVVAKRISPRVDDVVKSMYPPLDPKLLDAR (SEQ ID NO:237).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in fast growing tissues such as early development stage human tissues, immune/hematopoietic tissues, melanocytes, and tumor tissues, and to a lesser extent in some other tissues.
  • nucleic acids 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 the following diseases and conditions: growth disorders, immune and inflammatory disoders, skin and connective tissue disorders, and tumorigenesis.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cells particularly of the fast growing tissues such as early development stage human tissues, immune/hematopoietic tissues, skin and connective tissue, and tumor tissues
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., musculo-skeletal, skin, immune, developing, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., musculo-skeletal, skin, immune, developing, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 130 as residues: Pro-34 to Ser-43, Glu-54 to Ser-60.
  • tissue distribution suggests that the protein product of this clone is useful for the diagnosis and/or treatment of growth disorders, immune and inflammatory disorders, and tumorigenesis.
  • tissue distribution in melanocytes in 46
  • the protein product of this clone is useful for the treatment, diagnosis, and/or prevention of various skin disorders including 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), injuries and inflammation of the skin (i.e.
  • wounds wounds, rashes, prickly heat disorder, psoriasis, dermatitis), atherosclerosis, uticaria, eczema, photosensitivity, autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), keloids, striae, erythema, petechiae, purpura, and xanthelasma.
  • autoimmune disorders i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus
  • keloids striae, erythema, petechiae, purpura, and xanthelasma.
  • disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm).
  • Protein, as well as, antibodies directed against the protein may show utility as a tumor marker and immunotherapy targets for the above listed tumors and tissues.
  • 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 would be cumbersome.
  • a-b a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1448 of SEQ ID NO:33, b is an integer of 15 to 1462, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:33, and where b is greater than or equal to a + 14. 47
  • 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 of the invention comprise the following a m i n o a c i d s e q u e n c e s :
  • SLLNTLAQIHKGLCGQLAAILA SEQ ID NO:241
  • APGLQNYFLQCVAPGAAP HLTPFSAWALRHEYHLQYLALALAQK SEQ ID NO:242
  • AAALQPLPATHAA LYHGMALALLSRLLPGSEYLTHELLLSCVFR SEQ ID NO:243
  • LEFLPERTSG GPEAADFSDQLSLGSSRVPRCGQGTLLAQACQDL SEQ ID NO:244
  • PSIRNCYLTHCSPARASLLASQALHRGELQRVPTLLLPMPTEPLLPTDWPFLH Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • this gene is expressed primarily in hematopoietic tissues and fetal heart tissue, and to a lesser extent in brain and gall bladder tissues, and some other tissues.
  • nucleic acids 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 the following diseases and conditions: immune and inflammatory disorders, cardiovascular disorders, and growth disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., vascular, immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 131 as residues: Tyr-88 to Trp-102, Asp-105 to Ser-110.
  • tissue distribution in hematopoietic tissues indicates that the protein products of this clone are useful for the diagnosis and/or treatment of immune and inflammatory disorders and growth disorders.
  • 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.
  • polynucleotide sequences such as EST 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 49
  • preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2801 of SEQ ID NO:34, b is an integer of 15 to 2815, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 34, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequences: VGSVLGAFLTFPGLRLAQTHRDALT (SEQ ID NO:246). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is thought to reside on chromosome 19. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 19.
  • nucleic acids 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 the following diseases and conditions: hyperpituitarism and hypopituitarism.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., endocrine, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • This gene is found on the short arm of chromosome 19 and, therefore, is useful as a chromosome marker. 50
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 132 as residues: Met-1 to Pro-6, Gln-89 to Ala-94, Pro-161 to Cys-173.
  • the tissue distribution in pituitary tissue indicates that the protein products of this clone are useful for the diagnosis and/or treatment of pituitary disorders. More generally, the tissue distribution in pituitary tissue suggests that the protein product of this clone is useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly 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. 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.
  • various endocrine disorders and cancers particularly Addison's disease, Cushing's Syndrome, and disorders and/or cancers of
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:35 amino acid sequences
  • amino acid 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1064 of SEQ ID NO:35, b is an integer of 15 to 1078, 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.
  • nucleic acids 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 the following diseases and conditions: immune, developmental and reproductive disorders.
  • polypeptides and antibodies directed to those 51 are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of the following diseases and conditions: immune, developmental and reproductive disorders.
  • polypeptides and antibodies directed to those 51 are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of the following diseases and conditions: immune, developmental and reproductive disorders.
  • polypeptides and antibodies directed to those 51 are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of the following diseases and conditions: immune, developmental and reproductive disorders.
  • polypeptides and antibodies directed to those 51 are useful as reagents for differential identification of the tissue(s) or cell type
  • polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, developmental, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • the tissue distribution in bone marrow and placental tissue indicates that the protein products of this clone are useful for the diagnosis and/or treatment of immune and reproductive disorders.
  • the tissue distribution in bone marrow suggests that the protein product of this clone is useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia.
  • 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.
  • tissue distribution in placental tissue suggests that the protein product of this clone is useful for the diagnosis and/or treatment of disorders of the placenta.
  • Specific expression within the placenta suggests that this gene product may play a role in the proper establishment and maintenance of placental function.
  • this gene product may be 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.
  • this gene product in a vascular-rich tissue such as the placenta also suggests that this gene product may be produced more generally in endothelial cells or within the circulation. In such instances, it may play more generalized roles in 52
  • 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. 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.
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1203 of SEQ ID NO: 36, b is an integer of 15 to 1217, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:36, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequences:
  • nucleic acids 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 the following diseases and conditions: disorders in the prostate gland, vascular and connective tissues.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential 53
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., reproductive, vascular, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., reproductive, vascular, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • the tissue distribution in prostate and smooth muscle tissues indicates that the protein products of this clone are useful for the diagnosis and/or treatment of prostate gland, vascular and connective tissue disorders.
  • the tissue distribution in smooth muscle 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.
  • the expression in the prostate tissue may indicate the gene or its products can be used in the disorders of the prostate, including inflammatory disorders, such as chronic prostatitis, granulomatous prostatitis and malacoplakia, prostatic hyperplasia and prostate neoplastic disorders, including adenocarcinoma, transitional cell carcinomas, ductal carcinomas, squamous cell carcinomas, or as hormones or factors with systemic or reproductive functions.
  • 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: 37 is related to SEQ ID NO: 37 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1268 of SEQ ID NO:37, b is an integer of 15 to 1282, where both a and b correspond to the positions of 54
  • polypeptides of the invention comprise the following amino acid sequences: ESSFVPPAAHSSLC (SEQ ID NO:248). Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in human pituitary tissue.
  • nucleic acids 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 the following diseases and conditions: hyperpituitarism and hypopituitarism.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., endocrine, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • the tissue distribution in pituitary tissue indicates that the protein products of this clone are useful for the diagnosis and/or treatment of pituitary gland disorders such as hypopituitarism and hyperpituitarism. More generally, the tissue distribution in pituitary tissue suggests that the protein product of this clone is useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly 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.
  • pancrease e.g. diabetes mellitus
  • adrenal cortex e.g., ovaries
  • pituitary e.g., hyper-, hypopituitarism
  • thyroid e.g. hyper-, hypothyroidism
  • parathyroid
  • 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 56
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 545 of SEQ ID NO:38, b is an integer of 15 to 559, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:38, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following a m i n o a c i d s e q u e n c e s :
  • LLPGQQEATQCVEAGAGEGALTPMCPCRQEQFVDLYKEF EPSLVNSTV YIMAMAIQMAPFAIN YKVRPGPCXNIHCLPTQPHPMKPS VPHPH RARPSWRACPRTSPWCGVWQFHSWPSLACSSAPRPTSTASLASWTSLWSSS WSLPRSCSWTSAWRSWPTASCSSSWGPRS (SEQ ID NO:249), LLPGQQEATQCV EAGAGEGALTPMCPCRQEQFVDLYKEFEPSLVN (SEQ ID NO:250), STVYIMAMAIQMAPFAINYKVRPGPCXNIHCLPTQPHPMKPSVP ( S E Q I D N O : 2 5 1 ) ,
  • HPHRARPSWRACPRTSPWCGVWQFHSWPSLACSSAPRPTSTA (SEQ ID NO:252)
  • SLASWTSLWSSSWSLPRSCSWTSAWRSWPTASCSSSWG PRS (SEQ ID NO:253).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in human pituitary and breast tissues, and to a lesser extent in endometrial and ovarian cancer tissues.
  • nucleic acids 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 the following diseases and conditions: hyperpituitarism and hypopituitarism, and cancers of the female reproductive system.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 57
  • tissue(s) or cell type(s) For a number of disorders of the above tissues or cells, particularly of the endocrine and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., endocrine, reproductive, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., endocrine, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 136 as residues: Ser-3 to Lys- 8.
  • the tissue distribution in pituitary tissue indicates that the protein products of this clone are useful for the diagnosis and/or treatment of disorders in the pituitary gland. More generally, the tissue distribution in pituitary tissue suggests that the protein product of this clone is useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly 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.
  • tissue distribution in breast tissue and cancerous tissues of the endometrium and ovaries suggests that the translation product of this gene is useful for the detection and/or treatment of disorders and cancers of the female reproductive system, 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.
  • 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:39 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the 58
  • a-b where a is any integer between 1 to 789 of SEQ ID NO:39, b is an integer of 15 to 803, where both a and b correspond 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 sequences: TRNILSFIKCVIHNFWIPKESNEITIIINPYRETVCFSVEP VKKIFNY (SEQ ID NO:254). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., skeletal, connective, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 137 as residues: Thr-29 to Pro-34.
  • tissue distribution in synovial sarcoma tissue indicates that the protein products of this clone are useful for the diagnosis and/or treatment of diseases of the synovium.
  • the protein products of this clone are useful for the diagnosis and/or treatment of diseases of the synovium.
  • chondrodysplasias ie. spondyloepiphyseal dysplasia congenita, familial arthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid.
  • 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 1496 of SEQ ID NO:40, b is an integer of 15 to 1510, 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.
  • polypeptides of the invention comprise the following amino acid sequences: LVVLFASSNSRYLKYFFLVPLILGSAW (SEQ ID NO:255). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: malignant neoplasms and hematopoiesis.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells. 60
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., musculo-skeletal, immune, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., musculo-skeletal, immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 138 as residues: Gly-29 to Thr-35.
  • the tissue distribution in rhabdomyosarcoma and fetal liver/spleen tissues indicates that the protein products of this clone are useful for diagnosis and treatment of skeletal and immune disorders.
  • the expression in rhabdomyosarcoma tissue suggests that the protein product of this clone is useful for the detection, treatment, and/or prevention of various muscle disorders, such as muscular dystrophy, cardiomyopathy, fibroids, myomas, and rhabdomyosarcomas.
  • Expression of this gene product in fetal liver/spleen tissue suggests 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 may be 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 may be 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. 61
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1081 of SEQ ID NO:41, b is an integer of 15 to 1095, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:41, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: fibrosarcoma.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., musculo-skeletal, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 139 as residues: Ser-34 to Gln-40, Gly-42 to Glu-48, Tyr-56 to Leu-62.
  • SEQ ID NO. 139 residues: Ser-34 to Gln-40, Gly-42 to Glu-48, Tyr-56 to Leu-62.
  • fibrosarcoma's or other diorders related with fibrous tissue including fibroma, fibromatosis, fibromyoma, fibromyositis, fibrosis and fibrositis.
  • fibrous tissue including fibroma, fibromatosis, fibromyoma, fibromyositis, fibrosis and fibrositis.
  • the expression in fibrosarcoma tissue suggests that the protein product of this clone is useful for the detection, treatment, and/or prevention of various muscle disorders, such as muscular dystrophy, cardiomyopathy, myomas, and rhabdomyosarcomas.
  • 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 1148 of SEQ ID NO:42, b is an integer of 15 to 1162, 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.
  • nucleic acids 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 the following diseases and conditions: lymphoma, breast cancer, and neurological disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types 63
  • epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution in Hodgkins lymphoma, brain and breast cancer tissues suggests a role in the treatment, diagnosis and/or prognosis of breast cancer, immune and hematopoietic disorders including arthritis, asthma, immunodeficiency diseases, leukemia and Hodgkin's lymphoma and neurodegenerative disease states and behavioral disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder and panic disorder.
