Patent Publication Number: US-2003224425-A1

Title: ACRP30-like polynucleotides, polypeptides, and antibodies

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
     [0001] This application is a continuation-in-part of International Application No. PCT/US02/32432, filed Oct. 11, 2002, which claims benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 60/328,419, filed Oct. 12, 2001, each of which are hereby incorporated by reference in their entireties. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The present invention relates to novel ACRP30-Like proteins. More specifically, isolated nucleic acid molecules are provided encoding novel ACRP30-Like polypeptides. Novel ACRP30-Like polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human ACRP30-Like polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to these novel ACRP30-Like polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting the production and function of the polypeptides of the present invention.  
       BACKGROUND OF INVENTION  
       [0003] Over the past few decades, an increasing percentage of the population has become diabetic. Diabetes mellitus is categorized into two types: Type I Insulin-Dependent Diabetes Mellitus (IDDM) or Type II Non-Insulin-Dependent Diabetes Mellitus (NIDDM). Type I IDDM is an autoimmune disorder in which the insulin-secreting pancreatic beta cells are destroyed. In these individuals, recombinant insulin therapy is employed to maintain glucose homeostasis and normal energy metabolism. Type II NIDDM, on the other hand, is a polygenic disorder with no one gene responsible for the progression of the disease.  
       [0004] In NIDDM, insulin resistance eventually leads to the abolishment of insulin secretion resulting in insulin deficiency. Insulin resistance, at least in part, ensues from a block at the level of glucose uptake and phosphorylation in humans. Diabetics demonstrate a decrease in expression in adipose tissue of insulin-receptor substrate 1 (“IRS1”), glucose transporter 4 (“GLUT4”), and the novel abundant protein M gene transcript 1 (“apM1”), as well as other as of yet unidentified factors.  
       [0005] Insulin action in adipose and muscle tissues is mediated by the interaction of insulin with its receptor, subsequent phosphorylation events, protein-protein interactions, activation of phosphoinositide-3-kinase, downstream activation of protein kinase B (also known as Akt) and protein kinase C isoforms, and, ultimately, translocation of GLUT4 from a specialized intracellular compartment to the plasma membrane, allowing for glucose uptake. While the mechanism(s) of diabetes have been determined to some extent, all the genetic factors involved need to be elucidated.  
       [0006] Insulin affects fat, muscle, and liver. In fat, glucose is converted to alpha-glycerophosphate which then esterifies the free fatty acids to be used in triglyceride synthesis and storage. In muscle and liver, glucose is phosphorylated and directed for glycogen synthesis and storage. Thus, insulin plays a major role in energy homeostasis.  
       [0007] Insulin promotes GLUT4 translocation and adipocyte complement related protein 30 (“ACRP30”) secretion. ACRP30 or AdipoQ is the mouse ortholog of human apM1 also known as gelatin binding protein 28 kDa (“GBP28”) and adiponectin. lowering elevated levels of plasma free fatty acids. ACRP30 lowers blood glucose levels by enhancing the effect of insulin on hepatic glucose production, and lowers levels of plasma free fatty acids by increasing muscle fatty acid oxidation. Low levels of plasma ACRP30 are associated with, and related to, the degree of insulin resistance and hyperinsulinemia.  
       [0008] ACRP30 is homologous to complement factor Clq, hibernation-specific proteins HP-20, -25 &amp; -27, and cerebellin in its primary sequence. It has an amino-terminal signal sequence, a stretch of amino acids with no known homology, “Gly-X-Y” collagen-like repeats (where X and Y can be any amino acid), and a carboxy-terminal globular domain. The globular domain is similar in crystal structure to Clq and tumor necrosis factor alpha (“TNFα”). ACRP30 is specifically expressed in adipocytes over 100 fold during adipogenesis. TNFα has been implicated in insulin resistance in obesity and NIDDM. Due to their structural similarities, ACRP30 may act as an antagonist to TNFα and ameliorate and/or reverse insulin resistance. ACRP30 may also have immune-related functions in addition to its potential involvement in obesity and diabetes mellitus.  
       [0009] Insulin is the major regulator of energy metabolism. Malfunctioning of any step(s) in insulin secretion and/or action can lead to many disorders, for example the dysregulation of oxygen utilization, adipogenesis, glycogenesis, lipogenesis, glucose uptake, protein synthesis, thermogenesis, and maintenance of the basal metabolic rate. Said malfunctioning is detrimental, and results in diseases and/or disorders that include, but are not limited to, hyperinsulinemia, insulin resistance, insulin deficiency, hyperglycemia, hyperlipidemia, hyperketonemia, and diabetes.  
       [0010] Secondary effects can also be debilitating. They are numerous and include, but are not limited to, obesity, forms of blindness (cataracts and diabetic retinopathy), limb amputations, kidney failure, fatty liver, and coronary artery disease.  
       [0011] Current drugs used to treat insulin resistance and/or diabetes (e.g. insulin secratogogues—sulfonylurea, insulin sensitizers—thiazolidenediones and metformin, and alpha-glucosidase and lipase inhibitors) are inadequate. Accordingly, polynucleotides, polypeptides, and antibodies corresponding to ACRP30 or related homologs have utilities that include, but are not limited to, the prognosis, diagnosis, and/or treatment of insulin resistance and diabetes mellitus Types I and II in lean and obese patients.  
       SUMMARY OF THE INVENTION  
       [0012] The present invention includes isolated nucleic acid molecules comprising, or alternatively, consisting of a polynucleotide sequence disclosed in the sequence listing and/or contained in a human cDNA plasmid described in Table 1 and deposited with the American Type Culture Collection (ATCC). Fragments, variants, and derivatives of these nucleic acid molecules are also encompassed by the invention. The present invention also includes isolated nucleic acid molecules comprising, or alternatively, consisting of, a polynucleotide encoding ACRP30-Like polypeptides. The present invention further includes ACRP30-Like polypeptides encoded by these polynucleotides. Further provided for are amino acid sequences comprising, or alternatively, consisting of, ACRP30-Like polypeptides as disclosed in the sequence listing and/or encoded by the human cDNA plasmids described in Table 1 and deposited with the ATCC. Antibodies that bind these polypeptides are also encompassed by the invention. Polypeptide fragments, variants, and derivatives of these amino acid sequences are also encompassed by the invention, as are polynucleotides encoding these polypeptides and antibodies that bind these polypeptides.  
       DETAILED DESCRIPTION  
       [0013] Tables  
       [0014] Table 1 summarizes ATCC Deposits, Deposit dates, and ATCC designation numbers of deposits made with the ATCC in connection with the present application. Table 1 further summarizes the information pertaining to each “Gene No.” described below, including cDNA plasmid identifier, the type of vector contained in the cDNA plasmid identifier, the nucleotide sequence identifier number, nucleotides contained in the disclosed sequence, the location of the 5′ nucleotide of the start codon of the disclosed sequence, the amino acid sequence identifier number, and the last amino acid of the ORF encoded by the disclosed sequence.  
       [0015] Table 2 indicates public ESTs, of which at least one, two, three, four, five, ten, or more of any one or more of these public EST sequences are optionally excluded from certain embodiments of the invention.  
       [0016] Table 3 summarizes the expression profile of polynucleotides corresponding to the clones disclosed in Table 1. The first column provides a unique clone identifier, “cDNA Plasmid:V”, for a cDNA clone related to each contig sequence disclosed in Table 1. Column 2, “Library Code” shows the expression profile of tissue and/or cell line libraries which express the polynucleotides of the invention. Each Library Code in column 2 represents a tissue/cell source identifier code corresponding to the Library Code and Library description provided in Table 5. Expression of these polynucleotides was not observed in the other tissues and/or cell libraries tested. One of skill in the art could routinely use this information to identify tissues which show a predominant expression pattern of the corresponding polynucleotide of the invention or to identify polynucleotides which show predominant and/or specific tissue expression.  
       [0017] Table 4, column 1, provides a nucleotide sequence identifier, “SEQ ID NO:X,” that matches a nucleotide SEQ ID NO:X disclosed in Table 1, column 5. Table 4, column 2, provides the chromosomal location, “Cytologic Band or Chromosome,” of polynucleotides corresponding to SEQ ID NO:X. Chromosomal location was determined by finding exact matches to EST and cDNA sequences contained in the NCBI (National Center for Biotechnology Information) UniGene database. Given a presumptive chromosomal location, disease locus association was determined by comparison with the Morbid Map, derived from Online Mendelian Inheritance in Man (Online Mendelian Inheritance in Man, OMIM™. McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, Md.) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, Md.) 2000. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/). If the putative chromosomal location of the Query overlapped with the chromosomal location of a Morbid Map entry, the OMIM reference identification number of the morbid map entry is provided in Table 4, column 3, labelled “OMIM ID.” A key to the OMIM reference identification numbers is provided in Table 6.  
       [0018] Table 5, column 1, provides the Library Code disclosed in Table 3, column 2. Column 2 provides a description of the tissue or cell source from which the corresponding library was derived. Library codes corresponding to diseased tissues are indicated in column 3 with the word “disease”. The use of the word “disease” in column 3 is non-limiting. The tissue source of the library may be specific (e.g., a neoplasm), or may be disease-associated (e.g., a tissue sample from a normal portion of a diseased organ). Furthermore, libraries lacking the “disease” designation may still be derived from sources directly or indirectly involved in a disease state or disorder, and therefore may have a further utility in that disease state or disorder.  
       [0019] Table 6 provides a key to the OMIM reference identification numbers disclosed in Table 4, column 3. OMIM reference identification numbers (Column 1) were derived from Online Mendelian Inheritance in Man (Online Mendelian Inheritance in Man, OMIM. McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, Md.) and National Center for Biotechnology Information, National Library of Medicine, (Bethesda, Md.) 2000. World Wide Web URL: http://www.ncbi.nlm.nih.gov/omim/). Column 2 provides diseases associated with the cytologic band disclosed in Table 4, column 2, as determined from the Morbid Map database.  
       [0020] Definitions  
       [0021] The following definitions are provided to facilitate understanding of certain terms used throughout this specification.  
       [0022] In the present invention, “isolated” refers to material removed from its original environment (e.g., the natural environment if it is naturally occurring), and thus is altered “by the hand of man” from its natural state. For example, an isolated polynucleotide could be part of a vector or a composition of matter, or could be contained within a cell, and still be “isolated” because that vector, composition of matter, or particular cell is not the original environment of the polynucleotide. The term “isolated” does not refer to genomic or cDNA libraries, whole cell total or mRNA preparations, genomic DNA preparations (including those separated by electrophoresis and transferred onto blots), sheared whole cell genomic DNA preparations or other compositions where the art demonstrates no distinguishing features of the polynucleotide/sequences of the present invention.  
       [0023] As used herein, a “polynucleotide” refers to a molecule having a nucleic acid sequence contained in SEQ ID NO:X (as described in column 5 of Table 1), or cDNA plasmid:V (as described in column 2 of Table 1 and contained within a pool of plasmids deposited with the ATCC in ATCC Deposit No:Z). For example, the polynucleotide can contain the nucleotide sequence of the full length cDNA sequence, including the 5′ and 3′ untranslated sequences, the coding region, with or without a natural or artificial signal sequence, the protein coding region, as well as fragments, epitopes, domains, and variants of the nucleic acid sequence. Moreover, as used herein, a “polypeptide” refers to a molecule having an amino acid sequence encoded by a polynucleotide of the invention as broadly defined (obviously excluding poly-Phenylalanine or poly-Lysine peptide sequences which result from translation of a polyA tail of a sequence corresponding to a cDNA).  
       [0024] In the present invention, a representative plasmid containing the sequence of SEQ ID NO:X was deposited with the American Type Culture Collection (“ATCC”) and/or described in Table 1. As shown in Table 1, each plasmid is identified by a cDNA Plasmid Identifier and the ATCC Deposit Number (ATCC Deposit No:Z). Plasmids that were pooled and deposited as a single deposit have the same ATCC Deposit Number. The ATCC is located at 10801 University Boulevard, Manassas, Va. 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.  
       [0025] 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, or the complement thereof (e.g., the complement of any one, two, three, four, or more of the polynucleotide fragments described herein) and/or sequences contained in cDNA plasmid:V (e.g., the complement of any one, two, three, four, or more of the polynucleotide fragments described herein). “Stringent hybridization conditions” refers to an overnight incubation at 42 degree C. in a solution comprising 50% formamide, 5×SSC (750 mM NaCl, 75 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5× Denhardt&#39;s solution, 10% dextran sulfate, and 20 μg/ml denatured, sheared salmon sperm DNA, followed by washing the filters in 0.1×SSC at about 65 degree C.  
       [0026] Also included within “polynucleotides” of the present invention are nucleic acid molecules that hybridize to the polynucleotides of the present invention at lower stringency hybridization conditions. Changes in the stringency of hybridization and signal detection are primarily accomplished through the manipulation of formamide concentration (lower percentages of formamide result in lowered stringency); salt conditions, or temperature. For example, lower stringency conditions include an overnight incubation at 37 degree C. in a solution comprising 6×SSPE (20×SSPE=3M NaCl; 0.2M NaH 2 PO 4 ; 0.02M EDTA, pH 7.4), 0.5% SDS, 30% formamide, 100 μg/ml salmon sperm blocking DNA; followed by washes at 50 degree C. with 1×SSPE, 0.1% SDS. In addition, to achieve even lower stringency, washes performed following stringent hybridization can be done at higher salt concentrations (e.g. 5×SSC).  
       [0027] Note that variations in the above conditions may be accomplished through the inclusion and/or substitution of alternate blocking reagents used to suppress background in hybridization experiments. Typical blocking reagents include Denhardt&#39;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.  
       [0028] Of course, a polynucleotide which hybridizes only to polyA+ sequences (such as any 3′ terminal polyA+ tract of a cDNA shown in the sequence listing), or to a complementary stretch of T (or U) residues, would not be included in the definition of “polynucleotide,” since such a polynucleotide would hybridize to any nucleic acid molecule containing a poly (A) stretch or the complement thereof (e.g., practically any double-stranded cDNA clone generated using oligo dT as a primer).  
       [0029] The polynucleotides of the present invention can be composed of any polyribonucleotide or polydeoxribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. For example, polynucleotides can be composed of single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, the polynucleotide can be composed of triple-stranded regions comprising RNA or DNA or both RNA and DNA. A polynucleotide may also contain one or more modified bases or DNA or RNA backbones modified for stability 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.  
       [0030] In specific embodiments, the polynucleotides of the invention are at least 15, at least 30, at least 50, at least 100, at least 125, at least 500, or at least 1000 continuous nucleotides but are less than or equal to 300 kb, 200 kb, 100 kb, 50 kb, 15 kb, 10 kb, 7.5 kb, 5 kb, 2.5 kb, 2.0 kb, or 1 kb, in length. In a further embodiment, polynucleotides of the invention comprise a portion of the coding sequences, as disclosed herein, but do not comprise all or a portion of any intron. In another embodiment, the polynucleotides comprising coding sequences do not contain coding sequences of a genomic flanking gene (i.e., 5′ or 3′ to the gene of interest in the genome). In other embodiments, the polynucleotides of the invention do not contain the coding sequence of more than 1000, 500, 250, 100, 50, 25, 20, 15, 10, 5, 4, 3, 2, or 1 genomic flanking gene(s).  
       [0031] “SEQ ID NO:X” refers to a polynucleotide sequence described in column 5 of Table 1, while “SEQ ID NO:Y” refers to a polypeptide sequence described in column 10 of Table 1. SEQ ID NO:X is identified by an integer specified in column 6 of Table 1. The polypeptide sequence SEQ ID NO:Y is a translated open reading frame (ORF) encoded by polynucleotide SEQ ID NO:X. The polynucleotide sequences are shown in the sequence listing immediately followed by all of the polypeptide sequences. Thus, a polypeptide sequence corresponding to polynucleotide sequence SEQ ID NO:2 is the first polypeptide sequence shown in the sequence listing. The second polypeptide sequence corresponds to the polynucleotide sequence shown as SEQ ID NO:3, and so on.  
       [0032] The polypeptides of the present invention can be composed of amino acids joined to each other by peptide bonds or modified peptide bonds, i.e., peptide isosteres, and may contain amino acids other than the 20 gene-encoded amino acids. The polypeptides may be modified by either natural processes, such as posttranslational processing, or by chemical modification techniques which are well known in the art. Such modifications are well described in basic texts and in more detailed monographs, as well as in a voluminous research literature. Modifications can occur anywhere in a polypeptide, including the peptide backbone, the amino acid side-chains and the amino or carboxyl termini. It will be appreciated that the same type of modification may be present in the same or varying degrees at several sites in a given polypeptide. Also, a given polypeptide may contain many types of modifications. Polypeptides may be branched, for example, as a result of ubiquitination, and they may be cyclic, with or without branching. Cyclic, branched, and branched cyclic polypeptides may result from posttranslation natural processes or may be made by synthetic methods. Modifications include acetylation, 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. (See, for instance, PROTEINS—STRUCTURE AND MOLECULAR PROPERTIES, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, New York (1993); POSTTRANSLATIONAL COVALENT MODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York, pgs. 1-12 (1983); Seifter et al., Meth Enzymol 182:626-646 (1990); Rattan et al., Ann NY Acad Sci 663:48-62 (1992)).  
       [0033] The polypeptides of the invention can be prepared in any suitable manner. Such polypeptides include isolated naturally occurring polypeptides, recombinantly produced polypeptides, synthetically produced polypeptides, or polypeptides produced by a combination of these methods. Means for preparing such polypeptides are well understood in the art.  
       [0034] The polypeptides may be in the form of the secreted protein, including the mature form, or may be a part of a larger protein, such as a fusion protein (see below). It is often advantageous to include an additional amino acid sequence which contains secretory or leader sequences, pro-sequences, sequences which aid in purification, such as multiple histidine residues, or an additional sequence for stability during recombinant production.  
       [0035] The polypeptides of the present invention are preferably provided in an isolated form, and preferably are substantially purified. A recombinantly produced version of a polypeptide, including the secreted polypeptide, can be substantially purified using techniques described herein or otherwise known in the art, such as, for example, by the one-step method described in Smith and Johnson, Gene 67:31-40 (1988). Polypeptides of the invention also can be purified from natural, synthetic or recombinant sources using techniques described herein or otherwise known in the art, such as, for example, antibodies of the invention raised against the polypeptides of the present invention in methods which are well known in the art.  
       [0036] By a polypeptide demonstrating a “functional activity” is meant, a polypeptide capable of displaying one or more known functional activities associated with a full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity, antigenicity [ability to bind (or compete with a polypeptide for binding) to an anti-polypeptide antibody], immunogenicity (ability to generate antibody which binds to a specific polypeptide of the invention), ability to form multimers with polypeptides of the invention, and ability to bind to a receptor or ligand for a polypeptide.  
       [0037] “A polypeptide having functional 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 assay, such as, for example, a 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).  
       [0038] The functional activity of the polypeptides, and fragments, variants derivatives, and analogs thereof, can be assayed by various methods.  
       [0039] For example, in one embodiment where one is assaying for the ability to bind or compete with full-length polypeptide of the present invention for binding to an antibody to the full length polypeptide, various immunoassays known in the art can be used, including but not limited to, competitive and non-competitive assay systems using techniques such as radioimmunoassays, ELISA (enzyme linked immunosorbent assay), “sandwich” immunoassays, immunoradiometric assays, gel diffusion precipitation reactions, immunodiffusion assays, in situ immunoassays (using colloidal gold, enzyme or radioisotope labels, for example), western blots, precipitation reactions, agglutination assays (e.g., gel agglutination assays, hemagglutination assays), complement fixation assays, immunofluorescence assays, protein A assays, and immunoelectrophoresis assays, etc. In one embodiment, antibody binding is detected by detecting a label on the primary antibody. In another embodiment, the primary antibody is detected by detecting binding of a secondary antibody or reagent to the primary antibody. In a further embodiment, the secondary antibody is labeled. Many means are known in the art for detecting binding in an immunoassay and are within the scope of the present invention.  
       [0040] In another embodiment, where a ligand is identified, or the ability of a polypeptide fragment, variant or derivative of the invention to multimerize is being evaluated, binding can be assayed, e.g., by means well-known in the art, such as, for example, reducing and non-reducing gel chromatography, protein affinity chromatography, and affinity blotting. See generally, Phizicky, E., et al., Microbiol. Rev. 59:94-123 (1995). In another embodiment, physiological correlates polypeptide of the present invention binding to its substrates (signal transduction) can be assayed.  
       [0041] In addition, assays described herein (see Examples) and otherwise known in the art may routinely be applied to measure the ability of polypeptides of the present invention and fragments, variants derivatives and analogs thereof to elicit polypeptide related biological activity (either in vitro or in vivo). Other methods will be known to the skilled artisan and are within the scope of the invention.  
       [0042] Polynucleotides and Polypeptides of the Invention  
       [0043] Features of Protein Encoded by Gene No.: 1  
       [0044] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0045] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0046] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 50 as residues: Pro-94 to Lys-102, Phe-130 to Trp-136, Ser-172 to Asn-180, Phe-182 to Phe-189, Pro-191 to Phe-196, and Lys-198 to Glu-228. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0047] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 50 as residues Asp-92 to Leu-229. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0048] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 50 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0049] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0050] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0051] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 50: G-93 to L-229; P-94 to L-229; C-95 to L-229; P-96 to L-229; Q-97 to L-229; D-98 to L-229; E-99 to L-229; K-100 to L-229; L-101 to L-229; K-102 to L-229; D-103 to L-229; A-104 to L-229; F-105 to L-229; S-106 to L-229; H-107 to L-229; V-108 to L-229; V-109 to L-229; E-110 to L-229; N-111 to L-229; T-112 to L-229; A-113 to L-229; F-114 to L-229; F-115 to L-229; G-116 to L-229; D-117 to L-229; V-118 to L-229; V-119 to L-229; L-120 to L-229; R-121 to L-229; F-122 to L-229; P-123 to L-229; R-124 to L-229; I-125 to L-229; V-126 to L-229; H-127 to L-229; Y-128 to L-229; Y-129 to L-229; F-130 to L-229; D-131 to L-229; H-132 to L-229; N-133 to L-229; S-134 to L-229; N-135 to L-229; W-136 to L-229; N-137 to L-229; L-138 to L-229; L-139 to L-229; I-140 to L-229; R-141 to L-229; W-142 to L-229; G-143 to L-229; I-144 to L-229; S-145 to L-229; F-146 to L-229; C-147 to L-229; N-148 to L-229; Q-149 to L-229; T-150 to L-229; G-151 to L-229; V-152 to L-229; F-153 to L-229; N-154 to L-229; Q-155 to L-229; G-156 to L-229; P-157 to L-229; H-158 to L-229; S-159 to L-229; P-160 to L-229; I-161 to L-229; L-162 to L-229; S-163 to L-229; L-164 to L-229; M-165 to L-229; A-166 to L-229; Q-167 to L-229; E-168 to L-229; L-169 to L-229; G-170 to L-229; I-171 to L-229; S-172 to L-229; E-173 to L-229; K-174 to L-229; D-175 to L-229; S-176 to L-229; N-177 to L-229; F-178 to L-229; Q-179 to L-229; N-180 to L-229; P-181 to L-229; F-182 to L-229; K-183 to L-229; I-184 to L-229; D-185 to L-229; R-186 to L-229; T-187 to L-229; E-188 to L-229; F-189 to L-229; I-190 to L-229; P-191 to L-229; S-192 to L-229; T-193 to L-229; D-194 to L-229; P-195 to L-229; F-196 to L-229; Q-197 to L-229; K-198 to L-229; A-199 to L-229; L-200 to L-229; R-201 to L-229; E-202 to L-229; E-203 to L-229; E-204 to L-229; K-205 to L-229; R-206 to L-229; R-207 to L-229; K-208 to L-229; K-209 to L-229; E-210 to L-229; E-211 to L-229; K-212 to L-229; R-213 to L-229; K-214 to L-229; E-215 to L-229; I-216 to L-229; R-217 to L-229; K-218 to L-229; G-219 to L-229; P-220 to L-229; R-221 to L-229; I-222 to L-229; S-223 to L-229; and R-224 to L-229 of SEQ ID NO: 50.  
       [0052] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0053] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 50: D-92 to E-228; D-92 to S-227; D-92 to Q-226; D-92 to S-225; D-92 to R-224; D-92 to S-223; D-92 to I-222; D-92 to R-221; D-92 to P-220; D-92 to G-219; D-92 to K-218; D-92 to R-217; D-92 to I-216; D-92 to E-215; D-92 to K-214; D-92 to R-213; D-92 to K-212; D-92 to E-211; D-92 to E-210; D-92 to K-209; D-92 to K-208; D-92 to R-207; D-92 to R-206; D-92 to K-205; D-92 to E-204; D-92 to E-203; D-92 to E-202; D-92 to R-201; D-92 to L-200; D-92 to A-199; D-92 to K-198; D-92 to Q-197; D-92 to F-196; D-92 to P-195; D-92 to D-194; D-92 to T-193; D-92 to S-192; D-92 to P-191; D-92 to I-190; D-92 to F-189; D-92 to E-188; D-92 to T-187; D-92 to R-186; D-92 to D-185; D-92 to I-184; D-92 to K-183; D-92 to F-182; D-92 to P-181; D-92 to N-180; D-92 to Q-179; D-92 to F-178; D-92 to N-177; D-92 to S-176; D-92 to D-175; D-92 to K-174; D-92 to E-173; D-92 to S-172; D-92 to I-171; D-92 to G-170; D-92 to L-169; D-92 to E-168; D-92 to Q-167; D-92 to A-166; D-92 to M-165; D-92 to L-164; D-92 to S-163; D-92 to L-162; D-92 to I-161; D-92 to P-160; D-92 to S-159; D-92 to H-158; D-92 to P-157; D-92 to G-156; D-92 to Q-155; D-92 to N-154; D-92 to F-153; D-92 to V-152; D-92 to G-151; D-92 to T-150; D-92 to Q-149; D-92 to N-148; D-92 to C-147; D-92 to F-146; D-92 to S-145; D-92 to I-144; D-92 to G-143; D-92 to W-142; D-92 to R-141; D-92 to I-140; D-92 to L-139; D-92 to L-138; D-92 to N-137; D-92 to W-136; D-92 to N-135; D-92 to S-134; D-92 to N-133; D-92 to H-132; D-92 to D-131; D-92 to F-130; D-92 to Y-129; D-92 to Y-128; D-92 to H-127; D-92 to V-126; D-92 to I-125; D-92 to R-124; D-92 to P-123; D-92 to F-122; D-92 to R-121; D-92 to L-120; D-92 to V-119; D-92 to V-118; D-92 to D-117; D-92 to G-116; D-92 to F-115; D-92 to F-114; D-92 to A-113; D-92 to T-112; D-92 to N-111; D-92 to E-110; D-92 to V-109; D-92 to V-108; D-92 to H-107; D-92 to S-106; D-92 to F-105; D-92 to A-104; D-92 to D-103; D-92 to K-102; D-92 to L-101; D-92 to K-100; D-92 to E-99; and D-92 to D-98 of SEQ ID NO: 50.  
       [0054] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0055] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 50, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0056] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0057] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-844, where this portion excludes any integer of amino acid residues from 1 to about 223 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-844, or any integer of amino acid residues from 1 to about 223 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-844. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0058] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0059] Translation products of this gene stimulate glucose transport in adipocytes.  
       [0060] It has been discovered that this gene is strongly expressed in muscle tissue, and to a lesser extent in neutrophils and lung tissue.  
       [0061] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, and immunological disorders.  
       [0062] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., muscle, adipose, immune, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0063] The expression of this gene in muscle tissue and structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0064] In addition, expression of this gene in neutrophils and lung tissue and the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0065] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0066] Features for Protein Encoded by Gene No.: 2  
       [0067] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329840), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543, AAB06706, and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0068] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0069] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 51 as residues: Phe-30 to Cys-37, Arg-91 to Gly-98, Pro-170 to Ala-177, Pro-183 to Gly-193, Pro-206 to Gly-235, Pro-243 to Pro-260, Phe-283 to Gly-311. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0070] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 51 as residues Arg-246 to Pro-421. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0071] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 51 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0072] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0073] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0074] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 51: G-247 to P-421; P-248 to P-421; P-249 to P-421; G-250 to P-421; P-251 to P-421; P-252 to P-421; G-253 to P-421; P-254 to P-421; P-255 to P-421; G-256 to P-421; P-257 to P-421; P-258 to P-421; G-259 to P-421; P-260 to P-421; P-261 to P-421; A-262 to P-421; P-263 to P-421; V-264 to P-421; G-265 to P-421; P-266 to P-421; P-267 to P-421; H-268 to P-421; A-269 to P-421; R-270 to P-421; I-271 to P-421; S-272 to P-421; Q-273 to P-421; H-274 to P-421; G-275 to P-421; D-276 to P-421; P-277 to P-421; L-278 to P-421; L-279 to P-421; S-280 to P-421; N-281 to P-421; T-282 to P-421; F-283 to P-421; T-284 to P-421; E-285 to P-421; T-286 to P-421; N-287 to P-421; N-288 to P-421; H-289 to P-421; W-290 to P-421; P-291 to P-421; Q-292 to P-421; G-293 to P-421; P-294 to P-421; T-295 to P-421; G-296 to P-421; P-297 to P-421; P-298 to P-421; G-299 to P-421; P-300 to P-421; P-301 to P-421; G-302 to P-421; P-303 to P-421; M-304 to P-421; G-305 to P-421; P-306 to P-421; P-307 to P-421; G-308 to P-421; P-309 to P-421; P-310 to P-421; G-311 to P-421; P-312 to P-421; T-313 to P-421; G-314 to P-421; V-315 to P-421; P-316 to P-421; G-317 to P-421; S-318 to P-421; P-319 to P-421; G-320 to P-421; H-321 to P-421; I-322 to P-421; G-323 to P-421; P-324 to P-421; P-325 to P-421; G-326 to P-421; P-327 to P-421; T-328 to P-421; G-329 to P-421; P-330 to P-421; K-331 to P-421; G-332 to P-421; I-333 to P-421; S-334 to P-421; G-335 to P-421; H-336 to P-421; P-337 to P-421; G-338 to P-421; E-339 to P-421; K-340 to P-421; G-341 to P-421; E-342 to P-421; R-343 to P-421; G-344 to P-421; L-345 to P-421; R-346 to P-421; G-347 to P-421; E-348 to P-421; P-349 to P-421; G-350 to P-421; P-351 to P-421; Q-352 to P-421; G-353 to P-421; S-354 to P-421; A-355 to P-421; G-356 to P-421; Q-357 to P-421; R-358 to P-421; G-359 to P-421; E-360 to P-421; P-361 to P-421; G-362 to P-421; P-363 to P-421; K-364 to P-421; G-365 to P-421; D-366 to P-421; P-367 to P-421; G-368 to P-421; E-369 to P-421; K-370 to P-421; S-371 to P-421; H-372 to P-421; W-373 to P-421; N-374 to P-421; Q-375 to P-421; S-376 to P-421; W-377 to P-421; G-378 to P-421; L-379 to P-421; G-380 to P-421; R-381 to P-421; A-382 to P-421; L-383 to P-421; P-384 to P-421; A-385 to P-421; Q-386 to P-421; A-387 to P-421; P-388 to P-421; P-389 to P-421; A-390 to P-421; S-391 to P-421; F-392 to P-421; G-393 to P-421; A-394 to P-421; R-395 to P-421; G-396 to P-421; A-397 to P-421; D-398 to P-421; M-399 to P-421; Q-400 to P-421; P-401 to P-421; T-402 to P-421; T-403 to P-421; G-404 to P-421; S-405 to P-421; W-406 to P-421; P-407 to P-421; P-408 to P-421; G-409 to P-421; A-410 to P-421; G-411 to P-421; T-412 to P-421; R-413 to P-421; E-414 to P-421; A-415 to P-421; and E-416 to P-421 of SEQ ID NO: 51.  
       [0075] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0076] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 51: R-246 to G-420; R-246 to G-419; R-246 to G-418; R-246 to G-417; R-246 to E-416; R-246 to A-415; R-246 to E-414; R-246 to R-413; R-246 to T-412; R-246 to G-411; R-246 to A-410; R-246 to G-409; R-246 to P-408; R-246 to P-407; R-246 to W-406; R-246 to S-405; R-246 to G-404; R-246 to T-403; R-246 to T-402; R-246 to P-401; R-246 to Q-400; R-246 to M-399; R-246 to D-398; R-246 to A-397; R-246 to G-396; R-246 to R-395; R-246 to A-394; R-246 to G-393; R-246 to F-392; R-246 to S-391; R-246 to A-390; R-246 to P-389; R-246 to P-388; R-246 to A-387; R-246 to Q-386; R-246 to A-385; R-246 to P-384; R-246 to L-383; R-246 to A-382; R-246 to R-381; R-246 to G-380; R-246 to L-379; R-246 to G-378; R-246 to W-377; R-246 to S-376; R-246 to Q-375; R-246 to N-374; R-246 to W-373; R-246 to H-372; R-246 to S-371; R-246 to K-370; R-246 to E-369; R-246 to G-368; R-246 to P-367; R-246 to D-366; R-246 to G-365; R-246 to K-364; R-246 to P-363; R-246 to G-362; R-246 to P-361; R-246 to E-360; R-246 to G-359; R-246 to R-358; R-246 to Q-357; R-246 to G-356; R-246 to A-355; R-246 to S-354; R-246 to G-353; R-246 to Q-352; R-246 to P-351; R-246 to G-350; R-246 to P-349; R-246 to E-348; R-246 to G-347; R-246 to R-346; R-246 to L-345; R-246 to G-344; R-246 to R-343; R-246 to E-342; R-246 to G-341; R-246 to K-340; R-246 to E-339; R-246 to G-338; R-246 to P-337; R-246 to H-336; R-246 to G-335; R-246 to S-334; R-246 to I-333; R-246 to G-332; R-246 to K-331; R-246 to P-330; R-246 to G-329; R-246 to T-328; R-246 to P-327; R-246 to G-326; R-246 to P-325; R-246 to P-324; R-246 to G-323; R-246 to I-322; R-246 to H-321; R-246 to G-320; R-246 to P-319; R-246 to S-318; R-246 to G-317; R-246 to P-316; R-246 to V-315; R-246 to G-314; R-246 to T-313; R-246 to P-312; R-246 to G-311; R-246 to P-310; R-246 to P-309; R-246 to G-308; R-246 to P-307; R-246 to P-306; R-246 to G-305; R-246 to M-304; R-246 to P-303; R-246 to G-302; R-246 to P-301; R-246 to P-300; R-246 to G-299; R-246 to P-298; R-246 to P-297; R-246 to G-296; R-246 to T-295; R-246 to P-294; R-246 to G-293; R-246 to Q-292; R-246 to P-291; R-246 to W-290; R-246 to H-289; R-246 to N-288; R-246 to N-287; R-246 to T-286; R-246 to E-285; R-246 to T-284; R-246 to F-283; R-246 to T-282; R-246 to N-281; R-246 to S-280; R-246 to L-279; R-246 to L-278; R-246 to P-277; R-246 to D-276; R-246 to G-275; R-246 to H-274; R-246 to Q-273; R-246 to S-272; R-246 to I-271; R-246 to R-270; R-246 to A-269; R-246 to H-268; R-246 to P-267; R-246 to P-266; R-246 to G-265; R-246 to V-264; R-246 to P-263; R-246 to A-262; R-246 to P-261; R-246 to P-260; R-246 to G-259; R-246 to P-258; R-246 to P-257; R-246 to G-256; R-246 to P-255; R-246 to P-254; R-246 to G-253; and R-246 to P-252 of SEQ ID NO: 51.  
       [0077] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0078] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m-n of SEQ ID NO: 51, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0079] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-623, where this portion excludes any integer of amino acid residues from 1 to about 415 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-623, or any integer of amino acid residues from 1 to about 415 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-623. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0080] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0081] It has been discovered that this gene is expressed in the small and large intestine, stomach, lung, and prostate.  
       [0082] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism; obesity; and inflammation, including inflammatory disorders of the gastrointestinal tract and lungs.  
       [0083] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, gastrointestinal, and respiratory systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, gastrointestinal, pulmonary, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0084] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0085] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0086] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0087] Features for Protein Encoded by Gene No.: 3  
       [0088] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329840), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543, AAB06706, and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0089] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0090] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 52 as residues: Ser-11 to His-22, Ser-34 to Phe-40, Ala-66 to Phe-71, Leu-96 to Lys-104. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0091] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 52 as residues Leu-79 to Thr-240. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0092] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 52 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0093] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0094] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0095] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 52: P-80 to T-240; Q-81 to T-240; G-82 to T-240; A-83 to T-240; G-84 to T-240; L-85 to T-240; R-86 to T-240; L-87 to T-240; V-88 to T-240; G-89 to T-240; E-90 to T-240; A-91 to T-240; F-92 to T-240; H-93 to T-240; C-94 to T-240; R-95 to T-240; L-96 to T-240; Q-97 to T-240; G-98 to T-240; P-99 to T-240; R-100 to T-240; R-101 to T-240; V-102 to T-240; D-103 to T-240; K-104 to T-240; R-105 to T-240; T-106 to T-240; L-107 to T-240; V-108 to T-240; E-109 to T-240; L-110 to T-240; H-111 to T-240; G-112 to T-240; F-113 to T-240; Q-114 to T-240; A-115 to T-240; P-116 to T-240; A-117 to T-240; A-118 to T-240; Q-119 to T-240; G-120 to T-240; A-121 to T-240; F-122 to T-240; L-123 to T-240; R-124 to T-240; G-125 to T-240; S-126 to T-240; G-127 to T-240; L-128 to T-240; S-129 to T-240; L-130 to T-240; A-131 to T-240; S-132 to T-240; G-133 to T-240; R-134 to T-240; F-135 to T-240; T-136 to T-240; A-137 to T-240; P-138 to T-240; V-139 to T-240; S-140 to T-240; G-141 to T-240; I-142 to T-240; F-143 to T-240; Q-144 to T-240; F-145 to T-240; S-146 to T-240; A-147 to T-240; S-148 to T-240; L-149 to T-240; H-150 to T-240; V-151 to T-240; D-152 to T-240; H-153 to T-240; S-154 to T-240; E-155 to T-240; L-156 to T-240; Q-157 to T-240; G-158 to T-240; K-159 to T-240; A-160 to T-240; R-161 to T-240; L-162 to T-240; R-163 to T-240; A-164 to T-240; R-165 to T-240; D-166 to T-240; V-167 to T-240; V-168 to T-240; C-169 to T-240; V-170 to T-240; L-171 to T-240; I-172 to T-240; C-173 to T-240; I-174 to T-240; E-175 to T-240; S-176 to T-240; L-177 to T-240; C-178 to T-240; Q-179 to T-240; R-180 to T-240; H-181 to T-240; T-182 to T-240; C-183 to T-240; L-184 to T-240; E-185 to T-240; A-186 to T-240; V-187 to T-240; S-188 to T-240; G-189 to T-240; L-190 to T-240; E-191 to T-240; S-192 to T-240; N-193 to T-240; S-194 to T-240; R-195 to T-240; V-196 to T-240; F-197 to T-240; T-198 to T-240; L-199 to T-240; Q-200 to T-240; V-201 to T-240; Q-202 to T-240; G-203 to T-240; L-204 to T-240; L-205 to T-240; Q-206 to T-240; L-207 to T-240; Q-208 to T-240; A-209 to T-240; G-210 to T-240; Q-211 to T-240; Y-212 to T-240; A-213 to T-240; S-214 to T-240; V-215 to T-240; F-216 to T-240; V-217 to T-240; D-218 to T-240; N-219 to T-240; G-220 to T-240; S-221 to T-240; G-222 to T-240; A-223 to T-240; V-224 to T-240; L-225 to T-240; T-226 to T-240; I-227 to T-240; Q-228 to T-240; A-229 to T-240; G-230 to T-240; S-231 to T-240; S-232 to T-240; F-233 to T-240; S-234 to T-240; and G-235 to T-240 of SEQ ID NO: 52.  
       [0096] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0097] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 52: L-79 to G-239; L-79 to L-238; L-79 to L-237; L-79 to L-236; L-79 to G-235; L-79 to S-234; L-79 to F-233; L-79 to S-232; L-79 to S-231; L-79 to G-230; L-79 to A-229; L-79 to Q-228; L-79 to I-227; L-79 to T-226; L-79 to L-225; L-79 to V-224; L-79 to A-223; L-79 to G-222; L-79 to S-221; L-79 to G-220; L-79 to N-219; L-79 to D-218; L-79 to V-217; L-79 to F-216; L-79 to V-215; L-79 to S-214; L-79 to A-213; L-79 to Y-212; L-79 to Q-211; L-79 to G-210; L-79 to A-209; L-79 to Q-208; L-79 to L-207; L-79 to Q-206; L-79 to L-205; L-79 to L-204; L-79 to G-203; L-79 to Q-202; L-79 to V-201; L-79 to Q-200; L-79 to L-199; L-79 to T-198; L-79 to F-197; L-79 to V-196; L-79 to R-195; L-79 to S-194; L-79 to N-193; L-79 to S-192; L-79 to E-191; L-79 to L-190; L-79 to G-189; L-79 to S-188; L-79 to V-187; L-79 to A-186; L-79 to E-185; L-79 to L-184; L-79 to C-183; L-79 to T-182; L-79 to H-181; L-79 to R-180; L-79 to Q-179; L-79 to C-178; L-79 to L-177; L-79 to S-176; L-79 to E-175; L-79 to I-174; L-79 to C-173; L-79 to I-172; L-79 to L-171; L-79 to V-170; L-79 to C-169; L-79 to V-168; L-79 to V-167; L-79 to D-166; L-79 to R-165; L-79 to A-164; L-79 to R-163; L-79 to L-162; L-79 to R-161; L-79 to A-160; L-79 to K-159; L-79 to G-158; L-79 to Q-157; L-79 to L-156; L-79 to E-155; L-79 to S-154; L-79 to H-153; L-79 to D-152; L-79 to V-151; L-79 to H-150; L-79 to L-149; L-79 to S-148; L-79 to A-147; L-79 to S-146; L-79 to F-145; L-79 to Q-144; L-79 to F-143; L-79 to I-142; L-79 to G-141; L-79 to S-140; L-79 to V-139; L-79 to P-138; L-79 to A-137; L-79 to T-136; L-79 to F-135; L-79 to R-134; L-79 to G-133; L-79 to S-132; L-79 to A-131; L-79 to L-130; L-79 to S-129; L-79 to L-128; L-79 to G-127; L-79 to S-126; L-79 to G-125; L-79 to R-124; L-79 to L-123; L-79 to F-122; L-79 to A-121; L-79 to G-120; L-79 to Q-119; L-79 to A-118; L-79 to A-117; L-79 to P-116; L-79 to A-115; L-79 to Q-114; L-79 to F-113; L-79 to G-112; L-79 to H-111; L-79 to L-I 10; L-79 to E-109; L-79 to V-108; L-79 to L-107; L-79 to T-106; L-79 to R-105; L-79 to K-104; L-79 to D-103; L-79 to V-102; L-79 to R-101; L-79 to R-100; L-79 to P-99; L-79 to G-98; L-79 to Q-97; L-79 to L-96; L-79 to R-95; L-79 to C-94; L-79 to H-93; L-79 to F-92; L-79 to A-91; L-79 to E-90; L-79 to G-89; L-79 to V-88; L-79 to L-87; L-79 to R-86; and L-79 to L-85 of SEQ ID NO: 52.  
       [0098] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0099] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 52, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0100] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0101] It has been discovered that this gene is expressed in kidney, as well as cancer tissues.  
       [0102] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, obesity, as well as kidney disorders.  
       [0103] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and renal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, renal, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0104] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0105] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0106] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0107] Features for Protein Encoded by Gene No.: 4  
       [0108] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329840), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543, AAB06706, and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0109] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0110] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 53 as residues: Gln-31 to Gly-67, Cys-77 to Ser-82, Gly-99 to Gly-117, Ala-121 to Gly-132, Pro-137 to Ser-143, Gly-151 to Tyr-162. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0111] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 53 as residues Met-134 to Pro-281. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0112] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 53 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0113] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to a polypeptide of the invention), and ability to form multimers with polypeptides of the invention.  
       [0114] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0115] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 53: G-135 to P-281; A-136 to P-281; P-137 to P-281; G-138 to P-281; E-139 to P-281; R-140 to P-281; C-141 to P-281; K-142 to P-281; S-143 to P-281; H-144 to P-281; Y-145 to P-281; A-146 to P-281; A-147 to P-281; F-148 to P-281; S-149 to P-281; V-150 to P-281; G-151 to P-281; R-152 to P-281; K-153 to P-281; K-154 to P-281; P-155 to P-281; M-156 to P-281; H-157 to P-281; S-158 to P-281; N-159 to P-281; H-160 to P-281; Y-161 to P-281; Y-162 to P-281; Q-163 to P-281; T-164 to P-281; V-165 to P-281; I-166 to P-281; F-167 to P-281; D-168 to P-281; T-169 to P-281; E-170 to P-281; F-171 to P-281; V-172 to P-281; N-173 to P-281; L-174 to P-281; Y-175 to P-281; D-176 to P-281; H-177 to P-281; F-178 to P-281; N-179 to P-281; M-180 to P-281; F-181 to P-281; T-182 to P-281; G-183 to P-281; K-184 to P-281; F-185 to P-281; Y-186 to P-281; C-187 to P-281; Y-188 to P-281; V-189 to P-281; P-190 to P-281; G-191 to P-281; L-192 to P-281; Y-193 to P-281; F-194 to P-281; F-195 to P-281; S-196 to P-281; L-197 to P-281; N-198 to P-281; V-199 to P-281; H-200 to P-281; T-201 to P-281; W-202 to P-281; N-203 to P-281; Q-204 to P-281; K-205 to P-281; E-206 to P-281; T-207 to P-281; Y-208 to P-281; L-209 to P-281; H-210 to P-281; I-211 to P-281; M-212 to P-281; K-213 to P-281; N-214 to P-281; E-215 to P-281; E-216 to P-281; E-217 to P-281; V-218 to P-281; A-219 to P-281; I-220 to P-281; L-221 to P-281; F-222 to P-281; A-223 to P-281; Q-224 to P-281; V-225 to P-281; G-226 to P-281; D-227 to P-281; R-228 to P-281; S-229 to P-281; I-230 to P-281; M-231 to P-281; Q-232 to P-281; S-233 to P-281; Q-234 to P-281; S-235 to P-281; L-236 to P-281; M-237 to P-281; L-238 to P-281; E-239 to P-281; L-240 to P-281; R-241 to P-281; E-242 to P-281; Q-243 to P-281; D-244 to P-281; Q-245 to P-281; V-246 to P-281; W-247 to P-281; V-248 to P-281; R-249 to P-281; L-250 to P-281; Y-251 to P-281; K-252 to P-281; G-253 to P-281; E-254 to P-281; R-255 to P-281; E-256 to P-281; N-257 to P-281; A-258 to P-281; I-259 to P-281; F-260 to P-281; S-261 to P-281; E-262 to P-281; E-263 to P-281; L-264 to P-281; D-265 to P-281; T-266 to P-281; Y-267 to P-281; I-268 to P-281; T-269 to P-281; F-270 to P-281; S-271 to P-281; G-272 to P-281; Y-273 to P-281; L-274 to P-281; V-275 to P-281; K-276 to P-281; of SEQ ID NO: 53.  
       [0116] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0117] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 53: M-134 to E-280; M-134 to T-279; M-134 to A-278; M-134 to H-277; M-134 to K-276; M-134 to V-275; M-134 to L-274; M-134 to Y-273; M-134 to G-272; M-134 to S-271; M-134 to F-270; M-134 to T-269; M-134 to I-268; M-134 to Y-267; M-134 to T-266; M-134 to D-265; M-134 to L-264; M-134 to E-263; M-134 to E-262; M-134 to S-261; M-134 to F-260; M-134 to I-259; M-134 to A-258; M-134 to N-257; M-134 to E-256; M-134 to R-255; M-134 to E-254; M-134 to G-253; M-134 to K-252; M-134 to Y-251; M-134 to L-250; M-134 to R-249; M-134 to V-248; M-134 to W-247; M-134 to V-246; M-134 to Q-245; M-134 to D-244; M-134 to Q-243; M-134 to E-242; M-134 to R-241; M-134 to L-240; M-134 to E-239; M-134 to L-238; M-134 to M-237; M-134 to L-236; M-134 to S-235; M-134 to Q-234; M-134 to S-233; M-134 to Q-232; M-134 to M-231; M-134 to I-230; M-134 to S-229; M-134 to R-228; M-134 to D-227; M-134 to G-226; M-134 to V-225; M-134 to Q-224; M-134 to A-223; M-134 to F-222; M-134 to L-221; M-134 to I-220; M-134 to A-219; M-134 to V-218; M-134 to E-217; M-134 to E-216; M-134 to E-215; M-134 to N-214; M-134 to K-213; M-134 to M-212; M-134 to I-211; M-134 to H-210; M-134 to L-209; M-134 to Y-208; M-134 to T-207; M-134 to E-206; M-134 to K-205; M-134 to Q-204; M-134 to N-203; M-134 to W-202; M-134 to T-201; M-134 to H-200; M-134 to V-199; M-134 to N-198; M-134 to L-197; M-134 to S-196; M-134 to F-195; M-134 to F-194; M-134 to Y-193; M-134 to L-192; M-134 to G-191; M-134 to P-190; M-134 to V-189; M-134 to Y-188; M-134 to C-187; M-134 to Y-186; M-134 to F-185; M-134 to K-184; M-134 to G-183; M-134 to T-182; M-134 to F-181; M-134 to M-180; M-134 to N-179; M-134 to F-178; M-134 to H-177; M-134 to D-176; M-134 to Y-175; M-134 to L-174; M-134 to N-173; M-134 to V-172; M-134 to F-171; M-134 to E-170; M-134 to T-169; M-134 to D-168; M-134 to F-167; M-134 to I-166; M-134 to V-165; M-134 to T-164; M-134 to Q-163; M-134 to Y-162; M-134 to Y-161; M-134 to H-160; M-134 to N-159; M-134 to S-158; M-134 to H-157; M-134 to M-156; M-134 to P-155; M-134 to K-154; M-134 to K-153; M-134 to R-152; M-134 to G-151; M-134 to V-150; M-134 to S-149; M-134 to F-148; M-134 to A-147; M-134 to A-146; M-134 to Y-145; M-134 to H-144; M-134 to S-143; M-134 to K-142; M-134 to C-141; and M-134 to R-140 of SEQ ID NO: 53.  
       [0118] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0119] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 53, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0120] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-536, where this portion excludes any integer of amino acid residues from 1 to about 275 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-536, or any integer of amino acid residues from 1 to about 275 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-536. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0121] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0122] It has been discovered that this gene is expressed in adult and fetal heart, pancreas, liver, and human cerebellum.  
       [0123] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, obesity, as well as cardiovascular, immunological and neurological disorders.  
       [0124] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, cardiovascular, immune, and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, vascular, immune, neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0125] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0126] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0127] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0128] Features of Protein Encoded by Gene No.: 5  
       [0129] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including precerebellin (see, e.g., Swiss-Prot Accession Q9JHG0), which is involved in neural functions such as the control of food intake and catecholamine release, and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0130] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0131] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 54 as residues Gly-60 to Leu-205. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0132] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 54 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0133] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0134] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0135] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 54: G-61 to L-205; A-62 to L-205; A-63 to L-205; L-64 to L-205; G-65 to L-205; E-66 to L-205; A-67 to L-205; P-68 to L-205; P-69 to L-205; G-70 to L-205; R-71 to L-205; V-72 to L-205; A-73 to L-205; F-74 to L-205; A-75 to L-205; A-76 to L-205; V-77 to L-205; R-78 to L-205; S-79 to L-205; H-80 to L-205; H-81 to L-205; H-82 to L-205; E-83 to L-205; P-84 to L-205; A-85 to L-205; G-86 to L-205; E-87 to L-205; T-88 to L-205; G-89 to L-205; N-90 to L-205; G-91 to L-205; T-92 to L-205; S-93 to L-205; G-94 to L-205; A-95 to L-205; I-96 to L-205; Y-97 to L-205; F-98 to L-205; D-99 to L-205; Q-100 to L-205; V-101 to L-205; L-102 to L-205; V-103 to L-205; N-104 to L-205; E-105 to L-205; G-106 to L-205; G-107 to L-205; G-108 to L-205; F-109 to L-205; D-110 to L-205; R-111 to L-205; A-112 to L-205; S-113 to L-205; G-114 to L-205; S-115 to L-205; F-116 to L-205; V-117 to L-205; A-118 to L-205; P-119 to L-205; V-120 to L-205; R-121 to L-205; G-122 to L-205; V-123 to L-205; Y-124 to L-205; S-125 to L-205; F-126 to L-205; R-127 to L-205; F-128 to L-205; H-129 to L-205; V-130 to L-205; V-131 to L-205; K-132 to L-205; V-133 to L-205; Y-134 to L-205; N-135 to L-205; R-136 to L-205; Q-137 to L-205; T-138 to L-205; V-139 to L-205; Q-140 to L-205; V-141 to L-205; S-142 to L-205; L-143 to L-205; M-144 to L-205; L-145 to L-205; N-146 to L-205; T-147 to L-205; W-148 to L-205; P-149 to L-205; V-150 to L-205; I-151 to L-205; S-152 to L-205; A-153 to L-205; F-154 to L-205; A-155 to L-205; N-156 to L-205; D-157 to L-205; P-158 to L-205; D-159 to L-205; V-160 to L-205; T-161 to L-205; R-162 to L-205; E-163 to L-205; A-164 to L-205; A-165 to L-205; T-166 to L-205; S-167 to L-205; S-168 to L-205; V-169 to L-205; L-170 to L-205; L-171 to L-205; P-172 to L-205; L-173 to L-205; D-174 to L-205; P-175 to L-205; G-176 to L-205; D-177 to L-205; R-178 to L-205; V-179 to L-205; S-180 to L-205; L-181 to L-205; R-182 to L-205; L-183 to L-205; R-184 to L-205; R-185 to L-205; G-186 to L-205; N-187 to L-205; L-188 to L-205; L-189 to L-205; G-190 to L-205; G-191 to L-205; W-192 to L-205; K-193 to L-205; Y-194 to L-205; S-195 to L-205; S-196 to L-205; F-197 to L-205; S-198 to L-205; G-199 to L-205; and F-200 to L-205 of SEQ ID NO: 54.  
       [0136] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0137] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 54: G-60 to P-204; G-60 to F-203; G-60 to I-202; G-60 to L-201; G-60 to F-200; G-60 to G-199; G-60 to S-198; G-60 to F-197; G-60 to S-196; G-60 to S-195; G-60 to Y-194; G-60 to K-193; G-60 to W-192; G-60 to G-191; G-60 to G-190; G-60 to L-189; G-60 to L-188; G-60 to N-187; G-60 to G-186; G-60 to R-185; G-60 to R-184; G-60 to L-183; G-60 to R-182; G-60 to L-181; G-60 to S-180; G-60 to V-179; G-60 to R-178; G-60 to D-177; G-60 to G-176; G-60 to P-175; G-60 to D-174; G-60 to L-173; G-60 to P-172; G-60 to L-171; G-60 to L-170; G-60 to V-169; G-60 to S-168; G-60 to S-167; G-60 to T-166; G-60 to A-165; G-60 to A-164; G-60 to E-163; G-60 to R-162; G-60 to T-161; G-60 to V-160; G-60 to D-159; G-60 to P-158; G-60 to D-157; G-60 to N-156; G-60 to A-155; G-60 to F-154; G-60 to A-153; G-60 to S-152; G-60 to I-151; G-60 to V-150; G-60 to P-149; G-60 to W-148; G-60 to T-147; G-60 to N-146; G-60 to L-145; G-60 to M-144; G-60 to L-143; G-60 to S-142; G-60 to V-141; G-60 to Q-140; G-60 to V-139; G-60 to T-138; G-60 to Q-137; G-60 to R-136; G-60 to N-135; G-60 to Y-134; G-60 to V-133; G-60 to K-132; G-60 to V-131; G-60 to V-130; G-60 to H-129; G-60 to F-128; G-60 to R-127; G-60 to F-126; G-60 to S-125; G-60 to Y-124; G-60 to V-123; G-60 to G-122; G-60 to R-121; G-60 to V-120; G-60 to P-119; G-60 to A-118; G-60 to V-117; G-60 to F-116; G-60 to S-115; G-60 to G-114; G-60 to S-113; G-60 to A-112; G-60 to R-111; G-60 to D-110; G-60 to F-109; G-60 to G-108; G-60 to G-107; G-60 to G-106; G-60 to E-105; G-60 to N-104; G-60 to V-103; G-60 to L-102; G-60 to V-101; G-60 to Q-100; G-60 to D-99; G-60 to F-98; G-60 to Y-97; G-60 to I-96; G-60 to A-95; G-60 to G-94; G-60 to S-93; G-60 to T-92; G-60 to G-91; G-60 to N-90; G-60 to G-89; G-60 to T-88; G-60 to E-87; G-60 to G-86; G-60 to A-85; G-60 to P-84; G-60 to E-83; G-60 to H-82; G-60 to H-81; G-60 to H-80; G-60 to S-79; G-60 to R-78; G-60 to V-77; G-60 to A-76; G-60 to A-75; G-60 to F-74; G-60 to A-73; G-60 to V-72; G-60 to R-71; G-60 to G-70; G-60 to P-69; G-60 to P-68; G-60 to A-67; and G-60 to E-66 of SEQ ID NO: 54.  
       [0138] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0139] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 54, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0140] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0141] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, where this portion excludes any integer of amino acid residues from 1 to about 199 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, or any integer of amino acid residues from 1 to about 199 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-3696. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0142] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0143] It has been discovered that this gene is expressed in heart tissue, as well as human cerebellum, infant brain, fetal lung and spleen.  
       [0144] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, as well as cardiovascular, immunological and neurological disorders.  
       [0145] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, cardiovascular, immune, and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, cardiovascular, immune, neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0146] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0147] The expression of this gene in heart tissue, and the similarity of this gene to other members of the Clq family of proteins, suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of cardiovascular disorders (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below).  
       [0148] In addition, expression of this gene in lung and spleen tissue, and the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0149] More generally, the expression of this gene in human cerebellum and infant brain and homology to precerebellin (Swiss-Prot Accession Q9JHG0) indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of neurological disorders, such as those described herein under “Neural Activity and Neurological Diseases”.  
       [0150] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0151] Features of Protein Encoded by Gene No.: 6  
       [0152] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a cerebellin-like glycoprotein (see, e.g. Genbank Accession No. A60032), which is involved in neural functions such as the control of food intake and catecholamine release; and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0153] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0154] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 55 as residues Leu-47 to Leu-189. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0155] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 55 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0156] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0157] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0158] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 55: G-48 to L-189; I-49 to L-189; S-50 to L-189; V-51 to L-189; R-52 to L-189; S-53 to L-189; G-54 to L-189; S-55 to L-189; A-56 to L-189; K-57 to L-189; V-58 to L-189; A-59 to L-189; F-60 to L-189; S-61 to L-189; A-62 to L-189; T-63 to L-189; R-64 to L-189; S-65 to L-189; T-66 to L-189; N-67 to L-189; H-68 to L-189; E-69 to L-189; P-70 to L-189; S-71 to L-189; E-72 to L-189; M-73 to L-189; S-74 to L-189; N-75 to L-189; R-76 to L-189; T-77 to L-189; M-78 to L-189; T-79 to L-189; L-86 L-189; Y-81 to L-189; F-82 to L-189; D-83 to L-189; Q-84 to L-189; V-85 to L-189; L-86 to L-189; V-87 to L-189; N-88 to L-189; I-89 to L-189; G-90 to L-189; N-91 to L-189; H-92 to L-189; F-93 to L-189; D-94 to L-189; L-95 to L-189; A-96 to L-189; S-97 to L-189; S-98 to L-189; I-99 to L-189; F-100 to L-189; V-101 to L-189; A-102 to L-189; P-103 to L-189; R-104 to L-189; K-105 to L-189; G-106 to L-189; I-107 to L-189; Y-108 to L-189; S-109 to L-189; F-110 to L-189; S-111 to L-189; F-112 to L-189; H-1 13 to L-189; V-114 to L-189; V-115 to L-189; K-116 to L-189; V-117 to L-189; Y-118 to L-189; N-119 to L-189; R-120 to L-189; Q-121 to L-189; T-122 to L-189; I-123 to L-189; Q-124 to L-189; V-125 to L-189; S-126 to L-189; L-127 to L-189; M-128 to L-189; Q-129 to L-189; N-130 to L-189; G-131 to L-189; Y-132 to L-189; P-133 to L-189; V-134 to L-189; I-135 to L-189; S-136 to L-189; A-137 to L-189; F-138 to L-189; A-139 to L-189; G-140 to L-189; D-141 to L-189; Q-142 to L-189; D-143 to L-189; V-144 to L-189; T-145 to L-189; R-146 to L-189; E-147 to L-189; A-148 to L-189; A-149 to L-189; S-150 to L-189; N-151 to L-189; G-152 to L-189; V-153 to L-189; L-154 to L-189; L-155 to L-189; L-156 to L-189; M-157 to L-189; E-158 to L-189; R-159 to L-189; E-160 to L-189; D-161 to L-189; K-162 to L-189; V-163 to L-189; H-164 to L-189; L-165 to L-189; K-166 to L-189; L-167 to L-189; E-168 to L-189; R-169 to L-189; G-170 to L-189; N-171 to L-189; L-172 to L-189; M-173 to L-189; G-174 to L-189; G-175 to L-189; W-176 to L-189; K-177 to L-189; Y-178 to L-189; S-179 to L-189; T-180 to L-189; F-181 to L-189; S-182 to L-189; G-183 to L-189; and F-184 to L-189 of SEQ ID NO: 55.  
       [0159] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0160] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 55: L-47 to P-188; L-47 to F-187; L-47 to V-186; L-47 to L-185; L-47 to F-184; L-47 to G-183; L-47 to S-182; L-47 to F-181; L-47 to T-180; L-47 to S-179; L-47 to Y-178; L-47 to K-177; L-47 to W-176; L-47 to G-175; L-47 to G-174; L-47 to M-173; L-47 to L-172; L-47 to N-171; L-47 to G-170; L-47 to R-169; L-47 to E-168; L-47 to L-167; L-47 to K-166; L-47 to L-165; L-47 to H-164; L-47 to V-163; L-47 to K-162; L-47 to D-161; L-47 to E-160; L-47 to R-159; L-47 to E-158; L-47 to M-157; L-47 to L-156; L-47 to L-155; L-47 to L-154; L-47 to V-153; L-47 to G-152; L-47 to N-151; L-47 to S-150; L-47 to A-149; L-47 to A-148; L-47 to E-147; L-47 to R-146; L-47 to T-145; L-47 to V-144; L-47 to D-143; L-47 to Q-142; L-47 to D-141; L-47 to G-140; L-47 to A-139; L-47 to F-138; L-47 to A-137; L-47 to S-136; L-47 to I-135; L-47 to V-134; L-47 to P-133; L-47 to Y-132; L-47 to G-131; L-47 to N-130; L-47 to Q-129; L-47 to M-128; L-47 to L-127; L-47 to S-126; L-47 to V-125; L-47 to Q-124; L-47 to I-123; L-47 to T-122; L-47 to Q-121; L-47 to R-120; L-47 to N-119; L-47 to Y-118; L-47 to V-117; L-47 to K-116; L-47 to V-115; L-47 to V-114; L-47 to H-113; L-47 to F-112; L-47 to S-111; L-47 to F-110; L-47 to S-109; L-47 to Y-108; L-47 to I-107; L-47 to G-106; L-47 to K-105; L-47 to R-104; L-47 to P-103; L-47 to A-102; L-47 to V-101; L-47 to F-100; L-47 to I-99; L-47 to S-98; L-47 to S-97; L-47 to A-96; L-47 to L-95; L-47 to D-94; L-47 to F-93; L-47 to H-92; L-47 to N-91; L-47 to G-90; L-47 to I-89; L-47 to N-88; L-47 to V-87; L-47 to L-86; L-47 to V-85; L-47 to Q-84; L-47 to D-83; L-47 to F-82; L-47 to Y-81; L-47 to I-80; L-47 to T-79; L-47 to M-78; L-47 to T-77; L-47 to R-76; L-47 to N-75; L-47 to S-74; L-47 to M-73; L-47 to E-72; L-47 to S-71; L-47 to P-70; L-47 to E-69; L-47 to H-68; L-47 to N-67; L-47 to T-66; L-47 to S-65; L-47 to R-64; L-47 to T-63; L-47 to A-62; L-47 to S-61; L-47 to F-60; L-47 to A-59; L-47 to V-58; L-47 to K-57; L-47 to A-56; L-47 to S-55; L-47 to G-54; and L-47 to S-53 of SEQ ID NO: 55.  
       [0161] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0162] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 55, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0163] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0164] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, where this portion excludes any integer of amino acid residues from 1 to about 183 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, or any integer of amino acid residues from 1 to about 183 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0165] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0166] Translation products of this gene stimulate glucose transport in adipocytes.  
       [0167] It has been discovered that this gene is expressed in neural tissues, including infant/fetal brain, and human hypothalamus.  
       [0168] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, obesity, as well as neurological disorders.  
       [0169] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0170] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0171] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0172] More generally, the expression of this gene in infant/fetal brain and human hypothalamus and homology to a cerebellin-like glycoprotein indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of neurological disorders, such as those described herein under “Neural Activity and Neurological Diseases”.  
       [0173] Translation products of this gene, as well as -antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0174] Features of Protein Encoded by Gene No.: 7  
       [0175] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329841), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0176] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0177] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, or all four of the immunogenic epitopes shown in SEQ ID NO: 56 as residues: Pro-5 to Gly-15, Pro-20 to Gly-27, Pro-32 to Glu-43, and Ala-66 to Ser-77. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0178] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 56 as residues Thr-35 to Ala-201. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0179] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 56 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0180] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0181] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0182] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 56: G-51 to A-201; P-52 to A-201; A-53 to A-201; G-54 to A-201; E-55 to A-201; C-56 to A-201; S-57 to A-201; V-58 to A-201; P-59 to A-201; P-60 to A-201; R-61 to A-201; S-62 to A-201; A-63 to A-201; F-64 to A-201; S-65 to A-201; A-66 to A-201; K-67 to A-201; R-68 to A-201; S-69 to A-201; E-70 to A-201; S-71 to A-201; R-72 to A-201; V-73 to A-201; P-74 to A-201; P-75 to A-201; P-76 to A-201; S-77 to A-201; D-78 to A-201; A-79 to A-201; P-80 to A-201; L-81 to A-201; P-82 to A-201; F-83 to A-201; D-84 to A-201; R-85 to A-201; V-86 to A-201; L-87 to A-201; V-88 to A-201; N-89 to A-201; E-90 to A-201; Q-91 to A-201; G-92 to A-201; H-93 to A-201; Y-94 to A-201; D-95 to A-201; A-96 to A-201; V-97 to A-201; T-98 to A-201; G-99 to A-201; K-100 to A-201; F-101 to A-201; T-102 to A-201; C-103 to A-201; Q-104 to A-201; V-105 to A-201; P-106 to A-201; G-107 to A-201; V-108 to A-201; Y-109 to A-201; Y-110 to A-201; F-111 to A-201; A-112 to A-201; V-113 to A-201; H-114 to A-201; A-115 to A-201; T-116 to A-201; V-117 to A-201; Y-118 to A-201; R-119 to A-201; A-120 to A-201; S-121 to A-201; L-122 to A-201; Q-123 to A-201; F-124 to A-201; D-125 to A-201; L-126 to A-201; V-127 to A-201; K-128 to A-201; N-129 to A-201; G-130 to A-201; E-131 to A-201; S-132 to A-201; I-133 to A-201; A-134 to A-201; S-135 to A-201; F-136 to A-201; F-137 to A-201; Q-138 to A-201; F-139 to A-201; F-140 to A-201; G-141 to A-201; G-142 to A-201; W-143 to A-201; P-144 to A-201; K-145 to A-201; P-146 to A-201; A-147 to A-201; S-148 to A-201; L-149 to A-201; S-150 to A-201; G-151 to A-201; G-152 to A-201; A-153 to A-201; M-154 to A-201; V-155 to A-201; R-156 to A-201; L-157 to A-201; E-158 to A-201; P-159 to A-201; E-160 to A-201; D-161 to A-201; Q-162 to A-201; V-163 to A-201; W-164 to A-201; V-165 to A-201; Q-166 to A-201; V-167 to A-201; G-168 to A-201; V-169 to A-201; G-170 to A-201; D-171 to A-201; Y-172 to A-201; I-173 to A-201; G-174 to A-201; I-175 to A-201; Y-176 to A-201; A-177 to A-201; S-178 to A-201; I-179 to A-201; K-180 to A-201; T-181 to A-201; D-182 to A-201; S-183 to A-201; T-184 to A-201; F-185 to A-201; S-186 to A-201; G-187 to A-201; F-188 to A-201; L-189 to A-201; V-190 to A-201; Y-191 to A-201; S-192 to A-201; D-193 to A-201; W-194 to A-201; H-195 to A-201; and S-196 to A-201 of SEQ ID NO: 56.  
       [0183] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0184] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 56: T-50 to F-200; T-50 to V-199; T-50 to P-198; T-50 to S-197; T-50 to S-196; T-50 to H-195; T-50 to W-194; T-50 to D-193; T-50 to S-192; T-50 to Y-191; T-50 to V-190; T-50 to L-189; T-50 to F-188; T-50 to G-187; T-50 to S-186; T-50 to F-185; T-50 to T-184; T-50 to S-183; T-50 to D-182; T-50 to T-181; T-50 to K-180; T-50 to I-179; T-50 to S-178; T-50 to A-177; T-50 to Y-176; T-50 to I-175; T-50 to G-174; T-50 to I-173; T-50 to Y-172; T-50 to D-171; T-50 to G-170; T-50 to V-169; T-50 to G-168; T-50 to V-167; T-50 to Q-166; T-50 to V-165; T-50 to W-164; T-50 to V-163; T-50 to Q-162; T-50 to D-161; T-50 to E-160; T-50 to P-159; T-50 to E-158; T-50 to L-157; T-50 to R-156; T-50 to V-155; T-50 to M-154; T-50 to A-153; T-50 to G-152; T-50 to G-151; T-50 to S-150; T-50 to L-149; T-50 to S-148; T-50 to A-147; T-50 to P-146; T-50 to K-145; T-50 to P-144; T-50 to W-143; T-50 to G-142; T-50 to G-141; T-50 to F-140; T-50 to F-139; T-50 to Q-138; T-50 to F-137; T-50 to F-136; T-50 to S-135; T-50 to A-134; T-50 to I-133; T-50 to S-132; T-50 to E-131; T-50 to G-130; T-50 to N-129; T-50 to K-128; T-50 to V-127; T-50 to L-126; T-50 to D-125; T-50 to F-124; T-50 to Q-123; T-50 to L-122; T-50 to S-121; T-50 to A-120; T-50 to R-119; T-50 to Y-118; T-50 to V-117; T-50 to T-116; T-50 to A-115; T-50 to H-114; T-50 to V-113; T-50 to A-112; T-50 to F-111; T-50 to Y-110; T-50 to Y-109; T-50 to V-108; T-50 to G-107; T-50 to P-106; T-50 to V-105; T-50 to Q-104; T-50 to C-103; T-50 to T-102; T-50 to F-101; T-50 to K-100; T-50 to G-99; T-50 to T-98; T-50 to V-97; T-50 to A-96; T-50 to D-95; T-50 to Y-94; T-50 to H-93; T-50 to G-92; T-50 to Q-91; T-50 to E-90; T-50 to N-89; T-50 to V-88; T-50 to L-87; T-50 to V-86; T-50 to R-85; T-50 to D-84; T-50 to F-83; T-50 to P-82; T-50 to L-81; T-50 to P-80; T-50 to A-79; T-50 to D-78; T-50 to S-77; T-50 to P-76; T-50 to P-75; T-50 to P-74; T-50 to V-73; T-50 to R-72; T-50 to S-71; T-50 to E-70; T-50 to S-69; T-50 to R-68; T-50 to K-67; T-50 to A-66; T-50 to S-65; T-50 to F-64; T-50 to A-63; T-50 to S-62; T-50 to R-61; T-50 to P-60; T-50 to P-59; T-50 to V-58; T-50 to S-57; T-50 to C-56; of SEQ ID NO: 56.  
       [0185] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0186] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 56, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0187] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, where this portion excludes any integer of amino acid residues from 1 to about 195 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, or any integer of amino acid residues from 1 to about 195 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-3696. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0188] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0189] It has been discovered that this gene is expressed in fetal lung, colon tumor, fetal heart, human synovium, and human epididymus.  
       [0190] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, obesity, arthritis, inflammation, and immune system dysfunction.  
       [0191] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, metabolic, and immune systems expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, immune, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0192] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0193] In addition, the similarity of this gene to other members of the Clq family of proteins, including a TNF-related protein, suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0194] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0195] Features of Protein Encoded by Gene No.: 8  
       [0196] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including the complement subcomponent Clq chain C precursor (PIR Accession No. S14351), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0197] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0198] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 57 as residues: Arg-25 to Gly-31, Pro-45 to Gly-52, Pro-71 to Gly-76, Pro-81 to Gly-91, Glu-107 to Phe-118, Thr-125 to Pro-134, Pro-147 to Gly-156, Gly-194 to Asn-203. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0199] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 57 as residues Pro-108 to Asp-245. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0200] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 57 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0201] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0202] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0203] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 57: G-109 to D-245; E-110 to D-245; E-111 to D-245; G-112 to D-245; R-113 to D-245; Y-114 to D-245; K-115 to D-245; Q-116 to D-245; K-117 to D-245; F-118 to D-245; Q-119 to D-245; S-120 to D-245; V-121 to D-245; F-122 to D-245; T-123 to D-245; V-124 to D-245; T-125 to D-245; R-126 to D-245; Q-127 to D-245; T-128 to D-245; H-129 to D-245; Q-130 to D-245; P-131 to D-245; P-132 to D-245; A-133 to D-245; P-134 to D-245; N-135 to D-245; S-136 to D-245; L-137 to D-245; I-138 to D-245; R-139 to D-245; F-140 to D-245; N-141 to D-245; A-142 to D-245; V-143 to D-245; L-144 to D-245; T-145 to D-245; N-146 to D-245; P-147 to D-245; Q-148 to D-245; G-149 to D-245; D-150 to D-245; Y-151 to D-245; D-152 to D-245; T-153 to D-245; S-154 to D-245; T-155 to D-245; G-156 to D-245; K-157 to D-245; F-158 to D-245; T-159 to D-245; C-160 to D-245; K-161 to D-245; V-162 to D-245; P-163 to D-245; G-164 to D-245; L-165 to D-245; Y-166 to D-245; Y-167 to D-245; F-168 to D-245; V-169 to D-245; Y-170 to D-245; H-171 to D-245; A-172 to D-245; S-173 to D-245; H-174 to D-245; T-175 to D-245; A-176 to D-245; N-177 to D-245; L-178 to D-245; C-179 to D-245; V-180 to D-245; L-181 to D-245; L-182 to D-245; Y-183 to D-245; R-184 to D-245; S-185 to D-245; G-186 to D-245; V-187 to D-245; K-188 to D-245; V-189 to D-245; V-190 to D-245; T-191 to D-245; F-192 to D-245; C-193 to D-245; G-194 to D-245; H-195 to D-245; T-196 to D-245; S-197 to D-245; K-198 to D-245; T-199 to D-245; N-200 to D-245; Q-201 to D-245; V-202 to D-245; N-203 to D-245; S-204 to D-245; G-205 to D-245; G-206 to D-245; V-207 to D-245; L-208 to D-245; L-209 to D-245; R-210 to D-245; L-211 to D-245; Q-212 to D-245; V-213 to D-245; G-214 to D-245; E-215 to D-245; E-216 to D-245; V-217 to D-245; W-218 to D-245; L-219 to D-245; A-220 to D-245; V-221 to D-245; N-222 to D-245; D-223 to D-245; Y-224 to D-245; Y-225 to D-245; D-226 to D-245; M-227 to D-245; V-228 to D-245; G-229 to D-245; I-230 to D-245; Q-231 to D-245; G-232 to D-245; S-233 to D-245; D-234 to D-245; S-235 to D-245; V-236 to D-245; F-237 to D-245; S-238 to D-245; G-239 to D-245; and F-240 to D-245 of SEQ ID NO: 57.  
       [0204] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0205] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 57: P-108 to P-244; P-108 to F-243; P-108 to L-242; P-108 to L-241; P-108 to F-240; P-108 to G-239; P-108 to S-238; P-108 to F-237; P-108 to V-236; P-108 to S-235; P-108 to D-234; P-108 to S-233; P-108 to G-232; P-108 to Q-231; P-108 to I-230; P-108 to G-229; P-108 to V-228; P-108 to M-227; P-108 to D-226; P-108 to Y-225; P-108 to Y-224; P-108 to D-223; P-108 to N-222; P-108 to V-221; P-108 to A-220; P-108 to L-219; P-108 to W-218; P-108 to V-217; P-108 to E-216; P-108 to E-215; P-108 to G-214; P-108 to V-213; P-108 to Q-212; P-108 to L-211; P-108 to R-210; P-108 to L-209; P-108 to L-208; P-108 to V-207; P-108 to G-206; P-108 to G-205; P-108 to S-204; P-108 to N-203; P-108 to V-202; P-108 to Q-201; P-108 to N-200; P-108 to T-199; P-108 to K-198; P-108 to S-197; P-108 to T-196; P-108 to H-195; P-108 to G-194; P-108 to C-193; P-108 to F-192; P-108 to T-191; P-108 to V-190; P-108 to V-189; P-108 to K-188; P-108 to V-187; P-108 to G-186; P-108 to S-185; P-108 to R-184; P-108 to Y-183; P-108 to L-182; P-108 to L-181; P-108 to V-180; P-108 to C-179; P-108 to L-178; P-108 to N-177; P-108 to A-176; P-108 to T-175; P-108 to H-174; P-108 to S-173; P-108 to A-172; P-108 to H-171; P-108 to Y-170; P-108 to V-169; P-108 to F-168; P-108 to Y-167; P-108 to Y-166; P-108 to L-165; P-108 to G-164; P-108 to P-163; P-108 to V-162; P-108 to K-161; P-108 to C-160; P-108 to T-159; P-108 to F-158; P-108 to K-157; P-108 to G-156; P-108 to T-155; P-108 to S-154; P-108 to T-153; P-108 to D-152; P-108 to Y-151; P-108 to D-150; P-108 to G-149; P-108 to Q-148; P-108 to P-147; P-108 to N-146; P-108 to T-145; P-108 to L-144; P-108 to V-143; P-108 to A-142; P-108 to N-141; P-108 to F-140; P-108 to R-139; P-108 to I-138; P-108 to L-137; P-108 to S-136; P-108 to N-135; P-108 to P-134; P-108 to A-133; P-108 to P-132; P-108 to P-131; P-108 to Q-130; P-108 to H-129; P-108 to T-128; P-108 to Q-127; P-108 to R-126; P-108 to T-125; P-108 to V-124; P-108 to T-123; P-108 to F-122; P-108 to V-121; P-108 to S-120; P-108 to Q-119; P-108 to F-118; P-108 to K-117; P-108 to Q-116; P-108 to K-115; and P-108 to Y-114 of SEQ ID NO: 57.  
       [0206] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0207] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 57, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0208] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, where this portion excludes any integer of amino acid residues from 1 to about 239 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, or any integer of amino acid residues from 1 to about 239 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-3696. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0209] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0210] It has been discovered that this gene is expressed in spleen, as well as dendritic cells, and adult pulmonary tissues.  
       [0211] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, metabolic disorders, obesity, and immune system disorders.  
       [0212] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, metabolic, and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, immune, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0213] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0214] In addition, the expression of this gene in dendritic cells, spleen, and adult pulmonary tissues, and the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0215] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0216] Features of Protein Encoded by Gene No.: 9  
       [0217] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329842), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0218] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0219] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 58 as residues: Asp-55 to Asp-67, Ser-76 to His-81, Lys-96 to Gly-103, Met-111 to Gly-133, Gln-222 to Ile-228, and Lys-250 to Tyr-258. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0220] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 58 as residues Met-132 to Asp-278. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0221] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 58 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0222] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0223] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0224] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 58: G-133 to D-278; S-134 to D-278; P-135 to D-278; G-136 to D-278; A-137 to D-278; P-138 to D-278; C-139 to D-278; Q-140 to D-278; K-141 to D-278; R-142 to D-278; F-143 to D-278; F-144 to D-278; A-145 to D-278; F-146 to D-278; S-147 to D-278; V-148 to D-278; G-149 to D-278; R-150 to D-278; K-151 to D-278; T-152 to D-278; A-153 to D-278; L-154 to D-278; H-155 to D-278; H-156 to D-278; G-157 to D-278; E-158 to D-278; D-159 to D-278; F-160 to D-278; Q-161 to D-278; T-162 to D-278; L-163 to D-278; L-164 to D-278; F-165 to D-278; E-166 to D-278; R-167 to D-278; V-168 to D-278; F-169 to D-278; V-170 to D-278; N-171 to D-278; L-172 to D-278; D-173 to D-278; G-174 to D-278; C-175 to D-278; F-176 to D-278; D-177 to D-278; M-178 to D-278; A-179 to D-278; T-180 to D-278; G-181 to D-278; Q-182 to D-278; F-183 to D-278; A-184 to D-278; A-185 to D-278; P-186 to D-278; L-187 to D-278; R-188 to D-278; G-189 to D-278; I-190 to D-278; Y-191 to D-278; F-192 to D-278; F-193 to D-278; S-194 to D-278; L-195 to D-278; N-196 to D-278; V-197 to D-278; H-198 to D-278; S-199 to D-278; W-200 to D-278; N-201 to D-278; Y-202 to D-278; K-203 to D-278; E-204 to D-278; T-205 to D-278; Y-206 to D-278; V-207 to D-278; H-208 to D-278; I-209 to D-278; M-210 to D-278; H-211 to D-278; N-212 to D-278; Q-213 to D-278; K-214 to D-278; E-215 to D-278; A-216 to D-278; V-217 to D-278; I-218 to D-278; L-219 to D-278; Y-220 to D-278; A-221 to D-278; Q-222 to D-278; P-223 to D-278; S-224 to D-278; E-225 to D-278; R-226 to D-278; S-227 to D-278; I-228 to D-278; M-229 to D-278; Q-230 to D-278; S-231 to D-278; Q-232 to D-278; S-233 to D-278; V-234 to D-278; M-235 to D-278; L-236 to D-278; D-237 to D-278; L-238 to D-278; A-239 to D-278; Y-240 to D-278; G-241 to D-278; D-242 to D-278; R-243 to D-278; V-244 to D-278; W-245 to D-278; V-246 to D-278; R-247 to D-278; L-248 to D-278; F-249 to D-278; K-250 to D-278; R-251 to D-278; Q-252 to D-278; R-253 to D-278; E-254 to D-278; N-255 to D-278; A-256 to D-278; I-257 to D-278; Y-258 to D-278; S-259 to D-278; N-260 to D-278; D-261 to D-278; F-262 to D-278; D-263 to D-278; T-264 to D-278; Y-265 to D-278; I-266 to D-278; T-267 to D-278; F-268 to D-278; S-269 to D-278; G-270 to D-278; H-271 to D-278; L-272 to D-278; and I-273 to D-278 of SEQ ID NO: 58.  
       [0225] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0226] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 58: M-132 to D-277; M-132 to E-276; M-132 to A-275; M-132 to K-274; M-132 to I-273; M-132 to L-272; M-132 to H-271; M-132 to G-270; M-132 to S-269; M-132 to F-268; M-132 to T-267; M-132 to I-266; M-132 to Y-265; M-132 to T-264; M-132 to D-263; M-132 to F-262; M-132 to D-261; M-132 to N-260; M-132 to S-259; M-132 to Y-258; M-132 to I-257; M-132 to A-256; M-132 to N-255; M-132 to E-254; M-132 to R-253; M-132 to Q-252; M-132 to R-251; M-132 to K-250; M-132 to F-249; M-132 to L-248; M-132 to R-247; M-132 to V-246; M-132 to W-245; M-132 to V-244; M-132 to R-243; M-132 to D-242; M-132 to G-241; M-132 to Y-240; M-132 to A-239; M-132 to L-238; M-132 to D-237; M-132 to L-236; M-132 to M-235; M-132 to V-234; M-132 to S-233; M-132 to Q-232; M-132 to S-231; M-132 to Q-230; M-132 to M-229; M-132 to I-228; M-132 to S-227; M-132 to R-226; M-132 to E-225; M-132 to S-224; M-132 to P-223; M-132 to Q-222; M-132 to A-221; M-132 to Y-220; M-132 to L-219; M-132 to I-218; M-132 to V-217; M-132 to A-216; M-132 to E-215; M-132 to K-214; M-132 to Q-213; M-132 to N-212; M-132 to H-211; M-132 to M-210; M-132 to I-209; M-132 to H-208; M-132 to V-207; M-132 to Y-206; M-132 to T-205; M-132 to E-204; M-132 to K-203; M-132 to Y-202; M-132 to N-201; M-132 to W-200; M-132 to S-199; M-132 to H-198; M-132 to V-197; M-132 to N-196; M-132 to L-195; M-132 to S-194; M-132 to F-193; M-132 to F-192; M-132 to Y-191; M-132 to I-190; M-132 to G-189; M-132 to R-188; M-132 to L-187; M-132 to P-186; M-132 to A-185; M-132 to A-184; M-132 to F-183; M-132 to Q-182; M-132 to G-181; M-132 to T-180; M-132 to A-179; M-132 to M-178; M-132 to D-177; M-132 to F-176; M-132 to C-175; M-132 to G-174; M-132 to D-173; M-132 to L-172; M-132 to N-171; M-132 to V-170; M-132 to F-169; M-132 to V-168; M-132 to R-167; M-132 to E-166; M-132 to F-165; M-132 to L-164; M-132 to L-163; M-132 to T-162; M-132 to Q-161; M-132 to F-160; M-132 to D-159; M-132 to E-158; M-132 to G-157; M-132 to S-156; M-132 to H-155; M-132 to L-154; M-132 to A-153; M-132 to T-152; M-132 to K-151; M-132 to R-150; M-132 to G-149; M-132 to V-148; M-132 to S-147; M-132 to F-146; M-132 to A-145; M-132 to F-144; M-132 to F-143; M-132 to R-142; M-132 to K-141; M-132 to Q-140; M-132 to C-139; and M-132 to P-138 of SEQ ID NO: 58.  
       [0227] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0228] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 58, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0229] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0230] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. 203071, where this portion excludes any integer of amino acid residues from 1 to about 272 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. 203071, or any integer of amino acid residues from 1 to about 272 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 203071. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0231] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0232] It has been discovered that this gene is expressed in umbilical vein, fetal heart, microvascular endothelial cells, and placenta.  
       [0233] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, and cardiovascular disorders.  
       [0234] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and cardiovascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, vascular, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0235] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0236] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0237] More generally, the expression of this gene in tissues of the cardiovascular system and homology to the Clq family of proteins, including a TNF-related protein, indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of cardiovascular disorders (e.g., atherosclerosis, restenosis, and/or as described herein under “Cardiovascular Disorders”).  
       [0238] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0239] Features of Protein Encoded by Gene No.: 10  
       [0240] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329839), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties.). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0241] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0242] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 59 as residues Gly-16 to Pro-30, Pro-42 to Gly-56, Gly-62 to Gly-77, Glu-93 to Gly-104, Glu-109 to Glu-114, Pro-121 to Gly-134, Ser-157 to Arg-162, Glu-174 to Thr-182, and Ile-283 to Leu-289. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0243] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 59 as residues Pro-136 to Leu-289. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0244] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 59 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0245] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0246] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0247] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 59: G-137 to L-289; V-138 to L-289; C-139 to L-289; R-140 to L-289; C-141 to L-289; G-142 to L-289; S-143 to L-289; I-144 to L-289; V-145 to L-289; L-146 to L-289; K-147 to L-289; S-148 to L-289; A-149 to L-289; F-150 to L-289; S-151 to L-289; V-152 to L-289; G-153 to L-289; I-154 to L-289; T-155 to L-289; T-156 to L-289; S-157 to L-289; Y-158 to L-289; P-159 to L-289; E-160 to L-289; E-161 to L-289; R-162 to L-289; L-163 to L-289; P-164 to L-289; I-165 to L-289; I-166 to L-289; F-167 to L-289; N-168 to L-289; K-169 to L-289; V-170 to L-289; L-171 to L-289; F-172 to L-289; N-173 to L-289; E-174 to L-289; G-175 to L-289; E-176 to L-289; H-177 to L-289; Y-178 to L-289; N-179 to L-289; P-180 to L-289; A-181 to L-289; T-182 to L-289; G-183 to L-289; K-184 to L-289; F-185 to L-289; I-186 to L-289; C-187 to L-289; A-188 to L-289; F-189 to L-289; P-190 to L-289; G-191 to L-289; I-192 to L-289; Y-193 to L-289; Y-194 to L-289; F-195 to L-289; S-196 to L-289; Y-197 to L-289; D-198 to L-289; I-199 to L-289; T-200 to L-289; L-201 to L-289; A-202 to L-289; N-203 to L-289; K-204 to L-289; H-205 to L-289; L-206 to L-289; A-207 to L-289; I-208 to L-289; G-209 to L-289; L-210 to L-289; V-211 to L-289; H-212 to L-289; N-213 to L-289; G-214 to L-289; Q-215 to L-289; Y-216 to L-289; R-217 to L-289; I-218 to L-289; K-219 to L-289; T-220 to L-289; F-221 to L-289; D-222 to L-289; A-223 to L-289; N-224 to L-289; T-225 to L-289; G-226 to L-289; N-227 to L-289; H-228 to L-289; D-229 to L-289; V-230 to L-289; A-231 to L-289; S-232 to L-289; G-233 to L-289; S-234 to L-289; T-235 to L-289; V-236 to L-289; I-237 to L-289; Y-238 to L-289; L-239 to L-289; Q-240 to L-289; P-241 to L-289; E-242 to L-289; D-243 to L-289; E-244 to L-289; V-245 to L-289; W-246 to L-289; L-247 to L-289; E-248 to L-289; I-249 to L-289; F-250 to L-289; F-251 to L-289; T-252 to L-289; D-253 to L-289; Q-254 to L-289; N-255 to L-289; G-256 to L-289; L-257 to L-289; F-258 to L-289; S-259 to L-289; D-260 to L-289; P-261 to L-289; G-262 to L-289; W-263 to L-289; A-264 to L-289; D-265 to L-289; S-266 to L-289; L-267 to L-289; F-268 to L-289; S-269 to L-289; G-270 to L-289; F-271 to L-289; L-272 to L-289; L-273 to L-289; Y-274 to L-289; V-275 to L-289; D-276 to L-289; T-277 to L-289; D-278 to L-289; Y-279 to L-289; L-280 to L-289; D-281 to L-289; S-282 to L-289; I-283 to L-289; and S-284 to L-289 of SEQ ID NO: 59.  
       [0248] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0249] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 59: P-136 to E-288; P-136 to D-287; P-136 to D-286; P-136 to E-285; P-136 to S-284; P-136 to I-283; P-136 to S-282; P-136 to D-281; P-136 to L-280; P-136 to Y-279; P-136 to D-278; P-136 to T-277; P-136 to D-276; P-136 to V-275; P-136 to Y-274; P-136 to L-273; P-136 to L-272; P-136 to F-271; P-136 to G-270; P-136 to S-269; P-136 to F-268; P-136 to L-267; P-136 to S-266; P-136 to D-265; P-136 to A-264; P-136 to W-263; P-136 to G-262; P-136 to P-261; P-136 to D-260; P-136 to S-259; P-136 to F-258; P-136 to L-257; P-136 to G-256; P-136 to N-255; P-136 to Q-254; P-136 to D-253; P-136 to T-252; P-136 to F-251; P-136 to F-250; P-136 to I-249; P-136 to E-248; P-136 to L-247; P-136 to W-246; P-136 to V-245; P-136 to E-244; P-136 to D-243; P-136 to E-242; P-136 to P-241; P-136 to Q-240; P-136 to L-239; P-136 to Y-238; P-136 to I-237; P-136 to V-236; P-136 to T-235; P-136 to S-234; P-136 to G-233; P-136 to S-232; P-136 to A-231; P-136 to V-230; P-136 to D-229; P-136 to H-228; P-136 to N-227; P-136 to G-226; P-136 to T-225; P-136 to N-224; P-136 to A-223; P-136 to D-222; P-136 to F-221; P-136 to T-220; P-136 to K-219; P-136 to I-218; P-136 to R-217; P-136 to Y-216; P-136 to Q-215; P-136 to G-214; P-136 to N-213; P-136 to H-212; P-136 to V-211; P-136 to L-210; P-136 to G-209; P-136 to I-208; P-136 to A-207; P-136 to L-206; P-136 to H-205; P-136 to K-204; P-136 to N-203; P-136 to A-202; P-136 to L-201; P-136 to T-200; P-136 to I-199; P-136 to D-198; P-136 to Y-197; P-136 to S-196; P-136 to F-195; P-136 to Y-194; P-136 to Y-193; P-136 to I-192; P-136 to G-191; P-136 to P-190; P-136 to F-189; P-136 to A-188; P-136 to C-187; P-136 to I-186; P-136 to F-185; P-136 to K-184; P-136 to G-183; P-136 to T-182; P-136 to A-181; P-136 to P-180; P-136 to N-179; P-136 to Y-178; P-136 to H-177; P-136 to E-176; P-136 to G-175; P-136 to E-174; P-136 to N-173; P-136 to F-172; P-136 to L-171; P-136 to V-170; P-136 to K-169; P-136 to N-168; P-136 to F-167; P-136 to I-166; P-136 to I-165; P-136 to P-164; P-136 to L-163; P-136 to R-136 to E-161; P-136 to E-160; P-136 to P-159; P-136 to Y-158; P-136 to S-157; P-136 to T-156; P-136 to T-155; P-136 to I-154; P-136 to G-153; P-136 to V-152; P-136 to S-151; P-136 to F-150; P-136 to A-149; P-136 to S-148; P-136 to K-147; P-136 to L-146; P-136 to V-145; P-136 to I-144; P-136 to S-143; and P-136 to G-142 of SEQ ID NO: 59.  
       [0250] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0251] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 59, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0252] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0253] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. 209124, where this portion excludes any integer of amino acid residues from 1 to about 283 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. 209124, or any integer of amino acid residues from 1 to about 283 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 209124. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0254] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0255] It has been discovered that this gene is expressed in monocytes, skeletal muscle, and human schwanoma tissue.  
       [0256] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, as well as immunological and neurological disorders.  
       [0257] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include, but are not limited to, immunological disorders and neural or integumentary disorders, particularly neurofibroma. For a number of disorders of the above tissues or cells, particularly of the endocrine and of the peripheral and sympathetic nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, immune, neural, integumentary, extracellular matrix, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0258] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0259] In addition, the expression of this gene in monocytes and similarity of this gene to other members of the Clq family of proteins, including a complement Clq-TNFalpha related protein (Swiss-Prot Accession Q9BXJ2), suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0260] More generally, the expression of this gene in schwanoma tissue and homology to a complement Clq-TNFalpha related protein (Swiss-Prot Accession Q9BXJ2) indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of neurological disorders, such as for example, those disclosed herein under “Neural Activity and Neurological Diseases”.  
       [0261] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0262] Features of Protein Encoded by Gene No.: 11  
       [0263] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329836), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0264] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0265] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 60 as residues: Arg-25 to Ser-31, Pro-39 to Gly-49, Pro-63 to Gly-97, Ala-105 to Asn-114, Thr-116 to Gly-133, Gly-144 to Ser-150, Lys-158 to Leu-165, Glu-176 to Ser-184, Ser-254 to Phe-260, and Ala-277 to Glu-284. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0266] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 60 as residues Pro-138 to Val-285. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0267] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 60 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0268] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0269] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0270] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 60: G-139 to V-285; P-140 to V-285; C-141 to V-285; S-142 to V-285; C-143 to V-285; G-144 to V-285; S-145 to V-285; G-146 to V-285; H-147 to V-285; T-148 to V-285; K-149 to V-285; S-150 to V-285; A-151 to V-285; F-152 to V-285; S-153 to V-285; V-154 to V-285; A-155 to V-285; V-156 to V-285; T-157 to V-285; K-158 to V-285; S-159 to V-285; Y-160 to V-285; P-161 to V-285; R-162 to V-285; E-163 to V-285; R-164 to V-285; L-165 to V-285; P-166 to V-285; I-167 to V-285; K-168 to V-285; F-169 to V-285; D-170 to V-285; K-171 to V-285, 1-172 to V-285; L-173 to V-285; M-174 to V-285; N-175 to V-285; E-176 to V-285; G-177 to V-285; G-178 to V-285; H-179 to V-285; Y-180 to V-285; N-181 to V-285; A-182 to V-285; S-183 to V-285; S-184 to V-285; G-185 to V-285; K-186 to V-285; F-187 to V-285; V-188 to V-285; C-189 to V-285; G-190 to V-285; V-191 to V-285; P-192 to V-285; G-193 to V-285; I-194 to V-285; Y-195 to V-285; Y-196 to V-285; F-197 to V-285; T-198 to V-285; Y-199 to V-285; D-200 to V-285; I-201 to V-285; T-202 to V-285; L-203 to V-285; A-204 to V-285; N-205 to V-285; K-206 to V-285; H-207 to V-285; L-208 to V-285; A-209 to V-285; I-210 to V-285; G-211 to V-285; L-212 to V-285; V-213 to V-285; H-214 to V-285; N-215 to V-285; G-216 to V-285; Q-217 to V-285; Y-218 to V-285; R-219 to V-285; I-220 to V-285; R-221 to V-285; T-222 to V-285; F-223 to V-285; D-224 to V-285; A-225 to V-285; N-226 to V-285; T-227 to V-285; G-228 to V-285; N-229 to V-285; H-230 to V-285; D-231 to V-285; V-232 to V-285; A-233 to V-285; S-234 to V-285; G-235 to V-285; S-236 to V-285; T-237 to V-285; I-238 to V-285; L-239 to V-285; A-240 to V-285; L-241 to V-285; K-242 to V-285; Q-243 to V-285; G-244 to V-285; D-245 to V-285; E-246 to V-285; V-247 to V-285; W-248 to V-285; L-249 to V-285; Q-250 to V-285; I-251 to V-285; F-252 to V-285; Y-253 to V-285; S-254 to V-285; E-255 to V-285; Q-256 to V-285; N-257 to V-285; G-258 to V-285; L-259 to V-285; F-260 to V-285; Y-261 to V-285; D-262 to V-285; P-263 to V-285; Y-264 to V-285; W-265 to V-285; T-266 to V-285; D-267 to V-285; S-268 to V-285; L-269 to V-285; F-270 to V-285; T-271 to V-285; G-272 to V-285; F-273 to V-285; L-274 to V-285; I-275 to V-285; Y-276 to V-285; A-277 to V-285; D-278 to V-285; Q-279 to V-285; and D-280 to V-285 of SEQ ID NO: 60.  
       [0271] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0272] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 60: P-138 to E-284; P-138 to N-283; P-138 to P-282; P-138 to D-281; P-138 to D-280; P-138 to Q-279; P-138 to D-278; P-138 to A-277; P-138 to Y-276; P-138 to I-275; P-138 to L-274; P-138 to F-273; P-138 to G-272; P-138 to T-271; P-138 to F-270; P-138 to L-269; P-138 to S-268; P-138 to D-267; P-138 to T-266; P-138 to W-265; P-138 to Y-264; P-138 to P-263; P-138 to D-262; P-138 to Y-261; P-138 to F-260; P-138 to L-259; P-138 to G-258; P-138 to N-257; P-138 to Q-256; P-138 to E-255; P-138 to S-254; P-138 to Y-253; P-138 to F-252; P-138 to I-251; P-138 to Q-250; P-138 to L-249; P-138 to W-248; P-138 to V-247; P-138 to E-246; P-138 to D-245; P-138 to G-244; P-138 to Q-243; P-138 to K-242; P-138 to L-241; P-138 to A-240; P-138 to L-239; P-138 to I-238; P-138 to T-237; P-138 to S-236; P-138 to G-235; P-138 to S-234; P-138 to A-233; P-138 to V-232; P-138 to D-231; P-138 to H-230; P-138 to N-229; P-138 to G-228; P-138 to T-227; P-138 to N-226; P-138 to A-225; P-138 to D-224; P-138 to F-223; P-138 to T-222; P-138 to R-221; P-138 to I-220; P-138 to R-219; P-138 to Y-218; P-138 to Q-217; P-138 to G-216; P-138 to N-215; P-138 to H-214; P-138 to V-213; P-138 to L-212; P-138 to G-211; P-138 to I-210; P-138 to A-209; P-138 to L-208; P-138 to H-207; P-138 to K-206; P-138 to N-205; P-138 to A-204; P-138 to L-203; P-138 to T-202; P-138 to I-201; P-138 to D-200; P-138 to Y-199; P-138 to T-198; P-138 to F-197; P-138 to Y-196; P-138 to Y-195; P-138 to I-194; P-138 to G-193; P-138 to P-192; P-138 to V-191; P-138 to G-190; P-138 to C-189; P-138 to V-188; P-138 to F-187; P-138 to K-186; P-138 to G-185; P-138 to S-184; P-138 to S-183; P-138 to A-182; P-138 to N-181; P-138 to Y-180; P-138 to H-179; P-138 to G-178; P-138 to G-177; P-138 to E-176; P-138 to N-175; P-138 to M-174; P-138 to L-173; P-138 to I-172; P-138 to K-171; P-138 to D-170; P-138 to F-169; P-138 to K-168; P-138 to I-167; P-138 to P-166; P-138 to L-165; P-138 to R-164; P-138 to E-163; P-138 to R-162; P-138 to P-161; P-138 to Y-160; P-138 to S-159; P-138 to K-158; P-138 to T-157; P-138 to V-156; P-138 to A-155; P-138 to V-154; P-138 to S-153; P-138 to F-152; P-138 to A-151; P-138 to S-150; P-138 to K-149; P-138 to T-148; P-138 to H-147; P-138 to G-146; P-138 to S-145; and P-138 to G-144 of SEQ ID NO: 60.  
       [0273] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0274] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1 31  n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 60, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0275] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0276] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, where this portion excludes any integer of amino acid residues from 1 to about 279 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, or any integer of amino acid residues from 1 to about 279 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-3696. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0277] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0278] Translation products of this gene stimulate glucose transport in adipocytes.  
       [0279] It has been discovered that this gene is expressed in small intestine, as well as fetal brain and glioblastoma tissues.  
       [0280] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, and neurological disorders.  
       [0281] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, intestinal, neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0282] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0283] In addition, the similarity of this gene to other members of the Clq family of proteins, including a TNF-related protein, suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0284] More generally, the expression of this gene in neural tissues and homology to the Clq family of proteins indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of neurological disorders, such as for example, those disclosed herein under “Neural Activity and Neurological Diseases”.  
       [0285] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0286] Features of Protein Encoded by Gene No.: 12  
       [0287] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329838), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties.). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0288] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0289] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, or all three of the immunogenic epitopes shown in SEQ ID NO: 61 as residues: Ala-9 to Gln-16, Asp-77 to Gln-87, and Asp-107 to Lys-119. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0290] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 61 as residues Thr-1 to Leu-146. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0291] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 61 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0292] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0293] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0294] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 61: R-2 to L-146; S-3 to L-146; L-4 to L-146; V-5 to L-146; G-6 to L-146; S-7 to L-146; D-8 to L-146; A-9 to L-146; G-10 to L-146; P-11 to L-146; G-12 to L-146; P-13 to L-146; R-14 to L-146; H-15 to L-146; Q-16 to L-146; P-17 to L-146; L-18 to L-146; A-19 to L-146; F-20 to L-146; D-21 to L-146; T-22 to L-146; E-23 to L-146; F-24 to L-146; V-25 to L-146; N-26 to L-146; I-27 to L-146; G-28 to L-146; G-29 to L-146; D-30 to L-146; F-31 to L-146; D-32 to L-146; A-33 to L-146; A-34 to L-146; A-35 to L-146; G-36 to L-146; V-37 to L-146; F-38 to L-146; R-39 to L-146; C-40 to L-146; R-41 to L-146; L-42 to L-146; P-43 to L-146; G-44 to L-146; A-45 to L-146; Y-46 to L-146; F-47 to L-146; F-48 to L-146; S-49 to L-146; F-50 to L-146; T-51 to L-146; L-52 to L-146; G-53 to L-146; K-54 to L-146; L-55 to L-146; P-56 to L-146; R-57 to L-146; K-58 to L-146; T-59 to L-146; L-60 to L-146; S-61 to L-146; V-62 to L-146; K-63 to L-146; L-64 to L-146; M-65 to L-146; K-66 to L-146; N-67 to L-146; R-68 to L-146; D-69 to L-146; E-70 to L-146; V-71 to L-146; Q-72 to L-146; A-73 to L-146; M-74 to L-146; I-175 to L-146; Y-76 to L-146; D-77 to L-146; D-78 to L-146; G-79 to L-146; A-80 to L-146; S-81 to L-146; R-82 to L-146; R-83 to L-146; R-84 to L-146; E-85 to L-146; M-86 to L-146; Q-87 to L-146; S-88 to L-146; Q-89 to L-146; S-90 to L-146; V-91 to L-146; M-92 to L-146; L-93 to L-146; A-94 to L-146; L-95 to L-146; R-96 to L-146; R-97 to L-146; G-98 to L-146; D-99 to L-146; A-100 to L-146; V-101 to L-146; W-102 to L-146; L-103 to L-146; L-104 to L-146; S-105 to L-146; H-106 to L-146; D-107 to L-146; H-108 to L-146; D-109 to L-146; G-110 to L-146; Y-111 to L-146; G-112 to L-146; A-113 to L-146; Y-114 to L-146; S-115 to L-146; N-116 to L-146; H-117 to L-146; G-118 to L-146; K-119 to L-146; Y-120 to L-146; I-121 to L-146; T-122 to L-146; F-123 to L-146; S-124 to L-146; G-125 to L-146; F-126 to L-146; L-127 to L-146; V-128 to L-146; Y-129 to L-146; P-130 to L-146; D-131 to L-146; L-132 to L-146; A-133 to L-146; P-134 to L-146; A-135 to L-146; A-136 to L-146; P-137 to L-146; P-138 to L-146; G-139 to L-146; L-140 to L-146; and G-141 to L-146 of SEQ ID NO: 61.  
       [0295] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0296] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 61: T-1 to L-145; T-1 to E-144; T-1 to S-143; T-1 to A-142; T-1 to G-141; T-1 to L-140; T-1 to G-139; T-1 to P-138; T-1 to P-137; T-1 to A-136; T-1 to A-135; T-1 to P-134; T-1 to A-133; T-1 to L-132; T-1 to D-131; T-1 to P-130; T-1 to Y-129; T-1 to V-128; T-1 to L-127; T-1 to F-126; T-1 to G-125; T-1 to S-124; T-1 to F-123; T-1 to T-122; T-1 to I-121; T-1 to Y-120; T-1 to K-119; T-1 to G-118; T-1 to H-117; T-1 to N-116; T-1 to S-115; T-1 to Y-114; T-1 to A-113; T-1 to G-112; T-1 to Y-111; T-1 to G-110; T-1 to D-109; T-1 to H-108; T-1 to D-107; T-1 to H-106; T-1 to S-105; T-1 to L-104; T-1 to L-103; T-1 to W-102; T-1 to V-101; T-1 to A-100; T-1 to D-99; T-1 to G-98; T-1 to R-97; T-1 to R-96; T-1 to L-95; T-1 to A-94; T-1 to L-93; T-1 to M-92; T-1 to V-91; T-1 to S-90; T-1 to Q-89; T-1 to S-88; T-1 to Q-87; T-1 to M-86; T-1 to E-85; T-1 to R-84; T-1 to R-83; T-1 to R-82; T-1 to S-81; T-1 to A-80; T-1 to G-79; T-1 to D-78; T-1 to D-77; T-1 to Y-76; T-1 to I-75; T-1 to M-74; T-1 to A-73; T-1 to Q-72; T-1 to V-71; T-1 to E-70; T-1 to D-69; T-1 to R-68; T-1 to N-67; T-1 to K-66; T-1 to M-65; T-1 to L-64; T-1 to K-63; T-1 to V-62; T-1 to S-61; T-1 to L-60; T-1 to T-59; T-1 to K-58; T-1 to R-57; T-1 to P-56; T-1 to L-55; T-1 to K-54; T-1 to G-53; T-1 to L-52; T-1 to T-51; T-1 to F-50; T-1 to S-49; T-1 to F-48; T-1 to F-47; T-1 to Y-46; T-1 to A-45; T-l to G-44; T-1 to P-43; T-1 to L-42; T-1 to R-41; T-1 to C-40; T-1 to R-39; T-1 to F-38; T-1 to V-37; T-1 to G-36; T-1 to A-35; T-1 to A-34; T-1 to A-33; T-1 to D-32; T-1 to F-31; T-1 to D-30; T-1 to G-29; T-1 to G-28; T-1 to I-27; T-1 to N-26; T-1 to V-25; T-1 to F-24; T-1 to E-23; T-1 to T-22; T-1 to D-21; T-1 to F-20; T-1 to A-19; T-1 to L-18; T-1 to P-17; T-1 to Q-16; T-1 to H-15; T-1 to R-14; T-1 to P-13; T-1 to G-12; T-1 to P-11; T-1 to G-10; T-1 to A-9; T-1 to D-8; and T-1 to S-7 of SEQ ID NO: 61.  
       [0297] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0298] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 61, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0299] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, where this portion excludes any integer of amino acid residues from 1 to about 140 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3696, or any integer of amino acid residues from 1 to about 140 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-3696. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0300] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0301] It has been discovered that this gene is expressed in neural tissues (e.g., striatum, pituitary, and glioblastoma).  
       [0302] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, as well as neurological disorders.  
       [0303] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0304] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0305] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0306] More generally, the expression of this gene in neural tissues and homology to Clq family proteins indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of neurodegenerative disorders, such as those described herein under “Neural Activity and Neurological Diseases”.  
       [0307] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0308] Features of Protein Encoded by Gene No.: 13  
       [0309] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including a TNF-related protein (see, e.g. Genbank Accession No. AF329836), and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties.). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0310] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0311] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 62 as residues: Pro-45 to Gly-52, Asn-83 to Gly-97, Pro-105 to Thr-117, Arg-133 to Ile-138, Met-147 to Phe-158, Arg-184 to Ala-189. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0312] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 62 as residues Lys-108 to Ala-251. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0313] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 62 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0314] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0315] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0316] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 62: G-109 to A-251; E-110 to A-251; S-111 to A-251; G-112 to A-251; D-113 to A-251; Y-114 to A-251; K-115 to A-251; A-116 to A-251; T-117 to A-251; Q-118 to A-251; K-119 to A-251; I-120 to A-251; A-121 to A-251; F-122 to A-251; S-123 to A-251; A-124 to A-251; T-125 to A-251; R-126 to A-251; T-127 to A-251; I-128 to A-251; N-129 to A-251; V-130 to A-251; P-131 to A-251; L-132 to A-251; R-133 to A-251; R-134 to A-251; D-135 to A-251; Q-136 to A-251; T-137 to A-251; I-138 to A-251; R-139 to A-251; F-140 to A-251; D-141 to A-251; H-142 to A-251; V-143 to A-251; I-144 to A-251; T-145 to A-251; N-146 to A-251; M-147 to A-251; N-148 to A-251; N-149 to A-251; N-150 to A-251; Y-151 to A-251; E-152 to A-251; P-153 to A-251; R-154 to A-251; S-155 to A-251; G-156 to A-251; K-157 to A-251; F-158 to A-251; T-159 to A-251; C-160 to A-251; K-161 to A-251; V-162 to A-251; P-163 to A-251; G-164 to A-251; L-165 to A-251; Y-166 to A-251; Y-167 to A-251; F-168 to A-251; T-169 to A-251; Y-170 to A-251; H-171 to A-251; A-172 to A-251; S-173 to A-251; S-174 to A-251; R-175 to A-251; G-176 to A-251; N-177 to A-251; L-178 to A-251; C-179 to A-251; V-180 to A-251; N-181 to A-251; L-182 to A-251; M-183 to A-251; R-184 to A-251; G-185 to A-251; R-186 to A-251; E-187 to A-251; R-188 to A-251; A-189 to A-251; Q-190 to A-251; K-191 to A-251; V-192 to A-251; V-193 to A-251; T-194 to A-251; F-195 to A-251; C-196 to A-251; D-197 to A-251; Y-198 to A-251; A-199 to A-251; Y-200 to A-251; N-201 to A-251; T-202 to A-251; F-203 to A-251; Q-204 to A-251; V-205 to A-251; T-206 to A-251; T-207 to A-251; G-208 to A-251; G-209 to A-251; M-210 to A-251; V-211 to A-251; L-212 to A-251; K-213 to A-251; L-214 to A-251; E-215 to A-251; Q-216 to A-251; G-217 to A-251; E-218 to A-251; N-219 to A-251; V-220 to A-251; F-221 to A-251; L-222 to A-251; Q-223 to A-251; A-224 to A-251; T-225 to A-251; D-226 to A-251; K-227 to A-251; N-228 to A-251; S-229 to A-251; L-230 to A-251; L-231 to A-251; G-232 to A-251; M-233 to A-251; E-234 to A-251; G-235 to A-251; A-236 to A-251; N-237 to A-251; S-238 to A-251; I-239 to A-251; F-240 to A-251; S-241 to A-251; G-242 to A-251; F-243 to A-251; L-244 to A-251; L-245 to A-251; and F-246 to A-251 of SEQ ID NO: 62.  
       [0317] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0318] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 62: K-108 to E-250; K-108 to M-249; K-108 to D-248; K-108 to P-247; K-108 to F-246; K-108 to L-245; K-108 to L-244; K-108 to F-243; K-108 to G-242; K-108 to S-241; K-108 to F-240; K-108 to I-239; K-108 to S-238; K-108 to N-237; K-108 to A-236; K-108 to G-235; K-108 to E-234; K-108 to M-233; K-108 to G-232; K-108 to L-231; K-108 to L-230; K-108 to S-229; K-108 to N-228; K-108 to K-227; K-108 to D-226; K-108 to T-225; K-108 to A-224; K-108 to Q-223; K-108 to L-222; K-108 to F-221; K-108 to V-220; K-108 to N-219; K-108 to E-218; K-108 to G-217; K-108 to Q-216; K-108 to E-215; K-108 to L-214; K-108 to K-213; K-108 to L-212; K-108 to V-211; K-108 to M-210; K-108 to G-209; K-108 to G-208; K-108 to T-207; K-108 to T-206; K-108 to V-205; K-108 to Q-204; K-108 to F-203; K-108 to T-202; K-108 to N-201; K-108 to Y-200; K-108 to A-199; K-108 to Y-198; K-108 to D-197; K-108 to C-196; K-108 to F-195; K-108 to T-194; K-108 to V-193; K-108 to V-192; K-108 to K-191; K-108 to Q-190; K-108 to A-189; K-108 to R-188; K-108 to E-187; K-108 to R-186; K-108 to G-185; K-108 to R-184; K-108 to M-183; K-108 to L-182; K-108 to N-181; K-108 to V-180; K-108 to C-179; K-108 to L-178; K-108 to N-177; K-108 to G-176; K-108 to R-175; K-108 to S-174; K-108 to S-173; K-108 to A-172; K-108 to H-171; K-108 to Y-170; K-108 to T-169; K-108 to F-168; K-108 to Y-167; K-108 to Y-166; K-108 to L-165; K-108 to G-164; K-108 to P-163; K-108 to V-162; K-108 to K-161; K-108 to C-160; K-108 to T-159; K-108 to F-158; K-108 to K-157; K-108 to G-156; K-108 to S-155; K-108 to R-154; K-108 to P-153; K-108 to E-152; K-108 to Y-151; K-108 to N-150; K-108 to N-149; K-108 to N-148; K-108 to M-147; K-108 to N-146; K-108 to T-145; K-108 to I-144; K-108 to V-143; K-108 to H-142; K-108 to D-141; K-108 to F-140; K-108 to R-139; K-108 to I-138; K-108 to T-137; K-108 to Q-136; K-108 to D-135; K-108 to R-134; K-108 to R-133; K-108 to L-132; K-108 to P-131; K-108 to V-130; K-108 to N-129; K-108 to I-128; K-108 to T-127; K-108 to R-126; K-108 to T-125; K-108 to A-124; K-108 to S-123; K-108 to F-122; K-108 to A-121; K-108 to I-120; K-108 to K-119; K-108 to Q-118; K-108 to T-117; K-108 to A-116; K-108to K-115; and K-108 to Y-114 of SEQ ID NO: 62.  
       [0319] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0320] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 62, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0321] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, where this portion excludes any integer of amino acid residues from 1 to about 245 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, or any integer of amino acid residues from 1 to about 245 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0322] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0323] It has been discovered that this gene is expressed in tissues of the immune system, including primary dendritic cells, monocytes, bone marrow, spleen, and T cell lymphoma, as well as the colon.  
       [0324] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes and diseases and/or disorders involving dysfunctional fatty acid metabolism, as well as immunological and gastrointestinal disorders.  
       [0325] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, immune, and gastrointestinal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, immune, gastrointestinal, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0326] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0327] In addition, the expression of this gene in immune system cells and tissues, and similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0328] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0329] Features of Protein Encoded by Gene No.: 14  
       [0330] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0331] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0332] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 63 as residues: Pro-15 to Thr-23, Arg-36 to Thr-50, Arg-52 to Leu-80, Gly-84 to Trp-90, Asp-93 to Lys-105, Glu-132 to Arg-146, Ser-151 to Thr-159, Gly-163 to Gln-169, Asn-175 to Gly-180, Asp-193 to Glu-203, Leu-205 to Lys-210, Lys-263 to Tyr-268, Gln-276 to Ser-282, Glu-293 to Asn-303, Asn-317 to Ile-327, Ile-331 to Ile-338, Arg-351 to Asp-357, Pro-491 to Arg-496, Lys-515 to Asp-529, Gln-548 to Gly-557, Val-568 to Val-575, Leu-592 to Gln-600, Arg-671 to Gly-679, Pro-706 to Gly-735, Thr-738 to Arg-744, Pro-746 to Gly-762, Gly-789 to Gly-795, Pro-809 to Pro-815, Thr-835 to Ser-841, Gly-856 to Ser-862, and Glu-910 to Gly-919. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0333] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 63 as residues Pro-816 to Leu-975. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0334] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 63 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0335] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0336] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0337] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 63: V-817 to L-975; A-818 to L-975; S-819 to L-975; P-820 to L-975; G-821 to L-975; A-822 to L-975; P-823 to L-975; V-824 to L-975; P-825 to L-975; S-826 to L-975; L-827 to L-975; V-828 to L-975; S-829 to L-975; F-830 to L-975; S-831 to L-975; A-832 to L-975; G-833 to L-975; L-834 to L-975; T-835 to L-975; Q-836 to L-975; K-837 to L-975; P-838 to L-975; F-839 to L-975; P-840 to L-975; S-841 to L-975; D-842 to L-975; G-843 to L-975; G-844 to L-975; V-845 to L-975; V-846 to L-975; L-847 to L-975; F-848 to L-975; N-849 to L-975; K-850 to L-975; V-851 to L-975; L-852 to L-975; V-853 to L-975; N-854 to L-975; D-855 to L-975; G-856 to L-975; D-857 to L-975; V-858 to L-975; Y-859 to L-975; N-860 to L-975; P-861 to L-975; S-862 to L-975; T-863 to L-975; G-864 to L-975; V-865 to L-975; F-866 to L-975; T-867 to L-975; A-868 to L-975; P-869 to L-975; Y-870 to L-975; D-871 to L-975; G-872 to L-975; R-873 to L-975; Y-874 to L-975; L-875 to L-975; I-876 to L-975; T-877 to L-975; A-878 to L-975; T-879 to L-975; L-880 to L-975; T-881 to L-975; P-882 to L-975; E-883 to L-975; R-884 to L-975; D-885 to L-975; A-886 to L-975; Y-887 to L-975; V-888 to L-975; E-889 to L-975; A-890 to L-975; V-891 to L-975; L-892 to L-975; S-893 to L-975; V-894 to L-975; S-895 to L-975; N-896 to L-975; A-897 to L-975; S-898 to L-975; V-899 to L-975; A-900 to L-975; Q-901 to L-975; L-902 to L-975; H-903 to L-975; T-904 to L-975; A-905 to L-975; G-906 to L-975; Y-907 to L-975; R-908 to L-975; R-909 to L-975; E-910 to L-975; F-911 to L-975; L-912 to L-975; E-913 to L-975; Y-914 to L-975; H-915 to L-975; R-916 to L-975; P-917 to L-975; P-918 to L-975; G-919 to L-975; A-920 to L-975; L-921 to L-975; H-922 to L-975; T-923 to L-975; C-924 to L-975; G-925 to L-975; G-926 to L-975; P-927 to L-975; G-928 to L-975; A-929 to L-975; F-930 to L-975; H-931 to L-975; L-932 to L-975; I-933 to L-975; V-934 to L-975; H-935 to L-975; L-936 to L-975; K-937 to L-975; A-938 to L-975; G-939 to L-975; D-940 to L-975; A-941 to L-975; V-942 to L-975; N-943 to L-975; V-944 to L-975; V-945 to L-975; V-946 to L-975; T-947 to L-975; G-948 to L-975; G-949 to L-975; K-950 to L-975; L-951 to L-975; A-952 to L-975; H-953 to L-975; T-954 to L-975; D-955 to L-975; F-956 to L-975; D-957 to L-975; E-958 to L-975; M-959 to L-975; Y-960 to L-975; S-961 to L-975; T-962 to L-975; F-963 to L-975; S-964 to L-975; G-965 to L-975; V-966 to L-975; F-967 to L-975; L-968 to L-975; Y-969 to L-975; and P-970 to L-975 of SEQ ID NO: 63.  
       [0338] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0339] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 63: P-816 to H-974; P-816 to S-973; P-816 to L-972; P-816 to F-971; P-816 to P-970; P-816 to Y-969; P-816 to L-968; P-816 to F-967; P-816 to V-966; P-186 to G-965; P-816 to S-964; P-816 to F-963; P-816 to T-962; P-816 to S-961; P-816 to Y-960; P-816 to M-959; P-816 to E-958; P-816 to D-957; P-816 to F-956; P-816 to D-955; P-816 to T-954; P-816 to H-953; P-816 to A-952; P-816 to L-951; P-816 to K-950; P-816 to G-949; P-816 to G-948; P-816 to T-947; P-816 to V-946; P-816 to V-945; P-816 to V-944; P-816 to N-943; P-816 to V-942; P-816 to A-941; P-816 to D-940; P-816 to G-939; P-816 to A-938; P-816 to K-937; P-816 to L-936; P-816 to H-935; P-816 to V-934; P-816 to I-933; P-816 to L-932; P-816 to H-931; P-816 to F-930; P-816 to A-929; P-816 to G-928; P-816 to P-927; P-816 to G-926; P-816 to G-925; P-816 to C-924; P-816 to T-923; P-816 to H-922; P-816 to L-921; P-816 to A-920; P-816 to G-919; P-816 to P-918; P-816 to P-917; P-816 to R-916; P-816 to H-915; P-816 to Y-914; P-816 to E-913; P-816 to L-912; P-816 to F-911; P-816 to E-910; P-816 to R-909; P-816 to R-908; P-816 to Y-907; P-816 to G-906; P-816 to A-905; P-816 to T-904; P-816 to H-903; P-816 to L-902; P-816 to Q-901; P-816 to A-900; P-816 to V-899; P-816 to S-898; P-816 to A-897; P-816 to N-896; P-816 to S-895; P-816 to V-894; P-816 to S-893; P-816 to L-892; P-816 to V-891; P-816 to A-890; P-816 to E-889; P-816 to V-888; P-816 to Y-887; P-816 to A-886; P-816 to D-885; P-816 to R-884; P-816 to E-883; P-816 to P-882; P-816 to T-881; P-816 to L-880; P-816 to T-879; P-816 to A-878; P-816 to T-877; P-816 to I-876; P-816 to L-875; P-816 to Y-874; P-816 to R-873; P-816 to G-872; P-816 to D-871; P-816 to Y-870; P-816 to P-869; P-816 to A-868; P-816 to T-867; P-816 to F-866; P-816 to V-865; P-816 to G-864; P-816 to T-863; P-816 to S-862; P-816 to P-861; P-816 to N-860; P-816 to Y-859; P-816 to V-858; P-816 to D-857; P-816 to G-856; P-816 to D-855; P-816 to N-854; P-816 to V-853; P-816 to L-852; P-816 to V-851; P-816 to K-850; P-816 to N-849; P-816 to F-848; P-816 to L-847; P-816 to V-846; P-816 to V-845; P-816 to G-844; P-816 to G-843; P-816 to D-842; P-816 to S-841; P-816 to P-840; P-816 to F-839; P-816 to P-838; P-816 to K-837; P-816 to Q-836; P-816 to T-835; P-816 to L-834; P-816 to G-833; P-816 to A-832; P-816 to S-831; P-816 to F-830; P-816 to S-829; P-816 to V-828; P-816 to L-827; P-816 to S-826; P-816 to P-825; P-816 to V-824; P-816 to P-823; and P-816 to A-822 of SEQ ID NO: 63.  
       [0340] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0341] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 63, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0342] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0343] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, where this portion excludes any integer of amino acid residues from 1 to about 969 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, or any integer of amino acid residues from 1 to about 969 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0344] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0345] Translation products of this gene stimulate glucose transport in adipocytes.  
       [0346] It has been discovered that this gene is expressed in primary dendritic cells, monocytes, and macrophages.  
       [0347] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, and immunological disorders.  
       [0348] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and immune systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, immune, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0349] The structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0350] In addition, expression of this gene in primary dendritic cells, monocytes, and macrophages and the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0351] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0352] Features of Protein Encoded by Gene No.: 15  
       [0353] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0354] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0355] Preferred polypeptides of the present invention comprise, or alternatively consist of, one or both of the immunogenic epitopes shown in SEQ ID NO: 64 as residues: Asn-108 to Ser-118, and Ser-143 to Phe-150. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0356] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 64 as residues Pro-17 to Asp-158. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0357] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 64 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0358] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0359] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0360] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 64: V-18 to D-158; H-19 to D-158; V-20 to D-158; Y-21 to D-158; P-22 to D-158; L-23 to D-158; P-24 to D-158; Q-25 to D-158; Q-26 to D-158; M-27 to D-158; R-28 to D-158; V-29 to D-158; A-30 to D-158; F-31 to D-158; S-32 to D-158; A-33 to D-158; A-34 to D-158; R-35 to D-158; T-36 to D-158; S-37 to D-158; N-38 to D-158; L-39 to D-158; A-40 to D-158; P-41 to D-158; G-42 to D-158; T-43 to D-158; L-44 to D-158; D-45 to D-158; Q-46 to D-158; P-47 to D-158; I-48 to D-158; V-49 to D-158; F-50 to D-158; D-51 to D-158; L-52 to D-158; L-53 to D-158; L-54 to D-158; N-55 to D-158; N-56 to D-158; L-57 to D-158; G-58 to D-158; E-59 to D-158; T-60 to D-158; F-61 to D-158; D-62 to D-158; L-63 to D-158; Q-64 to D-158; L-65 to D-158; G-66 to D-158; R-67 to D-158; F-68 to D-158; N-69 to D-158; C-70 to D-158; P-71 to D-158; V-72 to D-158; N-73 to D-158; G-74 to D-158; T-75 to D-158; Y-76 to D-158; V-77 to D-158; F-78 to D-158; I-79 to D-158; F-80 to D-158; H-81 to D-158; M-82 to D-158; L-83 to D-158; K-84 to D-158; L-85 to D-158; A-86 to D-158; V-87 to D-158; N-88 to D-158; V-89 to D-158; P-90 to D-158; L-91 to D-158; Y-92 to D-158; V-93 to D-158; N-94 to D-158; L-95 to D-158; M-96 to D-158; K-97 to D-158; N-98 to D-158; E-99 to D-158; E-100 to D-158; V-101 to D-158; L-102 to D-158; V-103 to D-158; S-104 to D-158; A-105 to D-158; Y-106 to D-158; A-107 to D-158; N-108 to D-158; D-109 to D-158; G-110 to D-158; A-111 to D-158; P-112 to D-158; D-113 to D-158; H-114 to D-158; E-115 to D-158; T-116 to D-158; A-117 to D-158; S-118 to D-158; N-119 to D-158; H-120 to D-158; A-121 to D-158; I-122 to D-158; L-123 to D-158; Q-124 to D-158; L-125 to D-158; F-126 to D-158; Q-127 to D-158; G-128 to D-158; D-129 to D-158; Q-130 to D-158; I-131 to D-158; W-132 to D-158; L-133 to D-158; R-134 to D-158; L-135 to D-158; H-136 to D-158; R-137 to D-158; G-138 to D-158; A-139 to D-158; I-140 to D-158; Y-141 to D-158; G-142 to D-158; S-143 to D-158; S-144 to D-158; W-145 to D-158; K-146 to D-158; Y-147 to D-158; S-148 to D-158; T-149 to D-158; F-150 to D-158; S-151 to D-158; G-152 to D-158; and Y-153 to D-158 of SEQ ID NO: 64.  
       [0361] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0362] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 64: P-17 to Q-157; P-17 to Y-156; P-17 to L-155; P-17 to L-154; P-17 to Y-153; P-17 to G-152; P-17 to S-151; P-17 to F-150; P-17 to T-149; P-17 to S-148; P-17 to Y-147; P-17 to K-146; P-17 to W-145; P-17 to S-144; P-17 to S-143; P-17 to G-142; P-17 to Y-141; P-17 to I-140; P-17 to A-139; P-17 to G-138; P-17 to R-137; P-17 to H-136; P-17 to L-135; P-17 to R-134; P-17 to L-133; P-17 to W-132; P-17 to I-131; P-17 to Q-130; P-17 to D-129; P-17 to G-128; P-17 to Q-127; P-17 to F-126; P-17 to L-125; P-17 to Q-124; P-17 to L-123; P-17 to I-122; P-17 to A-121; P-17 to H-120; P-17 to N-119; P-17 to S-118; P-17 to A-117; P-17 to T-116; P-17 to E-115; P-17 to H-114; P-17 to D-113; P-17 to P-112; P-17 to A-111; P-17 to G-110; P-17 to D-109; P-17 to N-108; P-17 to A-107; P-17 to Y-106; P-17 to A-105; P-17 to S-104; P-17 to V-103; P-17 to L-102; P-17 to V-101; P-17 to E-100; P-17 to E-99; P-17 to N-98; P-17 to K-97; P-17 to M-96; P-17 to L-95; P-17 to N-94; P-17 to V-93; P-17 to Y-92; P-17 to L-91; P-17 to P-90; P-17 to V-89; P-17 to N-88; P-17 to V-87; P-17 to A-86; P-17 to L-85; P-17 to K-84; P-17 to L-83; P-17 to M-82; P-17 to H-81; P-17 to F-80; P-17 to I-79; P-17 to F-78; P-17 to Y-76; P-17 to T-75; P-17 to G-74; P-17 to N-73; P-17 to V-72; P-17 to P-71; P-17 to C-70; P-17 to N-69; P-17 to F-68; P-17 to R-67; P-17 to G-66; P-17 to L-65; P-17 to Q-64; P-17 to L-63; P-17 to D-62; P-17 to F-61; P-17 to T-60; P-17 to E-59; P-17 to G-58; P-17 to L-57; P-17 to N-56; P-17 to N-55; P-17 to L-54; P-17 to L-53; P-17 to L-52; P-17 to D-51; P-17 to F-50; P-17 to V-49; P-17 to I-48; P-17 to P-47; P-17 to Q-46; P-17 to D-45; P-17 to L-44; P-17 to T-43; P-17 to G-42; P-17 to P-41; P-17 to A-40; P-17 to L-39; P-17 to N-38; P-17 to S-37; P-17 to T-36; P-17 to R-35; P-17 to A-34; P-17 to A-33; P-17 to S-32; P-17 to F-31; P-17 to A-30; P-17 to V-29; P-17 to R-28; P-17 to M-27; P-17 to Q-26; P-17 to Q-25; P-17 to P-24; and P-17 to L-23 of SEQ ID NO: 64.  
       [0363] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0364] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 64, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0365] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0366] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, where this portion excludes any integer of amino acid residues from 1 to about 152 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, or any integer of amino acid residues from 1 to about 152 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0367] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0368] It has been discovered that this gene is expressed in skeletal muscle as well as neural tissues, including infant brain and neuron-derived libraries.  
       [0369] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, and neurological disorders.  
       [0370] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., muscle, adipose, neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0371] The expression of this gene in skeletal muscle and structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0372] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0373] More generally, the expression of this gene in neural tissues and homology to the Clq family of proteins indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of neurological disorders, such as for example, those disclosed herein under “Neural Activity and Neurological Diseases”.  
       [0374] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0375] Features of Protein Encoded by Gene No.: 16  
       [0376] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including alpha 1 (VIII) collagen (e.g., see Genbank Accession No. X57527), a matrix protein involved in tissue remodeling such as in injured arteries and atherosclerotic plaques; and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0377] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0378] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 65 as residues: Leu-6 to Gln-16, Pro-56 to His-63, Pro-77 to Gly-90, Arg-98 to Phe-106, Lys-115 to Met-120, Pro-141 to Leu-147, Pro-153 to Gln-159, Pro-191 to Glu-196, Pro-217 to Met-225, Pro-234 to Gly-239, Gln-283 to Gly-290, Pro-321 to Lys-328, Pro-349 to Gly-356, Pro-422 to Gly-430, Thr-438 to Leu-446, Tyr-462 to Pro-472, Tyr-501 to Thr-511, and Thr-549 to Phe-557. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0379] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 65 as residues Lys-466 to Met-605. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0380] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 65 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0381] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0382] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0383] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 65: G-467 to M-605; K-468 to M-605; N-469 to M-605; G-470 to M-605; G-471 to M-605; P-472 to M-605; A-473 to M-605; Y-474 to M-605; E-475 to M-605; M-476 to M-605; P-477 to M-605; A-478 to M-605; F-479 to M-605; T-480 to M-605; A-481 to M-605; E-482 to M-605; L-483 to M-605; T-484 to M-605; A-485 to M-605; P-486 to M-605; F-487 to M-605; P-488 to M-605; P-489 to M-605; V-490 to M-605; G-491 to M-605; A-492 to M-605; P-493 to M-605; V-494 to M-605; K-495 to M-605; F-496 to M-605; N-497 to M-605; K-498 to M-605; L-499 to M-605; L-500 to M-605; Y-501 to M-605; N-502 to M-605; G-503 to M-605; R-504 to M-605; Q-505 to M-605; N-506 to M-605; Y-507 to M-605; N-508 to M-605; P-509 to M-605; Q-510 to M-605; T-511 to M-605; G-512 to M-605; I-513 to M-605; F-514 to M-605; T-515 to M-605; C-516 to M-605; E-517 to M-605; V-518 to M-605; P-519 to M-605; G-520 to M-605; V-521 to M-605; Y-522 to M-605; Y-523 to M-605; F-524 to M-605; A-525 to M-605; Y-526 to M-605; H-527 to M-605; V-528 to M-605; H-529 to M-605; C-530 to M-605; K-531 to M-605; G-532 to M-605; G-533 to M-605; N-534 to M-605; V-535 to M-605; W-536 to M-605; V-537 to M-605; A-538 to M-605; L-539 to M-605; F-540 to M-605; K-541 to M-605; N-542 to M-605; N-543 to M-605; E-544 to M-605; P-545 to M-605; V-546 to M-605; M-547 to M-605; Y-548 to M-605; T-549 to M-605; Y-550 to M-605; D-551 to M-605; E-552 to M-605; Y-553 to M-605; K-554 to M-605; K-555 to M-605; G-556 to M-605; F-557 to M-605; L-558 to M-605; D-559 to M-605; Q-560 to M-605; A-561 to M-605; S-562 to M-605; G-563 to M-605; S-564 to M-605; A-565 to M-605; V-566 to M-605; L-567 to M-605; L-568 to M-605; L-569 to M-605; R-570 to M-605; P-571 to M-605; G-572 to M-605; D-573 to M-605; R-574 to M-605; V-575 to M-605; F-576 to M-605; L-577 to M-605; Q-578 to M-605; M-579 to M-605; P-580 to M-605; S-581 to M-605; E-582 to M-605; Q-583 to M-605; A-584 to M-605; A-585 to M-605; G-586 to M-605; L-587 to M-605; Y-588 to M-605; A-589 to M-605; G-590 to M-605; Q-591 to M-605; Y-592 to M-605; V-593 to M-605; H-594 to M-605; S-595 to M-605; S-596 to M-605; F-597 to M-605; S-598 to M-605; G-599 to M-605; and Y-600 to M-605 of SEQ ID NO: 65.  
       [0384] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0385] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 65: K-466 to P-604; K-466 to Y-603; K-466 to L-602; K-466 to L-601; K-466 to Y-600; K-466 to G-599; K-466 to S-598; K-466 to F-597; K-466 to S-596; K-466 to S-595; K-466 to H-594; K-466 to V-593; K-466 to Y-592; K-466 to Q-591; K-466 to G-590; K-466 to A-589; K-466 to Y-588; K-466 to L-587; K-466 to G-586; K-466 to A-585; K-466 to A-584; K-466 to Q-583; K-466 to E-582; K-466 to S-581; K-466 to P-580; K-466 to M-579; K-466 to Q-578; K-466 to L-577; K-466 to F-576; K-466 to V-575; K-466 to R-574; K-466 to D-573; K-466 to G-572; K-466 to P-571; K-466 to R-570; K-466 to L-569; K-466 to L-568; K-466 to L-567; K-466 to V-566; K-466 to A-565; K-466 to S-564; K-466 to G-563; K-466 to S-562; K-466 to A-561; K-466 to Q-560; K-466 to D-559; K-466 to L-558; K-466 to F-557; K-466 to G-556; K-466 to K-555; K-466 to K-554; K-466 to Y-553; K-466 to E-552; K-466 to D-551; K-466 to Y-550; K-466 to T-549; K-466 to Y-548; K-466 to M-547; K-466 to V-546; K-466 to P-545; K-466 to E-544; K-466 to N-543; K-466 to N-542; K-466 to K-541; K-466 to F-540; K-466 to L-539; K-466 to A-538; K-466 to V-537; K-466 to W-536; K-466 to V-535; K-466 to N-534; K-466 to G-533; K-466 to G-532; K-466 to K-531; K-466 to C-530; K-466 to H-529; K-466 to V-528; K-466 to H-527; K-466 to Y-526; K-466 to A-525; K-466 to F-524; K-466 to Y-523; K-466 to Y-522; K-466 to V-521; K-466 to G-520; K-466 to P-519; K-466 to V-518; K-466 to E-517; K-466 to C-516; K-466 to T-515; K-466 to F-514; K-466 to I-513; K-466 to G-512; K-466 to T-511; K-466 to Q-510; K-466 to P-509; K-466 to N-508; K-466 to Y-507; K-466 to N-506; K-466 to Q-505; K-466 to R-504; K-466 to G-503; K-466 to N-502; K-466 to Y-501; K-466 to L-500; K-466 to L-499; K-466 to K-498; K-466 to N-497; K-466 to F-496; K-466 to K-495; K-466 to V-494; K-466 to P-493; K-466 to A-492; K-466 to G-491; K-466 to V-490; K-466 to P-489; K-466 to P-488; K-466 to F-487; K-466 to P-486; K-466 to A-485; K-466 to T-484; K-466 to L-483; K-466 to E-482; K-466 to A-481; K-466 to T-480; K-466 to F-479; K-466 to A-478; K-466 to P-477; K-466 to M-476; K-466 to E-475; K-466 to Y-474; K-466 to A-473; and K-466 to P-472 of SEQ ID NO: 65.  
       [0386] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0387] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 65, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0388] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0389] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, where this portion excludes any integer of amino acid residues from 1 to about 599 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575, or any integer of amino acid residues from 1 to about 599 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit Nos. PTA-2574 and PTA-2575. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0390] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0391] It has been discovered that this gene is expressed in adipocytes, smooth muscle, osteoblast stromal cells, osteoclastoma stromal cells, and bone marrow stromal cells.  
       [0392] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, as well as cardiovascular and bone disorders.  
       [0393] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, cardiovascular, and musculoskeletal systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, muscle, bone, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0394] The expression of this gene in adipocytes and the structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0395] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0396] Alternatively, the expression of this gene in smooth muscle tissue, and homology to alpha 1 (VIII) collagen indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of cardiovacular disorders, such as for example, atherosclerosis, restenosis, and/or those disclosed herein under “Cardiovascular Disorders”.  
       [0397] Furthermore, the expression of this gene in a number of bone-related tissues and homology to alpha 1 (VIII) collagen indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of bone and joint disorders, including osteoporosis, arthritis, and cancers of bone tissue, such as described under “Hyperproliferative Disorders” herein.  
       [0398] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0399] Features of Protein Encoded by Gene No.: 17  
       [0400] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including alpha 2 (VIII) collagen (e.g., see Genbank Accession No. AAA62822), a matrix protein involved in tissue remodeling such as in injured arteries and atherosclerotic plaques; and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0401] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0402] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, or all four of the immunogenic epitopes shown in SEQ ID NO: 66 as residues: Pro-6 to Gly-22, Arg-87 to Pro-98, Asp-140 to Tyr-146, Pro-169 to Asn-174. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0403] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 66 as residues Phe-55 to Thr-194. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0404] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 66 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0405] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0406] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0407] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 66: G-56 to T-194; L-57 to T-194; G-58 to T-194; E-59 to T-194; L-60 to T-194; S-61 to T-194; A-62 to T-194; H-63 to T-194; A-64 to T-65 to T-194; P-66 to T-194; A-67 to T-194; F-68 to T-194; T-69 to T-194; A-70 to T-194; V-71 to T-194; L-72 to T-194; T-73 to T-194; S-74 to T-194; P-75 to T-194; F-76 to T-194; P-77 to T-194; A-78 to T-194; S-79 to T-194; G-80 to T-194; M-81 to T-194; P-82 to T-194; V-83 to T-194; K-84 to T-194; F-85 to T-194; D-86 to T-194; R-87 to T-194; T-88 to T-194; L-89 to T-194; Y-90 to T-194; N-91 to T-194; G-92 to T-194; H-93 to T-194; S-94 to T-194; G-95 to T-194; Y-96 to T-194; N-97 to T-194; P-98 to T-194; A-99 to T-194; T-100 to T-194; G-101 to T-194; I-102 to T-194; F-103 to T-194; T-104 to T-194; C-105 to T-194; P-106 to T-194; V-107 to T-194; G-108 to T-194; G-109 to T-194; V-110 to T-194; Y-111 to T-194; Y-112 to T-194; F-113 to T-194; A-114 to T-194; Y-115 to T-194; H-116 to T-194; V-117 to T-194; H-118 to T-194; V-119 to T-194; K-120 to T-194; G-121 to T-194; T-122 to T-194; N-123 to T-194; V-124 to T-194; W-125 to T-194; V-126 to T-194; A-127 to T-194; L-128 to T-194; Y-129 to T-194; K-130 to T-194; N-131 to T-194; N-132 to T-194; V-133 to T-194; P-134 to T-194; A-135 to T-194; T-136 to T-194; Y-137 to T-194; T-138 to T-194; Y-139 to T-194; D-140 to T-194; E-141 to T-194; Y-142 to T-194; K-143 to T-194; K-144 to T-194; G-145 to T-194; Y-146 to T-194; L-147 to T-194; D-148 to T-194; Q-149 to T-194; A-150 to T-194; S-151 to T-194; G-152 to T-194; G-153 to T-194; A-154 to T-194; V-155 to T-194; L-156 to T-194; Q-157 to T-194; L-158 to T-194; R-159 to T-194; P-160 to T-194; N-161 to T-194; D-162 to T-194; Q-163 to T-194; V-164 to T-194; W-165 to T-194; V-166 to T-194; Q-167 to T-194; M-168 to T-194; P-169 to T-194; S-170 to T-194; D-171 to T-194; Q-172 to T-194; A-173 to T-194; N-174 to T-194; G-175 to T-194; L-176 to T-194; Y-177 to T-194; S-178 to T-194; T-179 to T-194; E-180 to T-194; Y-181 to T-194; I-182 to T-194; H-183 to T-194; S-184 to T-194; S-185 to T-194; F-186 to T-194; S-187 to T-194; G-188 to T-194; and F-189 to T-194 of SEQ ID NO: 66.  
       [0408] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0409] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 66: F-55 to P-193; F-55 to C-192; F-55 to L-191; F-55 to L-190; F-55 to F-189; F-55 to G-188; F-55 to S-187; F-55 to F-186; F-55 to S-185; F-55 to S-184; F-55 to H-183; F-55 to I-182; F-55 to Y-181; F-55 to E-180; F-55 to T-179; F-55 to S-178; F-55 to Y-177; F-55 to L-176; F-55 to G-175; F-55 to N-174; F-55 to A-173; F-55 to Q-172; F-55 to D-171; F-55 to S-170; F-55 to P-169; F-55 to M-168; F-55 to Q-167; F-55 to V-166; F-55 to W-165; F-55 to V-164; F-55 to Q-163; F-55 to D-162; F-55 to N-161; F-55 to P-160; F-55 to R-159; F-55 to L-158; F-55 to Q-157; F-55 to L-156; F-55 to V-155; F-55 to A-154; F-55 to G-153; F-55 to G-152; F-55 to S-151; F-55 to A-150; F-55 to Q-149; F-55 to D-148; F-55 to L-147; F-55 to Y-146; F-55 to G-145; F-55 to K-144; F-55 to K-143; F-55 to Y-142; F-55 to E-141; F-55 to D-140; F-55 to Y-139; F-55 to T-138; F-55 to Y-137; F-55 to T-136; F-55 to A-135; F-55 to P-134; F-55 to V-133; F-55 to N-132; F-55 to N-131; F-55 to K-130; F-55 to Y-129; F-55 to L-128; F-55 to A-127; F-55 to V-126; F-55 to W-125; F-55 to V-124; F-55 to N-123; F-55 to T-122; F-55 to G-121; F-55 to K-120; F-55 to V-119; F-55 to H-118; F-55 to V-117; F-55 to H-116; F-55 to Y-115; F-55 to A-114; F-55 to F-113; F-55 to Y-112; F-55 to Y-111; F-55 to V-110; F-55 to G-109; F-55 to G-108; F-55 to V-107; F-55 to P-106; F-55 to C-105; F-55 to T-104; F-55 to F-103; F-55 to I-102; F-55 to G-101; F-55 to T-100; F-55 to A-99; F-55 to P-98; F-55 to N-97; F-55 to Y-96; F-55 to G-95; F-55 to S-94; F-55 to H-93; F-55 to G-92; F-55 to N-91; F-55 to Y-90; F-55 to L-89; F-55 to T-88; F-55 to R-87; F-55 to D-86; F-55 to F-85; F-55 to K-84; F-55 to V-83; F-55 to P-82; F-55 to M-81; F-55 to G-80; F-55 to S-79; F-55 to A-78; F-55 to P-77; F-55 to F-76; F-55 to P-75; F-55 to S-74; F-55 to T-73; F-55 to L-72; F-55 to V-71; F-55 to A-70; F-55 to T-69; F-55 to F-68; F-55 to A-67; F-55 to P-66; F-55 to T-65; F-55 to A-64; F-55 to H-63; F-55 to A-62; and F-55 to S-61 of SEQ ID NO: 66.  
       [0410] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0411] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 66, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0412] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0413] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0414] It has been discovered that this gene is expressed in adipocytes, macrophages, osteoblasts, chondrosarcoma, trabecular bone cells, and cerebellum.  
       [0415] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, as well as immune, bone, and neural disorders.  
       [0416] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, immune, musculoskeletal, and nervous systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, muscle, bone, neural, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0417] The expression of this gene in adipocytes and the structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0418] In addition, expression of this gene in macrophages and similarity to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0419] Furthermore, the expression of this gene in a number of bone-related tissues and homology to alpha 2 (VIII) collagen indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of bone and joint disorders, including osteoporosis, arthritis, and cancers of bone tissue, such as described under “Hyperproliferative Disorders” herein.  
       [0420] Alternatively, the expression of this gene in cerebellum, and homology to alpha 2 (VIII) collagen indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of neurodegenerative disorders, such as for example, those described herein under “Neural Activity and Neurological Diseases”.  
       [0421] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0422] Features of Protein Encoded by Gene No.: 18  
       [0423] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0424] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0425] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 67 as residues: Gly-15 to Gln-23, Pro-47 to Gly-69, Gln-98 to Glu-106, Phe-136 to Phe-150, Tyr-186 to Asp-195, Gly-217 to Gly-223, and Ala-226 to Ser-232. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0426] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 67 as residues Lys-101 to Asn-244. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0427] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 67 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0428] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0429] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0430] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 67: G-102 to N-244; E-103 to N-244; P-104 to N-244; G-105 to N-244; E-106 to N-244; G-107 to N-244; A-108 to N-244; Y-109 to N-244; V-110 to N-244; Y-111 to N-244; R-112 to N-244; S-113 to N-244; A-114 to N-244; F-115 to N-244; S-116 to N-244; V-117 to N-244; G-118 to N-244; L-119 to N-244; E-120 to N-244; T-121 to N-244; Y-122 to N-244; V-123 to N-244; T-124 to N-244; I-125 to N-244; P-126 to N-244; N-127 to N-244; M-128 to N-244; P-129 to N-244; I-130 to N-244; R-131 to N-244; F-132 to N-244; T-133 to N-244; K-134 to N-244; I-135 to N-244; F-136 to N-244; Y-137 to N-244; N-138 to N-244; Q-139 to N-244; Q-140 to N-244; N-141 to N-244; H-142 to N-244; Y-143 to N-244; D-144 to N-244; G-145 to N-244; S-146 to N-244; T-147 to N-244; G-148 to N-244; K-149 to N-244; F-150 to N-244; H-151 to N-244; C-152 to N-244; N-153 to N-244; I-154 to N-244; P-155 to N-244; G-156 to N-244; L-157 to N-244; Y-158 to N-244; Y-159 to N-244; F-160 to N-244; A-161 to N-244; Y-162 to N-244; H-163 to N-244; I-164 to N-244; T-165 to N-244; V-166 to N-244; Y-167 to N-244; M-168 to N-244; K-169 to N-244; D-170 to N-244; V-171 to N-244; K-172 to N-244; V-173 to N-244; S-174 to N-244; L-175 to N-244; F-176 to N-244; K-177 to N-244; K-178 to N-244; D-179 to N-244; K-180 to N-244; A-181 to N-244; M-182 to N-244; L-183 to N-244; F-184 to N-244; T-185 to N-244; Y-186 to N-244; D-187 to N-244; Q-188 to N-244; Y-189 to N-244; Q-190 to N-244; E-191 to N-244; N-192 to N-244; N-193 to N-244; V-194 to N-244; D-195 to N-244; Q-196 to N-244; A-197 to N-244; S-1 98 to N-244; G-199 to N-244; S-200 to N-244; V-201 to N-244; L-202 to N-244; L-203 to N-244; H-204 to N-244; L-205 to N-244; E-206 to N-244; V-207 to N-244; G-208 to N-244; D-209 to N-244; Q-210 to N-244; V-211 to N-244; W-212 to N-244; L-213 to N-244; Q-214 to N-244; V-215 to N-244; Y-216 to N-244; G-217 to N-244; E-218 to N-244; G-219 to N-244; E-220 to N-244; R-221 to N-244; N-222 to N-244; G-223 to N-244; L-224 to N-244; Y-225 to N-244; A-226 to N-244; D-227 to N-244; N-228 to N-244; D-229 to N-244; N-230 to N-244; D-231 to N-244; S-232 to N-244; T-233 to N-244; F-234 to N-244; T-235 to N-244; G-236 to N-244; F-237 to N-244; L-238 to N-244; and L-239 to N-244 of SEQ ID NO: 67.  
       [0431] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0432] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 67: K-101 to T-243; K-101 to D-242; K-101 to H-241; K-101 to Y-240; K-101 to L-239; K-101 to L-238; K-101 to F-237; K-101 to G-236; K-101 to T-235; K-101 to F-234; K-101 to T-233; K-110 to S-232; K-101 to D-231; K-101 to N-230; K-101 to D-229; K-101 to N-228; K-101 to D-227; K-101 to A-226; K-101 to Y-225; K-101 to L-224; K-101 to G-223; K-101 to N-222; K-101 to R-221; K-101 to E-220; K-101 to G-219; K-101 to E-218; K-101 to G-217; K-101 to Y-216; K-101 to V-215; K-101 to Q-214; K-101 to L-213; K-101 to W-212; K-101 to V-211; K-101 to Q-210; K-101 to D-209; K-101 to G-208; K-101 to V-207; K-101 to E-206; K-101 to L-205; K-101 to H-204; K-101 to L-203; K-101 to L-202; K-101 to V-201; K-101 to S-200; K-101 to G-199; K-101 to S-198; K-101 to A-197; K-101 to Q-196; K-101 to D-195; K-101 to V-194; K-101 to N-193; K-101 to N-192; K-101 to E-191; K-101 to Q-190; K-101 to Y-189; K-101 to Q-188; K-101 to D-187; K-101 to Y-186; K-101 to T-185; K-101 to F-184; K-101 to L-183; K-101 to M-182; K-101 to A-181; K-101 to K-180; K-101 to D-179; K-101 to K-178; K-101 to K-177; K-101 to F-176; K-101 to L-175; K-101 to S-174; K-101 to V-173; K-101 to K-172; K-101 to V-171; K-101 to D-170; K-101 to K-169; K-101 to M-168; K-101 to Y-167; K-101 to V-166; K-101 to T-165; K-101 to I-164; K-101 to H-163; K-101 to Y-162; K-101 to A-161; K-101 to F-160; K-101 to Y-159; K-101 to Y-158; K-101 to L-157; K-101 to G-156; K-101 to P-155; K-101 to I-154; K-101 to N-153; K-101 to C-152; K-101 to H-151; K-101 to F-150; K-101 to K-149; K-101 to G-148; K-101 to T-147; K-101 to S-146; K-101 to G-145; K-101 to D-144; K-101 to Y-143; K-101 to H-142; K-101 to N-141; K-101 to Q-140; K-101 to Q-139; K-101 to N-138; K-101 to Y-137; K-101 to F-136; K-101 to I-135; K-101 to K-134; K-101 to T-133; K-101 to F-132; K-101 to R-131; K-101 to I-130; K-101 to P-129; K-101 to M-128; K-101 to N-127; K-101 to P-126; K-101 I-125; K-101 to T-124; K-101 to V-123; K-101 to Y-122; K-101 to T-121; K-101 to E-120; K-101 to L-119; K-101 to G-118; K-101 to V-117; K-101 to S-116; K-101 to F-115; K-101 to A-114; K-101 to S-113; K-101 to R-112; K-101 to Y-111; K-101 to V-110; K-101 to Y-109; K-101 to A-108; and K-101 to G-107 of SEQ ID NO: 67.  
       [0433] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0434] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 67, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0435] The present invention is also directed to proteins containing polypeptides at least 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to a polypeptide sequence set forth herein as m−n. In preferred embodiments, the application is directed to proteins containing polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to polypeptides having the amino acid sequence of the specific N- and C-terminal deletions recited herein. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0436] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0437] It has been discovered that this gene is expressed in adipose tissue.  
       [0438] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism.  
       [0439] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0440] The expression of this gene in adipose tissue and the structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0441] In addition, expression of this gene in macrophages and similarity to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0442] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0443] Features of Protein Encoded by Gene No.: 19  
       [0444] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including EMILIN (e.g., see Genbank Accession No. AF088916), a secreted protein that regulates the formation of elastic fibers in various tissues including blood vessels, cartilage, skin, and lung; and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0445] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0446] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 68 as residues: Asn-35 to Arg-53, Arg-108 to Gln-115, Pro-170 to Glu-191, Pro-225 to Gly-230, Asp-241 to Glu-248, Asp-289 to Asn-300, and Pro-302 to Pro-310. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0447] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 68 as residues Glu-206 to Ala-361. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0448] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 68 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0449] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0450] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0451] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 68: G-207 to A-361; A-208 to A-361; P-209 to A-361; A-210 to A-361; A-211 to A-361; P-212 to A-361; V-213 to A-361; P-214 to A-361; Q-215 to A-361; V-216 to A-361; A-217 to A-361; F-218 to A-361; S-219 to A-361; A-220 to A-361; A-221 to A-361; L-222 to A-361; S-223 to A-361; L-224 to A-361; P-225 to A-361; R-226 to A-361; S-227 to A-361; E-228 to A-361; P-229 to A-361; G-230 to A-361; T-231 to A-361; V-232 to A-361; P-233 to A-361; F-234 to A-361; D-235 to A-361; R-236 to A-361; V-237 to A-361; L-238 to A-361; L-239 to A-361; N-240 to A-361; D-241 to A-361; G-242 to A-361; G-243 to A-361; Y-244 to A-361; Y-245 to A-361; D-246 to A-361; P-247 to A-361; E-248 to A-361; T-249 to A-361; G-250 to A-361; V-251 to A-361; F-252 to A-361; T-253 to A-361; A-254 to A-361; P-255 to A-361; L-256 to A-361; A-257 to A-361; G-258 to A-361; R-259 to A-361; Y-260 to A-361; L-261 to A-361; L-262 to A-361; S-263 to A-361; A-264 to A-361; V-265 to A-361; L-266 to A-361; T-267 to A-361; G-268 to A-361; H-269 to A-361; R-270 to A-361; H-271 to A-361; E-272 to A-361; K-273 to A-361; V-274 to A-361; E-275 to A-361; A-276 to A-361; V-277 to A-361; L-278 to A-361; S-279 to A-361; R-280 to A-361; S-281 to A-361; N-282 to A-361; Q-283 to A-361; G-284 to A-361; V-285 to A-361; A-286 to A-361; R-287 to A-361; V-288 to A-361; D-289 to A-361; S-290 to A-361; G-291 to A-361; G-292 to A-361; Y-293 to A-361; E-294 to A-361; P-295 to A-361; E-296 to A-361; G-297 to A-361; L-298 to A-361; E-299 to A-361; N-300 to A-361; K-301 to A-361; P-302 to A-361; V-303 to A-361; A-304 to A-361; E-305 to A-361; S-306 to A-361; Q-307 to A-361; P-308 to A-361; S-309 to A-361; P-310 to A-361; G-311 to A-361; T-312 to A-361; L-313 to A-361; G-314 to A-361; V-315 to A-361; F-316 to A-361; S-317 to A-361; L-318 to A-361; I-319 to A-361; L-320 to A-361; P-321 to A-361; L-322 to A-361; Q-323 to A-361; A-324 to A-361; G-325 to A-361; D-326 to A-361; T-327 to A-361; V-328 to A-361; C-329 to A-361; V-330 to A-361; D-331 to A-361; L-332 to A-361; V-333 to A-361; M-334 to A-361; G-335 to A-361; Q-336 to A-361; L-337 to A-361; A-338 to A-361; H-339 to A-361; S-340 to A-361; E-341 to A-361; E-342 to A-361; P-343 to A-361; L-344 to A-361; T-345 to A-361; I-346 to A-361; F-347 to A-361; S-348 to A-361; G-349 to A-361; A-350 to A-361; L-351 to A-361; L-352 to A-361; Y-353 to A-361; G-354 to A-361; D-355 to A-361; and P-356 to A-361 of SEQ ID NO: 68.  
       [0452] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0453] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 68: E-206 to H-360; E-206 to E-359; E-206 to L-358; E-206 to E-357; E-206 to P-356; E-206 to D-355; E-206 to G-354; E-206 to Y-353; E-206 to L-352; E-206 to L-351; E-206 to A-350; E-206 to G-349; E-206 to S-348; E-206 to F-347; E-206 to I-346; E-206 to T-345; E-206 to L-344; E-206 to P-343; E-206 to E-342; E-206 to E-341; E-206 to S-340; E-206 to H-339; E-206 to A-338; E-206 to L-337; E-206 to Q-336; E-206 to G-335; E-206 to M-334; E-206 to V-333; E-206 to L-332; E-206 to D-331; E-206 to V-330; E-206 to C-329; E-206 to V-328; E-206 to T-327; E-206 to D-326; E-206 to G-325; E-206 to A-324; E-206 to Q-323; E-206 to L-322; E-206 to P-321; E-206 to L-320; E-206 to I-319; E-206 to L-318; E-206 to S-317; E-206 to F-316; E-206 to V-315; E-206 to G-314; E-206 to L-313; E-206 to T-312; E-206 to G-311; E-206 to P-310; E-206 to S-309; E-206 to P-308; E-206 to Q-307; E-206 to S-306; E-206 to E-305; E-206 to A-304; E-206 to V-303; E-206 to P-302; E-206 to K-301; E-206 to N-300; E-206 to E-299; E-206 to L-298; E-206 to G-297; E-206 to E-296; E-206 to P-295; E-206 to E-294; E-206 to Y-293; E-206 to G-292; E-206 to G-291; E-206 to S-290; E-206 to D-289; E-206 to V-288; E-206 to R-287; E-206 to A-286; E-206 to V-285; E-206 to G-284; E-206 to Q-283; E-206 to N-282; E-206 to S-281; E-206 to R-280; E-206 to S-279; E-206 to L-278; E-206 to V-277; E-206 to A-276; E-206 to E-275; E-206 to V-274; E-206 to K-273; E-206 to E-272; E-206 to H-271; E-206 to R-270; E-206 to H-269; E-206 to G-268; E-206 to T-267; E-206 to L-266; E-206 to V-265; E-206 to A-264; E-206 to S-263; E-206 to L-262; E-206 to L-261; E-206 to Y-260; E-206 to R-259; E-206 to G-258; E-206 to A-257; E-206 to L-256; E-206 to P-255; E-206 to A-254; E-206 to T-253; E-206 to F-252; E-206 to V-251; E-206 to G-250; E-206 to T-249; E-206 to E-248; E-206 to P-247; E-206 to D-246; E-206 to Y-245; E-206 to Y-244; E-206 to G-243; E-206 to G-242; E-206 to D-241; E-206 to N-240; E-206 to L-239; E-206 to L-238; E-206 to V-237; E-206 to R-236; E-206 to D-235; E-206 to F-234; E-206 to P-233; E-206 to V-232; E-206 to T-231; E-206 to G-230; E-206 to P-229; E-206 to E-228; E-206 to S-227; E-206 to R-226; E-206 to P-225; E-206 to L-224; E-206 S-223; E-206 to L-222; E-206 to A-221; E-206 to A-220; E-206 to S-219; E-206 to F-218; E-206 to A-217; E-206 to V-216; E-206 to Q-215; E-206 to P-214; E-206 to V-213; and E-206 to P-212 of SEQ ID NO: 68.  
       [0454] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0455] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 68, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0456] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-791, where this portion excludes any integer of amino acid residues from 1 to about 355 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-791, or any integer of amino acid residues from 1 to about 355 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-791. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0457] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0458] It has been discovered that this gene is expressed in adipose tissue.  
       [0459] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism.  
       [0460] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine system, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0461] The expression of this gene in adipose tissue and the structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0462] In addition, the similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0463] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
       [0464] Features of Protein Encoded by Gene No.: 20  
       [0465] The translation product of this gene shares sequence and/or structural similarity with members of the Clq family of proteins, including collagen alpha 1(X) (e.g., see Genbank Accession No. S23297), a matrix protein involved in tissue remodeling such as in injured arteries and atherosclerotic plaques; and ACRP30, an adipocyte complement-related protein (see, e.g., Genbank Accession Numbers AAA80543 and Q15848; all references available through these accessions are herein incorporated by reference in their entireties). ACRP30 is an abundant serum protein secreted exclusively from fat cells, which is implicated in energy homeotasis and obesity. ACRP30 is a close homologue of the complement protein Clq, which is involved in the recognition of microbial surfaces and antibody-antigen complexes in the classical pathway of complement. The structure reveals a homology to the tumor necrosis factor (TNF) family. Identical folding topologies, key residue conservations, and similarity of trimer interfaces and intron positions firmly establish an evolutionary link between the TNF and Clq families. It has been suggested that TNFs, which control many aspects of inflammation, adaptive immunity, apoptosis and energy homeostasis arose by divergence from a primordial recognition molecule of the innate immune system. The evolutionary connection between Clq-like proteins and TNFs illuminates the shared functions of these two important groups of proteins (Shapiro and Scherer, Curr Biol 8:335-338 (1998).  
       [0466] The ACRP30 cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a stalk region (Gly-X-Y repeats), and a globular domain. The globular domain of ACRP30 is situated at the COOH-terminus and shares significant homology with subunits of complement factor Clq, collagen 1(X), the brain-specific factor cerebellin, hibernating proteins-20, 25, and 27, TNF alpha, CORS26, collagen VIII, Elastin Microfibril Interface-Located Proteins (EMILINs), and Multimerin. The expression of ACRP30 is highly specific to adipose tissue in both mouse and rat. Expression of ACRP30 is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain ACRP30 mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for ACRP30. Furthermore, the expression of ACRP30 mRNA is significantly reduced in the adipose tissues from obese mice and humans. The tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue (Liang and Spiegelman, J. Biol Chem. 271:10697-10703 (1996)). ACRP-30 is believed to play a role in clearing lipids from the blood by increasing free fatty acid (FFA) oxidation by muscle tissue. Also, FFAs are potent inhibitors of insulin signaling. Accordingly, homologs of ACRP-30, and corresponding agonists thereof such as antibodies, are useful for treating obesity and diabetes, as well as other metabolic and endocrine conditions or disorders.  
       [0467] Preferred polypeptides of the present invention comprise, or alternatively consist of, one, two, three, four, five, or more of the immunogenic epitopes shown in SEQ ID NO: 69 as residues: Asn-16 to Gly-26, Asn-33 to Gly-38, Pro-40 to Gly-80, Gly-89 to Lys-103, Glu-117 to Val-130, Pro-132 to Asn-141, Pro-160 to Glu-165, Pro-168 to Gly-173, Gly-182 to Lys-192, Glu-230 to Asp-235, Met-281 to Ala-287, and Asp-317 to Thr-322. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0468] In nonexclusive embodiments, polypeptides of the invention comprise, or alternatively consist of, the globular domain of the protein shown in SEQ ID NO: 69 as residues Lys-190 to Pro-333. Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0469] Also preferred are polypeptides comprising, or alternatively consisting of, fragments of the mature portion of the protein shown in SEQ ID NO: 69 demonstrating functional activity. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0470] By functional activity is meant, a polypeptide fragment capable of displaying one or more known functional activities associated with the full-length (complete) protein of the invention. Such functional activities include, but are not limited to, biological activity (e.g., modulating glucose transport in adipocytes, clearing lipids from the blood, ability to increase FFA oxidation by muscle tissue, and increased expression in response to insulin), antigenicity (ability to bind, or compete with a polypeptide of the invention for binding, to an antibody specific for the polypeptide of the invention), immunogenicity (ability to generate antibodies which specifically bind to the polypeptides of the invention), and ability to form multimers with polypeptides of the invention.  
       [0471] Even if deletion of one or more amino acids from the C-terminus of a protein results in modification or loss of one or more biological functions of the protein (e.g., ability to increase FFA oxidation by muscle tissue), other functional activities (e.g., biological activities, ability to multimerize, ability to induce antibodies, ability to bind antibodies) may still be retained. For example, the ability of the shortened polypeptide to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a polypeptide with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0472] More in particular, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of N-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 69: G-191 to P-333; K-192 to P-333; I-193 to P-333; G-194 to P-333; E-195 to P-333; T-196 to P-333; L-197 to P-333; V-198 to P-333; L-199 to P-333; P-200 to P-333; K-201 to P-333; S-202 to P-333; A-203 to P-333; F-204 to P-333; T-205 to P-333; V-206 to P-333; G-207 to P-333; L-208 to P-333; T-209 to P-333; V-210 to P-333; L-211 to P-333; S-212 to P-333; K-213 to P-333; F-214 to P-333; P-215 to P-333; S-216 to P-333; S-217 to P-333; D-218 to P-333; V-219 to P-333; P-220 to P-333; I-221 to P-333; K-222 to P-333; F-223 to P-333; D-224 to P-333; K-225 to P-333; I-226 to P-333; L-227 to P-333; Y-228 to P-333; N-229 to P-333; E-230 to P-333; F-231 to P-333; N-232 to P-333; H-233 to P-333; Y-234 to P-333; D-235 to P-333; T-236 to P-333; A-237 to P-333; A-238 to P-333; G-239 to P-333; K-240 to P-333; F-241 to P-333; T-242 to P-333; C-243 to P-333; H-244 to P-333; I-245 to P-333; A-246 to P-333; G-247 to P-333; V-248 to P-333; Y-249 to P-333; Y-250 to P-333; F-251 to P-333; T-252 to P-333; Y-253 to P-333; H-254 to P-333; I-255 to P-333; T-256 to P-333; V-257 to P-333; F-258 to P-333; S-259 to P-333; R-260 to P-333; N-261 to P-333; V-262 to P-333; Q-263 to P-333; V-264 to P-333; S-265 to P-333; L-266 to P-333; V-267 to P-333; K-268 to P-333; N-269 to P-333; G-270 to P-333; V-271 to P-333; K-272 to P-333; I-273 to P-333; L-274 to P-333; H-275 to P-333; T-276 to P-333; K-277 to P-333; D-278 to P-333; A-279 to P-333; Y-280 to P-333; M-281 to P-333; S-282 to P-333; S-283 to P-333; E-284 to P-333; D-285 to P-333; Q-286 to P-333; A-287 to P-333; S-288 to P-333; G-289 to P-333; G-290 to P-333; I-291 to P-333; V-292 to P-333; L-293 to P-333; Q-294 to P-333; L-295 to P-333; K-296 to P-333; L-297 to P-333; G-298 to P-333; D-299 to P-333; E-300 to P-333; V-301 to P-333; W-302 to P-333; L-303 to P-333; Q-304 to P-333; V-305 to P-333; T-306 to P-333; G-307 to P-333; G-308 to P-333; E-309 to P-333; R-310 to P-333; F-311 to P-333; N-312 to P-333; G-313 to P-333; L-314 to P-333; F-315 to P-333; A-316 to P-333; D-317 to P-333; E-318 to P-333; D-319 to P-333; D-320 to P-333; D-321 to P-333; T-322 to P-333; T-323 to P-333; F-324 to P-333; T-325 to P-333; G-326 to P-333; F-327 to P-333; and L-328 to P-333 of SEQ ID NO: 69.  
       [0473] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0474] Additionally, the invention provides polynucleotides encoding polypeptides comprising, or alternatively consisting of, an amino acid sequence selected from the group of C-terminal deletions of the globular domain of the polypeptide of the invention shown as SEQ ID NO: 69: K-190 to S-332; K-190 to S-331; K-190 to F-330; K-190 to L-329; K-190 to L-328; K-190 to F-327; K-190 to G-326; K-190 to T-325; K-190 to F-324; K-190 to T-323; K-190 to T-322; K-190 to D-321; K-190 to D-320; K-l90 to D-319; K-190 to E-318; K-190 to D-317; K-190 to A-316; K-190 to F-315; K-190 to L-314; K-190 to G-313; K-190 to N-312; K-190 to F-311; K-190 to R-310; K-190 to E-309; K-190 to G-308; K-190 to G-307; K-190 to T-306; K-190 to V-305; K-190 to Q-304; K-190 to L-303; K-190 to W-302; K-190 to V-301; K-190 to E-300; K-190 to D-299; K-190 to G-298; K-190 to L-297; K-190 to K-296; K-190 to L-295; K-190 to Q-294; K-190 to L-293; K-190 to V-292; K-190 to I-291; K-190 to G-290; K-190 to G-289; K-190 to S-288; K-190 to A-287; K-190 to Q-286; K-190 to D-285; K-190 to E-284; K-190 to S-283; K-190 to S-282; K-190 to M-281; K-190 to Y-280; K-190 to A-279; K-190 to D-278; K-190 to K-277; K-190 to T-276; K-190 to H-275; K-190 to L-274; K-190 to I-273; K-190 to K-272; K-190 to V-271; K-190 to G-270; K-190 to N-269; K-190 to K-268; K-190 to V-267; K-190 to L-266; K-190 to S-265; K-190 to V-264; K-190 to Q-263; K-190 to V-262; K-190 to N-261; K-190 to R-260; K-190 to S-259; K-190 to F-258; K-190 to V-257; K-190 to T-256; K-190 to I-255; K-190 to H-254; K-190 to Y-253; K-190 to T-252; K-190 to F-251; K-190 to Y-250; K-190 to Y-249; K-190 to V-248; K-190 to G-247; K-190 to A-246; K-190 to I-245; K-190 to H-244; K-190 to C-243; K-190 to T-242; K-190 to F-241; K-190 to K-240; K-190 to G-239; K-190 to A-238; K-190 to A-237; K-190 to T-236; K-190 to D-235; K-190 to Y-234; K-190 to H-233; K-190 to N-232; K-190 to F-231; K-190 to E-230; K-190 to N-229; K-190 to Y-228; K-190 to L-227; K-190 to I-226; K-190 to K-225; K-190 to D-224; K-190 to F-223; K-190 to K-222; K-190 to I-221; K-190 to P-220; K-190 to V-219; K-190 to D-218; K-190 to S-217; K-190 to S-216; K-190 to P-215; K-190 to F-214; K-190 to K-213; K-190 to S-212; K-190 to L-211; K-190 to V-210; K-190 to T-209; K-190 to L-208; K-190 to G-207; K-190 to V-206; K-190 to T-205; K-190 to F-204; K-190 to A-203; K-190 to S-202; K-190 to K-201; K-190 to P-200; K-190 to L-199; K-190 to V-198; K-190 to L-197; and K-190 to T-196 of SEQ ID NO: 69.  
       [0475] Polynucleotides encoding these polypeptides are also encompassed by the invention, as are antibodies that bind one or more of these polypeptides. Moreover, fragments and variants of these polypeptides (e.g., fragments as described herein, polypeptides at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to these polypeptides and polypeptides encoded by the polynucleotide which hybridizes, under stringent conditions, to the polynucleotide encoding these polypeptides, or the complement thereof) are encompassed by the invention. Antibodies that bind these fragments and variants of the invention are also encompassed by the invention. Polynucleotides encoding these fragments and variants are also encompassed by the invention.  
       [0476] N-terminal deletions of translation products of the instant invention may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. C-terminal deletions of translation products of the instant invention may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Any of the above listed N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides comprising, or alternatively consisting of, one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of SEQ ID NO: 69, where n and m are integers as described above. Fragments and/or variants of these polypeptides, such as, for example, fragments and/or variants as described herein, are encompassed by the invention. Polynucleotides encoding these polypeptides (including fragments and/or variants) are also encompassed by the invention, as are antibodies that bind these polypeptides.  
       [0477] Also included are polynucleotide sequences encoding a polypeptide consisting of a portion of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3449, where this portion excludes any integer of amino acid residues from 1 about 327 amino acids from the amino terminus of the complete amino acid sequence encoded by a cDNA clone contained in ATCC Deposit No. PTA-3449, or any integer of amino acid residues from 1 to about 327 amino acids from the carboxy terminus, or any combination of the above amino terminal and carboxy terminal deletions, of the complete amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. PTA-3449. Polypeptides encoded by these polynucleotides also are encompassed by the invention.  
       [0478] As described herein or otherwise known in the art, the polynucleotides of the invention have uses that include, but are not limited to, serving as probes or primers in chromosome identification, chromosome mapping, and linkage analysis.  
       [0479] It has been discovered that this gene is expressed in adipose tissue, bone marrow stem cells, neutrophils, skeletal muscle, and adult heart.  
       [0480] Therefore, polynucleotides and polypeptides of the invention are useful as reagents for differential identification of the tissue(s) or cell type(s) present in a biological sample and for diagnosis of diseases and conditions which include but are not limited to: diabetes, obesity, and diseases and/or disorders involving dysfunctional fatty acid metabolism, as well as immunological and cardiovascular disorders.  