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 643 of SEQ ID NO:43, b is an integer of 15 to 657, 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.
  • polypeptides of the invention comprise the following amino acid sequences: HEWKCKQKYSEGSGNTRIGN (SEQ ID NO:256).
  • nucleic acids 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 the following diseases and conditions: synovitis, renal disorders and male infertility.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., skeletal, renal, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 141 as residues: Met-33 to Pro-39, Ser-74 to Trp-79.
  • tissue distribution of this gene in chronic synovitis, testes, and kidneys suggests a role in the treatment, diagnosis and prognosis of synovial membrane disorders including synovitis, renal disorders including kidney failure, renal colic, renal diabetes, hypertension, osteodystrophy, tubular acidosis and kidney stones; and and male infertility.
  • tissue distribution in testes tissue indicates that the protein product of this clone is useful for the treatment and/or 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.
  • the testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be expressed in other specific 65
  • This gene product in synovium suggests a role in the detection and/or treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis as well as disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation), such as in the diagnosis or treatment of various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie.
  • connective tissues e.g. arthritis, trauma, tendonitis, chrondomalacia and inflammation
  • various autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (ie.
  • 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: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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1141 of SEQ ID NO:44, b is an integer of 15 to 1155, 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.
  • polypeptides of the invention comprise the following amino acid sequences: LLPLCFLGPRQVLEEFPSIV (SEQ ID NO:257). Polynucleotides encoding these polypeptides are also encompassed by the invention. 66
  • nucleic acids 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 the following diseases and conditions: neurological disorders and male reproductive disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • tissue distribution of this gene in brain tissue suggests a role in the diagnosis, prognosis and/or 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.
  • 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, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:45 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 would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1098 of SEQ ID NO:45, b 67
  • a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:45, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequences: PTRPSKHQEAGS (SEQ ID NO:258).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is thought to reside on chromosome 3. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3.
  • this gene is expressed primarily in adult and fetal heart tissue, and to a lesser extent in fetal lung and fetal liver/spleen tissues.
  • nucleic acids 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 the following diseases and conditions: cardiovascular and immune disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., vascular, immune, pulmonary, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 143 as residues: Val-2 to Ser- 14.
  • tissue distribution in heart, fetal liver and fetal spleen tissues suggests a role in the treatment and/or diagnosis of cardiovascular disorders including myocardial infarction, congestive heart failure, coronary failure, as well as immune disorders including autoimmune diseases, such as lupus, transplant rejection, allergic 68
  • tissue distribution in adult and 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.
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 4009 of SEQ ID NO:46, b is an integer of 15 to 4023, 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.
  • nucleic acids 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 the following diseases and conditions: male infertility and reproductive disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • testes tissues suggests a role in the treatment and/or diagnosis of male infertility, and testicular disorders including cancer. Furthermore, the tissue distribution in testes tissue indicates that the protein product of this clone is 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. Similarly, 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 may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 528 of SEQ ID NO:47, b is an integer of 15 to 542, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:47, and where b is greater than or equal to a + 14. 70
  • this gene is expressed primarily in apoptotic T- cells, and to a lesser extent in brain tissue.
  • nucleic acids 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 the following diseases and conditions: immune and neurological disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, neural, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 145 as residues: Glu-33 to Tyr-42.
  • tissue distribution in apoptotic T-cells suggests potential roles in the treatment and/or diagnosis of immune disorders including of immune and autoimmune diseases, such as lupus, transplant rejection, allergic reactions, arthritis, asthma, immunodeficiency diseases, leukemia, and AIDS.
  • immune and autoimmune diseases such as lupus, transplant rejection, allergic reactions, arthritis, asthma, immunodeficiency diseases, leukemia, and AIDS.
  • expression in brain tissue suggests a role in the treatment and/or diagnosis 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.
  • the tissue distribution in apoptotic T-cells indicates that the translation product of this gene may also be involved in apoptosis or tissue differentiation and could again be useful in cancer therapy.
  • 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 71
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1481 of SEQ ID NO:48, b is an integer of 15 to 1495, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:48, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with phosphomannomutase, which is thought to be important in mannose matabolism.
  • nucleic acids 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 the following diseases and conditions: meningioma related diseases.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 146 as residues: Ser-33 to Lys-43.
  • the gene product can be used for preventing microbial infection of the meninges, for imaging conjugates, or as a secretory factor as a endocrine with systemic, central or peripheral nerve functions.
  • 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: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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 804 of SEQ ID NO:49, b is an integer of 15 to 818, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:49, and where b is greater than or equal to a + 14.
  • this gene is expressed primarily in tonsils, osteoclastoma and retinoic acid treated teratocarcinoma cells, and to a lesser extent in macrophages, female bladder, adipose tissue, myeloid progenitor cells, prostate tissue, and number of other tissues and organs.
  • nucleic acids 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 the following diseases and conditions: tonsils and osteoclast related diseases.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, skeletal, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, 73
  • synovial fluid or spinal fluid taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 147 as residues: Glu-55 to Arg-61, Gln-84 to Ser-92, Ser-99 to Ser-104.
  • the tissue distribution in tonsils and osteoclastoma suggests that the protein product of this clone is useful for the diagnosis and/or intervention of diseases related to tonsils or osteoclasts.
  • Expression of this gene product in osteoclastoma suggests that it may play a role in the survival, proliferation, and/or growth of osteoclasts. Therefore, it may be useful in influencing bone mass in such conditions as osteoporosis.
  • this gene product suggests 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 may be 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.
  • 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.
  • Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are 74
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1697 of SEQ ID NO:50, b is an integer of 15 to 1711, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:50, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: T-cell related disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • tissue distribution in resting T-cells suggests that the protein product of this clone is useful for the diagnosis and/or intervention of T-cell related disorders, such as infection, inflammation, allergy, tissue/organ transplantation, immune deficiency etc.
  • the expression of this gene product in T cells also strongly suggests a role for this protein in immune function and immune surveillance.
  • 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. 75
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 735 of SEQ ID NO:51 , b is an integer of 15 to 749, where both a and b correspond 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 weak sequence homology with Human metastasis suppressor KiSS-1 fragment, which is thought to be important in the diagnosis, prevention, staging and/or treatment of cancers, such as melanoma (See Accession No. W 15789).
  • polypeptides of the invention comprise the following amino acid sequences: GQGPAGRWVRRLPCSRRAGGERGPHWGVWAGPQM SCGLXFGP (SEQ ID NO:259), WRTQGPMVLLWVVTCPATMLTEPQNPHLIGF VAYSGPSHTTQPHKYWLLLDGQADPAAAEGPVKRKAASVVWWPQALRHLS LLVHCWEESYEMNIGCQSLWAGGLASSGNGWDLGVAFRRDTCMSSSSLHW KEFKYAPGSLHYFALSFVLILTEICLVSSGMGFPQEGKHFSVLGSPDCSLWGR DEHVPREFA (S EQ ID NO : 260) , WRTQGPMVLLWVVTCPATMLTEPQNPHLIGFVAY SGPSHTTQ (SEQ ID NO:261), PHKYWLLLDGQADPAAAEGPVKRKAASVVWW PQALRHLSLL (SEQ ID NO:262), VHCWEES
  • polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 1.
  • this gene is expressed primarily in tonsils, osteoclastoma and teratocarcinoma tissues, and to a lesser extent in female bladder, adipose tissue, myeloid progenitor, prostate tissue, and number of other tissues.
  • nucleic acids 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 the following diseases and conditions: diseases related to tonsils and osteoclasts.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, skeletal, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • tonsils and osteoclastoma tissues suggests that the protein product of this clone is useful for the diagnosis and/or treatment of diseases related to tonsils and osteoclasts.
  • Expression of this gene product in osteoclastoma suggests that it may play a role in the survival, proliferation, and/or growth of osteoclasts. Therefore, it may be useful in influencing bone mass in such conditions as osteoporosis.
  • this gene product in tonsils suggests 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 may be involved in the regulation of cytokine production, antigen 77
  • 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 may be 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 1077 of SEQ ID NO:52, b is an integer of 15 to 1091, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:52, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with the Drosophila gene "maleless”, which is one of four known regulatory loci required for increased transcription (dosage compensation) of X-linked genes (See Genbank Accession No.: gill 57906). It has been discovered that this gene is expressed primarily in normal prostate tissue, testes tissue, whole 6-week old embryonic tissue, human colon carcinoma 78
  • HCC human breast cancer
  • nucleic acids 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 the following diseases and conditions: diseases of the prostate or colon, or male reproductive disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., colon, prostate, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 150 as residues: Val-39 to Ala-45.
  • tissue distribution in colon and prostate tissues suggests that the protein product of this clone is useful for the diagnosis and/or treatment of prostate disorders such as prostatitis, prostatic hyperplasia, prostate cancers, or human colon carcinoma, as well as cancers of other tissues where expression has been observed.
  • the tissue distribution in testes tissue in conjunction with the homology to the Drosophila maleless gene, suggests that the translation product of this gene is useful for the detection and/or treatment of disorders involving the testes or the transcription of X-linked genes.
  • the tissue distribution indicates that the protein product of this clone is 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.
  • testicular cancer The testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be 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: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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2240 of SEQ ID NO:53, b is an integer of 15 to 2254, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:53, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares weak sequence homology with Eimeria antigen Eam45 M3, which is thought to be important in uses as a vaccine for protecting chickens against coccidiosis. It has been discovered that this gene is expressed primarily in adrenal gland tissue, and to a lesser extent in activated T-cells.
  • nucleic acids 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 the following diseases and conditions: adrenal cortical insufficiency, adrenal cortical hyperfunction, neoplasia.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for 80
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., endocrine, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., endocrine, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • the tissue distribution in adrenal gland tissue suggests that the protein product of this clone is useful for the diagnosis and/or intervention of disorders caused by adrenal gland abnormalities, such as adrenal cortical insufficiency, adrenal cortical hyperfunction, and neoplasia. More generally, the tissue distribution suggests that the protein product of this clone is useful for the detection, treatment, and/or prevention of various endocrine disorders and cancers, particularly 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. 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.
  • various endocrine disorders and cancers
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 472 of SEQ ID NO:54, b is an integer of 15 to 486, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:54, and where b is greater than or equal to a + 14.
  • FEATURES OF PROTEIN ENCODED BY GENE NO: 45 The translation product of this gene shares sequence homology with neural thread protein, tumor necrosis factor related gene product, human alpha- 1C2 adrenalin receptor, which is thought to be important for diagnosing the presence of Alzheimer's disease, neuroectodermal tumours and a malignant astrocytoma, or diagnosis of hepatocellular carcinomas and preneoplastic or pathological conditions of the liver, and tumor immunity.
  • nucleic acids 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 the following diseases and conditions: Alzheimer's disease, neuroectodermal tumours and a malignant astrocytoma, hepatocellular carcinomas and tumors of various origins.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, endothelial, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 152 as residues: Arg-38 to Arg-47.
  • tissue distribution in immune and endothelial tissues, and the homology to neural thread protein, tumor necrosis factor related gene product, human alpha- 1C2 adrenalin receptor, or Smaller hepatocellular oncoprotein (hhcm) gene product suggests that the protein product of this clone is useful for the diagnosis and/or treatment of tumors of various origins, including neuroectodermal tumours and a malignant astrocytoma, hepatocellular carcinomas, as well as syndromes inflicted by these cancers.
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1256 of SEQ ID NO:55, b is an integer of 15 to 1270, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:55, and where b is greater than or equal to a + 14.
  • this gene is expressed primarily in tumor tissues such as hepatocellular tumor, hemangiopericytoma, chronic lymphocytic leukemia, and activated T-cells.
  • nucleic acids 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 the following diseases and conditions: tumors of various origins.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., liver, immune, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • tissue distribution in hepatocellular tumors suggests that the protein product of this clone is useful for the diagnosis and/or targeting of hepatocellular carcinomas, preneoplastic or pathological conditions of the liver, Alzheimer's disease, 83
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2045 of SEQ ID NO:56, b is an integer of 15 to 2059, 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.