       [0481] Similarly, polypeptides and antibodies directed to these polypeptides are useful in providing immunological probes for differential identification of the tissue(s) or cell type(s). For a number of disorders of the above tissues or cells, particularly of the endocrine, immune, and cardiovascular systems, expression of this gene at significantly higher or lower levels may be routinely detected in certain tissues or cell types (e.g., adipose, cancerous and wounded tissues) or bodily fluids (e.g., serum, plasma, urine, synovial fluid and spinal fluid) or another tissue or sample taken from an individual having such a disorder, relative to the standard gene expression level, i.e., the expression level in healthy tissue or bodily fluid from an individual not having the disorder.  
       [0482] The expression of this gene in adipose tissue and muscle tissue and the structural similarity of translation products of this gene to ACRP-30 indicates that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of diabetes and diabetes-related disorders, as well as obesity and other metabolic disorders, such as, for example, those described herein under “Endocrine Disorders”. Polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, and/or ameliorate both type I Insulin-Dependent Diabetes Mellitus, “IDDM”, and type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”. Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene, as well as agonists or antagonists thereof (including antibodies and small molecule drugs) may be used to treat, prevent, or ameliorate conditions associated with either type I Insulin-Dependent Diabetes Mellitus, “IDDM”, or type II Non-Insulin-Dependent Diabetes Mellitus, “NIDDM”, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations. In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0483] In addition, the expression of this gene in bone marrow stem cells and neutrophils, and similarity of this gene to other members of the Clq family of proteins suggests that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of immunological disorders, including inflammation, infection, autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, immune complex glomerulonephritis, autoimmune diabetes, autoimmune thrombocytopenic purpura, Grave&#39;s disease, Hashimoto&#39;s thyroiditis, etc.), cardiomyopathy (e.g., dilated cardiomyopathy), diabetes, diabetic complications (e.g., diabetic nephropathy, diabetic neuropathy, diabetic retinopathy), influenza, asthma, psoriasis, glomerulonephritis, septic shock, and ulcerative colitis, and/or those described herein under “Immune Activity”.  
       [0484] Alternatively, the expression of this gene in heart and muscle tissue, and homology to alpha 1 (X) collagen indicate that polynucleotides and polypeptides corresponding to this gene, including antibodies, are useful for the diagnosis, prognosis, prevention, and/or treatment of cardiovacular disorders, such as for example, atherosclerosis, restenosis, and/or those disclosed herein under “Cardiovascular Disorders”.  
       [0485] Translation products of this gene, as well as antibodies directed against translation products of this gene, may show utility as tumor markers and/or immunotherapy targets for the above listed tissues.  
                                                                       TABLE 1                                                           5′ NT                                                               of       First   Last                       ATCC       NT       5′ NT   3′ NT   5′ NT   First   AA   AA   AA   First                   Deposit       SEQ   Total   of   of   of   AA of   SEQ   of   of   AA of   Last       Gene   cDNA   No. and       ID   NT   Clone   Clone   Start   Signal   ID   Sig   Sig   Secreted   AA of       No.   Plasmid: V   Date   Vector   NO: X   Seq.   Seq.   Seq.   Codon   Pep   NO: Y   Pep   Pep   Portion   ORF                                                                                            1   HCE1P80   PTA-844   Uni-ZAP XR   2   3522   1   3522   93   93   50   1   19   20   229               Oct. 13, 1999       1   HCE1P80   PTA-844   Uni-ZAP XR   22   3543   1   3543   108   108   70   1   21   22   229               Oct. 13, 1999       1   HCE1P80   PTA-844   Uni-ZAP XR   23   3522   1   3522   93   93   71   1   21   22   229               Oct. 13, 1999       2   HUFGH53   PTA-623   pSport1   3   2007   1   1968   36   36   51   1   22   23   421               Sep. 2, 1999       2   HUFGH53   PTA-623   pSport1   24   1969   1   1969   36   36   72   1   22   23   459               Sep. 2, 1999       2   HUFGH53   PTA-623   pSport1   25   2189   1   2189   108   108   73   1   22   23   443               Sep. 2, 1999       2   HUFGH53   PTA-623   pSport1   26   1236   397   1236       108   74   1           12               Sep. 2, 1999       2   HUFGH53   PTA-623   pSport1   27   832   1   832       257   75   1   16   17   19               Sep. 2, 1999       2   HUFGH53   PTA-623   pSport1   28   1967   1   1967   36   36   76   1   22   23   421               Sep. 2, 1999       2   HUFGH53   PTA-623   pSport1   29   1967   1   1967   36   36   77   1   22   23   421               Sep. 2, 1999       2   HUFGH53   PTA-623   pSport1   30   2006   1   1967   36   36   78   1   22   23   458               Sep. 2, 1999       3   HWMMO59       pSport1   4   901   1   901       2   52   1   1   2   240       3   HWMMO59       pSport1   31   897   1   897       2   79   1   1   2   240       4   HSSJJ51   PTA-536   Uni-ZAP XR   5   1558   1   1558   278   278   53   1   25   26   281               Aug. 13, 1999       5   HCEWD38   PTA-3696   Uni-ZAP XR   6   1313   1   1313   120   120   54   1   32   33   205               Sep. 10, 2001       5   HCEWD38   PTA-3696   Uni-ZAP XR   32   990   68   990   193   193   80   1   32   33   256               Sep. 10, 2001       5   HCEWD38   PTA-3696   Uni-ZAP XR   33   1384   68   1179   193   193   81   1   35   36   205               Sep. 10, 2001       6   HUCMC56   PTA-2574   pSport1   7   1312   1   1312       2   55   1   29   30   189               PTA2575               Oct. 5, 2000       6   HUCMC56   PTA-2574   pSport1   34   809   1   809       2   82   1   1   2   180               PTA2575               Oct. 5, 2000       7   HWLZU06   PTA-3696   pSport1   8   1022   1   1022       3   56   1   11   12   201               Sep. 10, 2001       7   HWLZU06   PTA-3696   pSport1   35   1215   266   1215       82   83   1           241               Sep. 10, 2001       8   HDPBA69   PTA-3696   pCMVSport   9   1254   1   1254   73   73   57   1   28   29   245               Sep. 10, 2001   3.0       8   HDPBA69   PTA-3696   pCMVSport   36   1311   54   1311   119   119   84   1   28   29   245               Sep. 10, 2001   3.0       8   HDPBA69   PTA-3696   pCMVSport   37   350   240   350       17   85   1   6   7   76               Sep. 10, 2001   3.0       8   HDPBA69   PTA-3696   pCMVSport   38   622   277   622   68   68   86   1   28   29   185               Sep. 10, 2001   3.0       9   HLWAE11   203071   pCMVSport   10   1618   1   1618   28   28   58   1   46   47   278               07/27/98   3.0       10   HSZAF47   209124   Uni-ZAP XR   11   1336   1   1336   113   113   59   1   16   17   289               06/19/97       10   HSZAF47   209124   Uni-ZAP XR   39   1333   2   1333   107   107   87   1   18   19   127               06/19/97       11   HWTAY65   PTA-3696   Uni-ZAP XR   12   1114   1   1114   66   66   60   1   17   18   285               Sep. 10, 2001       11   HWTAY65   PTA-3696   Uni-ZAP XR   40   1211   1   1211   158   158   88   1   17   18   285               Sep. 10, 2001       12   HHGDP51   PTA-3696   Lambda ZAP   13   659   1   659       9   61   1   13   14   146               Sep. 10, 2001   II       12   HHGDP51   PTA-3696   Lambda ZAP   41   616   250   616       1   89   1   1   2   205               Sep. 10, 2001   II       13   HBCBS41   PTA-2574   Uni-ZAP XR   14   1195   551   1195   217   217   62   1   25   26   251               PTA2575               Oct. 5, 2000       13   HBCBS41   PTA-2574   Uni-ZAP XR   42   1161   513   1161   179   179   90   1   25   26   251               PTA2575               Oct. 5, 2000       13   HBCBS41   PTA-2574   Uni-ZAP XR   43   687   89   687       2   91   1   1   2   168               PTA2575               Oct. 5, 2000       13   HDMBJ47   PTA-2574   pSport1   44   1194   1   1194       158   92   1   1   2   255               PTA2575               Oct. 5, 2000       14   HDPRZ06   PTA-2574   pCMVSport   15   3951   2373   3951   135   135   63   1   30   31   975               PTA2575   3.0               Oct. 5, 2000       14   HDPRZ06   PTA-2574   pCMVSport   45   1792   1   1792       209   93   1   1   2   258               PTA2575   3.0               Oct. 5, 2000       14   HDPRZ06   PTA-2574   pCMVSport   46   1412   1   1412       3   94   1   1   2   232               PTA2575   3.0               Oct. 5, 2000       15   HKB1F69   PTA-2574   pCMVSport 1   16   1280   1   1230   386   386   64   1   1   2   158               PTA2575               Oct. 5, 2000       16   HOHBO69   PTA-2574   pCMVSport   17   3764   1   716   829   829   65   1   1   2   605               PTA2575   2.0               Oct. 5, 2000       16   HOHBO69   PTA-2574   pCMVSport   47   646   1   646   353   353   95   1   27   28   98               PTA2575   2.0               Oct. 5, 2000       17   HCEES60       Uni-ZAP XR   18   2485   1   2485       1   66   1   1   2   194       18   HDALV07       pCMVSport   19   1550   1   1550   42   42   67   1   17   18   244                   3.0       19   HEQAH47   PTA-791   pCMVSport   20   1518   1   1518       3   68   1   1   2   361               Sep. 27, 1999   3.0       19   HEQAH47   PTA-791   pCMVSport   48   2536   1023   2536   472   472   96   1   1   2   542               Sep. 27, 1999   3.0       20   HATNA88   PTA-3449   pCMVSport   21   1545   1   1545   342   342   69   1   19   20   333               Jun. 11, 2001   3.0       20   HATNA88   PTA-3449   pCMVSport   49   1530   1   1530   326   326   97   1   19   20   333               Jun. 11, 2001   3.0                  
 
       [0486] Table 1 summarizes the information corresponding to each “Gene No:” described above. The nucleotide sequence identified as “NT SEQ ID NO:X” was assembled from partially homologous (“overlapping”) sequences obtained from the “cDNA Plasmid:V” identified in Table 1 and, in some cases, from additional related DNA clones. The overlapping sequences were assembled into a single contiguous sequence of high redundancy (usually three to five overlapping sequences at each nucleotide position), resulting in a final sequence identified as SEQ ID NO:X.  
       [0487] The cDNA Plasmid:V was deposited on the date and given the corresponding deposit number listed in “ATCC Deposit No:Z and Date.” Some of the deposits contain multiple different clones corresponding to the same gene. “Vector” refers to the type of vector contained in cDNA Plasmid:V.  
       [0488] “Total NT Seq.” refers to the total number of nucleotides in the contig identified by “Gene No:”. The deposited plasmid contains all of these sequences, reflected by the nucleotide position indicated as “5′ NT of Clone Seq.” and the “3′ NT of Clone Seq.” of SEQ ID NO:X. The nucleotide position of SEQ ID NO:X of the putative methionine start codon (if present) is identified as “5′ NT of Start Codon.” Similarly, the nucleotide position of SEQ ID NO:X of the predicted signal sequence (if present) is identified as “5′ NT of First AA of Signal Pep.” 
       [0489] The translated amino acid sequence, beginning with the first translated codon of the polynucleotide sequence, is identified as “AA SEQ ID NO:Y,” although other reading frames can also be easily translated using known molecular biology techniques. The polypeptides produced by these alternative open reading frames are specifically contemplated by the present invention.  
       [0490] SEQ ID NO:X (where X may be any of the polynucleotide sequences disclosed in the sequence listing) and the translated SEQ ID NO:Y (where Y may be any of the polypeptide sequences disclosed in the sequence listing) are sufficiently accurate and otherwise suitable for a variety of uses well known in the art and described further below. For instance, SEQ ID NO:X has uses including, but not limited to, in designing nucleic acid hybridization probes that will detect nucleic acid sequences contained in SEQ ID NO:X or the cDNA contained in a deposited plasmid. These probes will also hybridize to nucleic acid molecules in biological samples, thereby enabling a variety of forensic and diagnostic methods of the invention. Similarly, polypeptides identified from SEQ ID NO:Y have uses that include, but are not limited to generating antibodies, which bind specifically to the secreted proteins encoded by the cDNA clones identified in Table 1.  
       [0491] Nevertheless, DNA sequences generated by sequencing reactions can contain sequencing errors. The errors exist as misidentified nucleotides, or as insertions or deletions of nucleotides in the generated DNA sequence. The erroneously inserted or deleted nucleotides cause frame shifts in the reading frames of the predicted amino acid sequence. In these cases, the predicted amino acid sequence diverges from the actual amino acid sequence, even though the generated DNA sequence may be greater than 99.9% identical to the actual DNA sequence (for example, one base insertion or deletion in an open reading frame of over 1000 bases).  
       [0492] Accordingly, for those applications requiring precision in the nucleotide sequence or the amino acid sequence, the present invention provides not only the generated nucleotide sequence identified as SEQ ID NO:X, and the predicted translated amino acid sequence identified as SEQ ID NO:Y, but also a sample of plasmid DNA containing a human cDNA of the invention deposited with the ATCC, as set forth in Table 1. The nucleotide sequence of each deposited plasmid can readily be determined by sequencing the deposited plasmid in accordance with known methods.  
       [0493] The predicted amino acid sequence can then be verified from such deposits. Moreover, the amino acid sequence of the protein encoded by a particular plasmid can also be directly determined by peptide sequencing or by expressing the protein in a suitable host cell containing the deposited human cDNA, collecting the protein, and determining its sequence.  
       [0494] Also provided in Table 1 is the name of the vector which contains the cDNA plasmid. Each vector is routinely used in the art. The following additional information is provided for convenience.  
       [0495] Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636), Uni-Zap XR (U.S. Pat. Nos. 5,128, 256 and 5,286,636), Zap Express (U.S. Pat. Nos. 5,128,256 and 5,286,636), pBluescript (pBS) (Short, J. M. et al.,  Nucleic Acids Res.  16:7583-7600 (1988); Alting-Mees, M. A. and Short, J. M.,  Nucleic Acids Res.  17:9494 (1989)) and pBK (Alting-Mees, M. A. et al.,  Strategies  5:58-61 (1992)) are commercially available from Stratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla, Calif., 92037. pBS contains an ampicillin resistance gene and pBK contains a neomycin resistance gene. Phagemid pBS may be excised from the Lambda Zap and Uni-Zap XR vectors, and phagemid pBK may be excised from the Zap Express vector. Both phagemids may be transformed into  E. coli  strain XL-1 Blue, also available from Stratagene.  
       [0496] Vectors pSport1, pCMVSport 1.0, pCMVSport 2.0 and pCMVSport 3.0, were obtained from Life Technologies, Inc., P. O. Box 6009, Gaithersburg, Md. 20897. All Sport vectors contain an ampicillin resistance gene and may be transformed into  E. coli  strain DH10B, also available from Life Technologies. See, for instance, Gruber, C. E., et al.,  Focus  15.59 (1993). Vector lafmid BA (Bento Soares, Columbia University, New York, N.Y.) contains an ampicillin resistance gene and can be transformed into  E. coli  strain XL-1 Blue. Vector pCR®2.1, which is available from Invitrogen, 1600 Faraday Avenue, Carlsbad, Calif. 92008, contains an ampicillin resistance gene and may be transformed into  E. coli  strain DH10B, available from Life Technologies. See, for instance, Clark, J. M.,  Nuc. Acids Res.  16:9677-9686 (1988) and Mead, D. et al.,  Bio/Technology  9: (1991).  
       [0497] The present invention also relates to the genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, and/or a deposited plasmid (cDNA plasmid:V). The corresponding gene can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include, but are not limited to, preparing probes or primers from the disclosed sequence and identifying or amplifying the corresponding gene from appropriate sources of genomic material.  
       [0498] Also provided in the present invention are allelic variants, orthologs, and/or species homologs. Procedures known in the art can be used to obtain full-length genes, allelic variants, splice variants, full-length coding portions, orthologs, and/or species homologs of genes corresponding to SEQ ID NO:X, SEQ ID NO:Y, and/or cDNA plasmid:V, using information from the sequences disclosed herein or the clones deposited with the ATCC. For example, allelic variants and/or species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source for allelic variants and/or the desired homologue.  
       [0499] The present invention provides a polynucleotide comprising, or alternatively consisting of, the nucleic acid sequence of SEQ ID NO:X and/or cDNA plasmid:V. The present invention also provides a polypeptide comprising, or alternatively, consisting of, the polypeptide sequence of SEQ ID NO:Y, a polypeptide encoded by SEQ ID NO:X, and/or a polypeptide encoded by the cDNA in cDNA plasmid:V. Polynucleotides encoding a polypeptide comprising, or alternatively consisting of the polypeptide sequence of SEQ ID NO:Y, a polypeptide encoded by SEQ ID NO:X and/or a polypeptide encoded by the cDNA in cDNA plasmid:V, are also encompassed by the invention. The present invention further encompasses a polynucleotide comprising, or alternatively consisting of the complement of the nucleic acid sequence of SEQ ID NO:X, and/or the complement of the coding strand of the cDNA in cDNA plasmid:V.  
       [0500] Many polynucleotide sequences, such as EST sequences, are publicly available and accessible through sequence databases 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 unduly burden the disclosure of this application. Accordingly, preferably excluded from SEQ ID NO:X are one or more polynucleotides comprising a nucleotide sequence described by the general formula of a−b, where a is any integer between 1 and the final nucleotide minus 15 of SEQ ID NO:X, b is an integer of 15 to the final nucleotide of SEQ ID NO:X, where both a and b correspond to the positions of nucleotide residues shown in SEQ ID NO:X, and where b is greater than or equal to a+14.  
       [0501] RACE Protocol for Recovery of Full-Length Genes  
       [0502] Partial cDNA clones can be made full-length by utilizing the rapid amplification of cDNA ends (RACE) procedure described in Frohman, M. A., et al., Proc. Nat&#39;l. Acad. Sci. USA, 85:8998-9002 (1988). A cDNA clone missing either the 5′ or 3′ end can be reconstructed to include the absent base pairs extending to the translational start or stop codon, respectively. In some cases, cDNAs are missing the start of translation, therefor. The following briefly describes a modification of this original 5′ RACE procedure. Poly A+ or total RNA is reverse transcribed with Superscript II (Gibco/BRL) and an antisense or complementary primer specific to the cDNA sequence. The primer is removed from the reaction with a Microcon Concentrator (Amicon). The first-strand cDNA is then tailed with dATP and terminal deoxynucleotide transferase (Gibco/BRL). Thus, an anchor sequence is produced which is needed for PCR amplification. The second strand is synthesized from the dA-tail in PCR buffer, Taq DNA polymerase (Perkin-Elmer Cetus), an oligo-dT primer containing three adjacent restriction sites (XhoI, SalI and ClaI) at the 5′ end and a primer containing just these restriction sites. This double-stranded cDNA is PCR amplified for 40 cycles with the same primers as well as a nested cDNA-specific antisense primer. The PCR products are size-separated on an ethidium bromide-agarose gel and the region of gel containing cDNA products the predicted size of missing protein-coding DNA is removed. cDNA is purified from the agarose with the Magic PCR Prep kit (Promega), restriction digested with XhoI or SalI, and ligated to a plasmid such as pBluescript SKII (Stratagene) at XhoI and EcoRV sites. This DNA is transformed into bacteria and the plasmid clones sequenced to identify the correct protein-coding inserts. Correct 5′ ends are confirmed by comparing this sequence with the putatively identified homologue and overlap with the partial cDNA clone. Similar methods known in the art and/or commercial kits are used to amplify and recover 3′ ends.  
       [0503] Several quality-controlled kits are commercially available for purchase. Similar reagents and methods to those above are supplied in kit form from Gibco/BRL for both 5′ and 3′ RACE for recovery of full length genes. A second kit is available from Clontech which is a modification of a related technique, SLIC (single-stranded ligation to single-stranded cDNA), developed by Dumas et al., Nucleic Acids Res., 19:5227-32 (1991). The major differences in procedure are that the RNA is alkaline hydrolyzed after reverse transcription and RNA ligase is used to join a restriction site-containing anchor primer to the first-strand cDNA. This obviates the necessity for the dA-tailing reaction which results in a polyT stretch that is difficult to sequence past.  
       [0504] An alternative to generating 5′ or 3′ cDNA from RNA is to use cDNA library double-stranded DNA. An asymmetric PCR-amplified antisense cDNA strand is synthesized with an antisense cDNA-specific primer and a plasmid-anchored primer. These primers are removed and a symmetric PCR reaction is performed with a nested cDNA-specific antisense primer and the plasmid-anchored primer.  
       [0505] RNA Ligase Protocol for Generating the 5′ or 3′ End Sequences to Obtain Full Length Genes  
       [0506] Once a gene of interest is identified, several methods are available for the identification of the 5′ or 3′ portions of the gene which may not be present in the original cDNA plasmid. These methods include, but are not limited to, filter probing, clone enrichment using specific probes and protocols similar and identical to 5′ and 3′RACE. While the full length gene may be present in the library and can be identified by probing, a useful method for generating the 5′ or 3′ end is to use the existing sequence information from the original cDNA to generate the missing information. A method similar to 5′RACE is available for generating the missing 5′ end of a desired full-length gene. (This method was published by Fromont-Racine et al., Nucleic Acids Res., 21(7):1683-1684 (1993)). Briefly, a specific RNA oligonucleotide is ligated to the 5′ ends of a population of RNA presumably containing full-length gene RNA transcript and a primer set containing a primer specific to the ligated RNA oligonucleotide and a primer specific to a known sequence of the gene of interest, is used to PCR amplify the 5′ portion of the desired full length gene which may then be sequenced and used to generate the full length gene. This method starts with total RNA isolated from the desired source, poly A RNA may be used but is not a prerequisite for this procedure. The RNA preparation may then be treated with phosphatase if necessary to eliminate 5′ phosphate groups on degraded or damaged RNA which may interfere with the later RNA ligase step. The phosphatase if used is then inactivated and the RNA is treated with tobacco acid pyrophosphatase in order to remove the cap structure present at the 5′ ends of messenger RNAs. This reaction leaves a 5′ phosphate group at the 5′ end of the cap cleaved RNA which can then be ligated to an RNA oligonucleotide using T4 RNA ligase. This modified RNA preparation can then be used as a template for first strand cDNA synthesis using a gene specific oligonucleotide. The first strand synthesis reaction can then be used as a template for PCR amplification of the desired 5′ end using a primer specific to the ligated RNA oligonucleotide and a primer specific to the known sequence of the ACRP30-Like gene of interest. The resultant product is then sequenced and analyzed to confirm that the 5′ end sequence belongs to the relevant ACRP30-Like gene.  
       [0507] Polynucleotide and Polypeptide Fragments  
       [0508] The present invention is also directed to polynucleotide fragments of the polynucleotides (nucleic acids) of the invention. In the present invention, a “polynucleotide fragment” refers to a polynucleotide having a nucleic acid sequence which: is a portion of the cDNA contained in cDNA plasmid:V or encoding the polypeptide encoded by the cDNA contained in cDNA plasmid:V; is a portion of the polynucleotide sequence in SEQ ID NO:X or the complementary strand thereto; is a polynucleotide sequence encoding a portion of the polypeptide of SEQ ID NO:Y; or is a polynucleotide sequence encoding a portion of a polypeptide encoded by SEQ ID NO:X. The nucleotide fragments of the invention are preferably at least about 15 nt, and more preferably at least about 20 nt, still more preferably at least about 30 nt, and even more preferably, at least about 40 nt, at least about 50 nt, at least about 75 nt, at least about 100 nt, at least about 125 nt, or at least about 150 nt in length. A fragment “at least 20 nt in length,” for example, is intended to include 20 or more contiguous bases from, for example, the sequence contained in the cDNA in cDNA plasmid:V, or the nucleotide sequence shown in SEQ ID NO:X or the complementary stand thereto. In this context “about” includes the particularly recited value, or a value larger or smaller by several (5, 4, 3, 2, or 1) nucleotides. These nucleotide fragments have uses that include, but are not limited to, as diagnostic probes and primers as discussed herein. Of course, larger fragments (e.g., at least 150, 175, 200, 250, 500, 600, 1000, or 2000 nucleotides in length) are also encompassed by the invention.  
       [0509] Moreover, representative examples of polynucleotide fragments of the invention, include, for example, fragments comprising, or alternatively consisting of, a sequence from about nucleotide number 1-50, 51-100, 101-150, 151-200, 201-250, 251-300, 301-350, 351-400, 401-450, 451-500, 501-550, 551-600, 601-650, 651-700, 701-750, 751-800, 801-850, 851-900, 901-950, 951-1000, 1001-1050, 1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951-2000, 2001-2050, 2051-2100, 2101-2150, 2151-2200, 2201-2250, 2251-2300, 2301-2350, 2351-2400, 2401-2450, 2451-2500, 2501-2550, 2551-2600, 2601-2650, 2651-2700, 2701-2750, 2751-2800, 2801-2850, 2851-2900, 2901-2950, 2951-3000, 3001-3050, 3051-3100, 3101-3150, 3151-3200, 3201-3250, 3251-3300, 3301-3350, 3351-3400, 3401-3450, 3451-3500, 3501-3550, 3551-3600, 3601-3650, 3651-3700, 3701-3750, and/or 3751-3764 of SEQ ID NO:X, or the complementary strand thereto. In this context “about” includes the particularly recited range or a range larger or smaller by several (5, 4, 3, 2, or 1) nucleotides, at either terminus or at both termini. Preferably, these fragments encode a polypeptide which has a functional activity (e.g. biological activity) of the polypeptide encoded by a polynucleotide of which the sequence is a portion. More preferably, these fragments can be used as probes or primers as discussed herein. Polynucleotides which hybridize to one or more of these fragments under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention, as are polypeptides encoded by these polynucleotides or fragments.  
       [0510] Moreover, representative examples of polynucleotide fragments of the invention, include, for example, fragments comprising, or alternatively consisting of, a sequence from about nucleotide number 1-50, 51-100, 101-150, 151-200, 201-250, 251-300, 301-350, 351-400, 401-450, 451-500, 501-550, 551-600, 601-650, 651-700, 701-750, 751-800, 801-850, 851-900, 901-950, 951-1000, 1001-1050, 1051-1100, 1101-1150, 1151-1200, 1201-1250, 1251-1300, 1301-1350, 1351-1400, 1401-1450, 1451-1500, 1501-1550, 1551-1600, 1601-1650, 1651-1700, 1701-1750, 1751-1800, 1801-1850, 1851-1900, 1901-1950, 1951-2000, 2001-2050, 2051-2100, 2101-2150, 2151-2200, 2201-2250, 2251-2300, 2301-2350, 2351-2400, 2401-2450, 2451-2500, 2501-2550, 2551-2600, 2601-2650, 2651-2700, 2701-2750, 2751-2800, 2801-2850, 2851-2900, 2901-2950, 2951-3000, 3001-3050, 3051-3100, 3101-3150, 3151-3200, 3201-3250, 3251-3300, 3301-3350, 3351-3400, 3401-3450, 3451-3500, 3501-3550, 3551-3600, 3601-3650, 3651-3700, 3701-3750, and/or 3751-3764 of the cDNA nucleotide sequence contained in cDNA plasmid:V, or the complementary strand thereto. In this context “about” includes the particularly recited range or a range larger or smaller by several (5, 4, 3, 2, or 1) nucleotides, at either terminus or at both termini. Preferably, these fragments encode a polypeptide which has a functional activity (e.g. biological activity) of the polypeptide encoded by the cDNA nucleotide sequence contained in cDNA plasmid:V. More preferably, these fragments can be used as probes or primers as discussed herein. Polynucleotides which hybridize to one or more of these fragments under stringent hybridization conditions, or alternatively, under lower stringency conditions are also encompassed by the invention, as are polypeptides encoded by these polynucleotides or fragments.  
       [0511] In the present invention, a “polypeptide fragment” refers to an amino acid sequence which is a portion of that contained in SEQ ID NO:Y, a portion of an amino acid sequence encoded by the polynucleotide sequence of SEQ ID NO:X, and/or encoded by the cDNA in cDNA plasmid:V. Protein (polypeptide) fragments may be “free-standing,” or comprised within a larger polypeptide of which the fragment forms a part or region, most preferably as a single continuous region. Representative examples of polypeptide fragments of the invention, include, for example, fragments comprising, or alternatively consisting of, an amino acid sequence from about amino acid number 1-20, 21-40, 41-60, 61-80, 81-100, 101-120, 121-140, 141-160, 161-180, 181-200, 201-220, 221-240, 241-260, 261-280, 281-300, 301-320, 321-340, 341-360, 361-380, 381-400, 401-420, 421-440, 441-460, 461-480, 481-500, 501-520, 521-540, 541-560, 561-580, 581-600, and/or 601-605 of the coding region of SEQ ID NO:Y. Moreover, polypeptide fragments of the invention may be at least about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 110, 120, 130, 140, or 150 amino acids in length. In this context “about” includes the particularly recited ranges or values, or ranges or values larger or smaller by several (5, 4, 3, 2, or 1) amino acids, at either terminus or at both termini. Polynucleotides encoding these polypeptide fragments are also encompassed by the invention.  
       [0512] Even if deletion of one or more amino acids from the N-terminus of a protein results in modification of loss of one or more biological functions of the protein, other functional activities (e.g., biological activities, ability to multimerize, ability to bind a ligand) may still be retained. For example, the ability of shortened muteins to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptides generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the N-terminus. Whether a particular polypeptide lacking N-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a mutein with a large number of deleted N-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0513] Accordingly, polypeptide fragments of the invention include the secreted protein as well as the mature form. Further preferred polypeptide fragments include the secreted protein or the mature form having a continuous series of deleted residues from the amino or the carboxy terminus, or both. For example, any number of amino acids, ranging from 1-60, can be deleted from the amino terminus of either the secreted polypeptide or the mature form. Similarly, any number of amino acids, ranging from 1-30, can be deleted from the carboxy terminus of the secreted protein or mature form. Furthermore, any combination of the above amino and carboxy terminus deletions are preferred. Similarly, polynucleotides encoding these polypeptide fragments are also preferred.  
       [0514] The present invention further provides polypeptides having one or more residues deleted from the amino terminus of the amino acid sequence of a polypeptide disclosed herein (e.g., a polypeptide of SEQ ID NO:Y, a polypeptide encoded by the polynucleotide sequence contained in SEQ ID NO:X, and/or a polypeptide encoded by the cDNA contained in cDNA plasmid:V). In particular, N-terminal deletions may be described by the general formula m−q, where q is a whole integer representing the total number of amino acid residues in a polypeptide of the invention (e.g., the polypeptide disclosed in SEQ ID NO:Y), and m is defined as any integer ranging from 2 to q−6. Polynucleotides encoding these polypeptides, including fragments and/or variants, are also encompassed by the invention.  
       [0515] Also as mentioned above, even if deletion of one or more amino acids from the C-terminus of a protein results in modification of loss of one or more biological functions of the protein, other functional activities (e.g., biological activities, ability to multimerize, ability to bind a ligand) may still be retained. For example the ability of the shortened mutein to induce and/or bind to antibodies which recognize the complete or mature forms of the polypeptide generally will be retained when less than the majority of the residues of the complete or mature polypeptide are removed from the C-terminus. Whether a particular polypeptide lacking C-terminal residues of a complete polypeptide retains such immunologic activities can readily be determined by routine methods described herein and otherwise known in the art. It is not unlikely that a mutein with a large number of deleted C-terminal amino acid residues may retain some biological or immunogenic activities. In fact, peptides composed of as few as six amino acid residues may often evoke an immune response.  
       [0516] Accordingly, the present invention further provides polypeptides having one or more residues from the carboxy terminus of the amino acid sequence of a polypeptide disclosed herein (e.g., a polypeptide of SEQ ID NO:Y, a polypeptide encoded by the polynucleotide sequence contained in SEQ ID NO:X, and/or a polypeptide encoded by the cDNA contained in cDNA plasmid:V). In particular, C-terminal deletions may be described by the general formula 1−n, where n is any whole integer ranging from 6 to q−1, and where n corresponds to the position of an amino acid residue in a polypeptide of the invention. Polynucleotides encoding these polypeptides, including fragments and/or variants, are also encompassed by the invention.  
       [0517] In addition, any of the above described N- or C-terminal deletions can be combined to produce a N- and C-terminal deleted polypeptide. The invention also provides polypeptides having one or more amino acids deleted from both the amino and the carboxyl termini, which may be described generally as having residues m−n of a polypeptide encoded by SEQ ID NO:X (e.g., including, but not limited to, the preferred polypeptide disclosed as SEQ ID NO:Y), and/or the cDNA in cDNA plasmid:V, and/or the complement thereof, where n and m are integers as described above. Polynucleotides encoding these polypeptides, including fragments and/or variants, are also encompassed by the invention.  
       [0518] Any polypeptide sequence contained in the polypeptide of SEQ ID NO:Y, encoded by the polynucleotide sequences set forth as SEQ ID NO:X, or encoded by the cDNA in cDNA plasmid:V may be analyzed to determine certain preferred regions of the polypeptide. For example, the amino acid sequence of a polypeptide encoded by a polynucleotide sequence of SEQ ID NO:X or the cDNA in cDNA plasmid:V may be analyzed using the default parameters of the DNASTAR computer algorithm (DNASTAR, Inc., 1228 S. Park St., Madison, Wis. 53715 USA; http://www.dnastar.com/).  
       [0519] Polypeptide regions that may be routinely obtained using the DNASTAR computer algorithm include, but are not limited to, Garnier-Robson alpha-regions, beta-regions, turn-regions, and coil-regions, Chou-Fasman alpha-regions, beta-regions, and turn-regions, Kyte-Doolittle hydrophilic regions and hydrophobic regions, Eisenberg alpha- and beta-amphipathic regions, Karplus-Schulz flexible regions, Emini surface-forming regions and Jameson-Wolf regions of high antigenic index. Among highly preferred polynucleotides of the invention in this regard are those that encode polypeptides comprising regions that combine several structural features, such as several (e.g., 1, 2, 3 or 4) of the features set out above.  
       [0520] Additionally, Kyte-Doolittle hydrophilic regions and hydrophobic regions, Emini surface-forming regions, and Jameson-Wolf regions of high antigenic index (i.e., containing four or more contiguous amino acids having an antigenic index of greater than or equal to 1.5, as identified using the default parameters of the Jameson-Wolf program) can routinely be used to determine polypeptide regions that exhibit a high degree of potential for antigenicity. Regions of high antigenicity are determined from data by DNASTAR analysis by choosing values which represent regions of the polypeptide which are likely to be exposed on the surface of the polypeptide in an environment in which antigen recognition may occur in the process of initiation of an immune response.  
       [0521] Preferred polypeptide fragments of the invention are fragments comprising, or alternatively, consisting of, an amino acid sequence that displays a functional activity (e.g. biological activity) of the polypeptide sequence of which the amino acid sequence is a fragment. By a polypeptide displaying a “functional activity” is meant a polypeptide capable of one or more known functional activities associated with a full-length protein, such as, for example, biological activity, antigenicity, immunogenicity, and/or multimerization, as described supra.  
       [0522] Other preferred polypeptide fragments are biologically active fragments. Biologically active fragments are those exhibiting activity similar, but not necessarily identical, to an activity of the polypeptide of the present invention. The biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity.  
       [0523] In preferred embodiments, polypeptides of the invention comprise, or alternatively consist of, one, two, three, four, five or more of the antigenic fragments of the polypeptide of SEQ ID NO:Y, or portions thereof. Polynucleotides encoding these polypeptides, including fragments and/or variants, are also encompassed by the invention.  
       [0524] The present invention encompasses polypeptides comprising, or alternatively consisting of, an epitope of the polypeptide sequence shown in SEQ ID NO:Y, or an epitope of the polypeptide sequence encoded by the cDNA in cDNA plasmid:V, or encoded by a polynucleotide that hybridizes to the complement of an epitope encoding sequence of SEQ ID NO:X, or an epitope encoding sequence contained in cDNA plasmid:V under stringent hybridization conditions, or alternatively, under lower stringency hybridization, as defined supra. The present invention further encompasses polynucleotide sequences encoding an epitope of a polypeptide sequence of the invention (such as, for example, the sequence disclosed in SEQ ID NO:X), polynucleotide sequences of the complementary strand of a polynucleotide sequence encoding an epitope of the invention, and polynucleotide sequences which hybridize to this complementary strand under stringent hybridization conditions, or alternatively, under lower stringency hybridization conditions, as defined supra.  
       [0525] The term “epitopes,” as used herein, refers to portions of a polypeptide having antigenic or immunogenic activity in an animal, preferably a mammal, and most preferably in a human. In a preferred embodiment, the present invention encompasses a polypeptide comprising an epitope, as well as the polynucleotide encoding this polypeptide. An “immunogenic epitope,” as used herein, is defined as a portion of a protein that elicits an antibody response in an animal, as determined by any method known in the art, for example, by the methods for generating antibodies described infra. (See, for example, Geysen et al., Proc. Natl. Acad. Sci. USA 81:3998-4002 (1983)). The term “antigenic epitope,” as used herein, is defined as a portion of a protein to which an antibody can immunospecifically bind its antigen as determined by any method well known in the art, for example, by the immunoassays described herein. Immunospecific binding excludes non-specific binding but does not necessarily exclude cross-reactivity with other antigens. Antigenic epitopes need not necessarily be immunogenic.  
       [0526] Fragments which function as epitopes may be produced by any conventional means. (See, e.g., Houghten, R. A., Proc. Natl. Acad. Sci. USA 82:5131-5135 (1985) further described in U.S. Pat. No. 4,631,211.)  
       [0527] In the present invention, antigenic epitopes preferably contain a sequence of at least 4, at least 5, at least 6, at least 7, more preferably at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, and, most preferably, between about 15 to about 30 amino acids. Preferred polypeptides comprising immunogenic or antigenic epitopes are at least 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 amino acid residues in length. Additional non-exclusive preferred antigenic epitopes include the antigenic epitopes disclosed herein, as well as portions thereof. Antigenic epitopes are useful, for example, to raise antibodies, including monoclonal antibodies, that specifically bind the epitope. Preferred antigenic epitopes include the antigenic epitopes disclosed herein, as well as any combination of two, three, four, five or more of these antigenic epitopes. Antigenic epitopes can be used as the target molecules in immunoassays. (See, for instance, Wilson et al., Cell 37:767-778 (1984); Sutcliffe et al., Science 219:660-666 (1983)).  
       [0528] Similarly, immunogenic epitopes can be used, for example, to induce antibodies according to methods well known in the art. (See, for instance, Sutcliffe et al., supra; Wilson et al., supra; Chow et al., Proc. Natl. Acad. Sci. USA 82:910-914; and Bittle et al., J. Gen. Virol. 66:2347-2354 (1985). Preferred immunogenic epitopes include the immunogenic epitopes disclosed herein, as well as any combination of two, three, four, five or more of these immunogenic epitopes. The polypeptides comprising one or more immunogenic epitopes may be presented for eliciting an antibody response together with a carrier protein, such as an albumin, to an animal system (such as rabbit or mouse), or, if the polypeptide is of sufficient length (at least about 25 amino acids), the polypeptide may be presented without a carrier. However, immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to raise antibodies capable of binding to, at the very least, linear epitopes in a denatured polypeptide (e.g., in Western blotting).  
       [0529] Epitope-bearing polypeptides of the present invention may be used to induce antibodies according to methods well known in the art including, but not limited to, in vivo immunization, in vitro immunization, and phage display methods. See, e.g., Sutcliffe et al., supra; Wilson et al., supra, and Bittle et al., J. Gen. Virol., 66:2347-2354 (1985). If in vivo immunization is used, animals may be immunized with free peptide; however, anti-peptide antibody titer may be boosted by coupling the peptide to a macromolecular carrier, such as keyhole limpet hemacyanin (KLH) or tetanus toxoid. For instance, peptides containing cysteine residues may be coupled to a carrier using a linker such as maleimidobenzoyl-N-hydroxysuccinimide ester (MBS), while other peptides may be coupled to carriers using a more general linking agent such as glutaraldehyde. Animals such as rabbits, rats and mice are immunized with either free or carrier-coupled peptides, for instance, by intraperitoneal and/or intradermal injection of emulsions containing about 100 μg of peptide or carrier protein and Freund&#39;s adjuvant or any other adjuvant known for stimulating an immune response. Several booster injections may be needed, for instance, at intervals of about two weeks, to provide a useful titer of anti-peptide antibody which can be detected, for example, by ELISA assay using free peptide adsorbed to a solid surface. The titer of anti-peptide antibodies in serum from an immunized animal may be increased by selection of anti-peptide antibodies, for instance, by adsorption to the peptide on a solid support and elution of the selected antibodies according to methods well known in the art.  
       [0530] As one of skill in the art will appreciate, and as discussed above, the polypeptides of the present invention and immunogenic and/or antigenic epitope fragments thereof can be fused to other polypeptide sequences. For example, the polypeptides of the present invention may be fused with the constant domain of immunoglobulins (IgA, IgE, IgG, IgM), or portions thereof (CH1, CH2, CH3, or any combination thereof and portions thereof) resulting in chimeric polypeptides. Such fusion proteins may facilitate purification and may increase half-life in vivo. This has been shown for chimeric proteins consisting of the first two domains of the human CD4-polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins. See, e.g., EP 394,827; Traunecker et al., Nature, 331:84-86 (1988). Enhanced delivery of an antigen across the epithelial barrier to the immune system has been demonstrated for antigens (e.g., insulin) conjugated to an FcRn binding partner such as IgG or Fc fragments (see, e.g., PCT Publications WO 96/22024 and WO 99/04813). IgG Fusion proteins that have a disulfide-linked dimeric structure due to the IgG portion desulfide bonds have also been found to be more efficient in binding and neutralizing other molecules than monomeric polypeptides or fragments thereof alone. See, e.g., Fountoulakis et al., J. Biochem., 270:3958-3964 (1995).  
       [0531] Similarly, EP-A-O 464 533 (Canadian counterpart 2045869) discloses fusion proteins comprising various portions of constant region of immunoglobulin molecules together with another human protein or part thereof. In many cases, the Fc part in a fusion protein is beneficial in therapy and diagnosis, and thus can result in, for example, improved pharmacokinetic properties. (EP-A 0232 262.) Alternatively, deleting the Fc part after the fusion protein has been expressed, detected, and purified, may be desired. For example, the Fc portion may hinder therapy and diagnosis if the fusion protein is used as an antigen for immunizations. In drug discovery, for example, human proteins, such as hIL-5, have been fused with Fc portions for the purpose of high-throughput screening assays to identify antagonists of hIL-5. (See, D. Bennett et al., J. Molecular Recognition 8:52-58 (1995); K. Johanson et al., J. Biol. Chem. 270:9459-9471 (1995)).  
       [0532] Moreover, the polypeptides of the present invention can be fused to marker sequences, such as a peptide which facilitates purification of the fused polypeptide. In preferred embodiments, the marker amino acid sequence is a hexa-histidine peptide, such as the tag provided in a pQE vector (QIAGEN, Inc., 9259 Eton Avenue, Chatsworth, Calif., 91311), among others, many of which are commercially available. As described in Gentz et al., Proc. Natl. Acad. Sci. USA 86:821-824 (1989), for instance, hexa-histidine provides for convenient purification of the fusion protein. Another peptide tag useful for purification, the “HA” tag, corresponds to an epitope derived from the influenza hemagglutinin protein. (Wilson et al., Cell 37:767 (1984)).  
       [0533] Thus, any of these above fusions can be engineered using the polynucleotides or the polypeptides of the present invention.  
       [0534] Nucleic acids encoding the above epitopes can also be recombined with a gene of interest as an epitope tag (e.g., the hemagglutinin (“HA”) tag or flag tag) to aid in detection and purification of the expressed polypeptide. For example, a system described by Janknecht et al. allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht et al., Proc. Natl. Acad. Sci. USA 88:8972-897 (1991)). In this system, the gene of interest is subcloned into a vaccinia recombination plasmid such that the open reading frame of the gene is translationally fused to an amino-terminal tag consisting of six histidine residues. The tag serves as a matrix binding domain for the fusion protein. Extracts from cells infected with the recombinant vaccinia virus are loaded onto Ni2+ nitriloacetic acid-agarose column and histidine-tagged proteins can be selectively eluted with imidazole-containing buffers.  
       [0535] Additional fusion proteins of the invention may be generated through the techniques of gene-shuffling, motif-shuffling, exon-shuffling, and/or codon-shuffling (collectively referred to as “DNA shuffling”). DNA shuffling may be employed to modulate the activities of polypeptides of the invention, such methods can be used to generate polypeptides with altered activity, as well as agonists and antagonists of the polypeptides. See, generally, U.S. Pat. Nos. 5,605,793; 5,811,238; 5,830,721; 5,834,252; and 5,837,458, and Patten et al., Curr. Opinion Biotechnol. 8:724-33 (1997); Harayama, Trends Biotechnol. 16(2):76-82 (1998); Hansson, et al., J. Mol. Biol. 287:265-76 (1999); and Lorenzo and Blasco, Biotechniques 24(2):308-13 (1998) (each of these patents and publications are hereby incorporated by reference in its entirety). In one embodiment, alteration of polynucleotides corresponding to SEQ ID NO:X and the polypeptides encoded by these polynucleotides may be achieved by DNA shuffling. DNA shuffling involves the assembly of two or more DNA segments by homologous or site-specific recombination to generate variation in the polynucleotide sequence. In another embodiment, polynucleotides of the invention, or the encoded polypeptides, may be altered by being subjected to random mutagenesis by error-prone PCR, random nucleotide insertion or other methods prior to recombination. In another embodiment, one or more components, motifs, sections, parts, domains, fragments, etc., of a polynucleotide encoding a polypeptide of the invention may be recombined with one or more components, motifs, sections, parts, domains, fragments, etc. of one or more heterologous molecules.  
       [0536] Polynucleotide and Polypeptide Variants  
       [0537] The invention also encompasses ACRP30-Like variants. The present invention is directed to variants of the polynucleotide sequence disclosed in SEQ ID NO:X or the complementary strand thereto, and/or the cDNA sequence contained in cDNA plasmid:V.  
       [0538] The present invention also encompasses variants of the polypeptide sequence disclosed in SEQ ID NO:Y, a polypeptide sequence encoded by the polynucleotide sequence in SEQ ID NO:X and/or a polypeptide sequence encoded by the cDNA in cDNA plasmid:V.  
       [0539] “Variant” refers to a polynucleotide or polypeptide differing from the polynucleotide or polypeptide of the present invention, but retaining properties thereof. Generally, variants are overall closely similar, and, in many regions, identical to the polynucleotide or polypeptide of the present invention.  
       [0540] Thus, one aspect of the invention provides an isolated nucleic acid molecule comprising, or alternatively consisting of, a polynucleotide having a nucleotide sequence selected from the group consisting of: (a) a nucleotide sequence described in SEQ ID NO:X or contained in the cDNA sequence of Plasmid:V; (b) a nucleotide sequence in SEQ ID NO:X or the cDNA in Plasmid:V which encodes the complete amino acid sequence of SEQ ID NO:Y or the complete amino acid sequence encoded by the cDNA in Plasmid:V; (c) a nucleotide sequence in SEQ ID NO:X or the cDNA in Plasmid:V which encodes a mature ACRP30-Like polypeptide; (d) a nucleotide sequence in SEQ ID NO:X or the cDNA sequence of Plasmid:V, which encodes a biologically active fragment of a ACRP30-Like polypeptide; (e) a nucleotide sequence in SEQ ID NO:X or the cDNA sequence of Plasmid:V, which encodes an antigenic fragment of a ACRP30-Like polypeptide; (f) a nucleotide sequence encoding a ACRP30-Like polypeptide comprising the complete amino acid sequence of SEQ ID NO:Y or the complete amino acid sequence encoded by the cDNA in Plasmid:V; (g) a nucleotide sequence encoding a mature ACRP30-Like polypeptide of the amino acid sequence of SEQ ID NO:Y or the amino acid sequence encoded by the cDNA in Plasmid:V; (h) a nucleotide sequence encoding a biologically active fragment of a ACRP30-Like polypeptide having the complete amino acid sequence of SEQ ID NO:Y or the complete amino acid sequence encoded by the cDNA in Plasmid:V; (i) a nucleotide sequence encoding an antigenic fragment of a ACRP30-Like polypeptide having the complete amino acid sequence of SEQ ID NO:Y or the complete amino acid sequence encoded by the cDNA in Plasmid:V; and (j) a nucleotide sequence complementary to any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h), or (i) above.  
       [0541] The present invention is also directed to nucleic acid molecules which comprise, or alternatively consist of, a nucleotide sequence which is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, identical to, for example, any of the nucleotide sequences in (a), (b), (c), (d), (e), (f), (g), (h), (i), or (j) above, the nucleotide coding sequence in SEQ ID NO:X or the complementary strand thereto, the nucleotide coding sequence of the cDNA contained in Plasmid:V or the complementary strand thereto, a nucleotide sequence encoding the polypeptide of SEQ ID NO:Y, a nucleotide sequence encoding a polypeptide sequence encoded by the nucleotide sequence in SEQ ID NO:X, a polypeptide sequence encoded by the complement of the polynucleotide sequence in SEQ ID NO:X, a nucleotide sequence encoding the polypeptide encoded by the cDNA contained in Plasmid:V, the nucleotide sequence in SEQ ID NO:X encoding the polypeptide sequence as defined in column 10 of Table 1 or the complementary strand thereto, nucleotide sequences encoding the polypeptide as defined in column 10 of Table 1 or the complementary strand thereto, and/or polynucleotide fragments of any of these nucleic acid molecules (e.g., those fragments described herein). Polynucleotides which hybridize to the complement of these nucleic acid molecules under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention, as are polypeptides encoded by these polynucleotides and nucleic acids.  
       [0542] In a preferred embodiment, the invention encompasses nucleic acid molecules which comprise, or alternatively, consist of a polynucleotide which hybridizes under stringent hybridization conditions, or alternatively, under lower stringency conditions, to a polynucleotide in (a), (b), (c), (d), (e), (f), (g), (h), or (i), above, as are polypeptides encoded by these polynucleotides. In another preferred embodiment, polynucleotides which hybridize to the complement of these nucleic acid molecules under stringent hybridization conditions, or alternatively, under lower stringency conditions, are also encompassed by the invention, as are polypeptides encoded by these polynucleotides.  
       [0543] In another embodiment, the invention provides a purified protein comprising, or alternatively consisting of, a polypeptide having an amino acid sequence selected from the group consisting of: (a) the complete amino acid sequence of SEQ ID NO:Y or the complete amino acid sequence encoded by the cDNA in Plasmid:V; (b) the amino acid sequence of a mature form of a ACRP30-Like polypeptide having the amino acid sequence of SEQ ID NO:Y or the amino acid sequence encoded by the cDNA in Plasmid:V; (c) the amino acid sequence of a biologically active fragment of a ACRP30-Like polypeptide having the complete amino acid sequence of SEQ ID NO:Y or the complete amino acid sequence encoded by the cDNA in Plasmid:V; and (d) the amino acid sequence of an antigenic fragment of a ACRP30-Like polypeptide having the complete amino acid sequence of SEQ ID NO:Y or the complete amino acid sequence encoded by the cDNA in Plasmid:V.  
       [0544] The present invention is also directed to proteins which comprise, or alternatively consist of, an amino acid sequence which is at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100%, identical to, for example, any of the amino acid sequences in (a), (b), (c), or (d), above, the amino acid sequence shown in SEQ ID NO:Y, the amino acid sequence encoded by the cDNA contained in Plasmid:V, the amino acid sequence as defined in column 10 of Table 1, an amino acid sequence encoded by the nucleotide sequence in SEQ ID NO:X, and an amino acid sequence encoded by the complement of the polynucleotide sequence in SEQ ID NO:X. Fragments of these polypeptides are also provided (e.g., those fragments described herein). Further proteins encoded by polynucleotides which hybridize to the complement of the nucleic acid molecules encoding these amino acid sequences under stringent hybridization conditions or alternatively, under lower stringency conditions, are also encompassed by the invention, as are the polynucleotides encoding these proteins.  
       [0545] By a nucleic acid having a nucleotide sequence at least, for example, 95% “identical” to a reference nucleotide sequence of the present invention, it is intended that the nucleotide sequence of the nucleic acid is identical to the reference sequence except that the nucleotide sequence may include up to five point mutations per each 100 nucleotides of the reference nucleotide sequence encoding the polypeptide. In other words, to obtain a nucleic acid having a nucleotide sequence at least 95% identical to a reference nucleotide sequence, up to 5% of the nucleotides in the reference sequence may be deleted or substituted with another nucleotide, or a number of nucleotides up to 5% of the total nucleotides in the reference sequence may be inserted into the reference sequence. The query sequence may be an entire sequence referred to in Table 1, the ORF (open reading frame), or any fragment specified as described herein.  
       [0546] As a practical matter, whether any particular nucleic acid molecule or polypeptide is at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to a nucleotide sequence of the present invention can be determined conventionally using known computer programs. A preferred method for determining the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci. 6:237-245 (1990)). In a sequence alignment the query and subject sequences are both DNA sequences. An RNA sequence can be compared by converting U&#39;s to T&#39;s. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB alignment of DNA sequences to calculate percent identity are: Matrix=Unitary, k-tuple=4, Mismatch Penalty=1, Joining Penalty=30, Randomization Group Length=0, Cutoff Score=1, Gap Penalty=5, Gap Size Penalty 0.05, Window Size=500 or the lenght of the subject nucleotide sequence, whichever is shorter.  
       [0547] If the subject sequence is shorter than the query sequence because of 5′ or 3′ deletions, not because of internal deletions, a manual correction must be made to the results. This is because the FASTDB program does not account for 5′ and 3′ truncations of the subject sequence when calculating percent identity. For subject sequences truncated at the 5′ or 3′ ends, relative to the query sequence, the percent identity is corrected by calculating the number of bases of the query sequence that are 5′ and 3′ of the subject sequence, which are not matched/aligned, as a percent of the total bases of the query sequence. Whether a nucleotide is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This corrected score is what is used for the purposes of the present invention. Only bases outside the 5′ and 3′ bases of the subject sequence, as displayed by the FASTDB alignment, which are not matched/aligned with the query sequence, are calculated for the purposes of manually adjusting the percent identity score.  
       [0548] For example, a 90 base subject sequence is aligned to a 100 base query sequence to determine percent identity. The deletions occur at the 5′ end of the subject sequence and therefore, the FASTDB alignment does not show a matched/alignment of the first 10 bases at 5′ end. The 10 unpaired bases represent 10% of the sequence (number of bases at the 5′ and 3′ ends not matched/total number of bases in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 bases were perfectly matched the final percent identity would be 90%. In another example, a 90 base subject sequence is compared with a 100 base query sequence. This time the deletions are internal deletions so that there are no bases on the 5′ or 3′ of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only bases 5′ and 3′ of the subject sequence which are not matched/aligned with the query sequence are manually corrected for. No other manual corrections are to made for the purposes of the present invention.  
       [0549] By a polypeptide having an amino acid sequence at least, for example, 95% “identical” to a query amino acid sequence of the present invention, it is intended that the amino acid sequence of the subject polypeptide is identical to the query sequence except that the subject polypeptide sequence may include up to five amino acid alterations per each 100 amino acids of the query amino acid sequence. In other words, to obtain a polypeptide having an amino acid sequence at least 95% identical to a query amino acid sequence, up to 5% of the amino acid residues in the subject sequence may be inserted, deleted, (indels) or substituted with another amino acid. These alterations of the reference sequence may occur at the amino or carboxy terminal positions of the reference amino acid sequence or anywhere between those terminal positions, interspersed either individually among residues in the reference sequence or in one or more contiguous groups within the reference sequence.  
       [0550] As a practical matter, whether any particular polypeptide is at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to, for instance, the amino acid sequence referred to in Table 1 or a fragment thereof, the amino acid sequence encoded by the nucleotide sequence in SEQ ID NO:X or a fragment thereof, or to the amino acid sequence encoded by the cDNA in cDNA plasmid:V, or a fragment thereof, can be determined conventionally using known computer programs. A preferred method for determining the best overall match between a query sequence (a sequence of the present invention) and a subject sequence, also referred to as a global sequence alignment, can be determined using the FASTDB computer program based on the algorithm of Brutlag et al. (Comp. App. Biosci.6:237-245(1990)). In a sequence alignment the query and subject sequences are either both nucleotide sequences or both amino acid sequences. The result of said global sequence alignment is in percent identity. Preferred parameters used in a FASTDB amino acid alignment are: Matrix=PAM 0, k-tuple=2, Mismatch Penalty=1, Joining Penalty=20, Randomization Group Length=0, Cutoff Score=1, Window Size=sequence length, Gap Penalty=5, Gap Size Penalty=0.05, Window Size=500 or the length of the subject amino acid sequence, whichever is shorter.  
       [0551] If the subject sequence is shorter than the query sequence due to N- or C-terminal deletions, not because of internal deletions, a manual correction must be made to the results. This is because the FASTDB program does not account for N- and C-terminal truncations of the subject sequence when calculating global percent identity. For subject sequences truncated at the N- and C-termini, relative to the query sequence, the percent identity is corrected by calculating the number of residues of the query sequence that are N- and C-terminal of the subject sequence, which are not matched/aligned with a corresponding subject residue, as a percent of the total bases of the query sequence. Whether a residue is matched/aligned is determined by results of the FASTDB sequence alignment. This percentage is then subtracted from the percent identity, calculated by the above FASTDB program using the specified parameters, to arrive at a final percent identity score. This final percent identity score is what is used for the purposes of the present invention. Only residues to the N- and C-termini of the subject sequence, which are not matched/aligned with the query sequence, are considered for the purposes of manually adjusting the percent identity score. That is, only query residue positions outside the farthest N- and C-terminal residues of the subject sequence.  
       [0552] For example, a 90 amino acid residue subject sequence is aligned with a 100 residue query sequence to determine percent identity. The deletion occurs at the N-terminus of the subject sequence and therefore, the FASTDB alignment does not show a matching/alignment of the first 10 residues at the N-terminus. The 10 unpaired residues represent 10% of the sequence (number of residues at the N- and C-termini not matched/total number of residues in the query sequence) so 10% is subtracted from the percent identity score calculated by the FASTDB program. If the remaining 90 residues were perfectly matched the final percent identity would be 90%. In another example, a 90 residue subject sequence is compared with a 100 residue query sequence. This time the deletions are internal deletions so there are no residues at the N- or C-termini of the subject sequence which are not matched/aligned with the query. In this case the percent identity calculated by FASTDB is not manually corrected. Once again, only residue positions outside the N- and C-terminal ends of the subject sequence, as displayed in the FASTDB alignment, which are not matched/aligned with the query sequence are manually corrected for. No other manual corrections are to made for the purposes of the present invention.  
       [0553] The variants may contain alterations in the coding regions, non-coding regions, or both. Especially preferred are polynucleotide variants containing alterations which produce silent substitutions, additions, or deletions, but do not alter the properties or activities of the encoded polypeptide. Nucleotide variants produced by silent substitutions due to the degeneracy of the genetic code are preferred. Moreover, variants in which less than 50, less than 40, less than 30, less than 20, less than 10, or 5-50, 5-25, 5-10, 1-5, or 1-2 amino acids are substituted, deleted, or added in any combination are also preferred. Polynucleotide variants can be produced for a variety of reasons, e.g., to optimize codon expression for a particular host (change codons in the human mRNA to those preferred by a bacterial host such as  E. coli ).  
       [0554] Naturally occurring variants are called “allelic variants,” and refer to one of several alternate forms of a gene occupying a given locus on a chromosome of an organism. (Genes II, Lewin, B., ed., John Wiley &amp; Sons, New York (1985)). These allelic variants can vary at either the polynucleotide and/or polypeptide level and are included in the present invention. Alternatively, non-naturally occurring variants may be produced by mutagenesis techniques or by direct synthesis.  
       [0555] Using known methods of protein engineering and recombinant DNA technology, variants may be generated to improve or alter the characteristics of the polypeptides of the present invention. For instance, as discussed herein, one or more amino acids can be deleted from the N-terminus or C-terminus of the polypeptide of the present invention without substantial loss of biological function. The authors of Ron et al., J. Biol. Chem. 268: 2984-2988 (1993), reported variant KGF proteins having heparin binding activity even after deleting 3, 8, or 27 amino-terminal amino acid residues. Similarly, Interferon gamma exhibited up to ten times higher activity after deleting 8-10 amino acid residues from the carboxy terminus of this protein. (Dobeli et al., J. Biotechnology 7:199-216 (1988)).  
       [0556] Moreover, ample evidence demonstrates that variants often retain a biological activity similar to that of the naturally occurring protein. For example, Gayle and coworkers (J. Biol. Chem 268:22105-22111 (1993)) conducted extensive mutational analysis of human cytokine IL-1a. They used random mutagenesis to generate over 3,500 individual IL-1a mutants that averaged 2.5 amino acid changes per variant over the entire length of the molecule. Multiple mutations were examined at every possible amino acid position. The investigators found that “[m]ost of the molecule could be altered with little effect on either [binding or biological activity].” (See, Abstract.) In fact, only 23 unique amino acid sequences, out of more than 3,500 nucleotide sequences examined, produced a protein that significantly differed in activity from wild-type.  
       [0557] Furthermore, as discussed herein, even if deleting one or more amino acids from the N-terminus or C-terminus of a polypeptide results in modification or loss of one or more biological functions, other biological activities may still be retained. For example, the ability of a deletion variant to induce and/or to bind antibodies which recognize the secreted form will likely be retained when less than the majority of the residues of the secreted form are removed from the N-terminus or C-terminus. Whether a particular polypeptide lacking N- or C-terminal residues of a protein retains such immunogenic activities can readily be determined by routine methods described herein and otherwise known in the art.  
       [0558] Thus, the invention further includes polypeptide variants which show a functional activity (e.g. biological activity) of the polypeptide of the invention, of which they are a variant. Such variants include deletions, insertions, inversions, repeats, and substitutions selected according to general rules known in the art so as have little effect on activity.  
       [0559] The present application is directed to nucleic acid molecules at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the nucleic acid sequences disclosed herein, (e.g., encoding a polypeptide having the amino acid sequence of an N and/or C terminal deletion), irrespective of whether they encode a polypeptide having functional activity. This is because even where a particular nucleic acid molecule does not encode a polypeptide having functional activity, one of skill in the art would still know how to use the nucleic acid molecule, for instance, as a hybridization probe or a polymerase chain reaction (PCR) primer. Uses of the nucleic acid molecules of the present invention that do not encode a polypeptide having functional activity include, inter alia, (1) isolating a gene or allelic or splice variants thereof in a cDNA library; (2) in situ hybridization (e.g., “FISH”) to metaphase chromosomal spreads to provide precise chromosomal location of the gene, as described in Verma et al., Human Chromosomes: A Manual of Basic Techniques, Pergamon Press, New York (1988); and (3) Northern Blot analysis for detecting mRNA expression in specific tissues.  
       [0560] Preferred, however, are nucleic acid molecules having sequences at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to the nucleic acid sequences disclosed herein, which do, in fact, encode a polypeptide having functional activity of a polypeptide of the invention.  
       [0561] Of course, due to the degeneracy of the genetic code, one of ordinary skill in the art will immediately recognize that a large number of the nucleic acid molecules having a sequence at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to, for example, the nucleic acid sequence of the cDNA in cDNA plasmid:V, the nucleic acid sequence referred to in Table 1 (SEQ ID NO:X), or fragments thereof, will encode polypeptides “having functional activity.” In fact, since degenerate variants of any of these nucleotide sequences all encode the same polypeptide, in many instances, this will be clear to the skilled artisan even without performing the above described comparison assay. It will be further recognized in the art that, for such nucleic acid molecules that are not degenerate variants, a reasonable number will also encode a polypeptide having functional activity. This is because the skilled artisan is fully aware of amino acid substitutions that are either less likely or not likely to significantly effect protein function (e.g., replacing one aliphatic amino acid with a second aliphatic amino acid), as further described below.  
       [0562] For example, guidance concerning how to make phenotypically silent amino acid substitutions is provided in Bowie et al., “Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions,” Science 247:1306-1310 (1990), wherein the authors indicate that there are two main strategies for studying the tolerance of an amino acid sequence to change.  
       [0563] The first strategy exploits the tolerance of amino acid substitutions by natural selection during the process of evolution. By comparing amino acid sequences in different species, conserved amino acids can be identified. These conserved amino acids are likely important for protein function. In contrast, the amino acid positions where substitutions have been tolerated by natural selection indicates that these positions are not critical for protein function. Thus, positions tolerating amino acid substitution could be modified while still maintaining biological activity of the protein.  
       [0564] The second strategy uses genetic engineering to introduce amino acid changes at specific positions of a cloned gene to identify regions critical for protein function. For example, site directed mutagenesis or alanine-scanning mutagenesis (introduction of single alanine mutations at every residue in the molecule) can be used. (Cunningham and Wells, Science 244:1081-1085 (1989)). The resulting mutant molecules can then be tested for biological activity.  
       [0565] As the authors state, these two strategies have revealed that proteins are surprisingly tolerant of amino acid substitutions. The authors further indicate which amino acid changes are likely to be permissive at certain amino acid positions in the protein. For example, most buried (within the tertiary structure of the protein) amino acid residues require nonpolar side chains, whereas few features of surface side chains are generally conserved. Moreover, tolerated conservative amino acid substitutions involve replacement of the aliphatic or hydrophobic amino acids Ala, Val, Leu and Ile; replacement of the hydroxyl residues Ser and Thr; replacement of the acidic residues Asp and Glu; replacement of the amide residues Asn and Gln, replacement of the basic residues Lys, Arg, and His; replacement of the aromatic residues Phe, Tyr, and Trp, and replacement of the small-sized amino acids Ala, Ser, Thr, Met, and Gly. Besides conservative amino acid substitution, variants of the present invention include (i) substitutions with one or more of the non-conserved amino acid residues, where the substituted amino acid residues may or may not be one encoded by the genetic code, or (ii) substitution with one or more of amino acid residues having a substituent group, or (iii) fusion of the mature polypeptide with another compound, such as a compound to increase the stability and/or solubility of the polypeptide (for example, polyethylene glycol), or (iv) fusion of the polypeptide with additional amino acids, such as, for example, an IgG Fc fusion region peptide, or leader or secretory sequence, or a sequence facilitating purification or (v) fusion of the polypeptide with another compound, such as albumin (including but not limited to recombinant albumin (see, e.g., U.S. Pat. No. 5,876,969, issued Mar. 2, 1999, EP Patent 0 413 622, and U.S. Pat. No. 5,766,883, issued Jun. 16, 1998, herein incorporated by reference in their entirety)). Such variant polypeptides are deemed to be within the scope of those skilled in the art from the teachings herein.  
       [0566] For example, polypeptide variants containing amino acid substitutions of charged amino acids with other charged or neutral amino acids may produce proteins with improved characteristics, such as less aggregation. Aggregation of pharmaceutical formulations both reduces activity and increases clearance due to the aggregate&#39;s immunogenic activity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967); Robbins et al., Diabetes 36: 838-845 (1987); Cleland et al., Crit. Rev. Therapeutic Drug Carrier Systems 10:307-377 (1993)).  
       [0567] A further embodiment of the invention relates to a polypeptide which comprises the amino acid sequence of a polypeptide having an amino acid sequence which contains at least one amino acid substitution, but not more than 50 amino acid substitutions, even more preferably, not more than 40 amino acid substitutions, still more preferably, not more than 30 amino acid substitutions, and still even more preferably, not more than 20 amino acid substitutions. Of course it is highly preferable for a polypeptide to have an amino acid sequence which comprises the amino acid sequence of a polypeptide of SEQ ID NO:Y; an amino acid sequence encoded by SEQ ID NO:X, and/or the amino acid sequence encoded by the cDNA in cDNA plasmid:V which contains, in order of ever-increasing preference, at least one, but not more than 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid substitutions. In specific embodiments, the number of additions, substitutions, and/or deletions in the amino acid sequence of SEQ ID NO:Y or fragments thereof (e.g., the mature form and/or other fragments described herein), an amino acid sequence encoded by SEQ ID NO:X or fragments thereof, and/or the amino acid sequence encoded by cDNA plasmid:V or fragments thereof, is 1-5, 5-10, 5-25, 5-50, 10-50 or 50-150, conservative amino acid substitutions are preferable. As discussed herein, any polypeptide of the present invention can be used to generate fusion proteins. For example, the polypeptide of the present invention, when fused to a second protein, can be used as an antigenic tag. Antibodies raised against the polypeptide of the present invention can be used to indirectly detect the second protein by binding to the polypeptide. Moreover, because secreted proteins target cellular locations based on trafficking signals, polypeptides of the present invention which are shown to be secreted can be used as targeting molecules once fused to other proteins.  
       [0568] Examples of domains that can be fused to polypeptides of the present invention include not only heterologous signal sequences, but also other heterologous functional regions. The fusion does not necessarily need to be direct, but may occur through linker sequences.  
       [0569] In certain preferred embodiments, proteins of the invention comprise fusion proteins wherein the polypeptides are N and/or C-terminal deletion mutants. In preferred embodiments, the application is directed to nucleic acid molecules at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to the nucleic acid sequences encoding polypeptides having the amino acid sequence of the specific N- and C-terminal deletions mutants. Polynucleotides encoding these polypeptides, including fragments and/or variants, are also encompassed by the invention.  
       [0570] Moreover, fusion proteins may also be engineered to improve characteristics of the polypeptide of the present invention. For instance, a region of additional amino acids, particularly charged amino acids, may be added to the N-terminus of the polypeptide to improve stability and persistence during purification from the host cell or subsequent handling and storage. Also, peptide moieties may be added to the polypeptide to facilitate purification. Such regions may be removed prior to final preparation of the polypeptide. The addition of peptide moieties to facilitate handling of polypeptides are familiar and routine techniques in the art.  
       [0571] As one of skill in the art will appreciate, polypeptides of the present invention of the present invention and the epitope-bearing fragments thereof described above can be combined with heterologous polypeptide sequences. For example, the polypeptides of the present invention may be fused with heterologous polypeptide sequences, for example, the polypeptides of the present invention may be fused with the constant domain of immunoglobulins (IgA, IgE, IgG, IgM) or portions thereof (CH1, CH2, CH3, and any combination thereof, including both entire domains and portions thereof), resulting in chimeric polypeptides. These fusion proteins facilitate purification and show an increased half-life in vivo. One reported example describes chimeric proteins consisting of the first two domains of the human CD4-polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins. (EP A 394,827; Traunecker et al., Nature 331:84-86 (1988)). Fusion proteins having disulfide-linked dimeric structures (due to the IgG) can also be more efficient in binding and neutralizing other molecules, than the monomeric protein or protein fragment alone. (Fountoulakis et al., J. Biochem. 270:3958-3964 (1995)).  
       [0572] Vectors, Host Cells, and Protein Production  
       [0573] The present invention also relates to vectors containing the polynucleotide of the present invention, host cells, and the production of polypeptides by recombinant techniques. The vector may be, for example, a phage, plasmid, viral, or retroviral vector. Retroviral vectors may be replication competent or replication defective. In the latter case, viral propagation generally will occur only in complementing host cells.  
       [0574] The polynucleotides of the invention may be joined to a vector containing a selectable marker for propagation in a host. Generally, a plasmid vector is introduced in a precipitate, such as a calcium phosphate precipitate, or in a complex with a charged lipid. If the vector is a virus, it may be packaged in vitro using an appropriate packaging cell line and then transduced into host cells.  
       [0575] The polynucleotide insert should be operatively linked to an appropriate promoter, such as the phage lambda PL promoter, the  E. coli  lac, trp, phoA and tac promoters, the SV40 early and late promoters and promoters of retroviral LTRs, to name a few. Other suitable promoters will be known to the skilled artisan. The expression constructs will further contain sites for transcription initiation, termination, and, in the transcribed region, a ribosome binding site for translation. The coding portion of the transcripts expressed by the constructs will preferably include a translation initiating codon at the beginning and a termination codon (UAA, UGA or UAG) appropriately positioned at the end of the polypeptide to be translated.  
       [0576] As indicated, the expression vectors will preferably include at least one selectable marker. Such markers include dihydrofolate reductase, G418 or neomycin resistance for eukaryotic cell culture and tetracycline, kanamycin or ampicillin resistance genes for culturing in  E. coli  and other bacteria. Representative examples of appropriate hosts include, but are not limited to, bacterial cells, such as  E. coli,  Streptomyces and  Salmonella typhimurium  cells; fungal cells, such as yeast cells (e.g.,  Saccharomyces cerevisiae  or  Pichia pastoris  (ATCC Accession No. 201178)); insect cells such as Drosophila S2 and Spodoptera Sf9 cells; animal cells such as CHO, COS, 293, and Bowes melanoma cells; and plant cells. Appropriate culture mediums and conditions for the above-described host cells are known in the art.  
       [0577] Among vectors preferred for use in bacteria include pQE70, pQE60 and pQE-9, available from QIAGEN, Inc.; pBluescript vectors, Phagescript vectors, pNH8A, pNH16a, pNH18A, pNH46A, available from Stratagene Cloning Systems, Inc.; and ptrc99a, pKK223-3, pKK233-3, pDR540, pRIT5 available from Pharmacia Biotech, Inc. Among preferred eukaryotic vectors are pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available from Stratagene; and pSVK3, pBPV, pMSG and pSVL available from Pharmacia. Preferred expression vectors for use in yeast systems include, but are not limited to pYES2, pYD1, pTEF1/Zeo, pYES2/GS, pPICZ, pGAPZ, pGAPZalph, pPIC9, pPIC3.5, pHIL-D2, pHIL-S1, pPIC3.5K, pPIC9K, and PAO815 (all available from Invitrogen, Carlbad, Calif.). Other suitable vectors will be readily apparent to the skilled artisan.  
       [0578] Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-dextran mediated transfection, cationic lipid-mediated transfection, electroporation, transduction, infection, or other methods. Such methods are described in many standard laboratory manuals, such as Davis et al., Basic Methods In Molecular Biology (1986). It is specifically contemplated that the polypeptides of the present invention may in fact be expressed by a host cell lacking a recombinant vector.  
       [0579] A polypeptide of this invention can be recovered and purified from recombinant cell cultures by well-known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Most preferably, high performance liquid chromatography (“HPLC”) is employed for purification.  
       [0580] Polypeptides of the present invention can also be recovered from: products purified from natural sources, including bodily fluids, tissues and cells, whether directly isolated or cultured; products of chemical synthetic procedures; and products produced by recombinant techniques from a prokaryotic or eukaryotic host, including, for example, bacterial, yeast, higher plant, insect, and mammalian cells. Depending upon the host employed in a recombinant production procedure, the polypeptides of the present invention may be glycosylated or may be non-glycosylated. In addition, polypeptides of the invention may also include an initial modified methionine residue, in some cases as a result of host-mediated processes. Thus, it is well known in the art that the N-terminal methionine encoded by the translation initiation codon generally is removed with high efficiency from any protein after translation in all eukaryotic cells. While the N-terminal methionine on most proteins also is efficiently removed in most prokaryotes, for some proteins, this prokaryotic removal process is inefficient, depending on the nature of the amino acid to which the N-terminal methionine is covalently linked.  
       [0581] In one embodiment, the yeast  Pichia pastoris  is used to express polypeptides of the invention in a eukaryotic system.  Pichia pastoris  is a methylotrophic yeast which can metabolize methanol as its sole carbon source. A main step in the methanol metabolization pathway is the oxidation of methanol to formaldehyde using O 2 . This reaction is catalyzed by the enzyme alcohol oxidase. In order to metabolize methanol as its sole carbon source,  Pichia pastoris  must generate high levels of alcohol oxidase due, in part, to the relatively low affinity of alcohol oxidase for O 2 . Consequently, in a growth medium depending on methanol as a main carbon source, the promoter region of one of the two alcohol oxidase genes (AOX1) is highly active. In the presence of methanol, alcohol oxidase produced from the AOX1 gene comprises up to approximately 30% of the total soluble protein in  Pichia pastoris.  See, Ellis, S. B., et al.,  Mol. Cell. Biol.  5:1111-21 (1985); Koutz, P. J, et al,  Yeast  5:167-77 (1989); Tschopp, J. F., et al.,  Nucl. Acids Res.  15:3859-76 (1987). Thus, a heterologous coding sequence, such as, for example, a polynucleotide of the present invention, under the transcriptional regulation of all or part of the AOX1 regulatory sequence is expressed at exceptionally high levels in Pichia yeast grown in the presence of methanol.  
       [0582] In one example, the plasmid vector pPIC9K is used to express DNA encoding a polypeptide of the invention, as set forth herein, in a Pichea yeast system essentially as described in “Pichia Protocols: Methods in Molecular Biology,” D. R. Higgins and J. Cregg, eds. The Humana Press, Totowa, N.J., 1998. This expression vector allows expression and secretion of a polypeptide of the invention by virtue of the strong AOX1 promoter linked to the  Pichia pastoris  alkaline phosphatase (PHO) secretory signal peptide (i.e., leader) located upstream of a multiple cloning site.  
       [0583] Many other yeast vectors could be used in place of pPIC9K, such as, pYES2, pYD1, pTEF1/Zeo, pYES2/GS, pPICZ, pGAPZ, pGAPZalpha, pPIC9, pPIC3.5, pHIL-D2, pHIL-S1, pPIC3.5K, and PAO815, as one skilled in the art would readily appreciate, as long as the proposed expression construct provides appropriately located signals for transcription, translation, secretion (if desired), and the like, including an in-frame AUG as required.  
       [0584] In another embodiment, high-level expression of a heterologous coding sequence, such as, for example, a polynucleotide of the present invention, may be achieved by cloning the heterologous polynucleotide of the invention into an expression vector such as, for example, pGAPZ or pGAPZalpha, and growing the yeast culture in the absence of methanol.  
       [0585] In addition to encompassing host cells containing the vector constructs discussed herein, the invention also encompasses primary, secondary, and immortalized host cells of vertebrate origin, particularly mammalian origin, that have been engineered to delete or replace endogenous genetic material (e.g., coding sequence), and/or to include genetic material (e.g., heterologous polynucleotide sequences) that is operably associated with polynucleotides of the invention, and which activates, alters, and/or amplifies endogenous polynucleotides. For example, techniques known in the art may be used to operably associate heterologous control regions (e.g., promoter and/or enhancer) and endogenous polynucleotide sequences via homologous recombination (see, e.g., U.S. Pat. No. 5,641,670, issued Jun. 24, 1997; International Publication No. WO 96/29411, published Sep. 26, 1996; International Publication No. WO 94/12650, published Aug. 4, 1994; Koller et al., Proc. Natl. Acad. Sci. USA 86:8932-8935 (1989); and Zijlstra et al., Nature 342:435-438 (1989), the disclosures of each of which are incorporated by reference in their entireties).  
       [0586] In addition, polypeptides of the invention can be chemically synthesized using techniques known in the art (e.g., see Creighton, 1983, Proteins: Structures and Molecular Principles, W. H. Freeman &amp; Co., N.Y., and Hunkapiller et al.,  Nature,  310:105-111 (1984)). For example, a polypeptide corresponding to a fragment of a polypeptide can be synthesized by use of a peptide synthesizer. Furthermore, if desired, nonclassical amino acids or chemical amino acid analogs can be introduced as a substitution or addition into the polypeptide sequence. Non-classical amino acids include, but are not limited to, to the D-isomers of the common amino acids, 2,4-diaminobutyric acid, a-amino isobutyric acid, 4-aminobutyric acid, Abu, 2-amino butyric acid, g-Abu, e-Ahx, 6-amino hexanoic acid, Aib, 2-amino isobutyric acid, 3-amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, b-alanine, fluoro-amino acids, designer amino acids such as b-methyl amino acids, Ca-methyl amino acids, Na-methyl amino acids, and amino acid analogs in general. Furthermore, the amino acid can be D (dextrorotary) or L (levorotary).  
       [0587] The invention encompasses polypeptides of the present invention which are differentially modified during or after translation, e.g., by glycosylation, acetylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, linkage to an antibody molecule or other cellular ligand, etc. Any of numerous chemical modifications may be carried out by known techniques, including but not limited, to specific chemical cleavage by cyanogen bromide, trypsin, chymotrypsin, papain, V8 protease, NaBH 4 ; acetylation, formylation, oxidation, reduction; metabolic synthesis in the presence of tunicamycin; etc.  
       [0588] Additional post-translational modifications encompassed by the invention include, for example, e.g., N-linked or O-linked carbohydrate chains, processing of N-terminal or C-terminal ends), attachment of chemical moieties to the amino acid backbone, chemical modifications of N-linked or O-linked carbohydrate chains, and addition or deletion of an N-terminal methionine residue as a result of procaryotic host cell expression. The polypeptides may also be modified with a detectable label, such as an enzymatic, fluorescent, isotopic or affinity label to allow for detection and isolation of the protein.  
       [0589] Also provided by the invention are chemically modified derivatives of the polypeptides of the invention which may provide additional advantages such as increased solubility, stability and circulating time of the polypeptide, or decreased immunogenicity (see U.S. Pat. No. 4,179,337). The chemical moieties for derivitization may be selected from water soluble polymers such as polyethylene glycol, ethylene glycol/propylene glycol copolymers, carboxymethylcellulose, dextran, polyvinyl alcohol and the like. The polypeptides may be modified at random positions within the molecule, or at predetermined positions within the molecule and may include one, two, three or more attached chemical moieties.  
       [0590] The polymer may be of any molecular weight, and may be branched or unbranched. For polyethylene glycol, the preferred molecular weight is between about 1 kDa and about 100 kDa (the term “about” indicating that in preparations of polyethylene glycol, some molecules will weigh more, some less, than the stated molecular weight) for ease in handling and manufacturing. Other sizes may be used, depending on the desired therapeutic profile (e.g., the duration of sustained release desired, the effects, if any on biological activity, the ease in handling, the degree or lack of antigenicity and other known effects of the polyethylene glycol to a therapeutic protein or analog).  
       [0591] The polyethylene glycol molecules (or other chemical moieties) should be attached to the protein with consideration of effects on functional or antigenic domains of the protein. There are a number of attachment methods available to those skilled in the art, e.g., EP 0 401 384, herein incorporated by reference (coupling PEG to G-CSF), see also Malik et al., Exp. Hematol. 20:1028-1035 (1992) (reporting pegylation of GM-CSF using tresyl chloride). For example, polyethylene glycol may be covalently bound through amino acid residues via a reactive group, such as, a free amino or carboxyl group. Reactive groups are those to which an activated polyethylene glycol molecule may be bound. The amino acid residues having a free amino group may include lysine residues and the N-terminal amino acid residues; those having a free carboxyl group may include aspartic acid residues glutamic acid residues and the C-terminal amino acid residue. Sulfhydryl groups may also be used as a reactive group for attaching the polyethylene glycol molecules. Preferred for therapeutic purposes is attachment at an amino group, such as attachment at the N-terminus or lysine group.  
       [0592] One may specifically desire proteins chemically modified at the N-terminus. Using polyethylene glycol as an illustration of the present composition, one may select from a variety of polyethylene glycol molecules (by molecular weight, branching, etc.), the proportion of polyethylene glycol molecules to protein (polypeptide) molecules in the reaction mix, the type of pegylation reaction to be performed, and the method of obtaining the selected N-terminally pegylated protein. The method of obtaining the N-terminally pegylated preparation (i.e., separating this moiety from other monopegylated moieties if necessary) may be by purification of the N-terminally pegylated material from a population of pegylated protein molecules. Selective proteins chemically modified at the N-terminus modification may be accomplished by reductive alkylation which exploits differential reactivity of different types of primary amino groups (lysine versus the N-terminal) available for derivatization in a particular protein. Under the appropriate reaction conditions, substantially selective derivatization of the protein at the N-terminus with a carbonyl group containing polymer is achieved.  
       [0593] The polypeptides of the invention may be in monomers or multimers (i.e., dimers, trimers, tetramers and higher multimers). Accordingly, the present invention relates to monomers and multimers of the polypeptides of the invention, their preparation, and compositions (preferably, Therapeutics) containing them. In specific embodiments, the polypeptides of the invention are monomers, dimers, trimers or tetramers. In additional embodiments, the multimers of the invention are at least dimers, at least trimers, or at least tetramers.  
       [0594] Multimers encompassed by the invention may be homomers or heteromers. As used herein, the term homomer, refers to a multimer containing only polypeptides corresponding to the amino acid sequence of SEQ ID NO:Y or an amino acid sequence encoded by SEQ ID NO:X or the complement of SEQ ID NO:X, and/or an amino acid sequence encoded by cDNA Plasmid:V (including fragments, variants, splice variants, and fusion proteins, corresponding to these as described herein). These homomers may contain polypeptides having identical or different amino acid sequences. In a specific embodiment, a homomer of the invention is a multimer containing only polypeptides having an identical amino acid sequence. In another specific embodiment, a homomer of the invention is a multimer containing polypeptides having different amino acid sequences. In specific embodiments, the multimer of the invention is a homodimer (e.g., containing polypeptides having identical or different amino acid sequences) or a homotrimer (e.g., containing polypeptides having identical and/or different amino acid sequences). In additional embodiments, the homomeric multimer of the invention is at least a homodimer, at least a homotrimer, or at least a homotetramer.  
       [0595] As used herein, the term heteromer refers to a multimer containing one or more heterologous polypeptides (i.e., polypeptides of different proteins) in addition to the polypeptides of the invention. In a specific embodiment, the multimer of the invention is a heterodimer, a heterotrimer, or a heterotetramer. In additional embodiments, the heteromeric multimer of the invention is at least a heterodimer, at least a heterotrimer, or at least a heterotetramer.  
       [0596] Multimers of the invention may be the result of hydrophobic, hydrophilic, ionic and/or covalent associations and/or may be indirectly linked, by for example, liposome formation. Thus, in one embodiment, multimers of the invention, such as, for example, homodimers or homotrimers, are formed when polypeptides of the invention contact one another in solution. In another embodiment, heteromultimers of the invention, such as, for example, heterotrimers or heterotetramers, are formed when polypeptides of the invention contact antibodies to the polypeptides of the invention (including antibodies to the heterologous polypeptide sequence in a fusion protein of the invention) in solution. In other embodiments, multimers of the invention are formed by covalent associations with and/or between the polypeptides of the invention. Such covalent associations may involve one or more amino acid residues contained in the polypeptide sequence (e.g., that recited in SEQ ID NO:Y, or contained in a polypeptide encoded by SEQ ID NO:X, and/or the cDNA plasmid:V). In one instance, the covalent associations are cross-linking between cysteine residues located within the polypeptide sequences which interact in the native (i.e., naturally occurring) polypeptide. In another instance, the covalent associations are the consequence of chemical or recombinant manipulation. Alternatively, such covalent associations may involve one or more amino acid residues contained in the heterologous polypeptide sequence in a fusion protein. In one example, covalent associations are between the heterologous sequence contained in a fusion protein of the invention (see, e.g., U.S. Pat. No. 5,478,925). In a specific example, the covalent associations are between the heterologous sequence contained in a Fc fusion protein of the invention (as described herein). In another specific example, covalent associations of fusion proteins of the invention are between heterologous polypeptide sequence from another protein that is capable of forming covalently associated multimers, such as for example, osteoprotegerin (see, e.g., International Publication NO: WO 98/49305, the contents of which are herein incorporated by reference in its entirety). In another embodiment, two or more polypeptides of the invention are joined through peptide linkers. Examples include those peptide linkers described in U.S. Pat. No. 5,073,627 (hereby incorporated by reference). Proteins comprising multiple polypeptides of the invention separated by peptide linkers may be produced using conventional recombinant DNA technology.  
       [0597] Another method for preparing multimer polypeptides of the invention involves use of polypeptides of the invention fused to a leucine zipper or isoleucine zipper polypeptide sequence. Leucine zipper and isoleucine zipper domains are polypeptides that promote multimerization of the proteins in which they are found. Leucine zippers were originally identified in several DNA-binding proteins (Landschulz et al., Science 240:1759, (1988)), and have since been found in a variety of different proteins. Among the known leucine zippers are naturally occurring peptides and derivatives thereof that dimerize or trimerize. Examples of leucine zipper domains suitable for producing soluble multimeric proteins of the invention are those described in PCT application WO 94/10308, hereby incorporated by reference. Recombinant fusion proteins comprising a polypeptide of the invention fused to a polypeptide sequence that dimerizes or trimerizes in solution are expressed in suitable host cells, and the resulting soluble multimeric fusion protein is recovered from the culture supernatant using techniques known in the art.  
       [0598] Trimeric polypeptides of the invention may offer the advantage of enhanced biological activity. Preferred leucine zipper moieties and isoleucine moieties are those that preferentially form trimers. One example is a leucine zipper derived from lung surfactant protein D (SPD), as described in Hoppe et al. (FEBS Letters 344:191, (1994)) and in U.S. patent application Ser. No. 08/446,922, hereby incorporated by reference. Other peptides derived from naturally occurring trimeric proteins may be employed in preparing trimeric polypeptides of the invention.  
       [0599] In another example, proteins of the invention are associated by interactions between Flag® polypeptide sequence contained in fusion proteins of the invention containing Flag® polypeptide seuqence. In a further embodiment, associations proteins of the invention are associated by interactions between heterologous polypeptide sequence contained in Flag® fusion proteins of the invention and anti-Flag® antibody.  
       [0600] The multimers of the invention may be generated using chemical techniques known in the art. For example, polypeptides desired to be contained in the multimers of the invention may be chemically cross-linked using linker molecules and linker molecule length optimization techniques known in the art (see, e.g., U.S. Pat. No. 5,478,925, which is herein incorporated by reference in its entirety). Additionally, multimers of the invention may be generated using techniques known in the art to form one or more inter-molecule cross-links between the cysteine residues located within the sequence of the polypeptides desired to be contained in the multimer (see, e.g., U.S. Pat. No. 5,478,925, which is herein incorporated by reference in its entirety). Further, polypeptides of the invention may be routinely modified by the addition of cysteine or biotin to the C-terminus or N-terminus of the polypeptide and techniques known in the art may be applied to generate multimers containing one or more of these modified polypeptides (see, e.g., U.S. Pat. No. 5,478,925, which is herein incorporated by reference in its entirety). Additionally, techniques known in the art may be applied to generate liposomes containing the polypeptide components desired to be contained in the multimer of the invention (see, e.g., U.S. Pat. No. 5,478,925, which is herein incorporated by reference in its entirety).  
       [0601] Alternatively, multimers of the invention may be generated using genetic engineering techniques known in the art. In one embodiment, polypeptides contained in multimers of the invention are produced recombinantly using fusion protein technology described herein or otherwise known in the art (see, e.g., U.S. Pat. No. 5,478,925, which is herein incorporated by reference in its entirety). In a specific embodiment, polynucleotides coding for a homodimer of the invention are generated by ligating a polynucleotide sequence encoding a polypeptide of the invention to a sequence encoding a linker polypeptide and then further to a synthetic polynucleotide encoding the translated product of the polypeptide in the reverse orientation from the original C-terminus to the N-terminus (lacking the leader sequence) (see, e.g., U.S. Pat. No. 5,478,925, which is herein incorporated by reference in its entirety). In another embodiment, recombinant techniques described herein or otherwise known in the art are applied to generate recombinant polypeptides of the invention which contain a transmembrane domain (or hyrophobic or signal peptide) and which can be incorporated by membrane reconstitution techniques into liposomes (see, e.g., U.S. Pat. No. 5,478,925, which is herein incorporated by reference in its entirety).  
       [0602] Antibodies  
       [0603] Further polypeptides of the invention relate to antibodies and T-cell antigen receptors (TCR) which immunospecifically bind a polypeptide, polypeptide fragment, or variant of SEQ ID NO:Y, and/or an epitope, of the present invention (as determined by immunoassays well known in the art for assaying specific antibody-antigen binding). Antibodies of the invention include, but are not limited to, polyclonal, monoclonal, multispecific, human, humanized or chimeric antibodies, single chain antibodies, Fab fragments, F(ab′) fragments, fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies (including, e.g., anti-Id antibodies to antibodies of the invention), and epitope-binding fragments of any of the above. The term “antibody,” as used herein, refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site that immunospecifically binds an antigen. The immunoglobulin molecules of the invention can be of any type (e.g., IgG, IgE, IgM, IgD, IgA and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass of immunoglobulin molecule.  
       [0604] Most preferably the antibodies are human antigen-binding antibody fragments of the present invention and include, but are not limited to, Fab, Fab′ and F(ab′)2, Fd, single-chain Fvs (scFv), single-chain antibodies, disulfide-linked Fvs (sdFv) and fragments comprising either a VL or VH domain. Antigen-binding antibody fragments, including single-chain antibodies, may comprise the variable region(s) alone or in combination with the entirety or a portion of the following: hinge region, CH1, CH2, and CH3 domains. Also included in the invention are antigen-binding fragments also comprising any combination of variable region(s) with a hinge region, CH1, CH2, and CH3 domains. The antibodies of the invention may be from any animal origin including birds and mammals. Preferably, the antibodies are human, murine (e.g., mouse and rat), donkey, ship rabbit, goat, guinea pig, camel, horse, or chicken. As used herein, “human” antibodies include antibodies having the amino acid sequence of a human immunoglobulin and include antibodies isolated from human immunoglobulin libraries or from animals transgenic for one or more human immunoglobulin and that do not express endogenous immunoglobulins, as described infra and, for example in, U.S. Pat. No. 5,939,598 by Kucherlapati et al.  
       [0605] The antibodies of the present invention may be monospecific, bispecific, trispecific or of greater multispecificity. Multispecific antibodies may be specific for different epitopes of a polypeptide of the present invention or may be specific for both a polypeptide of the present invention as well as for a heterologous epitope, such as a heterologous polypeptide or solid support material. See, e.g., PCT publications WO 93/17715; WO 92/08802; WO 91/00360; WO 92/05793; Tutt, et al., J. Immunol. 147:60-69 (1991); U.S. Pat. Nos. 4,474,893; 4,714,681; 4,925,648; 5,573,920; 5,601,819; Kostelny et al., J. Immunol. 148:1547-1553 (1992).  
       [0606] Antibodies of the present invention may be described or specified in terms of the epitope(s) or portion(s) of a polypeptide of the present invention which they recognize or specifically bind. The epitope(s) or polypeptide portion(s) may be specified as described herein, e.g., by N-terminal and C-terminal positions, or by size in contiguous amino acid residues. Antibodies which specifically bind any epitope or polypeptide of the present invention may also be excluded. Therefore, the present invention includes antibodies that specifically bind polypeptides of the present invention, and allows for the exclusion of the same.  
       [0607] Antibodies of the present invention may also be described or specified in terms of their cross-reactivity. Antibodies that do not bind any other analog, ortholog, or homolog of a polypeptide of the present invention are included. Antibodies that bind polypeptides with at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 70%, at least 65%, at least 60%, at least 55%, and at least 50% identity (as calculated using methods known in the art and described herein) to a polypeptide of the present invention are also included in the present invention. In specific embodiments, antibodies of the present invention cross-react with murine, rat and/or rabbit homologs of human proteins and the corresponding epitopes thereof. Antibodies that do not bind polypeptides with less than 95%, less than 90%, less than 85%, less than 80%, less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, and less than 50% identity (as calculated using methods known in the art and described herein) to a polypeptide of the present invention are also included in the present invention. In a specific embodiment, the above-described cross-reactivity is with respect to any single specific antigenic or immunogenic polypeptide, or combination(s) of 2, 3, 4, 5, or more of the specific antigenic and/or immunogenic polypeptides disclosed herein. Further included in the present invention are antibodies which bind polypeptides encoded by polynucleotides which hybridize to a polynucleotide of the present invention under stringent hybridization conditions (as described herein). Antibodies of the present invention may also be described or specified in terms of their binding affinity to a polypeptide of the invention. Preferred binding affinities include those with a dissociation constant or Kd less than 5×10 −2  M, 10 −2  M, 5×10 −3  M, 10 −3  M, 5×10 −4  M, 10 −4  M, 5×10 −5  M, 10 −5  M, 5×10 −6  M, 10 −6 M, 5×10 −7  M, 10 −7  M, 5×10 −8  M, 10 −8  M, 5×10 −9  M, 10 −9  M, 5×10 −10  M, 10 −10  M, 5×10 −11  M, 10 −11  M, 5×10 −12  M, 10 −12  M, 5×10 −13  M, 10 −13  M, 5×10 −14  M, 10 −14  M, 5×10 −15  M, or 10 −15  M.  
       [0608] The invention also provides antibodies that competitively inhibit binding of an antibody to an epitope of the invention as determined by any method known in the art for determining competitive binding, for example, the immunoassays described herein. In preferred embodiments, the antibody competitively inhibits binding to the epitope by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 70%, at least 60%, or at least 50%.  
       [0609] Antibodies of the present invention may act as agonists or antagonists of the polypeptides of the present invention. For example, the present invention includes antibodies which disrupt the receptor/ligand interactions with the polypeptides of the invention either partially or fully. Preferrably, antibodies of the present invention bind an antigenic epitope disclosed herein, or a portion thereof. The invention features both receptor-specific antibodies and ligand-specific antibodies. The invention also features receptor-specific antibodies which do not prevent ligand binding but prevent receptor activation. Receptor activation (i.e., signaling) may be determined by techniques described herein or otherwise known in the art. For example, receptor activation can be determined by detecting the phosphorylation (e.g., tyrosine or serine/threonine) of the receptor or its substrate by immunoprecipitation followed by western blot analysis (for example, as described supra). In specific embodiments, antibodies are provided that inhibit ligand activity or receptor activity by at least 95%, at least 90%, at least 85%, at least 80%, at least 75%, at least 70%, at least 60%, or at least 50% of the activity in absence of the antibody.  
       [0610] The invention also features receptor-specific antibodies which both prevent ligand binding and receptor activation as well as antibodies that recognize the receptor-ligand complex, and, preferably, do not specifically recognize the unbound receptor or the unbound ligand. Likewise, included in the invention are neutralizing antibodies which bind the ligand and prevent binding of the ligand to the receptor, as well as antibodies which bind the ligand, thereby preventing receptor activation, but do not prevent the ligand from binding the receptor. Further included in the invention are antibodies which activate the receptor. These antibodies may act as receptor agonists, i.e., potentiate or activate either all or a subset of the biological activities of the ligand-mediated receptor activation, for example, by inducing dimerization of the receptor. The antibodies may be specified as agonists, antagonists or inverse agonists for biological activities comprising the specific biological activities of the peptides of the invention disclosed herein. The above antibody agonists can be made using methods known in the art. See, e.g., PCT publication WO 96/40281; U.S. Pat. No. 5,811,097; Deng et al., Blood 92(6):1981-1988 (1998); Chen et al., Cancer Res. 58(16):3668-3678 (1998); Harrop et al., J. Immunol. 161(4):1786-1794 (1998); Zhu et al., Cancer Res. 58(15):3209-3214 (1998); Yoon et al., J. Immunol. 160(7):3170-3179 (1998); Prat et al., J. Cell. Sci. 111(Pt2):237-247 (1998); Pitard et al., J. Immunol. Methods 205(2):177-190 (1997); Liautard et al., Cytokine 9(4):233-241 (1997); Carlson et al., J. Biol. Chem. 272(17):11295-11301 (1997); Taryman et al., Neuron 14(4):755-762 (1995); Muller et al., Structure 6(9):1153-1167 (1998); Bartunek et al., Cytokine 8(1):14-20 (1996) (which are all incorporated by reference herein in their entireties).  
       [0611] Antibodies of the present invention may be used, for example, but not limited to, to purify, detect, and target the polypeptides of the present invention, including both in vitro and in vivo diagnostic and therapeutic methods. For example, the antibodies have use in immunoassays for qualitatively and quantitatively measuring levels of the polypeptides of the present invention in biological samples. See, e.g., Harlow et al., Antibodies: A Laboratory Manual, (Cold Spring Harbor Laboratory Press, 2nd ed. 1988) (incorporated by reference herein in its entirety).  
       [0612] As discussed in more detail below, the antibodies of the present invention may be used either alone or in combination with other compositions. The antibodies may further be recombinantly fused to a heterologous polypeptide at the N- or C-terminus or chemically conjugated (including covalently and non-covalently conjugations) to polypeptides or other compositions. For example, antibodies of the present invention may be recombinantly fused or conjugated to molecules useful as labels in detection assays and effector molecules such as heterologous polypeptides, drugs, radionuclides, or toxins. See, e.g., PCT publications WO 92/08495; WO 91/14438; WO 89/12624; U.S. Pat. No. 5,314,995; and EP 396,387.  
       [0613] The antibodies of the invention include derivatives that are modified, i.e, by the covalent attachment of any type of molecule to the antibody such that covalent attachment does not prevent the antibody from generating an anti-idiotypic response. For example, but not by way of limitation, the antibody derivatives include antibodies that have been modified, e.g., by glycosylation, acetylation, pegylation, phosphylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein, etc. Any of numerous chemical modifications may be carried out by known techniques, including, but not limited to specific chemical cleavage, acetylation, formylation, metabolic synthesis of tunicamycin, etc. Additionally, the derivative may contain one or more non-classical amino acids.  
       [0614] The antibodies of the present invention may be generated by any suitable method known in the art. Polyclonal antibodies to an antigen-of-interest can be produced by various procedures well known in the art. For example, a polypeptide of the invention can be administered to various host animals including, but not limited to, rabbits, mice, rats, etc. to induce the production of sera containing polyclonal antibodies specific for the antigen. Various adjuvants may be used to increase the immunological response, depending on the host species, and include but are not limited to, Freund&#39;s (complete and incomplete), mineral gels such as aluminum hydroxide, surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, keyhole limpet hemocyanins, dinitrophenol, and potentially useful human adjuvants such as BCG (bacille Calmette-Guerin) and  corynebacterium parvum.  Such adjuvants are also well known in the art.  
       [0615] Monoclonal antibodies can be prepared using a wide variety of techniques known in the art including the use of hybridoma, recombinant, and phage display technologies, or a combination thereof. For example, monoclonal antibodies can be produced using hybridoma techniques including those known in the art and taught, for example, in Harlow et al., Antibodies: A Laboratory Manual, (Cold Spring Harbor Laboratory Press, 2nd ed. 1988); Hammerling, et al., in: Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, N.Y., 1981) (said references incorporated by reference in their entireties). The term “monoclonal antibody” as used herein is not limited to antibodies produced through hybridoma technology. The term “monoclonal antibody” refers to an antibody that is derived from a single clone, including any eukaryotic, prokaryotic, or phage clone, and not the method by which it is produced.  
       [0616] Methods for producing and screening for specific antibodies using hybridoma technology are routine and well known in the art and are discussed in detail in the Examples. In a non-limiting example, mice can be immunized with a polypeptide of the invention or a cell expressing such peptide. Once an immune response is detected, e.g., antibodies specific for the antigen are detected in the mouse serum, the mouse spleen is harvested and splenocytes isolated. The splenocytes are then fused by well known techniques to any suitable myeloma cells, for example cells from cell line SP20 available from the ATCC. Hybridomas are selected and cloned by limited dilution. The hybridoma clones are then assayed by methods known in the art for cells that secrete antibodies capable of binding a polypeptide of the invention. Ascites fluid, which generally contains high levels of antibodies, can be generated by immunizing mice with positive hybridoma clones.  
       [0617] Accordingly, the present invention provides methods of generating monoclonal antibodies as well as antibodies produced by the method comprising culturing a hybridoma cell secreting an antibody of the invention wherein, preferably, the hybridoma is generated by fusing splenocytes isolated from a mouse immunized with an antigen of the invention with myeloma cells and then screening the hybridomas resulting from the fusion for hybridoma clones that secrete an antibody able to bind a polypeptide of the invention.  
       [0618] Antibody fragments which recognize specific epitopes may be generated by known techniques. For example, Fab and F(ab′)2 fragments of the invention may be produced by proteolytic cleavage of immunoglobulin molecules, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab′)2 fragments). F(ab′)2 fragments contain the variable region, the light chain constant region and the CH1 domain of the heavy chain. For example, the antibodies of the present invention can also be generated using various phage display methods known in the art. In phage display methods, functional antibody domains are displayed on the surface of phage particles which carry the polynucleotide sequences encoding them. In a particular embodiment, such phage can be utilized to display antigen binding domains expressed from a repertoire or combinatorial antibody library (e.g., human or murine). Phage expressing an antigen binding domain that binds the antigen of interest can be selected or identified with antigen, e.g., using labeled antigen or antigen bound or captured to a solid surface or bead. Phage used in these methods are typically filamentous phage including fd and M13 binding domains expressed from phage with Fab, Fv or disulfide stabilized Fv antibody domains recombinantly fused to either the phage gene III or gene VIII protein. Examples of phage display methods that can be used to make the antibodies of the present invention include those disclosed in Brinkman et al., J. Immunol. Methods 182:41-50 (1995); Ames et al., J. Immunol. Methods 184:177-186 (1995); Kettleborough et al., Eur. J. Immunol. 24:952-958 (1994); Persic et al., Gene 187 9-18 (1997); Burton et al., Advances in Immunology 57:191-280 (1994); PCT application No. PCT/GB91/01134; PCT publications WO 90/02809; WO 91/10737; WO 92/01047; WO 92/18619; WO 93/11236; WO 95/15982; WO 95/20401; and U.S. Pat. Nos. 5,698,426; 5,223,409; 5,403,484; 5,580,717; 5,427,908; 5,750,753; 5,821,047; 5,571,698; 5,427,908; 5,516,637; 5,780,225; 5,658,727; 5,733,743 and 5,969,108; each of which is incorporated herein by reference in its entirety.  
       [0619] As described in the above references, after phage selection, the antibody coding regions from the phage can be isolated and used to generate whole antibodies, including human antibodies, or any other desired antigen binding fragment, and expressed in any desired host, including mammalian cells, insect cells, plant cells, yeast, and bacteria, e.g., as described in detail below. For example, techniques to recombinantly produce Fab, Fab′ and F(ab′)2 fragments can also be employed using methods known in the art such as those disclosed in PCT publication WO 92/22324; Mullinax et al., BioTechniques 12(6):864-869 (1992); and Sawai et al., AJRI 34:26-34 (1995); and Better et al., Science 240:1041-1043 (1988) (said references incorporated by reference in their entireties).  
       [0620] Examples of techniques which can be used to produce single-chain Fvs and antibodies include those described in U.S. Pat. Nos. 4,946,778 and 5,258,498; Huston et al., Methods in Enzymology 203:46-88 (1991); Shu et al., PNAS 90:7995-7999 (1993); and Skerra et al., Science 240:1038-1040 (1988). For some uses, including in vivo use of antibodies in humans and in vitro detection assays, it may be preferable to use chimeric, humanized, or human antibodies. A chimeric antibody is a molecule in which different portions of the antibody are derived from different animal species, such as antibodies having a variable region derived from a murine monoclonal antibody and a human immunoglobulin constant region. Methods for producing chimeric antibodies are known in the art. See e.g., Morrison, Science 229:1202 (1985); Oi et al., BioTechniques 4:214 (1986); Gillies et al., (1989) J. Immunol. Methods 125:191-202; U.S. Pat. Nos. 5,807,715; 4,816,567; and 4,816,397, which are incorporated herein by reference in their entirety. Humanized antibodies are antibody molecules from non-human species antibody that binds the desired antigen having one or more complementarity determining regions (CDRs) from the non-human species and a framework regions from a human immunoglobulin molecule. Often, framework residues in the human framework regions will be substituted with the corresponding residue from the CDR donor antibody to alter, preferably improve, antigen binding. These framework substitutions are identified by methods well known in the art, e.g., by modeling of the interactions of the CDR and framework residues to identify framework residues important for antigen binding and sequence comparison to identify unusual framework residues at particular positions. (See, e.g., Queen et al., U.S. Pat. No. 5,585,089; Riechmann et al., Nature 332:323 (1988), which are incorporated herein by reference in their entireties.) Antibodies can be humanized using a variety of techniques known in the art including, for example, CDR-grafting (EP 239,400; PCT publication WO 91/09967; U.S. Pat. Nos. 5,225,539; 5,530,101; and 5,585,089), veneering or resurfacing (EP 592,106; EP 519,596; Padlan, Molecular Immunology 28(4/5):489-498 (1991); Studnicka et al., Protein Engineering 7(6):805-814 (1994); Roguska. et al., PNAS 91:969-973 (1994)), and chain shuffling (U.S. Pat. No. 5,565,332).  
       [0621] Completely human antibodies are particularly desirable for therapeutic treatment of human patients. Human antibodies can be made by a variety of methods known in the art including phage display methods described above using antibody libraries derived from human immunoglobulin sequences. See also, U.S. Pat. Nos. 4,444,887 and 4,716,111; and PCT publications WO 98/46645, WO 98/50433, WO 98/24893, WO 98/16654, WO 96/34096, WO 96/33735, and WO 91/10741; each of which is incorporated herein by reference in its entirety.  
       [0622] Human antibodies can also be produced using transgenic mice which are incapable of expressing functional endogenous immunoglobulins, but which can express human immunoglobulin genes. For example, the human heavy and light chain immunoglobulin gene complexes may be introduced randomly or by homologous recombination into mouse embryonic stem cells. Alternatively, the human variable region, constant region, and diversity region may be introduced into mouse embryonic stem cells in addition to the human heavy and light chain genes. The mouse heavy and light chain immunoglobulin genes may be rendered non-functional separately or simultaneously with the introduction of human immunoglobulin loci by homologous recombination. In particular, homozygous deletion of the JH region prevents endogenous antibody production. The modified embryonic stem cells are expanded and microinjected into blastocysts to produce chimeric mice. The chimeric mice are then bred to produce homozygous offspring which express human antibodies. The transgenic mice are immunized in the normal fashion with a selected antigen, e.g., all or a portion of a polypeptide of the invention. Monoclonal antibodies directed against the antigen can be obtained from the immunized, transgenic mice using conventional hybridoma technology. The human immunoglobulin transgenes harbored by the transgenic mice rearrange during B cell differentiation, and subsequently undergo class switching and somatic mutation. Thus, using such a technique, it is possible to produce therapeutically useful IgG, IgA, IgM and IgE antibodies. For an overview of this technology for producing human antibodies, see Lonberg and Huszar, Int. Rev. Immunol. 13:65-93 (1995). For a detailed discussion of this technology for producing human antibodies and human monoclonal antibodies and protocols for producing such antibodies, see, e.g., PCT publications WO 98/24893; WO 92/01047; WO 96/34096; WO 96/33735; European Patent No. 0 598 877; U.S. Pat. Nos. 5,413,923; 5,625,126; 5,633,425; 5,569,825; 5,661,016; 5,545,806; 5,814,318; 5,885,793; 5,916,771; and 5,939,598, which are incorporated by reference herein in their entirety. In addition, companies such as Abgenix, Inc. (Freemont, Calif.) and Genpharm (San Jose, Calif.) can be engaged to provide human antibodies directed against a selected antigen using technology similar to that described above.  
       [0623] Completely human antibodies which recognize a selected epitope can be generated using a technique referred to as “guided selection.” In this approach a selected non-human monoclonal antibody, e.g., a mouse antibody, is used to guide the selection of a completely human antibody recognizing the same epitope. (Jespers et al., Bio/technology 12:899-903 (1988)).  
       [0624] Further, antibodies to the polypeptides of the invention can, in turn, be utilized to generate anti-idiotype antibodies that “mimic” polypeptides of the invention using techniques well known to those skilled in the art. (See, e.g., Greenspan &amp; Bona, FASEB J. 7(5):437-444; (1989) and Nissinoff, J. Immunol. 147(8):2429-2438 (1991)). For example, antibodies which bind to and competitively inhibit polypeptide multimerization and/or binding of a polypeptide of the invention to a ligand can be used to generate anti-idiotypes that “mimic” the polypeptide multimerization and/or binding domain and, as a consequence, bind to and neutralize polypeptide and/or its ligand. Such neutralizing anti-idiotypes or Fab fragments of such anti-idiotypes can be used in therapeutic regimens to neutralize polypeptide ligand. For example, such anti-idiotypic antibodies can be used to bind a polypeptide of the invention and/or to bind its ligands/receptors, and thereby block its biological activity.  
       [0625] Polynucleotides Encoding Antibodies  
       [0626] The invention further provides polynucleotides comprising a nucleotide sequence encoding an antibody of the invention and fragments thereof. The invention also encompasses polynucleotides that hybridize under stringent or alternatively, under lower stringency hybridization conditions, e.g., as defined supra, to polynucleotides that encode an antibody, preferably, that specifically binds to a polypeptide of the invention, preferably, an antibody that binds to a polypeptide having the amino acid sequence of SEQ ID NO:Y.  
       [0627] The polynucleotides may be obtained, and the nucleotide sequence of the polynucleotides determined, by any method known in the art. For example, if the nucleotide sequence of the antibody is known, a polynucleotide encoding the antibody may be assembled from chemically synthesized oligonucleotides (e.g., as described in Kutmeier et al., BioTechniques 17:242 (1994)), which, briefly, involves the synthesis of overlapping oligonucleotides containing portions of the sequence encoding the antibody, annealing and ligating of those oligonucleotides, and then amplification of the ligated oligonucleotides by PCR.  
       [0628] Alternatively, a polynucleotide encoding an antibody may be generated from nucleic acid from a suitable source. If a clone containing a nucleic acid encoding a particular antibody is not available, but the sequence of the antibody molecule is known, a nucleic acid encoding the immunoglobulin may be chemically synthesized or obtained from a suitable source (e.g., an antibody cDNA library, or a cDNA library generated from, or nucleic acid, preferably poly A+ RNA, isolated from, any tissue or cells expressing the antibody, such as hybridoma cells selected to express an antibody of the invention) by PCR amplification using synthetic primers hybridizable to the 3′ and 5′ ends of the sequence or by cloning using an oligonucleotide probe specific for the particular gene sequence to identify, e.g., a cDNA clone from a cDNA library that encodes the antibody. Amplified nucleic acids generated by PCR may then be cloned into replicable cloning vectors using any method well known in the art.  
       [0629] Once the nucleotide sequence and corresponding amino acid sequence of the antibody is determined, the nucleotide sequence of the antibody may be manipulated using methods well known in the art for the manipulation of nucleotide sequences, e.g., recombinant DNA techniques, site directed mutagenesis, PCR, etc. (see, for example, the techniques described in Sambrook et al., 1990, Molecular Cloning, A Laboratory Manual, 2d Ed., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. and Ausubel et al., eds., 1998, Current Protocols in Molecular Biology, John Wiley &amp; Sons, NY, which are both incorporated by reference herein in their entireties), to generate antibodies having a different amino acid sequence, for example to create amino acid substitutions, deletions, and/or insertions.  
       [0630] In a specific embodiment, the amino acid sequence of the heavy and/or light chain variable domains may be inspected to identify the sequences of the complementarity determining regions (CDRs) by methods that are well know in the art, e.g., by comparison to known amino acid sequences of other heavy and light chain variable regions to determine the regions of sequence hypervariability. Using routine recombinant DNA techniques, one or more of the CDRs may be inserted within framework regions, e.g., into human framework regions to humanize a non-human antibody, as described supra. The framework regions may be naturally occurring or consensus framework regions, and preferably human framework regions (see, e.g., Chothia et al., J. Mol. Biol. 278: 457-479 (1998) for a listing of human framework regions). Preferably, the polynucleotide generated by the combination of the framework regions and CDRs encodes an antibody that specifically binds a polypeptide of the invention. Preferably, as discussed supra, one or more amino acid substitutions may be made within the framework regions, and, preferably, the amino acid substitutions improve binding of the antibody to its antigen. Additionally, such methods may be used to make amino acid substitutions or deletions of one or more variable region cysteine residues participating in an intrachain disulfide bond to generate antibody molecules lacking one or more intrachain disulfide bonds. Other alterations to the polynucleotide are encompassed by the present invention and within the skill of the art.  
       [0631] In addition, techniques developed for the production of “chimeric antibodies” (Morrison et al., Proc. Natl. Acad. Sci. 81:851-855 (1984); Neuberger et al., Nature 312:604-608 (1984); Takeda et al., Nature 314:452-454 (1985)) by splicing genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. As described supra, a chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region, e.g., humanized antibodies.  
       [0632] Alternatively, techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778; Bird, Science 242:423-42 (1988); Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883 (1988); and Ward et al., Nature 334:544-54 (1989)) can be adapted to produce single chain antibodies. Single chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, resulting in a single chain polypeptide. Techniques for the assembly of functional Fv fragments in  E. coli  may also be used (Skerra et al., Science 242:1038-1041 (1988)).  
       [0633] Methods of Producing Antibodies  
       [0634] The antibodies of the invention can be produced by any method known in the art for the synthesis of antibodies, in particular, by chemical synthesis or preferably, by recombinant expression techniques.  
       [0635] Recombinant expression of an antibody of the invention, or fragment, derivative or analog thereof, (e.g., a heavy or light chain of an antibody of the invention or a single chain antibody of the invention), requires construction of an expression vector containing a polynucleotide that encodes the antibody. Once a polynucleotide encoding an antibody molecule or a heavy or light chain of an antibody, or portion thereof (preferably containing the heavy or light chain variable domain), of the invention has been obtained, the vector for the production of the antibody molecule may be produced by recombinant DNA technology using techniques well known in the art. Thus, methods for preparing a protein by expressing a polynucleotide containing an antibody encoding nucleotide sequence are described herein. Methods which are well known to those skilled in the art can be used to construct expression vectors containing antibody coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. The invention, thus, provides replicable vectors comprising a nucleotide sequence encoding an antibody molecule of the invention, or a heavy or light chain thereof, or a heavy or light chain variable domain, operably linked to a promoter. Such vectors may include the nucleotide sequence encoding the constant region of the antibody molecule (see, e.g., PCT Publication WO 86/05807; PCT Publication WO 89/01036; and U.S. Pat. No. 5,122,464) and the variable domain of the antibody may be cloned into such a vector for expression of the entire heavy or light chain.  
       [0636] The expression vector is transferred to a host cell by conventional techniques and the transfected cells are then cultured by conventional techniques to produce an antibody of the invention. Thus, the invention includes host cells containing a polynucleotide encoding an antibody of the invention, or a heavy or light chain thereof, or a single chain antibody of the invention, operably linked to a heterologous promoter. In preferred embodiments for the expression of double-chained antibodies, vectors encoding both the heavy and light chains may be co-expressed in the host cell for expression of the entire immunoglobulin molecule, as detailed below.  
       [0637] A variety of host-expression vector systems may be utilized to express the antibody molecules of the invention. Such host-expression systems represent vehicles by which the coding sequences of interest may be produced and subsequently purified, but also represent cells which may, when transformed or transfected with the appropriate nucleotide coding sequences, express an antibody molecule of the invention in situ. These include but are not limited to microorganisms such as bacteria (e.g.,  E. coli, B. subtilis ) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing antibody coding sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing antibody coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing antibody coding sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing antibody coding sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3 cells) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter). Preferably, bacterial cells such as  Escherichia coli,  and more preferably, eukaryotic cells, especially for the expression of whole recombinant antibody molecule, are used for the expression of a recombinant antibody molecule. For example, mammalian cells such as Chinese hamster ovary cells (CHO), in conjunction with a vector such as the major intermediate early gene promoter element from human cytomegalovirus is an effective expression system for antibodies (Foecking et al., Gene 45:101 (1986); Cockett et al., Bio/Technology 8:2 (1990)).  
       [0638] In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the antibody molecule being expressed. For example, when a large quantity of such a protein is to be produced, for the generation of pharmaceutical compositions of an antibody molecule, vectors which direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited, to the  E. coli  expression vector pUR278 (Ruther et al., EMBO J. 2:1791 (1983)), in which the antibody coding sequence may be ligated individually into the vector in frame with the lac Z coding region so that a fusion protein is produced; pIN vectors (Inouye &amp; Inouye, Nucleic Acids Res. 13:3101-3109 (1985); Van Heeke &amp; Schuster, J. Biol. Chem. 24:5503-5509 (1989)); and the like. pGEX vectors may also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption and binding to matrix glutathione-agarose beads followed by elution in the presence of free glutathione. The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target gene product can be released from the GST moiety.  
       [0639] In an insect system,  Autographa californica  nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes. The virus grows in  Spodoptera frugiperda  cells. The antibody coding sequence may be cloned individually into non-essential regions (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter).  
       [0640] In mammalian host cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, the antibody coding sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric gene may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing the antibody molecule in infected hosts. (e.g., see Logan &amp; Shenk, Proc. Natl. Acad. Sci. USA 81:355-359 (1984)). Specific initiation signals may also be required for efficient translation of inserted antibody coding sequences. These signals include the ATG initiation codon and adjacent sequences. Furthermore, the initiation codon must be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see Bittner et al., Methods in Enzymol. 153:51-544 (1987)).  
       [0641] In addition, a host cell strain may be chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure the correct modification and processing of the foreign protein expressed. To this end, eukaryotic host cells which possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product may be used. Such mammalian host cells include but are not limited to CHO, VERY, BHK, Hela, COS, MDCK, 293, 3T3, W138, and in particular, breast cancer cell lines such as, for example, BT483, Hs578T, HTB2, BT20 and T47D, and normal mammary gland cell line such as, for example, CRL7030 and Hs578Bst.  
       [0642] For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines which stably express the antibody molecule may be engineered. Rather than using expression vectors which contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines which express the antibody molecule. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that interact directly or indirectly with the antibody molecule.  
       [0643] A number of selection systems may be used, including but not limited to the herpes simplex virus thymidine kinase (Wigler et al., Cell 11:223 (1977)), hypoxanthine-guanine phosphoribosyltransferase (Szybalska &amp; Szybalski, Proc. Natl. Acad. Sci. USA 48:202 (1992)), and adenine phosphoribosyltransferase (Lowy et al., Cell 22:817 (1980)) genes can be employed in tk-, hgprt- or aprt-cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler et al., Natl. Acad. Sci. USA 77:357 (1980); O&#39;Hare et al., Proc. Natl. Acad. Sci. USA 78:1527 (1981)); gpt, which confers resistance to mycophenolic acid (Mulligan &amp; Berg, Proc. Natl. Acad. Sci. USA 78:2072 (1981)); neo, which confers resistance to the aminoglycoside G-418 Clinical Pharmacy 12:488-505; Wu and Wu, Biotherapy 3:87-95 (1991); Tolstoshev, Ann. Rev. Pharmacol. Toxicol. 32:573-596 (1993); Mulligan, Science 260:926-932 (1993); and Morgan and Anderson, Ann. Rev. Biochem. 62:191-217 (1993); May, 1993, TIB TECH 11(5):155-215); and hygro, which confers resistance to hygromycin (Santerre et al., Gene 30:147 (1984)). Methods commonly known in the art of recombinant DNA technology may be routinely applied to select the desired recombinant clone, and such methods are described, for example, in Ausubel et al. (eds.), Current Protocols in Molecular Biology, John Wiley &amp; Sons, NY (1993); Kriegler, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY (1990); and in Chapters 12 and 13, Dracopoli et al. (eds), Current Protocols in Human Genetics, John Wiley &amp; Sons, NY (1994); Colberre-Garapin et al., J. Mol. Biol. 150:1 (1981), which are incorporated by reference herein in their entireties.  
       [0644] The expression levels of an antibody molecule can be increased by vector amplification (for a review, see Bebbington and Hentschel, The use of vectors based on gene amplification for the expression of cloned genes in mammalian cells in DNA cloning, Vol.3. (Academic Press, New York, 1987)). When a marker in the vector system expressing antibody is amplifiable, increase in the level of inhibitor present in culture of host cell will increase the number of copies of the marker gene. Since the amplified region is associated with the antibody gene, production of the antibody will also increase (Crouse et al., Mol. Cell. Biol. 3:257 (1983)).  
       [0645] The host cell may be co-transfected with two expression vectors of the invention, the first vector encoding a heavy chain derived polypeptide and the second vector encoding a light chain derived polypeptide. The two vectors may contain identical selectable markers which enable equal expression of heavy and light chain polypeptides. Alternatively, a single vector may be used which encodes, and is capable of expressing, both heavy and light chain polypeptides. In such situations, the light chain should be placed before the heavy chain to avoid an excess of toxic free heavy chain (Proudfoot, Nature 322:52 (1986); Kohler, Proc. Natl. Acad. Sci. USA 77:2197 (1980)). The coding sequences for the heavy and light chains may comprise cDNA or genomic DNA.  
       [0646] Once an antibody molecule of the invention has been produced by an animal, chemically synthesized, or recombinantly expressed, it may be purified by any method known in the art for purification of an immunoglobulin molecule, for example, by chromatography (e.g., ion exchange, affinity, particularly by affinity for the specific antigen after Protein A, and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for the purification of proteins. In addition, the antibodies of the present invention or fragments thereof can be fused to heterologous polypeptide sequences described herein or otherwise known in the art, to facilitate purification.  
       [0647] The present invention encompasses antibodies recombinantly fused or chemically conjugated (including both covalently and non-covalently conjugations) to a polypeptide (or portion thereof, preferably at least 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 amino acids of the polypeptide) of the present invention to generate fusion proteins. The fusion does not necessarily need to be direct, but may occur through linker sequences. The antibodies may be specific for antigens other than polypeptides (or portion thereof, preferably at least 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 amino acids of the polypeptide) of the present invention. For example, antibodies may be used to target the polypeptides of the present invention to particular cell types, either in vitro or in vivo, by fusing or conjugating the polypeptides of the present invention to antibodies specific for particular cell surface receptors. Antibodies fused or conjugated to the polypeptides of the present invention may also be used in in vitro immunoassays and purification methods using methods known in the art. See e.g., Harbor et al., supra, and PCT publication WO 93/21232; EP 439,095; Naramura et al., Immunol. Lett. 39:91-99 (1994); U.S. Pat. No. 5,474,981; Gillies et al., PNAS 89:1428-1432 (1992); Fell et al., J. Immunol. 146:2446-2452(1991), which are incorporated by reference in their entireties.  
       [0648] The present invention further includes compositions comprising the polypeptides of the present invention fused or conjugated to antibody domains other than the variable regions. For example, the polypeptides of the present invention may be fused or conjugated to an antibody Fc region, or portion thereof. The antibody portion fused to a polypeptide of the present invention may comprise the constant region, hinge region, CH1 domain, CH2 domain, and CH3 domain or any combination of whole domains or portions thereof. The polypeptides may also be fused or conjugated to the above antibody portions to form multimers. For example, Fc portions fused to the polypeptides of the present invention can form dimers through disulfide bonding between the Fc portions. Higher multimeric forms can be made by fusing the polypeptides to portions of IgA and IgM. Methods for fusing or conjugating the polypeptides of the present invention to antibody portions are known in the art. See, e.g., U.S. Pat. Nos. 5,336,603; 5,622,929; 5,359,046; 5,349,053; 5,447,851; 5,112,946; EP 307,434; EP 367,166; PCT publications WO 96/04388; WO 91/06570; Ashkenazi et al., Proc. Natl. Acad. Sci. USA 88:10535-10539 (1991); Zheng et al., J. Immunol. 154:5590-5600 (1995); and Vil et al., Proc. Natl. Acad. Sci. USA 89:11337-11341(1992) (said references incorporated by reference in their entireties).  
       [0649] As discussed, supra, the polypeptides corresponding to a polypeptide, polypeptide fragment, or a variant of SEQ ID NO:Y may be fused or conjugated to the above antibody portions to increase the in vivo half life of the polypeptides or for use in immunoassays using methods known in the art. Further, the polypeptides corresponding to SEQ ID NO:Y may be fused or conjugated to the above antibody portions to facilitate purification. One reported example describes chimeric proteins consisting of the first two domains of the human CD4-polypeptide and various domains of the constant regions of the heavy or light chains of mammalian immunoglobulins. (EP 394,827; Traunecker et al., Nature 331:84-86 (1988). The polypeptides of the present invention fused or conjugated to an antibody having disulfide-linked dimeric structures (due to the IgG) may also be more efficient in binding and neutralizing other molecules, than the monomeric secreted protein or protein fragment alone. (Fountoulakis et al., J. Biochem. 270:3958-3964 (1995)). In many cases, the Fc part in a fusion protein is beneficial in therapy and diagnosis, and thus can result in, for example, improved pharmacokinetic properties. (EP A 232,262). Alternatively, deleting the Fc part after the fusion protein has been expressed, detected, and purified, would be desired. For example, the Fc portion may hinder therapy and diagnosis if the fusion protein is used as an antigen for immunizations. In drug discovery, for example, human proteins, such as hIL-5, have been fused with Fc portions for the purpose of high-throughput screening assays to identify antagonists of hIL-5. (See, Bennett et al., J. Molecular Recognition 8:52-58 (1995); Johanson et al., J. Biol. Chem. 270:9459-9471 (1995).  
       [0650] Moreover, the antibodies or fragments thereof of the present invention can be fused to marker sequences, such as a peptide to facilitate purification. In preferred embodiments, the marker amino acid sequence is a hexa-histidine peptide, such as the tag provided in a pQE vector (QIAGEN, Inc., 9259 Eton Avenue, Chatsworth, Calif., 91311), among others, many of which are commercially available. As described in Gentz et al., Proc. Natl. Acad. Sci. USA 86:821-824 (1989), for instance, hexa-histidine provides for convenient purification of the fusion protein. Other peptide tags useful for purification include, but are not limited to, the “HA” tag, which corresponds to an epitope derived from the influenza hemagglutinin protein (Wilson et al., Cell 37:767 (1984)) and the “flag” tag.  
       [0651] The present invention further encompasses antibodies or fragments thereof conjugated to a diagnostic or therapeutic agent. The antibodies can be used diagnostically to, for example, monitor the development or progression of a tumor as part of a clinical testing procedure to, e.g., determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron emitting metals using various positron emission tomographies, and nonradioactive paramagnetic metal ions. The detectable substance may be coupled or conjugated either directly to the antibody (or fragment thereot) or indirectly, through an intermediate (such as, for example, a linker known in the art) using techniques known in the art. See, for example, U.S. Pat. No. 4,741,900 for metal ions which can be conjugated to antibodies for use as diagnostics according to the present invention. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin; and examples of suitable radioactive material include 125I, 131I, 111In or 99Tc.  
       [0652] Further, an antibody or fragment thereof may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, a therapeutic agent or a radioactive metal ion, e.g., alpha-emitters such as, for example, 213Bi. A cytotoxin or cytotoxic agent includes any agent that is detrimental to cells. Examples include paclitaxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof. Therapeutic agents include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin), anthracyclines (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., dactinomycin (formerly actinomycin), bleomycin, mithramycin, and anthramycin (AMC)), and anti-mitotic agents (e.g., vincristine and vinblastine).  
       [0653] The conjugates of the invention can be used for modifying a given biological response, the therapeutic agent or drug moiety is not to be construed as limited to classical chemical therapeutic agents. For example, the drug moiety may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin; a protein such as tumor necrosis factor, a-interferon, β-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator, an apoptotic agent, e.g., TNF-alpha, TNF-beta, AIM I (See, International Publication No. WO 97/33899), AIM II (See, International Publication No. WO 97/34911), Fas Ligand (Takahashi et al.,  Int. Immunol.,  6:1567-1574 (1994)), VEGI (See, International Publication No. WO 99/23105), a thrombotic agent or an anti-angiogenic agent, e.g., angiostatin or endostatin; or, biological response modifiers such as, for example, lymphokines, interleukin-1 (“IL-1”), interleukin-2 (“IL-2”), interleukin-6 (“IL-6”), granulocyte macrophage colony stimulating factor (“GM-CSF”), granulocyte colony stimulating factor (“G-CSF”), or other growth factors.  
       [0654] Antibodies may also be attached to solid supports, which are particularly useful for immunoassays or purification of the target antigen. Such solid supports include, but are not limited to, glass, cellulose, polyacrylamide, nylon, polystyrene, polyvinyl chloride or polypropylene.  
       [0655] Techniques for conjugating such therapeutic moiety to antibodies are well known, see, e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy”, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery”, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review”, in Monoclonal Antibodies &#39;84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy”, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., “The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates”, Immunol. Rev. 62:119-58 (1982).  
       [0656] Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Pat. No. 4,676,980, which is incorporated herein by reference in its entirety.  
       [0657] An antibody, with or without a therapeutic moiety conjugated to it, administered alone or in combination with cytotoxic factor(s) and/or cytokine(s) can be used as a therapeutic.  
       [0658] Immunophenotyping  
       [0659] The antibodies of the invention may be utilized for immunophenotyping of cell lines and biological samples. The translation product of the gene of the present invention may be useful as a cell specific marker, or more specifically as a cellular marker that is differentially expressed at various stages of differentiation and/or maturation of particular cell types. Monoclonal antibodies directed against a specific epitope, or combination of epitopes, will allow for the screening of cellular populations expressing the marker. Various techniques can be utilized using monoclonal antibodies to screen for cellular populations expressing the marker(s), and include magnetic separation using antibody-coated magnetic beads, “panning” with antibody attached to a solid matrix (i.e., plate), and flow cytometry (See, e.g., U.S. Pat. No. 5,985,660; and Morrison et al.,  Cell,  96:737-49 (1999)).  
       [0660] These techniques allow for the screening of particular populations of cells, such as might be found with hematological malignancies (i.e. minimal residual disease (MRD) in acute leukemic patients) and “non-self” cells in transplantations to prevent Graft-versus-Host Disease (GVHD). Alternatively, these techniques allow for the screening of hematopoietic stem and progenitor cells capable of undergoing proliferation and/or differentiation, as might be found in human umbilical cord blood.  
       [0661] Assays for Antibody Binding  
       [0662] The antibodies of the invention may be assayed for immunospecific binding by any method known in the art. The immunoassays which can be used include but are not limited to competitive and non-competitive assay systems using techniques such as western blots, radioimmunoassays, ELISA (enzyme linked immunosorbent assay), “sandwich” immunoassays, immunoprecipitation assays, precipitin reactions, gel diffusion precipitin reactions, immunodiffusion assays, agglutination assays, complement-fixation assays, immunoradiometric assays, fluorescent immunoassays, protein A immunoassays, to name but a few. Such assays are routine and well known in the art (see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley &amp; Sons, Inc., New York, which is incorporated by reference herein in its entirety). Exemplary immunoassays are described briefly below (but are not intended by way of limitation).  
       [0663] Immunoprecipitation protocols generally comprise lysing a population of cells in a lysis buffer such as RIPA buffer (1% NP-40 or Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 0.15 M NaCl, 0.01 M sodium phosphate at pH 7.2, 1% Trasylol) supplemented with protein phosphatase and/or protease inhibitors (e.g., EDTA, PMSF, aprotinin, sodium vanadate), adding the antibody of interest to the cell lysate, incubating for a period of time (e.g., 1-4 hours) at 4° C., adding protein A and/or protein G sepharose beads to the cell lysate, incubating for about an hour or more at 4° C., washing the beads in lysis buffer and resuspending the beads in SDS/sample buffer. The ability of the antibody of interest to immunoprecipitate a particular antigen can be assessed by, e.g., western blot analysis. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the binding of the antibody to an antigen and decrease the background (e.g., pre-clearing the cell lysate with sepharose beads). For further discussion regarding immunoprecipitation protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley &amp; Sons, Inc., New York at 10.16.1.  
       [0664] Western blot analysis generally comprises preparing protein samples, electrophoresis of the protein samples in a polyacrylamide gel (e.g., 8%-20% SDS-PAGE depending on the molecular weight of the antigen), transferring the protein sample from the polyacrylamide gel to a membrane such as nitrocellulose, PVDF or nylon, blocking the membrane in blocking solution (e.g., PBS with 3% BSA or non-fat milk), washing the membrane in washing buffer (e.g., PBS-Tween 20), blocking the membrane with primary antibody (the antibody of interest) diluted in blocking buffer, washing the membrane in washing buffer, blocking the membrane with a secondary antibody (which recognizes the primary antibody, e.g., an anti-human antibody) conjugated to an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) or radioactive molecule (e.g., 32P or 125I) diluted in blocking buffer, washing the membrane in wash buffer, and detecting the presence of the antigen. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected and to reduce the background noise. For further discussion regarding western blot protocols see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley &amp; Sons, Inc., New York at 10.8.1.  
       [0665] ELISAs comprise preparing antigen, coating the well of a 96 well microtiter plate with the antigen, adding the antibody of interest conjugated to a detectable compound such as an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) to the well and incubating for a period of time, and detecting the presence of the antigen. In ELISAs the antibody of interest does not have to be conjugated to a detectable compound; instead, a second antibody (which recognizes the antibody of interest) conjugated to a detectable compound may be added to the well. Further, instead of coating the well with the antigen, the antibody may be coated to the well. In this case, a second antibody conjugated to a detectable compound may be added following the addition of the antigen of interest to the coated well. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected as well as other variations of ELISAs known in the art. For further discussion regarding ELISAs see, e.g., Ausubel et al, eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley &amp; Sons, Inc., New York at 11.2.1.  
       [0666] The binding affinity of an antibody to an antigen and the off-rate of an antibody-antigen interaction can be determined by competitive binding assays. One example of a competitive binding assay is a radioimmunoassay comprising the incubation of labeled antigen (e.g., 3H or 125I) with the antibody of interest in the presence of increasing amounts of unlabeled antigen, and the detection of the antibody bound to the labeled antigen. The affinity of the antibody of interest for a particular antigen and the binding off-rates can be determined from the data by scatchard plot analysis. Competition with a second antibody can also be determined using radioimmunoassays. In this case, the antigen is incubated with antibody of interest conjugated to a labeled compound (e.g., 3H or 125I) in the presence of increasing amounts of an unlabeled second antibody.  
       [0667] Therapeutic Uses  
       [0668] The present invention is further directed to antibody-based therapies which involve administering antibodies of the invention to an animal, preferably a mammal, and most preferably a human, patient for treating one or more of the disclosed diseases, disorders, or conditions. Therapeutic compounds of the invention include, but are not limited to, antibodies of the invention (including fragments, analogs and derivatives thereof as described herein) and nucleic acids encoding antibodies of the invention (including fragments, analogs and derivatives thereof and anti-idiotypic antibodies as described herein). The antibodies of the invention can be used to treat, inhibit or prevent diseases, disorders or conditions associated with aberrant expression and/or activity of a polypeptide of the invention, including, but not limited to, any one or more of the diseases, disorders, or conditions described herein. The treatment and/or prevention of diseases, disorders, or conditions associated with aberrant expression and/or activity of a polypeptide of the invention includes, but is not limited to, alleviating symptoms associated with those diseases, disorders or conditions. Antibodies of the invention may be provided in pharmaceutically acceptable compositions as known in the art or as described herein.  
       [0669] A summary of the ways in which the antibodies of the present invention may be used therapeutically includes binding polynucleotides or polypeptides of the present invention locally or systemically in the body or by direct cytotoxicity of the antibody, e.g. as mediated by complement (CDC) or by effector cells (ADCC). Some of these approaches are described in more detail below. Armed with the teachings provided herein, one of ordinary skill in the art will know how to use the antibodies of the present invention for diagnostic, monitoring or therapeutic purposes without undue experimentation.  
       [0670] The antibodies of this invention may be advantageously utilized in combination with other monoclonal or chimeric antibodies, or with lymphokines or hematopoietic growth factors (such as, e.g., IL-2, IL-3 and IL-7), for example, which serve to increase the number or activity of effector cells which interact with the antibodies.  
       [0671] The antibodies of the invention may be administered alone or in combination with other types of treatments (e.g., radiation therapy, chemotherapy, hormonal therapy, immunotherapy and anti-tumor agents). Generally, administration of products of a species origin or species reactivity (in the case of antibodies) that is the same species as that of the patient is preferred. Thus, in a preferred embodiment, human antibodies, fragments derivatives, analogs, or nucleic acids, are administered to a human patient for therapy or prophylaxis.  
       [0672] It is preferred to use high affinity and/or potent in vivo inhibiting and/or neutralizing antibodies against polypeptides or polynucleotides of the present invention, fragments or regions thereof, for both immunoassays directed to and therapy of disorders related to polynucleotides or polypeptides, including fragments thereof, of the present invention. Such antibodies, fragments, or regions, will preferably have an affinity for polynucleotides or polypeptides of the invention, including fragments thereof. Preferred binding affinities include those with a dissociation constant or Kd less than 5×10 −2  M, 10 −2  M, 5×10 −3  M, 10 −3  M, 5×10 −4  M, 10 −4  M, 5×10 −5  M, 10 −5  M, 5×10 −6  M, 10 −6  M, 5×10 −7  M, 10 −7  M, 5×10 −8  M, 10 −8  M, 5×10 −9  M, 10 −9  M, 5×10 −10  M, 10 −10  M, 5×10 −11  M, 10 −11  M, 5×10 −12  M, 10 −12  M, 5×10 −13  M, 10 −13  M, 5×10 −14  M, 10 −14  M, 5×10 −15  M, and 10 −15  M.  
       [0673] Gene Therapy  
       [0674] In a specific embodiment, nucleic acids comprising sequences encoding antibodies or functional derivatives thereof, are administered to treat, inhibit or prevent a disease or disorder associated with aberrant expression and/or activity of a polypeptide of the invention, by way of gene therapy. Gene therapy refers to therapy performed by the administration to a subject of an expressed or expressible nucleic acid. In this embodiment of the invention, the nucleic acids produce their encoded protein that mediates a therapeutic effect.  
       [0675] Any of the methods for gene therapy available in the art can be used according to the present invention. Exemplary methods are described below.  
       [0676] For general reviews of the methods of gene therapy, see Goldspiel et al., Clinical Pharmacy 12:488-505 (1993); Wu and Wu, Biotherapy 3:87-95 (1991); Tolstoshev, Ann. Rev. Pharmacol. Toxicol. 32:573-596 (1993); Mulligan, Science 260:926-932 (1993); and Morgan and Anderson, Ann. Rev. Biochem. 62:191-217 (1993); May, TIBTECH 11(5):155-215 (1993). Methods commonly known in the art of recombinant DNA technology which can be used are described in Ausubel et al. (eds.), Current Protocols in Molecular Biology, John Wiley &amp; Sons, NY (1993); and Kriegler, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY (1990).  
       [0677] In a preferred aspect, the compound comprises nucleic acid sequences encoding an antibody, said nucleic acid sequences being part of expression vectors that express the antibody or fragments or chimeric proteins or heavy or light chains thereof in a suitable host. In particular, such nucleic acid sequences have promoters operably linked to the antibody coding region, said promoter being inducible or constitutive, and, optionally, tissue-specific. In another particular embodiment, nucleic acid molecules are used in which the antibody coding sequences and any other desired sequences are flanked by regions that promote homologous recombination at a desired site in the genome, thus providing for intrachromosomal expression of the antibody encoding nucleic acids (Koller and Smithies, Proc. Natl. Acad. Sci. USA 86:8932-8935 (1989); Zijlstra et al., Nature 342:435-438 (1989). In specific embodiments, the expressed antibody molecule is a single chain antibody; alternatively, the nucleic acid sequences include sequences encoding both the heavy and light chains, or fragments thereof, of the antibody.  
       [0678] Delivery of the nucleic acids into a patient may be either direct, in which case the patient is directly exposed to the nucleic acid or nucleic acid-carrying vectors, or indirect, in which case, cells are first transformed with the nucleic acids in vitro, then transplanted into the patient. These two approaches are known, respectively, as in vivo or ex vivo gene therapy.  
       [0679] In a specific embodiment, the nucleic acid sequences are directly administered in vivo, where it is expressed to produce the encoded product. This can be accomplished by any of numerous methods known in the art, e.g., by constructing them as part of an appropriate nucleic acid expression vector and administering it so that they become intracellular, e.g., by infection using defective or attenuated retrovirals or other viral vectors (see U.S. Pat. No. 4,980,286), or by direct injection of naked DNA, or by use of microparticle bombardment (e.g., a gene gun; Biolistic, Dupont), or coating with lipids or cell-surface receptors or transfecting agents, encapsulation in liposomes, microparticles, or microcapsules, or by administering them in linkage to a peptide which is known to enter the nucleus, by administering it in linkage to a ligand subject to receptor-mediated endocytosis (see, e.g., Wu and Wu, J. Biol. Chem. 262:4429-4432 (1987)) (which can be used to target cell types specifically expressing the receptors), etc. In another embodiment, nucleic acid-ligand complexes can be formed in which the ligand comprises a fusogenic viral peptide to disrupt endosomes, allowing the nucleic acid to avoid lysosomal degradation. In yet another embodiment, the nucleic acid can be targeted in vivo for cell specific uptake and expression, by targeting a specific receptor (see, e.g., PCT Publications WO 92/06180; WO 92/22635; WO92/20316; WO93/14188, WO 93/20221). Alternatively, the nucleic acid can be introduced intracellularly and incorporated within host cell DNA for expression, by homologous recombination (Koller and Smithies, Proc. Natl. Acad. Sci. USA 86:8932-8935 (1989); Zijlstra et al., Nature 342:435-438 (1989)).  
       [0680] In a specific embodiment, viral vectors that contains nucleic acid sequences encoding an antibody of the invention are used. For example, a retroviral vector can be used (see Miller et al., Meth. Enzymol. 217:581-599 (1993)). These retroviral vectors contain the components necessary for the correct packaging of the viral genome and integration into the host cell DNA. The nucleic acid sequences encoding the antibody to be used in gene therapy are cloned into one or more vectors, which facilitates delivery of the gene into a patient. More detail about retroviral vectors can be found in Boesen et al., Biotherapy 6:291-302 (1994), which describes the use of a retroviral vector to deliver the mdr1 gene to hematopoietic stem cells in order to make the stem cells more resistant to chemotherapy. Other references illustrating the use of retroviral vectors in gene therapy are: Clowes et al., J. Clin. Invest. 93:644-651 (1994); Kiem et al., Blood 83:1467-1473 (1994); Salmons and Gunzberg, Human Gene Therapy 4:129-141 (1993); and Grossman and Wilson, Curr. Opin. in Genetics and Devel. 3:110-114 (1993).  
       [0681] Adenoviruses are other viral vectors that can be used in gene therapy. Adenoviruses are especially attractive vehicles for delivering genes to respiratory epithelia. Adenoviruses naturally infect respiratory epithelia where they cause a mild disease. Other targets for adenovirus-based delivery systems are liver, the central nervous system, endothelial cells, and muscle. Adenoviruses have the advantage of being capable of infecting non-dividing cells. Kozarsky and Wilson, Current Opinion in Genetics and Development 3:499-503 (1993) present a review of adenovirus-based gene therapy. Bout et al., Human Gene Therapy 5:3-10 (1994) demonstrated the use of adenovirus vectors to transfer genes to the respiratory epithelia of rhesus monkeys. Other instances of the use of adenoviruses in gene therapy can be found in Rosenfeld et al., Science 252:431-434 (1991); Rosenfeld et al., Cell 68:143-155 (1992); Mastrangeli et al., J. Clin. Invest. 91:225-234 (1993); PCT Publication WO94/12649; and Wang, et al., Gene Therapy 2:775-783 (1995). In a preferred embodiment, adenovirus vectors are used.  
       [0682] Adeno-associated virus (AAV) has also been proposed for use in gene therapy (Walsh et al., Proc. Soc. Exp. Biol. Med. 204:289-300 (1993); U.S. Pat. No. 5,436,146).  
       [0683] Another approach to gene therapy involves transferring a gene to cells in tissue culture by such methods as electroporation, lipofection, calcium phosphate mediated transfection, or viral infection. Usually, the method of transfer includes the transfer of a selectable marker to the cells. The cells are then placed under selection to isolate those cells that have taken up and are expressing the transferred gene. Those cells are then delivered to a patient.  
       [0684] In this embodiment, the nucleic acid is introduced into a cell prior to administration in vivo of the resulting recombinant cell. Such introduction can be carried out by any method known in the art, including but not limited to transfection, electroporation, microinjection, infection with a viral or bacteriophage vector containing the nucleic acid sequences, cell fusion, chromosome-mediated gene transfer, microcell-mediated gene transfer, spheroplast fusion, etc. Numerous techniques are known in the art for the introduction of foreign genes into cells (see, e.g., Loeffler and Behr, Meth. Enzymol. 217:599-618 (1993); Cohen et al., Meth. Enzymol. 217:618-644 (1993); Cline, Pharmac. Ther. 29:69-92m (1985) and may be used in accordance with the present invention, provided that the necessary developmental and physiological functions of the recipient cells are not disrupted. The technique should provide for the stable transfer of the nucleic acid to the cell, so that the nucleic acid is expressible by the cell and preferably heritable and expressible by its cell progeny.  
       [0685] The resulting recombinant cells can be delivered to a patient by various methods known in the art. Recombinant blood cells (e.g., hematopoietic stem or progenitor cells) are preferably administered intravenously. The amount of cells envisioned for use depends on the desired effect, patient state, etc., and can be determined by one skilled in the art.  
       [0686] Cells into which a nucleic acid can be introduced for purposes of gene therapy encompass any desired, available cell type, and include but are not limited to epithelial cells, endothelial cells, keratinocytes, fibroblasts, muscle cells, hepatocytes; blood cells such as T lymphocytes, B lymphocytes, monocytes, macrophages, neutrophils, eosinophils, megakaryocytes, granulocytes; various stem or progenitor cells, in particular hematopoietic stem or progenitor cells, e.g., as obtained from bone marrow, umbilical cord blood, peripheral blood, fetal liver, etc.  
       [0687] In a preferred embodiment, the cell used for gene therapy is autologous to the patient.  
       [0688] In an embodiment in which recombinant cells are used in gene therapy, nucleic acid sequences encoding an antibody are introduced into the cells such that they are expressible by the cells or their progeny, and the recombinant cells are then administered in vivo for therapeutic effect. In a specific embodiment, stem or progenitor cells are used. Any stem and/or progenitor cells which can be isolated and maintained in vitro can potentially be used in accordance with this embodiment of the present invention (see e.g. PCT Publication WO 94/08598; Stemple and Anderson, Cell 71:973-985 (1992); Rheinwald, Meth. Cell Bio. 21A:229 (1980); and Pittelkow and Scott, Mayo Clinic Proc. 61:771 (1986)).  
       [0689] In a specific embodiment, the nucleic acid to be introduced for purposes of gene therapy comprises an inducible promoter operably linked to the coding region, such that expression of the nucleic acid is controllable by controlling the presence or absence of the appropriate inducer of transcription. Demonstration of Therapeutic or Prophylactic Activity  
       [0690] The compounds or pharmaceutical compositions of the invention are preferably tested in vitro, and then in vivo for the desired therapeutic or prophylactic activity, prior to use in humans. For example, in vitro assays to demonstrate the therapeutic or prophylactic utility of a compound or pharmaceutical composition include, the effect of a compound on a cell line or a patient tissue sample. The effect of the compound or composition on the cell line and/or tissue sample can be determined utilizing techniques known to those of skill in the art including, but not limited to, rosette formation assays and cell lysis assays. In accordance with the invention, in vitro assays which can be used to determine whether administration of a specific compound is indicated, include in vitro cell culture assays in which a patient tissue sample is grown in culture, and exposed to or otherwise administered a compound, and the effect of such compound upon the tissue sample is observed.  
       [0691] Therapeutic/Prophylactic Administration and Composition  
       [0692] The invention provides methods of treatment, inhibition and prophylaxis by administration to a subject of an effective amount of a compound or pharmaceutical composition of the invention, preferably a polypeptide or antibody of the invention. In a preferred aspect, the compound is substantially purified (e.g., substantially free from substances that limit its effect or produce undesired side-effects). The subject is preferably an animal, including but not limited to animals such as cows, pigs, horses, chickens, cats, dogs, etc., and is preferably a mammal, and most preferably human.  
       [0693] Formulations and methods of administration that can be employed when the compound comprises a nucleic acid or an immunoglobulin are described above; additional appropriate formulations and routes of administration can be selected from among those described herein below.  
       [0694] Various delivery systems are known and can be used to administer a compound of the invention, e.g., encapsulation in liposomes, microparticles, microcapsules, recombinat cells capable of expressing the compound, receptor-mediated endocytosis (see, e.g., Wu and Wu, J. Biol. Chem. 262:4429-4432 (1987)), construction of a nucleic acid as part of a retroviral or other vector, etc. Methods of introduction include but are not limited to intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes. The compounds or compositions may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically active agents. Administration can be systemic or local. In addition, it may be desirable to introduce the pharmaceutical compounds or compositions of the invention into the central nervous system by any suitable route, including intraventricular and intrathecal injection; intraventricular injection may be facilitated by an intraventricular catheter, for example, attached to a reservoir, such as an Ommaya reservoir. Pulmonary administration can also be employed, e.g., by use of an inhaler or nebulizer, and formulation with an aerosolizing agent.  
       [0695] In a specific embodiment, it may be desirable to administer the pharmaceutical compounds or compositions of the invention locally to the area in need of treatment; this may be achieved by, for example, and not by way of limitation, local infusion during surgery, topical application, e.g., in conjunction with a wound dressing after surgery, by injection, by means of a catheter, by means of a suppository, or by means of an implant, said implant being of a porous, non-porous, or gelatinous material, including membranes, such as sialastic membranes, or fibers. Preferably, when administering a protein, including an antibody, of the invention, care must be taken to use materials to which the protein does not absorb.  
       [0696] In another embodiment, the compound or composition can be delivered in a vesicle, in particular a liposome (see Langer, Science 249:1527-1533 (1990); Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein and Fidler (eds.), Liss, New York, pp. 353-365 (1989); Lopez-Berestein, ibid., pp. 317-327; see generally ibid.)  
       [0697] In yet another embodiment, the compound or composition can be delivered in a controlled release system. In one embodiment, a pump may be used (see Langer, supra; Sefton, CRC Crit. Ref. Biomed. Eng. 14:201 (1987); Buchwald et al., Surgery 88:507 (1980); Saudek et al., N. Engl. J. Med. 321:574 (1989)). In another embodiment, polymeric materials can be used (see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Pres., Boca Raton, Fla. (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, J., Macromol. Sci. Rev. Macromol. Chem. 23:61 (1983); see also Levy et al., Science 228:190 (1985); During et al., Ann. Neurol. 25:351 (1989); Howard et al., J.Neurosurg. 71:105 (1989)). In yet another embodiment, a controlled release system can be placed in proximity of the therapeutic target, i.e., the brain, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol. 2, pp. 115-138 (1984)).  
       [0698] Other controlled release systems are discussed in the review by Langer (Science 249:1527-1533 (1990)).  
       [0699] In a specific embodiment where the compound of the invention is a nucleic acid encoding a protein, the nucleic acid can be administered in vivo to promote expression of its encoded protein, by constructing it as part of an appropriate nucleic acid expression vector and administering it so that it becomes intracellular, e.g., by use of a retroviral vector (see U.S. Pat. No. 4,980,286), or by direct injection, or by use of microparticle bombardment (e.g., a gene gun; Biolistic, Dupont), or coating with lipids or cell-surface receptors or transfecting agents, or by administering it in linkage to a homeobox-like peptide which is known to enter the nucleus (see e.g., Joliot et al., Proc. Natl. Acad. Sci. USA 88:1864-1868 (1991)), etc. Alternatively, a nucleic acid can be introduced intracellularly and incorporated within host cell DNA for expression, by homologous recombination.  
       [0700] The present invention also provides pharmaceutical compositions. Such compositions comprise a therapeutically effective amount of a compound, and a pharmaceutically acceptable carrier. In a specific embodiment, the term “pharmaceutically acceptable” means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans. The term “carrier” refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is a preferred carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. These compositions can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained-release formulations and the like. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Examples of suitable pharmaceutical carriers are described in “Remington&#39;s Pharmaceutical Sciences” by E. W. Martin. Such compositions will contain a therapeutically effective amount of the compound, preferably in purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the patient. The formulation should suit the mode of administration.  
       [0701] In a preferred embodiment, the composition is formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous administration to human beings. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the composition may also include a solubilizing agent and a local anesthetic such as lignocaine to ease pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. Where the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the composition is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.  
       [0702] The compounds of the invention can be formulated as neutral or salt forms. Pharmaceutically acceptable salts include those formed with anions such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with cations such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, procaine, etc.  
       [0703] The amount of the compound of the invention which will be effective in the treatment, inhibition and prevention of a disease or disorder associated with aberrant expression and/or activity of a polypeptide of the invention can be determined by standard clinical techniques. In addition, in vitro assays may optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the formulation will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each patient&#39;s circumstances. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.  
       [0704] For antibodies, the dosage administered to a patient is typically 0.1 mg/kg to 100 mg/kg of the patient&#39;s body weight. Preferably, the dosage administered to a patient is between 0.1 mg/kg and 20 mg/kg of the patient&#39;s body weight, more preferably 1 mg/kg to 10 mg/kg of the patient&#39;s body weight. Generally, human antibodies have a longer half-life within the human body than antibodies from other species due to the immune response to the foreign polypeptides. Thus, lower dosages of human antibodies and less frequent administration is often possible. Further, the dosage and frequency of administration of antibodies of the invention may be reduced by enhancing uptake and tissue penetration (e.g., into the brain) of the antibodies by modifications such as, for example, lipidation.  
       [0705] The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration.  
       [0706] Diagnosis and Imaging  
       [0707] Labeled antibodies, and derivatives and analogs thereof, which specifically bind to a polypeptide of interest can be used for diagnostic purposes to detect, diagnose, or monitor diseases, disorders, and/or conditions associated with the aberrant expression and/or activity of a polypeptide of the invention. The invention provides for the detection of aberrant expression of a polypeptide of interest, comprising (a) assaying the expression of the polypeptide of interest in cells or body fluid of an individual using one or more antibodies specific to the polypeptide interest and (b) comparing the level of gene expression with a standard gene expression level, whereby an increase or decrease in the assayed polypeptide gene expression level compared to the standard expression level is indicative of aberrant expression.  
       [0708] The invention provides a diagnostic assay for diagnosing a disorder, comprising (a) assaying the expression of the polypeptide of interest in cells or body fluid of an individual using one or more antibodies specific to the polypeptide interest and (b) comparing the level of gene expression with a standard gene expression level, whereby an increase or decrease in the assayed polypeptide gene expression level compared to the standard expression level is indicative of a particular disorder. With respect to cancer, the presence of a relatively high amount of transcript in biopsied tissue from an individual may indicate a predisposition for the development of the disease, or may provide a means for detecting the disease prior to the appearance of actual clinical symptoms. A more definitive diagnosis of this type may allow health professionals to employ preventative measures or aggressive treatment earlier thereby preventing the development or further progression of the cancer.  
       [0709] Antibodies of the invention can be used to assay protein levels in a biological sample using classical immunohistological methods known to those of skill in the art (e.g., see Jalkanen, et al., J. Cell. Biol. 101:976-985 (1985); Jalkanen, et al., J. Cell. Biol. 105:3087-3096 (1987)). Other antibody-based methods useful for detecting protein gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assay labels are known in the art and include enzyme labels, such as, glucose oxidase; radioisotopes, such as iodine (125I, 121I), carbon (14C), sulfur (35S), tritium (3H), indium (112In), and technetium (99Tc); luminescent labels, such as luminol; and fluorescent labels, such as fluorescein and rhodamine, and biotin.  
       [0710] One aspect of the invention is the detection and diagnosis of a disease or disorder associated with aberrant expression of a polypeptide of interest in an animal, preferably a mammal and most preferably a human. In one embodiment, diagnosis comprises: a) administering (for example, parenterally, subcutaneously, or intraperitoneally) to a subject an effective amount of a labeled molecule which specifically binds to the polypeptide of interest; b) waiting for a time interval following the administering for permitting the labeled molecule to preferentially concentrate at sites in the subject where the polypeptide is expressed (and for unbound labeled molecule to be cleared to background level); c) determining background level; and d) detecting the labeled molecule in the subject, such that detection of labeled molecule above the background level indicates that the subject has a particular disease or disorder associated with aberrant expression of the polypeptide of interest. Background level can be determined by various methods including, comparing the amount of labeled molecule detected to a standard value previously determined for a particular system.  
       [0711] It will be understood in the art that the size of the subject and the imaging system used will determine the quantity of imaging moiety needed to produce diagnostic images. In the case of a radioisotope moiety, for a human subject, the quantity of radioactivity injected will normally range from about 5 to 20 millicuries of 99 mTc. The labeled antibody or antibody fragment will then preferentially accumulate at the location of cells which contain the specific protein. In vivo tumor imaging is described in S. W. Burchiel et al., “Immunopharmacokinetics of Radiolabeled Antibodies and Their Fragments.” (Chapter 13 in Tumor Imaging: The Radiochemical Detection of Cancer, S. W. Burchiel and B. A. Rhodes, eds., Masson Publishing Inc. (1982).  
       [0712] Depending on several variables, including the type of label used and the mode of administration, the time interval following the administration for permitting the labeled molecule to preferentially concentrate at sites in the subject and for unbound labeled molecule to be cleared to background level is 6 to 48 hours or 6 to 24 hours or 6 to 12 hours. In another embodiment the time interval following administration is 5 to 20 days or 5 to 10 days.  
       [0713] In an embodiment, monitoring of the disease or disorder is carried out by repeating the method for diagnosing the disease or disease, for example, one month after initial diagnosis, six months after initial diagnosis, one year after initial diagnosis, etc.  
       [0714] Presence of the labeled molecule can be detected in the patient using methods known in the art for in vivo scanning. These methods depend upon the type of label used. Skilled artisans will be able to determine the appropriate method for detecting a particular label. Methods and devices that may be used in the diagnostic methods of the invention include, but are not limited to, computed tomography (CT), whole body scan such as position emission tomography (PET), magnetic resonance imaging (MRI), and sonography.  
       [0715] In a specific embodiment, the molecule is labeled with a radioisotope and is detected in the patient using a radiation responsive surgical instrument (Thurston et al., U.S. Pat. No. 5,441,050). In another embodiment, the molecule is labeled with a fluorescent compound and is detected in the patient using a fluorescence responsive scanning instrument. In another embodiment, the molecule is labeled with a positron emitting metal and is detected in the patent using positron emission-tomography. In yet another embodiment, the molecule is labeled with a paramagnetic label and is detected in a patient using magnetic resonance imaging (MRI).  
       [0716] Kits  
       [0717] The present invention provides kits that can be used in the above methods. In one embodiment, a kit comprises an antibody of the invention, preferably a purified antibody, in one or more containers. In a specific embodiment, the kits of the present invention contain a substantially isolated polypeptide comprising an epitope which is specifically immunoreactive with an antibody included in the kit. Preferably, the kits of the present invention further comprise a control antibody which does not react with the polypeptide of interest. In another specific embodiment, the kits of the present invention contain a means for detecting the binding of an antibody to a polypeptide of interest (e.g., the antibody may be conjugated to a detectable substrate such as a fluorescent compound, an enzymatic substrate, a radioactive compound or a luminescent compound, or a second antibody which recognizes the first antibody may be conjugated to a detectable substrate).  
       [0718] In another specific embodiment of the present invention, the kit is a diagnostic kit for use in screening serum containing antibodies specific against proliferative and/or cancerous polynucleotides and polypeptides. Such a kit may include a control antibody that does not react with the polypeptide of interest. Such a kit may include a substantially isolated polypeptide antigen comprising an epitope which is specifically immunoreactive with at least one anti-polypeptide antigen antibody. Further, such a kit includes means for detecting the binding of said antibody to the antigen (e.g., the antibody may be conjugated to a fluorescent compound such as fluorescein or rhodamine which can be detected by flow cytometry). In specific embodiments, the kit may include a recombinantly produced or chemically synthesized polypeptide antigen. The polypeptide antigen of the kit may also be attached to a solid support.  
       [0719] In a more specific embodiment the detecting means of the above-described kit includes a solid support to which said polypeptide antigen is attached. Such a kit may also include a non-attached reporter-labeled anti-human antibody. In this embodiment, binding of the antibody to the polypeptide antigen can be detected by binding of the said reporter-labeled antibody.  
       [0720] In an additional embodiment, the invention includes a diagnostic kit for use in screening serum containing antigens of the polypeptide of the invention. The diagnostic kit includes a substantially isolated antibody specifically immunoreactive with polypeptide or polynucleotide antigens, and means for detecting the binding of the polynucleotide or polypeptide antigen to the antibody. In one embodiment, the antibody is attached to a solid support. In a specific embodiment, the antibody may be a monoclonal antibody. The detecting means of the kit may include a second, labeled monoclonal antibody. Alternatively, or in addition, the detecting means may include a labeled, competing antigen.  
       [0721] In one diagnostic configuration, test serum is reacted with a solid phase reagent having a surface-bound antigen obtained by the methods of the present invention. After binding with specific antigen antibody to the reagent and removing unbound serum components by washing, the reagent is reacted with reporter-labeled anti-human antibody to bind reporter to the reagent in proportion to the amount of bound anti-antigen antibody on the solid support. The reagent is again washed to remove unbound labeled antibody, and the amount of reporter associated with the reagent is determined. Typically, the reporter is an enzyme which is detected by incubating the solid phase in the presence of a suitable fluorometric, luminescent or colorimetric substrate (Sigma, St. Louis, Mo.).  
       [0722] The solid surface reagent in the above assay is prepared by known techniques for attaching protein material to solid support material, such as polymeric beads, dip sticks, 96-well plate or filter material. These attachment methods generally include non-specific adsorption of the protein to the support or covalent attachment of the protein, typically through a free amine group, to a chemically reactive group on the solid support, such as an activated carboxyl, hydroxyl, or aldehyde group. Alternatively, streptavidin coated plates can be used in conjunction with biotinylated antigen(s).  
       [0723] Thus, the invention provides an assay system or kit for carrying out this diagnostic method. The kit generally includes a support with surface-bound recombinant antigens, and a reporter-labeled anti-human antibody for detecting surface-bound anti-antigen antibody.  
       [0724] Uses of the Polynucleotides  
       [0725] Each of the polynucleotides identified herein can be used in numerous ways as reagents. The following description should be considered exemplary and utilizes known techniques.  
       [0726] The polynucleotides of the present invention are useful for chromosome identification. There exists an ongoing need to identify new chromosome markers, since few chromosome marking reagents, based on actual sequence data (repeat polymorphisms), are presently available. Each sequence is specifically targeted to and can hybridize with a particular location on an individual human chromosome, thus each polynucleotide of the present invention can routinely be used as a chromosome marker using techniques known in the art.  
       [0727] Briefly, sequences can be mapped to chromosomes by preparing PCR primers (preferably at least 15 bp (e.g., 15-25 bp) from the sequences shown in SEQ ID NO:X. Primers can optionally be selected using computer analysis so that primers do not span more than one predicted exon in the genomic DNA. These primers are then used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to SEQ ID NO:X will yield an amplified fragment.  
       [0728] Similarly, somatic hybrids provide a rapid method of PCR mapping the polynucleotides to particular chromosomes. Three or more clones can be assigned per day using a single thermal cycler. Moreover, sublocalization of the polynucleotides can be achieved with panels of specific chromosome fragments. Other gene mapping strategies that can be used include in situ hybridization, prescreening with labeled flow-sorted chromosomes, preselection by hybridization to construct chromosome specific-cDNA libraries, and computer mapping techniques (See, e.g., Shuler, Trends Biotechnol 16:456-459 (1998) which is hereby incorporated by reference in its entirety).  
       [0729] Precise chromosomal location of the polynucleotides can also be achieved using fluorescence in situ hybridization (FISH) of a metaphase chromosomal spread. This technique uses polynucleotides as short as 500 or 600 bases; however, polynucleotides 2,000-4,000 bp are preferred. For a review of this technique, see Verma et al., “Human Chromosomes: a Manual of Basic Techniques,” Pergamon Press, New York (1988).  
       [0730] For chromosome mapping, the polynucleotides can be used individually (to mark a single chromosome or a single site on that chromosome) or in panels (for marking multiple sites and/or multiple chromosomes).  
       [0731] Thus, the present invention also provides a method for chromosomal localization which involves (a) preparing PCR primers from the polynucleotide sequences in Table 1 and SEQ ID NO:X and (b) screening somatic cell hybrids containing individual chromosomes.  
       [0732] The polynucleotides of the present invention would likewise be useful for radiation hybrid mapping, HAPPY mapping, and long range restriction mapping. For a review of these techniques and others known in the art, see, e.g. Dear, “Genome Mapping: A Practical Approach,” IRL Press at Oxford University Press, London (1997); Aydin, J. Mol. Med. 77:691-694 (1999); Hacia et al., Mol. Psychiatry 3:483-492 (1998); Herrick et al., Chromosome Res. 7:409-423 (1999); Hamilton et al., Methods Cell Biol. 62:265-280 (2000); and/or Ott, J. Hered. 90:68-70 (1999) each of which is hereby incorporated by reference in its entirety.  
       [0733] Once a polynucleotide has been mapped to a precise chromosomal location, the physical position of the polynucleotide can be used in linkage analysis. Linkage analysis establishes coinheritance between a chromosomal location and presentation of a particular disease. (Disease mapping data are found, for example, in V. McKusick, Mendelian Inheritance in Man (available on line through Johns Hopkins University Welch Medical Library)). Assuming 1 megabase mapping resolution and one gene per 20 kb, a cDNA precisely localized to a chromosomal region associated with the disease could be one of 50-500 potential causative genes.  
       [0734] Thus, once coinheritance is established, differences in a polynucleotide of the invention and the corresponding gene between affected and unaffected individuals can be examined. First, visible structural alterations in the chromosomes, such as deletions or translocations, are examined in chromosome spreads or by PCR. If no structural alterations exist, the presence of point mutations are ascertained. Mutations observed in some or all affected individuals, but not in normal individuals, indicates that the mutation may cause the disease. However, complete sequencing of the polypeptide and the corresponding gene from several normal individuals is required to distinguish the mutation from a polymorphism. If a new polymorphism is identified, this polymorphic polypeptide can be used for further linkage analysis.  
       [0735] Furthermore, increased or decreased expression of the gene in affected individuals as compared to unaffected individuals can be assessed using the polynucleotides of the invention. Any of these alterations (altered expression, chromosomal rearrangement, or mutation) can be used as a diagnostic or prognostic marker.  
       [0736] Thus, the invention also provides a diagnostic method useful during diagnosis of a disorder, involving measuring the expression level of polynucleotides of the present invention in cells or body fluid from an individual and comparing the measured gene expression level with a standard level of polynucleotide expression level, whereby an increase or decrease in the gene expression level compared to the standard is indicative of a disorder.  
       [0737] In still another embodiment, the invention includes a kit for analyzing samples for the presence of proliferative and/or cancerous polynucleotides derived from a test subject. In a general embodiment, the kit includes at least one polynucleotide probe containing a nucleotide sequence that will specifically hybridize with a polynucleotide of the invention and a suitable container. In a specific embodiment, the kit includes two polynucleotide probes defining an internal region of the polynucleotide of the invention, where each probe has one strand containing a 31′mer-end internal to the region. In a further embodiment, the probes may be useful as primers for polymerase chain reaction amplification.  
       [0738] Where a diagnosis of a related disorder, including, for example, diagnosis of a tumor, has already been made according to conventional methods, the present invention is useful as a prognostic indicator, whereby patients exhibiting enhanced or depressed polynucleotide of the invention expression will experience a worse clinical outcome relative to patients expressing the gene at a level nearer the standard level.  
       [0739] By “measuring the expression level of polynucleotides of the invention” is intended qualitatively or quantitatively measuring or estimating the level of the polypeptide of the invention or the level of the mRNA encoding the polypeptide of the invention in a first biological sample either directly (e.g., by determining or estimating absolute protein level or mRNA level) or relatively (e.g., by comparing to the polypeptide level or mRNA level in a second biological sample). Preferably, the polypeptide level or mRNA level in the first biological sample is measured or estimated and compared to a standard polypeptide level or mRNA level, the standard being taken from a second biological sample obtained from an individual not having the related disorder or being determined by averaging levels from a population of individuals not having a related disorder. As will be appreciated in the art, once a standard polypeptide level or mRNA level is known, it can be used repeatedly as a standard for comparison.  
       [0740] By “biological sample” is intended any biological sample obtained from an individual, body fluid, cell line, tissue culture, or other source which contains polypeptide of the present invention or the corresponding mRNA. As indicated, biological samples include body fluids (such as semen, lymph, sera, plasma, urine, synovial fluid and spinal fluid) which contain the polypeptide of the present invention, and tissue sources found to express the polypeptide of the present invention. Methods for obtaining tissue biopsies and body fluids from mammals are well known in the art. Where the biological sample is to include mRNA, a tissue biopsy is the preferred source.  
       [0741] The method(s) provided above may preferrably be applied in a diagnostic method and/or kits in which polynucleotides and/or polypeptides of the invention are attached to a solid support. In one exemplary method, the support may be a “gene chip” or a “biological chip” as described in U.S. Pat. Nos. 5,837,832, 5,874,219, and 5,856,174. Further, such a gene chip with polynucleotides of the invention attached may be used to identify polymorphisms between the isolated polynucleotide sequences of the invention, with polynucleotides isolated from a test subject. The knowledge of such polymorphisms (i.e. their location, as well as, their existence) would be beneficial in identifying disease loci for many disorders, such as for example, in neural disorders, immune system disorders, muscular disorders, reproductive disorders, gastrointestinal disorders, pulmonary disorders, cardiovascular disorders, renal disorders, proliferative disorders, and/or cancerous diseases and conditions. Such a method is described in U.S. Pat. Nos. 5,858,659 and 5,856,104. The U.S. patents referenced supra are hereby incorporated by reference in their entirety herein.  
       [0742] The present invention encompasses polynucleotides of the present invention that are chemically synthesized, or reproduced as peptide nucleic acids (PNA), or according to other methods known in the art. The use of PNAs would serve as the preferred form if the polynucleotides of the invention are incorporated onto a solid support, or gene chip. For the purposes of the present invention, a peptide nucleic acid (PNA) is a polyamide type of DNA analog and the monomeric units for adenine, guanine, thymine and cytosine are available commercially (Perceptive Biosystems). Certain components of DNA, such as phosphorus, phosphorus oxides, or deoxyribose derivatives, are not present in PNAs. As disclosed by P. E. Nielsen, M. Egholm, R. H. Berg and O. Buchardt, Science 254, 1497 (1991); and M. Egholm, O. Buchardt, L.Christensen, C. Behrens, S. M. Freier, D. A. Driver, R. H. Berg, S. K. Kim, B. Norden, and P. E. Nielsen, Nature 365, 666 (1993), PNAs bind specifically and tightly to complementary DNA strands and are not degraded by nucleases. In fact, PNA binds more strongly to DNA than DNA itself does. This is probably because there is no electrostatic repulsion between the two strands, and also the polyamide backbone is more flexible. Because of this, PNA/DNA duplexes bind under a wider range of stringency conditions than DNA/DNA duplexes, making it easier to perform multiplex hybridization. Smaller probes can be used than with DNA due to the strong binding. In addition, it is more likely that single base mismatches can be determined with PNA/DNA hybridization because a single mismatch in a PNA/DNA 15-mer lowers the melting point (T.sub.m) by 8°-20° C., vs. 4°-16° C. for the DNA/DNA 15-mer duplex. Also, the absence of charge groups in PNA means that hybridization can be done at low ionic strengths and reduce possible interference by salt during the analysis.  
       [0743] The present invention have uses which include, but are not limited to, detecting cancer in mammals. In particular the invention is useful during diagnosis of pathological cell proliferative neoplasias which include, but are not limited to: acute myelogenous leukemias including acute monocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute erythroleukemia, acute megakaryocytic leukemia, and acute undifferentiated leukemia, etc.; and chronic myelogenous leukemias including chronic myelomonocytic leukemia, chronic granulocytic leukemia, etc. Preferred mammals include monkeys, apes, cats, dogs, cows, pigs, horses, rabbits and humans. Particularly preferred are humans.  