  • this gene is expressed primarily in glioblastoma, ulcerative colitis, and hemangiopericytoma.
  • nucleic acids 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 the following diseases and conditions: glioblastoma, hemangiopericytoma and their inflicted disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g..
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 154 as residues: Pro-31 to Ala-37.
  • tissue distribution suggests that the protein product of this clone would be useful for the diagnosis, targeting and/or treatment of tumors in the brain, such as glioblastoma and hemangiopericytoma. Additionally, the gene products can be useful agent for the diagnosis and treatment of ulcerative colitis. 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 854 of SEQ ID NO:57, b is an integer of 15 to 868, 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.
  • nucleic acids 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 the following diseases and conditions: immunodeficiency, tumor necrosis, infection, lymphomas, auto-immunities, cancer, inflammation, anemias (leukemia) and other hematopoeitic disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types 85
  • epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution in bone marrow suggests that the protein product of this clone is useful for the diagnosis and/or treatment of immune disorders including: leukemias, lymphomas, auto-immunities, immunodeficiencies (e.g. AIDS), immuno- supressive conditions (transplantation) and hematopoeitic disorders.
  • this gene product may be applicable in conditions of general microbial infection, inflammation or cancer.
  • the tissue distribution in bone marrow suggests that the protein product of this clone is useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia.
  • 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. 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.
  • sequences are related to SEQ ID NO:58 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 would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the 86
  • a-b where a is any integer between 1 to 972 of SEQ ID NO:58, b is an integer of 15 to 986, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:58, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: immunodeficiency, tumor necrosis, infection, lymphomas, auto-immunities, cancer, inflammation, anemias (leukemia) and other hematopoeitic disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 156 as residues: Leu-40 to Cys-47.
  • the bone marrow tissue distribution suggests that the protein product of this clone would be 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 may be applicable in conditions of general microbial infection, inflammation or cancer.
  • the tissue distribution in bone marrow suggests that the protein product of this clone is useful for the treatment and diagnosis of hematopoietic related disorders such as anemia, pancytopenia, leukopenia, thrombocytopenia or leukemia.
  • 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. 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 681 of SEQ ID NO:59, b is an integer of 15 to 695, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:59, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: IAQGTVPLTKRGVQSSGPDYPEGTLTPLPRG (SEQ ID NO:266 and 267). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: immune disorders and related conditions such as leukemias, lymphomas, inflammation, hematopoeitic disfunction, arthritis and asthma.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of dendritic cells.
  • tissue or cell types e.g., dendritic cells, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution in dendritic cells suggests that the protein product of this clone is useful for the diagnosis and/or treatment of immune disorders including: leukemias, lymphomas, auto-immunities, immunodeficiencies (e.g. AIDS), immuno- supressive conditions (transplantation) and hematopoeitic disorders.
  • this gene product may be applicable in conditions of general microbial infection, inflammation or cancer.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:60 is related to SEQ ID NO:60 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 300 of SEQ ID NO:60, b is an integer of 15 to 314, where both a and b correspond to the positions of 89
  • polypeptides of the invention comprise the following amino acid sequence: DCLYLALSFPWHCHCHHHPPSGSLLYPF (SEQ ID NO:268). Polynucleotides encoding these polypeptides are also encompassed by the invention. The translation product of this gene shares sequence homology with a C. elegans protein of unknown function (See Genbank Accession No.: gill 947142 (AF000264)).
  • nucleic acids 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 the following diseases and conditions: tissue necrosis, wound healing, ulceration, neoplasms or cancer.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., vascular, endothelial, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution in healing abdominal wound tissue suggests that the protein product of this clone is useful for the treatment and/or diagnosis of conditions involving tissue repair and wound healing.
  • Tissue repair may be indicated in cases of injury to the skin or internal organs, ulceration, cellular necrosis or other conditions involving healing of both diseased or non-diseased, traumatized tissue.
  • the protein product of this gene may have indications in the diagnosis and treatment of neoplasms and cancer.
  • the tissue distribution in endothelial 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.
  • the tissue distribution further suggests that the protein product of this clone is useful for the treatment, diagnosis, and/or prevention of various skin disorders including 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
  • injuries and inflammation of the skin i.e.wounds, rashes, prickly heat disorder, psoriasis, dermatitis
  • atherosclerosis i.e. rashes, prickly heat disorder, psoriasis, dermatitis
  • atherosclerosis uticaria, eczema
  • photosensitivity autoimmune disorders
  • lupus erythematosus vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus
  • keloids striae, erythema, petechiae, purpura, and xanthelasma.
  • disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm).
  • the protein product of this clone may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).
  • various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation
  • autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well
  • 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 91
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 720 of SEQ ID NO:61, b is an integer of 15 to 734, 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 FAR- 17A, which is an androgen induced protein, absent in castrated hamsters (See Genbank Accession No.: gill91315), as well as a male hormone-dependent gene product (See GenSeq Accession No.: R10612).
  • the gene encoding the disclosed cDNA is thought to reside on chromosome 6. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 6.
  • polypeptides of the invention comprise the following amino acid sequences: ASLPPSRSRPLANMALVPCQVLRMAILLSYCSILCNYKA IEMPSHQTYGGSWKFLTFIDLVIQAVFFGICVLTDLSSLLTRGSGNQEQERQLK KLISLRDW (SEQ ID NO:269). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: immune disorders including leukemias, lymphomas; reproductive and endocrine disorders, including testicular cancer; and liver disorders (e.g. hepatoblastoma, metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells).
  • diseases and conditions include leukemias, lymphomas; reproductive and endocrine disorders, including testicular cancer; and liver disorders (e.g. hepatoblastoma, metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells).
  • polypeptides and antibodies directed to those polypeptides are useful to provide 92
  • immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue(s) or cell type(s) For .a number of disorders of the above tissues or cells, particularly of the immune and reproductive systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, reproductive, cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., immune, reproductive, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 159 as residues; Thr-59 to Gly-70, Tyr- 132 to Glu- 150.
  • tissue distribution and homology to FAR-17A suggests that the protein product of this clone is useful for the treatment and/or diagnosis of androgen related conditions and disorders.
  • Male reproductive and endocrine disorders would be potential area of application (e.g. endocrine function, sperm maturation). It may also prove to be valuable in the diagnosis and treatment of testicular cancer.
  • the protein product of this clone may be useful for the treatment and/or 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. Similarly, the protein is believed to be useful in the treatment and/or diagnosis of testicular cancer.
  • the testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body.
  • this gene product may be 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.
  • Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are 93
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1396 of SEQ ID NO:62, b is an integer of 15 to 1410, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 62, and where b is greater than or equal to a + 14.
  • polynucleotides and polypeptides have uses which include, but are not limited to, activating monocytes.
  • polypeptides of the invention comprise the following amino acid sequence: MSRSSRISGLSCPWLL (SEQ ID NO:270). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 1. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 1. It has been discovered that this gene is expressed primarily in T-cells.
  • nucleic acids 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 the following diseases and conditions: immune and hematopoietic diseases and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 160 as residues: Pro-42 to Cys-50, Leu-61 to Ala-66.
  • tissue distribution in T-cells combined with the detected calcium flux activity in monocytes suggests that the protein product of this clone would be useful for the treatment and diagnosis of immune and hematopoietic disorders. Morever, the expression of this gene product suggests a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be 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 may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues.
  • immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS,
  • 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 in the differentiation and/or proliferation of various cell types. Protein, as well as, 95
  • 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 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1217 of SEQ ID NO:63, b is an integer of 15 to 1231, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:63, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: DHWPAGFLPPAPGLKFPVALEVFRKVLPAVCPTDCSGS AGKERNS (SEQ ID NO:271). Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in liver.
  • nucleic acids 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 the following diseases and conditions: metabolic diseases and liver conditions.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., hepatic, liver, metabolic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, bile, serum, plasma, urine, synovial fluid or spinal fluid
  • the expression level in healthy tissue from an individual not having the disorder is compared to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 161 as residues: Ser-31 to Gln-41.
  • the tissue distribution in liver suggests that the protein product of this clone would be useful for treatment and diagnosis of disorders of the metabolic system and liver disorders. Morever, the protein product of this clone is useful for the detection and treatment of liver disorders and cancers (e.g. hepatoblastoma, jaundice, hepatitis, liver metabolic diseases and conditions that are attributable to the differentiation of hepatocyte progenitor cells).
  • 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 598 of SEQ ID NO:64, b is an integer of 15 to 612, 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.
  • EGRl epidermal growth response gene 1
  • EGRl promoter containing the EGRl promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation.
  • nucleic acids 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 the following diseases and conditions: immune and haemopoietic disorders and cancer such as colon cancer, but also such cancers as breast cancer, cardiac tumors, pancreatic cancer, melanoma, retinoblastoma, glioblastoma, lung cancer, intestinal cancer, testicular cancer, stomach cancer, neuroblastoma, myxoma, myoma, lymphoma, endothelioma, osteoblastoma, osteoclastoma, adenoma, and the like.
  • immune and haemopoietic disorders and cancer such as colon cancer, but also such cancers as breast cancer, cardiac tumors, pancreatic cancer, melanoma, retinoblastoma, glioblastoma, lung cancer, intestinal cancer, testicular cancer, stomach cancer, neuroblastoma, myx
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 162 as residues: Glu-63 to Trp-72.
  • the tissue distribution in T-cells and monocytes, combined with the detected EGRl biological activity suggests that the protein product of this clone would be useful for treatment and diagnosis of disorders of the immune and haemopoietic systems and colon and other cancers.
  • This gene product may be 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 may be involved in immune functions. Therefore it may be also used as an 98
  • agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues.
  • immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia
  • 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 in the differentiation and/or proliferation of various cell types. Expression cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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 are specifically excluded from the scope of the present invention.
  • a-b is any integer between 1 to 2256 of SEQ ID NO:65
  • b is an integer of 15 to 2270
  • both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:65
  • b is greater than or equal to a + 14.
  • the translation product of this gene has homology with several human keratin genes at the nucleotide level (see, for example, Troyanovsky, et al., Eur. J. Cell Biol. 59:127-137 (1992) which is hereby incorporated by reference herein). Based on the sequence similarity, the translation product of this clone is expected to share biological activities with keratin and growth factor proteins. Such activities are known in the art, and some of which are described elsewhere herein.
  • nucleic acids 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 the following diseases and conditions: immune and haemopoietic disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • sequence homology of the polynucleotides and polypeptides of the present invention with a number of human cytokeratin molecules, such as CK-8, CK-15, and CK-17, indicate that molecules of the present invention can be used diagnostically as markers of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial stem cells, as well as markers of the differentiation of other cell types such as neutrophils or other immune cells.
  • Molecules of the present invention, or agonists or antagonists thereof can also be used therapeutically to treat differentiation disorders of epithelial, neutrophil or other immune cell differentiation or activation. 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1269 of SEQ ID NO:66, b is an integer of 15 to 1283, 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.
  • polypeptides of the invention comprise the following amino acid sequence: EEIATSIEPIRDFLAIVFFASIGLHVFPTFVAYELTVLVF LTLSVVV (SEQ ID NO:272). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • osteosarcoma including, among others, bone marrow, palate, pituitary gland, and in tissue derived from osteosarcoma and chondrosarcoma.
  • nucleic acids 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 the following diseases and conditions: developmental disorders, as well as disorders of the musculoskeletal and haematopoietic systems, and cancers including especially osteosarcoma and chondrosarcoma, but also other cancers including breast cancer, colon cancer, cardiac tumors, pancreatic cancer, melanoma, retinoblastoma, glioblastoma, lung cancer, intestinal cancer, testicular cancer, stomach cancer, neuroblastoma, myxoma, myoma, lymphoma, endothelioma, osteoblastoma, osteoclastoma, adenoma, and the like.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., synovium, placenta, stromal, immune, hematopoietic, skeletal, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 164 as residues: Pro-81 to Ser-88.
  • tissue distribution in placenta suggests that the protein product of this clone would be useful for treatment and diagnosis of developmental disorders.
  • Polynucleotides and polypeptides of the present invention can be used diagnostically and therapeutically to detect and treat many cancers, particularly osteosarcoma and chondrosarcoma.
  • the expression of this gene product in synovium would suggest a role in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, tendonitis, chrondomalacia and 102
  • autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).
  • chondrodysplasias i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid.
  • the protein is useful in the detection, treatment, and/or prevention of a variety of vascular disorders and condtions, which include, but are not limited to miscrovascular disease, vascular leak syndrome, aneurysm, stroke, embolism, thrombosis, coronary artery disease, arteriosclerosis, and/or atherosclerosis.
  • vascular disorders and condtions include, but are not limited to miscrovascular disease, vascular leak syndrome, aneurysm, stroke, embolism, thrombosis, coronary artery disease, arteriosclerosis, and/or atherosclerosis.
  • 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:67 amino acid sequences
  • amino acid 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1249 of SEQ ID NO:67, b is an integer of 15 to 1263, 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: YCNLQCR (SEQ ID NO:273). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: developmental or reproductive diseases and/or disorders, in addition to the following and ovarian cancer, as well as other cancers including breast cancer, colon cancer, cardiac tumors, pancreatic cancer, melanoma, retinoblastoma, glioblastoma, lung cancer, intestinal cancer, testicular cancer, stomach cancer, neuroblastoma, myxoma, myoma, lymphoma, endothelioma, osteoblastoma, osteoclastoma, osteosarcoma, chondrosarcoma, adenoma, and the like.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue(s) or cell type(s) e.g., developmental, reproductive, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissue distribution in embryonic and ovarian tissue suggests that the protein product of this clone would be useful for tretment and diagnosis of developmental disorders as well as ovarian and other cancers.
  • Expression within embryonic tissue and other cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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 104
  • SMA spinal muscular atrophy
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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.
  • 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 1603 of SEQ ID NO:68, b is an integer of 15 to 1617, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:68, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: SALIGNPKGCFGCFSPVVLREWSVESWKSLRPFQAICK LKTNFR (SEQ ID NO:274). Polynucleotides encoding these polypeptides are also encompassed by the invention. 105
  • nucleic acids 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 the following diseases and conditions: neurological and inflammatory defects, diseases, and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue e.g., neural, immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • the tissue distribution in hypothalamus and T-cells suggests that the protein product of this clone would be useful for study and treatment of immune and nervous system disorders.
  • the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • elevated neurodegenerative disease states behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease
  • this gene product in regions of the brain suggests it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal 106
  • this gene product suggests a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells.
  • This gene product may be 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 may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues.
  • immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS,
  • 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 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.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:69 is related to SEQ ID NO:69 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 would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1375 of SEQ ID NO:69, b 107
  • a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:69, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares nucleotide sequence homology with the human PKD1 gene which is thought to be important in polycystic kidney disease.
  • This gene is expressed widely with a predominant expression exhibited in liver, pediatric kidney, and in the whole 8 week old developing human embryo.
  • nucleic acids 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 the following diseases and conditions: cancer, growth, renal, and metabolic defects, diseases, and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., renal, metabolic, hepatic, developmental, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, amniotic fluid, bile, serum, plasma, urine, synovial fluid or spinal fluid
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • 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. 108
  • this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders, particularly of the liver and other organs.
  • 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
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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 NOJ0 amino acid sequence sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NOJ0 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1882 of SEQ ID NOJ0, b is an integer of 15 to 1896, 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 of the invention comprise the following amino acid sequence: HEAALRGP (SEQ ID NO:275). Polynucleotides encoding these polypeptides are also encompassed by the invention. 109
  • nucleic acids 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 the following diseases and conditions: stroke, in addition to other, neurologically-related diseases and/or defects.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cells particularly of the central nervous system
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues (e.g., neural, musculoskeletal, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissue e.g., neural, musculoskeletal, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • the tissue distribution in human striatum depression suggests that the protein product of this clone would be useful for study and treatment of central nervous system orders, such as seizures and other neurological conditions.
  • the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • elevated neurodegenerative disease states behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease,
  • this gene product in regions of the brain suggests it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal 110
  • 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 NOJ1 amino acid sequence sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NOJ1 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 294 of SEQ ID NOJ1, b is an integer of 15 to 308, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:71, and where b is greater than or equal to a + 14.
  • This clone has homology to a cystine rich granulin peptide(s) from leucocyte(s) which has been termed Granulin E.
  • Granulins inhibit keratinocytes and is useful topically for wound healing.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 3. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 3.
  • nucleic acids 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 the following diseases and conditions: neurological, developmental, and growth defects.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues (e.g., neural, developmental, growth, and cancerous and wounded tissues) or bodily fluids (e.g., 111
  • the polypeptide of the present invention can be used to inhibit keratinocytes and promote wound healing.
  • the tissue distribution in infant brain suggests that the protein product of this clone would be useful for study and treatment of nervous system, neurodegenerative and developmental disorders.
  • the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • elevated neurodegenerative disease states behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington
  • this gene product in regions of the brain suggests 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. 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 granulin proteins suggest the protein product of this clone is useful for the treatment, diagnosis, and/or prevention of various skin disorders including 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
  • injuries and inflammation of the skin i.e. wounds, rashes, prickly heat disorder, psoriasis, dermatitis
  • atherosclerosis i.e. wounds, rashes, prickly heat disorder, psoriasis, dermatitis
  • atherosclerosis i.e. wounds, rashes, prickly heat disorder, psoriasis, dermatitis
  • atherosclerosis uticaria, eczema
  • photosensitivity autoimmune disorders (i.e. lupus erythematosus, vitiligo, dermatomyositis, morphea, scleroderma, pemphigoid, and pemphigus), 1 12
  • keloids striae, erythema, petechiae, purpura, and xanthelasma.
  • disorders may predispose increased susceptibility to viral and bacterial infections of the skin (i.e. cold sores, warts, chickenpox, molluscum contagiosum, herpes zoster, boils, cellulitis, erysipelas, impetigo, tinea, althletes foot, and ringworm).
  • the protein product of this clone may also be useful for the treatment or diagnosis of various connective tissue disorders such as arthritis, trauma, tendonitis, chrondomalacia and inflammation, autoimmune disorders such as rheumatoid arthritis, lupus, scleroderma, and dermatomyositis as well as dwarfism, spinal deformation, and specific joint abnormalities as well as chondrodysplasias (i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid).
  • 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 1674 of SEQ ID NO:72, b is an integer of 15 to 1688, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:72, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: SNAAGNVVRAFLYINHLKL GCKVGLA (SEQ ID NO:276). Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in prostate cancer and dendritic cells. 113
  • nucleic acids 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 the following diseases and conditions: reproductive, immune, and hematopoietic diseases, defects and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 170 as residues: Trp-47 to Thr-54.
  • the tissue distribution in prostate cells and tissues indicates that the protein products of this clone are useful for study, diagnosis and treatment of neoplasias, esp. of the prostate, and hormonal and metabolic disorders. Moreover, the protein product of this clone is 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 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. 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1124 of SEQ ID NOJ3, b is an integer of 15 to 1138, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NOJ3, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: NWAVLNMLLSKGKITIFLGPLECGS (SEQ ID NO:277). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: immune and hematopoietic diseases, disorders, and/or defects, particularly cancers.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • the tissue distribution in B cell lymphoma suggests that the protein product of this clone would be useful for study and treatment of blood and immune disorders and neoplasias, esp. of the lymphatic system.
  • the protein product of this clone is 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 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. 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:74 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: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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 763 of SEQ ID NOJ4, b is an integer of 15 to 777, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 74, and where b is greater than or equal to a + 14.
  • nucleic acids 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 the following diseases and conditions: immune and hematopoietic diseases, disorders, and/or defects, particularly cancer.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • the tissue distribution in B cell lymphoma suggests that the protein product of this clone would be useful for study and treatment of neplasias, esp. of lymphatic organs, and immune disorders.
  • the protein product of this clone is 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 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. 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 ID NOJ5 and may have been publicly available prior to conception of 117
  • polynucleotides are specifically excluded from the scope of the present invention.
  • a-b is any integer between 1 to 1046 of SEQ ID NO:75
  • b is an integer of 15 to 1060
  • both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:75
  • b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with a rat protein phosphatase, in addition to, a human heterogeneous nuclear ribonucleoprotein R (See Genbank Accession No.gil2697103 (AF000364)).
  • EGRl early growth response gene 1
  • EGRl is a separate signal transduction pathway from Jak-STAT, genes containing the EGRl promoter are induced in various tissues and cell types upon activation, leading the cells to undergo differentiation and proliferation. This gene also showed activity in sensory neurons using the EGR assay described in the Example section.
  • polypeptides of the invention comprise the following amino acid sequence: PSHQTRKGKSAKLLDRPPEALRMKIITTTLLLACHLQLEV G V V V G G E V D ( S E Q I D N O:278),
  • RMPP PIRGRGRGGGRGGYG (SEQ ID NO:282), DYRGGYEDPYYGYDDGYAV RGRGGGR (SEQ ID NO:283), PPPRGRAGYSQRGAPLGPPRGSRGGRGG (SEQ ID NO:284), and/or ADGYNQPDSK RRQPTTNRTGVPNPSLSSRFSKVVT (SEQ ID NO: 285).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 1. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 1.
  • nucleic acids 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 the following diseases and conditions: reproductive, immune, or pulmonary diseases and/or disorders, particularly breast cancer.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, immune, pulmonary, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • tissue distribution in breast cancer cells and tissues, in addition to immune cells, combined with the homology to a protein phosphatase suggests that the protein product of this clone would be useful for diagnosis and treatment of breast cancer and abnormalities of the lung and the immune system. Morever, the expression of this gene product suggests a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be 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). 119
  • the gene Since the gene is expressed in cells of lymphoid origin, the natural gene product may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues.
  • immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS,
  • 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 in the differentiation and/or proliferation of various cell types.
  • the protein is useful in modulating the immune response to aberrant cells and cell types, particularly proliferative cells (e.g. protein may increase the immunogenicity of tumor antigens either directly or indirectly, or may activate apoptosis).
  • the protein is useful in treating, detecting, and/or preventing various pulmonary disorders, which include, but are not limited to, ARDS, emphysema, and cystic fibrosis. 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 NOJ6 sequences are related to SEQ ID NOJ6 and may have been publicly available prior to conception of the present invention.
  • polynucleotides are specifically excluded from the scope of the present invention. To list every related sequence would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1489 of SEQ ID NOJ6, b is an integer of 15 to 1503, where both a and b correspond to the positions of 120
  • polypeptides of the invention comprise the following amino acid sequence: LQIPPSSQSLGLKNADSSI (SEQ ID NO:286), GGPPESAPW LPAVLRAPVLTSRCASSDSEGPVWFCQPGSGPSSTEMSCHCILGPGSSCLCVL RGSMWTPSVPGWPQPAKETGASSCSVFSANNGSCPLPLHNHQRQASLDTGL SLEHVPGESYFYSPVG (SEQ ID NO:287), SSDSEGPVWFCQPGSGPSSTEMSC HCILGPGSSC (SEQ ID NO.288), WTPSVPGWPQPAKETGASSCSVFSANNG (SEQ ID NO:289), and/or QRQASLDTGL SLEHVPGESYF (SEQ ID NO:290).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: immune or hematopoietic diseases and/or disorders, particularly B cell lymphoma.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • tissue distribution in B-cell lymphoma suggests that the protein product of this clone would be useful for diagnosis and treatment of immune or hematopoietic diseases and/or disorders, particularly proliferative conditions. Morever, the expression of this gene product suggests a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including 121
  • This gene product may be 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 may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues.
  • immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS,
  • 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 in the differentiation and/or proliferation of various cell types.
  • 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.
  • 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 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 122
  • a-b a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 858 of SEQ ID NO:77, b is an integer of 15 to 872, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NOJ7, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: SSSLVLTIRSQTLFLASFIHSTSIFCALN (SEQ ID NO:291). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: osteoarthritis and other bone/cartilage disorders, particularly degenerative conditions.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of these tissue(s) or cell type(s).