       [0744] Pathological cell proliferative disorders are often associated with inappropriate activation of proto-oncogenes. (Gelmann, E. P. et al., “The Etiology of Acute Leukemia: Molecular Genetics and Viral Oncology,” in Neoplastic Diseases of the Blood, Vol 1., Wiernik, P. H. et al. eds., 161-182 (1985)). Neoplasias are now believed to result from the qualitative alteration of a normal cellular gene product, or from the quantitative modification of gene expression by insertion into the chromosome of a viral sequence, by chromosomal translocation of a gene to a more actively transcribed region, or by some other mechanism. (Gelmann et al., supra) It is likely that mutated or altered expression of specific genes is involved in the pathogenesis of some leukemias, among other tissues and cell types. (Gelmann et al., supra) Indeed, the human counterparts of the oncogenes involved in some animal neoplasias have been amplified or translocated in some cases of human leukemia and carcinoma. (Gelmann et al., supra)  
       [0745] For example, c-myc expression is highly amplified in the non-lymphocytic leukemia cell line HL-60. When HL-60 cells are chemically induced to stop proliferation, the level of c-myc is found to be downregulated. (International Publication Number WO 91/15580). However, it has been shown that exposure of HL-60 cells to a DNA construct that is complementary to the 5′ end of c-myc or c-myb blocks translation of the corresponding mRNAs which downregulates expression of the c-myc or c-myb proteins and causes arrest of cell proliferation and differentiation of the treated cells. (International Publication Number WO 91/15580; Wickstrom et al., Proc. Natl. Acad. Sci. 85:1028 (1988); Anfossi et al., Proc. Natl. Acad. Sci. 86:3379 (1989)). However, the skilled artisan would appreciate the present invention&#39;s usefulness is not be limited to treatment of proliferative disorders of hematopoietic cells and tissues, in light of the numerous cells and cell types of varying origins which are known to exhibit proliferative phenotypes.  
       [0746] In addition to the foregoing, a polynucleotide of the present invention can be used to control gene expression through triple helix formation or through antisense DNA or RNA. Antisense techniques are discussed, for example, in Okano, J. Neurochem. 56: 560 (1991); “Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988). Triple helix formation is discussed in, for instance Lee et al., Nucleic Acids Research 6: 3073 (1979); Cooney et al., Science 241: 456 (1988); and Dervan et al., Science 251: 1360 (1991). Both methods rely on binding of the polynucleotide to a complementary DNA or RNA. For these techniques, preferred polynucleotides are usually oligonucleotides 20 to 40 bases in length and complementary to either the region of the gene involved in transcription (triple helix—see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991)) or to the mRNA itself (antisense—Okano, J. Neurochem. 56:560 (1991); Oligodeoxy-nucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988)). Triple helix formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. The oligonucleotide described above can also be delivered to cells such that the antisense RNA or DNA may be expressed in vivo to inhibit production of polypeptide of the present invention antigens. Both techniques are effective in model systems, and the information disclosed herein can be used to design antisense or triple helix polynucleotides in an effort to treat disease, and in particular, for the treatment of proliferative diseases and/or conditions.  
       [0747] Polynucleotides of the present invention are also useful in gene therapy. One goal of gene therapy is to insert a normal gene into an organism having a defective gene, in an effort to correct the genetic defect. The polynucleotides disclosed in the present invention offer a means of targeting such genetic defects in a highly accurate manner. Another goal is to insert a new gene that was not present in the host genome, thereby producing a new trait in the host cell.  
       [0748] The polynucleotides are also useful for identifying individuals from minute biological samples. The United States military, for example, is considering the use of restriction fragment length polymorphism (RFLP) for identification of its personnel. In this technique, an individual&#39;s genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identifying personnel. This method does not suffer from the current limitations of “Dog Tags” which can be lost, switched, or stolen, making positive identification difficult. The polynucleotides of the present invention can be used as additional DNA markers for RFLP.  
       [0749] The polynucleotides of the present invention can also be used as an alternative to RFLP, by determining the actual base-by-base DNA sequence of selected portions of an individual&#39;s genome. These sequences can be used to prepare PCR primers for amplifying and isolating such selected DNA, which can then be sequenced. Using this technique, individuals can be identified because each individual will have a unique set of DNA sequences. Once an unique ID database is established for an individual, positive identification of that individual, living or dead, can be made from extremely small tissue samples.  
       [0750] Forensic biology also benefits from using DNA-based identification techniques as disclosed herein. DNA sequences taken from very small biological samples such as tissues, e.g., hair or skin, or body fluids, e.g., blood, saliva, semen, synovial fluid, amniotic fluid, breast milk, lymph, pulmonary sputum or surfactant, urine, fecal matter, etc., can be amplified using PCR. In one prior art technique, gene sequences amplified from polymorphic loci, such as DQa class II HLA gene, are used in forensic biology to identify individuals. (Erlich, H., PCR Technology, Freeman and Co. (1992)). Once these specific polymorphic loci are amplified, they are digested with one or more restriction enzymes, yielding an identifying set of bands on a Southern blot probed with DNA corresponding to the DQa class II HLA gene. Similarly, polynucleotides of the present invention can be used as polymorphic markers for forensic purposes.  
       [0751] There is also a need for reagents capable of identifying the source of a particular tissue. Such need arises, for example, in forensics when presented with tissue of unknown origin. Appropriate reagents can comprise, for example, DNA probes or primers prepared from the sequences of the present invention. Panels of such reagents can identify tissue by species and/or by organ type. In a similar fashion, these reagents can be used to screen tissue cultures for contamination.  
       [0752] The polynucleotides of the present invention are also useful as hybridization probes for differential identification of the tissue(s) or cell type(s) present in a biological sample. Similarly, polypeptides and antibodies directed to polypeptides of the present invention are useful to provide immunological probes for differential identification of the tissue(s) (e.g., immunohistochemistry assays) or cell type(s) (e.g., immunocytochemistry assays). In addition, for a number of disorders of the above tissues or cells, significantly higher or lower levels of gene expression of the polynucleotides/polypeptides of the present invention may be detected in certain tissues (e.g., tissues expressing polypeptides and/or polynucleotides of the present invention and/or cancerous and/or 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 a “standard” gene expression level, i.e., the expression level in healthy tissue from an individual not having the disorder.  
       [0753] Thus, the invention provides a diagnostic method of a disorder, which involves: (a) assaying gene expression level in cells or body fluid of an individual; (b) comparing the gene expression level with a standard gene expression level, whereby an increase or decrease in the assayed gene expression level compared to the standard expression level is indicative of a disorder.  
       [0754] In the very least, the polynucleotides of the present invention can be used as molecular weight markers on Southern gels, as diagnostic probes for the presence of a specific mRNA in a particular cell type, as a probe to “subtract-out” known sequences in the process of discovering novel polynucleotides, for selecting and making oligomers for attachment to a “gene chip” or other support, to raise anti-DNA antibodies using DNA immunization techniques, and as an antigen to elicit an immune response.  
       [0755] Uses of the Polypeptides  
       [0756] Each of the polypeptides identified herein can be used in numerous ways. The following description should be considered exemplary and utilizes known techniques.  
       [0757] Polypeptides and antibodies directed to polypeptides of the present invention are useful to provide immunological probes for differential identification of the tissue(s) (e.g., immunohistochemistry assays such as, for example, ABC immunoperoxidase (Hsu et al., J. Histochem. Cytochem. 29:577-580 (1981)) or cell type(s) (e.g., immunocytochemistry assays).  
       [0758] Antibodies can be used to assay levels of polypeptides encoded by polynucleotides of the invention in a biological sample using classical immunohistological methods known to those of skill in the art (e.g., see Jalkanen, et al., J. Cell. Biol. 101:976-985 (1985); Jalkanen, et al., J. Cell. Biol. 105:3087-3096 (1987)). Other antibody-based methods useful for detecting protein gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assay labels are known in the art and include enzyme labels, such as, glucose oxidase; radioisotopes, such as iodine ( 131 I,  125 I,  123 I,  121 I), carbon ( 14 C), sulfur ( 35 S), tritium ( 3 H), indium ( 115m In,  113m In,  112 In,  111 In), and technetium ( 99 Tc,  99m Tc), thallium ( 201 Ti), gallium ( 68 Ga,  67 Ga), palladium ( 103 Pd), molybdenum ( 99 Mo), xenon ( 133 Xe), fluorine ( 18 F),  153 Sm,  177 Lu,  159 Gd,  149 Pm,  140 La,  175 Yb,  166 Ho,  90 Y,  47 Sc,  186 Re,  188 Re,  142 Pr,  105 Rh,  97 Ru; luminescent labels, such as luminol; and fluorescent labels, such as fluorescein and rhodamine, and biotin.  
       [0759] In addition to assaying levels of polypeptide of the present invention in a biological sample, proteins can also be detected in vivo by imaging. Antibody labels or markers for in vivo imaging of protein include those detectable by X-radiography, NMR or ESR. For X-radiography, suitable labels include radioisotopes such as barium or cesium, which emit detectable radiation but are not overtly harmful to the subject. Suitable markers for NMR and ESR include those with a detectable characteristic spin, such as deuterium, which may be incorporated into the antibody by labeling of nutrients for the relevant hybridoma.  
       [0760] A protein-specific antibody or antibody fragment which has been labeled with an appropriate detectable imaging moiety, such as a radioisotope (for example,  131 I,  112 In,  99m Tc, ( 131 I,  125 I,  123 I,  121 I), carbon ( 14 C), sulfur ( 35 S), tritium ( 3 H), indium ( 115m In,  113m In,  112 In,  111 In), and technetium ( 99 Tc,  99m Tc), thallium ( 201 Ti), gallium ( 68 Ga,  67 Ga), palladium ( 103 Pd), molybdenum ( 99 Mo), xenon ( 133 Xe), fluorine ( 18 F,  153 Sm,  177 Lu,  159 Gd,  149 Pm,  140 La,  175 Yb,  166 Ho,  90 Y,  47 Sc,  186 Re,  188 Re,  142 Pr,  105 Rh,  97 Ru), a radio-opaque substance, or a material detectable by nuclear magnetic resonance, is introduced (for example, parenterally, subcutaneously or intraperitoneally) into the mammal to be examined for immune system disorder. It will be understood in the art that the size of the subject and the imaging system used will determine the quantity of imaging moiety needed to produce diagnostic images. In the case of a radioisotope moiety, for a human subject, the quantity of radioactivity injected will normally range from about 5 to 20 millicuries of  99m Tc. The labeled antibody or antibody fragment will then preferentially accumulate at the location of cells which express the polypeptide encoded by a polynucleotide of the invention. In vivo tumor imaging is described in S. W. Burchiel et al., “Immunopharmacokinetics of Radiolabeled Antibodies and Their Fragments” (Chapter 13 in  Tumor Imaging: The Radiochemical Detection of Cancer , S. W. Burchiel and B. A. Rhodes, eds., Masson Publishing Inc. (1982)).  
       [0761] In one embodiment, the invention provides a method for the specific delivery of compositions of the invention to cells by administering polypeptides of the invention (e.g., polypeptides encoded by polynucleotides of the invention and/or antibodies) that are associated with heterologous polypeptides or nucleic acids. In one example, the invention provides a method for delivering a therapeutic protein into the targeted cell. In another example, the invention provides a method for delivering a single stranded nucleic acid (e.g., antisense or ribozymes) or double stranded nucleic acid (e.g., DNA that can integrate into the cell&#39;s genome or replicate episomally and that can be transcribed) into the targeted cell.  
       [0762] In another embodiment, the invention provides a method for the specific destruction of cells (e.g., the destruction of tumor cells) by administering polypeptides of the invention in association with toxins or cytotoxic prodrugs.  
       [0763] By “toxin” is meant one or more compounds that bind and activate endogenous cytotoxic effector systems, radioisotopes, holotoxins, modified toxins, catalytic subunits of toxins, or any molecules or enzymes not normally present in or on the surface of a cell that under defined conditions cause the cell&#39;s death. Toxins that may be used according to the methods of the invention include, but are not limited to, radioisotopes known in the art, compounds such as, for example, antibodies (or complement fixing containing portions thereof) that bind an inherent or induced endogenous cytotoxic effector system, thymidine kinase, endonuclease, RNAse, alpha toxin, ricin, abrin, Pseudomonas exotoxin A, diphtheria toxin, saporin, momordin, gelonin, pokeweed antiviral protein, alpha-sarcin and cholera toxin. “Toxin” also includes a cytostatic or cytocidal agent, a therapeutic agent or a radioactive metal ion, e.g., alpha-emitters such as, for example,  213 Bi, or other radioisotopes such as, for example,  103 Pd,  133 Xe,  131 I,  68 Ge,  57 Co,  65 Zn,  85 Sr,  35 S,  90 Y,  153 Sm,  153 Gd,  169 Yb,  51 Cr,  54 Mn,  75 Se,  113 Sn,  90 Yttrium,  117 Tin,  186 Rhenium,  166 Holmium, and  188 Rhenium; luminescent labels, such as luminol; and fluorescent labels, such as fluorescein and rhodamine, and biotin.  
       [0764] Techniques known in the art may be applied to label polypeptides of the invention (including antibodies). Such techniques include, but are not limited to, the use of bifunctional conjugating agents (see e.g., U.S. Pat. Nos. 5,756,065; 5,714,631; 5,696,239; 5,652,361; 5,505,931; 5,489,425; 5,435,990; 5,428,139; 5,342,604; 5,274,119; 4,994,560; and 5,808,003; the contents of each of which are hereby incorporated by reference in its entirety).  
       [0765] Thus, the invention provides a diagnostic method of a disorder, which involves (a) assaying the expression level of a polypeptide of the present invention in cells or body fluid of an individual; and (b) comparing the assayed polypeptide expression level with a standard polypeptide expression level, whereby an increase or decrease in the assayed polypeptide expression level compared to the standard expression level is indicative of a disorder. With respect to cancer, the presence of a relatively high amount of transcript in biopsied tissue from an individual may indicate a predisposition for the development of the disease, or may provide a means for detecting the disease prior to the appearance of actual clinical symptoms. A more definitive diagnosis of this type may allow health professionals to employ preventative measures or aggressive treatment earlier thereby preventing the development or further progression of the cancer.  
       [0766] Moreover, polypeptides of the present invention can be used to treat or prevent diseases or conditions such as, for example, neural disorders, immune system disorders, muscular disorders, reproductive disorders, gastrointestinal disorders, pulmonary disorders, cardiovascular disorders, renal disorders, proliferative disorders, and/or cancerous diseases and conditions. For example, patients can be administered a polypeptide of the present invention in an effort to replace absent or decreased levels of the polypeptide (e.g., insulin), to supplement absent or decreased levels of a different polypeptide (e.g., hemoglobin S for hemoglobin B, SOD, catalase, DNA repair proteins), to inhibit the activity of a polypeptide (e.g., an oncogene or tumor supressor), to activate the activity of a polypeptide (e.g., by binding to a receptor), to reduce the activity of a membrane bound receptor by competing with it for free ligand (e.g., soluble TNF receptors used in reducing inflammation), or to bring about a desired response (e.g., blood vessel growth inhibition, enhancement of the immune response to proliferative cells or tissues).  
       [0767] Similarly, antibodies directed to a polypeptide of the present invention can also be used to treat disease (as described supra, and elsewhere herein). For example, administration of an antibody directed to a polypeptide of the present invention can bind, and/or neutralize the polypeptide, and/or reduce overproduction of the polypeptide. Similarly, administration of an antibody can activate the polypeptide, such as by binding to a polypeptide bound to a membrane (receptor).  
       [0768] At the very least, the polypeptides of the present invention can be used as molecular weight markers on SDS-PAGE gels or on molecular sieve gel filtration columns using methods well known to those of skill in the art. Polypeptides can also be used to raise antibodies, which in turn are used to measure protein expression from a recombinant cell, as a way of assessing transformation of the host cell. Moreover, the polypeptides of the present invention can be used to test the following biological activities.  
       [0769] Diagnostic Assays  
       [0770] The compounds of the present invention are useful for diagnosis, treatment, prevention and/or prognosis of various disorders in mammals, preferably humans. Such disorders include, but are not limited to, neural disorders (e.g., as described in “Neural Activity and Neurological Diseases” below), immune system disorders (e.g., as described in “Immune Activity” below), muscular disorders (e.g., as described in “Neural Activity and Neurological Diseases” below), reproductive disorders (e.g., as described in “Anti-Angiogenesis Activity” below), pulmonary disorders (e.g., as described in “Immune Activity” below), cardiovascular disorders (e.g., as described in “Cardiovascular Disorders” below), infectious diseases (e.g., as described in “Infectious Disease” below), proliferative disorders (e.g., as described in “Hyperproliferative Disorders”, “Anti-Angiogenesis Activity” and “Diseases at the Cellular Level” below), cancerous diseases and conditions (e.g., as described in “Hyperproliferative Disorders”, “Anti-Angiogenesis Activity” and “Diseases at the Cellular Level” below), and/or metabolic disorders (e.g., as described in “Endocrine Disorders” below).  
       [0771] ACRP30-Like proteins are believed to be involved in biological activities associated with glucose uptake, energy homeostasis, inflammation/immuneresponses, and angiogenesis/vascular repair. Accordingly, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of diseases and/or disorders associated with aberrant ACRP30-Like activity.  
       [0772] In preferred embodiments, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of Types I and II diabetes mellitus, obesity, and/or metabolic disorders described herein under “Endocrine Disorders”. In additional embodiments, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of complications and disorders associated with Type I and II diabetes mellitus, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations.  
       [0773] In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0774] In other embodiments, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of diseases and/or disorders relating to immune disorders, endocrine disorders, and/or cardiovascular disorders as described under the sections entitled “Immune activity”, “Endocrine Disorders”, and “Cardiovascular Disorders” herein.  
       [0775] In certain embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to diagnose and/or prognose diseases and/or disorders disclosed in “Polynucleotides and Polypeptides of the Invention”; Table 4, column 3 (OMIM Reference(s)); as well as diseases and/or disorders associated with the tissue(s) in which the polypeptide of the invention is expressed, including the tissues disclosed in “Polynucleotides and Polypeptides of the Invention”, and/or one, two, three, four, five, or more tissues disclosed in Table 3, column 2 (Library Code).  
       [0776] For a number of disorders, substantially altered (increased or decreased) levels of ACRP30-Like gene expression can be detected in tissues, cells or bodily fluids (e.g., sera, plasma, urine, semen, synovial fluid or spinal fluid) taken from an individual having such a disorder, relative to a “standard” ACRP30-Like gene expression level, that is, the ACRP30-Like expression level in tissues or bodily fluids from an individual not having the disorder. Thus, the invention provides a diagnostic method useful during diagnosis of a disorder, which involves measuring the expression level of the gene encoding the ACRP30-Like polypeptide in tissues, cells or body fluid from an individual and comparing the measured gene expression level with a standard ACRP30-Like gene expression level, whereby an increase or decrease in the gene expression level(s) compared to the standard is indicative of a ACRP30-Like disorder. These diagnostic assays may be performed in vivo or in vitro, such as, for example, on blood samples, biopsy tissue or autopsy tissue.  
       [0777] The present invention is also useful as a prognostic indicator, whereby patients exhibiting enhanced or depressed ACRP30-Like gene expression will experience a worse clinical outcome relative to patients expressing the gene at a level nearer the standard level.  
       [0778] By “assaying the expression level of the gene encoding the ACRP30-Like polypeptide” is intended qualitatively or quantitatively measuring or estimating the level of the ACRP30-Like polypeptide or the level of the mRNA encoding the ACRP30-Like polypeptide in a first biological sample either directly (e.g., by determining or estimating absolute protein level or mRNA level) or relatively (e.g., by comparing to the ACRP30-Like polypeptide level or mRNA level in a second biological sample). Preferably, the ACRP30-Like polypeptide expression level or mRNA level in the first biological sample is measured or estimated and compared to a standard ACRP30-Like polypeptide level or mRNA level, the standard being taken from a second biological sample obtained from an individual not having the disorder or being determined by averaging levels from a population of individuals not having the disorder. As will be appreciated in the art, once a standard ACRP30-Like polypeptide level or mRNA level is known, it can be used repeatedly as a standard for comparison.  
       [0779] By “biological sample” is intended any biological sample obtained from an individual, cell line, tissue culture, or other source containing ACRP30-Like polypeptides (including portions thereof) or mRNA. As indicated, biological samples include body fluids (such as sera, plasma, urine, synovial fluid and spinal fluid) and tissue sources found to express the full length or fragments thereof of a ACRP30-Like polypeptide. Methods for obtaining tissue biopsies and body fluids from mammals are well known in the art. Where the biological sample is to include mRNA, a tissue biopsy is the preferred source.  
       [0780] Total cellular RNA can be isolated from a biological sample using any suitable technique such as the single-step guanidinium-thiocyanate-phenol-chloroform method described in Chomczynski and Sacchi, Anal. Biochem. 162:156-159 (1987). Levels of mRNA encoding the ACRP30-Like polypeptides are then assayed using any appropriate method. These include Northern blot analysis, S1 nuclease mapping, the polymerase chain reaction (PCR), reverse transcription in combination with the polymerase chain reaction (RT-PCR), and reverse transcription in combination with the ligase chain reaction (RT-LCR).  
       [0781] The present invention also relates to diagnostic assays such as quantitative and diagnostic assays for detecting levels of ACRP30-Like polypeptides, in a biological sample (e.g., cells and tissues), including determination of normal and abnormal levels of polypeptides. Thus, for instance, a diagnostic assay in accordance with the invention for detecting over-expression of ACRP30-Like polypeptides compared to normal control tissue samples may be used to detect the presence of tumors. Assay techniques that can be used to determine levels of a polypeptide, such as a ACRP30-Like polypeptide of the present invention in a sample derived from a host are well-known to those of skill in the art. Such assay methods include radioimmunoassays, competitive-binding assays, Western Blot analysis and ELISA assays. Assaying ACRP30-Like polypeptide levels in a biological sample can occur using any art-known method.  
       [0782] Assaying ACRP30-Like polypeptide levels in a biological sample can occur using antibody-based techniques. For example, ACRP30-Like polypeptide expression in tissues can be studied with classical immunohistological methods (Jalkanen et al., J. Cell. Biol. 101:976-985 (1985); Jalkanen, M., et al.,  J. Cell Biol.,  105:3087-3096 (1987)). Other antibody-based methods useful for detecting ACRP30-Like polypeptide gene expression include immunoassays, such as the enzyme linked immunosorbent assay (ELISA) and the radioimmunoassay (RIA). Suitable antibody assay labels are known in the art and include enzyme labels, such as, glucose oxidase, and radioisotopes, such as iodine ( 125 I,  121 I), carbon ( 14 C), sulfur ( 35 S), tritium ( 3 H), indium ( 112 In), and technetium ( 99m Tc), and fluorescent labels, such as fluorescein and rhodamine, and biotin.  
       [0783] The tissue or cell type to be analyzed will generally include those which are known, or suspected, to express the ACRP30-Like gene (such as, for example, cancer). The protein isolation methods employed herein may, for example, be such as those described in Harlow and Lane (Harlow, E. and Lane, D., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.), which is incorporated herein by reference in its entirety. The isolated cells can be derived from cell culture or from a patient. The analysis of cells taken from culture may be a necessary step in the assessment of cells that could be used as part of a cell-based gene therapy technique or, alternatively, to test the effect of compounds on the expression of the ACRP30-Like gene.  
       [0784] For example, antibodies, or fragments of antibodies, such as those described herein, may be used to quantitatively or qualitatively detect the presence of ACRP30-Like gene products or conserved variants or peptide fragments thereof. This can be accomplished, for example, by immunofluorescence techniques employing a fluorescently labeled antibody coupled with light microscopic, flow cytometric, or fluorimetric detection.  
       [0785] In a preferred embodiment, antibodies, or fragments of antibodies directed to any one or all of the predicted epitope domains of the ACRP30-Like polypeptides may be used to quantitatively or qualitatively detect the presence of ACRP30-Like gene products or conserved variants or peptide fragments thereof. This can be accomplished, for example, by immunofluorescence techniques employing a fluorescently labeled antibody coupled with light microscopic, flow cytometric, or fluorimetric detection.  
       [0786] In an additional preferred embodiment, antibodies, or fragments of antibodies directed to a conformational epitope of a ACRP30-Like polypeptide may be used to quantitatively or qualitatively detect the presence of ACRP30-Like gene products or conserved variants or peptide fragments thereof. This can be accomplished, for example, by immunofluorescence techniques employing a fluorescently labeled antibody coupled with light microscopic, flow cytometric, or fluorimetric detection.  
       [0787] The antibodies (or fragments thereof), and/or ACRP30-Like polypeptides of the present invention may, additionally, be employed histologically, as in immunofluorescence, immunoelectron microscopy or non-immunological assays, for in situ detection of ACRP30-Like gene products or conserved variants or peptide fragments thereof. In situ detection may be accomplished by removing a histological specimen from a patient, and applying thereto a labeled antibody or ACRP30-Like polypeptide of the present invention. The antibody (or fragment thereof) or ACRP30-Like polypeptide is preferably applied by overlaying the labeled antibody (or fragment) onto a biological sample. Through the use of such a procedure, it is possible to determine not only the presence of the ACRP30-Like gene product, or conserved variants or peptide fragments, or ACRP30-Like polypeptide binding, but also its distribution in the examined tissue. Using the present invention, those of ordinary skill will readily perceive that any of a wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection.  
       [0788] Immunoassays and non-immunoassays for ACRP30-Like gene products or conserved variants or peptide fragments thereof will typically comprise incubating a sample, such as a biological fluid, a tissue extract, freshly harvested cells, or lysates of cells which have been incubated in cell culture, in the presence of a detectably labeled antibody capable of binding ACRP30-Like gene products or conserved variants or peptide fragments thereof, and detecting the bound antibody by any of a number of techniques well-known in the art.  
       [0789] The biological sample may be brought in contact with and immobilized onto a solid phase support or carrier such as nitrocellulose, or other solid support which is capable of immobilizing cells, cell particles or soluble proteins. The support may then be washed with suitable buffers followed by treatment with the detectably labeled anti-ACRP30-Like polypeptide antibody or detectable ACRP30-Like polypeptide. The solid phase support may then be washed with the buffer a second time to remove unbound antibody or polypeptide. Optionally the antibody is subsequently labeled. The amount of bound label on solid support may then be detected by conventional means.  
       [0790] By “solid phase support or carrier” is intended any support capable of binding an antigen or an antibody. Well-known supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the support configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tube, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, test strip, etc. Preferred supports include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation.  
       [0791] The binding activity of a given lot of anti-ACRP30-Like polypeptide antibody or ACRP30-Like antigen polypeptide may be determined according to well known methods. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation.  
       [0792] In addition to assaying ACRP30-Like polypeptide levels or polynucleotide levels in a biological sample obtained from an individual, ACRP30-Like polypeptide or polynucleotide can also be detected in vivo by imaging. For example, in one embodiment of the invention, ACRP30-Like polypeptide and/or anti-ACRP30-Like antigen antibodies are used to image diseased cells, such as neoplasms. In another embodiment, ACRP30-Like polynucleotides of the invention (e.g., polynucleotides complementary to all or a portion of a particular ACRP30-Like mRNA transcript) and/or anti-ACRP30-Like antibodies (e.g., antibodies directed to any one or a combination of the epitopes of a ACRP30-Like polypeptide of the invention, antibodies directed to a conformational epitope of a ACRP30-Like polypeptide of the invention, or antibodies directed to the full length polypeptide expressed on the cell surface of a mammalian cell) are used to image diseased or neoplastic cells.  
       [0793] Antibody labels or markers for in vivo imaging of ACRP30-Like polypeptides include those detectable by X-radiography, NMR, MRI, CAT-scans or ESR. For X-radiography, suitable labels include radioisotopes such as barium or cesium, which emit detectable radiation but are not overtly harmful to the subject. Suitable markers for NMR and ESR include those with a detectable characteristic spin, such as deuterium, which may be incorporated into the antibody by labeling of nutrients for the relevant hybridoma. Where in vivo imaging is used to detect enhanced levels of ACRP30-Like polypeptides for diagnosis in humans, it may be preferable to use human antibodies or “humanized” chimeric monoclonal antibodies. Such antibodies can be produced using techniques described herein or otherwise known in the art. For example methods for producing chimeric antibodies are known in the art. See, for review, Morrison,  Science  229:1202 (1985); Oi et al.,  BioTechniques  4:214 (1986); Cabilly et al., U.S. Pat. No. 4,816,567; Taniguchi et al., EP 171496; Morrison et al., EP 173494; Neuberger et al., WO 8601533; Robinson et al., WO 8702671; Boulianne et al.,  Nature  312:643 (1984); Neuberger et al.,  Nature  314:268 (1985).  
       [0794] Additionally, any ACRP30-Like polypeptides whose presence can be detected, can be administered. For example, ACRP30-Like polypeptides labeled with a radio-opaque or other appropriate compound can be administered and visualized in vivo, as discussed, above for labeled antibodies. Further such ACRP30-Like polypeptides can be utilized for in vitro diagnostic procedures.  
       [0795] A ACRP30-Like polypeptide-specific antibody or antibody fragment which has been labeled with an appropriate detectable imaging moiety, such as a radioisotope (for example,  131 I,  112 In,  99m Tc), a radio-opaque substance, or a material detectable by nuclear magnetic resonance, is introduced (for example, parenterally, subcutaneously or intraperitoneally) into the mammal to be examined for a disorder. It will be understood in the art that the size of the subject and the imaging system used will determine the quantity of imaging moiety needed to produce diagnostic images. In the case of a radioisotope moiety, for a human subject, the quantity of radioactivity injected will normally range from about 5 to 20 millicuries of  99m Tc. The labeled antibody or antibody fragment will then preferentially accumulate at the location of cells which contain ACRP30-Like protein. In vivo tumor imaging is described in S. W. Burchiel et al., “Immunopharmacokinetics of Radiolabeled Antibodies and Their Fragments” (Chapter 13 in  Tumor Imaging: The Radiochemical Detection of Cancer , S. W. Burchiel and B. A. Rhodes, eds., Masson Publishing Inc. (1982)).  
       [0796] With respect to antibodies, one of the ways in which the anti-ACRP30-Like polypeptide antibody can be detectably labeled is by linking the same to a reporter enzyme and using the linked product in an enzyme immunoassay (EIA) (Voller, A., “The Enzyme Linked Immunosorbent Assay (ELISA)”, 1978, Diagnostic Horizons 2:1-7, Microbiological Associates Quarterly Publication, Walkersville, Md.); Voller et al.,  J. Clin. Pathol.  31:507-520 (1978); Butler, J. E.,  Meth. Enzymol.  73:482-523 (1981); Maggio, E. (ed.), 1980, Enzyme Immunoassay, CRC Press, Boca Raton, Fla.,; Ishikawa, E. et al., (eds.), 1981, Enzyme Immunoassay, Kgaku Shoin, Tokyo). The reporter enzyme which is bound to the antibody will react with an appropriate substrate, preferably a chromogenic substrate, in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorimetric or by visual means. Reporter enzymes which can be used to detectably label the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate, dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. Additionally, the detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the reporter enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards.  
       [0797] Detection may also be accomplished using any of a variety of other immunoassays. For example, by radioactively labeling the antibodies or antibody fragments, it is possible to detect ACRP30-Like polypeptides through the use of a radioimmunoassay (RIA) (see, for example, Weintraub, B., Principles of Radioimmunoassays, Seventh Training Course on Radioligand Assay Techniques, The Endocrine Society, March, 1986, which is incorporated by reference herein). The radioactive isotope can be detected by means including, but not limited to, a gamma counter, a scintillation counter, or autoradiography.  
       [0798] It is also possible to label the antibody with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wave length, its presence can then be detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, ophthaldehyde and fluorescamine.  
       [0799] The antibody can also be detectably labeled using fluorescence emitting metals such as  152 Eu, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriaminepentacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).  
       [0800] The antibody also can be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.  
       [0801] Likewise, a bioluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in, which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence of a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aequorin.  
       [0802] Methods for Detecting Diseases  
       [0803] In general, a disease may be detected in a patient based on the presence of one or more ACRP30-Like proteins of the invention and/or polynucleotides encoding such proteins in a biological sample (for example, blood, sera, urine, and/or tumor biopsies) obtained from the patient. In other words, such proteins may be used as markers to indicate the presence or absence of a disease or disorder, including cancer and/or as described elsewhere herein. In addition, such proteins may be useful for the detection of other diseases and cancers. The binding agents provided herein generally permit detection of the level of antigen that binds to the agent in the biological sample. Polynucleotide primers and probes may be used to detect the level of mRNA encoding ACRP30-Like polypeptides, which is also indicative of the presence or absence of a disease or disorder, including cancer. In general, ACRP30-Like polypeptides should be present at a level that is at least three fold higher in diseased tissue than in normal tissue.  
       [0804] There are a variety of assay formats known to those of ordinary skill in the art for using a binding agent to detect polypeptide markers in a sample. See, e.g., Harlow and Lane, supra. In general, the presence or absence of a disease in a patient may be determined by (a) contacting a biological sample obtained from a patient with a binding agent; (b) detecting in the sample a level of polypeptide that binds to the binding agent; and (c) comparing the level of polypeptide with a predetermined cut-off value.  
       [0805] In a preferred embodiment, the assay involves the use of a binding agent(s) immobilized on a solid support to bind to and remove the ACRP30-Like polypeptide of the invention from the remainder of the sample. The bound polypeptide may then be detected using a detection reagent that contains a reporter group and specifically binds to the binding agent/polypeptide complex. Such detection reagents may comprise, for example, a binding agent that specifically binds to the polypeptide or an antibody or other agent that specifically binds to the binding agent, such as an anti-immunoglobulin, protein G, protein A or a lectin. Alternatively, a competitive assay may be utilized, in which a polypeptide is labeled with a reporter group and allowed to bind to the immobilized binding agent after incubation of the binding agent with the sample. The extent to which components of the sample inhibit the binding of the labeled polypeptide to the binding agent is indicative of the reactivity of the sample with the immobilized binding agent. Suitable polypeptides for use within such assays include ACRP30-Like polypeptides and portions thereof, or antibodies, to which the binding agent binds, as described above.  
       [0806] The solid support may be any material known to those of skill in the art to which ACRP30-Like polypeptides of the invention may be attached. For example, the solid support may be a test well in a microtiter plate or a nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or disc, such as glass fiberglass, latex or a plastic material such as polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U.S. Pat. No. 5,359,681. The binding agent may be immobilized on the solid support using a variety of techniques known to those of skill in the art, which are amply described in the patent and scientific literature. In the context of the present invention, the term “immobilization” refers to both noncovalent association, such as adsorption, and covalent attachment (which may be a direct linkage between the agent and functional groups on the support or may be a linkage by way of a cross-linking agent). Immobilization by adsorption to a well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the binding agent, in a suitable buffer, with the solid support for the suitable amount of time. The contact time varies with temperature, but is typically between about 1 hour and about 1 day. In general, contacting a well of plastic microtiter plate (such as polystyrene or polyvinylchloride) with an amount of binding agent ranging from about 10 ng to about 10 ug, and preferably about 100 ng to about 1 ug, is sufficient to immobilize an adequate amount of binding agent.  
       [0807] Covalent attachment of binding agent to a solid support may generally be achieved by first reacting the support with a bifunctional reagent that will react with both the support and a functional group, such as a hydroxyl or amino group, on the binding agent. For example, the binding agent may be covalently attached to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the binding partner (see, e.g., Pierce Immunotechnology Catalog and Handbook, 1991, at A12-A13).  
       [0808] Gene Therapy Methods  
       [0809] Another aspect of the present invention is to gene therapy methods for treating or preventing disorders, diseases and conditions. The gene therapy methods relate to the introduction of nucleic acid (DNA, RNA and antisense DNA or RNA) sequences into an animal to achieve expression of the polypeptide of the present invention. This method requires a polynucleotide which codes for a polypeptide of the present invention operatively linked to a promoter and any other genetic elements necessary for the expression of the polypeptide by the target tissue. Such gene therapy and delivery techniques are known in the art, see, for example, WO90/11092, which is herein incorporated by reference.  
       [0810] Thus, for example, cells from a patient may be engineered with a polynucleotide (DNA or RNA) comprising a promoter operably linked to a polynucleotide of the present invention ex vivo, with the engineered cells then being provided to a patient to be treated with the polypeptide of the present invention. Such methods are well-known in the art. For example, see Belldegrun, A., et al., J. Natl. Cancer Inst. 85: 207-216 (1993); Ferrantini, M. et al., Cancer Research 53: 1107-1112 (1993); Ferrantini, M. et al., J. Immunology 153: 4604-4615 (1994); Kaido, T., et al., Int. J. Cancer 60: 221-229 (1995); Ogura, H., et al., Cancer Research 50: 5102-5106 (1990); Santodonato, L., et al., Human Gene Therapy 7:1-10 (1996); Santodonato, L., et al., Gene Therapy 4:1246-1255 (1997); and Zhang, J.-F. et al., Cancer Gene Therapy 3: 31-38 (1996)), which are herein incorporated by reference. In one embodiment, the cells which are engineered are arterial cells. The arterial cells may be reintroduced into the patient through direct injection to the artery, the tissues surrounding the artery, or through catheter injection.  
       [0811] As discussed in more detail below, the polynucleotide constructs can be delivered by any method that delivers injectable materials to the cells of an animal, such as, injection into the interstitial space of tissues (heart, muscle, skin, lung, liver, and the like). The polynucleotide constructs may be delivered in a pharmaceutically acceptable liquid or aqueous carrier.  
       [0812] In one embodiment, the polynucleotide of the present invention is delivered as a naked polynucleotide. The term “naked” polynucleotide, DNA or RNA refers to sequences that are free from any delivery vehicle that acts to assist, promote or facilitate entry into the cell, including viral sequences, viral particles, liposome formulations, lipofectin or precipitating agents and the like. However, the polynucleotide of the present invention can also be delivered in liposome formulations and lipofectin formulations and the like can be prepared by methods well known to those skilled in the art. Such methods are described, for example, in U.S. Pat. Nos. 5,593,972, 5,589,466, and 5,580,859, which are herein incorporated by reference.  
       [0813] The polynucleotide vector constructs used in the gene therapy method are preferably constructs that will not integrate into the host genome nor will they contain sequences that allow for replication. Appropriate vectors include pWLNEO, pSV2CAT, pOG44, pXT1 and pSG available from Stratagene; pSVK3, pBPV, pMSG and pSVL available from Pharmacia; and pEF1/V5, pcDNA3.1, and pRc/CMV2 available from Invitrogen. Other suitable vectors will be readily apparent to the skilled artisan.  
       [0814] Any strong promoter known to those skilled in the art can be used for driving the expression of the polynucleotide sequence. Suitable promoters include adenoviral promoters, such as the adenoviral major late promoter; or heterologous promoters, such as the cytomegalovirus (CMV) promoter; the respiratory syncytial virus (RSV) promoter; inducible promoters, such as the MMT promoter, the metallothionein promoter; heat shock promoters; the albumin promoter; the ApoAI promoter; human globin promoters; viral thymidine kinase promoters, such as the Herpes Simplex thymidine kinase promoter; retroviral LTRs; the b-actin promoter; and human growth hormone promoters. The promoter also may be the native promoter for the polynucleotide of the present invention.  
       [0815] Unlike other gene therapy techniques, one major advantage of introducing naked nucleic acid sequences into target cells is the transitory nature of the polynucleotide synthesis in the cells. Studies have shown that non-replicating DNA sequences can be introduced into cells to provide production of the desired polypeptide for periods of up to six months.  
       [0816] The polynucleotide construct can be delivered to the interstitial space of tissues within the an animal, including of muscle, skin, brain, lung, liver, spleen, bone marrow, thymus, heart, lymph, blood, bone, cartilage, pancreas, kidney, gall bladder, stomach, intestine, testis, ovary, uterus, rectum, nervous system, eye, gland, and connective tissue. Interstitial space of the tissues comprises the intercellular, fluid, mucopolysaccharide matrix among the reticular fibers of organ tissues, elastic fibers in the walls of vessels or chambers, collagen fibers of fibrous tissues, or that same matrix within connective tissue ensheathing muscle cells or in the lacunae of bone. It is similarly the space occupied by the plasma of the circulation and the lymph fluid of the lymphatic channels. Delivery to the interstitial space of muscle tissue is preferred for the reasons discussed below. They may be conveniently delivered by injection into the tissues comprising these cells. They are preferably delivered to and expressed in persistent, non-dividing cells which are differentiated, although delivery and expression may be achieved in non-differentiated or less completely differentiated cells, such as, for example, stem cells of blood or skin fibroblasts. In vivo muscle cells are particularly competent in their ability to take up and express polynucleotides.  
       [0817] For the naked nucleic acid sequence injection, an effective dosage amount of DNA or RNA will be in the range of from about 0.05 mg/kg body weight to about 50 mg/kg body weight. Preferably the dosage will be from about 0.005 mg/kg to about 20 mg/kg and more preferably from about 0.05 mg/kg to about 5 mg/kg. Of course, as the artisan of ordinary skill will appreciate, this dosage will vary according to the tissue site of injection. The appropriate and effective dosage of nucleic acid sequence can readily be determined by those of ordinary skill in the art and may depend on the condition being treated and the route of administration.  
       [0818] The preferred route of administration is by the parenteral route of injection into the interstitial space of tissues. However, other parenteral routes may also be used, such as, inhalation of an aerosol formulation particularly for delivery to lungs or bronchial tissues, throat or mucous membranes of the nose. In addition, naked DNA constructs can be delivered to arteries during angioplasty by the catheter used in the procedure.  
       [0819] The naked polynucleotides are delivered by any method known in the art, including, but not limited to, direct needle injection at the delivery site, intravenous injection, topical administration, catheter infusion, and so-called “gene guns”. These delivery methods are known in the art.  
       [0820] The constructs may also be delivered with delivery vehicles such as viral sequences, viral particles, liposome formulations, lipofectin, precipitating agents, etc. Such methods of delivery are known in the art.  
       [0821] In certain embodiments, the polynucleotide constructs are complexed in a liposome preparation. Liposomal preparations for use in the instant invention include cationic (positively charged), anionic (negatively charged) and neutral preparations. However, cationic liposomes are particularly preferred because a tight charge complex can be formed between the cationic liposome and the polyanionic nucleic acid. Cationic liposomes have been shown to mediate intracellular delivery of plasmid DNA (Felgner et al., Proc. Natl. Acad. Sci. USA (1987) 84:7413-7416, which is herein incorporated by reference); mRNA (Malone et al., Proc. Natl. Acad. Sci. USA (1989) 86:6077-6081, which is herein incorporated by reference); and purified transcription factors (Debs et al., J. Biol. Chem. (1990) 265:10189-10192, which is herein incorporated by reference), in functional form.  
       [0822] Cationic liposomes are readily available. For example, N[1-2,3-dioleyloxy)propyl]-N,N,N-triethylammonium (DOTMA) liposomes are particularly useful and are available under the trademark Lipofectin, from GIBCO BRL, Grand Island, N.Y. (See, also, Felgner et al., Proc. Natl Acad. Sci. USA (1987) 84:7413-7416, which is herein incorporated by reference). Other commercially available liposomes include transfectace (DDAB/DOPE) and DOTAP/DOPE (Boehringer).  
       [0823] Other cationic liposomes can be prepared from readily available materials using techniques well known in the art. See, e.g. PCT Publication No. WO 90/11092 (which is herein incorporated by reference) for a description of the synthesis of DOTAP (1,2-bis(oleoyloxy)-3-(trimethylammonio)propane) liposomes. Preparation of DOTMA liposomes is explained in the literature, see, e.g., P. Felgner et al., Proc. Natl. Acad. Sci. USA 84:7413-7417, which is herein incorporated by reference. Similar methods can be used to prepare liposomes from other cationic lipid materials.  
       [0824] Similarly, anionic and neutral liposomes are readily available, such as from Avanti Polar Lipids (Birmingham, Ala.), or can be easily prepared using readily available materials. Such materials include phosphatidyl, choline, cholesterol, phosphatidyl ethanolamine, dioleoylphosphatidyl choline (DOPC), dioleoylphosphatidyl glycerol (DOPG), dioleoylphoshatidyl ethanolamine (DOPE), among others. These materials can also be mixed with the DOTMA and DOTAP starting materials in appropriate ratios. Methods for making liposomes using these materials are well known in the art.  
       [0825] For example, commercially dioleoylphosphatidyl choline (DOPC), dioleoylphosphatidyl glycerol (DOPG), and dioleoylphosphatidyl ethanolamine (DOPE) can be used in various combinations to make conventional liposomes, with or without the addition of cholesterol. Thus, for example, DOPG/DOPC vesicles can be prepared by drying 50 mg each of DOPG and DOPC under a stream of nitrogen gas into a sonication vial. The sample is placed under a vacuum pump overnight and is hydrated the following day with deionized water. The sample is then sonicated for 2 hours in a capped vial, using a Heat Systems model 350 sonicator equipped with an inverted cup (bath type) probe at the maximum setting while the bath is circulated at 15EC. Alternatively, negatively charged vesicles can be prepared without sonication to produce multilamellar vesicles or by extrusion through nucleopore membranes to produce unilamellar vesicles of discrete size. Other methods are known and available to those of skill in the art.  
       [0826] The liposomes can comprise multilamellar vesicles (MLVs), small unilamellar vesicles (SUVs), or large unilamellar vesicles (LUVs), with SUVs being preferred. The various liposome-nucleic acid complexes are prepared using methods well known in the art. See, e.g., Straubinger et al., Methods of Immunology (1983), 101:512-527, which is herein incorporated by reference. For example, MLVs containing nucleic acid can be prepared by depositing a thin film of phospholipid on the walls of a glass tube and subsequently hydrating with a solution of the material to be encapsulated. SUVs are prepared by extended sonication of MLVs to produce a homogeneous population of unilamellar liposomes. The material to be entrapped is added to a suspension of preformed MLVs and then sonicated. When using liposomes containing cationic lipids, the dried lipid film is resuspended in an appropriate solution such as sterile water or an isotonic buffer solution such as 10 mM Tris/NaCl, sonicated, and then the preformed liposomes are mixed directly with the DNA. The liposome and DNA form a very stable complex due to binding of the positively charged liposomes to the cationic DNA. SUVs find use with small nucleic acid fragments. LUVs are prepared by a number of methods, well known in the art. Commonly used methods include Ca 2+ -EDTA chelation (Papahadjopoulos et al., Biochim. Biophys. Acta (1975) 394:483; Wilson et al., Cell (1979) 17:77); ether injection (Deamer, D. and Bangham, A., Biochim. Biophys. Acta (1976) 443:629; Ostro et al., Biochem. Biophys. Res. Commun. (1977) 76:836; Fraley et al., Proc. Natl. Acad. Sci. USA (1979) 76:3348); detergent dialysis (Enoch, H. and Strittmatter, P., Proc. Natl. Acad. Sci. USA (1979) 76:145); and reverse-phase evaporation (REV) (Fraley et al., J. Biol. Chem. (1980) 255:10431; Szoka, F. and Papahadjopoulos, D., Proc. Natl. Acad. Sci. USA (1978) 75:145; Schaefer-Ridder et al., Science (1982) 215:166), which are herein incorporated by reference.  
       [0827] Generally, the ratio of DNA to liposomes will be from about 10:1 to about 1:10. Preferably, the ration will be from about 5:1 to about 1:5. More preferably, the ration will be about 3:1 to about 1:3. Still more preferably, the ratio will be about 1:1.  
       [0828] U.S. Pat. No. 5,676,954 (which is herein incorporated by reference) reports on the injection of genetic material, complexed with cationic liposomes carriers, into mice. U.S. Pat. Nos. 4,897,355, 4,946,787, 5,049,386, 5,459,127, 5,589,466, 5,693,622, 5,580,859, 5,703,055, and international publication no. WO 94/9469 (which are herein incorporated by reference) provide cationic lipids for use in transfecting DNA into cells and mammals. U.S. Pat. Nos. 5,589,466, 5,693,622, 5,580,859, 5,703,055, and international publication no. WO 94/9469 (which are herein incorporated by reference) provide methods for delivering DNA-cationic lipid complexes to mammals.  
       [0829] In certain embodiments, cells are engineered, ex vivo or in vivo, using a retroviral particle containing RNA which comprises a sequence encoding a polypeptide of the present invention. Retroviruses from which the retroviral plasmid vectors may be derived include, but are not limited to, Moloney Murine Leukemia Virus, spleen necrosis virus, Rous sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, gibbon ape leukemia virus, human immunodeficiency virus, Myeloproliferative Sarcoma Virus, and mammary tumor virus.  
       [0830] The retroviral plasmid vector is employed to transduce packaging cell lines to form producer cell lines. Examples of packaging cells which may be transfected include, but are not limited to, the PE501, PA317, R-2, R-AM, PA12, T19-14X, VT-19-17-H2, RCRE, RCRIP, GP+E-86, GP+envAm12, and DAN cell lines as described in Miller, Human Gene Therapy 1:5-14 (1990), which is incorporated herein by reference in its entirety. The vector may transduce the packaging cells through any means known in the art. Such means include, but are not limited to, electroporation, the use of liposomes, and CaPO 4  precipitation. In one alternative, the retroviral plasmid vector may be encapsulated into a liposome, or coupled to a lipid, and then administered to a host.  
       [0831] The producer cell line generates infectious retroviral vector particles which include polynucleotide encoding a polypeptide of the present invention. Such retroviral vector particles then may be employed, to transduce eukaryotic cells, either in vitro or in vivo. The transduced eukaryotic cells will express a polypeptide of the present invention.  
       [0832] In certain other embodiments, cells are engineered, ex vivo or in vivo, with polynucleotide contained in an adenovirus vector. Adenovirus can be manipulated such that it encodes and expresses a polypeptide of the present invention, and at the same time is inactivated in terms of its ability to replicate in a normal lytic viral life cycle. Adenovirus expression is achieved without integration of the viral DNA into the host cell chromosome, thereby alleviating concerns about insertional mutagenesis. Furthermore, adenoviruses have been used as live enteric vaccines for many years with an excellent safety profile (Schwartz, A. R. et al. (1974) Am. Rev. Respir. Dis.109:233-238). Finally, adenovirus mediated gene transfer has been demonstrated in a number of instances including transfer of alpha-1-antitrypsin and CFTR to the lungs of cotton rats (Rosenfeld, M. A. et al. (1991) Science 252:431-434; Rosenfeld et al., (1992) Cell 68:143-155). Furthermore, extensive studies to attempt to establish adenovirus as a causative agent in human cancer were uniformly negative (Green, M. et al. (1979) Proc. Natl. Acad. Sci. USA 76:6606).  
       [0833] Suitable adenoviral vectors useful in the present invention are described, for example, in Kozarsky and Wilson, Curr. Opin. Genet. Devel. 3:499-503 (1993); Rosenfeld et al., Cell 68:143-155 (1992); Engelhardt et al., Human Genet. Ther. 4:759-769 (1993); Yang et al., Nature Genet. 7:362-369 (1994); Wilson et al., Nature 365:691-692 (1993); and U.S. Pat. No. 5,652,224, which are herein incorporated by reference. For example, the adenovirus vector Ad2 is useful and can be grown in human 293 cells. These cells contain the E1 region of adenovirus and constitutively express E1a and E1b, which complement the defective adenoviruses by providing the products of the genes deleted from the vector. In addition to Ad2, other varieties of adenovirus (e.g., Ad3, Ad5, and Ad7) are also useful in the present invention.  
       [0834] Preferably, the adenoviruses used in the present invention are replication deficient. Replication deficient adenoviruses require the aid of a helper virus and/or packaging cell line to form infectious particles. The resulting virus is capable of infecting cells and can express a polynucleotide of interest which is operably linked to a promoter, but cannot replicate in most cells. Replication deficient adenoviruses may be deleted in one or more of all or a portion of the following genes: E1a, E1b, E3, E4, E2a, or L1 through L5.  
       [0835] In certain other embodiments, the cells are engineered, ex vivo or in vivo, using an adeno-associated virus (AAV). AAVs are naturally occurring defective viruses that require helper viruses to produce infectious particles (Muzyczka, N., Curr. Topics in Microbiol. Immunol. 158:97 (1992)). It is also one of the few viruses that may integrate its DNA into non-dividing cells. Vectors containing as little as 300 base pairs of AAV can be packaged and can integrate, but space for exogenous DNA is limited to about 4.5 kb. Methods for producing and using such AAVs are known in the art. See, for example, U.S. Pat. Nos. 5,139,941, 5,173,414, 5,354,678, 5,436,146, 5,474,935, 5,478,745, and 5,589,377.  
       [0836] For example, an appropriate AAV vector for use in the present invention will include all the sequences necessary for DNA replication, encapsidation, and host-cell integration. The polynucleotide construct is inserted into the AAV vector using standard cloning methods, such as those found in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press (1989). The recombinant AAV vector is then transfected into packaging cells which are infected with a helper virus, using any standard technique, including lipofection, electroporation, calcium phosphate precipitation, etc. Appropriate helper viruses include adenoviruses, cytomegaloviruses, vaccinia viruses, or herpes viruses. Once the packaging cells are transfected and infected, they will produce infectious AAV viral particles which contain the polynucleotide construct. These viral particles are then used to transduce eukaryotic cells, either ex vivo or in vivo. The transduced cells will contain the polynucleotide construct integrated into its genome, and will express a polypeptide of the invention.  
       [0837] Another method of gene therapy involves operably associating heterologous control regions and endogenous polynucleotide sequences (e.g. encoding a polypeptide of the present invention) via homologous recombination (see, e.g., U.S. Pat. No. 5,641,670, issued Jun. 24, 1997; International Publication No. WO 96/29411, published Sep. 26, 1996; International Publication No. WO 94/12650, published Aug. 4, 1994; Koller et al., Proc. Natl. Acad. Sci. USA 86:8932-8935 (1989); and Zijlstra et al., Nature 342:435-438 (1989). This method involves the activation of a gene which is present in the target cells, but which is not normally expressed in the cells, or is expressed at a lower level than desired.  
       [0838] Polynucleotide constructs are made, using standard techniques known in the art, which contain the promoter with targeting sequences flanking the promoter. Suitable promoters are described herein. The targeting sequence is sufficiently complementary to an endogenous sequence to permit homologous recombination of the promoter-targeting sequence with the endogenous sequence. The targeting sequence will be sufficiently near the 5′ end of the desired endogenous polynucleotide sequence so the promoter will be operably linked to the endogenous sequence upon homologous recombination.  
       [0839] The promoter and the targeting sequences can be amplified using PCR. Preferably, the amplified promoter contains distinct restriction enzyme sites on the 5′ and 3′ ends. Preferably, the 3′ end of the first targeting sequence contains the same restriction enzyme site as the 5′ end of the amplified promoter and the 5′ end of the second targeting sequence contains the same restriction site as the 3′ end of the amplified promoter. The amplified promoter and targeting sequences are digested and ligated together.  
       [0840] The promoter-targeting sequence construct is delivered to the cells, either as naked polynucleotide, or in conjunction with transfection-facilitating agents, such as liposomes, viral sequences, viral particles, whole viruses, lipofection, precipitating agents, etc., described in more detail above. The P promoter-targeting sequence can be delivered by any method, included direct needle injection, intravenous injection, topical administration, catheter infusion, particle accelerators, etc. The methods are described in more detail below.  
       [0841] The promoter-targeting sequence construct is taken up by cells. Homologous recombination between the construct and the endogenous sequence takes place, such that an endogenous sequence is placed under the control of the promoter. The promoter then drives the expression of the endogenous sequence.  
       [0842] Preferably, the polynucleotide encoding a polypeptide of the present invention contains a secretory signal sequence that facilitates secretion of the protein. Typically, the signal sequence is positioned in the coding region of the polynucleotide to be expressed towards or at the 5′ end of the coding region. The signal sequence may be homologous or heterologous to the polynucleotide of interest and may be homologous or heterologous to the cells to be transfected. Additionally, the signal sequence may be chemically synthesized using methods known in the art.  
       [0843] Any mode of administration of any of the above-described polynucleotides constructs can be used so long as the mode results in the expression of one or more molecules in an amount sufficient to provide a therapeutic effect. This includes direct needle injection, systemic injection, catheter infusion, biolistic injectors, particle accelerators (i.e., “gene guns”), gelfoam sponge depots, other commercially available depot materials, osmotic pumps (e.g., Alza minipumps), oral or suppositorial solid (tablet or pill) pharmaceutical formulations, and decanting or topical applications during surgery. For example, direct injection of naked calcium phosphate-precipitated plasmid into rat liver and rat spleen or a protein-coated plasmid into the portal vein has resulted in gene expression of the foreign gene in the rat livers (Kaneda et al., Science 243:375 (1989)).  
       [0844] A preferred method of local administration is by direct injection. Preferably, a recombinant molecule of the present invention complexed with a delivery vehicle is administered by direct injection into or locally within the area of arteries. Administration of a composition locally within the area of arteries refers to injecting the composition centimeters and preferably, millimeters within arteries.  
       [0845] Another method of local administration is to contact a polynucleotide construct of the present invention in or around a surgical wound. For example, a patient can undergo surgery and the polynucleotide construct can be coated on the surface of tissue inside the wound or the construct can be injected into areas of tissue inside the wound.  
       [0846] Therapeutic compositions useful in systemic administration, include recombinant molecules of the present invention complexed to a targeted delivery vehicle of the present invention. Suitable delivery vehicles for use with systemic administration comprise liposomes comprising ligands for targeting the vehicle to a particular site.  
       [0847] Preferred methods of systemic administration, include intravenous injection, aerosol, oral and percutaneous (topical) delivery. Intravenous injections can be performed using methods standard in the art. Aerosol delivery can also be performed using methods standard in the art (see, for example, Stribling et al., Proc. Natl. Acad. Sci. USA 189:11277-11281, 1992, which is incorporated herein by reference). Oral delivery can be performed by complexing a polynucleotide construct of the present invention to a carrier capable of withstanding degradation by digestive enzymes in the gut of an animal. Examples of such carriers, include plastic capsules or tablets, such as those known in the art. Topical delivery can be performed by mixing a polynucleotide construct of the present invention with a lipophilic reagent (e.g., DMSO) that is capable of passing into the skin.  
       [0848] Determining an effective amount of substance to be delivered can depend upon a number of factors including, for example, the chemical structure and biological activity of the substance, the age and weight of the animal, the precise condition requiring treatment and its severity, and the route of administration. The frequency of treatments depends upon a number of factors, such as the amount of polynucleotide constructs administered per dose, as well as the health and history of the subject. The precise amount, number of doses, and timing of doses will be determined by the attending physician or veterinarian.  
       [0849] Therapeutic compositions of the present invention can be administered to any animal, preferably to mammals and birds. Preferred mammals include humans, dogs, cats, mice, rats, rabbits sheep, cattle, horses and pigs, with humans being particularly preferred.  
       [0850] Biological Activities  
       [0851] Polynucleotides or polypeptides, or agonists or antagonists of the present invention, can be used in assays to test for one or more biological activities. If these polynucleotides or polypeptides, or agonists or antagonists of the present invention, do exhibit activity in a particular assay, it is likely that these molecules may be involved in the diseases associated with the biological activity. Thus, the polynucleotides and polypeptides, and agonists or antagonists could be used to treat the associated disease.  
       [0852] ACRP30-Like proteins are believed to be involved in biological activities associated with glucose uptake, energy homeostasis, inflammation/immune responses, and angiogenesis/vascular repair. Accordingly, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of diseases and/or disorders associated with aberrant ACRP30-Like activity.  
       [0853] In preferred embodiments, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of Types I and II diabetes mellitus, obesity, and/or metabolic disorders described herein under “Endocrine Disorders”. In additional embodiments, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of complications and disorders associated with Type I and II diabetes mellitus, including, but not limited to, seizures, mental confusion, drowsiness, nonketotic hyperglycemic-hyperosmolar coma, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section below), dyslipidemia, kidney disease (e.g., renal failure, nephropathy and/or as described in the “Renal Disorders” section below), endocrine disorders (as described in the “Endocrine Disorders” section below), obesity, nerve damage, neuropathy, impotence, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section below, especially of the urinary tract and skin), carpal tunnel syndrome, Dupuytren&#39;s contracture, and amputations.  
       [0854] In additional preferred embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to regulate weight gain, weight loss, and/or obesity.  
       [0855] In other embodiments, compositions of the invention (including polynucleotides, polypeptides and antibodies of the invention, and fragments and variants thereof) may be used in the diagnosis, prognosis, prevention, and/or treatment of diseases and/or disorders relating to immune disorders, endocrine disorders, and/or cardiovascular disorders as described under the sections entitled “Immune activity”, “Endocrine Disorders”, and “Cardiovascular Disorders” herein.  
       [0856] In certain embodiments, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to diagnose and/or prognose diseases and/or disorders disclosed in “Polynucleotides and Polypeptides of the Invention”; Table 4, column 3 (OMIM Reference(s)); as well as diseases and/or disorders associated with the tissue(s) in which the polypeptide of the invention is expressed, including the tissues disclosed in “Polynucleotides and Polypeptides of the Invention”, and/or one, two, three, four, five, or more tissues disclosed in Table 3, column 2 (Library Code).  
       [0857] More generally, polynucleotides, translation products and antibodies corresponding to this gene may be useful for the diagnosis, detection and/or treatment of diseases and/or disorders associated with the following systems.  
       [0858] Immune Activity  
       [0859] Polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, diagnosing and/or prognosing diseases, disorders, and/or conditions of the immune system, by, for example, activating or inhibiting the proliferation, differentiation, or mobilization (chemotaxis) of immune cells. Immune cells develop through a process called hematopoiesis, producing myeloid (platelets, red blood cells, neutrophils, and macrophages) and lymphoid (B and T lymphocytes) cells from pluripotent stem cells. The etiology of these immune diseases, disorders, and/or conditions may be genetic, somatic, such as cancer and some autoimmune diseases, acquired (e.g., by chemotherapy or toxins), or infectious. Moreover, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention can be used as a marker or detector of a particular immune system disease or disorder.  
       [0860] In another embodiment, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to treat diseases and disorders of the immune system and/or to inhibit or enhance an immune response generated by cells associated with the tissue(s) in which the polypeptide of the invention is expressed, including one, two, three, four, five, or more tissues disclosed in Table 3, column 2 (Library Code).  
       [0861] Polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, diagnosing, and/or prognosing immunodeficiencies, including both congenital and acquired immunodeficiencies. Examples of B cell immunodeficiencies in which immunoglobulin levels B cell function and/or cell numbers are decreased include: X-linked agammaglobulinemia (Bruton&#39;s disease), X-linked infantile agammaglobulinemia, X-linked immunodeficiency with hyper IgM, non X-linked immunodeficiency with hyper IgM, X-linked lymphoproliferative syndrome (XLP), agammaglobulinemia including congenital and acquired agammaglobulinemia, adult onset agammaglobulinemia, late-onset agammaglobulinemia, dysgammaglobulinemia, hypogammaglobulinemia, unspecified hypogammaglobulinemia, recessive agammaglobulinemia (Swiss type), Selective IgM deficiency, selective IgA deficiency, selective IgG subclass deficiencies, IgG subclass deficiency (with or without IgA deficiency), Ig deficiency with increased IgM, IgG and IgA deficiency with increased IgM, antibody deficiency with normal or elevated Igs, Ig heavy chain deletions, kappa chain deficiency, B cell lymphoproliferative disorder (BLPD), common variable immunodeficiency (CVID), common variable immunodeficiency (CVI) (acquired), and transient hypogammaglobulinemia of infancy.  
       [0862] In specific embodiments, ataxia-telangiectasia or conditions associated with ataxia-telangiectasia are treated, prevented, diagnosed, and/or prognosing using the polypeptides or polynucleotides of the invention, and/or agonists or antagonists thereof.  
       [0863] Examples of congenital immunodeficiencies in which T cell and/or B cell function and/or number is decreased include, but are not limited to: DiGeorge anomaly, severe combined immunodeficiencies (SCID) (including, but not limited to, X-linked SCID, autosomal recessive SCID, adenosine deaminase deficiency, purine nucleoside phosphorylase (PNP) deficiency, Class II MHC deficiency (Bare lymphocyte syndrome), Wiskott-Aldrich syndrome, and ataxia telangiectasia), thymic hypoplasia, third and fourth pharyngeal pouch syndrome, 22q11.2 deletion, chronic mucocutaneous candidiasis, natural killer cell deficiency (NK), idiopathic CD4+ T-lymphocytopenia, immunodeficiency with predominant T cell defect (unspecified), and unspecified immunodeficiency of cell mediated immunity.  
       [0864] In specific embodiments, DiGeorge anomaly or conditions associated with DiGeorge anomaly are treated, prevented, diagnosed, and/or prognosed using polypeptides or polynucleotides of the invention, or antagonists or agonists thereof.  
       [0865] Other immunodeficiencies that may be treated, prevented, diagnosed, and/or prognosed using polypeptides or polynucleotides of the invention, and/or agonists or antagonists thereof, include, but are not limited to, chronic granulomatous disease, Chédiak-Higashi syndrome, myeloperoxidase deficiency, leukocyte glucose-6-phosphate dehydrogenase deficiency, X-linked lymphoproliferative syndrome (XLP), leukocyte adhesion deficiency, complement component deficiencies (including C1, C2, C3, C4, C5, C6, C7, C8 and/or C9 deficiencies), reticular dysgenesis, thymic alymphoplasia-aplasia, immunodeficiency with thymoma, severe congenital leukopenia, dysplasia with immunodeficiency, neonatal neutropenia, short limbed dwarfism, and Nezelof syndrome-combined immunodeficiency with Igs.  
       [0866] In a preferred embodiment, the immunodeficiencies and/or conditions associated with the immunodeficiencies recited above are treated, prevented, diagnosed and/or prognosed using polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention.  
       [0867] In a preferred embodiment polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention could be used as an agent to boost immunoresponsiveness among immunodeficient individuals. In specific embodiments, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention could be used as an agent to boost immunoresponsiveness among B cell and/or T cell immunodeficient individuals.  
       [0868] The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, diagnosing and/or prognosing autoimmune disorders. Many autoimmune disorders result from inappropriate recognition of self as foreign material by immune cells. This inappropriate recognition results in an immune response leading to the destruction of the host tissue. Therefore, the administration of polynucleotides and polypeptides of the invention that can inhibit an immune response, particularly the proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing autoimmune disorders.  
       [0869] Autoimmune diseases or disorders that may be treated, prevented, diagnosed and/or prognosed by polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention include, but are not limited to, one or more of the following: systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, autoimmune thyroiditis, Hashimoto&#39;s thyroiditis, autoimmune hemolytic anemia, hemolytic anemia, thrombocytopenia, autoimmune thrombocytopenia purpura, autoimmune neonatal thrombocytopenia, idiopathic thrombocytopenia purpura, purpura (e.g., Henloch-Scoenlein purpura), autoimmunocytopenia, Goodpasture&#39;s syndrome, Pemphigus vulgaris, myasthenia gravis, Grave&#39;s disease (hyperthyroidism), and insulin-resistant diabetes mellitus.  
       [0870] Additional disorders that are likely to have an autoimmune component that may be treated, prevented, and/or diagnosed with the compositions of the invention include, but are not limited to, type II collagen-induced arthritis, antiphospholipid syndrome, dermatitis, allergic encephalomyelitis, myocarditis, relapsing polychondritis, rheumatic heart disease, neuritis, uveitis ophthalmia, polyendocrinopathies, Reiter&#39;s Disease, Stiff-Man Syndrome, autoimmune pulmonary inflammation, autism, Guillain-Barre Syndrome, insulin dependent diabetes mellitus, and autoimmune inflammatory eye disorders.  
       [0871] Additional disorders that are likely to have an autoimmune component that may be treated, prevented, diagnosed and/or prognosed with the compositions of the invention include, but are not limited to, scleroderma with anti-collagen antibodies (often characterized, e.g., by nucleolar and other nuclear antibodies), mixed connective tissue disease (often characterized, e.g., by antibodies to extractable nuclear antigens (e.g., ribonucleoprotein)), polymyositis (often characterized, e.g., by nonhistone ANA), pernicious anemia (often characterized, e.g., by antiparietal cell, microsomes, and intrinsic factor antibodies), idiopathic Addison&#39;s disease (often characterized, e.g., by humoral and cell-mediated adrenal cytotoxicity, infertility (often characterized, e.g., by antispermatozoal antibodies), glomerulonephritis (often characterized, e.g., by glomerular basement membrane antibodies or immune complexes), bullous pemphigoid (often characterized, e.g., by IgG and complement in basement membrane), Sjogren&#39;s syndrome (often characterized, e.g., by multiple tissue antibodies, and/or a specific nonhistone ANA (SS-B)), diabetes mellitus (often characterized, e.g., by cell-mediated and humoral islet cell antibodies), and adrenergic drug resistance (including adrenergic drug resistance with asthma or cystic fibrosis) (often characterized, e.g., by beta-adrenergic receptor antibodies).  
       [0872] Additional disorders that may have an autoimmune component that may be treated, prevented, diagnosed and/or prognosed with the compositions of the invention include, but are not limited to, chronic active hepatitis (often characterized, e.g., by smooth muscle antibodies), primary biliary cirrhosis (often characterized, e.g., by mitochondria antibodies), other endocrine gland failure (often characterized, e.g., by specific tissue antibodies in some cases), vitiligo (often characterized, e.g., by melanocyte antibodies), vasculitis (often characterized, e.g., by Ig and complement in vessel walls and/or low serum complement), post-MI (often characterized, e.g., by myocardial antibodies), cardiotomy syndrome (often characterized, e.g., by myocardial antibodies), urticaria (often characterized, e.g., by IgG and IgM antibodies to IgE), atopic dermatitis (often characterized, e.g., by IgG and IgM antibodies to IgE), asthma (often characterized, e.g., by IgG and IgM antibodies to IgE), and many other inflammatory, granulomatous, degenerative, and atrophic disorders.  
       [0873] In a preferred embodiment, the autoimmune diseases and disorders and/or conditions associated with the diseases and disorders recited above are treated, prevented, diagnosed and/or prognosed using for example, antagonists or agonists, polypeptides or polynucleotides, or antibodies of the present invention. In a specific preferred embodiment, rheumatoid arthritis is treated, prevented, and/or diagnosed using polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention.  
       [0874] In another specific preferred embodiment, systemic lupus erythematosus is treated, prevented, and/or diagnosed using polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention. In another specific preferred embodiment, idiopathic thrombocytopenia purpura is treated, prevented, and/or diagnosed using polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention.  
       [0875] In another specific preferred embodiment IgA nephropathy is treated, prevented, and/or diagnosed using polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention.  
       [0876] In a preferred embodiment, the autoimmune diseases and disorders and/or conditions associated with the diseases and disorders recited above are treated, prevented, diagnosed and/or prognosed using polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention  
       [0877] In preferred embodiments, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a immunosuppressive agent(s).  
       [0878] Polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, prognosing, and/or diagnosing diseases, disorders, and/or conditions of hematopoietic cells. Polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention could be used to increase differentiation and proliferation of hematopoietic cells, including the pluripotent stem cells, in an effort to treat or prevent those diseases, disorders, and/or conditions associated with a decrease in certain (or many) types hematopoietic cells, including but not limited to, leukopenia, neutropenia, anemia, and thrombocytopenia. Alternatively, Polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention could be used to increase differentiation and proliferation of hematopoietic cells, including the pluripotent stem cells, in an effort to treat or prevent those diseases, disorders, and/or conditions associated with an increase in certain (or many) types of hematopoietic cells, including but not limited to, histiocytosis.  
       [0879] Allergic reactions and conditions, such as asthma (particularly allergic asthma) or other respiratory problems, may also be treated, prevented, diagnosed and/or prognosed using polypeptides, antibodies, or polynucleotides of the invention, and/or agonists or antagonists thereof. Moreover, these molecules can be used to treat, prevent, prognose, and/or diagnose anaphylaxis, hypersensitivity to an antigenic molecule, or blood group incompatibility.  
       [0880] Additionally, polypeptides or polynucleotides of the invention, and/or agonists or antagonists thereof, may be used to treat, prevent, diagnose and/or prognose IgE-mediated allergic reactions. Such allergic reactions include, but are not limited to, asthma, rhinitis, and eczema. In specific embodiments, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to modulate IgE concentrations in vitro or in vivo.  
       [0881] Moreover, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention have uses in the diagnosis, prognosis, prevention, and/or treatment of inflammatory conditions. For example, since polypeptides, antibodies, or polynucleotides of the invention, and/or agonists or antagonists of the invention may inhibit the activation, proliferation and/or differentiation of cells involved in an inflammatory response, these molecules can be used to prevent and/or treat chronic and acute inflammatory conditions. Such inflammatory conditions include, but are not limited to, for example, inflammation associated with infection (e.g., septic shock, sepsis, or systemic inflammatory response syndrome), ischemia-reperfusion injury, endotoxin lethality, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine induced lung injury, inflammatory bowel disease, Crohn&#39;s disease, over production of cytokines (e.g., TNF or IL-1.), respiratory disorders (e.g., asthma and allergy); gastrointestinal disorders (e.g., inflammatory bowel disease); cancers (e.g., gastric, ovarian, lung, bladder, liver, and breast); CNS disorders (e.g., multiple sclerosis; ischemic brain injury and/or stroke, traumatic brain injury, neurodegenerative disorders (e.g., Parkinson&#39;s disease and Alzheimer&#39;s disease); AIDS-related dementia; and prion disease); cardiovascular disorders (e.g., atherosclerosis, myocarditis, cardiovascular disease, and cardiopulmonary bypass complications); as well as many additional diseases, conditions, and disorders that are characterized by inflammation (e.g., hepatitis, rheumatoid arthritis, gout, trauma, pancreatitis, sarcoidosis, dermatitis, renal ischemia-reperfusion injury, Grave&#39;s disease, systemic lupus erythematosus, diabetes mellitus, and allogenic transplant rejection).  
       [0882] Because inflammation is a fundamental defense mechanism, inflammatory disorders can effect virtually any tissue of the body. Accordingly, polynucleotides, polypeptides, and antibodies of the invention, as well as agonists or antagonists thereof, have uses in the treatment of tissue-specific inflammatory disorders, including, but not limited to, adrenalitis, alveolitis, angiocholecystitis, appendicitis, balanitis, blepharitis, bronchitis, bursitis, carditis, cellulitis, cervicitis, cholecystitis, chorditis, cochlitis, colitis, conjunctivitis, cystitis, dermatitis, diverticulitis, encephalitis, endocarditis, esophagitis, eustachitis, fibrositis, folliculitis, gastritis, gastroenteritis, gingivitis, glossitis, hepatosplenitis, keratitis, labyrinthitis, laryngitis, lymphangitis, mastitis, media otitis, meningitis, metritis, mucitis, myocarditis, myosititis, myringitis, nephritis, neuritis, orchitis, osteochondritis, otitis, pericarditis, peritendonitis, peritonitis, pharyngitis, phlebitis, poliomyelitis, prostatitis, pulpitis, retinitis, rhinitis, salpingitis, scleritis, sclerochoroiditis, scrotitis, sinusitis, spondylitis, steatitis, stomatitis, synovitis, syringitis, tendonitis, tonsillitis, urethritis, and vaginitis.  
       [0883] In specific embodiments, polypeptides, antibodies, or polynucleotides of the invention, and/or agonists or antagonists thereof, are useful to diagnose, prognose, prevent, and/or treat organ transplant rejections and graft-versus-host disease. Organ rejection occurs by host immune cell destruction of the transplanted tissue through an immune response. Similarly, an immune response is also involved in GVHD, but, in this case, the foreign transplanted immune cells destroy the host tissues. Polypeptides, antibodies, or polynucleotides of the invention, and/or agonists or antagonists thereof, that inhibit an immune response, particularly the activation, proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing organ rejection or GVHD. In specific embodiments, polypeptides, antibodies, or polynucleotides of the invention, and/or agonists or antagonists thereof, that inhibit an immune response, particularly the activation, proliferation, differentiation, or chemotaxis of T-cells, may be an effective therapy in preventing experimental allergic and hyperacute xenograft rejection.  
       [0884] In other embodiments, polypeptides, antibodies, or polynucleotides of the invention, and/or agonists or antagonists thereof, are useful to diagnose, prognose, prevent, and/or treat immune complex diseases, including, but not limited to, serum sickness, post streptococcal glomerulonephritis, polyarteritis nodosa, and immune complex-induced vasculitis.  
       [0885] Polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the invention can be used to treat, detect, and/or prevent infectious agents. For example, by increasing the immune response, particularly increasing the proliferation activation and/or differentiation of B and/or T cells, infectious diseases may be treated, detected, and/or prevented. The immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response. Alternatively, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may also directly inhibit the infectious agent (refer to section of application listing infectious agents, etc), without necessarily eliciting an immune response.  
       [0886] In another embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a vaccine adjuvant that enhances immune responsiveness to an antigen. In a specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an adjuvant to enhance tumor-specific immune responses.  
       [0887] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an adjuvant to enhance anti-viral immune responses. Anti-viral immune responses that may be enhanced using the compositions of the invention as an adjuvant, include virus and virus associated diseases or symptoms described herein or otherwise known in the art. In specific embodiments, the compositions of the invention are used as an adjuvant to enhance an immune response to a virus, disease, or symptom selected from the group consisting of: AIDS, meningitis, Dengue, EBV, and hepatitis (e.g., hepatitis B). In another specific embodiment, the compositions of the invention are used as an adjuvant to enhance an immune response to a virus, disease, or symptom selected from the group consisting of: HIV/AIDS, respiratory syncytial virus, Dengue, rotavirus, Japanese B encephalitis, influenza A and B, parainfluenza, measles, cytomegalovirus, rabies, Junin, Chikungunya, Rift Valley Fever, herpes simplex, and yellow fever.  
       [0888] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an adjuvant to enhance anti-bacterial or anti-fungal immune responses. Anti-bacterial or anti-fungal immune responses that may be enhanced using the compositions of the invention as an adjuvant, include bacteria or fungus and bacteria or fungus associated diseases or symptoms described herein or otherwise known in the art. In specific embodiments, the compositions of the invention are used as an adjuvant to enhance an immune response to a bacteria or fungus, disease, or symptom selected from the group consisting of: tetanus, Diphtheria, botulism, and meningitis type B.  
       [0889] In another specific embodiment, the compositions of the invention are used as an adjuvant to enhance an immune response to a bacteria or fungus, disease, or symptom selected from the group consisting of:  Vibrio cholerae, Mycobacterium leprae, Salmonella typhi, Salmonella paratyphi, Meisseria meningilidis, Streptococcus pneumoniae , Group B streptococcus, Shigella spp., Enterotoxigenic  Escherichia coli , Enterohemorrhagic  E. coli , and  Borrelia burgdorferi.    
       [0890] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an adjuvant to enhance anti-parasitic immune responses. Anti-parasitic immune responses that may be enhanced using the compositions of the invention as an adjuvant, include parasite and parasite associated diseases or symptoms described herein or otherwise known in the art. In specific embodiments, the compositions of the invention are used as an adjuvant to enhance an immune response to a parasite. In another specific embodiment, the compositions of the invention are used as an adjuvant to enhance an immune response to Plasmodium (malaria) or Leishmania.  
       [0891] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention may also be employed to treat infectious diseases including silicosis, sarcoidosis, and idiopathic pulmonary fibrosis; for example, by preventing the recruitment and activation of mononuclear phagocytes.  
       [0892] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an antigen for the generation of antibodies to inhibit or enhance immune mediated responses against polypeptides of the invention.  
       [0893] In one embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are administered to an animal (e.g., mouse, rat, rabbit, hamster, guinea pig, pigs, micro-pig, chicken, camel, goat, horse, cow, sheep, dog, cat, non-human primate, and human, most preferably human) to boost the immune system to produce increased quantities of one or more antibodies (e.g., IgG, IgA, IgM, and IgE), to induce higher affinity antibody production and immunoglobulin class switching (e.g., IgG, IgA, IgM, and IgE), and/or to increase an immune response.  
       [0894] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a stimulator of B cell responsiveness to pathogens.  
       [0895] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an activator of T cells.  
       [0896] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent that elevates the immune status of an individual prior to their receipt of immunosuppressive therapies.  
       [0897] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent to induce higher affinity antibodies.  
       [0898] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent to increase serum immunoglobulin concentrations.  
       [0899] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent to accelerate recovery of immunocompromised individuals.  
       [0900] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent to boost immunoresponsiveness among aged populations and/or neonates.  
       [0901] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an immune system enhancer prior to, during, or after bone marrow transplant and/or other transplants (e.g., allogeneic or xenogeneic organ transplantation). With respect to transplantation, compositions of the invention may be administered prior to, concomitant with, and/or after transplantation. In a specific embodiment, compositions of the invention are administered after transplantation, prior to the beginning of recovery of T-cell populations. In another specific embodiment, compositions of the invention are first administered after transplantation after the beginning of recovery of T cell populations, but prior to full recovery of B cell populations.  
       [0902] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent to boost immunoresponsiveness among individuals having an acquired loss of B cell function. Conditions resulting in an acquired loss of B cell function that may be ameliorated or treated by administering the polypeptides, antibodies, polynucleotides and/or agonists or antagonists thereof, include, but are not limited to, HIV Infection, AIDS, bone marrow transplant, and B cell chronic lymphocytic leukemia (CLL).  
       [0903] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent to boost immunoresponsiveness among individuals having a temporary immune deficiency. Conditions resulting in a temporary immune deficiency that may be ameliorated or treated by administering the polypeptides, antibodies, polynucleotides and/or agonists or antagonists thereof, include, but are not limited to, recovery from viral infections (e.g., influenza), conditions associated with malnutrition, recovery from infectious mononucleosis, or conditions associated with stress, recovery from measles, recovery from blood transfusion, and recovery from surgery.  
       [0904] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a regulator of antigen presentation by monocytes, dendritic cells, and/or B-cells. In one embodiment, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention enhance antigen presentation or antagonizes antigen presentation in vitro or in vivo. Moreover, in related embodiments, said enhancement or antagonism of antigen presentation may be useful as an anti-tumor treatment or to modulate the immune system.  
       [0905] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as an agent to direct an individual&#39;s immune system towards development of a humoral response (i.e. TH2) as opposed to a TH1 cellular response.  
       [0906] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a means to induce tumor proliferation and thus make it more susceptible to anti-neoplastic agents. For example, multiple myeloma is a slowly dividing disease and is thus refractory to virtually all anti-neoplastic regimens. If these cells were forced to proliferate more rapidly their susceptibility profile would likely change.  
       [0907] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a stimulator of B cell production in pathologies such as AIDS, chronic lymphocyte disorder and/or Common Variable Immunodificiency.  
       [0908] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a therapy for generation and/or regeneration of lymphoid tissues following surgery, trauma or genetic defect. In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used in the pretreatment of bone marrow samples prior to transplant.  
       [0909] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a gene-based therapy for genetically inherited disorders resulting in immuno-incompetence/immunodeficiency such as observed among SCID patients.  
       [0910] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a means of activating monocytes/macrophages to defend against parasitic diseases that effect monocytes such as Leishmania.  
       [0911] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a means of regulating secreted cytokines that are elicited by polypeptides of the invention.  
       [0912] In another embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used in one or more of the applications described herein, as they may apply to veterinary medicine.  
       [0913] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a means of blocking various aspects of immune responses to foreign agents or self. Examples of diseases or conditions in which blocking of certain aspects of immune responses may be desired include autoimmune disorders such as lupus, and arthritis, as well as immunoresponsiveness to skin allergies, inflammation, bowel disease, injury and diseases/disorders associated with pathogens.  
       [0914] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a therapy for preventing the B cell proliferation and Ig secretion associated with autoimmune diseases such as idiopathic thrombocytopenic purpura, systemic lupus erythematosus and multiple sclerosis.  
       [0915] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a inhibitor of B and/or T cell migration in endothelial cells. This activity disrupts tissue architecture or cognate responses and is useful, for example in disrupting immune responses, and blocking sepsis.  
       [0916] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a therapy for chronic hypergammaglobulinemia evident in such diseases as monoclonal gammopathy of undetermined significance (MGUS), Waldenstrom&#39;s disease, related idiopathic monoclonal gammopathies, and plasmacytomas.  
       [0917] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention may be employed for instance to inhibit polypeptide chemotaxis and activation of macrophages and their precursors, and of neutrophils, basophils, B lymphocytes and some T-cell subsets, e.g., activated and CD8 cytotoxic T cells and natural killer cells, in certain autoimmune and chronic inflammatory and infective diseases. Examples of autoimmune diseases are described herein and include multiple sclerosis, and insulin-dependent diabetes.  
       [0918] The polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention may also be employed to treat idiopathic hyper-eosinophilic syndrome by, for example, preventing eosinophil production and migration.  
       [0919] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used to enhance or inhibit complement mediated cell lysis.  
       [0920] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used to enhance or inhibit antibody dependent cellular cytotoxicity.  
       [0921] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention may also be employed for treating atherosclerosis, for example, by preventing monocyte infiltration in the artery wall.  
       [0922] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention may be employed to treat adult respiratory distress syndrome (ARDS).  
       [0923] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention may be useful for stimulating wound and tissue repair, stimulating angiogenesis, and/or stimulating the repair of vascular or lymphatic diseases or disorders. Additionally, agonists and antagonists of the invention may be used to stimulate the regeneration of mucosal surfaces.  
       [0924] In a specific embodiment, polynucleotides or polypeptides, and/or agonists thereof are used to diagnose, prognose, treat, and/or prevent a disorder characterized by primary or acquired immunodeficiency, deficient serum immunoglobulin production, recurrent infections, and/or immune system dysfunction. Moreover, polynucleotides or polypeptides, and/or agonists thereof may be used to treat or prevent infections of the joints, bones, skin, and/or parotid glands, blood-borne infections (e.g., sepsis, meningitis, septic arthritis, and/or osteomyelitis), autoimmune diseases (e.g., those disclosed herein), inflammatory disorders, and malignancies, and/or any disease or disorder or condition associated with these infections, diseases, disorders and/or malignancies) including, but not limited to, CVID, other primary immune deficiencies, HIV disease, CLL, recurrent bronchitis, sinusitis, otitis media, conjunctivitis, pneumonia, hepatitis, meningitis, herpes zoster (e.g., severe herpes zoster), and/or pneumocystis carnii. Other diseases and disorders that may be prevented, diagnosed, prognosed, and/or treated with polynucleotides or polypeptides, and/or agonists of the present invention include, but are not limited to, HIV infection, HTLV-BLV infection, lymphopenia, phagocyte bactericidal dysfunction anemia, thrombocytopenia, and hemoglobinuria.  
       [0925] In another embodiment, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention are used to treat, and/or diagnose an individual having common variable immunodeficiency disease (“CVID”; also known as “acquired agammaglobulinemia” and “acquired hypogammaglobulinemia”) or a subset of this disease.  
       [0926] In a specific embodiment, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to diagnose, prognose, prevent, and/or treat cancers or neoplasms including immune cell or immune tissue-related cancers or neoplasms. Examples of cancers or neoplasms that may be prevented, diagnosed, or treated by polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention include, but are not limited to, acute myelogenous leukemia, chronic myelogenous leukemia, Hodgkin&#39;s disease, non-Hodgkin&#39;s lymphoma, acute lymphocytic anemia (ALL) Chronic lymphocyte leukemia, plasmacytomas, multiple myeloma, Burkitt&#39;s lymphoma, EBV-transformed diseases, and/or diseases and disorders described in the section entitled “Hyperproliferative Disorders” elsewhere herein.  
       [0927] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a therapy for decreasing cellular proliferation of Large B-cell Lymphomas.  
       [0928] In another specific embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are used as a means of decreasing the involvement of B cells and Ig associated with Chronic Myelogenous Leukemia.  
       [0929] In specific embodiments, the compositions of the invention are used as an agent to boost immunoresponsiveness among B cell immunodeficient individuals, such as, for example, an individual who has undergone a partial or complete splenectomy.  
       [0930] Antagonists of the invention include, for example, binding and/or inhibitory antibodies, antisense nucleic acids, ribozymes or soluble forms of the polypeptides of the present invention (e.g., Fc fusion protein; see, e.g., Example 9). Agonists of the invention include, for example, binding or stimulatory antibodies, and soluble forms of the polypeptides (e.g., Fc fusion proteins; see, e.g., Example 9). polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention may be employed in a composition with a pharmaceutically acceptable carrier, e.g., as described herein.  
       [0931] In another embodiment, polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention are administered to an animal (including, but not limited to, those listed above, and also including transgenic animals) incapable of producing functional endogenous antibody molecules or having an otherwise compromised endogenous immune system, but which is capable of producing human immunoglobulin molecules by means of a reconstituted or partially reconstituted immune system from another animal (see, e.g., published PCT Application Nos. WO98/24893, WO/9634096, WO/9633735, and WO/9110741). Administration of polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention to such animals is useful for the generation of monoclonal antibodies against the polypeptides, antibodies, polynucleotides and/or agonists or antagonists of the present invention.  