  • tissue or cell types e.g., skeletal, joint, autoimmune, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • osteoarthritic cartilage suggests that the protein product of this clone would be useful for the diagnosis, treatment, and/or prevention of osteoarthritis.
  • the gene product is useful in the detection and treatment of disorders and conditions affecting the skeletal system, in particular osteoporosis, bone cancer, as well as, disorders afflicting connective tissues (e.g. arthritis, trauma, 123
  • chondrodysplasias i.e. spondyloepiphyseal dysplasia congenita, familial osteoarthritis, Atelosteogenesis type II, metaphyseal chondrodysplasia type Schmid.
  • 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 559 of SEQ ID NOJ8, b is an integer of 15 to 573, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:78, and where b is greater than or equal to a + 14.
  • 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. It has been discovered that this gene is expressed primarily in fetal brain, pharynx carcinoma, and Hodgkin's lymphoma.
  • nucleic acids 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 the following diseases and conditions: developmental and/or proliferative diseases and disorders, particularly pharynx carcinoma, and Hodgkin's lymphoma.
  • polypeptides and antibodies directed to those polypeptides are useful to 124
  • tissue(s) or cell type(s) For a number of disorders of the above tissues or cells, particularly of the digestive and immune systems, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., developmental, proliferative cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, amniotic fluid, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., developmental, proliferative cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, amniotic fluid, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 176 as residues: Tyr-30 to Ser-40.
  • tissue distribution in pharynx carcinoma and Hodgkin's lymphoma suggests that the protein product of this clone would be useful for diagnosis and treatment of immune and proliferative conditions.
  • expression within fetal tissue and other cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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). 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, 125
  • this gene product in regions of the brain suggests 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. 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 NOJ9 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NOJ9 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1495 of SEQ ID NOJ9, b is an integer of 15 to 1509, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NOJ9, and where b is greater than or equal to a + 14.
  • FEATURES OF PROTEIN ENCODED BY GENE NO: 70 The translation product of this gene shares sequence homology with insulinlike growth factor binding protein. Moreover, the protein has homology to the human Slit-1 protein (See Genbank Accession No. gnllPIDId 1036170 (AB017167)), which is thought to play an integral role in neural development. In Drosophila embryogenesis, the slit gene has been shown to play a critical role in CNS midline formation. Each Slit gene encodes a putative secreted protein, which contains conserved protein- protein interaction domains including leucine-rich repeats (LRR) and epidermal 126
  • LRR leucine-rich repeats
  • EGF growth factor
  • polypeptides of the invention comprise the following amino acid sequence: the EGF-like domain: CCCRLGLSGPKC (SEQ ID NO:292); in addition to the following: RAFWGLGALQLLDLSANQLEAL (SEQ ID NO:293), HASGRRTGSADDGLQGRTGSGPPTAGAGGGGAAP (SEQ ID NO:294), VSAAAGARLAPRAPGAPAGCRPMRGCAARAAARKSLVPVLPAGWRSGPAA AARPGPRRLAHAPS AARSRAGPGAVARPLPRRHLAAAHGRGCGPAAARAGA GSGPGARRAARVPTAGRPPGTHVHTSGQSGAPRDPEGEALADTWAQTGQGD SSSNSSSSGRGRDQEGPRMGAAPPPPAPAVGGPLPVRPWSPSSAEPVLRPDAW ( S E Q I D N O : 2 9 5 ) ,
  • GCRPMRGCAARAAARKSLVPVLPAGWRSGP AAAARPGPRRLAHAPSA (SEQ ID NO:297), PGAVARPLPRRHLAAAHGRGCG PAAARAGA (SEQ ID NO:298), S GQS GAPRDPEGEALADTWAQTGQ (SEQ ID NO : 299) , PPAPAVGGPLPVRPWSPSSAEPV (SEQ ID NO:300), APRTTGSRD AQAAGLPPRVPGAGGLP (SEQ ID NO:301), GPRPRGPWAPRTAPRCARACRE (SEQ ID NO:302), AVPPGLSLRLRALLLDHNRVRALPPGAFAGA (SEQ ID NO:303), LGALQLLDLSANQLEALAPGTFAP (SEQ ID NO:304), PPGAFAGAG ALQRLDLRENGLHSVHVRAFWGLGALQ (SEQ ID NO:305), RNLSLAGNRLA RLEPAALGALPLLRSLS (SEQ ID NO:306), LPALDALHLRGNPWGCGCALRP
  • nucleic acids 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 the following diseases and conditions: neural, reproductive, and proliferative diseases and/or disorders, particularly breast cancer and degenerative conditions.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, reproductive, and proliferative cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 177 as residues: Met-1 to Arg-10, Arg-64 to Ala-71, Gly-124 to Gly-131, Pro-189 to Arg- 194, Val-223 to Gly-228.
  • the tissue distribution in a breast cancer cells and tissues and homology to insulin-like growth factor binding protien suggests that the protein product of this clone would be useful for diagnosis and treatment of breast cancer, and other forms of cancer.
  • the homology to the conserved human slit-1 protein suggests that the protein is useful in the treatment, diagnosis, and/or prevention of neural disorders, particularly developmental and degenerative conditions.
  • the protein is useful for the treatment and/or diagnosis of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, 128
  • this gene product in regions of the brain suggests 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. 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: 80 amino acid sequences
  • amino acid sequences are related to SEQ ID NO: 80 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1095 of SEQ ID NO:80, b is an integer of 15 to 1109, 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.
  • polypeptides of the invention comprise the following amino acid sequence: HASGRPDRSSAPIGNSGLPCPDLEPLGGLQSKCRLCAPTE ARGLWSRSLCSDRCDTWRS (SEQ ID NO:311), and/or GLPCPDLEPLGGLQSK CRLCAPTEARGLW (SEQ ID NO:312).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention. This gene also maps to chromosome 1, and therefore can be used in linkage analysis as a marker for chromosome 1.
  • nucleic acids 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 the following diseases and conditions: colon carcinoma and other digestive system or gastrointestinal diseases and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., digestive system, gastrointestinal, metabolic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, chyme, bile, synovial fluid or spinal fluid
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 178 as residues: Val-34 to Leu-39, Ser-64 to Cys-74, Ser-86 to Ser-95, Arg-128 to Ala- 136.
  • tissue distribution in salivary gland and colon carcinoma suggests that the protein product of this clone would be useful for the treatment and diagnosis colon cancer and other digestive system diseases and/or disorders, such as ulcers, and other proliferative conditions.
  • 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: 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 would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the 130
  • a-b where a is any integer between 1 to 793 of SEQ ID NO:81, b is an integer of 15 to 807, 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.
  • polypeptides of the invention comprise the following amino acid sequence: QEWESELGERRKPLQA (SEQ ID NO:313). Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in 6 week old human embryos.
  • nucleic acids 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 the following diseases and conditions: embryological defects; aberrant development; aberrant cellular proliferation (e.g. cancers), and other developmentally related or proliferative diseases and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developmental, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, amniotic fluid, urine, synovial fluid or spinal fluid
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • this gene product in tissues - particularly adult tissues - may correlate with patterns of abnormal cellular proliferation, such as found in various cancers. Moreover, this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders. Similarly, 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
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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 ID NO: 82 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1029 of SEQ ID NO: 82, b is an integer of 15 to 1043, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 82, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: CQSSNLIFFQFVNILFNLMMDILVDFSITKMPINSIFSLYF 132
  • CYEII SEQ ID NO:3144.
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: abnormal embryonic development; abnormal cellular proliferation; developmental defects, and other developmentally related or proliferative diseases and/or conditions.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developmental, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, amniotic fluid, urine, synovial fluid or spinal fluid
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissue distribution in 6 week old human embryo suggests that the protein product of this clone would be useful for the diagnosis and treatment of disorders of human embryonic development.
  • Expression of this clone in developing embryos suggests that it plays a critical role in early human development. Alternatively, it may be involved in key cellular proliferation events that occur during embryogenesis. Therefore misexpression of this gene in adult tissues may lead to abnormal patterns of cellular proliferation and cancer.
  • expression within embryonic tissue and other cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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 133
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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 1159 of SEQ ID NO:83, b is an integer of 15 to 1173, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:83, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: GPVWLFCFLTLCRKPSQLFSQENSCMDVAGGVTTCLPP WFSRGAPAQMSQWPPSSDHGAVRAGRDSRVGPVQPSHLTCEGGKEEREKNK KAEVNPPTGMGLANRIPRDDITLKLRNQGKLRTKENRTQSAKRHP (SEQ ID NO:315), VACKPENRTKTHFASSPACDGHALGGQVGFAICFLSCLFPPM (SEQ ID NO:316), and/or SHPMPNTPQKQLLFSEDNELLVSLRTGRKPTLQAALRVTG (SEQ ID NO:317). Polynucleotides encoding these polypeptides are also encompassed by the invention. 134
  • this gene is expressed primarily in pleural cancer and endometrial tumors, and, to a lesser extent, in bone marrow & apoptotic T cells.
  • nucleic acids 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 the following diseases and conditions: pleural cancer; endometrial tumors; hematopoietic disorders; immune dysfunction.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., immune, hematopoietic, reproductive, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • tissue distribution in pleural cancer and endometrial tumors indicates that the protein products of this clone are useful for the diagnosis and treatment of various reproductive cancers, including pleural cancer and endometrial tumors.
  • this gene product may also be useful in the diagnosis and/or treatment of a variety of hematopoietic disorders, including defects in immune surveillance, inflammation, impaired immune function, and T cell lymphomas. Use of this gene product may be appropriate in situations designed to affect the proliferation, survival, and/or differentiation of various hematopoietic cell lineages, including blood stem cells.
  • this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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 135
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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 ID NO: 84 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1547 of SEQ ID NO:84, b is an integer of 15 to 1561, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 84, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following a m i n o a c i d s e q u e n c e :
  • EGDPRGRPRPRPLGPPPQLTLPTALXDILRQVRAPGLRLSRA LEVGRKGSPIFKIQIYL SEQ ID NO:318), IRLLTWDVKDTLLRLRHPLGEAYA TKA (SEQ ID NO:320), LEQGFRQAYRAQSHSFPNYGLSHG (SEQ ID NO:321), HLAGVQDAQAVAPIAEQLYKDFSHPC (SEQ ID NO:322), VLDGAEDTLRECR TRGLRLAVIS (SEQ ID NO:323), REHFDFVLTSEAAGWPKPDPRIFQEA (SEQ ID NO:324), EPVVAAHVGDNYLCDYQGPRAVGMHSFL (SEQ ID NO:325), and/or VVRDSVPKEHILPSLAHLLPALD (SEQ ID NO:326).
  • polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in tumors of the pancreas & thymus and to a lesser extent in a variety of fetal tissues, including fetal brain, liver, spleen, and kidney.
  • nucleic acids 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 the following diseases and conditions: pancreatic cancer; thymic cancer; disorders of fetal development; abnormal cellular proliferation; hematopoietic disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developmental, metabolic, immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, amniotic fluid, urine, synovial fluid or spinal fluid
  • tissue distribution in proliferative and developmental cells and tissues indicates that the protein products of this clone are useful for the diagnosis and treatment of cancers, particularly pancreatic and thymic cancer.
  • Expression of this gene product within various fetal tissues also indicates that it is useful in the diagnosis and/or treatment of human developmental disorders.
  • this gene product is expressed in cancers and in fetal tissues indicates that it plays a role in proliferation and/or differentiation events that are associated with early development. Misexpression of this gene product in adult tissues, therefore, may directly contribute to abnormal cellular proliferation and/or dedifferentiation that accompanies cancer.
  • this gene product in fetal liver/spleen also suggests that it plays a role in hematopoiesis, and is useful in the diagnosis and/or treatment of a variety of disorders of the immune 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.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 85 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 85 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1419 of SEQ ID NO:85, b is an integer of 15 to 1433, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:85, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: IRKLGPGLAPCSCRSGQVFPRV (SEQ ID NO:327).
  • polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in frontal cortex, particularly derived from epileptic patients.