       [0932] Blood-Related Disorders  
       [0933] The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to modulate hemostatic (the stopping of bleeding) or thrombolytic (clot dissolving) activity. For example, by increasing hemostatic or thrombolytic activity, polynucleotides or polypeptides, and/or agonists or antagonists of the present invention could be used to treat or prevent blood coagulation diseases, disorders, and/or conditions (e.g., afibrinogenemia, factor deficiencies, hemophilia), blood platelet diseases, disorders, and/or conditions (e.g., thrombocytopenia), or wounds resulting from trauma, surgery, or other causes. Alternatively, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention that can decrease hemostatic or thrombolytic activity could be used to inhibit or dissolve clotting. These molecules could be important in the treatment or prevention of heart attacks (infarction), strokes, or scarring.  
       [0934] In specific embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to prevent, diagnose, prognose, and/or treat thrombosis, arterial thrombosis, venous thrombosis, thromboembolism, pulmonary embolism, atherosclerosis, myocardial infarction, transient ischemic attack, unstable angina. In specific embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used for the prevention of occulsion of saphenous grafts, for reducing the risk of periprocedural thrombosis as might accompany angioplasty procedures, for reducing the risk of stroke in patients with atrial fibrillation including nonrheumatic atrial fibrillation, for reducing the risk of embolism associated with mechanical heart valves and or mitral valves disease. Other uses for the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention, include, but are not limited to, the prevention of occlusions in extrcorporeal devices (e.g., intravascular canulas, vascular access shunts in hemodialysis patients, hemodialysis machines, and cardiopulmonary bypass machines).  
       [0935] In another embodiment, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to prevent, diagnose, prognose, and/or treat diseases and disorders of the blood and/or blood forming organs associated with the tissue(s) in which the polypeptide of the invention is expressed, including one, two, three, four, five, or more tissues disclosed in Table 3, column 2 (Library Code).  
       [0936] The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to modulate hematopoietic activity (the formation of blood cells). For example, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to increase the quantity of all or subsets of blood cells, such as, for example, erythrocytes, lymphocytes (B or T cells), myeloid cells (e.g., basophils, eosinophils, neutrophils, mast cells, macrophages) and platelets. The ability to decrease the quantity of blood cells or subsets of blood cells may be useful in the prevention, detection, diagnosis and/or treatment of anemias and leukopenias described below. Alternatively, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to decrease the quantity of all or subsets of blood cells, such as, for example, erythrocytes, lymphocytes (B or T cells), myeloid cells (e.g., basophils, eosinophils, neutrophils, mast cells, macrophages) and platelets. The ability to decrease the quantity of blood cells or subsets of blood cells may be useful in the prevention, detection, diagnosis and/or treatment of leukocytoses, such as, for example eosinophilia.  
       [0937] The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be used to prevent, treat, or diagnose blood dyscrasia.  
       [0938] Anemias are conditions in which the number of red blood cells or amount of hemoglobin (the protein that carries oxygen) in them is below normal. Anemia may be caused by excessive bleeding, decreased red blood cell production, or increased red blood cell destruction (hemolysis). The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, and/or diagnosing anemias. Anemias that may be treated prevented or diagnosed by the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention include iron deficiency anemia, hypochromic anemia, microcytic anemia, chlorosis, hereditary siderob;astic anemia, idiopathic acquired sideroblastic anemia, red cell aplasia, megaloblastic anemia (e.g., pernicious anemia, (vitamin B12 deficiency) and folic acid deficiency anemia), aplastic anemia, hemolytic anemias (e.g., autoimmune helolytic anemia, microangiopathic hemolytic anemia, and paroxysmal nocturnal hemoglobinuria). The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, and/or diagnosing anemias associated with diseases including but not limited to, anemias associated with systemic lupus erythematosus, cancers, lymphomas, chronic renal disease, and enlarged spleens. The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, and/or diagnosing anemias arising from drug treatments such as anemias associated with methyldopa, dapsone, and/or sulfadrugs. Additionally, rhe polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, and/or diagnosing anemias associated with abnormal red blood cell architecture including but not limited to, hereditary spherocytosis, hereditary elliptocytosis, glucose-6-phosphate dehydrogenase deficiency, and sickle cell anemia.  
       [0939] The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, and/or diagnosing hemoglobin abnormalities, (e.g., those associated with sickle cell anemia, hemoglobin C disease, hemoglobin S-C disease, and hemoglobin E disease). Additionally, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating thalassemias, including, but not limited to major and minor forms of alpha-thalassemia and beta-thalassemia.  
       [0940] In another embodiment, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating bleeding disorders including, but not limited to, thrombocytopenia (e.g., idiopathic thrombocytopenic purpura, and thrombotic thrombocytopenic purpura), Von Willebrand&#39;s disease, hereditary platelet disorders (e.g., storage pool disease such as Chediak-Higashi and Hermansky-Pudlak syndromes, thromboxane A2 dysfunction, thromboasthenia, and Bernard-Soulier syndrome), hemolytic-uremic syndrome, hemophelias such as hemophelia A or Factor VII deficiency and Christmas disease or Factor IX deficiency, Hereditary Hemorhhagic Telangiectsia, also known as Rendu-Osler-Weber syndrome, allergic purpura (Henoch Schonlein purpura) and disseminated intravascular coagulation.  
       [0941] The effect of the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention on the clotting time of blood may be monitored using any of the clotting tests known in the art including, but not limited to, whole blood partial thromboplastin time (PTT), the activated partial thromboplastin time (aPTT), the activated clotting time (ACT), the recalcified activated clotting time, or the Lee-White Clotting time.  
       [0942] Several diseases and a variety of drugs can cause platelet dysfunction. Thus, in a specific embodiment, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating acquired platelet dysfunction such as platelet dysfunction accompanying kidney failure, leukemia, multiple myeloma, cirrhosis of the liver, and systemic lupus erythematosus as well as platelet dysfunction associated with drug treatments, including treatment with aspirin, ticlopidine, nonsteroidal anti-inflammatory drugs (used for arthritis, pain, and sprains), and penicillin in high doses.  
       [0943] In another embodiment, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating diseases and disorders characterized by or associated with increased or decreased numbers of white blood cells. Leukopenia occurs when the number of white blood cells decreases below normal. Leukopenias include, but are not limited to, neutropenia and lymphocytopenia. An increase in the number of white blood cells compared to normal is known as leukocytosis. The body generates increased numbers of white blood cells during infection. Thus, leukocytosis may simply be a normal physiological parameter that reflects infection. Alternatively, leukocytosis may be an indicator of injury or other disease such as cancer. Leokocytoses, include but are not limited to, eosinophilia, and accumulations of macrophages. In specific embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating leukopenia. In other specific embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating leukocytosis.  
       [0944] Leukopenia may be a generalized decreased in all types of white blood cells, or may be a specific depletion of particular types of white blood cells. Thus, in specific embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating decreases in neutrophil numbers, known as neutropenia. Neutropenias that may be diagnosed, prognosed, prevented, and/or treated by the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention include, but are not limited to, infantile genetic agranulocytosis, familial neutropenia, cyclic neutropenia, neutropenias resulting from or associated with dietary deficiencies (e.g., vitamin B 12 deficiency or folic acid deficiency), neutropenias resulting from or associated with drug treatments (e.g., antibiotic regimens such as penicillin treatment, sulfonamide treatment, anticoagulant treatment, anticonvulsant drugs, anti-thyroid drugs, and cancer chemotherapy), and neutropenias resulting from increased neutrophil destruction that may occur in association with some bacterial or viral infections, allergic disorders, autoimmune diseases, conditions in which an individual has an enlarged spleen (e.g., Felty syndrome, malaria and sarcoidosis), and some drug treatment regimens.  
       [0945] The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating lymphocytopenias (decreased numbers of B and/or T lymphocytes), including, but not limited lymphocytopenias resulting from or associated with stress, drug treatments (e.g., drug treatment with corticosteroids, cancer chemotherapies, and/or radiation therapies), AIDS infection and/or other diseases such as, for example, cancer, rheumatoid arthritis, systemic lupus erythematosus, chronic infections, some viral infections and/or hereditary disorders (e.g., DiGeorge syndrome, Wiskott-Aldrich Syndome, severe combined immunodeficiency, ataxia telangiectsia).  
       [0946] The polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating diseases and disorders associated with macrophage numbers and/or macrophage function including, but not limited to, Gaucher&#39;s disease, Niemann-Pick disease, Letterer-Siwe disease and Hand-Schuller-Christian disease.  
       [0947] In another embodiment, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating diseases and disorders associated with eosinophil numbers and/or eosinophil function including, but not limited to, idiopathic hypereosinophilic syndrome, eosinophilia-myalgia syndrome, and Hand-Schuller-Christian disease.  
       [0948] In yet another embodiment, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating leukemias and lymphomas including, but not limited to, acute lymphocytic (lymphpblastic) leukemia (ALL), acute myeloid (myelocytic, myelogenous, myeloblastic, or myelomonocytic) leukemia, chronic lymphocytic leukemia (e.g., B cell leukemias, T cell leukemias, Sezary syndrome, and Hairy cell leukenia), chronic myelocytic (myeloid, myelogenous, or granulocytic) leukemia, Hodgkin&#39;s lymphoma, non-hodgkin&#39;s lymphoma, Burkitt&#39;s lymphoma, and mycosis fungoides.  
       [0949] In other embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in diagnosing, prognosing, preventing, and/or treating diseases and disorders of plasma cells including, but not limited to, plasma cell dyscrasias, monoclonal gammaopathies, monoclonal gammopathies of undetermined significance, multiple myeloma, macroglobulinemia, Waldenstrom&#39;s macroglobulinemia, cryoglobulinemia, and Raynaud&#39;s phenomenon.  
       [0950] In other embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in treating, preventing, and/or diagnosing myeloproliferative disorders, including but not limited to, polycythemia vera, relative polycythemia, secondary polycythemia, myclofibrosis, acute myelofibrosis, agonogenic myelod metaplasia, thrombocythemia, (including both primary and seconday thrombocythemia) and chronic myelocytic leukemia.  
       [0951] In other embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful as a treatment prior to surgery, to increase blood cell production.  
       [0952] In other embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful as an agent to enhance the migration, phagocytosis, superoxide production, antibody dependent cellular cytotoxicity of neutrophils, eosionophils and macrophages.  
       [0953] In other embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful as an agent to increase the number of stem cells in circulation prior to stem cells pheresis. In another specific embodiment, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful as an agent to increase the number of stem cells in circulation prior to platelet pheresis.  
       [0954] In other embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful as an agent to increase cytokine production.  
       [0955] In other embodiments, the polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention may be useful in preventing, diagnosing, and/or treating primary hematopoietic disorders.  
       [0956] Hyperproliferative Disorders  
       [0957] In certain embodiments, polynucleotides or polypeptides, or agonists or antagonists of the present invention can be used to treat or detect hyperproliferative disorders, including neoplasms. Polynucleotides or polypeptides, or agonists or antagonists of the present invention may inhibit the proliferation of the disorder through direct or indirect interactions. Alternatively, Polynucleotides or polypeptides, or agonists or antagonists of the present invention may proliferate other cells which can inhibit the hyperproliferative disorder.  
       [0958] For example, by increasing an immune response, particularly increasing antigenic qualities of the hyperproliferative disorder or by proliferating, differentiating, or mobilizing T-cells, hyperproliferative disorders can be treated. This immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response. Alternatively, decreasing an immune response may also be a method of treating hyperproliferative disorders, such as a chemotherapeutic agent.  
       [0959] Examples of hyperproliferative disorders that can be treated or detected by polynucleotides or polypeptides, or agonists or antagonists of the present invention include, but are not limited to neoplasms located in the: colon, abdomen, bone, breast, digestive system, liver, pancreas, peritoneum, endocrine glands (adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid), eye, head and neck, nervous (central and peripheral), lymphatic system, pelvis, skin, soft tissue, spleen, thorax, and urogenital tract.  
       [0960] Similarly, other hyperproliferative disorders can also be treated or detected by polynucleotides or polypeptides, or agonists or antagonists of the present invention. Examples of such hyperproliferative disorders include, but are not limited to: Acute Childhood Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, Acute Lymphocytic Leukemia, Acute Myeloid Leukemia, Adrenocortical Carcinoma, Adult (Primary) Hepatocellular Cancer, Adult (Primary) Liver Cancer, Adult Acute Lymphocytic Leukemia, Adult Acute Myeloid Leukemia, Adult Hodgkin&#39;s Disease, Adult Hodgkin&#39;s Lymphoma, Adult Lymphocytic Leukemia, Adult Non-Hodgkin&#39;s Lymphoma, Adult Primary Liver Cancer, Adult Soft Tissue Sarcoma, AIDS-Related Lymphoma, AIDS-Related Malignancies, Anal Cancer, Astrocytoma, Bile Duct Cancer, Bladder Cancer, Bone Cancer, Brain Stem Glioma, Brain Tumors, Breast Cancer, Cancer of the Renal Pelvis and Ureter, Central Nervous System (Primary) Lymphoma, Central Nervous System Lymphoma, Cerebellar Astrocytoma, Cerebral Astrocytoma, Cervical Cancer, Childhood (Primary) Hepatocellular Cancer, Childhood (Primary) Liver Cancer, Childhood Acute Lymphoblastic Leukemia, Childhood Acute Myeloid Leukemia, Childhood Brain Stem Glioma, Childhood Cerebellar Astrocytoma, Childhood Cerebral Astrocytoma, Childhood Extracranial Germ Cell Tumors, Childhood Hodgkin&#39;s Disease, Childhood Hodgkin&#39;s Lymphoma, Childhood Hypothalamic and Visual Pathway Glioma, Childhood Lymphoblastic Leukemia, Childhood Medulloblastoma, Childhood Non-Hodgkin&#39;s Lymphoma, Childhood Pineal and Supratentorial Primitive Neuroectodermal Tumors, Childhood Primary Liver Cancer, Childhood Rhabdomyosarcoma, Childhood Soft Tissue Sarcoma, Childhood Visual Pathway and Hypothalamic Glioma, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Colon Cancer, Cutaneous T-Cell Lymphoma, Endocrine Pancreas Islet Cell Carcinoma, Endometrial Cancer, Ependymoma, Epithelial Cancer, Esophageal Cancer, Ewing&#39;s Sarcoma and Related Tumors, Exocrine Pancreatic Cancer, Extracranial Germ Cell Tumor, Extragonadal Germ Cell Tumor, Extrahepatic Bile Duct Cancer, Eye Cancer, Female Breast Cancer, Gaucher&#39;s Disease, Gallbladder Cancer, Gastric Cancer, Gastrointestinal Carcinoid Tumor, Gastrointestinal Tumors, Germ Cell Tumors, Gestational Trophoblastic Tumor, Hairy Cell Leukemia, Head and Neck Cancer, Hepatocellular Cancer, Hodgkin&#39;s Disease, Hodgkin&#39;s Lymphoma, Hypergammaglobulinemia, Hypopharyngeal Cancer, Intestinal Cancers, Intraocular Melanoma, Islet Cell Carcinoma, Islet Cell Pancreatic Cancer, Kaposi&#39;s Sarcoma, Kidney Cancer, Laryngeal Cancer, Lip and Oral Cavity Cancer, Liver Cancer, Lung Cancer, Lymphoproliferative Disorders, Macroglobulinemia, Male Breast Cancer, Malignant Mesothelioma, Malignant Thymoma, Medulloblastoma, Melanoma, Mesothelioma, Metastatic Occult Primary Squamous Neck Cancer, Metastatic Primary Squamous Neck Cancer, Metastatic Squamous Neck Cancer, Multiple Myeloma, Multiple Myeloma/Plasma Cell Neoplasm, Myelodysplastic Syndrome, Myelogenous Leukemia, Myeloid Leukemia, Myeloproliferative Disorders, Nasal Cavity and Paranasal Sinus Cancer, Nasopharyngeal Cancer, Neuroblastoma, Non-Hodgkin&#39;s Lymphoma During Pregnancy, Nonmelanoma Skin Cancer, Non-Small Cell Lung Cancer, Occult Primary Metastatic Squamous Neck Cancer, Oropharyngeal Cancer, Osteo-/Malignant Fibrous Sarcoma, Osteosarcoma/Malignant Fibrous Histiocytoma, Osteosarcoma/Malignant Fibrous Histiocytoma of Bone, Ovarian Epithelial Cancer, Ovarian Germ Cell Tumor, Ovarian Low Malignant Potential Tumor, Pancreatic Cancer, Paraproteinemias, Purpura, Parathyroid Cancer, Penile Cancer, Pheochromocytoma, Pituitary Tumor, Plasma Cell Neoplasm/Multiple Myeloma, Primary Central Nervous System Lymphoma, Primary Liver Cancer, Prostate Cancer, Rectal Cancer, Renal Cell Cancer, Renal Pelvis and Ureter Cancer, Retinoblastoma, Rhabdomyosarcoma, Salivary Gland Cancer, Sarcoidosis Sarcomas, Sezary Syndrome, Skin Cancer, Small Cell Lung Cancer, Small Intestine Cancer, Soft Tissue Sarcoma, Squamous Neck Cancer, Stomach Cancer, Supratentorial Primitive Neuroectodermal and Pineal Tumors, T-Cell Lymphoma, Testicular Cancer, Thymoma, Thyroid Cancer, Transitional Cell Cancer of the Renal Pelvis and Ureter, Transitional Renal Pelvis and Ureter Cancer, Trophoblastic Tumors, Ureter and Renal Pelvis Cell Cancer, Urethral Cancer, Uterine Cancer, Uterine Sarcoma, Vaginal Cancer, Visual Pathway and Hypothalamic Glioma, Vulvar Cancer, Waldenstrom&#39;s Macroglobulinemia, Wilms&#39; Tumor, and any other hyperproliferative disease, besides neoplasia, located in an organ system listed above.  
       [0961] In another preferred embodiment, polynucleotides or polypeptides, or agonists or antagonists of the present invention are used to diagnose, prognose, prevent, and/or treat premalignant conditions and to prevent progression to a neoplastic or malignant state, including but not limited to those disorders described above. Such uses are indicated in conditions known or suspected of preceding progression to neoplasia or cancer, in particular, where non-neoplastic cell growth consisting of hyperplasia, metaplasia, or most particularly, dysplasia has occurred (for review of such abnormal growth conditions, see Robbins and Angell, 1976, Basic Pathology, 2d Ed., W. B. Saunders Co., Philadelphia, pp. 68-79.)  
       [0962] Hyperplasia is a form of controlled cell proliferation, involving an increase in cell number in a tissue or organ, without significant alteration in structure or function. Hyperplastic disorders which can be diagnosed, prognosed, prevented, and/or treated with compositions of the invention (including polynucleotides, polypeptides, agonists or antagonists) include, but are not limited to, angiofollicular mediastinal lymph node hyperplasia, angiolymphoid hyperplasia with eosinophilia, atypical melanocytic hyperplasia, basal cell hyperplasia, benign giant lymph node hyperplasia, cementum hyperplasia, congenital adrenal hyperplasia, congenital sebaceous hyperplasia, cystic hyperplasia, cystic hyperplasia of the breast, denture hyperplasia, ductal hyperplasia, endometrial hyperplasia, fibromuscular hyperplasia, focal epithelial hyperplasia, gingival hyperplasia, inflammatory fibrous hyperplasia, inflammatory papillary hyperplasia, intravascular papillary endothelial hyperplasia, nodular hyperplasia of prostate, nodular regenerative hyperplasia, pseudoepitheliomatous hyperplasia, senile sebaceous hyperplasia, and verrucous hyperplasia.  
       [0963] Metaplasia is a form of controlled cell growth in which one type of adult or fully differentiated cell substitutes for another type of adult cell. Metaplastic disorders which can be diagnosed, prognosed, prevented, and/or treated with compositions of the invention (including polynucleotides, polypeptides, agonists or antagonists) include, but are not limited to, agnogenic myeloid metaplasia, apocrine metaplasia, atypical metaplasia, autoparenchymatous metaplasia, connective tissue metaplasia, epithelial metaplasia, intestinal metaplasia, metaplastic anemia, metaplastic ossification, metaplastic polyps, myeloid metaplasia, primary myeloid metaplasia, secondary myeloid metaplasia, squamous metaplasia, squamous metaplasia of amnion, and symptomatic myeloid metaplasia.  
       [0964] Dysplasia is frequently a forerunner of cancer, and is found mainly in the epithelia; it is the most disorderly form of non-neoplastic cell growth, involving a loss in individual cell uniformity and in the architectural orientation of cells. Dysplastic cells often have abnormally large, deeply stained nuclei, and exhibit pleomorphism. Dysplasia characteristically occurs where there exists chronic irritation or inflammation. Dysplastic disorders which can be diagnosed, prognosed, prevented, and/or treated with compositions of the invention (including polynucleotides, polypeptides, agonists or antagonists) include, but are not limited to, anhidrotic ectodermal dysplasia, anterofacial dysplasia, asphyxiating thoracic dysplasia, atriodigital dysplasia, bronchopulmonary dysplasia, cerebral dysplasia, cervical dysplasia, chondroectodermal dysplasia, cleidocranial dysplasia, congenital ectodermal dysplasia, craniodiaphysial dysplasia, craniocarpotarsal dysplasia, craniometaphysial dysplasia, dentin dysplasia, diaphysial dysplasia, ectodermal dysplasia, enamel dysplasia, encephalo-ophthalmic dysplasia, dysplasia epiphysialis hemimelia, dysplasia epiphysialis multiplex, dysplasia epiphysialis punctata, epithelial dysplasia, faciodigitogenital dysplasia, familial fibrous dysplasia of jaws, familial white folded dysplasia, fibromuscular dysplasia, fibrous dysplasia of bone, florid osseous dysplasia, hereditary renal-retinal dysplasia, hidrotic ectodermal dysplasia, hypohidrotic ectodermal dysplasia, lymphopenic thymic dysplasia, mammary dysplasia, mandibulofacial dysplasia, metaphysial dysplasia, Mondini dysplasia, monostotic fibrous dysplasia, mucoepithelial dysplasia, multiple epiphysial dysplasia, oculoauriculovertebral dysplasia, oculodentodigital dysplasia, oculovertebral dysplasia, odontogenic dysplasia, ophthalmomandibulomelic dysplasia, periapical cemental dysplasia, polyostotic fibrous dysplasia, pseudoachondroplastic spondyloepiphysial dysplasia, retinal dysplasia, septo-optic dysplasia, spondyloepiphysial dysplasia, and ventriculoradial dysplasia.  
       [0965] Additional pre-neoplastic disorders which can be diagnosed, prognosed, prevented, and/or treated with compositions of the invention (including polynucleotides, polypeptides, agonists or antagonists) include, but are not limited to, benign dysproliferative disorders (e.g., benign tumors, fibrocystic conditions, tissue hypertrophy, intestinal polyps, colon polyps, and esophageal dysplasia), leukoplakia, keratoses, Bowen&#39;s disease, Farmer&#39;s Skin, solar cheilitis, and solar keratosis.  
       [0966] In another embodiment, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to diagnose and/or prognose disorders associated with the tissue(s) in which the polypeptide of the invention is expressed, including one, two, three, four, five, or more tissues disclosed in Table 3, column 2 (Library Code).  
       [0967] In another embodiment, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention conjugated to a toxin or a radioactive isotope, as described herein, may be used to treat cancers and neoplasms, including, but not limited to those described herein. In a further preferred embodiment, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention conjugated to a toxin or a radioactive isotope, as described herein, may be used to treat acute myelogenous leukemia.  
       [0968] Additionally, polynucleotides, polypeptides, and/or agonists or antagonists of the invention may affect apoptosis, and therefore, would be useful in treating a number of diseases associated with increased cell survival or the inhibition of apoptosis. For example, diseases associated with increased cell survival or the inhibition of apoptosis that could be diagnosed, prognosed, prevented, and/or treated by polynucleotides, polypeptides, and/or agonists or antagonists of the invention, include cancers (such as follicular lymphomas, carcinomas with p53 mutations, and hormone-dependent tumors, including, but not limited to 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, breast cancer, prostate cancer, Kaposi&#39;s sarcoma and ovarian cancer); autoimmune disorders such as, multiple sclerosis, Sjogren&#39;s syndrome, Hashimoto&#39;s thyroiditis, biliary cirrhosis, Behcet&#39;s disease, Crohn&#39;s disease, polymyositis, systemic lupus erythematosus and immune-related glomerulonephritis and rheumatoid arthritis) and viral infections (such as herpes viruses, pox viruses and adenoviruses), inflammation, graft v. host disease, acute graft rejection, and chronic graft rejection.  
       [0969] In preferred embodiments, polynucleotides, polypeptides, and/or agonists or antagonists of the invention are used to inhibit growth, progression, and/or metastasis of cancers, in particular those listed above.  
       [0970] Additional diseases or conditions associated with increased cell survival that could be diagnosed, prognosed, prevented, and/or treated by polynucleotides, polypeptides, and/or agonists or antagonists of the invention, include, but are not limited to, progression, and/or metastases of malignancies and related disorders such as leukemia (including acute leukemias (e.g., acute lymphocytic leukemia, acute myelocytic leukemia (including myeloblastic, promyelocytic, myclomonocytic, monocytic, and erythroleukemia)) and chronic leukemias (e.g., chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia)), polycythemia vera, lymphomas (e.g., Hodgkin&#39;s disease and non-Hodgkin&#39;s disease), multiple myeloma, Waldenstrom&#39;s macroglobulinemia, heavy chain disease, and solid tumors including, but not limited to, sarcomas and carcinomas such as fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing&#39;s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm&#39;s tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, emangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma, and retinoblastoma.  
       [0971] Diseases associated with increased apoptosis that could be diagnosed, prognosed, prevented, and/or treated by polynucleotides, polypeptides, and/or agonists or antagonists of the invention, include AIDS; neurodegenerative disorders (such as Alzheimer&#39;s disease, Parkinson&#39;s disease, amyotrophic lateral sclerosis, retinitis pigmentosa, cerebellar degeneration and brain tumor or prior associated disease); autoimmune disorders (such as, multiple sclerosis, Sjogren&#39;s syndrome, Hashimoto&#39;s thyroiditis, biliary cirrhosis, Behcet&#39;s disease, Crohn&#39;s disease, polymyositis, systemic lupus erythematosus and immune-related glomerulonephritis and rheumatoid arthritis) myelodysplastic syndromes (such as aplastic anemia), graft v. host disease, ischemic injury (such as that caused by myocardial infarction, stroke and reperfusion injury), liver injury (e.g., hepatitis related liver injury, ischemia/reperfusion injury, cholestosis (bile duct injury) and liver cancer); toxin-induced liver disease (such as that caused by alcohol), septic shock, cachexia and anorexia.  
       [0972] Hyperproliferative diseases and/or disorders that could be diagnosed, prognosed, prevented, and/or treated by polynucleotides, polypeptides, and/or agonists or antagonists of the invention, include, but are not limited to, neoplasms located in the liver, abdomen, bone, breast, digestive system, pancreas, peritoneum, endocrine glands (adrenal, parathyroid, pituitary, testicles, ovary, thymus, thyroid), eye, head and neck, nervous system (central and peripheral), lymphatic system, pelvis, skin, soft tissue, spleen, thorax, and urogenital tract.  
       [0973] Similarly, other hyperproliferative disorders can also be diagnosed, prognosed, prevented, and/or treated by polynucleotides, polypeptides, and/or agonists or antagonists of the invention. Examples of such hyperproliferative disorders include, but are not limited to: hypergammaglobulinemia, lymphoproliferative disorders, paraproteinemias, purpura, sarcoidosis, Sezary Syndrome, Waldenstron&#39;s macroglobulinemia, Gaucher&#39;s Disease, histiocytosis, and any other hyperproliferative disease, besides neoplasia, located in an organ system listed above.  
       [0974] Another preferred embodiment utilizes polynucleotides of the present invention to inhibit aberrant cellular division, by gene therapy using the present invention, and/or protein fusions or fragments thereof.  
       [0975] Thus, the present invention provides a method for treating cell proliferative disorders by inserting into an abnormally proliferating cell a polynucleotide of the present invention, wherein said polynucleotide represses said expression.  
       [0976] Another embodiment of the present invention provides a method of treating cell-proliferative disorders in individuals comprising administration of one or more active gene copies of the present invention to an abnormally proliferating cell or cells. In a preferred embodiment, polynucleotides of the present invention is a DNA construct comprising a recombinant expression vector effective in expressing a DNA sequence encoding said polynucleotides. In another preferred embodiment of the present invention, the DNA construct encoding the poynucleotides of the present invention is inserted into cells to be treated utilizing a retrovirus, or more preferably an adenoviral vector (See G J. Nabel, et. al., PNAS 1999 96: 324-326, which is hereby incorporated by reference). In a most preferred embodiment, the viral vector is defective and will not transform non-proliferating cells, only proliferating cells. Moreover, in a preferred embodiment, the polynucleotides of the present invention inserted into proliferating cells either alone, or in combination with or fused to other polynucleotides, can then be modulated via an external stimulus (i.e. magnetic, specific small molecule, chemical, or drug administration, etc.), which acts upon the promoter upstream of said polynucleotides to induce expression of the encoded protein product. As such the beneficial therapeutic affect of the present invention may be expressly modulated (i.e. to increase, decrease, or inhibit expression of the present invention) based upon said external stimulus.  
       [0977] Polynucleotides of the present invention may be useful in repressing expression of oncogenic genes or antigens. By “repressing expression of the oncogenic genes” is intended the suppression of the transcription of the gene, the degradation of the gene transcript (pre-message RNA), the inhibition of splicing, the destruction of the messenger RNA, the prevention of the post-translational modifications of the protein, the destruction of the protein, or the inhibition of the normal function of the protein.  
       [0978] For local administration to abnormally proliferating cells, polynucleotides of the present invention may be administered by any method known to those of skill in the art including, but not limited to transfection, electroporation, microinjection of cells, or in vehicles such as liposomes, lipofectin, or as naked polynucleotides, or any other method described throughout the specification. The polynucleotide of the present invention may be delivered by known gene delivery systems such as, but not limited to, retroviral vectors (Gilboa, J. Virology 44:845 (1982); Hocke, Nature 320:275 (1986); Wilson, et al., Proc. Natl. Acad. Sci. U.S.A. 85:3014), vaccinia virus system (Chakrabarty et al., Mol. Cell Biol. 5:3403 (1985) or other efficient DNA delivery systems (Yates et al., Nature 313:812 (1985)) known to those skilled in the art. These references are exemplary only and are hereby incorporated by reference. In order to specifically deliver or transfect cells which are abnormally proliferating and spare non-dividing cells, it is preferable to utilize a retrovirus, or adenoviral (as described in the art and elsewhere herein) delivery system known to those of skill in the art. Since host DNA replication is required for retroviral DNA to integrate and the retrovirus will be unable to self replicate due to the lack of the retrovirus genes needed for its life cycle. Utilizing such a retroviral delivery system for polynucleotides of the present invention will target said gene and constructs to abnormally proliferating cells and will spare the non-dividing normal cells.  
       [0979] The polynucleotides of the present invention may be delivered directly to cell proliferative disorder/disease sites in internal organs, body cavities and the like by use of imaging devices used to guide an injecting needle directly to the disease site. The polynucleotides of the present invention may also be administered to disease sites at the time of surgical intervention.  
       [0980] By “cell proliferative disease” is meant any human or animal disease or disorder, affecting any one or any combination of organs, cavities, or body parts, which is characterized by single or multiple local abnormal proliferations of cells, groups of cells, or tissues, whether benign or malignant.  
       [0981] Any amount of the polynucleotides of the present invention may be administered as long as it has a biologically inhibiting effect on the proliferation of the treated cells. Moreover, it is possible to administer more than one of the polynucleotide of the present invention simultaneously to the same site. By “biologically inhibiting” is meant partial or total growth inhibition as well as decreases in the rate of proliferation or growth of the cells. The biologically inhibitory dose may be determined by assessing the effects of the polynucleotides of the present invention on target malignant or abnormally proliferating cell growth in tissue culture, tumor growth in animals and cell cultures, or any other method known to one of ordinary skill in the art.  
       [0982] The present invention is further directed to antibody-based therapies which involve administering of anti-polypeptides and anti-polynucleotide antibodies to a mammalian, preferably human, patient for treating one or more of the described disorders. Methods for producing anti-polypeptides and anti-polynucleotide antibodies polyclonal and monoclonal antibodies are described in detail elsewhere herein. Such antibodies may be provided in pharmaceutically acceptable compositions as known in the art or as described herein.  
       [0983] A summary of the ways in which the antibodies of the present invention may be used therapeutically includes binding polynucleotides or polypeptides of the present invention locally or systemically in the body or by direct cytotoxicity of the antibody, e.g. as mediated by complement (CDC) or by effector cells (ADCC). Some of these approaches are described in more detail below. Armed with the teachings provided herein, one of ordinary skill in the art will know how to use the antibodies of the present invention for diagnostic, monitoring or therapeutic purposes without undue experimentation.  
       [0984] In particular, the antibodies, fragments and derivatives of the present invention are useful for treating a subject having or developing cell proliferative and/or differentiation disorders as described herein. Such treatment comprises administering a single or multiple doses of the antibody, or a fragment, derivative, or a conjugate thereof.  
       [0985] The antibodies of this invention may be advantageously utilized in combination with other monoclonal or chimeric antibodies, or with lymphokines or hematopoietic growth factors, for example., which serve to increase the number or activity of effector cells which interact with the antibodies.  
       [0986] It is preferred to use high affinity and/or potent in vivo inhibiting and/or neutralizing antibodies against polypeptides or polynucleotides of the present invention, fragments or regions thereof, for both immunoassays directed to and therapy of disorders related to polynucleotides or polypeptides, including fragements thereof, of the present invention. Such antibodies, fragments, or regions, will preferably have an affinity for polynucleotides or polypeptides, including fragements thereof. Preferred binding affinities include those with a dissociation constant or Kd less than 5×10 −6 M, 10 −6 M, 5×10 −7 M, 10 −7 M, 5×10 −8 M, 10 −8 M, 5×10 −9 M, 10 −9 M, 5×10 −10 M, 10 −10 M, 5×10 −11 M, 10 −11 M, 5×10 −12 M, 10 −12 M, 5×10 −13 M, 10 −13 M, 5×10 −14 M, 10 −14 M, 5×10 −15 M, or 10 −15 M.  
       [0987] Moreover, polypeptides of the present invention are useful in inhibiting the angiogenesis of proliferative cells or tissues, either alone, as a protein fusion, or in combination with other polypeptides directly or indirectly, as described elsewhere herein. In a most preferred embodiment, said anti-angiogenesis effect may be achieved indirectly, for example, through the inhibition of hematopoietic, tumor-specific cells, such as tumor-associated macrophages (See Joseph I B, et al. J Natl Cancer Inst, 90(21):1648-53 (1998), which is hereby incorporated by reference). Antibodies directed to polypeptides or polynucleotides of the present invention may also result in inhibition of angiogenesis directly, or indirectly (See Witte L, et al., Cancer Metastasis Rev. 17(2):155-61 (1998), which is hereby incorporated by reference)).  
       [0988] Polypeptides, including protein fusions, of the present invention, or fragments thereof may be useful in inhibiting proliferative cells or tissues through the induction of apoptosis. Said polypeptides may act either directly, or indirectly to induce apoptosis of proliferative cells and tissues, for example in the activation of a death-domain receptor, such as tumor necrosis factor (TNF) receptor-1, CD95 (Fas/APO-1), TNF-receptor-related apoptosis-mediated protein (TRAMP) and TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 and -2 (See Schulze-Osthoff K, et.al., Eur J Biochem 254(3):439-59 (1998), which is hereby incorporated by reference). Moreover, in another preferred embodiment of the present invention, said polypeptides may induce apoptosis through other mechanisms, such as in the activation of other proteins which will activate apoptosis, or through stimulating the expression of said proteins, either alone or in combination with small molecule drugs or adjuviants, such as apoptonin, galectins, thioredoxins, anti-inflammatory proteins (See for example, Mutat Res 400(1-2):447-55 (1998), Med Hypotheses.50(5):423-33 (1998), Chem Biol Interact. April 24;111-112:23-34 (1998), J Mol Med.76(6):402-12 (1998), Int J Tissue React;20(1):3-15 (1998), which are all he incorporated by reference).  
       [0989] Polypeptides, including protein fusions to, or fragments thereof, of the present invention are useful in inhibiting the metastasis of proliferative cells or tissues. Inhibition may occur as a direct result of administering polypeptides, or antibodies directed to said polypeptides as described elsewere herein, or indirectly, such as activating the expression of proteins known to inhibit metastasis, for example alpha 4 integrins, (See, e.g., Curr Top Microbiol Immunol 1998;231:125-41, which is hereby incorporated by reference). Such thereapeutic affects of the present invention may be achieved either alone, or in combination with small molecule drugs or adjuvants.  
       [0990] In another embodiment, the invention provides a method of delivering compositions containing the polypeptides of the invention (e.g., compositions containing polypeptides or polypeptide antibodes associated with heterologous polypeptides, heterologous nucleic acids, toxins, or prodrugs) to targeted cells expressing the polypeptide of the present invention. Polypeptides or polypeptide antibodes of the invention may be associated with with heterologous polypeptides, heterologous nucleic acids, toxins, or prodrugs via hydrophobic, hydrophilic, ionic and/or covalent interactions.  
       [0991] Polypeptides, protein fusions to, or fragments thereof, of the present invention are useful in enhancing the immunogenicity and/or antigenicity of proliferating cells or tissues, either directly, such as would occur if the polypeptides of the present invention ‘vaccinated’ the immune response to respond to proliferative antigens and immunogens, or indirectly, such as in activating the expression of proteins known to enhance the immune response (e.g. chemokines), to said antigens and immunogens.  
       [0992] Renal Disorders  
       [0993] Polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention, may be used to treat, prevent, diagnose, and/or prognose disorders of the renal system. Renal disorders which can be diagnosed, prognosed, prevented, and/or treated with compositions of the invention include, but are not limited to, kidney failure, nephritis, blood vessel disorders of kidney, metabolic and congenital kidney disorders, urinary disorders of the kidney, autoimmune disorders, sclerosis and necrosis, electrolyte imbalance, and kidney cancers.  
       [0994] Kidney diseases which can be diagnosed, prognosed, prevented, and/or treated with compositions of the invention include, but are not limited to, acute kidney failure, chronic kidney failure, atheroembolic renal failure, end-stage renal disease, inflammatory diseases of the kidney (e.g., acute glomerulonephritis, postinfectious glomerulonephritis, rapidly progressive glomerulonephritis, nephrotic syndrome, membranous glomerulonephritis, familial nephrotic syndrome, membranoproliferative glomerulonephritis I and II, mesangial proliferative glomerulonephritis, chronic glomerulonephritis, acute tubulointerstitial nephritis, chronic tubulointerstitial nephritis, acute post-streptococcal glomerulonephritis (PSGN), pyelonephritis, lupus nephritis, chronic nephritis, interstitial nephritis, and post-streptococcal glomerulonephritis), blood vessel disorders of the kidneys (e.g., kidney infarction, atheroembolic kidney disease, cortical necrosis, malignant nephrosclerosis, renal vein thrombosis, renal underperfusion, renal retinopathy, renal ischemia-reperfusion, renal artery embolism, and renal artery stenosis), and kidney disorders resulting form urinary tract disease (e.g., pyelonephritis, hydronephrosis, urolithiasis (renal lithiasis, nephrolithiasis), reflux nephropathy, urinary tract infections, urinary retention, and acute or chronic unilateral obstructive uropathy.)  
       [0995] In addition, compositions of the invention can be used to diagnose, prognose, prevent, and/or treat metabolic and congenital disorders of the kidney (e.g., uremia, renal amyloidosis, renal osteodystrophy, renal tubular acidosis, renal glycosuria, nephrogenic diabetes insipidus, cystinuria, Fanconi&#39;s syndrome, renal fibrocystic osteosis (renal rickets), Hartnup disease, Bartter&#39;s syndrome, Liddle&#39;s syndrome, polycystic kidney disease, medullary cystic disease, medullary sponge kidney, Alport&#39;s syndrome, nail-patella syndrome, congenital nephrotic syndrome, CRUSH syndrome, horseshoe kidney, diabetic nephropathy, nephrogenic diabetes insipidus, analgesic nephropathy, kidney stones, and membranous nephropathy), and autoimmune disorders of the kidney (e.g., systemic lupus erythematosus (SLE), Goodpasture syndrome, IgA nephropathy, and IgM mesangial proliferative glomerulonephritis).  
       [0996] Compositions of the invention can also be used to diagnose, prognose, prevent, and/or treat sclerotic or necrotic disorders of the kidney (e.g., glomerulosclerosis, diabetic nephropathy, focal segmental glomerulosclerosis (FSGS), necrotizing glomerulonephritis, and renal papillary necrosis), cancers of the kidney (e.g., nephroma, hypemephroma, nephroblastoma, renal cell cancer, transitional cell cancer, renal adenocarcinoma, squamous cell cancer, and Wilm&#39;s tumor), and electrolyte imbalances (e.g., nephrocalcinosis, pyuria, edema, hydronephritis, proteinuria, hyponatremia, hypernatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypophosphatemia, and hyperphosphatemia).  
       [0997] Polypeptides may be administered using any method known in the art, including, but not limited to, direct needle injection at the delivery site, intravenous injection, topical administration, catheter infusion, biolistic injectors, particle accelerators, gelfoam sponge depots, other commercially available depot materials, osmotic pumps, oral or suppositorial solid pharmaceutical formulations, decanting or topical applications during surgery, aerosol delivery. Such methods are known in the art. Polypeptides may be administered as part of a Therapeutic, described in more detail below. Methods of delivering polynucleotides are described in more detail herein.  
       [0998] Cardiovascular Disorders  
       [0999] Polynucleotides or polypeptides, or agonists or antagonists of the present invention, may be used to treat, prevent, diagnose, and/or prognose cardiovascular disorders, including, but not limited to, peripheral artery disease, such as limb ischemia.  
       [1000] Cardiovascular disorders include, but are not limited to, cardiovascular abnormalities, such as arterio-arterial fistula, arteriovenous fistula, cerebral arteriovenous malformations, congenital heart defects, pulmonary atresia, and Scimitar Syndrome. Congenital heart defects include, but are not limited to, aortic coarctation, cor triatriatum, coronary vessel anomalies, crisscross heart, dextrocardia, patent ductus arteriosus, Ebstein&#39;s anomaly, Eisenmenger complex, hypoplastic left heart syndrome, levocardia, tetralogy of fallot, transposition of great vessels, double outlet right ventricle, tricuspid atresia, persistent truncus arteriosus, and heart septal defects, such as aortopulmonary septal defect, endocardial cushion defects, Lutembacher&#39;s Syndrome, trilogy of Fallot, ventricular heart septal defects.  
       [1001] Cardiovascular disorders also include, but are not limited to, heart disease, such as arrhythmias, carcinoid heart disease, high cardiac output, low cardiac output, cardiac tamponade, endocarditis (including bacterial), heart aneurysm, cardiac arrest, congestive heart failure, congestive cardiomyopathy, paroxysmal dyspnea, cardiac edema, heart hypertrophy, congestive cardiomyopathy, left ventricular hypertrophy, right ventricular hypertrophy, post-infarction heart rupture, ventricular septal rupture, heart valve diseases, myocardial diseases, myocardial ischemia, pericardial effusion, pericarditis (including constrictive and tuberculous), pneumopericardium, postpericardiotomy syndrome, pulmonary heart disease, rheumatic heart disease, ventricular dysfunction, hyperemia, cardiovascular pregnancy complications, Scimitar Syndrome, cardiovascular syphilis, and cardiovascular tuberculosis.  
       [1002] Arrhythmias include, but are not limited to, sinus arrhythmia, atrial fibrillation, atrial flutter, bradycardia, extrasystole, Adams-Stokes Syndrome, bundle-branch block, sinoatrial block, long QT syndrome, parasystole, Lown-Ganong-Levine Syndrome, Mahaim-type pre-excitation syndrome, Wolff-Parkinson-White syndrome, sick sinus syndrome, tachycardias, and ventricular fibrillation. Tachycardias include paroxysmal tachycardia, supraventricular tachycardia, accelerated idioventricular rhythm, atrioventricular nodal reentry tachycardia, ectopic atrial tachycardia, ectopic junctional tachycardia, sinoatrial nodal reentry tachycardia, sinus tachycardia, Torsades de Pointes, and ventricular tachycardia.  
       [1003] Heart valve diseases include, but are not limited to, aortic valve insufficiency, aortic valve stenosis, hear murmurs, aortic valve prolapse, mitral valve prolapse, tricuspid valve prolapse, mitral valve insufficiency, mitral valve stenosis, pulmonary atresia, pulmonary valve insufficiency, pulmonary valve stenosis, tricuspid atresia, tricuspid valve insufficiency, and tricuspid valve stenosis.  
       [1004] Myocardial diseases include, but are not limited to, alcoholic cardiomyopathy, congestive cardiomyopathy, hypertrophic cardiomyopathy, aortic subvalvular stenosis, pulmonary subvalvular stenosis, restrictive cardiomyopathy, Chagas cardiomyopathy, endocardial fibroelastosis, endomyocardial fibrosis, Kearns Syndrome, myocardial reperfusion injury, and myocarditis.  
       [1005] Myocardial ischemias include, but are not limited to, coronary disease, such as angina pectoris, coronary aneurysm, coronary arteriosclerosis, coronary thrombosis, coronary vasospasm, myocardial infarction and myocardial stunning.  
       [1006] Cardiovascular diseases also include vascular diseases such as aneurysms, angiodysplasia, angiomatosis, bacillary angiomatosis, Hippel-Lindau Disease, Klippel-Trenaunay-Weber Syndrome, Sturge-Weber Syndrome, angioneurotic edema, aortic diseases, Takayasu&#39;s Arteritis, aortitis, Leriche&#39;s Syndrome, arterial occlusive diseases, arteritis, enarteritis, polyarteritis nodosa, cerebrovascular disorders, diabetic angiopathies, diabetic retinopathy, embolisms, thrombosis, erythromelalgia, hemorrhoids, hepatic veno-occlusive disease, hypertension, hypotension, ischemia, peripheral vascular diseases, phlebitis, pulmonary veno-occlusive disease, Raynaud&#39;s disease, CREST syndrome, retinal vein occlusion, Scimitar syndrome, superior vena cava syndrome, telangiectasia, atacia telangiectasia, hereditary hemorrhagic telangiectasia, varicocele, varicose veins, varicose ulcer, vasculitis, and venous insufficiency.  
       [1007] Aneurysms include, but are not limited to, dissecting aneurysms, false aneurysms, infected aneurysms, ruptured aneurysms, aortic aneurysms, cerebral aneurysms, coronary aneurysms, heart aneurysms, and iliac aneurysms.  
       [1008] Arterial occlusive diseases include, but are not limited to, arteriosclerosis, intermittent claudication, carotid stenosis, fibromuscular dysplasias, mesenteric vascular occlusion, Moyamoya disease, renal artery obstruction, retinal artery occlusion, and thromboangiitis obliterans.  
       [1009] Cerebrovascular disorders include, but are not limited to, carotid artery diseases, cerebral amyloid angiopathy, cerebral aneurysm, cerebral anoxia, cerebral arteriosclerosis, cerebral arteriovenous malformation, cerebral artery diseases, cerebral embolism and thrombosis, carotid artery thrombosis, sinus thrombosis, Wallenberg&#39;s syndrome, cerebral hemorrhage, epidural hematoma, subdural hematoma, subaraxhnoid hemorrhage, cerebral infarction, cerebral ischemia (including transient), subclavian steal syndrome, periventricular leukomalacia, vascular headache, cluster headache, migraine, and vertebrobasilar insufficiency.  
       [1010] Embolisms include, but are not limited to, air embolisms, amniotic fluid embolisms, cholesterol embolisms, blue toe syndrome, fat embolisms, pulmonary embolisms, and thromoboembolisms. Thrombosis include, but are not limited to, coronary thrombosis, hepatic vein thrombosis, retinal vein occlusion, carotid artery thrombosis, sinus thrombosis, Wallenberg&#39;s syndrome, and thrombophlebitis.  
       [1011] Ischemic disorders include, but are not limited to, cerebral ischemia, ischemic colitis, compartment syndromes, anterior compartment syndrome, myocardial ischemia, reperfusion injuries, and peripheral limb ischemia. Vasculitis includes, but is not limited to, aortitis, arteritis, Behcet&#39;s Syndrome, Churg-Strauss Syndrome, mucocutaneous lymph node syndrome, thromboangiitis obliterans, hypersensitivity vasculitis, Schoenlein-Henoch purpura, allergic cutaneous vasculitis, and Wegener&#39;s granulomatosis.  
       [1012] Polypeptides may be administered using any method known in the art, including, but not limited to, direct needle injection at the delivery site, intravenous injection, topical administration, catheter infusion, biolistic injectors, particle accelerators, gelfoam sponge depots, other commercially available depot materials, osmotic pumps, oral or suppositorial solid pharmaceutical formulations, decanting or topical applications during surgery, aerosol delivery. Such methods are known in the art. Polypeptides may be administered as part of a Therapeutic, described in more detail below. Methods of delivering polynucleotides are described in more detail herein.  
       [1013] Respiratory Disorders  
       [1014] Polynucleotides or polypeptides, or agonists or antagonists of the present invention may be used to treat, prevent, diagnose, and/or prognose diseases and/or disorders of the respiratory system.  
       [1015] Diseases and disorders of the respiratory system include, but are not limited to, nasal vestibulitis, nonallergic rhinitis (e.g., acute rhinitis, chronic rhinitis, atrophic rhinitis, vasomotor rhinitis), nasal polyps, and sinusitis, juvenile angiofibromas, cancer of the nose and juvenile papillomas, vocal cord polyps, nodules (singer&#39;s nodules), contact ulcers, vocal cord paralysis, laryngoceles, pharyngitis (e.g., viral and bacterial), tonsillitis, tonsillar cellulitis, parapharyngeal abscess, laryngitis, laryngoceles, and throat cancers (e.g., cancer of the nasopharynx, tonsil cancer, larynx cancer), lung cancer (e.g., squamous cell carcinoma, small cell (oat cell) carcinoma, large cell carcinoma, and adenocarcinoma), allergic disorders (eosinophilic pneumonia, hypersensitivity pneumonitis (e.g., extrinsic allergic alveolitis, allergic interstitial pneumonitis, organic dust pneumoconiosis, allergic bronchopulmonary aspergillosis, asthma, Wegener&#39;s granulomatosis (granulomatous vasculitis), Goodpasture&#39;s syndrome)), pneumonia (e.g., bacterial pneumonia (e.g.,  Streptococcus pneumoniae  (pneumoncoccal pneumonia),  Staphylococcus aureus  (staphylococcal pneumonia), Gram-negative bacterial pneumonia (caused by, e.g., Klebsiella and Pseudomas spp.),  Mycoplasma pneumoniae  pneumonia,  Hemophilus influenzae  pneumonia,  Legionella pneumophila  (Legionnaires&#39; disease), and  Chlamydia psittaci  (Psittacosis)), and viral pneumonia (e.g., influenza, chickenpox (varicella).  
       [1016] Additional diseases and disorders of the respiratory system include, but are not limited to bronchiolitis, polio (poliomyelitis), croup, respiratory syncytial viral infection, mumps, erythema infectiosum (fifth disease), roseola infantum, progressive rubella panencephalitis, german measles, and subacute sclerosing panencephalitis), fungal pneumonia (e.g., Histoplasmosis, Coccidioidomycosis, Blastomycosis, fungal infections in people with severely suppressed immune systems (e.g., cryptococcosis, caused by  Cryptococcus neoformans;  aspergillosis, caused by Aspergillus spp.; candidiasis, caused by Candida; and mucormycosis)),  Pneumocystis carinii  (pneumocystis pneumonia), atypical pneumonias (e.g., Mycoplasma and Chlamydia spp.), opportunistic infection pneumonia, nosocomial pneumonia, chemical pneumonitis, and aspiration pneumonia, pleural disorders (e.g., pleurisy, pleural effusion, and pneumothorax (e.g., simple spontaneous pneumothorax, complicated spontaneous pneumothorax, tension pneumothorax)), obstructive airway diseases (e.g., asthma, chronic obstructive pulmonary disease (COPD), emphysema, chronic or acute bronchitis), occupational lung diseases (e.g., silicosis, black lung (coal workers&#39; pneumoconiosis), asbestosis, berylliosis, occupational asthsma, byssinosis, and benign pneumoconioses), Infiltrative Lung Disease (e.g., pulmonary fibrosis (e.g., fibrosing alveolitis, usual interstitial pneumonia), idiopathic pulmonary fibrosis, desquamative interstitial pneumonia, lymphoid interstitial pneumonia, histiocytosis X (e.g., Letterer-Siwe disease, Hand-Schüller-Christian disease, eosinophilic granuloma), idiopathic pulmonary hemosiderosis, sarcoidosis and pulmonary alveolar proteinosis), Acute respiratory distress syndrome (also called, e.g., adult respiratory distress syndrome), edema, pulmonary embolism, bronchitis (e.g., viral, bacterial), bronchiectasis, atelectasis, lung abscess (caused by, e.g.,  Staphylococcus aureus  or  Legionella pneumophila ), and cystic fibrosis.  
       [1017] Anti-Angiogenesis Activity  
       [1018] The naturally occurring balance between endogenous stimulators and inhibitors of angiogenesis is one in which inhibitory influences predominate. Rastinejad et al.,  Cell  56:345-355 (1989). In those rare instances in which neovascularization occurs under normal physiological conditions, such as wound healing, organ regeneration, embryonic development, and female reproductive processes, angiogenesis is stringently regulated and spatially and temporally delimited. Under conditions of pathological angiogenesis such as that characterizing solid tumor growth, these regulatory controls fail. Unregulated angiogenesis becomes pathologic and sustains progression of many neoplastic and non-neoplastic diseases. A number of serious diseases are dominated by abnormal neovascularization including solid tumor growth and metastases, arthritis, some types of eye disorders, and psoriasis. See, e.g., reviews by Moses et al.,  Biotech.  9:630-634 (1991); Folkman et al.,  N. Engl. J. Med.,  333:1757-1763 (1995); Auerbach et al.,  J. Microvasc. Res.  29:401-411 (1985); Folkman, Advances in Cancer Research, eds. Klein and Weinhouse, Academic Press, New York, pp. 175-203 (1985); Patz,  Am. J. Opthalmol.  94:715-743 (1982); and Folkman et al., Science 221:719-725 (1983). In a number of pathological conditions, the process of angiogenesis contributes to the disease state. For example, significant data have accumulated which suggest that the growth of solid tumors is dependent on angiogenesis. Folkman and Klagsbrun,  Science  235:442-447 (1987).  
       [1019] The present invention provides for treatment of diseases or disorders associated with neovascularization by administration of the polynucleotides and/or polypeptides of the invention, as well as agonists or antagonists of the present invention. Malignant and metastatic conditions which can be treated with the polynucleotides and polypeptides, or agonists or antagonists of the invention include, but are not limited to, malignancies, solid tumors, and cancers described herein and otherwise known in the art (for a review of such disorders, see Fishman et al., Medicine, 2d Ed., J. B. Lippincott Co., Philadelphia (1985)). Thus, the present invention provides a method of treating an angiogenesis-related disease and/or disorder, comprising administering to an individual in need thereof a therapeutically effective amount of a polynucleotide, polypeptide, antagonist and/or agonist of the invention. For example, polynucleotides, polypeptides, antagonists and/or agonists may be utilized in a variety of additional methods in order to therapeutically treat a cancer or tumor. Cancers which may be treated with polynucleotides, polypeptides, antagonists and/or agonists include, but are not limited to solid tumors, including prostate, lung, breast, ovarian, stomach, pancreas, larynx, esophagus, testes, liver, parotid, biliary tract, colon, rectum, cervix, uterus, endometrium, kidney, bladder, thyroid cancer; primary tumors and metastases; melanomas; glioblastoma; Kaposi&#39;s sarcoma; leiomyosarcoma; non-small cell lung cancer; colorectal cancer; advanced malignancies; and blood born tumors such as leukemias. For example, polynucleotides, polypeptides, antagonists and/or agonists may be delivered topically, in order to treat cancers such as skin cancer, head and neck tumors, breast tumors, and Kaposi&#39;s sarcoma.  
       [1020] Within yet other aspects, polynucleotides, polypeptides, antagonists and/or agonists may be utilized to treat superficial forms of bladder cancer by, for example, intravesical administration. Polynucleotides, polypeptides, antagonists and/or agonists may be delivered directly into the tumor, or near the tumor site, via injection or a catheter. Of course, as the artisan of ordinary skill will appreciate, the appropriate mode of administration will vary according to the cancer to be treated. Other modes of delivery are discussed herein.  
       [1021] Polynucleotides, polypeptides, antagonists and/or agonists may be useful in treating other disorders, besides cancers, which involve angiogenesis. These disorders include, but are not limited to: benign tumors, for example hemangiomas, acoustic neuromas, neurofibromas, trachomas, and pyogenic granulomas; artheroscleric plaques; ocular angiogenic diseases, for example, diabetic retinopathy, retinopathy of prematurity, macular degeneration, corneal graft rejection, neovascular glaucoma, retrolental fibroplasia, rubeosis, retinoblastoma, uvietis and Pterygia (abnormal blood vessel growth) of the eye; rheumatoid arthritis; psoriasis; delayed wound healing; endometriosis; vasculogenesis; granulations; hypertrophic scars (keloids); nonunion fractures; scleroderma; trachoma; vascular adhesions; myocardial angiogenesis; coronary collaterals; cerebral collaterals; arteriovenous malformations; ischemic limb angiogenesis; Osler-Webber Syndrome; plaque neovascularization; telangiectasia; hemophiliac joints; angiofibroma; fibromuscular dysplasia; wound granulation; Crohn&#39;s disease; and atherosclerosis.  
       [1022] For example, within one aspect of the present invention methods are provided for treating hypertrophic scars and keloids, comprising the step of administering a polynucleotide, polypeptide, antagonist and/or agonist of the invention to a hypertrophic scar or keloid.  
       [1023] Within one embodiment of the present invention polynucleotides, polypeptides, antagonists and/or agonists of the invention are directly injected into a hypertrophic scar or keloid, in order to prevent the progression of these lesions. This therapy is of particular value in the prophylactic treatment of conditions which are known to result in the development of hypertrophic scars and keloids (e.g., burns), and is preferably initiated after the proliferative phase has had time to progress (approximately 14 days after the initial injury), but before hypertrophic scar or keloid development. As noted above, the present invention also provides methods for treating neovascular diseases of the eye, including for example, corneal neovascularization, neovascular glaucoma, proliferative diabetic retinopathy, retrolental fibroplasia and macular degeneration.  
       [1024] Moreover, Ocular disorders associated with neovascularization which can be treated with the polynucleotides and polypeptides of the present invention (including agonists and/or antagonists) include, but are not limited to: neovascular glaucoma, diabetic retinopathy, retinoblastoma, retrolental fibroplasia, uveitis, retinopathy of prematurity macular degeneration, corneal graft neovascularization, as well as other eye inflammatory diseases, ocular tumors and diseases associated with choroidal or iris neovascularization. See, e.g., reviews by Waltman et al.,  Am. J. Ophthal  85:704-710 (1978) and Gartner et al.,  Surv. Ophthal.  22:291-312 (1978).  
       [1025] Thus, within one aspect of the present invention methods are provided for treating neovascular diseases of the eye such as corneal neovascularization (including corneal graft neovascularization), comprising the step of administering to a patient a therapeutically effective amount of a compound (as described above) to the cornea, such that the formation of blood vessels is inhibited. Briefly, the cornea is a tissue which normally lacks blood vessels. In certain pathological conditions however, capillaries may extend into the cornea from the pericorneal vascular plexus of the limbus. When the cornea becomes vascularized, it also becomes clouded, resulting in a decline in the patient&#39;s visual acuity. Visual loss may become complete if the cornea completely opacitates. A wide variety of disorders can result in corneal neovascularization, including for example, corneal infections (e.g., trachoma, herpes simplex keratitis, leishmaniasis and onchocerciasis), immunological processes (e.g., graft rejection and Stevens-Johnson&#39;s syndrome), alkali burns, trauma, inflammation (of any cause), toxic and nutritional deficiency states, and as a complication of wearing contact lenses.  
       [1026] Within particularly preferred embodiments of the invention, may be prepared for topical administration in saline (combined with any of the preservatives and antimicrobial agents commonly used in ocular preparations), and administered in eyedrop form. The solution or suspension may be prepared in its pure form and administered several times daily. Alternatively, anti-angiogenic compositions, prepared as described above, may also be administered directly to the cornea. Within preferred embodiments, the anti-angiogenic composition is prepared with a muco-adhesive polymer which binds to cornea. Within further embodiments, the anti-angiogenic factors or anti-angiogenic compositions may be utilized as an adjunct to conventional steroid therapy. Topical therapy may also be useful prophylactically in corneal lesions which are known to have a high probability of inducing an angiogenic response (such as chemical burns). In these instances the treatment, likely in combination with steroids, may be instituted immediately to help prevent subsequent complications.  
       [1027] Within other embodiments, the compounds described above may be injected directly into the corneal stroma by an ophthalmologist under microscopic guidance. The preferred site of injection may vary with the morphology of the individual lesion, but the goal of the administration would be to place the composition at the advancing front of the vasculature (i.e., interspersed between the blood vessels and the normal cornea). In most cases this would involve perilimbic corneal injection to “protect” the cornea from the advancing blood vessels. This method may also be utilized shortly after a corneal insult in order to prophylactically prevent corneal neovascularization. In this situation the material could be injected in the perilimbic cornea interspersed between the corneal lesion and its undesired potential limbic blood supply. Such methods may also be utilized in a similar fashion to prevent capillary invasion of transplanted corneas. In a sustained-release form injections might only be required 2-3 times per year. A steroid could also be added to the injection solution to reduce inflammation resulting from the injection itself.  
       [1028] Within another aspect of the present invention, methods are provided for treating neovascular glaucoma, comprising the step of administering to a patient a therapeutically effective amount of a polynucleotide, polypeptide, antagonist and/or agonist to the eye, such that the formation of blood vessels is inhibited. In one embodiment, the compound may be administered topically to the eye in order to treat early forms of neovascular glaucoma. Within other embodiments, the compound may be implanted by injection into the region of the anterior chamber angle. Within other embodiments, the compound may also be placed in any location such that the compound is continuously released into the aqueous humor. Within another aspect of the present invention, methods are provided for treating proliferative diabetic retinopathy, comprising the step of administering to a patient a therapeutically effective amount of a polynucleotide, polypeptide, antagonist and/or agonist to the eyes, such that the formation of blood vessels is inhibited.  
       [1029] Within particularly preferred embodiments of the invention, proliferative diabetic retinopathy may be treated by injection into the aqueous humor or the vitreous, in order to increase the local concentration of the polynucleotide, polypeptide, antagonist and/or agonist in the retina. Preferably, this treatment should be initiated prior to the acquisition of severe disease requiring photocoagulation.  
       [1030] Within another aspect of the present invention, methods are provided for treating retrolental fibroplasia, comprising the step of administering to a patient a therapeutically effective amount of a polynucleotide, polypeptide, antagonist and/or agonist to the eye, such that the formation of blood vessels is inhibited. The compound may be administered topically, via intravitreous injection and/or via intraocular implants.  
       [1031] Additionally, disorders which can be treated with the polynucleotides, polypeptides, agonists and/or agonists include, but are not limited to, hemangioma, arthritis, psoriasis, angiofibroma, atherosclerotic plaques, delayed wound healing, granulations, hemophilic joints, hypertrophic scars, nonunion fractures, Osler-Weber syndrome, pyogenic granuloma, scleroderma, trachoma, and vascular adhesions.  
       [1032] Moreover, disorders and/or states, which can be treated, prevented, diagnosed, and/or prognosed with the the polynucleotides, polypeptides, agonists and/or agonists of the invention include, but are not limited to, solid tumors, blood born tumors such as leukemias, tumor metastasis, Kaposi&#39;s sarcoma, benign tumors, for example hemangiomas, acoustic neuromas, neurofibromas, trachomas, and pyogenic granulomas, rheumatoid arthritis, psoriasis, ocular angiogenic diseases, for example, diabetic retinopathy, retinopathy of prematurity, macular degeneration, corneal graft rejection, neovascular glaucoma, retrolental fibroplasia, rubeosis, retinoblastoma, and uvietis, delayed wound healing, endometriosis, vascluogenesis, granulations, hypertrophic scars (keloids), nonunion fractures, scleroderma, trachoma, vascular adhesions, myocardial angiogenesis, coronary collaterals, cerebral collaterals, arteriovenous malformations, ischemic limb angiogenesis, Osler-Webber Syndrome, plaque neovascularization, telangiectasia, hemophiliac joints, angiofibroma fibromuscular dysplasia, wound granulation, Crohn&#39;s disease, atherosclerosis, birth control agent by preventing vascularization required for embryo implantation controlling menstruation, diseases that have angiogenesis as a pathologic consequence such as cat scratch disease (Rochele minalia quintosa), ulcers (Helicobacter pylori), Bartonellosis and bacillary angiomatosis.  
       [1033] In one aspect of the birth control method, an amount of the compound sufficient to block embryo implantation is administered before or after intercourse and fertilization have occurred, thus providing an effective method of birth control, possibly a “morning after” method. Polynucleotides, polypeptides, agonists and/or agonists may also be used in controlling menstruation or administered as either a peritoneal lavage fluid or for peritoneal implantation in the treatment of endometriosis.  
       [1034] Polynucleotides, polypeptides, agonists and/or agonists of the present invention may be incorporated into surgical sutures in order to prevent stitch granulomas.  
       [1035] Polynucleotides, polypeptides, agonists and/or agonists may be utilized in a wide variety of surgical procedures. For example, within one aspect of the present invention a compositions (in the form of, for example, a spray or film) may be utilized to coat or spray an area prior to removal of a tumor, in order to isolate normal surrounding tissues from malignant tissue, and/or to prevent the spread of disease to surrounding tissues. Within other aspects of the present invention, compositions (e.g., in the form of a spray) may be delivered via endoscopic procedures in order to coat tumors, or inhibit angiogenesis in a desired locale. Within yet other aspects of the present invention, surgical meshes which have been coated with anti-angiogenic compositions of the present invention may be utilized in any procedure wherein a surgical mesh might be utilized. For example, within one embodiment of the invention a surgical mesh laden with an anti-angiogenic composition may be utilized during abdominal cancer resection surgery (e.g., subsequent to colon resection) in order to provide support to the structure, and to release an amount of the anti-angiogenic factor.  
       [1036] Within further aspects of the present invention, methods are provided for treating tumor excision sites, comprising administering a polynucleotide, polypeptide, agonist and/or agonist to the resection margins of a tumor subsequent to excision, such that the local recurrence of cancer and the formation of new blood vessels at the site is inhibited. Within one embodiment of the invention, the anti-angiogenic compound is administered directly to the tumor excision site (e.g., applied by swabbing, brushing or otherwise coating the resection margins of the tumor with the anti-angiogenic compound). Alternatively, the anti-angiogenic compounds may be incorporated into known surgical pastes prior to administration. Within particularly preferred embodiments of the invention, the anti-angiogenic compounds are applied after hepatic resections for malignancy, and after neurosurgical operations.  
       [1037] Within one aspect of the present invention, polynucleotides, polypeptides, agonists and/or agonists may be administered to the resection margin of a wide variety of tumors, including for example, breast, colon, brain and hepatic tumors. For example, within one embodiment of the invention, anti-angiogenic compounds may be administered to the site of a neurological tumor subsequent to excision, such that the formation of new blood vessels at the site are inhibited.  
       [1038] The polynucleotides, polypeptides, agonists and/or agonists of the present invention may also be administered along with other anti-angiogenic factors. Representative examples of other anti-angiogenic factors include: Anti-Invasive Factor, retinoic acid and derivatives thereof, paclitaxel, Suramin, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2, Plasminogen Activator Inhibitor-1, Plasminogen Activator Inhibitor-2, and various forms of the lighter “d group” transition metals.  
       [1039] Lighter “d group” transition metals include, for example, vanadium, molybdenum, tungsten, titanium, niobium, and tantalum species. Such transition metal species may form transition metal complexes. Suitable complexes of the above-mentioned transition metal species include oxo transition metal complexes.  
       [1040] Representative examples of vanadium complexes include oxo vanadium complexes such as vanadate and vanadyl complexes. Suitable vanadate complexes include metavanadate and orthovanadate complexes such as, for example, ammonium metavanadate, sodium metavanadate, and sodium orthovanadate. Suitable vanadyl complexes include, for example, vanadyl acetylacetonate and vanadyl sulfate including vanadyl sulfate hydrates such as vanadyl sulfate mono- and trihydrates.  
       [1041] Representative examples of tungsten and molybdenum complexes also include oxo complexes. Suitable oxo tungsten complexes include tungstate and tungsten oxide complexes. Suitable tungstate complexes include ammonium tungstate, calcium tungstate, sodium tungstate dihydrate, and tungstic acid. Suitable tungsten oxides include tungsten (IV) oxide and tungsten (VI) oxide. Suitable oxo molybdenum complexes include molybdate, molybdenum oxide, and molybdenyl complexes. Suitable molybdate complexes include ammonium molybdate and its hydrates, sodium molybdate and its hydrates, and potassium molybdate and its hydrates. Suitable molybdenum oxides include molybdenum (VI) oxide, molybdenum (VI) oxide, and molybdic acid. Suitable molybdenyl complexes include, for example, molybdenyl acetylacetonate. Other suitable tungsten and molybdenum complexes include hydroxo derivatives derived from, for example, glycerol, tartaric acid, and sugars.  
       [1042] A wide variety of other anti-angiogenic factors may also be utilized within the context of the present invention. Representative examples include platelet factor 4; protamine sulphate; sulphated chitin derivatives (prepared from queen crab shells), (Murata et al., Cancer Res. 51:22-26, 1991); Sulphated Polysaccharide Peptidoglycan Complex (SP-PG) (the function of this compound may be enhanced by the presence of steroids such as estrogen, and tamoxifen citrate); Staurosporine; modulators of matrix metabolism, including for example, proline analogs, cishydroxyproline, d,L-3,4-dehydroproline, Thiaproline, alpha,alpha-dipyridyl, aminopropionitrile fumarate; 4-propyl-5-(4-pyridinyl)-2(3 H)-oxazolone; Methotrexate; Mitoxantrone; Heparin; Interferons; 2 Macroglobulin-serum; ChIMP-3 (Pavloff et al., J. Bio. Chem. 267:17321-17326, 1992); Chymostatin (Tomkinson et al., Biochem J. 286:475-480, 1992); Cyclodextrin Tetradecasulfate; Eponemycin; Camptothecin; Fumagillin (Ingber et al., Nature 348:555-557, 1990); Gold Sodium Thiomalate (“GST”; Matsubara and Ziff, J. Clin. Invest. 79:1440-1446, 1987); anticollagenase-serum; alpha2-antiplasmin (Holmes et al., J. Biol. Chem. 262(4):1659-1664, 1987); Bisantrene (National Cancer Institute); Lobenzarit disodium (N-(2)-carboxyphenyl-4-chloroanthronilic acid disodium or “CCA”; Takeuchi et al., Agents Actions 36:312-316, 1992); Thalidomide; Angostatic steroid; AGM-1470; carboxynaminolmidazole; and metalloproteinase inhibitors such as BB94.  
       [1043] Diseases at the Cellular Level  
       [1044] Diseases associated with increased cell survival or the inhibition of apoptosis that could be treated, prevented, diagnosed, and/or prognosed using polynucleotides or polypeptides, as well as antagonists or agonists of the present invention, include cancers (such as follicular lymphomas, carcinomas with p53 mutations, and hormone-dependent tumors, including, but not limited to 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, breast cancer, prostate cancer, Kaposi&#39;s sarcoma and ovarian cancer); autoimmune disorders (such as, multiple sclerosis, Sjogren&#39;s syndrome, Hashimoto&#39;s thyroiditis, biliary cirrhosis, Behcet&#39;s disease, Crohn&#39;s disease, polymyositis, systemic lupus erythematosus and immune-related glomerulonephritis and rheumatoid arthritis) and viral infections (such as herpes viruses, pox viruses and adenoviruses), inflammation, graft v. host disease, acute graft rejection, and chronic graft rejection.  
       [1045] In preferred embodiments, polynucleotides, polypeptides, and/or antagonists of the invention are used to inhibit growth, progression, and/or metasis of cancers, in particular those listed above.  
       [1046] Additional diseases or conditions associated with increased cell survival that could be treated or detected by polynucleotides or polypeptides, or agonists or antagonists of the present invention include, but are not limited to, progression, and/or metastases of malignancies and related disorders such as leukemia (including acute leukemias (e.g., acute lymphocytic leukemia, acute myelocytic leukemia (including myeloblastic, promyelocytic, myelomonocytic, monocytic, and erythroleukemia)) and chronic leukemias (e.g., chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia)), polycythemia vera, lymphomas (e.g., Hodgkin&#39;s disease and non-Hodgkin&#39;s disease), multiple myeloma, Waldenstrom&#39;s macroglobulinemia, heavy chain disease, and solid tumors including, but not limited to, sarcomas and carcinomas such as fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing&#39;s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm&#39;s tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, menangioma, melanoma, neuroblastoma, and retinoblastoma.  
       [1047] Diseases associated with increased apoptosis that could be treated, prevented, diagnosed, and/or prognesed using polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, include, but are not limited to, AIDS; neurodegenerative disorders (such as Alzheimer&#39;s disease, Parkinson&#39;s disease, Amyotrophic lateral sclerosis, Retinitis pigmentosa, Cerebellar degeneration and brain tumor or prior associated disease); autoimmune disorders (such as, multiple sclerosis, Sjogren&#39;s syndrome, Hashimoto&#39;s thyroiditis, biliary cirrhosis, Behcet&#39;s disease, Crohn&#39;s disease, polymyositis, systemic lupus erythematosus and immune-related glomerulonephritis and rheumatoid arthritis) myelodysplastic syndromes (such as aplastic anemia), graft v. host disease, ischemic injury (such as that caused by myocardial infarction, stroke and reperfusion injury), liver injury (e.g., hepatitis related liver injury, ischemia/reperfusion injury, cholestosis (bile duct injury) and liver cancer); toxin-induced liver disease (such as that caused by alcohol), septic shock, cachexia and anorexia.  
       [1048] Wound Healing and Epithelial Cell Proliferation  
       [1049] In accordance with yet a further aspect of the present invention, there is provided a process for utilizing polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, for therapeutic purposes, for example, to stimulate epithelial cell proliferation and basal keratinocytes for the purpose of wound healing, and to stimulate hair follicle production and healing of dermal wounds. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, may be clinically useful in stimulating wound healing including surgical wounds, excisional wounds, deep wounds involving damage of the dermis and epidermis, eye tissue wounds, dental tissue wounds, oral cavity wounds, diabetic ulcers, dermal ulcers, cubitus ulcers, arterial ulcers, venous stasis ulcers, burns resulting from heat exposure or chemicals, and other abnormal wound healing conditions such as uremia, malnutrition, vitamin deficiencies and complications associated with systemic treatment with steroids, radiation therapy and antineoplastic drugs and antimetabolites. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to promote dermal reestablishment subsequent to dermal loss  
       [1050] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to increase the adherence of skin grafts to a wound bed and to stimulate re-epithelialization from the wound bed. The following are types of grafts that polynucleotides or polypeptides, agonists or antagonists of the present invention, could be used to increase adherence to a wound bed: autografts, artificial skin, allografts, autodermic graft, autoepdermic grafts, avacular grafts, Blair-Brown grafts, bone graft, brephoplastic grafts, cutis graft, delayed graft, dermic graft, epidermic graft, fascia graft, full thickness graft, heterologous graft, xenograft, homologous graft, hyperplastic graft, lamellar graft, mesh graft, mucosal graft, Ollier-Thiersch graft, omenpal graft, patch graft, pedicle graft, penetrating graft, split skin graft, thick split graft. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, can be used to promote skin strength and to improve the appearance of aged skin.  
       [1051] It is believed that polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, will also produce changes in hepatocyte proliferation, and epithelial cell proliferation in the lung, breast, pancreas, stomach, small intestine, and large intestine. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could promote proliferation of epithelial cells such as sebocytes, hair follicles, hepatocytes, type II pneumocytes, mucin-producing goblet cells, and other epithelial cells and their progenitors contained within the skin, lung, liver, and gastrointestinal tract. Polynucleotides or polypeptides, agonists or antagonists of the present invention, may promote proliferation of endothelial cells, keratinocytes, and basal keratinocytes.  
       [1052] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could also be used to reduce the side effects of gut toxicity that result from radiation, chemotherapy treatments or viral infections. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, may have a cytoprotective effect on the small intestine mucosa. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, may also stimulate healing of mucositis (mouth ulcers) that result from chemotherapy and viral infections.  
       [1053] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could further be used in full regeneration of skin in full and partial thickness skin defects, including burns, (i.e., repopulation of hair follicles, sweat glands, and sebaceous glands), treatment of other skin defects such as psoriasis. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to treat epidermolysis bullosa, a defect in adherence of the epidermis to the underlying dermis which results in frequent, open and painful blisters by accelerating reepithelialization of these lesions. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could also be used to treat gastric and doudenal ulcers and help heal by scar formation of the mucosal lining and regeneration of glandular mucosa and duodenal mucosal lining more rapidly. Inflammatory bowel diseases, such as Crohn&#39;s disease and ulcerative colitis, are diseases which result in destruction of the mucosal surface of the small or large intestine, respectively. Thus, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to promote the resurfacing of the mucosal surface to aid more rapid healing and to prevent progression of inflammatory bowel disease. Treatment with polynucleotides or polypeptides, agonists or antagonists of the present invention, is expected to have a significant effect on the production of mucus throughout the gastrointestinal tract and could be used to protect the intestinal mucosa from injurious substances that are ingested or following surgery. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to treat diseases associate with the under expression.  
       [1054] Moreover, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to prevent and heal damage to the lungs due to various pathological states. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, which could stimulate proliferation and differentiation and promote the repair of alveoli and brochiolar epithelium to prevent or treat acute or chronic lung damage. For example, emphysema, which results in the progressive loss of aveoli, and inhalation injuries, i.e., resulting from smoke inhalation and burns, that cause necrosis of the bronchiolar epithelium and alveoli could be effectively treated using polynucleotides or polypeptides, agonists or antagonists of the present invention. Also, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to stimulate the proliferation of and differentiation of type II pneumocytes, which may help treat or prevent disease such as hyaline membrane diseases, such as infant respiratory distress syndrome and bronchopulmonary displasia, in premature infants.  
       [1055] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could stimulate the proliferation and differentiation of hepatocytes and, thus, could be used to alleviate or treat liver diseases and pathologies such as fulminant liver failure caused by cirrhosis, liver damage caused by viral hepatitis and toxic substances (i.e., acetaminophen, carbon tetraholoride and other hepatotoxins known in the art).  
       [1056] In addition, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used treat or prevent the onset of diabetes mellitus. In patients with newly diagnosed Types I and II diabetes, where some islet cell function remains, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used to maintain the islet function so as to alleviate, delay or prevent permanent manifestation of the disease. Also, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, could be used as an auxiliary in islet cell transplantation to improve or promote islet cell function.  
       [1057] Neural Activity and Neurological Diseases  
       [1058] The polynucleotides, polypeptides and agonists or antagonists of the invention may be used for the diagnosis and/or treatment of diseases, disorders, damage or injury of the brain and/or nervous system. Nervous system disorders that can be treated with the compositions of the invention (e.g., polypeptides, polynucleotides, and/or agonists or antagonists), include, but are not limited to, nervous system injuries, and diseases or disorders which result in either a disconnection of axons, a diminution or degeneration of neurons, or demyelination. Nervous system lesions which may be treated in a patient (including human and non-human mammalian patients) according to the methods of the invention, include but are not limited to, the following lesions of either the central (including spinal cord, brain) or peripheral nervous systems: (1) ischemic lesions, in which a lack of oxygen in a portion of the nervous system results in neuronal injury or death, including cerebral infarction or ischemia, or spinal cord infarction or ischemia; (2) traumatic lesions, including lesions caused by physical injury or associated with surgery, for example, lesions which sever a portion of the nervous system, or compression injuries; (3) malignant lesions, in which a portion of the nervous system is destroyed or injured by malignant tissue which is either a nervous system associated malignancy or a malignancy derived from non-nervous system tissue; (4) infectious lesions, in which a portion of the nervous system is destroyed or injured as a result of infection, for example, by an abscess or associated with infection by human immunodeficiency virus, herpes zoster, or herpes simplex virus or with Lyme disease, tuberculosis, or syphilis; (5) degenerative lesions, in which a portion of the nervous system is destroyed or injured as a result of a degenerative process including but not limited to, degeneration associated with Parkinson&#39;s disease, Alzheimer&#39;s disease, Huntington&#39;s chorea, or amyotrophic lateral sclerosis (ALS); (6) lesions associated with nutritional diseases or disorders, in which a portion of the nervous system is destroyed or injured by a nutritional disorder or disorder of metabolism including, but not limited to, vitamin B12 deficiency, folic acid deficiency, Wernicke disease, tobacco-alcohol amblyopia, Marchiafava-Bignami disease (primary degeneration of the corpus callosum), and alcoholic cerebellar degeneration; (7) neurological lesions associated with systemic diseases including, but not limited to, diabetes (diabetic neuropathy, Bell&#39;s palsy), systemic lupus erythematosus, carcinoma, or sarcoidosis; (8) lesions caused by toxic substances including alcohol, lead, or particular neurotoxins; and (9) demyelinated lesions in which a portion of the nervous system is destroyed or injured by a demyelinating disease including, but not limited to, multiple sclerosis, human immunodeficiency virus-associated myelopathy, transverse myelopathy or various etiologies, progressive multifocal leukoencephalopathy, and central pontine myelinolysis.  
       [1059] In one embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention are used to protect neural cells from the damaging effects of hypoxia. In a further preferred embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention are used to protect neural cells from the damaging effects of cerebral hypoxia. According to this embodiment, the compositions of the invention are used to treat or prevent neural cell injury associated with cerebral hypoxia. In one non-exclusive aspect of this embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention, are used to treat or prevent neural cell injury associated with cerebral ischemia. In another non-exclusive aspect of this embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention are used to treat or prevent neural cell injury associated with cerebral infarction.  
       [1060] In another preferred embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention are used to treat or prevent neural cell injury associated with a stroke. In a specific embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention are used to treat or prevent cerebral neural cell injury associated with a stroke.  
       [1061] In another preferred embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention are used to treat or prevent neural cell injury associated with a heart attack. In a specific embodiment, the polypeptides, polynucleotides, or agonists or antagonists of the invention are used to treat or prevent cerebral neural cell injury associated with a heart attack.  
       [1062] The compositions of the invention which are useful for treating or preventing a nervous system disorder may be selected by testing for biological activity in promoting the survival or differentiation of neurons. For example, and not by way of limitation, compositions of the invention which elicit any of the following effects may be useful according to the invention: (1) increased survival time of neurons in culture either in the presence or absence of hypoxia or hypoxic conditions; (2) increased sprouting of neurons in culture or in vivo; (3) increased production of a neuron-associated molecule in culture or in vivo, e.g., choline acetyltransferase or acetylcholinesterase with respect to motor neurons; or (4) decreased symptoms of neuron dysfunction in vivo. Such effects may be measured by any method known in the art. In preferred, non-limiting embodiments, increased survival of neurons may routinely be measured using a method set forth herein or otherwise known in the art, such as, for example, in Zhang et al.,  Proc Natl Acad Sci USA  97:3637-42 (2000) or in Arakawa et al.,  J. Neurosci.,  10:3507-15 (1990); increased sprouting of neurons may be detected by methods known in the art, such as, for example, the methods set forth in Pestronk et al.,  Exp. Neurol.,  70:65-82 (1980), or Brown et al.,  Ann. Rev. Neurosci.,  4:17-42 (1981); increased production of neuron-associated molecules may be measured by bioassay, enzymatic assay, antibody binding, Northern blot assay, etc., using techniques known in the art and depending on the molecule to be measured; and motor neuron dysfunction may be measured by assessing the physical manifestation of motor neuron disorder, e.g., weakness, motor neuron conduction velocity, or functional disability.  
       [1063] In specific embodiments, motor neuron disorders that may be treated according to the invention include, but are not limited to, disorders such as infarction, infection, exposure to toxin, trauma, surgical damage, degenerative disease or malignancy that may affect motor neurons as well as other components of the nervous system, as well as disorders that selectively affect neurons such as amyotrophic lateral sclerosis, and including, but not limited to, progressive spinal muscular atrophy, progressive bulbar palsy, primary lateral sclerosis, infantile and juvenile muscular atrophy, progressive bulbar paralysis of childhood (Fazio-Londe syndrome), poliomyelitis and the post polio syndrome, and Hereditary Motorsensory Neuropathy (Charcot-Marie-Tooth Disease).  
       [1064] Further, polypeptides or polynucleotides of the invention may play a role in neuronal survival; synapse formation; conductance; neural differentiation, etc. Thus, compositions of the invention (including polynucleotides, polypeptides, and agonists or antagonists) may be used to diagnose and/or treat or prevent diseases or disorders associated with these roles, including, but not limited to, learning and/or cognition disorders. The compositions of the invention may also be useful in the treatment or prevention of neurodegenerative disease states and/or behavioural disorders. Such neurodegenerative disease states and/or behavioral disorders include, but are not limited to, Alzheimer&#39;s Disease, Parkinson&#39;s Disease, Huntington&#39;s Disease, Tourette Syndrome, schizophrenia, mania, dementia, paranoia, obsessive compulsive disorder, panic disorder, learning disabilities, ALS, psychoses, autism, and altered behaviors, including disorders in feeding, sleep patterns, balance, and perception. In addition, compositions of the invention may also play a role in the treatment, prevention and/or detection of developmental disorders associated with the developing embryo, or sexually-linked disorders.  
       [1065] Additionally, polypeptides, polynucleotides and/or agonists or antagonists of the invention, may be useful in protecting neural cells from diseases, damage, disorders, or injury, associated with cerebrovascular disorders including, but not limited to, carotid artery diseases (e.g., carotid artery thrombosis, carotid stenosis, or Moyamoya Disease), cerebral amyloid angiopathy, cerebral aneurysm, cerebral anoxia, cerebral arteriosclerosis, cerebral arteriovenous malformations, cerebral artery diseases, cerebral embolism and thrombosis (e.g., carotid artery thrombosis, sinus thrombosis, or Wallenberg&#39;s Syndrome), cerebral hemorrhage (e.g., epidural or subdural hematoma, or subarachnoid hemorrhage), cerebral infarction, cerebral ischemia (e.g., transient cerebral ischemia, Subclavian Steal Syndrome, or vertebrobasilar insufficiency), vascular dementia (e.g., multi-infarct), leukomalacia, periventricular, and vascular headache (e.g., cluster headache or migraines).  
       [1066] In accordance with yet a further aspect of the present invention, there is provided a process for utilizing polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, for therapeutic purposes, for example, to stimulate neurological cell proliferation and/or differentiation. Therefore, polynucleotides, polypeptides, agonists and/or antagonists of the invention may be used to treat and/or detect neurologic diseases. Moreover, polynucleotides or polypeptides, or agonists or antagonists of the invention, can be used as a marker or detector of a particular nervous system disease or disorder.  
       [1067] Examples of neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include brain diseases, such as metabolic brain diseases which includes phenylketonuria such as maternal phenylketonuria, pyruvate carboxylase deficiency, pyruvate dehydrogenase complex deficiency, Wernicke&#39;s Encephalopathy, brain edema, brain neoplasms such as cerebellar neoplasms which include infratentorial neoplasms, cerebral ventricle neoplasms such as choroid plexus neoplasms, hypothalamic neoplasms, supratentorial neoplasms, canavan disease, cerebellar diseases such as cerebellar ataxia which include spinocerebellar degeneration such as ataxia telangiectasia, cerebellar dyssynergia, Friederich&#39;s Ataxia, Machado-Joseph Disease, olivopontocerebellar atrophy, cerebellar neoplasms such as infratentorial neoplasms, diffuse cerebral sclerosis such as encephalitis periaxialis, globoid cell leukodystrophy, metachromatic leukodystrophy and subacute sclerosing panencephalitis.  
       [1068] Additional neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include cerebrovascular disorders (such as carotid artery diseases which include carotid artery thrombosis, carotid stenosis and Moyamoya Disease), cerebral amyloid angiopathy, cerebral aneurysm, cerebral anoxia, cerebral arteriosclerosis, cerebral arteriovenous malformations, cerebral artery diseases, cerebral embolism and thrombosis such as carotid artery thrombosis, sinus thrombosis and Wallenberg&#39;s Syndrome, cerebral hemorrhage such as epidural hematoma, subdural hematoma and subarachnoid hemorrhage, cerebral infarction, cerebral ischemia such as transient cerebral ischemia, Subclavian Steal Syndrome and vertebrobasilar insufficiency, vascular dementia such as multi-infarct dementia, periventricular leukomalacia, vascular headache such as cluster headache and migraine.  
       [1069] Additional neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include dementia such as AIDS Dementia Complex, presenile dementia such as Alzheimer&#39;s Disease and Creutzfeldt-Jakob Syndrome, senile dementia such as Alzheimer&#39;s Disease and progressive supranuclear palsy, vascular dementia such as multi-infarct dementia, encephalitis which include encephalitis periaxialis, viral encephalitis such as epidemic encephalitis, Japanese Encephalitis, St. Louis Encephalitis, tick-borne encephalitis and West Nile Fever, acute disseminated encephalomyelitis, meningoencephalitis such as uveomeningoencephalitic syndrome, Postencephalitic Parkinson Disease and subacute sclerosing panencephalitis, encephalomalacia such as periventricular leukomalacia, epilepsy such as generalized epilepsy which includes infantile spasms, absence epilepsy, myoclonic epilepsy which includes MERRF Syndrome, tonic-clonic epilepsy, partial epilepsy such as complex partial epilepsy, frontal lobe epilepsy and temporal lobe epilepsy, post-traumatic epilepsy, status epilepticus such as Epilepsia Partialis Continua, and Hallervorden-Spatz Syndrome.  
       [1070] Additional neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include hydrocephalus such as Dandy-Walker Syndrome and normal pressure hydrocephalus, hypothalamic diseases such as hypothalamic neoplasms, cerebral malaria, narcolepsy which includes cataplexy, bulbar poliomyelitis, cerebri pseudotumor, Rett Syndrome, Reye&#39;s Syndrome, thalamic diseases, cerebral toxoplasmosis, intracranial tuberculoma and Zellweger Syndrome, central nervous system infections such as AIDS Dementia Complex, Brain Abscess, subdural empyema, encephalomyelitis such as Equine Encephalomyelitis, Venezuelan Equine Encephalomyelitis, Necrotizing Hemorrhagic Encephalomyelitis, Visna, and cerebral malaria.  
       [1071] Additional neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include meningitis such as arachnoiditis, aseptic meningtitis such as viral meningtitis which includes lymphocytic choriomeningitis, Bacterial meningtitis which includes Haemophilus Meningtitis, Listeria Meningtitis, Meningococcal Meningtitis such as Waterhouse-Friderichsen Syndrome, Pneumococcal Meningtitis and meningeal tuberculosis, fungal meningitis such as Cryptococcal Meningtitis, subdural effusion, meningoencephalitis such as uvemeningoencephalitic syndrome, myelitis such as transverse myelitis, neurosyphilis such as tabes dorsalis, poliomyelitis which includes bulbar poliomyelitis and postpoliomyelitis syndrome, prion diseases (such as Creutzfeldt-Jakob Syndrome, Bovine Spongiform Encephalopathy, Gerstmann-Straussler Syndrome, Kuru, Scrapie), and cerebral toxoplasmosis.  
       [1072] Additional neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include central nervous system neoplasms such as brain neoplasms that include cerebellar neoplasms such as infratentorial neoplasms, cerebral ventricle neoplasms such as choroid plexus neoplasms, hypothalamic neoplasms and supratentorial neoplasms, meningeal neoplasms, spinal cord neoplasms which include epidural neoplasms, demyelinating diseases such as Canavan Diseases, diffuse cerebral sceloris which includes adrenoleukodystrophy, encephalitis periaxialis, globoid cell leukodystrophy, diffuse cerebral sclerosis such as metachromatic leukodystrophy, allergic encephalomyelitis, necrotizing hemorrhagic encephalomyelitis, progressive multifocal leukoencephalopathy, multiple sclerosis, central pontine myelinolysis, transverse myelitis, neuromyelitis optica, Scrapie, Swayback, Chronic Fatigue Syndrome, Visna, High Pressure Nervous Syndrome, Meningism, spinal cord diseases such as amyotonia congenita, amyotrophic lateral sclerosis, spinal muscular atrophy such as Werdnig-Hoffmann Disease, spinal cord compression, spinal cord neoplasms such as epidural neoplasms, syringomyelia, Tabes Dorsalis, Stiff-Man Syndrome, mental retardation such as Angelman Syndrome, Cri-du-Chat Syndrome, De Lange&#39;s Syndrome, Down Syndrome, Gangliosidoses such as gangliosidoses G(M1), Sandhoff Disease, Tay-Sachs Disease, Hartnup Disease, homocystinuria, Laurence-Moon-Biedl Syndrome, Lesch-Nyhan Syndrome, Maple Syrup Urine Disease, mucolipidosis such as fucosidosis, neuronal ceroid-lipofuscinosis, oculocerebrorenal syndrome, phenylketonuria such as maternal phenylketonuria, Prader-Willi Syndrome, Rett Syndrome, Rubinstein-Taybi Syndrome, Tuberous Sclerosis, WAGR Syndrome, nervous system abnormalities such as holoprosencephaly, neural tube defects such as anencephaly which includes hydrangencephaly, Arnold-Chairi Deformity, encephalocele, meningocele, meningomyelocele, spinal dysraphism such as spina bifida cystica and spina bifida occulta.  
       [1073] Additional neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include hereditary motor and sensory neuropathies which include Charcot-Marie Disease, Hereditary optic atrophy, Refsum&#39;s Disease, hereditary spastic paraplegia, Werdnig-Hoffmann Disease, Hereditary Sensory and Autonomic Neuropathies such as Congenital Analgesia and Familial Dysautonomia, Neurologic manifestations (such as agnosia that include Gerstmann&#39;s Syndrome, Amnesia such as retrograde amnesia, apraxia, neurogenic bladder, cataplexy, communicative disorders such as hearing disorders that includes deafness, partial hearing loss, loudness recruitment and tinnitus, language disorders such as aphasia which include agraphia, anomia, broca aphasia, and Wernicke Aphasia, Dyslexia such as Acquired Dyslexia, language development disorders, speech disorders such as aphasia which includes anomia, broca aphasia and Wernicke Aphasia, articulation disorders, communicative disorders such as speech disorders which include dysarthria, echolalia, mutism and stuttering, voice disorders such as aphonia and hoarseness, decerebrate state, delirium, fasciculation, hallucinations, meningism, movement disorders such as angelman syndrome, ataxia, athetosis, chorea, dystonia, hypokinesia, muscle hypotonia, myoclonus, tic, torticollis and tremor, muscle hypertonia such as muscle rigidity such as stiff-man syndrome, muscle spasticity, paralysis such as facial paralysis which includes Herpes Zoster Oticus, Gastroparesis, Hemiplegia, ophthalmoplegia such as diplopia, Duane&#39;s Syndrome, Horner&#39;s Syndrome, Chronic progressive external ophthalmoplegia such as Kearns Syndrome, Bulbar Paralysis, Tropical Spastic Paraparesis, Paraplegia such as Brown-Sequard Syndrome, quadriplegia, respiratory paralysis and vocal cord paralysis, paresis, phantom limb, taste disorders such as ageusia and dysgeusia, vision disorders such as amblyopia, blindness, color vision defects, diplopia, hemianopsia, scotoma and subnormal vision, sleep disorders such as hypersomnia which includes Kleine-Levin Syndrome, insomnia, and somnambulism, spasm such as trismus, unconsciousness such as coma, persistent vegetative state and syncope and vertigo, neuromuscular diseases such as amyotonia congenita, amyotrophic lateral sclerosis, Lambert-Eaton Myasthenic Syndrome, motor neuron disease, muscular atrophy such as spinal muscular atrophy, Charcot-Marie Disease and Werdnig-Hoffmann Disease, Postpoliomyelitis Syndrome, Muscular Dystrophy, Myasthenia Gravis, Myotonia Atrophica, Myotonia Confenita, Nemaline Myopathy, Familial Periodic Paralysis, Multiplex Paramyloclonus, Tropical Spastic Paraparesis and Stiff-Man Syndrome, peripheral nervous system diseases such as acrodynia, amyloid neuropathies, autonomic nervous system diseases such as Adie&#39;s Syndrome, Barre-Lieou Syndrome, Familial Dysautonomia, Horner&#39;s Syndrome, Reflex Sympathetic Dystrophy and Shy-Drager Syndrome, Cranial Nerve Diseases such as Acoustic Nerve Diseases such as Acoustic Neuroma which includes Neurofibromatosis 2, Facial Nerve Diseases such as Facial Neuralgia,Melkersson-Rosenthal Syndrome, ocular motility disorders which includes amblyopia, nystagmus, oculomotor nerve paralysis, ophthalmoplegia such as Duane&#39;s Syndrome, Horner&#39;s Syndrome, Chronic Progressive External Ophthalmoplegia which includes Kearns Syndrome, Strabismus such as Esotropia and Exotropia, Oculomotor Nerve Paralysis, Optic Nerve Diseases such as Optic Atrophy which includes Hereditary Optic Atrophy, Optic Disk Drusen, Optic Neuritis such as Neuromyelitis Optica, Papilledema, Trigeminal Neuralgia, Vocal Cord Paralysis, Demyelinating Diseases such as Neuromyelitis Optica and Swayback, and Diabetic neuropathies such as diabetic foot.  
       [1074] Additional neurologic diseases which can be treated or detected with polynucleotides, polypeptides, agonists, and/or antagonists of the present invention include nerve compression syndromes such as carpal tunnel syndrome, tarsal tunnel syndrome, thoracic outlet syndrome such as cervical rib syndrome, ulnar nerve compression syndrome, neuralgia such as causalgia, cervico-brachial neuralgia, facial neuralgia and trigeminal neuralgia, neuritis such as experimental allergic neuritis, optic neuritis, polyneuritis, polyradiculoneuritis and radiculities such as polyradiculitis, hereditary motor and sensory neuropathies such as Charcot-Marie Disease, Hereditary Optic Atrophy, Refsum&#39;s Disease, Hereditary Spastic Paraplegia and Werdnig-Hoffmann Disease, Hereditary Sensory and Autonomic Neuropathies which include Congenital Analgesia and Familial Dysautonomia, POEMS Syndrome, Sciatica, Gustatory Sweating and Tetany).  
       [1075] Endocrine Disorders  
       [1076] Polynucleotides or polypeptides, or agonists or antagonists of the present invention, may be used to treat, prevent, diagnose, and/or prognose disorders and/or diseases related to hormone imbalance, and/or disorders or diseases of the endocrine system.  
       [1077] Hormones secreted by the glands of the endocrine system control physical growth, sexual function, metabolism, and other functions. Disorders may be classified in two ways: disturbances in the production of hormones, and the inability of tissues to respond to hormones. The etiology of these hormone imbalance or endocrine system diseases, disorders or conditions may be genetic, somatic, such as cancer and some autoimmune diseases, acquired (e.g., by chemotherapy, injury or toxins), or infectious. Moreover, polynucleotides, polypeptides, antibodies, and/or agonists or antagonists of the present invention can be used as a marker or detector of a particular disease or disorder related to the endocrine system and/or hormone imbalance.  
       [1078] Endocrine system and/or hormone imbalance and/or diseases encompass disorders of uterine motility including, but not limited to: complications with pregnancy and labor (e.g., pre-term labor, post-term pregnancy, spontaneous abortion, and slow or stopped labor); and disorders and/or diseases of the menstrual cycle (e.g., dysmenorrhea and endometriosis).  
       [1079] Endocrine system and/or hormone imbalance disorders and/or diseases include disorders and/or diseases of the pancreas, such as, for example, diabetes mellitus, diabetes insipidus, congenital pancreatic agenesis, pheochromocytoma—islet cell tumor syndrome; disorders and/or diseases of the adrenal glands such as, for example, Addison&#39;s Disease, corticosteroid deficiency, virilizing disease, hirsutism, Cushing&#39;s Syndrome, hyperaldosteronism, pheochromocytoma; disorders and/or diseases of the pituitary gland, such as, for example, hyperpituitarism, hypopituitarism, pituitary dwarfism, pituitary adenoma, panhypopituitarism, acromegaly, gigantism; disorders and/or diseases of the thyroid, including but not limited to, hyperthyroidism, hypothyroidism, Plummer&#39;s disease, Graves&#39; disease (toxic diffuse goiter), toxic nodular goiter, thyroiditis (Hashimoto&#39;s thyroiditis, subacute granulomatous thyroiditis, and silent lymphocytic thyroiditis), Pendred&#39;s syndrome, myxedema, cretinism, thyrotoxicosis, thyroid hormone coupling defect, thymic aplasia, Hurthle cell tumours of the thyroid, thyroid cancer, thyroid carcinoma, Medullary thyroid carcinoma; disorders and/or diseases of the parathyroid, such as, for example, hyperparathyroidism, hypoparathyroidism; disorders and/or diseases of the hypothalamus.  
       [1080] In specific embodiments, the polynucleotides and/or polypeptides corresponding to this gene and/or agonists or antagonists of those polypeptides (including antibodies) as well as fragments and variants of those polynucleotides, polypeptides, agonists and antagonists, may be used to diagnose, prognose, treat, prevent, or ameliorate diseases and disorders associated with aberrant glucose metabolism or glucose uptake into cells.  
       [1081] In a specific embodiment, the polynucleotides and/or polypeptides corresponding to this gene and/or agonists and/or antagonists thereof may be used to diagnose, prognose, treat, prevent, and/or ameliorate type I diabetes mellitus (insulin dependent diabetes mellitus, IDDM).  
       [1082] In another embodiment, the polynucleotides and/or polypeptides corresponding to this gene and/or agonists and/or antagonists thereof may be used to diagnose, prognose, treat, prevent, and/or ameliorate type II diabetes mellitus (insulin resistant diabetes mellitus).  
       [1083] Additionally, in other embodiments, the polynucleotides and/or polypeptides corresponding to this gene and/or antagonists thereof (especially neutralizing or antagonistic antibodies) may be used to diagnose, prognose, treat, prevent, or ameliorate conditions associated with (type I or type II) diabetes mellitus, including, but not limited to, diabetic ketoacidosis, diabetic coma, nonketotic hyperglycemic-hyperosmolar coma, seizures, mental confusion, drowsiness, cardiovascular disease (e.g., heart disease, atherosclerosis, microvascular disease, hypertension, stroke, and other diseases and disorders as described in the “Cardiovascular Disorders” section), dyslipidemia, kidney disease (e.g., renal failure, nephropathy other diseases and disorders as described in the “Renal Disorders” section), nerve damage, neuropathy, vision impairment (e.g., diabetic retinopathy and blindness), ulcers and impaired wound healing, infections (e.g., infectious diseases and disorders as described in the “Infectious Diseases” section, especially of the urinary tract and skin), carpal tunnel syndrome and Dupuytren&#39;s contracture.  
       [1084] In other embodiments, the polynucleotides and/or polypeptides corresponding to this gene and/or agonists or antagonists thereof are administered to an animal, preferably a mammal, and most preferably a human, in order to regulate the animal&#39;s weight. In specific embodiments the polynucleotides and/or polypeptides corresponding to this gene and/or agonists or antagonists thereof are administered to an animal, preferably a mammal, and most preferably a human, in order to control the animal&#39;s weight by modulating a biochemical pathway involving insulin. In still other embodiments the polynucleotides and/or polypeptides corresponding to this gene and/or agonists or antagonists thereof are administered to an animal, preferably a mammal, and most preferably a human, in order to control the animal&#39;s weight by modulating a biochemical pathway involving insulin-like growth factor.  
       [1085] In addition, endocrine system and/or hormone imbalance disorders and/or diseases may also include disorders and/or diseases of the testes or ovaries, including cancer. Other disorders and/or diseases of the testes or ovaries further include, for example, ovarian cancer, polycystic ovary syndrome, Klinefelter&#39;s syndrome, vanishing testes syndrome (bilateral anorchia), congenital absence of Leydig&#39;s cells, cryptorchidism, Noonan&#39;s syndrome, myotonic dystrophy, capillary haemangioma of the testis (benign), neoplasias of the testis and neo-testis.  
       [1086] Moreover, endocrine system and/or hormone imbalance disorders and/or diseases may also include disorders and/or diseases such as, for example, polyglandular deficiency syndromes, pheochromocytoma, neuroblastoma, multiple Endocrine neoplasia, and disorders and/or cancers of endocrine tissues.  
       [1087] In another embodiment, a polypeptide of the invention, or polynucleotides, antibodies, agonists, or antagonists corresponding to that polypeptide, may be used to diagnose, prognose, prevent, and/or treat endocrine diseases and/or disorders associated with the tissue(s) in which the polypeptide of the invention is expressed, including one, two, three, four, five, or more tissues disclosed in Table 3, column 2 (Library Code).  
       [1088] Reproductive System Disorders  
       [1089] The polynucleotides or polypeptides, or agonists or antagonists of the invention may be used for the diagnosis, treatment, or prevention of diseases and/or disorders of the reproductive system. Reproductive system disorders that can be treated by the compositions of the invention, include, but are not limited to, reproductive system injuries, infections, neoplastic disorders, congenital defects, and diseases or disorders which result in infertility, complications with pregnancy, labor, or parturition, and postpartum difficulties.  
       [1090] Reproductive system disorders and/or diseases include diseases and/or disorders of the testes, including testicular atrophy, testicular feminization, cryptorchism (unilateral and bilateral), anorchia, ectopic testis, epididymitis and orchitis (typically resulting from infections such as, for example, gonorrhea, mumps, tuberculosis, and syphilis), testicular torsion, vasitis nodosa, germ cell tumors (e.g., seminomas, embryonal cell carcinomas, teratocarcinomas, choriocarcinomas, yolk sac tumors, and teratomas), stromal tumors (e.g., Leydig cell tumors), hydrocele, hematocele, varicocele, spermatocele, inguinal hernia, and disorders of sperm production (e.g., immotile cilia syndrome, aspermia, asthenozoospermia, azoospermia, oligospermia, and teratozoospermia).  
       [1091] Reproductive system disorders also include disorders of the prostate gland, such as acute non-bacterial prostatitis, chronic non-bacterial prostatitis, acute bacterial prostatitis, chronic bacterial prostatitis, prostatodystonia, prostatosis, granulomatous prostatitis, malacoplakia, benign prostatic hypertrophy or hyperplasia, and prostate neoplastic disorders, including adenocarcinomas, transitional cell carcinomas, ductal carcinomas, and squamous cell carcinomas.  
       [1092] Additionally, the compositions of the invention may be useful in the diagnosis, treatment, and/or prevention of disorders or diseases of the penis and urethra, including inflammatory disorders, such as balanoposthitis, balanitis xerotica obliterans, phimosis, paraphimosis, syphilis, herpes simplex virus, gonorrhea, non-gonococcal urethritis, chlamydia, mycoplasma, trichomonas, HIV, AIDS, Reiter&#39;s syndrome, condyloma acuminatum, condyloma latum, and pearly penile papules; urethral abnormalities, such as hypospadias, epispadias, and phimosis; premalignant lesions, including Erythroplasia of Queyrat, Bowen&#39;s disease, Bowenoid paplosis, giant condyloma of Buscke-Lowenstein, and varrucous carcinoma; penile cancers, including squamous cell carcinomas, carcinoma in situ, verrucous carcinoma, and disseminated penile carcinoma; urethral neoplastic disorders, including penile urethral carcinoma, bulbomembranous urethral carcinoma, and prostatic urethral carcinoma; and erectile disorders, such as priapism, Peyronie&#39;s disease, erectile dysfunction, and impotence.  
       [1093] Moreover, diseases and/or disorders of the vas deferens include vasculititis and CBAVD (congenital bilateral absence of the vas deferens); additionally, the polynucleotides, polypeptides, and agonists or antagonists of the present invention may be used in the diagnosis, treatment, and/or prevention of diseases and/or disorders of the seminal vesicles, including hydatid disease, congenital chloride diarrhea, and polycystic kidney disease.  
       [1094] Other disorders and/or diseases of the male reproductive system include, for example, Klinefelter&#39;s syndrome, Young&#39;s syndrome, premature ejaculation, diabetes mellitus, cystic fibrosis, Kartagener&#39;s syndrome, high fever, multiple sclerosis, and gynecomastia.  
       [1095] Further, the polynucleotides, polypeptides, and agonists or antagonists of the present invention may be used in the diagnosis, treatment, and/or prevention of diseases and/or disorders of the vagina and vulva, including bacterial vaginosis, candida vaginitis, herpes simplex virus, chancroid, granuloma inguinale, lymphogranuloma venereum, scabies, human papillomavirus, vaginal trauma, vulvar trauma, adenosis, chlamydia vaginitis, gonorrhea, trichomonas vaginitis, condyloma acuminatum, syphilis, molluscum contagiosum, atrophic vaginitis, Paget&#39;s disease, lichen sclerosus, lichen planus, vulvodynia, toxic shock syndrome, vaginismus, vulvovaginitis, vulvar vestibulitis, and neoplastic disorders, such as squamous cell hyperplasia, clear cell carcinoma, basal cell carcinoma, melanomas, cancer of Bartholin&#39;s gland, and vulvar intraepithelial neoplasia.  
       [1096] Disorders and/or diseases of the uterus include dysmenorrhea, retroverted uterus, endometriosis, fibroids, adenomyosis, anovulatory bleeding, amenorrhea, Cushing&#39;s syndrome, hydatidiform moles, Asherman&#39;s syndrome, premature menopause, precocious puberty, uterine polyps, dysfunctional uterine bleeding (e.g., due to aberrant hormonal signals), and neoplastic disorders, such as adenocarcinomas, keiomyosarcomas, and sarcomas. Additionally, the polypeptides, polynucleotides, or agonists or antagonists of the invention may be useful as a marker or detector of, as well as in the diagnosis, treatment, and/or prevention of congenital uterine abnormalities, such as bicornuate uterus, septate uterus, simple unicornuate uterus, unicornuate uterus with a noncavitary rudimentary horn, unicomuate uterus with a non-communicating cavitary rudimentary horn, unicornuate uterus with a communicating cavitary horn, arcuate uterus, uterine didelfus, and T-shaped uterus.  
       [1097] Ovarian diseases and/or disorders include anovulation, polycystic ovary syndrome (Stein-Leventhal syndrome), ovarian cysts, ovarian hypofunction, ovarian insensitivity to gonadotropins, ovarian overproduction of androgens, right ovarian vein syndrome, amenorrhea, hirutism, and ovarian cancer (including, but not limited to, primary and secondary cancerous growth, Sertoli-Leydig tumors, endometriod carcinoma of the ovary, ovarian papillary serous adenocarcinoma, ovarian mucinous adenocarcinoma, and Ovarian Krukenberg tumors).  
       [1098] Cervical diseases and/or disorders include cervicitis, chronic cervicitis, mucopurulent cervicitis, cervical dysplasia, cervical polyps, Nabothian cysts, cervical erosion, cervical incompetence, and cervical neoplasms (including, for example, cervical carcinoma, squamous metaplasia, squamous cell carcinoma, adenosquamous cell neoplasia, and columnar cell neoplasia).  
       [1099] Additionally, diseases and/or disorders of the reproductive system include disorders and/or diseases of pregnancy, including miscarriage and stillbirth, such as early abortion, late abortion, spontaneous abortion, induced abortion, therapeutic abortion, threatened abortion, missed abortion, incomplete abortion, complete abortion, habitual abortion, missed abortion, and septic abortion; ectopic pregnancy, anemia, Rh incompatibility, vaginal bleeding during pregnancy, gestational diabetes, intrauterine growth retardation, polyhydramnios, HELLP syndrome, abruptio placentae, placenta previa, hyperemesis, preeclampsia, eclampsia, herpes gestationis, and urticaria of pregnancy. Additionally, the polynucleotides, polypeptides, and agonists or antagonists of the present invention may be used in the diagnosis, treatment, and/or prevention of diseases that can complicate pregnancy, including heart disease, heart failure, rheumatic heart disease, congenital heart disease, mitral valve prolapse, high blood pressure, anemia, kidney disease, infectious disease (e.g., rubella, cytomegalovirus, toxoplasmosis, infectious hepatitis, chlamydia, HIV, AIDS, and genital herpes), diabetes mellitus, Graves&#39; disease, thyroiditis, hypothyroidism, Hashimoto&#39;s thyroiditis, chronic active hepatitis, cirrhosis of the liver, primary biliary cirrhosis, asthma, systemic lupus eryematosis, rheumatoid arthritis, myasthenia gravis, idiopathic thrombocytopenic purpura, appendicitis, ovarian cysts, gallbladder disorders,and obstruction of the intestine.  
       [1100] Complications associated with labor and parturition include premature rupture of the membranes, pre-term labor, post-term pregnancy, postmaturity, labor that progresses too slowly, fetal distress (e.g., abnormal heart rate (fetal or maternal), breathing problems, and abnormal fetal position), shoulder dystocia, prolapsed umbilical cord, amniotic fluid embolism, and aberrant uterine bleeding.  
       [1101] Further, diseases and/or disorders of the postdelivery period, including endometritis, myometritis, parametritis, peritonitis, pelvic thrombophlebitis, pulmonary embolism, endotoxemia, pyelonephritis, saphenous thrombophlebitis, mastitis, cystitis, postpartum hemorrhage, and inverted uterus.  
       [1102] Other disorders and/or diseases of the female reproductive system that may be diagnosed, treated, and/or prevented by the polynucleotides, polypeptides, and agonists or antagonists of the present invention include, for example, Turner&#39;s syndrome, pseudohermaphroditism, premenstrual syndrome, pelvic inflammatory disease, pelvic congestion (vascular engorgement), frigidity, anorgasmia, dyspareunia, ruptured fallopian tube, and Mittelschmerz.  
       [1103] Infectious Disease  
       [1104] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention can be used to treat or detect infectious agents. For example, by increasing the immune response, particularly increasing the proliferation and differentiation of B and/or T cells, infectious diseases may be treated. The immune response may be increased by either enhancing an existing immune response, or by initiating a new immune response. Alternatively, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention may also directly inhibit the infectious agent, without necessarily eliciting an immune response.  
       [1105] Viruses are one example of an infectious agent that can cause disease or symptoms that can be treated or detected by a polynucleotide or polypeptide and/or agonist or antagonist of the present invention. Examples of viruses, include, but are not limited to Examples of viruses, include, but are not limited to the following DNA and RNA viruses and viral families: Arbovirus, Adenoviridae, Arenaviridae, Arterivirus, Birnaviridae, Bunyaviridae, Caliciviridae, Circoviridae, Coronaviridae, Dengue, EBV, HIV, Flaviviridae, Hepadnaviridae (Hepatitis), Herpesviridae (such as, Cytomegalovirus, Herpes Simplex, Herpes Zoster), Mononegavirus (e.g., Paramyxoviridae, Morbillivirus, Rhabdoviridae), Orthomyxoviridae (e.g., Influenza A, Influenza B, and parainfluenza), Papiloma virus, Papovaviridae, Parvoviridae, Picornaviridae, Poxviridae (such as Smallpox or Vaccinia), Reoviridae (e.g., Rotavirus), Retroviridae (HTLV-I, HTLV-II, Lentivirus), and Togaviridae (e.g., Rubivirus). Viruses falling within these families can cause a variety of diseases or symptoms, including, but not limited to: arthritis, bronchiollitis, respiratory syncytial virus, encephalitis, eye infections (e.g., conjunctivitis, keratitis), chronic fatigue syndrome, hepatitis (A, B, C, E, Chronic Active, Delta), Japanese B encephalitis, Junin, Chikungunya, Rift Valley fever, yellow fever, meningitis, opportunistic infections (e.g., AIDS), pneumonia, Burkitt&#39;s Lymphoma, chickenpox, hemorrhagic fever, Measles, Mumps, Parainfluenza, Rabies, the common cold, Polio, leukemia, Rubella, sexually transmitted diseases, skin diseases (e.g., Kaposi&#39;s, warts), and viremia. polynucleotides or polypeptides, or agonists or antagonists of the invention, can be used to treat or detect any of these symptoms or diseases. In specific embodiments, polynucleotides, polypeptides, or agonists or antagonists of the invention are used to treat: meningitis, Dengue, EBV, and/or hepatitis (e.g., hepatitis B). In an additional specific embodiment polynucleotides, polypeptides, or agonists or antagonists of the invention are used to treat patients nonresponsive to one or more other commercially available hepatitis vaccines. In a further specific embodiment polynucleotides, polypeptides, or agonists or antagonists of the invention are used to treat AIDS.  
       [1106] Similarly, bacterial and fungal agents that can cause disease or symptoms and that can be treated or detected by a polynucleotide or polypeptide and/or agonist or antagonist of the present invention include, but not limited to, the following Gram-Negative and Gram-positive bacteria, bacterial families, and fungi: Actinomyces (e.g., Norcardia), Acinetobacter,  Cryptococcus neoformans,  Aspergillus, Bacillaceae (e.g.,  Bacillus anthrasis ), Bacteroides (e.g.,  Bacteroides fragilis ), Blastomycosis, Bordetella, Borrelia (e.g.,  Borrelia burgdorferi ), Brucella, Candidia, Campylobacter, Chlamydia, Clostridium (e.g.,  Clostridium botulinum, Clostridium dificile, Clostridium perfringens, Clostridium tetani ), Coccidioides, Corynebacterium (e.g.,  Corynebacterium diptheriae ), Cryptococcus, Dermatocycoses,  E. coli  (e.g., Enterotoxigenic  E. coli  and Enterohemorrhagic  E. coli ), Enterobacter (e.g.  Enterobacter aerogenes ), Enterobacteriaceae (Klebsiella, Salmonella (e.g.,  Salmonella typhi, Salmonella enteritidis, Salmonella typhi ), Serratia, Yersinia, Shigella), Erysipelothrix, Haemophilus (e.g.,  Haemophilus influenza  type B), Helicobacter, Legionella (e.g.,  Legionella pneumophila ), Leptospira, Listeria (e.g.,  Listeria monocytogenes ), Mycoplasma, Mycobacterium (e.g.,  Mycobacterium leprae  and  Mycobacterium tuberculosis ), Vibrio (e.g.,  Vibrio cholerae ), Neisseriaceae (e.g.,  Neisseria gonorrhea, Neisseria meningitidis ), Pasteurellacea, Proteus, Pseudomonas (e.g.,  Pseudomonas aeruginosa ), Rickettsiaceae, Spirochetes (e.g., Treponema spp., Leptospira spp., Borrelia spp.), Shigella spp., Staphylococcus (e.g.,  Staphylococcus aureus ), Meningiococcus, Pneumococcus and Streptococcus (e.g.,  Streptococcus pneumoniae  and Groups A, B, and C Streptococci), and Ureaplasmas. These bacterial, parasitic, and fungal families can cause diseases or symptoms, including, but not limited to: antibiotic-resistant infections, bacteremia, endocarditis, septicemia, eye infections (e.g., conjunctivitis), uveitis, tuberculosis, gingivitis, bacterial diarrhea, opportunistic infections (e.g., AIDS related infections), paronychia, prosthesis-related infections, dental caries, Reiter&#39;s Disease, respiratory tract infections, such as Whooping Cough or Empyema, sepsis, Lyme Disease, Cat-Scratch Disease, dysentery, paratyphoid fever, food poisoning, Legionella disease, chronic and acute inflammation, erythema, yeast infections, typhoid, pneumonia, gonorrhea, meningitis (e.g., mengitis types A and B), chlamydia, syphillis, diphtheria, leprosy, brucellosis, peptic ulcers, anthrax, spontaneous abortions, birth defects, pneumonia, lung infections, ear infections, deafness, blindness, lethargy, malaise, vomiting, chronic diarrhea, Crohn&#39;s disease, colitis, vaginosis, sterility, pelvic inflammatory diseases, candidiasis, paratuberculosis, tuberculosis, lupus, botulism, gangrene, tetanus, impetigo, Rheumatic Fever, Scarlet Fever, sexually transmitted diseases, skin diseases (e.g., cellulitis, dermatocycoses), toxemia, urinary tract infections, wound infections, noscomial infections. Polynucleotides or polypeptides, agonists or antagonists of the invention, can be used to treat or detect any of these symptoms or diseases. In specific embodiments, polynucleotides, polypeptides, agonists or antagonists of the invention are used to treat: tetanus, diptheria, botulism, and/or meningitis type B.  
       [1107] Moreover, parasitic agents causing disease or symptoms that can be treated, prevented, and/or diagnosed by a polynucleotide or polypeptide and/or agonist or antagonist of the present invention include, but not limited to, the following families or class: Amebiasis, Babesiosis, Coccidiosis, Cryptosporidiosis, Dientamoebiasis, Dourine, Ectoparasitic, Giardias, Helminthiasis, Leishmaniasis, Schistisoma, Theileriasis, Toxoplasmosis, Trypanosomiasis, and Trichomonas and Sporozoans (e.g.,  Plasmodium virax, Plasmodium falciparium, Plasmodium malariae  and  Plasmodium ovale ). These parasites can cause a variety of diseases or symptoms, including, but not limited to: Scabies, Trombiculiasis, eye infections, intestinal disease (e.g., dysentery, giardiasis), liver disease, lung disease, opportunistic infections (e.g., AIDS related), malaria, pregnancy complications, and toxoplasmosis. polynucleotides or polypeptides, or agonists or antagonists of the invention, can be used to treat, prevent, and/or diagnose any of these symptoms or diseases. In specific embodiments, polynucleotides, polypeptides, or agonists or antagonists of the invention are used to treat, prevent, and/or diagnose malaria.  
       [1108] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention of the present invention could either be by administering an effective amount of a polypeptide to the patient, or by removing cells from the patient, supplying the cells with a polynucleotide of the present invention, and returning the engineered cells to the patient (ex vivo therapy). Moreover, the polypeptide or polynucleotide of the present invention can be used as an antigen in a vaccine to raise an immune response against infectious disease.  
       [1109] Regeneration  
       [1110] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention can be used to differentiate, proliferate, and attract cells, leading to the regeneration of tissues. (See, Science 276:59-87 (1997)). The regeneration of tissues could be used to repair, replace, or protect tissue damaged by congenital defects, trauma (wounds, burns, incisions, or ulcers), age, disease (e.g. osteoporosis, osteocarthritis, periodontal disease, liver failure), surgery, including cosmetic plastic surgery, fibrosis, reperfusion injury, or systemic cytokine damage.  
       [1111] Tissues that could be regenerated using the present invention include organs (e.g., pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac), vasculature (including vascular and lymphatics), nervous, hematopoietic, and skeletal (bone, cartilage, tendon, and ligament) tissue. Preferably, regeneration occurs without or decreased scarring. Regeneration also may include angiogenesis.  
       [1112] Moreover, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, may increase regeneration of tissues difficult to heal. For example, increased tendon/ligament regeneration would quicken recovery time after damage. Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention could also be used prophylactically in an effort to avoid damage. Specific diseases that could be treated include of tendinitis, carpal tunnel syndrome, and other tendon or ligament defects. A further example of tissue regeneration of non-healing wounds includes pressure ulcers, ulcers associated with vascular insufficiency, surgical, and traumatic wounds.  
       [1113] Similarly, nerve and brain tissue could also be regenerated by using polynucleotides or polypeptides, as well as agonists or antagonists of the present invention, to proliferate and differentiate nerve cells. Diseases that could be treated using this method include central and peripheral nervous system diseases, neuropathies, or mechanical and traumatic disorders (e.g., spinal cord disorders, head trauma, cerebrovascular disease, and stoke). Specifically, diseases associated with peripheral nerve injuries, peripheral neuropathy (e.g., resulting from chemotherapy or other medical therapies), localized neuropathies, and central nervous system diseases (e.g., Alzheimer&#39;s disease, Parkinson&#39;s disease, Huntington&#39;s disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome), could all be treated using the polynucleotides or polypeptides, as well as agonists or antagonists of the present invention.  
       [1114] Gastrointestinal Disorders  
       [1115] Polynucleotides or polypeptides, or agonists or antagonists of the present invention, may be used to treat, prevent, diagnose, and/or prognose gastrointestinal disorders, including inflammatory diseases and/or conditions, infections, cancers (e.g., intestinal neoplasms (carcinoid tumor of the small intestine, non-Hodgkin&#39;s lymphoma of the small intestine, small bowl lymphoma)), and ulcers, such as peptic ulcers.  
       [1116] Gastrointestinal disorders include dysphagia, odynophagia, inflammation of the esophagus, peptic esophagitis, gastric reflux, submucosal fibrosis and stricturing, Mallory-Weiss lesions, leiomyomas, lipomas, epidermal cancers, adeoncarcinomas, gastric retention disorders, gastroenteritis, gastric atrophy, gastric/stomach cancers, polyps of the stomach, autoimmune disorders such as pernicious anemia, pyloric stenosis, gastritis (bacterial, viral, eosinophilic, stress-induced, chronic erosive, atrophic, plasma cell, and Ménétrier&#39;s), and peritoneal diseases (e.g., chyloperioneum, hemoperitoneum, mesenteric cyst, mesenteric lymphadenitis, mesenteric vascular occlusion, panniculitis, neoplasms, peritonitis, pneumoperitoneum, bubphrenic abscess,).  
       [1117] Gastrointestinal disorders also include disorders associated with the small intestine, such as malabsorption syndromes, distension, irritable bowel syndrome, sugar intolerance, celiac disease, duodenal ulcers, duodenitis, tropical sprue, Whipple&#39;s disease, intestinal lymphangiectasia, Crohn&#39;s disease, appendicitis, obstructions of the ileum, Meckel&#39;s diverticulum, multiple diverticula, failure of complete rotation of the small and large intestine, lymphoma, and bacterial and parasitic diseases (such as Traveler&#39;s diarrhea, typhoid and paratyphoid, cholera, infection by Roundworms ( Ascariasis lumbricoides ), Hookworms ( Ancylostoma duodenale ), Threadworms ( Enterobius vermicularis ), Tapeworms ( Taenia saginata, Echinococcus granulosus,  Diphyllobothrium spp., and  T. solium ).  
       [1118] Liver diseases and/or disorders include intrahepatic cholestasis (alagille syndrome, biliary liver cirrhosis), fatty liver (alcoholic fatty liver, reye syndrome), hepatic vein thrombosis, hepatolentricular degeneration, hepatomegaly, hepatopulmonary syndrome, hepatorenal syndrome, portal hypertension (esophageal and gastric varices), liver abscess (amebic liver abscess), liver cirrhosis (alcoholic, biliary and experimental), alcoholic liver diseases (fatty liver, hepatitis, cirrhosis), parasitic (hepatic echinococcosis, fascioliasis, amebic liver abscess), jaundice (hemolytic, hepatocellular, and cholestatic), cholestasis, portal hypertension, liver enlargement, ascites, hepatitis (alcoholic hepatitis, animal hepatitis, chronic hepatitis (autoimmune, hepatitis B, hepatitis C, hepatitis D, drug induced), toxic hepatitis, viral human hepatitis (hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E), Wilson&#39;s disease, granulomatous hepatitis, secondary biliary cirrhosis, hepatic encephalopathy, portal hypertension, varices, hepatic encephalopathy, primary biliary cirrhosis, primary sclerosing cholangitis, hepatocellular adenoma, hemangiomas, bile stones, liver failure (hepatic encephalopathy, acute liver failure), and liver neoplasms (angiomyolipoma, calcified liver metastases, cystic liver metastases, epithelial tumors, fibrolamellar hepatocarcinoma, focal nodular hyperplasia, hepatic adenoma, hepatobiliary cystadenoma, hepatoblastoma, hepatocellular carcinoma, hepatoma, liver cancer, liver hemangioendothelioma, mesenchymal hamartoma, mesenchymal tumors of liver, nodular regenerative hyperplasia, benign liver tumors (Hepatic cysts [Simple cysts, Polycystic liver disease, Hepatobiliary cystadenoma, Choledochal cyst], Mesenchymal tumors [Mesenchymal hamartoma, Infantile hemangioendothelioma, Hemangioma, Peliosis hepatis, Lipomas, Inflammatory pseudotumor, Miscellaneous], Epithelial tumors [Bile duct epithelium (Bile duct hamartoma, Bile duct adenoma), Hepatocyte (Adenoma, Focal nodular hyperplasia, Nodular regenerative hyperplasia)], malignant liver tumors [hepatocellular, hepatoblastoma, hepatocellular carcinoma, cholangiocellular, cholangiocarcinoma, cystadenocarcinoma, tumors of blood vessels, angiosarcoma, Karposi&#39;s sarcoma, hemangioendothelioma, other tumors, embryonal sarcoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, carcinosarcoma, teratoma, carcinoid, squamous carcinoma, primary lymphoma]), peliosis hepatis, erythrohepatic porphyria, hepatic porphyria (acute intermittent porphyria, porphyria cutanea tarda), Zellweger syndrome).  
       [1119] Pancreatic diseases and/or disorders include acute pancreatitis, chronic pancreatitis (acute necrotizing pancreatitis, alcoholic pancreatitis), neoplasms (adenocarcinoma of the pancreas, cystadenocarcinoma, insulinoma, gastrinoma, and glucagonoma, cystic neoplasms, islet-cell tumors, pancreoblastoma), and other pancreatic diseases (e.g., cystic fibrosis, cyst (pancreatic pseudocyst, pancreatic fistula, insufficiency)).  
       [1120] Gallbladder diseases include gallstones (cholelithiasis and choledocholithiasis), postcholecystectomy syndrome, diverticulosis of the gallbladder, acute cholecystitis, chronic cholecystitis, bile duct tumors, and mucocele.  
       [1121] Diseases and/or disorders of the large intestine include antibiotic-associated colitis, diverticulitis, ulcerative colitis, acquired megacolon, abscesses, fungal and bacterial infections, anorectal disorders (e.g., fissures, hemorrhoids), colonic diseases (colitis, colonic neoplasms [colon cancer, adenomatous colon polyps (e.g., villous adenoma), colon carcinoma, colorectal cancer], colonic diverticulitis, colonic diverticulosis, megacolon [Hirschsprung disease, toxic megacolon]; sigmoid diseases [proctocolitis, sigmoin neoplasms]), constipation, Crohn&#39;s disease, diarrhea (infantile diarrhea, dysentery), duodenal diseases (duodenal neoplasms, duodenal obstruction, duodenal ulcer, duodenitis), enteritis (enterocolitis), HIV enteropathy, ileal diseases (ileal neoplasms, ileitis), immunoproliferative small intestinal disease, inflammatory bowel disease (ulcerative colitis, Crohn&#39;s disease), intestinal atresia, parasitic diseases (anisakiasis, balantidiasis, blastocystis infections, cryptosporidiosis, dientamoebiasis, amebic dysentery, giardiasis), intestinal fistula (rectal fistula), intestinal neoplasms (cecal neoplasms, colonic neoplasms, duodenal neoplasms, ileal neoplasms, intestinal polyps, jejunal neoplasms, rectal neoplasms), intestinal obstruction (afferent loop syndrome, duodenal obstruction, impacted feces, intestinal pseudo-obstruction [cecal volvulus], intussusception), intestinal perforation, intestinal polyps (colonic polyps, gardner syndrome, peutz-jeghers syndrome), jejunal diseases (jejunal neoplasms), malabsorption syndromes (blind loop syndrome, celiac disease, lactose intolerance, short bowl syndrome, tropical sprue, whipple&#39;s disease), mesenteric vascular occlusion, pneumatosis cystoides intestinalis, protein-losing enteropathies (intestinal lymphagiectasis), rectal diseases (anus diseases, fecal incontinence, hemorrhoids, proctitis, rectal fistula, rectal prolapse, rectocele), peptic ulcer (duodenal ulcer, peptic esophagitis, hemorrhage, perforation, stomach ulcer, Zollinger-Ellison syndrome), postgastrectomy syndromes (dumping syndrome), stomach diseases (e.g., achlorhydria, duodenogastric reflux (bile reflux), gastric antral vascular ectasia, gastric fistula, gastric outlet obstruction, gastritis (atrophic or hypertrophic), gastroparesis, stomach dilatation, stomach diverticulum, stomach neoplasms (gastric cancer, gastric polyps, gastric adenocarcinoma, hyperplastic gastric polyp), stomach rupture, stomach ulcer, stomach volvulus), tuberculosis, visceroptosis, vomiting (e.g., hematemesis, hyperemesis gravidarum, postoperative nausea and vomiting) and hemorrhagic colitis.  
       [1122] Further diseases and/or disorders of the gastrointestinal system include biliary tract diseases, such as, gastroschisis, fistula (e.g., biliary fistula, esophageal fistula, gastric fistula, intestinal fistula, pancreatic fistula), neoplasms (e.g., biliary tract neoplasms, esophageal neoplasms, such as adenocarcinoma of the esophagus, esophageal squamous cell carcinoma, gastrointestinal neoplasms, pancreatic neoplasms, such as adenocarcinoma of the pancreas, mucinous cystic neoplasm of the pancreas, pancreatic cystic neoplasms, pancreatoblastoma, and peritoneal neoplasms), esophageal disease (e.g., bullous diseases, candidiasis, glycogenic acanthosis, ulceration, barrett esophagus varices, atresia, cyst, diverticulum (e.g., Zenker&#39;s diverticulum), fistula (e.g., tracheoesophageal fistula), motility disorders (e.g., CREST syndrome, deglutition disorders, achalasia, spasm, gastroesophageal reflux), neoplasms, perforation (e.g., Boerhaave syndrome, Mallory-Weiss syndrome), stenosis, esophagitis, diaphragmatic hernia (e.g., hiatal hernia); gastrointestinal diseases, such as, gastroenteritis (e.g., cholera morbus, norwalk virus infection), hemorrhage (e.g., hematemesis, melena, peptic ulcer hemorrhage), stomach neoplasms (gastric cancer, gastric polyps, gastric adenocarcinoma, stomach cancer)), hernia (e.g., congenital diaphragmatic hernia, femoral hernia, inguinal hernia, obturator hernia, umbilical hernia, ventral hernia), and intestinal diseases (e.g., cecal diseases (appendicitis, cecal neoplasms)).  
       [1123] Chemotaxis  
       [1124] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention may have chemotaxis activity. A chemotaxic molecule attracts or mobilizes cells (e.g., monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells) to a particular site in the body, such as inflammation, infection, or site of hyperproliferation. The mobilized cells can then fight off and/or heal the particular trauma or abnormality.  
       [1125] Polynucleotides or polypeptides, as well as agonists or antagonists of the present invention may increase chemotaxic activity of particular cells. These chemotactic molecules can then be used to treat inflammation, infection, hyperproliferative disorders, or any immune system disorder by increasing the number of cells targeted to a particular location in the body. For example, chemotaxic molecules can be used to treat wounds and other trauma to tissues by attracting immune cells to the injured location. Chemotactic molecules of the present invention can also attract fibroblasts, which can be used to treat wounds.  
       [1126] It is also contemplated that polynucleotides or polypeptides, as well as agonists or antagonists of the present invention may inhibit chemotactic activity. These molecules could also be used to treat disorders. Thus, polynucleotides or polypeptides, as well as agonists or antagonists of the present invention could be used as an inhibitor of chemotaxis.  
       [1127] Binding Activity  
       [1128] A polypeptide of the present invention may be used to screen for molecules that bind to the polypeptide or for molecules to which the polypeptide binds. The binding of the polypeptide and the molecule may activate (agonist), increase, inhibit (antagonist), or decrease activity of the polypeptide or the molecule bound. Examples of such molecules include antibodies, oligonucleotides, proteins (e.g., receptors),or small molecules.  
       [1129] Preferably, the molecule is closely related to the natural ligand of the polypeptide, e.g., a fragment of the ligand, or a natural substrate, a ligand, a structural or functional mimetic. (See, Coligan et al., Current Protocols in Immunology 1(2):Chapter 5 (1991)). Similarly, the molecule can be closely related to the natural receptor to which the polypeptide binds, or at least, a fragment of the receptor capable of being bound by the polypeptide (e.g., active site). In either case, the molecule can be rationally designed using known techniques.  
       [1130] Preferably, the screening for these molecules involves producing appropriate cells which express the polypeptide. Preferred cells include cells from mammals, yeast, Drosophila, or  E. coli.  Cells expressing the polypeptide (or cell membrane containing the expressed polypeptide) are then preferably contacted with a test compound potentially containing the molecule to observe binding, stimulation, or inhibition of activity of either the polypeptide or the molecule.  
       [1131] The assay may simply test binding of a candidate compound to the polypeptide, wherein binding is detected by a label, or in an assay involving competition with a labeled competitor. Further, the assay may test whether the candidate compound results in a signal generated by binding to the polypeptide.  
       [1132] Alternatively, the assay can be carried out using cell-free preparations, polypeptide/molecule affixed to a solid support, chemical libraries, or natural product mixtures. The assay may also simply comprise the steps of mixing a candidate compound with a solution containing a polypeptide, measuring polypeptide/molecule activity or binding, and comparing the polypeptide/molecule activity or binding to a standard.  
       [1133] Preferably, an ELISA assay can measure polypeptide level or activity in a sample (e.g., biological sample) using a monoclonal or polyclonal antibody. The antibody can measure polypeptide level or activity by either binding, directly or indirectly, to the polypeptide or by competing with the polypeptide for a substrate.  
       [1134] Additionally, the receptor to which the polypeptide of the present invention binds can be identified by numerous methods known to those of skill in the art, for example, ligand panning and FACS sorting (Coligan, et al., Current Protocols in Immun., 1(2), Chapter 5, (1991)). For example, expression cloning is employed wherein polyadenylated RNA is prepared from a cell responsive to the polypeptides, for example, NIH3T3 cells which are known to contain multiple receptors for the FGF family proteins, and SC-3 cells, and a cDNA library created from this RNA is divided into pools and used to transfect COS cells or other cells that are not responsive to the polypeptides. Transfected cells which are grown on glass slides are exposed to the polypeptide of the present invention, after they have been labeled. The polypeptides can be labeled by a variety of means including iodination or inclusion of a recognition site for a site-specific protein kinase.  
       [1135] Following fixation and incubation, the slides are subjected to auto-radiographic analysis. Positive pools are identified and sub-pools are prepared and re-transfected using an iterative sub-pooling and re-screening process, eventually yielding a single clones that encodes the putative receptor.  
       [1136] As an alternative approach for receptor identification, the labeled polypeptides can be photoaffinity linked with cell membrane or extract preparations that express the receptor molecule. Cross-linked material is resolved by PAGE analysis and exposed to X-ray film. The labeled complex containing the receptors of the polypeptides can be excised, resolved into peptide fragments, and subjected to protein microsequencing. The amino acid sequence obtained from microsequencing would be used to design a set of degenerate oligonucleotide probes to screen a cDNA library to identify the genes encoding the putative receptors.  
       [1137] Moreover, the techniques of gene-shuffling, motif-shuffling, exon-shuffling, and/or codon-shuffling (collectively referred to as “DNA shuffling”) may be employed to modulate the activities of the polypeptide of the present invention thereby effectively generating agonists and antagonists of the polypeptide of the present invention. See generally, U.S. Pat. Nos. 5,605,793, 5,811,238, 5,830,721, 5,834,252, and 5,837,458, and Patten, P. A., et al.,  Curr. Opinion Biotechnol.  8:724-33 (1997); Harayama, S.  Trends Biotechnol.  16(2):76-82 (1998); Hansson, L. O., et al.,  J. Mol. Biol.  287:265-76 (1999); and Lorenzo, M. M. and Blasco, R.  Biotechniques  24(2):308-13 (1998); each of these patents and publications are hereby incorporated by reference). In one embodiment, alteration of polynucleotides and corresponding polypeptides may be achieved by DNA shuffling. DNA shuffling involves the assembly of two or more DNA segments into a desired molecule by homologous, or site-specific, recombination. In another embodiment, polynucleotides and corresponding polypeptides may be altered by being subjected to random mutagenesis by error-prone PCR, random nucleotide insertion or other methods prior to recombination. In another embodiment, one or more components, motifs, sections, parts, domains, fragments, etc., of the polypeptide of the present invention may be recombined with one or more components, motifs, sections, parts, domains, fragments, etc. of one or more heterologous molecules. In preferred embodiments, the heterologous molecules are family members. In further preferred embodiments, the heterologous molecule is a growth factor such as, for example, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-I), transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), fibroblast growth factor (FGF), TGF-beta, bone morphogenetic protein (BMP)-2, BMP-4, BMP-5, BMP-6, BMP-7, activins A and B, decapentaplegic(dpp), 60A, OP-2, dorsalin, growth differentiation factors (GDFs), nodal, MIS, inhibin-alpha, TGF-betal, TGF-beta2, TGF-beta3, TGF-beta5, and glial-derived neurotrophic factor (GDNF).  
       [1138] Other preferred fragments are biologically active fragments of the polypeptide of the present invention. Biologically active fragments are those exhibiting activity similar, but not necessarily identical, to an activity of the polypeptide of the present invention. The biological activity of the fragments may include an improved desired activity, or a decreased undesirable activity.  
       [1139] Additionally, this invention provides a method of screening compounds to identify those which modulate the action of the polypeptide of the present invention. An example of such an assay comprises combining a mammalian fibroblast cell, a the polypeptide of the present invention, the compound to be screened and  3 [H] thymidine under cell culture conditions where the fibroblast cell would normally proliferate. A control assay may be performed in the absence of the compound to be screened and compared to the amount of fibroblast proliferation in the presence of the compound to determine if the compound stimulates proliferation by determining the uptake of  3 [H] thymidine in each case. The amount of fibroblast cell proliferation is measured by liquid scintillation chromatography which measures the incorporation of  3 [H] thymidine. Both agonist and antagonist compounds may be identified by this procedure.  
       [1140] In another method, a mammalian cell or membrane preparation expressing a receptor for a polypeptide of the present invention is incubated with a labeled polypeptide of the present invention in the presence of the compound. The ability of the compound to enhance or block this interaction could then be measured. Alternatively, the response of a known second messenger system following interaction of a compound to be screened and the receptor is measured and the ability of the compound to bind to the receptor and elicit a second messenger response is measured to determine if the compound is a potential agonist or antagonist. Such second messenger systems include but are not limited to, cAMP guanylate cyclase, ion channels or phosphoinositide hydrolysis.  
       [1141] All of these above assays can be used as diagnostic or prognostic markers. The molecules discovered using these assays can be used to treat disease or to bring about a particular result in a patient (e.g., blood vessel growth) by activating or inhibiting the polypeptide/molecule. Moreover, the assays can discover agents which may inhibit or enhance the production of the polypeptides of the invention from suitably manipulated cells or tissues.  
       [1142] Therefore, the invention includes a method of identifying compounds which bind to a polypeptide of the invention comprising the steps of: (a) incubating a candidate binding compound with a polypeptide of the present invention; and (b) determining if binding has occurred. Moreover, the invention includes a method of identifying agonists/antagonists comprising the steps of: (a) incubating a candidate compound with a polypeptide of the present invention, (b) assaying a biological activity, and (b) determining if a biological activity of the polypeptide has been altered.  
       [1143] Targeted Delivery  
       [1144] In another embodiment, the invention provides a method of delivering compositions to targeted cells expressing a receptor for a polypeptide of the invention, or cells expressing a cell bound form of a polypeptide of the invention.  
       [1145] As discussed herein, polypeptides or antibodies of the invention may be associated with heterologous polypeptides, heterologous nucleic acids, toxins, or prodrugs via hydrophobic, hydrophilic, ionic and/or covalent interactions. In one embodiment, the invention provides a method for the specific delivery of compositions of the invention to cells by administering polypeptides of the invention (including antibodies) that are associated with heterologous polypeptides or nucleic acids. In one example, the invention provides a method for delivering a therapeutic protein into the targeted cell. In another example, the invention provides a method for delivering a single stranded nucleic acid (e.g., antisense or ribozymes) or double stranded nucleic acid (e.g., DNA that can integrate into the cell&#39;s genome or replicate episomally and that can be transcribed) into the targeted cell.  
       [1146] In another embodiment, the invention provides a method for the specific destruction of cells (e.g., the destruction of tumor cells) by administering polypeptides of the invention (e.g., polypeptides of the invention or antibodies of the invention) in association with toxins or cytotoxic prodrugs.  
       [1147] By “toxin” is meant compounds that bind and activate endogenous cytotoxic effector systems, radioisotopes, holotoxins, modified toxins, catalytic subunits of toxins, or any molecules or enzymes not normally present in or on the surface of a cell that under defined conditions cause the cell&#39;s death. Toxins that may be used according to the methods of the invention include, but are not limited to, radioisotopes known in the art, compounds such as, for example, antibodies (or complement fixing containing portions thereof) that bind an inherent or induced endogenous cytotoxic effector system, thymidine kinase, endonuclease, RNAse, alpha toxin, ricin, abrin, Pseudomonas exotoxin A, diphtheria toxin, saporin, momordin, gelonin, pokeweed antiviral protein, alpha-sarcin and cholera toxin. By “cytotoxic prodrug” is meant a non-toxic compound that is converted by an enzyme, normally present in the cell, into a cytotoxic compound. Cytotoxic prodrugs that may be used according to the methods of the invention include, but are not limited to, glutamyl derivatives of benzoic acid mustard alkylating agent, phosphate derivatives of etoposide or mitomycin C, cytosine arabinoside, daunorubisin, and phenoxyacetamide derivatives of doxorubicin.  
       [1148] Drug Screening  
       [1149] Further contemplated is the use of the polypeptides of the present invention, or the polynucleotides encoding these polypeptides, to screen for molecules which modify the activities of the polypeptides of the present invention. Such a method would include contacting the polypeptide of the present invention with a selected compound(s) suspected of having antagonist or agonist activity, and assaying the activity of these polypeptides following binding.  
       [1150] This invention is particularly useful for screening therapeutic compounds by using the polypeptides of the present invention, or binding fragments thereof, in any of a variety of drug screening techniques. The polypeptide or fragment employed in such a test may be affixed to a solid support, expressed on a cell surface, free in solution, or located intracellularly. One method of drug screening utilizes eukaryotic or prokaryotic host cells which are stably transformed with recombinant nucleic acids expressing the polypeptide or fragment. Drugs are screened against such transformed cells in competitive binding assays. One may measure, for example, the formulation of complexes between the agent being tested and a polypeptide of the present invention.  
       [1151] Thus, the present invention provides methods of screening for drugs or any other agents which affect activities mediated by the polypeptides of the present invention. These methods comprise contacting such an agent with a polypeptide of the present invention or a fragment thereof and assaying for the presence of a complex between the agent and the polypeptide or a fragment thereof, by methods well known in the art. In such a competitive binding assay, the agents to screen are typically labeled. Following incubation, free agent is separated from that present in bound form, and the amount of free or uncomplexed label is a measure of the ability of a particular agent to bind to the polypeptides of the present invention.  
       [1152] Another technique for drug screening provides high throughput screening for compounds having suitable binding affinity to the polypeptides of the present invention, and is described in great detail in European Patent Application 84/03564, published on Sep. 13, 1984, which is incorporated herein by reference herein. Briefly stated, large numbers of different small peptide test compounds are synthesized on a solid substrate, such as plastic pins or some other surface. The peptide test compounds are reacted with polypeptides of the present invention and washed. Bound polypeptides are then detected by methods well known in the art. Purified polypeptides are coated directly onto plates for use in the aforementioned drug screening techniques. In addition, non-neutralizing antibodies may be used to capture the peptide and immobilize it on the solid support.  
       [1153] This invention also contemplates the use of competitive drug screening assays in which neutralizing antibodies capable of binding polypeptides of the present invention specifically compete with a test compound for binding to the polypeptides or fragments thereof. In this manner, the antibodies are used to detect the presence of any peptide which shares one or more antigenic epitopes with a polypeptide of the invention.  
       [1154] Antisense and Ribozyme (Antagonists)  
       [1155] In specific embodiments, antagonists according to the present invention are nucleic acids corresponding to the sequences contained in SEQ ID NO:X, or the complementary strand thereof, and/or to cDNA sequences contained in cDNA plasmid:Z identified for example, in Table 1. In one embodiment, antisense sequence is generated internally, by the organism, in another embodiment, the antisense sequence is separately administered (see, for example, O&#39;Connor, J., Neurochem. 56:560 (1991). Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988). Antisense technology can be used to control gene expression through antisense DNA or RNA, or through triple-helix formation. Antisense techniques are discussed for example, in Okano, J., Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988). Triple helix formation is discussed in, for instance, Lee et al., Nucleic Acids Research 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1300 (1991). The methods are based on binding of a polynucleotide to a complementary DNA or RNA.  
       [1156] For example, the use of c-myc and c-myb antisense RNA constructs to inhibit the growth of the non-lymphocytic leukemia cell line HL-60 and other cell lines was previously described. (Wickstrom et al. (1988); Anfossi et al. (1989)). These experiments were performed in vitro by incubating cells with the oligoribonucleotide. A similar procedure for in vivo use is described in WO 91/15580. Briefly, a pair of oligonucleotides for a given antisense RNA is produced as follows: A sequence complimentary to the first 15 bases of the open reading frame is flanked by an EcoR1 site on the 5 end and a HindIII site on the 3 end. Next, the pair of oligonucleotides is heated at 90° C. for one minute and then annealed in 2× ligation buffer (20 mM TRIS HCl pH 7.5, 10 mM MgCl2, 10MM dithiothreitol (DTT) and 0.2 mM ATP) and then ligated to the EcoR1/Hind III site of the retroviral vector PMV7 (WO 91/15580).  
       [1157] For example, the 5′ coding portion of a polynucleotide that encodes the polypeptide of the present invention may be used to design an antisense RNA oligonucleotide of from about 10 to 40 base pairs in length. A DNA oligonucleotide is designed to be complementary to a region of the gene involved in transcription thereby preventing transcription and the production of the receptor. The antisense RNA oligonucleotide hybridizes to the mRNA in vivo and blocks translation of the mRNA molecule into receptor polypeptide.  
       [1158] In one embodiment, the antisense nucleic acid of the invention is produced intracellularly by transcription from an exogenous sequence. For example, a vector or a portion thereof, is transcribed, producing an antisense nucleic acid (RNA) of the invention. Such a vector would contain a sequence encoding the antisense nucleic acid. Such a vector can remain episomal or become chromosomally integrated, as long as it can be transcribed to produce the desired antisense RNA. Such vectors can be constructed by recombinant DNA technology methods standard in the art. Vectors can be plasmid, viral, or others known in the art, used for replication and expression in vertebrate cells. Expression of the sequence encoding the polypeptide of the present invention or fragments thereof, can be by any promoter known in the art to act in vertebrate, preferably human cells. Such promoters can be inducible or constitutive. Such promoters include, but are not limited to, the SV40 early promoter region (Bernoist and Chambon, Nature 29:304-310 (1981), the promoter contained in the 3′ long terminal repeat of Rous sarcoma virus (Yamamoto et al., Cell 22:787-797 (1980), the herpes thymidine promoter (Wagner et al., Proc. Natl. Acad. Sci. U.S.A. 78:1441-1445 (1981), the regulatory sequences of the metallothionein gene (Brinster, et al., Nature 296:39-42 (1982)), etc.  
       [1159] The antisense nucleic acids of the invention comprise a sequence complementary to at least a portion of an RNA transcript of a gene of the present invention. However, absolute complementarity, although preferred, is not required. A sequence “complementary to at least a portion of an RNA,” referred to herein, means a sequence having sufficient complementarity to be able to hybridize with the RNA, forming a stable duplex; in the case of double stranded antisense nucleic acids, a single strand of the duplex DNA may thus be tested, or triplex formation may be assayed. The ability to hybridize will depend on both the degree of complementarity and the length of the antisense nucleic acid. Generally, the larger the hybridizing nucleic acid, the more base mismatches with a RNA it may contain and still form a stable duplex (or triplex as the case may be). One skilled in the art can ascertain a tolerable degree of mismatch by use of standard procedures to determine the melting point of the hybridized complex.  
       [1160] Oligonucleotides that are complementary to the 5′ end of the message, e.g., the 5′ untranslated sequence up to and including the AUG initiation codon, should work most efficiently at inhibiting translation. However, sequences complementary to the 3′ untranslated sequences of mRNAs have been shown to be effective at inhibiting translation of mRNAs as well. See generally, Wagner, R., 1994, Nature 372:333-335. Thus, oligonucleotides complementary to either the 5′- or 3′-non-translated, non-coding regions of polynucleotide sequences described herein could be used in an antisense approach to inhibit translation of endogenous mRNA. Oligonucleotides complementary to the 5′ untranslated region of the mRNA should include the complement of the AUG start codon. Antisense oligonucleotides complementary to mRNA coding regions are less efficient inhibitors of translation but could be used in accordance with the invention. Whether designed to hybridize to the 5′-, 3′- or coding region of mRNA of the present invention, antisense nucleic acids should be at least six nucleotides in length, and are preferably oligonucleotides ranging from 6 to about 50 nucleotides in length. In specific aspects the oligonucleotide is at least 10 nucleotides, at least 17 nucleotides, at least 25 nucleotides or at least 50 nucleotides.  
       [1161] The polynucleotides of the invention can be DNA or RNA or chimeric mixtures or derivatives or modified versions thereof, single-stranded or double-stranded. The oligonucleotide can be modified at the base moiety, sugar moiety, or phosphate backbone, for example, to improve stability of the molecule, hybridization, etc. The oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger et al., 1989, Proc. Natl. Acad. Sci. U.S.A. 86:6553-6556; Lemaitre et al., 1987, Proc. Natl. Acad. Sci. 84:648-652; PCT Publication No. WO88/09810, published Dec. 15, 1988) or the blood-brain barrier (see, e.g., PCT Publication No. WO89/10134, published Apr. 25, 1988), hybridization-triggered cleavage agents. (See, e.g., Krol et al., 1988, BioTechniques 6:958-976) or intercalating agents. (See, e.g., Zon, 1988, Pharm. Res. 5:539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, hybridization triggered cross-linking agent, transport agent, hybridization-triggered cleavage agent, etc.  
       [1162] The antisense oligonucleotide may comprise at least one modified base moiety which is selected from the group including, but not limited to, 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine.  
       [1163] The antisense oligonucleotide may also comprise at least one modified sugar moiety selected from the group including, but not limited to, arabinose, 2-fluoroarabinose, xylulose, and hexose.  
       [1164] In yet another embodiment, the antisense oligonucleotide comprises at least one modified phosphate backbone selected from the group including, but not limited to, a phosphorothioate, a phosphorodithioate, a phosphoramidothioate, a phosphoramidate, a phosphordiamidate, a methylphosphonate, an alkyl phosphotriester, and a formacetal or analog thereof.  
       [1165] In yet another embodiment, the antisense oligonucleotide is an a-anomeric oligonucleotide. An a-anomeric oligonucleotide forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual b-units, the strands run parallel to each other (Gautier et al., 1987, Nucl. Acids Res. 15:6625-6641). The oligonucleotide is a 2′-0-methylribonucleotide (Inoue et al., 1987, Nucl. Acids Res. 15:6131-6148), or a chimeric RNA-DNA analogue (Inoue et al., 1987, FEBS Lett. 215:327-330).  
       [1166] Polynucleotides of the invention may be synthesized by standard methods known in the art, e.g. by use of an automated DNA synthesizer (such as are commercially available from Biosearch, Applied Biosystems, etc.). As examples, phosphorothioate oligonucleotides may be synthesized by the method of Stein et al. (1988, Nucl. Acids Res. 16:3209), methylphosphonate oligonucleotides can be prepared by use of controlled pore glass polymer supports (Sarin et al., 1988, Proc. Natl. Acad. Sci. U.S.A. 85:7448-7451), etc.  
       [1167] While antisense nucleotides complementary to the coding region sequence could be used, those complementary to the transcribed untranslated region are most preferred.  
       [1168] Potential antagonists according to the invention also include catalytic RNA, or a ribozyme (See, e.g., PCT International Publication WO 90/11364, published Oct. 4, 1990; Sarver et al, Science 247:1222-1225 (1990). While ribozymes that cleave mRNA at site specific recognition sequences can be used to destroy mRNAs, the use of hammerhead ribozymes is preferred. Hammerhead ribozymes cleave mRNAs at locations dictated by flanking regions that form complementary base pairs with the target mRNA. The sole requirement is that the target mRNA have the following sequence of two bases: 5′-UG-3′. The construction and production of hammerhead ribozymes is well known in the art and is described more fully in Haseloff and Gerlach, Nature 334:585-591 (1988). There are numerous potential hammerhead ribozyme cleavage sites within the nucleotide sequence of SEQ ID NO:X. Preferably, the ribozyme is engineered so that the cleavage recognition site is located near the 5′ end of the mRNA; i.e., to increase efficiency and minimize the intracellular accumulation of non-functional mRNA transcripts.  
       [1169] As in the antisense approach, the ribozymes of the invention can be composed of modified oligonucleotides (e.g., for improved stability, targeting, etc.) and should be delivered to cells which express in vivo. DNA constructs encoding the ribozyme may be introduced into the cell in the same manner as described above for the introduction of antisense encoding DNA. A preferred method of delivery involves using a DNA construct “encoding” the ribozyme under the control of a strong constitutive promoter, such as, for example, pol III or pol II promoter, so that transfected cells will produce sufficient quantities of the ribozyme to destroy endogenous messages and inhibit translation. Since ribozymes unlike antisense molecules, are catalytic, a lower intracellular concentration is required for efficiency.  
       [1170] Antagonist/agonist compounds may be employed to inhibit the cell growth and proliferation effects of the polypeptides of the present invention on neoplastic cells and tissues, i.e. stimulation of angiogenesis of tumors, and, therefore, retard or prevent abnormal cellular growth and proliferation, for example, in tumor formation or growth.  
       [1171] The antagonist/agonist may also be employed to prevent hyper-vascular diseases, and prevent the proliferation of epithelial lens cells after extracapsular cataract surgery. Prevention of the mitogenic activity of the polypeptides of the present invention may also be desirous in cases such as restenosis after balloon angioplasty.  
       [1172] The antagonist/agonist may also be employed to prevent the growth of scar tissue during wound healing.  
       [1173] The antagonist/agonist may also be employed to treat the diseases described herein.  
       [1174] Thus, the invention provides a method of treating disorders or diseases, including but not limited to the disorders or diseases listed throughout this application, associated with overexpression of a polynucleotide of the present invention by administering to a patient (a) an antisense molecule directed to the polynucleotide of the present invention, and/or (b) a ribozyme directed to the polynucleotide of the present invention.  
       [1175] Binding Peptides and other Molecules  
       [1176] The invention also encompasses screening methods for identifying polypeptides and nonpolypeptides that bind polypeptides of the invention, and the binding molecules identified thereby. These binding molecules are useful, for example, as agonists and antagonists of the polypeptides of the invention. Such agonists and antagonists can be used, in accordance with the invention, in the therapeutic embodiments described in detail, below.  
       [1177] This method comprises the steps of:  
       [1178] 1. contacting polypeptides of the invention with a plurality of molecules; and  
       [1179] 2. identifying a molecule that binds the polypeptides of the invention.  
       [1180] The step of contacting the polypeptides of the invention with the plurality of molecules may be effected in a number of ways. For example, one may contemplate immobilizing the polypeptides on a solid support and bringing a solution of the plurality of molecules in contact with the immobilized polypeptides. Such a procedure would be akin to an affinity chromatographic process, with the affinity matrix being comprised of the immobilized polypeptides of the invention. The molecules having a selective affinity for the polypeptides can then be purified by affinity selection. The nature of the solid support, process for attachment of the polypeptides to the solid support, solvent, and conditions of the affinity isolation or selection are largely conventional and well known to those of ordinary skill in the art.  
       [1181] Alternatively, one may also separate a plurality of polypeptides into substantially separate fractions comprising a subset of or individual polypeptides. For instance, one can separate the plurality of polypeptides by gel electrophoresis, column chromatography, or like method known to those of ordinary skill for the separation of polypeptides. The individual polypeptides can also be produced by a transformed host cell in such a way as to be expressed on or about its outer surface (e.g., a recombinant phage). Individual isolates can then be “probed” by the polypeptides of the invention, optionally in the presence of an inducer should one be required for expression, to determine if any selective affinity interaction takes place between the polypeptides and the individual clone. Prior to contacting the polypeptides with each fraction comprising individual polypeptides, the polypeptides could first be transferred to a solid support for additional convenience. Such a solid support may simply be a piece of filter membrane, such as one made of nitrocellulose or nylon. In this manner, positive clones could be identified from a collection of transformed host cells of an expression library, which harbor a DNA construct encoding a polypeptide having a selective affinity for polypeptides of the invention. Furthermore, the amino acid sequence of the polypeptide having a selective affinity for the polypeptides of the invention can be determined directly by conventional means or the coding sequence of the DNA encoding the polypeptide can frequently be determined more conveniently. The primary sequence can then be deduced from the corresponding DNA sequence. If the amino acid sequence is to be determined from the polypeptide itself, one may use microsequencing techniques. The sequencing technique may include mass spectroscopy.  
       [1182] In certain situations, it may be desirable to wash away any unbound polypeptides from a mixture of the polypeptides of the invention and the plurality of polypeptides prior to attempting to determine or to detect the presence of a selective affinity interaction. Such a wash step may be particularly desirable when the polypeptides of the invention or the plurality of polypeptides are bound to a solid support.  
       [1183] The plurality of molecules provided according to this method may be provided by way of diversity libraries, such as random or combinatorial peptide or nonpeptide libraries which can be screened for molecules that specifically bind polypeptides of the invention. Many libraries are known in the art that can be used, e.g., chemically synthesized libraries, recombinant (e.g., phage display libraries), and in vitro translation-based libraries. Examples of chemically synthesized libraries are described in Fodor et al., 1991, Science 251:767-773; Houghten et al., 1991, Nature 354:84-86; Lam et al., 1991, Nature 354:82-84; Medynski, 1994, Bio/Technology 12:709-710;Gallop et al., 1994, J. Medicinal Chemistry 37(9):1233-1251; Ohlmeyer et al., 1993, Proc. Natl. Acad. Sci. USA 90:10922-10926; Erb et al., 1994, Proc. Natl. Acad. Sci. USA 91:11422-11426; Houghten et al., 1992, Biotechniques 13:412; Jayawickreme et al., 1994, Proc. Natl. Acad. Sci. USA 91:1614-1618; Salmon et al., 1993, Proc. Natl. Acad. Sci. USA 90:11708-11712; PCT Publication No. WO 93/20242; and Brenner and Lerner, 1992, Proc. Natl. Acad. Sci. USA 89:5381-5383.  
       [1184] Examples of phage display libraries are described in Scott and Smith, 1990, Science 249:386-390; Devlin et al., 1990, Science, 249:404-406; Christian, R. B., et al., 1992, J. Mol. Biol. 227:711-718); Lenstra, 1992, J. Immunol. Meth. 152:149-157; Kay et al., 1993, Gene 128:59-65; and PCT Publication No. WO 94/18318 dated Aug. 18, 1994.  
       [1185] In vitro translation-based libraries include but are not limited to those described in PCT Publication No. WO 91/05058 dated Apr. 18, 1991; and Mattheakis et al., 1994, Proc. Natl. Acad. Sci. USA 91:9022-9026.  
       [1186] By way of examples of nonpeptide libraries, a benzodiazepine library (see e.g., Bunin et al., 1994, Proc. Natl. Acad. Sci. USA 91:4708-4712) can be adapted for use. Peptoid libraries (Simon et al., 1992, Proc. Natl. Acad. Sci. USA 89:9367-9371) can also be used. Another example of a library that can be used, in which the amide functionalities in peptides have been permethylated to generate a chemically transformed combinatorial library, is described by Ostresh et al. (1994, Proc. Natl. Acad. Sci. USA 91:11138-11142).  
       [1187] The variety of non-peptide libraries that are useful in the present invention is great. For example, Ecker and Crooke, 1995, Bio/Technology 13:351-360 list benzodiazepines, hydantoins, piperazinediones, biphenyls, sugar analogs, beta-mercaptoketones, arylacetic acids, acylpiperidines, benzopyrans, cubanes, xanthines, aminimides, and oxazolones as among the chemical species that form the basis of various libraries.  
       [1188] Non-peptide libraries can be classified broadly into two types: decorated monomers and oligomers. Decorated monomer libraries employ a relatively simple scaffold structure upon which a variety functional groups is added. Often the scaffold will be a molecule with a known useful pharmacological activity. For example, the scaffold might be the benzodiazepine structure.  
       [1189] Non-peptide oligomer libraries utilize a large number of monomers that are assembled together in ways that create new shapes that depend on the order of the monomers. Among the monomer units that have been used are carbamates, pyrrolinones, and morpholinos. Peptoids, peptide-like oligomers in which the side chain is attached to the alpha amino group rather than the alpha carbon, form the basis of another version of non-peptide oligomer libraries. The first non-peptide oligomer libraries utilized a single type of monomer and thus contained a repeating backbone. Recent libraries have utilized more than one monomer, giving the libraries added flexibility.  
       [1190] Screening the libraries can be accomplished by any of a variety of commonly known methods. See, e.g., the following references, which disclose screening of peptide libraries: Parmley and Smith, 1989, Adv. Exp. Med. Biol. 251:215-218; Scott and Smith, 1990, Science 249:386-390; Fowlkes et al., 1992; BioTechniques 13:422-427; Oldenburg et al., 1992, Proc. Natl. Acad. Sci. USA 89:5393-5397; Yu et al., 1994, Cell 76:933-945; Staudt et al., 1988, Science 241:577-580; Bock et al., 1992, Nature 355:564-566; Tuerk et al., 1992, Proc. Natl. Acad. Sci. USA 89:6988-6992; Ellington et al., 1992, Nature 355:850-852; U.S. Pat. No. 5,096,815, U.S. Pat. No. 5,223,409, and U.S. Pat. No. 5,198,346, all to Ladner et al.; Rebar and Pabo, 1993, Science 263:671-673; and CT Publication No. WO 94/18318.  
       [1191] In a specific embodiment, screening to identify a molecule that binds polypeptides of the invention can be carried out by contacting the library members with polypeptides of the invention immobilized on a solid phase and harvesting those library members that bind to the polypeptides of the invention. Examples of such screening methods, termed “panning” techniques are described by way of example in Parmley and Smith, 1988, Gene 73:305-318; Fowlkes et al., 1992, BioTechniques 13:422-427; PCT Publication No. WO 94/18318; and in references cited herein.  
       [1192] In another embodiment, the two-hybrid system for selecting interacting proteins in yeast (Fields and Song, 1989, Nature 340:245-246; Chien et al., 1991, Proc. Natl. Acad. Sci. USA 88:9578-9582) can be used to identify molecules that specifically bind to polypeptides of the invention.  
       [1193] Where the binding molecule is a polypeptide, the polypeptide can be conveniently selected from any peptide library, including random peptide libraries, combinatorial peptide libraries, or biased peptide libraries. The term “biased” is used herein to mean that the method of generating the library is manipulated so as to restrict one or more parameters that govern the diversity of the resulting collection of molecules, in this case peptides.  
       [1194] Thus, a truly random peptide library would generate a collection of peptides in which the probability of finding a particular amino acid at a given position of the peptide is the same for all 20 amino acids. A bias can be introduced into the library, however, by specifying, for example, that a lysine occur every fifth amino acid or that positions 4, 8, and 9 of a decapeptide library be fixed to include only arginine. Clearly, many types of biases can be contemplated, and the present invention is not restricted to any particular bias. Furthermore, the present invention contemplates specific types of peptide libraries, such as phage displayed peptide libraries and those that utilize a DNA construct comprising a lambda phage vector with a DNA insert.  
       [1195] As mentioned above, in the case of a binding molecule that is a polypeptide, the polypeptide may have about 6 to less than about 60 amino acid residues, preferably about 6 to about 10 amino acid residues, and most preferably, about 6 to about 22 amino acids. In another embodiment, a binding polypeptide has in the range of 15-100 amino acids, or 20-50 amino acids.  
       [1196] The selected binding polypeptide can be obtained by chemical synthesis or recombinant expression.  
       [1197] Other Activities  
       [1198] A polypeptide, polynucleotide, agonist, or antagonist of the present invention, as a result of the ability to stimulate vascular endothelial cell growth, may be employed in treatment for stimulating re-vascularization of ischemic tissues due to various disease conditions such as thrombosis, arteriosclerosis, and other cardiovascular conditions. The polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be employed to stimulate angiogenesis and limb regeneration, as discussed above.  
       [1199] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be employed for treating wounds due to injuries, burns, post-operative tissue repair, and ulcers since they are mitogenic to various cells of different origins, such as fibroblast cells and skeletal muscle cells, and therefore, facilitate the repair or replacement of damaged or diseased tissue.  
       [1200] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be employed stimulate neuronal growth and to treat and prevent neuronal damage which occurs in certain neuronal disorders or neuro-degenerative conditions such as Alzheimer&#39;s disease, Parkinson&#39;s disease, and AIDS-related complex. A polypeptide, polynucleotide, agonist, or antagonist of the present invention may have the ability to stimulate chondrocyte growth, therefore, they may be employed to enhance bone and periodontal regeneration and aid in tissue transplants or bone grafts.  
       [1201] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may be also be employed to prevent skin aging due to sunburn by stimulating keratinocyte growth.  
       [1202] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be employed for preventing hair loss, since FGF family members activate hair-forming cells and promotes melanocyte growth. Along the same lines, a polypeptide, polynucleotide, agonist, or antagonist of the present invention may be employed to stimulate growth and differentiation of hematopoietic cells and bone marrow cells when used in combination with other cytokines.  
       [1203] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be employed to maintain organs before transplantation or for supporting cell culture of primary tissues. A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be employed for inducing tissue of mesodermal origin to differentiate in early embryos.  
       [1204] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also increase or decrease the differentiation or proliferation of embryonic stem cells, besides, as discussed above, hematopoietic lineage.  
       [1205] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be used to modulate mammalian characteristics, such as body height, weight, hair color, eye color, skin, percentage of adipose tissue, pigmentation, size, and shape (e.g., cosmetic surgery). Similarly, a polypeptide, polynucleotide, agonist, or antagonist of the present invention may be used to modulate mammalian metabolism affecting catabolism, anabolism, processing, utilization, and storage of energy.  
       [1206] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may be used to treat weight disorders, including but not limited to, obesity, cachexia, wasting disease, anorexia, and bulimia.  
       [1207] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may be used to change a mammal&#39;s mental state or physical state by influencing biorhythms, caricadic rhythms, depression (including depressive disorders), tendency for violence, tolerance for pain, reproductive capabilities (preferably by Activin or Inhibin-like activity), hormonal or endocrine levels, appetite, libido, memory, stress, or other cognitive qualities.  
       [1208] A polypeptide, polynucleotide, agonist, or antagonist of the present invention may also be used as a food additive or preservative, such as to increase or decrease storage capabilities, fat content, lipid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional components.  
       [1209] The above-recited applications have uses in a wide variety of hosts. Such hosts include, but are not limited to, human, murine, rabbit, goat, guinea pig, camel, horse, mouse, rat, hamster, pig, micro-pig, chicken, goat, cow, sheep, dog, cat, non-human primate, and human. In specific embodiments, the host is a mouse, rabbit, goat, guinea pig, chicken, rat, hamster, pig, sheep, dog or cat. In preferred embodiments, the host is a mammal. In most preferred embodiments, the host is a human.  
       [1210] Other Preferred Embodiments  
       [1211] Other preferred embodiments of the claimed invention include an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 50 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X or the complementary strand thereto, and/or cDNA plasmid:V.  
       [1212] Also preferred is a nucleic acid molecule wherein said sequence of contiguous nucleotides is included in the nucleotide sequence of SEQ ID NO:X in the range of positions identified for SEQ ID NO:X in Table 1.  
       [1213] Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 150 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X or the complementary strand thereto, and/or cDNA plasmid:V.  
       [1214] Further preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least about 500 contiguous nucleotides in the nucleotide sequence of SEQ ID NO:X or the complementary strand thereto, and/or cDNA plasmid:V.  
       [1215] A further preferred embodiment is a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NO:X in the range of positions identified for SEQ ID NO:X in Table 1.  
       [1216] A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence of SEQ ID NO:X or the complementary strand thereto, and/or cDNA plasmid:V.  
       [1217] Also preferred is an isolated nucleic acid molecule which hybridizes under stringent hybridization conditions to a nucleic acid molecule comprising a nucleotide sequence of SEQ ID NO:X or the complementary strand thereto and/or cDNA plasmid:V, wherein said nucleic acid molecule which hybridizes does not hybridize under stringent hybridization conditions to a nucleic acid molecule having a nucleotide sequence consisting of only A residues or of only T residues.  
       [1218] Also preferred is a composition of matter comprising a DNA molecule which comprises cDNA plasmid:V.  
       [1219] Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in the nucleotide sequence of cDNA plasmid:V.  
       [1220] Also preferred is an isolated nucleic acid molecule, wherein said sequence of at least 50 contiguous nucleotides is included in the nucleotide sequence of an open reading frame sequence encoded by cDNA plasmid:V.  
       [1221] Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to sequence of at least 150 contiguous nucleotides in the nucleotide sequence encoded by cDNA plasmid:V.  
       [1222] A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to sequence of at least 500 contiguous nucleotides in the nucleotide sequence encoded by cDNA plasmid:V.  
       [1223] A further preferred embodiment is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to the complete nucleotide sequence encoded by cDNA plasmid:V.  
       [1224] A further preferred embodiment is a method for detecting in a biological sample a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X or the complementary strand thereto and a nucleotide sequence encoded by cDNA plasmid:V; which method comprises a step of comparing a nucleotide sequence of at least one nucleic acid molecule in said sample with a sequence selected from said group and determining whether the sequence of said nucleic acid molecule in said sample is at least 95% identical to said selected sequence.  
       [1225] Also preferred is the above method wherein said step of comparing sequences comprises determining the extent of nucleic acid hybridization between nucleic acid molecules in said sample and a nucleic acid molecule comprising said sequence selected from said group. Similarly, also preferred is the above method wherein said step of comparing sequences is performed by comparing the nucleotide sequence determined from a nucleic acid molecule in said sample with said sequence selected from said group. The nucleic acid molecules can comprise DNA molecules or RNA molecules.  
       [1226] A further preferred embodiment is a method for identifying the species, tissue or cell type of a biological sample which method comprises a step of detecting nucleic acid molecules in said sample, if any, comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X or the complementary strand thereto and a nucleotide sequence encoded by cDNA plasmid:V.  
       [1227] The method for identifying the species, tissue or cell type of a biological sample can comprise a step of detecting nucleic acid molecules comprising a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from said group.  
       [1228] Also preferred is a method for diagnosing in a subject a pathological condition associated with abnormal structure or expression of a nucleotide sequence of SEQ ID NO:X or the complementary strand thereto or cDNA plasmid:V which encodes a protein, wherein the method comprises a step of detecting in a biological sample obtained from said subject nucleic acid molecules, if any, comprising a nucleotide sequence that is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X or the complementary strand thereto and a nucleotide sequence of cDNA plasmid:V.  
       [1229] The method for diagnosing a pathological condition can comprise a step of detecting nucleic acid molecules comprising a nucleotide sequence in a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from said group.  
       [1230] Also preferred is a composition of matter comprising isolated nucleic acid molecules wherein the nucleotide sequences of said nucleic acid molecules comprise a panel of at least two nucleotide sequences, wherein at least one sequence in said panel is at least 95% identical to a sequence of at least 50 contiguous nucleotides in a sequence selected from the group consisting of: a nucleotide sequence of SEQ ID NO:X or the complementary strand thereto and a nucleotide sequence encoded by cDNA plasmid:V. The nucleic acid molecules can comprise DNA molecules or RNA molecules.  
       [1231] Also preferred is an isolated polypeptide comprising an amino acid sequence at least 90% identical to a sequence of at least about 10 contiguous amino acids in the polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and/or a polypeptide encoded by cDNA plasmid:V.  
       [1232] Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 30 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and/or a polypeptide encoded by cDNA plasmid:V.  
       [1233] Further preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 100 contiguous amino acids in the amino acid sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and/or a polypeptide encoded by cDNA plasmid:V.  
       [1234] Further preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to the complete amino acid sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and/or a polypeptide encoded by cDNA plasmid:V.  