  • nucleic acids 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 the following diseases and conditions: epilepsy; neurodegenerative 138
  • tissue(s) or cell type(s) are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., neural, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., neural, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • tissue distribution in frontal cortex tissue suggests that the protein product of this clone would be useful for the diagnosis and/or treatment of disorders of the brain and nervous system, particularly epilepsy.
  • the expression of this gene product suggests that it may play a role in various critical processes of the nervous system, including nerve survival, pathfinding, signal conductance, and/or synapse formation. It may have effects on various processes including homeostasis, learning, motor function, language, etc. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neuronal differentiation or survival. 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 ID NO: 86 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1363 of SEQ ID NO: 86, b is an integer of 15 to 1377, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 86, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following a m i n o a c i d s e q u e n c e : KPLRMARPGGPEHNEYALVSAWHSSGSYLDSEGLRHQDD
  • PGGPEHNEYALVSAWHSS GSYLDSEGLR (SEQ ID NO:334), DVSLLVCHCAAPFEEQGEAERHVLR (SEQ ID NO:335), RLTADMRRFRKPPRLPPEPEAPGSSAGS (SEQ ID NO:336), GEASGLI LAPGPAPLFPPLAAEVGM (SEQ ID NO:337), TLWKRLFLLEPPGPDRLRLGGRL (SEQ ID NO:338), and/or LAELEELLEAVHAKSIGDIDPQLDCFLS (SEQ ID NO:339).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 140
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., hematopoietic, immune, gastrointestinal, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 184 as residues: Leu- 16 to Ser-23, Ser-38 to Pro-43, Gly-53 to Leu-60.
  • tissue distribution in colon adenocarcinoma suggests that the protein product of this clone would be useful for the diagnosis and/or treatment of gastrointestinal diseases and/or disorders, particularly proliferative conditions.
  • Expression of this gene product in fetal and proliferative cells and tissues suggests that it may be a marker cancers, and that it's misregulated expression may in fact contribute to the development or progression of the types of cancers dictated by its expression.
  • this gene product may play a role in a variety of hematopoietic processes, including the survival, proliferation, activation, and/or differentiation of all blood cell lineages, including the totipotent hematopoietic stem cell. Such a gene product may therefore play a role in a variety of hematopoietic disorders including inflammation; immune dysfunction; defects in immune surveillance; and hematopoietic cancers and lymphomas.
  • 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 141
  • SMA spinal muscular atrophy
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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:87 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 1701 of SEQ ID NO: 87
  • b is an integer of 15 to 1715
  • both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:87
  • b is greater than or equal to a + 14.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 20. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 20.
  • nucleic acids 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 the following diseases and conditions: neurodegenerative diseases and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) 142
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., neural, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • This gene is believed to reside on chromosome 20, D20S111- D20S195. Polynucleotides corresponding to this gene are useful, therefore, as chromosome markers.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • the tissue distribution in brain tissue indicates that the protein products of this clone are useful for diagnosis and treatment of disorders of the central nervous system. Moreover, the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • neurodegenerative disease states including, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis
  • this gene product in regions of the brain suggests 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. 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 143
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 403 of SEQ ID NO:88, b is an integer of 15 to 417, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:88, and where b is greater than or equal to a + 14.
  • GAS gamma activating sequence
  • polypeptides of the invention comprise the following amino acid sequence: FQLYFNPELIFKHFQIWRLITNFLFFGPVGFNFLFNMIFLY RYCRMLEEGSFRGRTADFVFMFLFGGFLMTLFGLFVSLVFLGQAFTIMLVYV WSRXNPYVRMNFFGLLNFQAPFLPWVLMGFSLLLGNSIIVDLLGIAVGHIYFF LEDVFPNQPGGIRILKTPSILKAIFDTPDEDPNYNPLPEERPGGFAWGEGQ SEQ I D N O : 3 4 0 ) ,
  • WSRXNPYV (SEQ ID NO:344), VLMGFSLLLGNSIIVDLLGIA (SEQ ID NO:345), NQPGGIRILKTPSILKAIFDTPDED (SEQ ID NO:346), RLEYLQIPPVSRAYTTAC VLTTAAVQLE (SEQ ID NO: 347), and/or RLITNFLFFGPVGFNFLFNMIFLYRYC RMLE (SEQ ID NO:348).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • 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.
  • nucleic acids 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 the following diseases and conditions: developmental diseases, immune- related diseases, neural disorders, and vascular diseases and conditions.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developmental, vascular, immune, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, amniotic fluid, urine, synovial fluid or spinal fluid
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • the tissue distribution in fetal liver, macrophage, and fetal brain indicates that the protein products of this clone are useful for treating and diagosis of immune system-related diseases and CNS diseases.
  • the protein product of this clone is 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 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 145
  • 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.
  • fetal tissue and other cellular sources marked by proliferating cells combined with the GAS biological activity, suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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.
  • polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:89 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 would be cumbersome. Accordingly, preferably excluded from the present invention 146
  • a-b is any integer between 1 to 1153 of SEQ ID NO:89
  • b is an integer of 15 to 1167, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 89, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with proacrosin binding proteins (sp32) from non-human mammalian species.
  • the binding of sp32 to proacrosin may be involved in packaging the acrosin zymogen into the acrosomal matrix.
  • sp32 proacrosin binding proteins
  • polynucleotides and polypeptides have uses which include, but are not limited to, activating
  • polypeptides of the invention comprise the following amino acid sequence : HASAGPDGSSPA (SEQ ID NO:349), ELLLEKPKPWQPPAAAPHRALLVLCYSIVENTCIITPTAKAWKYMEEEILGFG KSVCDSLGRRHMSTCALCDFCSLKLEQCHSEASLQRQQCDTSHKTPFAAPCL P P R A C P S A T R ( S E Q I D N O : 3 5 0 ) ,
  • NRNRKVSRMRCLQNETYSALSPGKSEDVVLRWSQEFSTLTLGQFG SEQ ID NO:351
  • SPVLLPAFPPLPVPLLALPVSAPLPACVLVSAPACAPLLAPACAL ALAPGFPGTRRIVGALPRCC SEQ ID NO:352
  • LLVLCYSIVENTCIITPTAK AWKYMEEEILGFGKS SEQ ID NO:353
  • LKLEQCHSEASLQRQQC DTSHKTPFA SEQ ID NO:354
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 12. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 12.
  • nucleic acids 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 the following diseases and conditions: reproductive disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., reproductive, testis, prostate, epidiymus, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, seminal fluid, serum, plasma, urine, synovial fluid or spinal fluid
  • This gene is believed to map to chromosome 12 and is thought to be useful as a chromosome marker.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 187 as residues: Asp-27 to Ser-32, Pro-52 to Thr-58, Arg-63 to Asn-70, Gln-78 to Gly-83, Thr-107 to Asn-113, Thr-160 to Val-176, Ser-188 to Gly-241, Leu-248 to Pro-265, Tyr-302 to Gly-314.
  • tissue distribution in testis combined with the specific homology to the sp32 protein indicates that the protein products of this clone are useful for the diagnosis, treating, and/or prevention of reproductive diseases and/or disorders.
  • 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. 148
  • the protein is believed to be useful in the treatment and/or diagnosis of testicular cancer.
  • the testes are also a site of active gene expression of transcripts that may be expressed, particularly at low levels, in other tissues of the body. Therefore, this gene product may be 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.
  • the protein is useful in application and utility as a contraceptive, either directly or indirectly. Based upon the detected calcium flux activity, the protein may also be useful as an effect treatment for infertility (i.e. for inhibiting autoimmune 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.
  • 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:90 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1878 of SEQ ID NO:90, b is an integer of 15 to 1892, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 90, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: QVSGLILSLSCGMDGLALDGSPSPSPXTEKAGRCISQTSL (SEQ ID NO:355), QVSGLILSLSCGMDGLALDGSPSPSPXTEKAGRCISQTSLP
  • GKWEV (SEQ ID NO:356), RASKTVPRMPPNWPAKMPCLCHIRTVEHLGTIS 149
  • nucleic acids 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 immune disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • molecules of the present invention can be used to regulate transcription and translation of genes in cells of the immune system, as well as in other cell types. Such transcriptional and translation regulation is useful for diagnosing and treating a number of disorders in which an alterred state of transcription and translation may be a factor in the disorder.
  • Such disorders include many viral infections, particularly of immune cells, including HIV-1, HIV-2, human T-cell lymphotropic virus (HTLV)-I, and HTLV-II, as well as other DNA and RNA viruses such as herpes simplex virus (HSV)-l, HSV-2, HSV-6, cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes sammati, adenoviruses, rhinoviruses, influenza viruses, reoviruses, and the like.
  • HSV herpes simplex virus
  • CMV cytomegalovirus
  • EBV Epstein-Barr virus
  • herpes sammati adenoviruses
  • rhinoviruses influenza viruses
  • reoviruses reoviruses, and the like.
  • translation is useful in the diagnosis and treatment of many types of cancers, particularly those of the immune system, including ovarian cancer, breast cancer, colon cancer, cardiac tumors, pancreatic cancer, melanoma, retinoblastoma, glioblastoma, lung cancer, intestinal cancer, testicular cancer, stomach cancer, neuroblastoma, myxoma, myoma, lymphoma, endothelioma, osteoblastoma, osteoclastoma, osteosarcoma, chondrosarcoma, adenoma, and the like.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 188 as residues: Gln-2 to Trp-12, Ala-30 to Glu-35, Gln-42 to Ser-51.
  • tissue distribution in neutrophils combined with the homology to viral tat proteins suggests that the protein product of this clone is useful for the diagnosis and treatment of immune disorders, particularly viral infections and proliferative disorders. Further, since this clone has a high degree of sequence relatedness to factors which are involved in the regulation of transcription and translation, this clone is useful as a regulator of such processes. 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:91 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:91 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 509 of SEQ ID NO:91, b is an integer of 15 to 523, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:91, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: PCADCLSAWA (SEQ ID NO:363).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 5. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 5.
  • this gene is expressed primarily in adipocytes and striatum depression, and in lower abundance in prostate, whole brain, fetal liver, and spleen.
  • nucleic acids 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 the following diseases and conditions: Prostate cancer, CNS diseases, immune disorders .
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, hematopoietic, immune, and cancerous and wounded tissues
  • bodily fluids e.g., seminal fluid, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid
  • the translation product of this clone has a high degree of sequence relatedness to many thioredoxins, it can be used as a food additive to improve flour quality or to suppress the anti-nutritional effects of leguminous plants.
  • Molecules of the present invention can further used to inactivate toxins, for example, bee or snake venom.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 189 as residues: Trp-43 to Ala-49, Pro-68 to Ala-74, Glu-100 to Gly-111, Glu-120 to Asn-125, Pro-141 to Ala-154, Asp-157 to Lys-171, Cys-177 to Ile-182, Ser-248 to Leu-253, Thr-280 to Glu-285, Gly-353 to Val-359. 152
  • tissue distribution in whole brain suggests that the protein product of this clone would be useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • neurodegenerative disease states behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies,
  • this gene product in regions of the brain suggests 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 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. Typical of these are 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 hyperproliferative diseases; for regulation of metabolism, and behavior.
  • 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
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:92 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:92 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1368 of SEQ ID NO:92, b is an integer of 15 to 1382, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:92, and where b is greater than or equal to a + 14.
  • ISRE interferon-sensitive responsive element
  • polypeptides of the invention comprise the following amino acid sequence: HASGYLCIVLL (SEQ ID NO:364). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: kidney and other urinary tract 154
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., renal, kidney, urogenital, immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, ⁇ serum, plasma, urine, synovial fluid or spinal fluid
  • Molecules of the present invention are particularly useful in the diagnosis and treatment of disorders related to transplantation, particularly kidney transplantation.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 190 as residues: Asn-49 to Gln-54, Glu- 150 to Asp- 159.
  • SEQ ID NO. 190 residues: Asn-49 to Gln-54, Glu- 150 to Asp- 159.
  • 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 is useful in modulating the immune response to aberrant kidney proteins, including autoantigens and aberrant proteins which are often present in degenerative and proliferative conditions.
  • 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 ID NO:93 and may have been publicly available prior to conception of 155
  • polynucleotides are specifically excluded from the scope of the present invention.
  • a-b is any integer between 1 to 1733 of SEQ ID NO:93
  • b is an integer of 15 to 1747
  • both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:93
  • b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with the conserved MAL and plasmolipin protein (Magyar, et al, Gene 189:269-275 (1997); See Genbank Accession No.gnllPIDIe 183885), which are thought to be important in modulating T cell function, and proper CNS function, respectively.
  • GAS gamma activating sequence
  • 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 of the invention comprise the following amino acid sequence: NSARAARAEIVLGLLVWTLIAGTEYFRVPAFGWV (SEQ ID NO:365). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 immune, hematopoietic, and neural diseases and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue(s) or cell type(s) For a number of disorders of the above tissues or cells, particularly of the immune system, expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., immune, hematopoietic, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Nucleic acids of the present invention are useful as probes for detecting traumatic and pathological changes in the central and peripheral nervous systems.
  • Molecules of the present invention may be involved in regulating the growth of Schwann cells and other neural cells. Molecules of the present invention are also useful as modulators of the interaction between Schwann cells and other neural cells and the extracellular matrix and is therefore useful for the therapeutic intervention in nerve damage primarily by facilitating regeneration of damaged axons and regenerating nerve cells in damaged nervous system tissues.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 191 as residues: Ser-58 to His-64.
  • tissue distribution in T-cells combined with the homology to the MAL and plasmolipin proteins and the detected GAS biological activity suggests that the protein product of this clone would be useful for the diagnosis and treatment of immune disorders including, but not limited to, AIDS and other immunodeficiencies. Morever, the expression of this gene product suggests a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be 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 may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, 157
  • neutropenia neutrophilia
  • 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues.
  • 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 in the differentiation and/or proliferation of various cell types.
  • 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. Typical of these are 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 hyperproliferative diseases; for regulation of metabolism, and behavior.
  • 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 158
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 586 of SEQ ID NO:94, b is an integer of 15 to 600, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:94, and where b is greater than or equal to a + 14.
  • the translation product of this clone has sequence identity to a protein tyrosine kinase reported by Oates and Wilks (The Worm Breeders Gazette 14:87-87 (1995), which is hereby incorporated by reference herein).
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 2. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 2.
  • nucleic acids 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 the following diseases and conditions: neural, visual, and renal diseases and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the CNS, retina, and kidney cortex.
  • Expression of this gene at significantly higher or lower levels may be detected in certain tissues or cell types (e.g., neural, visual, renal, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues or cell types e.g., neural, visual, renal, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • the tissue distribution in cerebellum, adult brain, and spinal cord tissue suggests that the protein product of this clone would be useful for the diagnosis and treatment of neural diseases and disorders.
  • the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • elevated neurodegenerative disease states including, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease
  • this gene product in regions of the brain suggests 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 product of this clone 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.
  • 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:95 amino acid sequences
  • b 160 amino acid sequences
  • a-b nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 572 of SEQ ID NO:95, b 160
  • a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:95, and where b is greater than or equal to a + 14.
  • the translation product of this clone has homology to trkB, and it is thought that the protein of the present invention is a novel novel neural receptor protein- tyrosine kinase, a trkB homolog (See for example, ).
  • This protein is likely to be derived from a gene for a ligand-regulated receptor closely related to the human trk oncogene.
  • Northern (RNA) analysis showed that the trkB gene is expressed predominantly in the brain and that trkB expresses multiple mRNAs, ranging from 0.7 to 9 kb. Hybridization of cerebral mRNAs with a variety of probes indicates that there are mRNAs encoding truncated trkB receptors.
  • polypeptides of the invention comprise the sequence PCSPPDSPPLPGAFVWRVLWVC (SEQ ID NO:366). Polynucleotides encoding this polypeptide are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: breast cancer, colon tumor. B-cell lymphoma.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, gastrointestinal, immune, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 193 as residues: Ser-29 to Asn-40.
  • the tissue distribution in proliferative cells and tissues suggests that the protein product of this clone would be useful for the treatment, detection, and/or prevention of cancer, particularly in the indicated tissues.
  • the expression within cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • the homology to the trkB protein suggests the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • elevated expression of this gene product in regions of the brain suggests it plays a role in normal neural function. Potentially, this gene product is involved in synapse formation, neurotransmission, learning, cognition, homeostasis, or neurodegenerative disease
  • 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:96 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:96 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 788 of SEQ ID NO:96, b is an integer of 15 to 802, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:96, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: ARACFAYNGVCSEGRCWDSHFHGSV (SEQ ID NO:367), MSNMGKIPSLSLHIPINKYICSRIPKFIQKVNKSTVLQICLKRQIILNKNKMSDH SKIGKANLVQIDIHSLGIVETGCVPSKRYCTLLTEQSGFPFLSHP (SEQ ID NO:368),
  • MAGCCLKLFGVLSLCFLCGLISIERVICNPVSADFQVSTFCQRHCLLR SKVMFXIKGXTATIEVINENCTLVAAPPIGFPIXFL (SEQ ID NO:369), MSDHS KIGKANLVQIDIHSLGIVETGCVPSKRYCTLLTEQSGFPFLSHP (SEQ ID NO:370), MAGCCLKLFGVLSLCFLCGLISIERVICNPVSADFQVSTFCQRHCL LRSK (SEQ ID NO:371), VMFXIKGXTATIEVINENCTLVAAPPIGFPIXFL (SEQ ID NO:372).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: immune, hematopoietic, and vascular diseases and/or disorders.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cells particularly of the immune
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues (e.g., immune, hematopoietic, smooth muscle vascular, and cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues e.g., immune, hematopoietic, smooth muscle vascular, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 194 as residues: Asp-40 to Ser-52.
  • tissue distribution in dendritic cells suggests that the protein product of this clone would be useful for immune disorders.
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO:97 Some of these sequences are related to SEQ ID NO:97 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1212 of SEQ ID NO:97, b is an integer of 15 to 1226, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:97, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: PTEGRQKVLKTFTVPRSALAMTKTSTCIYHFLVLSWYTF LNYYISQEGKDEVKPKILANGARWKY (SEQ ID NO:373), PTEGRQKVLKTF TVPRSALAMTKT (SEQ ID NO:375), PRSALAMTKTSTCIYHFLVLSWYTFLN YYISQEGK (SEQ ID NO:374), and/or FLNYYISQEGKDEVKPKILANGARWKY (SEQ ID NO:376). Polynucleotides encoding these polypeptides are also encompassed by the invention.
  • nucleic acids 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 the following diseases and conditions: disorders of secretory cells including cells in the lung, colon, testis and the skin.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cells particularly of the secretory epithelial cells in the lung, intestine, testis and skin
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissues e.g., cancerous and wounded tissues
  • bodily fluids e.g., serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 195 as residues: Val-21 to Asp-30, Pro- 101 to Thr-109.
  • tissue distribution and homology to androgen regulated protein suggests that the protein product of this clone would be useful for treating disorders that involve highly secretory cells including those in the colon, testis, and skin. It may be useful for diagnosing disorders such as colon, lung, or testicular cancer and may be 165
  • the 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 may be expressed, particularly at low levels, in other tissues of the body.
  • this gene product may be 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.
  • 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:98 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1106 of SEQ ID NO:98, b is an integer of 15 to 1120, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:98, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with dec-205 a transmembrane protein which is thought to be important in antigen presentation in dendritic cells and T-cells.
  • nucleic acids 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 the following diseases and conditions: inflammatory diseases such as ulcerative colitis.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cells particularly of the immune system
  • expression of this gene at significantly higher or lower levels may be detected in certain tissues (e.g., cancerous and wounded tissues) or bodily fluids (e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.
  • tissue e.g., cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • polynucleotide sequences such as EST sequences, are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO:99 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 would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2582 of SEQ ID NO:99, b is an integer of 15 to 2596, where both a and b correspond to the positions of 167
  • FEATURES OFPROTEINENCODEDBY GENENO 90 This gene maps to chromosome 22 and therefore polynucleotides of the present invention can be used in linkage analysis as a marker for chromosome 22.
  • polypeptides of the invention comprise the sequence FKDQLVYPLLAFT (SEQ ID NO: 377) and/or RQALNLPDVFGLV (SEQ ID NO:379). Polnucleotides encoding these polypeptides are also encompassed by the invention.
  • this gene is expressed primarily in fetal spleen and liver as well as cd34 positive cells and to a lesser extent in several tissues suggesting a presence in blood or blood forming tissues.
  • nucleic acids 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 the following diseases and conditions: developmental defects in the blood and blood forming cells.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., fetal spleen and liver as well as cd34 positive cells, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 197 as residues: Gln-54 to Gly-61, Asn-79 to Leu-91, Glu-99 to Thr-105, Pro-120 to Gin- 126, Pro- 128 to Phe- 134, Arg- 150 to Arg- 156, Arg- 160 to Arg- 170.
  • the tissue distribution in fetal spleen and liver as well as cd34 positive cells suggests that the protein product of this clone would be useful for treating disorders in 168
  • polynucleotide sequences such as EST sequences
  • SEQ ID NO: 100 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1006 of SEQ ID NO: 100, b is an integer of 15 to 1020, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 100, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: ATASHDLLLF (SEQ ID NO: 379), MSINICLMQSKTQGSCQ YLLLPHPVPIILKVSTVFSLLSLFRLLFLSFCPHPKKCSYLLKYYGPLEGHKTLX YLRTNLGVIQPPLRMYAAEDCNGIG (SEQ ID NO:380), MSINICLMQSKTQG SCQYLLLPHPVPIILKVSTVFSLLSLFRLLFL (SEQ ID NO:381), and/or SFCPHPK KCSYLLKYYGPLEGHKTLXYLRTNLGVIQPPLRMYAAEDCNGIG (SEQ ID NO:382).
  • Polynucleotides encoding these polypeptides are also encompassed by the invention. It has been discovered that this gene is expressed primarily in T cells, fetal heart and chronic lymphocytic leukemia and to a lesser extent in kidney, lung, and 16 week embryos.
  • nucleic acids 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 the following diseases and conditions: disorders of the blood including abnormalities in T cell function or blood cell proliferation such as leukemia . 169
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., T cells, fetal heart and chronic lymphocytic leukemia, cancerous and wounded tissues
  • bodily fluids e.g., lymph, serum, plasma, urine, synovial fluid or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO.
  • the tissue distribution in T cells, fetal heart and chronic lymphocytic leukemia suggests that the protein product of this clone would be useful for treating abnormalities of the blood particularly those involving T-cells and the abnormal proliferation of blood cells such as lymphocytic leukemia.
  • the protein product of this clone is useful for the diagnosis and treatment of a variety of immune system disorders. Morever, the expression of this gene product suggests a role in regulating the proliferation; survival; differentiation; and/or activation of hematopoietic cell lineages, including blood stem cells. This gene product may be 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 may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, 170
  • 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 in the differentiation and/or proliferation of various cell types.
  • 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
  • tissue distribution in embryonic tissue suggests the protein product of this clone is useful for the diagnosis, detection, and/or treatment of developmental disorders.
  • Expression within embryonic tissue and other cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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: 101 amino acid sequences
  • amino acid sequences are publicly available and accessible through sequence databases. Some of these sequences are related to SEQ ID NO: 101 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1506 of SEQ ID NO: 101, b is an integer of 15 to 1520, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 101, and where b is greater than or equal to a + 14.
  • the translation product of this gene shares sequence homology with ctg4 which is a glutamine repeat containing gene thought to be a candidate genetic disease locus.
  • polypeptides of the invention comprise the sequence KEEDDDTERLPSKCEVCKLLSTE (SEQ ID NO:383 and 384) LQAELSRTGRSR EVLELGQ (SEQ ID NO:385 and 386), RQAVIVCRRRFV (SEQ ID NO:387), PPRWAHPKAPEGSPDPPSPPSALGLSVLPWSDSDPWHISVSPCAQREHYSPGS AHINSLRPLPALSLKRCKARVSSSCLYPAPAPAPAPLEIDRCDSVPPVALCSAA YTLRICWASVLCHRPPPSTSQPKPRARPKKGKAIFPTAQVP (SEQ ID NO:388), PPRWAHPKAPEGSPDPPSPPSALGLSVLPWSDSDPWHISVSPCAQREHYSPGS AHINSLRPLPALSLKRCK (SEQ ID NO:389), and/or ARVSSSCLYPAPAPAPAPL EIDRCDSVPPVALCSAAYTLRICWASVLCHRPPPSTSQPKPRARPKKGKAIFPT AQVP (SEQ ID NO:
  • nucleic acids 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 the following diseases and conditions: inherited developmental disorders possibly with a neuropsychiatric component.
  • polypeptides and antibodies directed to those polypeptides are useful to provide 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 or spinal fluid
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 199 as residues: Lys-25 to Ser-36, Ser-53 to Glu-60, Thr-70 to Arg-75, Arg-111 to Thr- 119, Glu-161 to Leu- 189.
  • tissue distribution and homology to glutamine repeat family member CTG4 suggests that the protein product of this clone would be useful for identifying and treating specific diseases related to nucleotide triplet expansion.
  • the tissue distribution in embryonic tissue suggests the protein product of this clone is useful for the diagnosis, detection, and/or treatment of developmental disorders.
  • the relatively specific expression of this gene product during embryogenesis suggests it may be a key player in the proliferation, maintenance, and/or differentiation of various cell types during development. It may also act as a morphogen to control cell and tissue type specification. Because of potential roles in proliferation and differentiation, this gene product may have applications in the adult for tissue regeneration and the treatment of cancers.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 1292 of SEQ ID NO: 102, b is an integer of 15 to 1306, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 102, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the following amino acid sequence: EEKLFTSAPGRDFWVMGETRDGNEEN (SEQ ID NO:391). Polynucleotides encoding these polypeptides are also encompassed by the invention. The gene encoding the disclosed cDNA is believed to reside on chromosome 16. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 16.
  • nucleic acids 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 the following diseases and conditions: cancer, developmental anomalies or fetal deficiencies.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., developmental, reproductive, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid
  • expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 200 as residues: Met-1 to Ser-6.
  • the tissue distribution in fetal tissue suggests that the protein product of this clone would be useful for the treatment and diagnosis of developmental anomalies or fetal deficiencies.
  • expression in a variety of cancerous tissues suggests a role in the treatment and diagnosis of uncontrolled cell proliferation and/or differentiation (e.g. cancer).
  • the expression within embryonic tissue and other cellular sources marked by proliferating cells suggests this protein may play a role in the regulation of cellular division, and may show utility in the diagnosis and treatment of cancer and other proliferative disorders.
  • 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 would be useful in the detection, treatment, and/or prevention of degenerative or proliferative conditions and diseases.
  • 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: 103 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 would be cumbersome. Accordingly, preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the 175
  • a-b where a is any integer between 1 to 771 of SEQ ID NO: 103, b is an integer of 15 to 785, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 103, and where b is greater than or equal to a + 14.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 10. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 10. This gene is expressed primarily in hypothalamus, T-cells, and adipose tissue.
  • nucleic acids 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 the following diseases and conditions: immune (e.g. immunodeficiencies, autoimmunities, inflammation, leukemias & lymphomas) and neurological (e.g. Alzheimer's disease, dementia, schizophrenia) disorders.
  • immune e.g. immunodeficiencies, autoimmunities, inflammation, leukemias & lymphomas
  • neurological e.g. Alzheimer's disease, dementia, schizophrenia
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue distribution suggests that the protein product of this clone would be useful in the intervention or detection of pathologies associated with the hematopoietic and immune systems, such as anemias (leukemias).
  • epitopes include those comprising a sequence shown in SEQ ID NO.
  • tissue distribution in hypothallamus suggests the protein product of this clone is useful for the detection, treatment, and/or prevention of neurodegenerative disease states, behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies, neoplasia, trauma, congenital malformations, spinal cord injuries, 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.
  • neurodegenerative disease states behavioral disorders, or inflammatory conditions which include, but are not limited to Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Tourette Syndrome, meningitis, encephalitis, demyelinating diseases, peripheral neuropathies,
  • this gene product in regions of the brain suggests 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. This gene product may be 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 may be involved in immune functions. Therefore it may be also used as an agent for immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS, leukemia, rheumatoid arthritis, granulomatous disease, inflammatory bowel disease, sepsis, acne, neutropenia, neutrophilia, 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, demyelination, systemic lupus erythematosis, drug induced hemolytic anemia, rheumatoid arthritis, Sjogren's disease, scleroderma and tissues.
  • immunological disorders including arthritis, asthma, immunodeficiency diseases such as AIDS,
  • 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 in the differentiation and/or proliferation of various cell types.
  • the protein 177 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 in the differentiation and/or proliferation of various cell types.
  • the protein 177 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 in the differentiation and/or proliferation of various cell types.
  • the protein 177 may represent a secrete
  • product of this clone is useful for the diagnosis, prevention, and/or treatment of various metabolic disorders which include, but are not limited to, Tay-Sachs disease, phenylkenonuria, galactosemia, hyperlipidemias, porphyrias, and Hurler's syndrome.
  • the protein is useful in the treatment and/or prevention of neurodegenerative conditions, particularly those which occur secondary to aberrant fatty acid metabolism (i.e. defects which affect the synthesis and integrity of the myelin sheath). 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 ID NO: 104 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 2001 of SEQ ID NO: 104, b is an integer of 15 to 2015, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 104, and where b is greater than or equal to a + 14.
  • polypeptides of the invention comprise the sequence:QKPTFALGELYPPLINLWEAGKEKSTSLKVKATVIGLPTNMS (SEQ ID NO: 392). Polynucleotides encoding this polypeptide are also encompassed by the invention.
  • the gene encoding the disclosed cDNA is believed to reside on chromosome 7. Accordingly, polynucleotides related to this invention are useful as a marker in linkage analysis for chromosome 7. 178
  • nucleic acids 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 the following diseases and conditions: immunodeficiency, tumor necrosis, infection, lymphomas, auto-immunities, cancer, inflammation, anemias (leukemia) and other hematopoeitic disorders, neurological diseases of the brain such as depression, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, dementia and specific brain tumors.
  • polypeptides and antibodies directed to those polypeptides are useful to provide immunological probes for differential identification of the tissue(s) or cell type(s).
  • tissue or cell types e.g., neural, immune, hematopoietic, and cancerous and wounded tissues
  • bodily fluids e.g., lymph, amniotic fluid, serum, plasma, urine, synovial fluid or spinal fluid
  • the standard gene expression level i.e., the expression level in healthy tissue from an individual not having the disorder.
  • Preferred epitopes include those comprising a sequence shown in SEQ ID NO. 202 as residues: Met-24 to Gly-29, Ala-57 to Thr-63.
  • tissue distribution in T-cells suggests that the protein product of this clone would be 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 may be applicable in conditions of general microbial infection, inflammation or cancer.
  • the expression in brain combined with the homology to the leucine-rich repeat protein suggests that the protein product of this clone would be useful for the treatment and diagnosis of developmental, degenerative and behavioral conditions of the brain and nervous system, such as depression, schizophrenia, Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette Syndrome, mania, dementia, paranoia, addictive behavior, obsessive-compulsisve disorder and 179
  • 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: 105 Some of these sequences are related to SEQ ID NO: 105 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 would be cumbersome.
  • polynucleotides comprising a nucleotide sequence described by the general formula of a-b, where a is any integer between 1 to 353 of SEQ ID NO: 105, b is an integer of 15 to 367, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO: 105, and where b is greater than or equal to a + 14.
  • HLDCD04 209628 pCMVSport 106 1889 1 1889 193 193 203 32 33 57 02/12/98 3.0

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Abstract

La présente invention concerne des nouvelles protéines humaines sécrétées, ainsi que des acides nucléiques isolés contenant les régions codantes des gènes codant de telles protéines. L'invention concerne également des vecteurs, des cellules hôtes, des anticorps et des procédés de recombinaison servant à produire des protéines humaines sécrétées. L'invention concerne encore des méthodes diagnostiques et thérapeutiques utiles pour diagnostiquer et traiter des troubles associés à ces nouvelles protéines humaines sécrétées.
EP99916140A 1998-03-19 1999-03-18 95 proteines humaines secretees Withdrawn EP1064297A4 (fr)

Applications Claiming Priority (25)

Application Number Priority Date Filing Date Title
US7856398P 1998-03-19 1998-03-19
US7857698P 1998-03-19 1998-03-19
US7858198P 1998-03-19 1998-03-19
US7857498P 1998-03-19 1998-03-19
US7857998P 1998-03-19 1998-03-19
US7857898P 1998-03-19 1998-03-19
US7857398P 1998-03-19 1998-03-19
US7857798P 1998-03-19 1998-03-19
US7856698P 1998-03-19 1998-03-19
US78574P 1998-03-19
US78566P 1998-03-19
US78577P 1998-03-19
US78578P 1998-03-19
US78563P 1998-03-19
US78576P 1998-03-19
US78581P 1998-03-19
US78573P 1998-03-19
US78579P 1998-03-19
US8031498P 1998-04-01 1998-04-01
US8031398P 1998-04-01 1998-04-01
US8031298P 1998-04-01 1998-04-01
US80313P 1998-04-01
US80314P 1998-04-01
US80312P 1998-04-01
PCT/US1999/005804 WO1999047540A1 (fr) 1998-03-19 1999-03-18 95 proteines humaines secretees

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WO2002068638A1 (fr) * 2001-02-23 2002-09-06 Human Genome Sciences, Inc. 83 proteines secretees humaines
US7223727B2 (en) 1998-04-09 2007-05-29 Serono Genetics Institute S.A. GSSP4 polynucleotides and polypeptides and uses thereof
JP2002534116A (ja) * 1999-01-15 2002-10-15 インサイト・ファーマスーティカルズ・インコーポレイテッド 概日リズム関連タンパク質
EP1165591A4 (fr) * 1999-03-26 2002-09-25 Human Genome Sciences Inc 47 proteines humaines secretees
EP1171458A4 (fr) * 1999-03-26 2003-04-02 Human Genome Sciences Inc 50 proteines secretees d'origine humaine
EP1185652A2 (fr) * 1999-06-11 2002-03-13 The Burnham Institute Acides nucleiques codant pour les proteines participant a la decomposition de proteines et produits et procedes qui y sont lies
US7087386B2 (en) 1999-06-11 2006-08-08 The Burnham Institute Nucleic acid encoding proteins involved in protein degradation, products and methods related thereto
US6638734B1 (en) 1999-06-11 2003-10-28 The Burnham Institute Nucleic acid encoding proteins involved in protein degradation, products and methods related thereto
US7504253B2 (en) 1999-06-11 2009-03-17 The Burnham Institute For Medical Research Nucleic acid encoding proteins involved in protein degradation, products and methods related thereof
CA2311201A1 (fr) 1999-08-05 2001-02-05 Genset S.A. Sequences marqueurs exprimees et proteines humaines codees
CA2386641A1 (fr) * 1999-10-29 2001-05-10 Human Genome Sciences, Inc. 32 proteines humaines secretees
CA2389326A1 (fr) * 1999-11-12 2001-05-17 Human Genome Sciences, Inc. 35 proteines humaines secretees
JP2003516734A (ja) * 1999-12-01 2003-05-20 ルードヴィッヒ インスティテュート フォー キャンサー リサーチ 癌関連抗原およびその使用
AU2001233026A1 (en) 2000-01-28 2001-08-07 Incyte Genomics, Inc. Phosphodiesterases
WO2001090374A2 (fr) * 2000-05-22 2001-11-29 Millennium Pharmaceuticals, Inc. 26493, a novel human must dgtpase family member and uses thereof
CA2426588A1 (fr) * 2000-10-26 2002-07-18 Curagen Corporation Proteines humaines, polynucleotides les codant et procedes d'utilisation correspondants
AU2002227239A1 (en) * 2000-12-06 2002-06-18 Curagen Corporation Proteins and nucleic acids encoding same
US6903201B2 (en) 2001-01-05 2005-06-07 Curagen Corporation Proteins and nucleic acids encoding same
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US20050186577A1 (en) 2004-02-20 2005-08-25 Yixin Wang Breast cancer prognostics
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