       [1235] Further preferred is an isolated polypeptide comprising an amino acid sequence at least 90% identical to a sequence of at least about 10 contiguous amino acids in the complete amino acid sequence of a polypeptide encoded by cDNA plasmid:V.  
       [1236] Also preferred is a polypeptide wherein said sequence of contiguous amino acids is included in the amino acid sequence of a portion of said polypeptide encoded by cDNA plasmid:V; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and/or the polypeptide sequence of SEQ ID NO:Y.  
       [1237] Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 30 contiguous amino acids in the amino acid sequence of a polypeptide encoded by cDNA plasmid:V.  
       [1238] Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to a sequence of at least about 100 contiguous amino acids in the amino acid sequence of a polypeptide encoded by cDNA plasmid:V.  
       [1239] Also preferred is an isolated polypeptide comprising an amino acid sequence at least 95% identical to the amino acid sequence of a polypeptide encoded by cDNA plasmid:V.  
       [1240] Further preferred is an isolated antibody which binds specifically to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: a polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and a polypeptide encoded by cDNA plasmid:V.  
       [1241] Further preferred is a method for detecting in a biological sample a polypeptide comprising an amino acid sequence which is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: a polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and a polypeptide encoded by cDNA plasmid:V; which method comprises a step of comparing an amino acid sequence of at least one polypeptide molecule in said sample with a sequence selected from said group and determining whether the sequence of said polypeptide molecule in said sample is at least 90% identical to said sequence of at least 10 contiguous amino acids.  
       [1242] Also preferred is the above method wherein said step of comparing an amino acid sequence of at least one polypeptide molecule in said sample with a sequence selected from said group comprises determining the extent of specific binding of polypeptides in said sample to an antibody which binds specifically to a polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: a polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and a polypeptide encoded by cDNA plasmid:V.  
       [1243] Also preferred is the above method wherein said step of comparing sequences is performed by comparing the amino acid sequence determined from a polypeptide molecule in said sample with said sequence selected from said group.  
       [1244] Also preferred is a method for identifying the species, tissue or cell type of a biological sample which method comprises a step of detecting polypeptide molecules in said sample, if any, comprising an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and a polypeptide encoded by cDNA plasmid:V.  
       [1245] Also preferred is the above method for identifying the species, tissue or cell type of a biological sample, which method comprises a step of detecting polypeptide molecules comprising an amino acid sequence in a panel of at least two amino acid sequences, wherein at least one sequence in said panel is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the above group.  
       [1246] Also preferred is a method for diagnosing in a subject a pathological condition associated with abnormal structure or expression of a nucleic acid sequence identified in Table 1 encoding a polypeptide, which method comprises a step of detecting in a biological sample obtained from said subject polypeptide molecules comprising an amino acid sequence in a panel of at least two amino acid sequences, wherein at least one sequence in said panel is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and a polypeptide encoded by cDNA plasmid:V.  
       [1247] In any of these methods, the step of detecting said polypeptide molecules includes using an antibody.  
       [1248] Also preferred is an isolated nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a nucleotide sequence encoding a polypeptide wherein said polypeptide comprises an amino acid sequence that is at least 90% identical to a sequence of at least 10 contiguous amino acids in a sequence selected from the group consisting of: polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and a polypeptide encoded by cDNA plasmid:V.  
       [1249] Also preferred is an isolated nucleic acid molecule, wherein said nucleotide sequence encoding a polypeptide has been optimized for expression of said polypeptide in a prokaryotic host.  
       [1250] Also preferred is an isolated nucleic acid molecule, wherein said polypeptide comprises an amino acid sequence selected from the group consisting of: polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the comlementary strand thereto and a polypeptide encoded by cDNA plasmid:V.  
       [1251] Further preferred is a method of making a recombinant vector comprising inserting any of the above isolated nucleic acid molecule into a vector. Also preferred is the recombinant vector produced by this method. Also preferred is a method of making a recombinant host cell comprising introducing the vector into a host cell, as well as the recombinant host cell produced by this method.  
       [1252] Also preferred is a method of making an isolated polypeptide comprising culturing this recombinant host cell under conditions such that said polypeptide is expressed and recovering said polypeptide. Also preferred is this method of making an isolated polypeptide, wherein said recombinant host cell is a eukaryotic cell and said polypeptide is a human protein comprising an amino acid sequence selected from the group consisting of: polypeptide sequence of SEQ ID NO:Y; a polypeptide encoded by SEQ ID NO:X or the complementary strand thereto and a polypeptide encoded by cDNA plasmid:V. The isolated polypeptide produced by this method is also preferred.  
       [1253] Also preferred is a method of treatment of an individual in need of an increased level of a protein activity, which method comprises administering to such an individual a Therapeutic comprising an amount of an isolated polypeptide, polynucleotide, immunogenic fragment or analogue thereof, binding agent, antibody, or antigen binding fragment of the claimed invention effective to increase the level of said protein activity in said individual.  
       [1254] Also preferred is a method of treatment of an individual in need of a decreased level of a protein activity, which method comprised administering to such an individual a Therapeutic comprising an amount of an isolated polypeptide, polynucleotide, immunogenic fragment or analogue thereof, binding agent, antibody, or antigen binding fragment of the claimed invention effective to decrease the level of said protein activity in said individual.  
       [1255] In specific embodiments of the invention, for each “Contig ID” listed in the fourth column of Table 2, preferably excluded are one or more polynucleotides comprising, or alternatively consisting of, a nucleotide sequence referenced in the fifth column of Table 2 and described by the general formula of a−b, whereas a and b are uniquely determined for the corresponding SEQ ID NO:X referred to in column 3 of Table 2. Further specific embodiments are directed to polynucleotide sequences excluding one, two, three, four, or more of the specific polynucleotide sequences referred to in the fifth column of Table 2.  
       [1256] Preferably excluded from the present invention are one or more polynucleotides comprising a nucleotide sequence described by the general formula of c−d, where both c and d correspond to the positions of nucleotide residues shown in SEQ ID NO:X, and where d is greater than or equal to c+14.  
       [1257] In no way is this listing meant to encompass all of the sequences which may be excluded by the general formula, it is just a representative example. All references available through these accessions are hereby incorporated by reference in their entirety.  
                               TABLE 2                               NT                   cDNA   SEQ ID       Gene No.   Plasmid: V   NO: X   Contig ID   Public Accession Numbers                                                    1   HCE1P80   2   973903   BG033745, AA476827, AV704156, AL137944,                       AI971680, AW297211, BF760130, AI520706,                       BF833782, BE907421, BE242671, AW936474,                       AW936371, AW190143, AW519008, AI432598,                       AI393538, AW295856, AA393801, BF687731,                       AI765546, BF898133, AA146856, BF217337,                       BE146273, AL532972, AI204615, BF437991,                       AA146855, AL021453.1, AK026002.1,                       AL355838.3, AL009047.1, AL354696.11,                       AL356806.4, AC010460.6, AC010977.4,                       AC013242.7, AP000426.3, AL512268.10,                       AC009245.10, AP001001.4, AC022415.5,                       AC018517.6, AC005521.1, AC008163.2,                       AL138878.10, AC007881.4, AL136531.16,                       AL138976.5, AL050350.14, AL160254.10,                       AC004584.1, AL356379.10, AL158815.14,                       AL109751.19, AC005384.2, AC008736.6,                       AC022542.4, AL136160.18, AL591807.1,                       AL031681.16.       1   HCE1P80   22   1315876       1   HCE1P80   23   1055553       2   HUFGH53   3   1143339   AI672862, AI972278, AI090242, AI365229,                       AA524422, AI916766, AW242863, AW014261,                       AA044337, AI863149, AI658700, AI491865,                       AI344186, BF001214, AI658683, AW972265,                       AI680049, AI638089, AA044219, AA775576,                       AA034372, AI023942, AI276995, W25392,                       AA603067, AA034373, AI197784, W35182,                       AA339233, H55506, AW084219, AW168373,                       AA807088, AW151785, AI866798, AI673256,                       BF817402, AI473598, AI347701, AI799199,                       AI569309, AI866002, BF885085, BF815196,                       BG251264, AI474107, AI635367, AI682075,                       AI828731, AW089179, AW151714, AI633419,                       BE964767, AI696819, AW189424, AV682807,                       AW983822, AI491783, AI250848, AI933785,                       AI365256, AW085786, AI874151, AI932949,                       AW149869, AW023590, AI873644, AI697324,                       AI274013, AI539771, BG260144, AV682802,                       AI308032, AI251830, AI344785, BG058039,                       AI648502, AW954031, AW088899, AW168485,                       AI280670, AI590999, AI699011, AW088903,                       BG027280, BE613727, AI922901, AI922561,                       AI799195, AW004886, AI620868, AI859464,                       AI818578, BF921092, AW130863, AI687009,                       AW152550, AI538342, BF968910, BE963918,                       AI432736, AI249962, AI446373, AI636619,                       AW191892, AW129230, AW167238, BF914091,                       AI860045, AI433976, AW079159, AI619716,                       AW082060, AI890806, AW087938, AI687065,                       AI539153, AI612759, BE963035, AW151729,                       BF816785, BF816455, AI867042, BF526861,                       AI566630, AI280661, BE061389, AI866608,                       BF814541, AI537617, BE963286, AI919345,                       AI922577, BF915537, AW834355, AI888621,                       AI476109, BF915208, BE072233, AI366549,                       AI636719, AI570966, AI610645, AI434242,                       BF904180, AI620093, AI811168, AI611743,                       AW083804, AA830821, AI696626, AI589993,                       BE964497, BE538466, AW265004, BE393551,                       AI598061, AI587606, AI677797, AI431909,                       BE965169, AI811684, AW118518, AI613449,                       AI254727, AI783861, AW192288, AW002174,                       N74355, AI520702, AI433021, AI859402,                       AW149227, AI800138, AI890182, AI628833,                       BF344652, BF795712, AW168031, AW264029,                       AW169275, AW167448, AW264727, AW083189,                       AW193203, AI680498, AI805688, AI953880,                       AI554427, BE907440, AW172723, BG249582,                       AI475394, AW169001, AI915576, AI868831,                       AW847410, AW163823, BF811780, BE928768,                       AI471548, AI559599, AV755332, AI689571,                       AI355849, AI860783, AI174394, AW189415,                       AI680457, AI805769, BF814449, BF920893,                       AI567351, BF339322, AI863321, AI569328,                       AI521386, AI371228, AI567243, AI952064,                       AI554218, AW081255, AI888944, AW198075,                       AW088134, AW079739, AI812015, AI498579,                       AI702406, AI470284, AI590686, AI468872,                       AI382670, AI921734, AL036638, AI802240,                       AW167918, AI560052, AL110306, AI584140,                       AI862144, AW085667, BG150947, AI628217,                       AI520810, AI866786, AI648567, AI400725,                       BE543089, Y07848.1, AL031186.8, Z95116.1,                       AL050138.1, BC008983.1, AL137461.1,                       Y14314.1, AL133645.1, BC006201.1,                       AL137463.1, AK024538.1, AK026408.1,                       AK026597.1, AL389939.1, AL133075.1,                       AL389978.1, AL137705.1, AB060929.1,                       AK026533.1, AK025349.1, AF218031.1,                       BC005151.1, AF358829.1, AL137556.1,                       BC003105.1, BC005678.1, AF091084.1,                       AK026591.1, AL359618.1, AL162062.1,                       AK025312.1, U39656.1, X69819.1, AL137300.1,                       AL080137.1, AB056768.1, AK026504.1,                       BC005858.1, AK000647.1, AF217987.1,                       AB048974.1, AF090903.1, AL389982.1,                       AL136749.1, AL080086.1, AF321617.1,                       BC003650.1, AK000450.1, AF026816.2,                       AK026947.1, BC001349.1, AJ242859.1,                       AF000145.1, BC008365.1, AF081197.1,                       AF081195.1, AL080060.1, AL137273.1,                       AL512761.1, AB052200.1, AF125949.1,                       AB049758.1, AK025383.1, BC006412.1,                       AL050393.1, BC006133.1, BC009033.1,                       BC003683.1, BC007355.1, AL133014.1,                       U80742.1, AL137294.1, AK026532.1,                       BC009341.1, AK000652.1, AL162083.1,                       AF159141.1, BC002839.1, AB048919.1,                       BC002343.1, BC006494.1, AB063084.1,                       AB049848.1, AB019565.1, AL122098.1,                       AL133104.1, AL133565.1, AL512754.1,                       BC004370.1, AB056427.1, AB060905.1,                       AB060211.1, BC007641.1, AL157479.1,                       BC000316.1, BC003682.1, AK025708.1,                       AL080074.1, AB055361.1, AL390167.1,                       AL117649.1, AF162270.1, BC006508.1,                       BC006164.1, AB063008.1, BC008485.1,                       AB063079.1, AL080158.1, BC000556.1,                       BC003687.1, AL442072.1, AF242525.1,                       S61953.1, AC002467.1, BC008780.1,                       AL136928.1, AB060912.1, AL122049.1,                       AK026086.1, AB048964.1, AK026528.1,                       AF217966.1, AL122050.1, AF218014.1,                       AL162003.1, AL137271.1, AF177336.1,                       AL359583.1, AL136844.1, AL133665.1,                       AL133098.1, AK027182.1, AL512746.1,                       AK024601.1, AB047801.1, AL133557.1,                       AB060852.1, AL110221.1, BC006807.1,                       AK026608.1, AL157431.1, AL133568.1,                       AL136845.1, AL133113.1, BC008893.1,                       AL136784.1, AB047887.1, AF225424.1,                       AB055366.1, AK025491.1, AL136843.1,                       AL110280.1, AL080127.1, AL050149.1,                       AF217991.1, AL122093.1, AF003737.1,                       BC009026.1, AK026057.1, BC005890.1,                       AL049382.1, BC008417.1, AB063088.1,                       AK027193.1, AF113222.1, AL137538.1,                       AB055368.1, AK025524.1, BC009253.1,                       BC007198.1, AL136799.1, AK026865.1,                       AF078844.1, AL512718.1, AF219137.1,                       AK000445.1, AK026642.1, AL049465.1,                       AK026164.1, AF104032.1, AL133081.1,                       BC004951.1, AL122111.1, AB060863.1,                       AK025209.1, AL137648.1, AL162006.1,                       AK026592.1, AL117585.1, AK025573.1,                       AL136789.1, BC002342.1, AL353940.1,                       AF207829.1, AK027116.1, AL117432.1,                       AL512719.1, AL136790.1, AL050277.1,                       AL080124.1, AF271350.1, BC008387.1,                       AL359941.1, AL136622.1, AL133077.1,                       AK026526.1, AB047615.1, AK025906.1,                       AK026045.1, AB050534.1, AL353957.1,                       AK026885.1, L30117.1, AF183393.1,                       AK027164.1, AB060903.1, AL117440.1,                       AK026551.1, AL117435.1, AL110222.1,                       AK000718.1, AK026534.1, AF111112.1,                       AL162002.1, AK026855.1, AL137429.1,                       AK027113.1, AL137526.1, L19437.2,                       BC008070.1, AB055315.1.       2   HUFGH53   24   894857   AI672862, AI972278, AI090242, AI365229,                       AA524422, AI916766, AW242863, AW014261,                       AA044337, AI863149, AI658700, AI491865,                       AI344186, BF001214, AI658683, AW972265,                       AI680049, AI638089, AA044219, AA775576,                       AA034372, AI023942, AI276995, W25392,                       AA603067, AA034373, AI197784, W35182,                       H55506, AA339233, AL031186.8, Y07848.1,                       Z95116.1.       2   HUFGH53   25   1407421       2   HUFGH53   26   1407330       2   HUFGH53   27   1407326       2   HUFGH53   28   1324108       2   HUFGH53   29   1143314       2   HUFGH53   30   1124368       3   HWMMO59   4   1426876   AI634846, BF589994, AI660577, AW873053,                       BE906672, AI241049, AW008561, BF750885,                       BE963035, AI280661, BF816455, AW088899,                       AI446003, AI566630, BF694790, BG120816,                       AI702073, AI537617, BE061389, AI919345,                       AI633419, AI610645, BF038804, AI554218,                       AI866002, BF817402, AI867042, AI539028,                       BE963918, AI859464, AW083804, AI921386,                       BF968504, AI674912, AI469811, AI627880,                       AI636719, AI608676, BF904180, BF726504,                       AI250663, AI433976, BF815196, AI619716,                       AI561299, AI612759, AW151729, AI699011,                       BF811780, BF909758, BE621256, AI364788,                       AI611743, BF914091, BE613727, AW168485,                       BF814335, BE968711, BF913616, AW103371,                       AI697324, AI933785, AI805688, BF915537,                       BG026746, AI365256, AW079159, AI251830,                       BE964767, BG058039, AI689175, BE928768,                       AI635464, BE875407, AW087938, AI366549,                       AI539153, BF816785, BF726237, AW131954,                       AW090494, AW834355, BF344652, BE393551,                       BE964089, BG031664, AI494201, AI610756,                       AA830821, AI963040, AI679916, AL079794,                       AW102785, BF814409, BE887861, AI921176,                       AW084219, AW103886, AI499652, AW082594,                       AI633306, BE967016, BE897632, BF814541,                       AI345746, N80094, AW858254, AI251205,                       BF915208, AV682496, AI868831, AI888953,                       AI886124, AI655932, AW151785, AV683272,                       AI431909, BF885085, AV690007, AI828731,                       BF795712, AI432736, AI687065, AW089179,                       AI696819, AI783861, BE785868, AI680498,                       AW192375, AI520809, AI922577, AI799234,                       AI498579, BE875786, AI696626, AW198075,                       BE904051, BE072233, AI589993, BE544111,                       BG179099, AI566507, AI264741, AI952360,                       BF726603, AI866741, AI680457, AI468872,                       AI866608, BE963286, AI698401, BE884910,                       AW079572, AI572418, AW172723, AI400725,                       AI568870, AI241819, BE964497, BE538466,                       BF854113, AW029263, AI952920, AW020095,                       AW103893, AI805638, AI805769, AI963062,                       AW195957, AI624668, BF342070, BE966388,                       AW071417, AI628292, AW021588, AW085667,                       AI801605, AI888429, BG181012, AI885974,                       AI493559, AL041772, AI613017, AI432040,                       BE964981, AW089258, AI628217, AI866887,                       AI812015, AW235035, BF910810, AW192226,                       AW168031, AI474076, AI886022, AI891157,                       AI249962, AI872914, AW104146, BG171779,                       BF037484, AW088903, AW151714, AW129230,                       BE246734, AI471361, AI678443, AI587288,                       AI696378, AW088134, BE965060, AI598113,                       AW051107, BF752252, BE964198, AI648502,                       BF924882, AI590645, AI539771, AA425380,                       AW082040, AW103195, AW084131, AI677797,                       BF921092, BF792469, AW117907, AI569616,                       BE965481, BF910849, BF812933, BF204484,                       AL110306, AI745713, BF725863, AL119791,                       AI888621, AL041150, AI888944, BE964512,                       AW858243, BG030364, BE966947, AI922365,                       AI274769, AI540850, N74355, AI133489,                       AI929108, AI648663, BC001349.1, BC003683.1,                       AK025414.1, AB056427.1, AK025209.1,                       AK025906.1, AL133104.1, AK000652.1,                       AL512718.1, AB063100.1, AL389978.1,                       AK000753.1, AK025383.1, AK026865.1,                       AK024538.1, AK025958.1, AB063008.1,                       BC008417.1, AF225424.1, BC003548.1,                       AB060826.1, AL080124.1, AL137556.1,                       AB063046.1, AB019565.1, AL122098.1,                       BC007198.1, BC008893.1, AL080060.1,                       AK026642.1, BC005678.1, AF104032.1,                       AL050024.1, AL512719.1, AB050534.1,                       AK025491.1, AL136928.1, AL512761.1,                       AK024601.1, AK027116.1, AB049758.1,                       AL389939.1, AF271350.1, AL050138.1,                       AL136843.1, U80742.1, AB060214.1,                       AL137526.1, BC006164.1, U39656.1, X69819.1,                       AB060929.1, AB056768.1, AL390167.1,                       AK027868.1, AL512754.1, BC003687.1,                       AB060863.1, AB063079.1, AK026608.1,                       AB060839.1, AL117432.1, AF111112.1,                       BC009033.1, AK026592.1, AF177336.1,                       BC008485.1, AB047801.1, AF207829.1,                       AK025772.1, BC008899.1, AL080137.1,                       BC006807.1, AL133077.1, AK026532.1,                       AK000618.1, AK027113.1, AK026959.1,                       AB052191.1, AL133093.1, AB047887.1,                       Z82022.1, AK026947.1, AK027193.1,                       AF162270.1, AB063084.1, BC009341.1,                       AL137476.1, AK026533.1, AK027114.1,                       AB051158.1, AF146568.1, AB050510.1,                       AK026045.1, BC008280.1, BC003682.1,                       AL080127.1, AL133075.1, Y14314.1,                       AL117440.1, AL136845.1, AK026551.1,                       AK000718.1, AL122110.1, AL122049.1,                       AK026480.1, AL133080.1, AL049382.1,                       AL133640.1, AB048919.1, AL117583.1,                       AL133098.1, AK026784.1, AL117585.1,                       AL162062.1, AL136864.1, AL133113.1,                       AL133072.1, AL122123.1, X72889.1,                       AF348209.1, AL353625.5, AK026597.1,                       AB055374.1, AK027200.1, AB049848.1,                       AB060912.1, AK026086.1, AK000647.1,                       BC004951.1, AL359583.1, AL359618.1,                       AL162006.1, AL137538.1, AK026630.1,                       AK026452.1, AF125949.1, AF260566.1,                       AL353940.1, AL050277.1, BC004370.1,                       AF090901.1, AL137527.1, BC008387.1,                       AL133565.1, AL122121.1, AL136799.1,                       AK026408.1, AF078844.1, AK026464.1,                       X82434.1, AK026504.1, BC005890.1,                       AB063070.1, AF217966.1, AK000137.1,                       AF217987.1, BC004958.1, AK027164.1,                       AK025312.1, AK025524.1, AL442072.1,                       BC006412.1, BC008365.1, AL110280.1,                       AL136749.1, AL162002.1, BC008382.1,                       AL049466.1, BC008070.1, BC002839.1,                       AL512684.1, AK000445.1, AL080159.1,                       AK000432.1, AK026583.1, AB047615.1,                       L30117.1, AB056420.1, AB055366.1,                       AK025092.1, BC009212.1, S78214.1,                       AK025632.1, AL136768.1, AL050116.1,                       AL133016.1, AK025254.1, BC007021.1,                       AK000323.1, AK000391.1, AL136586.1,                       AK026534.1, AL137463.1, S61953.1,                       BC008780.1, AL162083.1, AB048964.1,                       AK025391.1, AB048953.1, AL122050.1,                       AF218014.1, AL136844.1, AL137459.1,                       AF113222.1, AL512746.1, AL117460.1,                       AB062938.1, AL133557.1, AB055303.1,                       AL359601.1, AB060887.1, AL117457.1,                       AL096744.1, AL359615.1, AL157431.1,                       AL133568.1, AL133014.1, AL359620.1,                       U91329.1, AF106862.1, AL110196.1,                       AK026542.1, AF219137.1, AF090896.1,                       AL359941.1, AL133067.1, Y16645.1,                       AL136786.1, AL080074.1, AK027204.1,                       AK025573.1, AK000486.1, AL110221.1,                       AK025484.1, AK026855.1, AJ012755.1,                       AK024524.1, AF003737.1, AF090934.1,                       AL137283.1, BC005151.1, AK026528.1,                       AK026629.1, AL359596.1, AB060916.1,                       AF183393.1, AK027160.1, AK025798.1,                       AB060852.1.       3   HWMMO59   31   1356977       4   HSSJJ51   5   900561   BF526701, BF873331, BF929164, BF221973,                       AV688712, BF743216, AI682301, BF929165,                       AA368885, BE295879, AI078870, BE270667,                       AI611295, BF963547, AA323287, BF763407,                       BF002002, BF002176.       5   HCEWD38   6   1284936   AA746177, AI510718, R37382, AI247745,                       R52665, AA323018, H49570, N55573, BG236027,                       AW966998, AA323159, AL039810, R13472,                       AL039789, BF332816, AW955388, BF879416,                       AA304816, AW964665, AA323409, R52713.       5   HCEWD38   32   616396   AA323018, AA323159, AW966998, R13472,                       AW955388, AA304816, AW964665, AA323409,                       R52713, AL132800.4.       5   HCEWD38   33   411082   R37382, AA746177, AI510718, R52665,                       AI247745, AA323018, N55573, BG236027,                       H49570, AW966998, AA323159, R13472,                       AW955388, AL039810, AA304816, BF879416,                       AW964665, AA323409, AL039789, BF332816,                       R52713.       6   HUCMC56   7   1310874   R20045, AW965432, AA332557, R36770, R60458,                       AA340432, AW163243, AX018985, AX018987,                       M58583, S76975, AL117383.       6   HUCMC56   34   967258   R60458, AW163243.       7   HWLZU06   8   1310875   BF055285, BF882978, AW070344, AI805087,                       BF906443, AI083823, W92687, AI085548,                       AI083824, W92830, BE138819, AW192716,                       AW150070, BF588518, AA775561, BF764330,                       AW172659, M91217, AI393090, AW137263,                       F33371, W05570, R70460, AA339837, AI564511,                       AA359338, AW380993, AW960500, AW192211,                       AI924106, AA377546, AI346326, AI825277,                       BF724241, AI432310, AI144286, AA301724,                       AI619600, AI783751, AI470161, AI457948,                       AW190639, AI338249, AW025095, AL110261,                       AF086482.       7   HWLZU06   35   933581   BF055285, BF882978, AI346326, AI432310,                       AI144286, AI805087, AW070344, AI338249,                       BF906443, AI457948, AI083823, AI470161,                       AI085548, W92687, AI083824, W92830,                       BE138819, AW192716, AW150070, BF588518,                       AA775561, BF764330, AW172659, AI393090,                       M91217, F33371, W05570, AW137263, R70460,                       AA339837, AI928593, AI564511, AA359338,                       AW380993, AW960500, AI924106, AA377546,                       AW192211, AI825277, AA301724, AI619600,                       AI783751, BF724241, AA704632, AW190639,                       N76120, AW025095.       8   HDPBA69   9   905708   BF343049, BF525949, AI300176, BF342466,                       AI193100, AW953836, N32601, AA894528,                       BF526118, AI749282, AA917673, AI200645,                       AA577400, AW001112, AI342526, AI561024,                       AA922077, BF339231, BG060138, AI274361,                       AW629891, AI811138, AI682589, AI598054,                       BF821354, AA703086, BF821349, AW000838,                       AI687717, BF879161, AI346224, AI283829,                       AW966426, BF878968, AI718510, N38801,                       AA609464, AA443822, AI285277, AI141075,                       C17007, AA827271, AI274203, AI278912,                       AW953891, AA485613, AI291153, AI184968,                       AI815092, BF879241, AA922163, AA954441,                       W92736, AI523358, AI582743, AI272748, T95291,                       AI304507, AW858976, BF823040, R47871,                       H90673, R71353, AV689909, W92820,                       AW515183, AA640081, R47872, AI749077,                       AA508675, AA025765, AI352318, H66699,                       R66274, T27046, H78056, AI873364, H66689,                       AW029317, AI336608, H64116, AI872250,                       H42114, T95371, AA383872, R24350, AI749260,                       BF087543, T72087, AA025953, BF820542,                       BF737942, AA371827, N90491, BG012708,                       AI459266, D31533, H64951, BE769806,                       AA368991, N69227, H01130, BF821339, H89819,                       R72785, BE769826, H01871, R62666, BF349116,                       N45434, R72786, AW374237, AW953834,                       H78057, T16823, AA295668, BE140683,                       AW277068, AW135690, AI088641, BF881707,                       AW374232, AW610099, H73228, R24669,                       H26462, T72232, T23681, H27838, H64952,                       BE769808, H70128, N47826, R43349, H83150,                       BF991147, AI476021, AI202813, AL514919,                       AL513597, AW605902, AL514627, AL513907,                       AL514791, AL513643, AL514691, AL513553,                       AI560012, AW105588, AL513693, AL514087,                       AL513911, AL514015, AI500553, AL513631,                       AL514473, BE966388, AI697137, AW195957,                       AI873731, AI567351, AI687728, AL514793,                       AI699857, AI630928, AW268253, BE785905,                       AI285735, AI436456, BG105445, AI613017,                       AV757455, AI499393, AI934036, BG260037,                       AL515041, AI679724, AI920968, AI862142,                       BF037097, BE964741, AI349645, AI625079,                       AI619502, AI281762, AI349772, AL047042,                       AI857296, AL514359, AL121270, AL513977,                       BF883916, AV706777, AL036396, BE047863,                       BF882343, BG058208, AI671679, AI271786,                       AW148320, AL514929, BF055737, AW827249,                       AL513763, AI874109, AV711509, AL515375,                       AL119049, AL514867, AI597750, AI597918,                       AL514261, BE048071, AW827203, AI538716,                       AV655645, AV682476, AV729890, AI281745,                       AL045500, AI064830, BG036846, AI475134,                       AI673256, AL036802, AI580984, BG179993,                       AI863014, AV755207, BF724691, AL046849,                       AI868831, BE964812, BE965111, BF795712,                       BG257535, AL513999, BF971016, BG178488,                       BF726322, BG180996, AL513803, AV755581,                       AW071349, AV681857, AL515413, AI445025,                       AL121365, BF343172.       8   HDPBA69   36   906482   BF343049, BF525949, AI300176, BF342466,                       AW953836, AI749282, AA894528, N32601,                       BF526118, AI193100, AA577400, AI200645,                       AA917673, AW001112, AA703086, AI687717,                       AI342526, AI561024, BF339231, AI141075,                       AA922077, AW629891, AI274361, AI184968,                       AA922163, AI815092, BF821349, W92736,                       BF821354, AI682589, AW000838, BF879161,                       BF878968, AI346224, AI718510, AI283829,                       N38801, AW966426, AA443822, AA609464,                       C17007, AI285277, BG060138, AA827271,                       AW953891, AI274203, AA485613, AI811138,                       AI278912, BF879241, AI291153, AI598054,                       AA954441, AW515183, AI272748, AI304507,                       T95291, AA508675, AW858976, AI582743,                       BF823040, R47871, R71353, AV689909, W92820,                       AA640081, R47872, AI749077, AI523358,                       AA025765, AI459266, H64116, T27046,                       AI352318, H66689, R66274, H78056, AI873364,                       H90673, H42114, AI336608, T95371, AA383872,                       R24350, AI749260, AW029317, BF087543,                       T72087, AA025953, AW135690, BF820542,                       H64951, BF737942, AA371827, H01130, H66699,                       N90491, BG012708, D31533, H01871, AI872250,                       BE769806, AA368991, N69227, H89819,                       BF821339, R72785, BE769826, R62666,                       BF349116, N45434, R72786, AW374237,                       AW953834, T16823, AA295668, BE140683,                       AW277068, AI088641, H78057, H73228,                       BF881707, AW374232, AW610099, H26462,                       R24669, AI202813, T23681, T72232, H27838,                       H64952, BE769808, H70128, N47826, R43349,                       H83150, AI281745, BF991147, AI476021,                       AL513597, AL513907, AL514791, AL514627,                       AI500553, AL514919, AL514691, AW605902,                       AL514473, AL513911, AL513553, AL514087,                       BE785905, AV757455, AL513693, AL514359,                       AL515041, AL515375, BE966388, AL513803,                       AL047042, AV706777, AI349772, AI285735,                       AL513631, BG058208, BF054789, AI873731,                       AV682476, AL514793, BE048071, AW827203,                       AI567351, AI064830, AL119049, AL513643,                       BF724691, AI687728, AV729890, BF795712,                       BF726322, AL121270, AV681857, AV755581,                       BE964994, AI679724, AW071349, AL046849,                       AI868831, AV758806, AI349645, AI863014,                       BG179993, AI815383, AI560012, AV757639,                       AI906328, AV655645, AL513817, BF970162,                       BG108147, AL515373, BE047863, AI673256,                       AL515047, AV682249, AI499393, AV758110,                       AV682772, BG257535, AL514935, BG036846,                       AV682441, AV681716, BG168696, BF883916,                       AV682330, BE964812, BG260037, AW162071,                       AW827211, AV681668, BF971016, AI934036,                       AI697137, AV733397, AI436456, AV682351,                       AV710479, AW195957, AV756477, AV681951,                       BE048135, AV682466, BF793644, AI671679,                       AV757327, AV681630, AL514543, AV682252,                       BF343172, AV711924, AL514803, AW268253,                       AV711509, AL515413, AV733326, AL514015,                       BE965891, AI521012, R17629, AA835433.       8   HDPBA69   37   906481   AI346224, AI291153, AA922163, AI352318,                       AI342526, W92736, AA577400, AW000838,                       AA508675, AI598054, AI815092, AI749077,                       AI523358, AA703086, N38801, AI718510,                       AW001112, AA025765, AI561024, H66689,                       AW515183, H66699, R47872, AI873364,                       AI184968, AA894528, N32601, AI274361,                       AI274203, AI459266, AI200645, AI687717,                       AI682589, AI285277, AA917673, BG060138,                       AI193100, AA922077, AI283829, AI749260,                       AI272748, AA827271, AI141075, AA443822,                       AI300176, AI749282, AA609464, AI278912,                       AI088641, T95291, AI582743, H90673,                       AA954441, H78057, AI304507, AI811138,                       AI336608, AW277068, AI202813, AW135690,                       H64952, H73228, T23681, N69227, R43349,                       T16823, AW966426, R72785, R72786, AA383872,                       AI281745, BF087543, R71353, BF820542,                       BF823040, AW610099, AW605902, BF879161,                       BF821354, D31533, BF879241, BF878968,                       AI281707, BE011964, AW858976, R24350,                       AA835433, AW105588.       8   HDPBA69   38   906480   BF343049, BF525949, BF339231, AW629891,                       R47871, T27046, H42114, H64116, BF342466,                       H64951, N90491, H01871, H01130, H89819,                       N45434, H26462, H27838, BF526118, T72232,                       H83150, BF991147, AA640081, N47826,                       BE769806, AV689909, BF737942, R17629.       9   HLWAE11   10   783071   AI344312, AI276017, AI476822, AI139478,                       AI160906, AI240398, AW001088, AA425919,                       AA011278, AA428788, AI354692, AI089176,                       AA622689, BF431807, AI968918, N68826,                       AI467807, BF436247, AW673768, AW135943,                       R24434, R16812, R31419, R31434, R24435,                       H83155, AI865939, R31418, AW673133, W67349,                       R31433, AA027080, R28030, BE542160, T81223,                       AI631986, AA677315, BF760063, AI872675,                       BF331923, BE926682, BE926741, AF329842.1,                       Z82188.2.       10   HSZAF47   11   1283068   AW298370, AI433823, AI239867, D62170,                       D61860.       10   HSZAF47   39   456551   AW298370, AI433823, AI239867, D62170,                       D61860, AF329839.1, AC007016.5.       11   HWTAY65   12   908762   AI916779, AW304481, AA732948, AI288625,                       AW965223, AA443244, AA194106, W79527,                       BF511014, AI038644, AA443206, W93527,                       AA346195, W79559, BE296248, BE269743,                       AF329836.1.       11   HWTAY65   40   905611   AI916779, AW304481, AA732948, AI288625,                       AW965223, AA443244, AA194106, W79527,                       BF511014, AI038644, AA443206, W93527,                       AA346195, W79559, BE296248, AW975618,                       AW960414, AV724520, D51799, C14389, C14331,                       AW960553, AW966531, AW964468, AV718692,                       AW956397, AV720791, AV718489, AW973541,                       AW965175, AW949645, AW978634, AW966013,                       AW973307, AV720533, AW973474, D81030,                       AW949642, AW966059, AV720211, C14429,                       AW959202, AW966053, D80212, AW964756,                       AW960465, AW959136, D80166, AV718707,                       AV719822, AV719557, AW959799, AV720731,                       D59859, AW964477, AW966022, AW966029,                       AV718938, D80188, AV718633, AW975613,                       D51423, D59619, AW965177, AW949630,                       AW978661, D80210, AW966075, AW973488,                       D80240, D80253, AW966065, AV719324,                       AW949629, AW975605, AW973334, AV718931,                       AV720878, AW966032, AW966534, AV699447,                       D58283, AW958993, AV722801, AV723927,                       AW949656, AW966041, AW949631, AW949643,                       AW949618, AW949657, D59275, AW973482,                       AV721386, D80022, AV700889, D80195,                       AA305578, D80219, AW975621, AW978648,                       D80043, AW959597, D59467, AW960473,                       AW959570, AW949654, AW965163, D80391,                       D80164, AW966030, AW966054, AV720203,                       AV720150, AW966050, AV719188, D59787,                       AW958992, D80227, AW966062, AV718440,                       AV719783, AV720028, D59502, AV699550,                       AW959628, AW962082, BE269743, AV719468,                       AV718800, AW965185, AW965197, AW965196,                       AW973485, AW965184, AW960454, D57483,                       AV718844, AV720464, AV718770, AW959062,                       AW956434, AW964488, AW949641, D59610,                       AV699927, AA305409, D80366, D80024, D59889,                       D80196, AW973330, C15076, AW973447,                       AW949632, AW959582, D59927, AW949653,                       AW949655, D80269, D80038, D50979,                       AW959469, D51022, D80193, AW177440,                       D50995, AW964532, AW962245, AW964737,                       AW965158, AW949646, AW949633, AW949658,                       D80241, AW960532, D80378, AW966043,                       AV720812, D80045, AV720220, D51060,                       AW753053, AW966023, AV723097, AV699866,                       AW179328, D80248, AW960564, AW973490,                       D81026, AW752082, AW960504, AW965176,                       AW966389, AW975623, AV744690, AV699652,                       AW966330, AW178893, AV699746, AV718530,                       AV720616, D80522, AV701004, C14014,                       AV700229, AW973445, AW973465, T03269,                       C75259, AW960570, AV699479, AW962395,                       AV701335, AV718681, AV701043, AV701332,                       AV701017, AV701248, AV719000, AV701431,                       AV699682, AA514188, AA514186, AV719628,                       AV720654, D80268, D80251, AV742001,                       AV742667, AW753067, AV701125, AV701166,                       AV742430, AV701149, AW378532, AV742048,                       D80133, AV699669, AW966331, AW360811,                       AW377671, AV738340, AW177501, AW973473,                       AW177511, AW966332, AV720151.       12   HHGDP51   13   1310873   AI652297, BF967925, AW769372, BE857943,                       AA446941, BF115527, AI209086, AA443365,                       BF059139, D59611, AW204677, AI446405,                       AI918554, BE538466, BE965527, AW079768,                       BF816041, BF816031, AW082600, AW893295,                       BF885675, BF915537, AI537837, AA464646,                       AI582912, BF987113, AA835966, AI865116,                       AI620093, AI573026, AW058233, AV735118,                       AI889147, AI371228, AI349957, AA848053,                       AI345005, AI627880, AW084132, AW020592,                       BE613727, BG057418, AI345014, AW022494,                       N22406, AW020288, AI560679, BF913615,                       AW059713, AI636719, BE966928, BF817746,                       BF925348, BF915316, AI349814, BE875407,                       AW858254, AI583578, AW083804, AA830821,                       BG105895, AW075084, AI310925, BE904051,                       AI312399, AI349937, AI623736, AI334884,                       AI307543, AW411043, AI345251, BE245461,                       AW071412, AI307708, AI312325, AW071395,                       AV738918, BE964937, AI242736, AI340659,                       AW071377, AI311159, AI340644, BE138684,                       BF885000, AV736474, AI334930, AI309443,                       AI471909, AI307520, AI345026, AI307454,                       AI752007, AI340664, AI310592, AI307542,                       AI569632, AW151138, AI345817, BE621040,                       AI345739, AI345674, AI312143, BE965355,                       AI349637, AI334920, AW071276, AI310927,                       AI307578, AI336488, F32537, AI364788,                       AW082623, BE155168, AI636619, BG179295,                       AI349955, AW075093, AL046463, AI312432,                       AW084097, AI918408, BE172412, AI312357,                       BE907440, AI475151, AI680226, AI312237,                       W33163, AI250627, AW500379, AI950664,                       BE897632, AI873638, AI537643, AI866608,                       BE964700, AW073898, AW268261, BE271279,                       AA468418, AA514684, BF038804, AI805688,                       AI349213, AI611743, BE965169, AW263804,                       AI249877, BE965503, AI804505, AW900453,                       AI951222, AI888621, BF868927, AI696626,                       AI357599, AW149876, AI589993, AI365256,                       AW079334, BF909758, BE964497, BE910005,                       AI553669, AW085786, AI345677, AI636788,                       BF814449, AW265004, AW999906, BE393551,                       AI886055, AV738628, AI472536, AI677797,                       AI452857, AW196105, W81248, AW191844,                       BG113493, AI366959, AW074301, AI249946,                       AI244380, AI784233, AA493923, AI344935,                       AV648263, BG113236, BG178735, AW130430,                       AI828574, AW059828, AI738867, AI589428,                       AI805769, AI434242, AI345397, AW025533,                       BF572734, BE172499, BF924897, BE313517,                       BE964078, AW193467, BF872670, AI280670,                       AI802372, AI921420, AI446124, AI688848,                       AI499986, AI540606, AW089572, AI345737,                       AV738730, BG058217, AI345114, N99092,                       BE138712, AI915295, AI254226, BF814072,                       AI307210, AI590423, AI866786, AI336513,                       AI500659, AI336662, BG001293, AI336634,                       AI345261, AI868204, AI702301, AI307569,                       BF680133, AW079432, AI348895, AI345736,                       AW068845, AI313320, AI050666, AW081383,                       AI336495, N74355, AF120268, I41145, AI8777,                       AK024545, AF085809, AF107847, AL049460,                       AR068466, L13297, AJ301634, AF219137,                       S77771, AL137521, I89947, I48978, A08913,                       AF155148, AL389935, I89931, A08912, A08910,                       A08911, AR087170, A08909, AR038854, A08907,                       AL133104, A08908, AL122111, AF119856,                       AF125949, AF090896, X62773, S76508, I89934,                       AB019565, X62580, U42031, AF113676, E02253,                       E01812, AF254119, U91329, AF207829,                       AL035458, AF271350, AF094850, AK024601,                       AB025103, AF176651, AL080158, AB048995,                       E08631, AL137300, AK000652, AL133093,                       X87582, AK026590, AB051158, AF305835,                       AF217991, AB049848, X99257, AK026651,                       AB049629, AF114818, AL133098, AJ242859,                       AL117585, AL080127, U00686, AF040751,                       AL137705, A12297, A93016, I00734, AK026395,                       AL162083, AF119894, AK024594, AK000445,                       L40363, AB047897, AL133081, AK000212,                       AK025669, AK025573, AF188698, AB049758,                       E00617, E00717, E00778, AX027129, AF261883,                       A18788, AJ006417, U75370, U57352, AK025889,                       E02914, AL137283, AL133645, X70685, U57715,                       AK026541, I17767, AB046642, AB044390,                       AK000291, AL110225, AL389951, S53987,                       AL117394, AF119358, AF057300, AF057299,                       AF242525, I89944, AK026592, AK027105,                       AF117959, I09360, AK026571, AR038969,                       E15582, AK026924, AF111847, AL137547,                       X59414, AL110222, AK024538, AK026608,                       D55641, Z22828, AK026591, AF078844,                       AL080060, Y16258, Y16257, E02756, Y16256,                       AF065135, AF130054, Z72491, AF203473,                       AL353957, AF119909, AK025208, AL137648,                       U66274, AR079011, AR079012, A90832,                       AL137555, AL137659, AL117629, U77594,                       AK025383, AF030165, AF012536, AF003737,                       AK026533, AF116676, AB047248, AL389978,                       AF159141, AK027104, AF067420, U90884,                       AL359600, AF116644, AF031147,I26207,                       AL157479, AF017790, AK025541, AL117578,                       AK026452, X54971, AX011676, AL080137,                       AF000145, U72620, AB047904, AC004227,                       AK026600, A08916, AK026629, S75997,                       AF113694, AR068751, AF110329, AL133067,                       AL049464, S63521, AF022813, AL137557,                       AL133558, AX046603, AK026353, AF051325,                       AB047966, AX005848, AX005804, AX014095,                       AK025084, I46765, AL137459, AB026675,                       AK025491, AK025349, AF311287, AB038698,                       U68233, I92592, E07108, AR059883, AF130068,                       AF036268, AF260566, AK000391, AF016271,                       AF178432, AL389939, AF040723, AB029065,                       AF114168, AC010128, AC005902, AL137276,                       AL110171, AF314091, Y10655, AF116691,                       X76228, AL133054, AF090943, AF218031,                       AK025391, AK027129, AF218004, AB047615,                       AK025906, AF069506, AK026164, AL359596,                       M30514, AL050280, I52013.       12   HHGDP51   41   857703   AI652297, BF967925, AW769372, BE857943,                       BF115527, AA446941, AI209086, AA443365,                       D59611, BF059139, AW204677.       13   HBCBS41,   14   1310706   BF525534, BF525878, AI188462, AV706177,           HDMBJ47           AA835791, AI573089, AV706657, AA828067,                       BF338495, AI141312, AI961924, AA563724,                       AI829025, AV733099, AA464950, AA845819,                       AA618072, AI343736, AA576567, AI370917,                       AA622849, AI591077, AA039329, AW084144,                       AI719443, AA978073, BE819803, AI968544,                       AA910242, AI344535, AI554230, BF994888,                       AI299970, AA948689, AA828804, BE219403,                       AI298788, AA775331, AV702739, AA937438,                       N49449, T70926, AI299637, AA516376, H27042,                       AI565682, AA933874, AV706862, AA953314,                       AW951361, AA838059, AA865068, AA663921,                       AA338264, R68898, AV707811, AV703148,                       AI097249, AI879461, AA394279, AA582298,                       BE138913, AA879122, AW238763, H26166,                       AA039414, AW383740, BF951235, AW951363,                       AI125081, AA577157, AA582289, BF591527,                       AA603650, AA465026, AA837695, N54606,                       T95006, AI299684, AA828747, AW137828,                       BF945969, AI720693, AA834499, H26167,                       T91949, N33604, AW087254, AA295894,                       AA293797, R68796, BG236868, AA988656,                       AI817977, T49380, AA628820, AA379748,                       AW628890, AI589170, AI582116, T49379,                       AW516492, BF842441, AW815770, AA984912,                       AI581583, AI000183, T84931, T53963, AI079151,                       R36633, T71284, T53830, AA369370, BG059309,                       AA369514, AI869893, T94953, BE465572,                       T86178, AI950559, T70988, T86179, AI749183,                       AA369395, AI344355, BG153207, AI582011,                       AI826458, AW797707, AA486985, T72982,                       AA913653, AA362998, R28940, T72203,                       AI749099, BF951201, N76686, AW798220,                       AA369611, T71421, AA603651, AI676040,                       T28386, AL080021, BF379002, AA369396,                       BG012359, R39712, AI734970, AL047857,                       AA913190, AA318607, AW816674, AI719214,                       D45294, R10854, BF870900, X03084, K03430,                       M36278, BG272985, BG677431.       13   HBCBS41,   42   1225229   BF525534, BF525878, AI188462, AV706177,           HDMBJ47           AI573089, AA835791, AV706657, AA828067,                       BF338495, AI141312, AI961924, AA563724,                       AI829025, AV733099, AA576567, AA464950,                       AA845819, AA618072, AI343736, AI370917,                       AA622849, AW084144, AA039329, AI591077,                       AI719443, AA978073, BE819803, AI968544,                       AA910242, AI344535, AI554230, BF994888,                       AI299970, AI298788, AA948689, AA828804,                       BE219403, AV702739, AA775331, AA937438,                       N49449, AI299637, AA516376, T70926, H27042,                       AI565682, AA933874, AV706862, AA953314,                       AW951361, AA838059, AA865068, AI097249,                       AA663921, AA338264, R68898, AV707811,                       AV703148, AI879461, AA394279, AA582298,                       BE138913, AA879122, AW238763, H26166,                       AA039414, AW383740, BF951235, AW951363,                       AI125081, AA577157, AA582289, BF591527,                       AI299684, AA603650, AA465026, AA837695,                       AW137828, N54606, T95006, AA828747,                       BF945969, AI720693, AA834499, H26167,                       T91949, N33604, BG236868, AW087254,                       AA295894, AA293797, R68796, AA988656,                       AI817977, T49380, AA628820, AA379748,                       AW628890, AI589170, AW516492, AI079151,                       AI582116, T49379, BF842441, AW815770,                       AA984912, AI581583, AI000183, T84931, T53963,                       R36633, T71284, T53830, AA369370, AI950559,                       BG059309, AA369514, AI869893, T94953,                       BE465572, T86178, T70988, T86179, AI749183,                       AA369395, AI344355, AI826458, BG153207,                       AI582011, AW797707, AA486985, T72982,                       AA913653, AA362998, R28940, T72203,                       AI749099, BF951201, N76686, AW798220,                       AA369611, AI676040, T71421, AA603651,                       T28386, AL080021, BF379002, AA369396,                       BG012359, R39712, AI734970, AL047857,                       AA913190, AA318607, AW816674, AI719214,                       D45294, R10854, BF870900.       13   HBCBS41,   43   933547   AI188462, AA835791, AV706657, BF338495,           HDMBJ47           AI141312, AA563724, AA828067, AI573089,                       AI829025, AI961924, AA576567, AV733099,                       AA464950, AA622849, AW084144, AI370917,                       AA845819, AA618072, AI343736, AA039329,                       AI591077, AA910242, AI719443, AA978073,                       AI968544, AI344535, AI298788, AI554230,                       AV702739, AI299970, AA948689, BF994888,                       T70926, AI299637, AA516376, BF525534,                       BE219403, AA775331, AA937438, N49449,                       H27042, AI565682, AI097249, AA838059,                       AA933874, AA865068, AV706862, AA953314,                       AA663921, BF945969, BE819803, AV706177,                       R68898, AA879122, BF525878, AA582298,                       AV707811, AI879461, AV703148, AA603650,                       AA394279, AA039414, BE138913, AW383740,                       H26166, AW238763, AA582289, BF951235,                       AA577157, BF591527, AI299684, AW951361,                       AI125081, N54606, T95006, N33604, AI720693,                       AW137828, AA834499, H26167, BG236868,                       AA465026, T91949, AA828804, AA295894,                       AW087254, R68796, AA293797, AW951363,                       AI817977, T49380, AA988656, AA628820,                       AW628890, AW516492, BF842441, AI079151,                       AW815770, AI582116, AI589170, AA984912,                       R36633, AI000183, AI581583, AA837695,                       T71284, T53830, AI950559, AA369370,                       BG059309, T94953, AI869893, BE465572,                       AI826458, T86179, T86178, AI749183, T53963,                       AA369395, AI344355, BG153207, AA486985,                       R28940, AA913653, AW797707, AI582011,                       AI749099, AW798220, AA369514, BF951201,                       AA603651, AA379748, AI676040, T71421,                       T28386, N76686, R39712, AI734970, AA362998,                       AL047857, AA913190, AA369611, BF379002,                       AA318607, T70988, AW816674, AA369396,                       T72203, AI719214, BF870900.       13   HBCBS41,   44   967511   BF525534, BF525878, AV706657, AI188462,           HDMBJ47           AV706177, AW084144, AA618072, AI573089,                       AA835791, BF338495, AA828067, AI141312,                       AI961924, AA563724, AI829025, AV733099,                       AA576567, AA464950, AA845819, AI343736,                       AI370917, AA838059, AA622849, AA039329,                       AI591077, BE138913, AI719443, AA978073,                       BE819803, AI968544, AA910242, AI344535,                       AI554230, BF994888, A1299970, AA948689,                       AA828804, BE219403, AI298788, AI565682,                       AA775331, N54606, AV702739, AA937438,                       N49449, N33604, AI299637, AA516376, T70926,                       AI079151, H27042, AI817977, R68796,                       AV706862, T95006, AA933874, AW951361,                       AA953314, AA865068, AA988656, AA663921,                       AA338264, AI097249, R68898, AA984912,                       AV707811, AV703148, AI879461, AA582298,                       AA394279, AA879122, AW238763, H26166,                       AA039414, AW383740, BF951235, R36633,                       AW951363, AA582289, AI125081, BF591527,                       T86179, AA603650, AA465026, AA577157,                       AA837695, AI299684, AA569124, BF945969,                       AA828747, AW137828, AI582011, AI720693,                       AA834499, H26167, AA913653, T91949,                       AA486985, AW087254, AA295894, AA293797,                       BG236868, T71421, T49380, AA628820,                       AA379748, AI589170, AW628890, AW516492,                       AI582116, T49379, BF842441, AW815770,                       AI000183, T84931, AI581583, T53963, T71284,                       T53830, AA913190, AI734970, AA369370,                       AI869893, BE465572, AA369514, T94953,                       AI950559, T86178, BG059309, T70988, AI749183,                       AA369395, AI344355, BG153207, AI826458,                       AW797707, T72982, AA362998, R28940,                       AI749099, T72203, BF951201, N76686,                       AW798220, AA369611, AI473594, AA603651,                       AI676040, AL080021, T28386, BF379002,                       AA369396, BG012359, R39712, AL047857,                       BF437726, AA318607, AW816674, BF870900,                       AI719214, D45294, BF870899, R10854.       14   HDPRZ06   15   1384228   BE622709, BE622543, AW195694, AA449506,                       BE349118, AW836407, BE218589, BE018663,                       AI671569, AI990535, AI338971, AI656295,                       BF352595, BF352547, BF353066, AA449077,                       BF902513, BF756315, AA991669, AA971051,                       AA009692, AA837005, AA009411, AA639511,                       AA365182, AA365181, AW236877, AI766763,                       BF214429, AW983562, AV704180, BF195732,                       AV703542, BF352031, AA045125, AV706910,                       BF368967, T03588, BE142783, AV704660,                       AV706223, AV727314, AV701643, AV660516,                       AV727978, AV726502, AV703591, AV731070,                       AV703266, AV660258, AV705550, AV727238,                       AV728436, AV706851, AV652001, AV705518,                       AV725577, AV727954, AV729424, AV727139,                       AV702322, AV725618, AV705992, AV726337,                       AV653353, AV704626, AW959346, AV727822,                       AV728743, AV702149, AV652528, AV728404,                       AV651897, AV725441, AV725031, AV707024,                       AV708786, AV725582, AV709580, AV708872,                       AV726194, AV704144, AV726392, AV727618,                       AV727583, AW955629, AV725991, AV729255,                       AV703168, AV726590, AV725255, AV703632,                       AV725596, AV701516, AV708858, AV651955,                       AV705481, AV728309, AV704590, AV729473,                       AV742050, AV707151, AW952013, AV687342,                       AV701874, AV706147, AV726830, AV729366,                       AV708520, AV704376, AV707882, AV728464,                       AV661286, AV703366, AV726480, AV704605,                       AW956292, AV706677, AV705453, AV704916,                       AV703086, AV706076, AV706718, AV707311,                       AV728546, AV702498, AV726542, AV706290,                       AV725321, AV706871, AV706734, AV702958,                       AV727018, AV709356, AV703417, AV727347,                       AV707770, AV701876, AV703761, AV703367,                       AV707556, AV701873, AV656240, AV702463,                       AV702781, AV652156, AV661744, AV709222,                       AV707009, AV726156, AV705234, AV702721,                       AV660096, AV708347, AV707329, AV706025,                       AV654287, AV725617, AV725393, AV703214,                       AV701879, AV706683, AV709939, AV704712,                       AV705655, AV727576, AV702417, AV701754,                       AV701184, AV703505, AV702164, AV709596,                       AV701704, AV728874, AV709776, AV729408,                       AV725927, AV703213, AV702280, AV729532,                       AV703388, AV707322, AV704879, AV647692,                       AV707268, AV726755, AV707088, AV703232,                       AV704442, AV727469, AV702783, AV706874,                       AV703927, AV702600, AV707401, AV702409,                       AV706035, AV705239, AV707420, AV706991,                       AV706104, AV709326, AV703137, AV704217,                       AV701783, AV706012, AV651075, AV709880,                       AV706330, AV704865, AV702102, AV651704,                       AV702673, AV705267, AV702637, AV646347,                       AV707640, AV729219, AV654035, AV703783,                       AV688061, AV706410, AV726628, AV701669,                       AV709886, AV701499, AV697350, AV702800,                       AV708320, AV702671, AV707589, AV707264,                       AV709256, AV703320, AV729220, AV729129,                       AV703844, AV702851, AV702625, AV727932,                       AV706882, AV648619, AV702817, AV727047,                       AV702354, AV655067, AV704954, AV702725,                       AV704245, AV647654, AF270513.1,                       AL117592.1, AJ244005.1, AJ244004.1,                       D78345.1, AJ244003.1, U94592.1, AJ244007.1,                       D50010.1, D13316.1, AB025273.1, AF144029.1,                       AJ276256.1, AJ276254.1, Z30183.1,                       AF058696.1, AB028859.1, Y14219.1,                       AB002449.1, X67155.2, AF271371.1,                       AF144028.1, AJ244006.1, D34614.1, D88547.1,                       AB005666.1, AB038216.1, X82834.1,                       AJ276255.1, AA887644.       14   HDPRZ06   45   1303540   BE622709, BE622543, AW195694, BE349118,                       AA449506, BE218589, AI671569, AI990535,                       AI656295, AA449077, BF902513, BE018663,                       AA971051, AA991669, AA009411, AA009692,                       AA837005, AA639511, AA365182, AA365181,                       AW236877, AI766763, BF214429, BE142783,                       AW971745, AA887644, AL134524, AW968355,                       AW877209, AW972092, AL119324, AW968356,                       AI432644, AW861944, AI623302, AW972093,                       AW968729, AW971740, AW858525, AI432653,                       AW858522, AW081103, AW972091, AI432654,                       AI431351, AI431323, AI432650, AL119457,                       AW972090, AW969229, AL119399, BE672759,                       AI431307, AI431316, AI432677, AL042544,                       AI431230, AI431328, AI431238, AL045327,                       AW804686, AW128900, AI431353, AI431312,                       AI432666, AI432655, AI431310, AW858455,                       AI431354, AL043152, AI431347, AI492519,                       BF448552, AW604723, AL043168, AI431321,                       AI431315, AI432675, AW858526, BE672748,                       AI432661, Z99396, AI431337, AI431246,                       AL042508, BE672745, AI791349, BE672719,                       BE672732, AI431243, AX041928, AL117592,                       AX041927, AR080280, AX030435, Y17793,                       AX030436, AR066494, AX046357, AJ251859,                       AF019249, AB026436, AR071207, AL133076,                       AF064854, AL133053, AL133049, AL133074,                       AR060234, AL122101, AR054110, AX040974,                       AX041002, A81671, AJ279014, AL133068,                       AX040958, AL096720, AR069079, AL049423,                       AL133655, U30290, AC012104, E13998.       14   HDPRZ06   46   1223606       15   HKB1F69   16   1286614   AI417523, BG120479, AI749321, AW057748,                       AW043700, AW057920, AW305168, AA608713,                       AW474850, AA404349, BF594226, BF541540,                       AW022120, AA579971, AA629969, AI127940,                       AU151624, AW005378, AA705289, AW377397,                       AI610162, AA625142, AI689091, AA887126,                       AA835810, AA181946, AI084438, AW450806,                       BE378048, BF149104, AA133172, AI269303,                       AI378772, AA470804, R56253, AA707300,                       AA725191, R99908, W42777, AI540847,                       AA766559, AA496910, T78435, AA256605,                       AA683171, AI536732, AW021074, BF589574,                       BF062307, AI359641, AA694404, AA903168,                       AA258076, AI537144, AI264091, AW191603,                       R42797, BF727469, N95366, AA354837,                       AA083067, AA134604, AW301165, Z41690,                       R48102, H48756, N66512, R40560, AI270253,                       C01933, AW473992, AA497072, R44523, R47988,                       T97892, AA362636, R49171, T23045, F04485,                       R55714, AW889340, BE155973, AA775162,                       AW902313, BE243585, T75572, AI967943,                       AL119457, AL042544, AL119399, AL119511,                       AW877209, AL119324, T97891, AA258647,                       AL042382, AL043152, AL079794, BG032704,                       AW970048, AL043168, AL037081, T61538,                       AL042866, BG113493, AW971745, BG164558,                       AL037104, AI554245, AI538028, BG168640,                       AL134524, BF525578, AI133559, BE536058,                       BG260144, BG029053, BE968711, BF970449,                       AW827289, AW827276, AV756359, BE047852,                       BF338723, BE785868, AI784219, BE876033,                       AI364788, BF038131, BG256592, BE880182,                       BF806065, BG034459, BF822127, BE874133,                       AW673679, BG028528, BF885082, AV682462,                       BF726894, BE542893, BE782605, BF970362,                       BE893142, BG106619, AW088903, AI926669,                       AL079741, AV682052, BE877372, AA715307,                       AV755840, BG034373, BG033357, BE548542,                       BG163297, BE896632, BE881131, BG256705,                       BG110797, BG250841, AW020693, BF726237,                       BE874997, BF752999, BF814447, AI540759,                       BE011880, AW772685, BF032768, BF339322,                       BF032910, BE047952, AL045500, BE622183,                       BF107493, AI468872, BG027766, AW148716,                       AL045349, AV756030, BG254352, BG032208,                       BE910373, AW129230, BF916181, BF816037,                       AA938092, BE887488, BE904178, AI539771,                       AI916419, BE877769, BG032994, AI830259,                       AW162194, BF726207, BG168646, AW172723,                       AA641818, BF811793, AV729119, AI866082,                       BG109711, BG249582, AI269862, AI680498,                       AI494201, BE047737, BF753056, AW191003,                       BF911528, BE620444, BF968910, AI619723,                       AI224027, BF885080, BE895765, AI564448,                       BG110704, AV682467, BG251840, BG026482,                       BF814420, BE875243, AI699011, BE048071,                       AI436429, BF794756, BE963286, BF338002,                       AW151714, AV648430, AI610557, AI648684,                       BG034609, BG029667, AW834325, BF339594,                       AL042628, AL036214, AI433157, AI538885,                       AI554821, AW858243, BG252929, AW151136,                       BE897632, AC010198, AK026222, AK024247,                       U77594, AX030435, AJ251859, Y11587,                       AK024524, AK025431, I00734, E00617, E00717,                       E00778, AL162062, L10353, AL122049, U96683,                       A08916, A08910, A08909, AR080280, AL162002,                       AL390167, AK026647, I48978, S68736,                       AL389935, AF008439, AF130087, S61953,                       AF314091, AF067728, AX042059, AL389939,                       AJ238278, AL122098, AF177401, AF119337,                       AF162270, I89947, AK026959, A08913, L30117,                       I89931, AK024538, AB026436, AK025798,                       AL080127, X93495, AR087170, AB047904,                       AK025015, AL133072, AF183393, AL080159,                       AF155221, AF116644, AB048964, AF119909,                       AL117440, AL080137, AL137476, AX040958,                       AF119896, AR000496, U39656, X52128,                       AF090901, X81464, AK026408, I33392,                       AR059958, AK025524, AK027188, AB049758,                       AL137548, AL122110, AF113019, AL049283,                       AK026480, AL133080, AL049466, AK000432,                       AL162003, AK026885, I17767, AK026927,                       AL133077, AK026551, AL050393, AL389982,                       AL122121, AF116639, AK026464, AK025857,                       E05822, AL049382, Z82022, AF153205,                       AK027160, AL359601, Y14314, AR038854,                       AL133031, AL137463, AK027182, AF113689,                       AK025391, AF017152, AK000310, AF116649,                       A08912, AL359620, AL050138, AF113013,                       AJ012755, AF116631, AF271350, AF119883,                       E03348, AL137526, L19437, AF097996,                       AF028823, AF218031, A65341, AB041801,                       AK026045, AB050534, AF130100, AF177336,                       AK025209, AX040974, AF130092, AL110221,                       E15569, S78214, AR020905, X76228, A07588,                       AF119878, E02349, AF110640, AF218034,                       AF090900, AL133014, AK026532, AF111112,                       AF003737, AK026533, AF017437, AK026086,                       AK027121, AF106827, AL110296, AL049452,                       AK026624, E07108, AF158248, AL359618,                       AF061573, E07361, AL080124, AL080060,                       AK000652, AL137556, I48979, AL389978,                       AF130055, AK026597, AL049430, AK026642,                       AF132676, AF225424, AB047941, AR070212,                       AF061836, AF111851, AB048974, AX020124,                       AK025312, AF125948, AF113676, AK000718,                       AK026534, AK027116, AK026865, AF078844,                       AL050277, AL357195, AL050024, AX019230,                       AF217966, AB047887, AK000137, AX014095,                       Z72491, AK027164, Y09972, AL137550,                       AK026452, AF205861, AK000690, AK000486,                       AF104032, AF175983, AF207829, AF026816,                       AL080086, AL359941, A18777, AF130066,                       AK024588, AK027096, AL162008, AF119875,                       AK026583, AL133640, AB048919, AF119871,                       AF210052, AB052191, AK025084, AF217987,                       AF017790, AK025092, AL162006, AB048975,                       AK025632, A93350, AF116646, AK000647,                       AL117457, AL133016, AK025254, A45787,                       AK000323, AX010492, AF146568, AL122093,                       AK025208, AL133565, AL133606, AK027136,                       AJ006417, AL137479, X98834, AK026462,                       BE552256.       16   HOHBO69   17   1282370   BG114252, BF344333, AW029321, BE619018,                       BF591735, AI084509, BE877796, AW068693,                       BF002157, AW068694, AA872420, N23787,                       AW613589, AI752218, AW630180, AI752219,                       AI752163, AI750192, AI753307, AI752164,                       N24399, AA789067, BF197886, W19235,                       AI424724, AA233788, AW392772, AW068274,                       AA627580, AA853772, AA853676, H99150,                       H89055, AA853685, BF448509, BF741968,                       BF132395, AA577443, AW392783, H99383,                       D79968, D62487, AA853675, AA290849,                       AA283763, W25429, AA853686, X57527, J05042,                       X66977, AF044969, AF054891, S63458, X66976,                       AF055330, AC007275, AF170702, AL022143.       16   HOHBO69   47   1280342   None       17   HCEES60   18   1305240   BG251391, AL138070, AA639738, AL138071,                       R38469, AA317570, W30872, AA043621,                       AA853712, AI806793, AA702490, AA780815,                       AI751694, AL138787, M60832, M60833.       18   HDALV07   19   1316192   AR034253, D45371, AB012165, AJ131461,                       AR034252, U49915, AJ131460, AB012164.       19   HEQAH47   20   877634   AL519977, BE383449, AL043766, BF061686,                       BF221776, BF310701, BF060773, BF434074,                       BF062728, AI659849, BE313561, BF314046,                       BF316323, AI659290, AI824840, BF061701,                       BF312471, AI751263, AI685765, AI591068,                       AI587181, AI920932, AI400351, AI148305,                       AI955664, AI652541, AI675888, AI653379,                       AI424943, AI128448, BE313794, BF437698,                       AI275016, BF590996, AI561014, AI660936,                       AI491938, AI968617, BE047763, AI127265,                       AA643524, BF313828, AI866540, AI751264,                       AI828892, AI824814, AA970985, BE855979,                       AI589275, AI768084, AA477627, AW371357,                       AI926713, AI969893, AI335684, AA057195,                       AA478085, AW193325, AW002099, AI672890,                       AI991492, AI225080, AW191017, AI804237,                       AI918988, AI215462, AI660046, AW263221,                       AW166456, AW361968, AI923034, BF939318,                       AI672957, AW008276, AI421034, BF941981,                       AA101823, AI474549, BF514389, AA968480,                       AW591386, AI972480, AI758252, AI277535,                       AI611291, AI446797, AA627406, AW082500,                       AI673160, AA127893, AW085658, AA101824,                       AI491939, AI445814, AW513225, AI656563,                       W21432, AW590943, AA128143, AW196052,                       AW452957, AI419247, AI356191, BF593921,                       AI339204, AA973738, BF196865, AA973140,                       BF941530, AA423796, AA962026, AI572714,                       BF593478, AA057129, AA834119, AI333104,                       AI401697, AI539260, AI628325, AI345415,                       AW163834, AI590043, AI698391, AI440238,                       AL047763, AW130362, AI523973, AW150622,                       AW008166, BF531023, AA565269, AL042567,                       AI361701, AI619820, AI434731, AI653402,                       AI880111, AI500061, AI345688, AI862067,                       AI800648, BE393784, AL037602, AI872423,                       AI524179, AI289791, AI927233, AI565172,                       AL037582, AI866469, AI370623, AL079963,                       AI678446, BG250475, AW189716, BF909758,                       AW196720, AW129659, AW081383, AI784214,                       BE964705, AV659072, AI244343, AI445611,                       AI680467, AI250646, BG260772, BE877401,                       BE907624, BG034598, AI699823, BF724420,                       BE904851, BF750886, AI869125, AI869377,                       AI582932, BE957870, AI638644, AA659688,                       AL036241, AI972112, AI345612, BE867194,                       BF035213, BE905161, BE873695, BE877904,                       AI345416, BE967004, AI627714, AW188525,                       AI251221, AL036673, BG169738, BF525838,                       AI290677, BG256090, AI470717, AI499570,                       BE963809, AW051088, AW983832, AW117882,                       AI471282, AI621341, AI440239, AW130104,                       AI866127, W45039, AI536574, AI583558,                       AI583578, BG118199, AI889189, AW075382,                       AI348847, AW083572, AW161202, AI366959,                       AI633125, AI800341, AI310575, AI869765,                       AI860027, AI538564, AI335476, AI866040,                       AI915291, AW152182, AI538817, AW130534,                       AI274655, AW025279, AI284060, BE965159,                       AI866770, BF811804, AI581362, AI270295,                       BE891834, BF669151, AV681858, AW073824,                       AI589428, AL050138.1, AF088916.1,                       BC007530.1, AF162780.1, Y09340.1,                       AL137480.1, BC000090.1, AK026542.1,                       AL080146.1, BC007522.1, BC001675.1,                       BC002491.1, AL162002.1, AB060889.1,                       BC006091.1, AJ012582.1, AL137558.1,                       AL389935.1, BC001199.1, AK026462.1,                       AL161802.15, AL117587.1, BC001166.1,                       AF183393.1, BC007571.1, BC003104.1,                       BC002631.1, AB055303.1, AB060887.1,                       BC007767.1, AL136765.1, BC006345.1,                       AK000618.1, BC008708.1, BC006119.1,                       Y14040.1, BC008364.1, BC001785.1,                       BC004925.1, AF249267.3, AL080154.1,                       AK027161.1, AL080110.1, AL117438.1,                       BC003410.1, BC003569.1, BC008382.1,                       AK024974.1, AK027160.1, AL136864.1,                       BC003101.1, AK000655.1, AL049382.1,                       AB047627.1, AL137292.1, BC008591.1,                       AL137530.1, AK027102.1, AK025435.1,                       AF044323.1, BC001964.1, U73682.1,                       AB060876.1, BC002911.1, BC003587.1,                       BC002370.1, AL442083.1, AF132730.1,                       BC000570.1, AL136752.1, AL136893.1,                       AL137495.1, AK026633.1, AL359583.1,                       BC002535.1, AL117416.1, BC006410.1,                       AL512718.1, AL137574.1, BC003590.1,                       AL133088.1, X66417.1, AL137461.1, U70981.1,                       AK024533.1, BC003573.1, AB050410.1,                       BC003591.1, AK025099.1, Z82022.1,                       AF271781.1, BC002471.1, AB050431.1,                       BC005854.1, AK025113.1, AL137256.1,                       AF369701.1, AL080148.1, AL133049.1,                       X53587.1, AF026816.2, AL359941.1,                       BC004945.1, BC004292.1, AK000418.1,                       AL136850.1, AL080159.1, AB060897.1,                       AF339775.1, BC004908.1, BC009333.1,                       AL137533.1, AF195092.1, BC007381.1,                       BC008649.1, AK027095.1, S76508.1,                       BC005002.1, X83544.1, BC004119.1, Y14314.1,                       BC000235.1, AL389982.1, BC006181.1,                       AL136784.1, BC001082.1, BC000751.1,                       AK024588.1, AK025860.1, AK025084.1,                       AB063074.1, S77771.1, U37359.1, BC002473.1,                       AL136774.1, BC005070.1, BC000860.1,                       AL133559.1, S61953.1, AK000476.1,                       BC000199.1, AB060864.1, AF245044.1,                       AL137478.1, BC008686.1, BC006103.1,                       BC005816.1, BC007460.1, AK025798.1,                       BC002466.1, AF124728.1, AF104032.1,                       AL137550.1, AF106862.1, X82434.1, L19437.2,                       AL137557.1, AL162003.1, BC004899.1,                       AK026164.1, AL137271.1, AB060837.1,                       AF141289.1, AB060916.1, BC004395.1,                       AK025350.1, AL137554.1, BC002356.1,                       AL353956.1, BC001844.1, AL080126.1,                       AL050092.1, BC008078.1, BC008417.1,                       AF271350.1, AL512751.1, BC007453.1,                       BC009026.1, AF131773.1, AL136615.1,                       BC000253.1, AK026647.1, AK026744.1,                       AL136844.1, AB056420.1, BC008717.1,                       BC008723.1, AL133062.1, BC006161.1,                       AF081571.1, AL050155.1, AF230496.1,                       AC026464.6, AF242525.1, BC002516.1,                       AF239683.1, BC004349.1, AL512684.1,                       AL133081.1, AF131821.1, AB047953.1,                       BC001763.1, AB048974.1, AJ299431.1,                       AL050149.1, BC005843.1, AF184965.1,                       AL136586.1, AL137488.1, AK024747.1,                       AL136768.1, AL122121.1, AL110280.1,                       AC006288.1, AK026506.1, BC004960.1,                       AL136884.1.       19   HEQAH47   48   1254417       20   HATNA88   21   1282006   BG032839, AI217963, AW665995, BG178505,                       AI032401, AI016792, AW973741, AA889643,                       BE041602, AW983637, AW983608, AW983601,                       AW983610, AW983628, AW983645, AW983688,                       AW983603, AW983607, AW983625, AW983640,                       AW983612, AW983642, AW983617, AW983624,                       AW983634, AW983687, AW983602, AW983630,                       AW983635, AW983636, AW983689, AW983616,                       AW983639, AW983609, AW983644, AW983618,                       AW983604, AW983611, AW983615, AW983619,                       AW983686, AW983622, AW983633, AW983605,                       AW983626, AW983631, AW983643, AW983627,                       AW983620, AW983638, AW983632, AW983613,                       AW983685, AW983621, AW983592, AA559283,                       AW983641, AW983623, AW983589, AW983593,                       BF349085, AW983594, AW983614, AA583866,                       AA883836, AA557662, AA593227, BF512098,                       AI275909, AA578056, AL445985, AX047347,                       AF178931.       20   HATNA88   49   1285117                  
 
       [1258]                   TABLE 3                       cDNA           Plasmid: V   Library Code(s)                  HCE1P80   H0052 H0179 H0253 H0266 H0375 H0543 H0551 H0575 H0618 H0790           L1290 S0027       HUFGH53   H0009 H0012 H0024 H0059 H0087 H0208 H0483 H0506 H0529           H0540 H0617 H0622 H0624 H0625 H0660 H0672 H0687 L1290           S0038 S0354 S0374 S0418 S0444 S6026       HWMMO59   H0024 H0392 H0617 L1290 S0358 S0444       HSSJJ51   H0030 H0052 H0087 H0100 H0251 H0253 H0286 H0318 H0445           H0486 H0550 H0594 H0599 H0618 H0619 H0693 H0713 H0757           H0762 L1290 S0037 S0196 S0280 S0378 S0436 S0476       HCEWD38   H0052 H0194 H0261 H0581 L1290       HUCMC56   H0013 H0144 H0178 H0244 H0563 H0570 H0624 L1290 S0051 S0442       HWLZU06   H0549 S0222 S0406 S0436       HDPBA69   H0009 H0014 H0031 H0039 H0062 H0063 H0090 H0108 H0122           H0123 H0163 H0189 H0213 H0252 H0264 H0309 H0333 H0343           H0345 H0352 H0375 H0376 H0427 H0444 H0445 H0486 H0506           H0509 H0510 H0521 H0522 H0553 H0555 H0570 H0575 H0581           H0583 H0595 H0597 H0619 H0620 H0622 H0638 H0644 H0652           H0658 H0661 H0662 H0663 H0666 H0668 H0672 H0682 H0710           H0713 H0726 H0753 H0754 H0757 H0762 H0773 H0774 H0777           L1290 S0106 S0190 S0212 S0280 S0282 S0330 S0354 S0358           S0360 S0362 S0374 S0376 S0378 S0384 S0406 S0408 S0434           S0436 S0438 S0440 S0442       HLWAE11   H0050 H0056 H0266 H0521 H0553 L1290       HSZAF47   H0013 H0321 L1290       HWTAY65   H0012 H0013 H0019 H0123 H0351 H0352 H0550 H0553 H0570 L1290           S0007       HHGDP51   H0424 H0455 H0617 L1290       HBCBS41   H0004 H0009 H0014 H0031 H0042 H0068 H0086 H0087 H0090           H0124 H0144 H0190 H0255 H0263 H0309 H0327 H0329 H0351           H0370 H0375 H0376 H0393 H0415 H0421 H0427 H0441 H0445           H0486 H0489 H0521 H0522 H0538 H0549 H0550 H0553 H0555           H0575 H0581 H0583 H0587 H0591 H0592 H0606 H0617 H0638           H0641 H0644 H0646 H0649 H0653 H0658 H0659 H0662 H0672           H0673 H0689 H0690 H0710 H0716 H0722 H0726 H0753 H0754           H0755 H0762 H0768 H0777 H0778 H0789 L1290 S0010 S0031           S0036 S0044 S0260 S0280 S0328 S0354 S0356 S0358 S0360           S0374 S0376 S0406 S0408 S0434 S0436 S0440 S0442 S0444           T0068       HDPRZ06   H0124 H0188 H0250 H0271 H0328 H0486 H0521 H0522 H0539           H0540 H0580 H0638 H0641 H0645 L1290 S0044 S0116 S0344           S0426 S0434 T0006       HKB1F69   H0013 H0384 H0412 H0616 H0659 H0688 L1290 S0007 S0026           S0222 S0402 S0444       HOHBO69   H0024 H0050 H0100 H0266 H0486 H0519 H0538 H0544 H0545           H0550 H0551 H0575 H0593 H0615 H0619 H0622 H0623 H0653           H0665 H0667 H0770 H0771 L1290 S0015 S0022 S0028 S0032           S0040 S0126 S0134 S0180 S0196 S0208 S0212 S0250 S0276           S0298 S0360 S0390 S0418 S0420 S0434 S3014       HCEES60   H0052 H0123 H0135 H0144 H0251 H0594 H0615 H0622 H0628           H0645 L1290 S0040 S0126 S0142 S0344 S0420 S0430 T0082       HDALV07   H0081 H0427 H0706 H0713 H0716 H0717 H0725 L1290 S0212 S0260           S0280 S6022       HEQAH47   H0544       HATNA88   H0599 H0616 H0708 H0713 L1290 S0216                    
       [1259]                       TABLE 4                           Cytologic Band           SEQ ID   or       NO: X   Chromosome:   OMIM Reference(s):                                            2   22q13.2   188826 602049       4   17q25.2   603967 606800       5   14q11.2   162080 182600 186880 190195 600243 602279               603593 605463 606439 606675       7   11q23.3   176000 236680 261640 600644 602574 603113               604763 605201 607086       9   22q13.1   103050 124030 138981 182380 188826 190040               218040 602049 603590       12   11q11     606860       13   1p36.13-p34.1   115665 116600 120550 120570 120575 121800               130500 138140 142461 153390 153454 155600               164780 167410 171760 172411 172430 178300               185470 211420 256700 600423 600975 601990               602023 603324 603490 603688 603776 604630               604933 605225 605425 605747 605909 605995               606210 606324 606693 606811 606928 606953               606996 607093 607215       17    7p15-p12   107776 138079 139191 142958 142959 153880               165240 180104 203740 261670 600994 601472               601583 603023 603284 606224 606246       18    3q27     109565 120520 142640 210200 228960 600044               602322 603273 603285 603945 603959 605229               605441 605552 607037                    
       [1260]                       TABLE 5                       Library               Code   Library Description   Disease                  H0004   Human Adult Spleen           H0009   Human Fetal Brain       H0012   Human Fetal Kidney       H0013   Human 8 Week Whole Embryo       H0014   Human Gall Bladder       H0019   Human Fetal Heart       H0024   Human Fetal Lung III       H0030   Human Placenta       H0031   Human Placenta       H0039   Human Pancreas Tumor   disease       H0042   Human Adult Pulmonary       H0050   Human Fetal Heart       H0052   Human Cerebellum       H0056   Human Umbilical Vein, Endo. remake       H0059   Human Uterine Cancer   disease       H0062   Human Thymus       H0063   Human Thymus       H0068   Human Skin Tumor   disease       H0081   Human Fetal Epithelium (Skin)       H0086   Human epithelioid sarcoma   disease       H0087   Human Thymus       H0090   Human T-Cell Lymphoma   disease       H0100   Human Whole Six Week Old Embryo       H0108   Human Adult Lymph Node, subtracted       H0122   Human Adult Skeletal Muscle       H0123   Human Fetal Dura Mater       H0124   Human Rhabdomyosarcoma   disease       H0135   Human Synovial Sarcoma       H0144   Nine Week Old Early Stage Human       H0163   Human Synovium       H0178   Human Fetal Brain       H0179   Human Neutrophil       H0188   Human Normal Breast       H0189   Human Resting Macrophage       H0190   Human Activated Macrophage (LPS)       H0194   Human Cerebellum, subtracted       H0208   Early Stage Human Lung, subtracted       H0213   Human Pituitary, subtracted       H0244   Human 8 Week Whole Embryo, subtracted       H0250   Human Activated Monocytes       H0251   Human Chondrosarcoma   disease       H0252   Human Osteosarcoma   disease       H0253   Human adult testis, large inserts       H0255   breast lymph node CDNA library       H0261   H. cerebellum, Enzyme subtracted       H0263   human colon cancer   disease       H0264   human tonsils       H0266   Human Microvascular Endothelial Cells, fract. A       H0271   Human Neutrophil, Activated       H0286   Human OB MG63 treated (10 nM E2) fraction I       H0309   Human Chronic Synovitis   disease       H0318   HUMAN B CELL LYMPHOMA   disease       H0321   HUMAN SCHWANOMA   disease       H0327   human corpus colosum       H0328   human ovarian cancer   disease       H0329   Dermatofibrosarcoma Protuberance   disease       H0333   Hemangiopericytoma   disease       H0343   stomach cancer (human)   disease       H0345   SKIN       H0351   Glioblastoma   disease       H0352   wilm&#39;s tumor   disease       H0370   H. Lymph node breast Cancer   disease       H0375   Human Lung       H0376   Human Spleen       H0384   Brain, Kozak       H0392   H. Meningioma, M1       H0393   Fetal Liver, subtraction II       H0412   Human umbilical vein endothelial cells, IL-4 induced       H0415   H. Ovarian Tumor, II, OV5232   disease       H0421   Human Bone Marrow, re-excision       H0424   Human Pituitary, subt IX       H0427   Human Adipose       H0441   H. Kidney Cortex, subtracted       H0444   Spleen metastic melanoma   disease       H0445   Spleen, Chronic lymphocytic leukemia   disease       H0455   H. Striatum Depression, subt       H0483   Breast Cancer cell line, MDA 36       H0486   Hodgkin&#39;s Lymphoma II   disease       H0489   Crohn&#39;s Disease   disease       H0506   Ulcerative Colitis       H0509   Liver, Hepatoma   disease       H0510   Human Liver, normal       H0519   NTERA2, control       H0521   Primary Dendritic Cells, lib 1       H0522   Primary Dendritic cells, frac 2       H0529   Myoloid Progenitor Cell Line       H0538   Merkel Cells       H0539   Pancreas Islet Cell Tumor   disease       H0540   Skin, burned       H0543   T cell helper II       H0544   Human endometrial stromal cells       H0545   Human endometrial stromal cells-treated with           progesterone       H0549   H. Epididiymus, caput &amp; corpus       H0550   H. Epididiymus, cauda       H0551   Human Thymus Stromal Cells       H0553   Human Placenta       H0555   Rejected Kidney, lib 4   disease       H0563   Human Fetal Brain, normalized 50021F       H0570   Human Fetal Brain, normalized C500H       H0575   Human Adult Pulmonary, re-excision       H0580   Dendritic cells, pooled       H0581   Human Bone Marrow, treated       H0583   B Cell lymphoma   disease       H0587   Healing groin wound, 7.5 hours post incision   disease       H0591   Human T-cell lymphoma, re-excision   disease       H0592   Healing groin wound - zero hr post-incision (control)   disease       H0593   Olfactory epithelium, nasalcavity       H0594   Human Lung Cancer, re-excision   disease       H0595   Stomach cancer (human), re-excision   disease       H0597   Human Colon, re-excision       H0599   Human Adult Heart, re-excision       H0606   Human Primary Breast Cancer, re-excision   disease       H0615   Human Ovarian Cancer Reexcision   disease       H0616   Human Testes, Reexcision       H0617   Human Primary Breast Cancer Reexcision   disease       H0618   Human Adult Testes, Large Inserts, Reexcision       H0619   Fetal Heart, reexcision       H0620   Human Fetal Kidney, Reexcision       H0622   Human Pancreas Tumor, Reexcision   disease       H0623   Human Umbilical Vein, Reexcision       H0624   12 Week Early Stage Human II, Reexcision       H0625   Ku 812F Basophils Line       H0628   Human Pre-Differentiated Adipocytes       H0638   CD40 activated monocyte dendridic cells       H0641   LPS activated derived dendritic cells       H0644   Human Placenta (re-excision)       H0645   Fetal Heart, re-excision       H0646   Lung, Cancer (4005313 A3): Invasive Poorly           Differentiated Lung Adenocarcinoma,        H0649   Lung, Normal: (4005313 B1)       H0652   Lung, Normal: (4005313 B1)       H0653   Stromal Cells       H0658   Ovary, Cancer (9809C332): Poorly differentiated   disease           adenocarcinoma       H0659   Ovary, Cancer (15395A1F): Grade II Papillary   disease           Carcinoma       H0660   Ovary, Cancer: (15799A1F) Poorly differentiated   disease           carcinoma       H0661   Breast, Cancer: (4004943 A5)   disease       H0662   Breast, Normal: (4005522B2)       H0663   Breast, Cancer: (4005522 A2)   disease       H0665   Stromal cells 3.88       H0666   Ovary, Cancer: (4004332 A2)   disease       H0667   Stromal cells(HBM3.18)       H0668   stromal cell clone 2.5       H0672   Ovary, Cancer: (4004576 A8)       H0673   Human Prostate Cancer, Stage B2, re-excision       H0682   Ovarian cancer, Serous Papillary Adenocarcinoma       H0687   Human normal ovary(#9610G215)       H0688   Human Ovarian Cancer(#9807G017)       H0689   Ovarian Cancer       H0690   Ovarian Cancer, #9702G001       H0693   Normal Prostate #ODQ3958EN       H0706   Human Adult Skeletal Muscle       H0708   Human Skeletal Muscle       H0710   Acute Myeloid Leukemia /SGAH (Patient #6)       H0713   Adipose tissue (diabetic type I, obese) #41706       H0716   Adipose tissue (diabetic type II)#41689       H0717   Adipose tissue (diabetic type II) #41661       H0722   Diabetic Liver 99-09-A281a       H0725   Normal Adipose Tissue #41838-08       H0726   Normal skeletal muscle #96-08-A171       H0753   pancreatic cancer sample # 4004959A1       H0754   Pancreatic cancer #14677A1L       H0755   Pancreatic cancer sample#4004959 A1       H0757   normal pancreas #400556A8       H0762   Normal Pancreas 42206       H0768   Lung cancer       H0770   Esophageal Cancer #2109A5A ductal carcinoma       H0771   esophageal cancer #0011C075Ra       H0773   Malignant Esophagus #9706C049       H0774   Prostate infiltrated by adenocarcinoma #4007645B1       H0777   esophageal cancer #9902C094       H0778   Esophageal Cancer #9804C013Rb       H0789   renal cell carcinoma of kidney       H0790   HMC-1 untreated       L1290   Soares_testis_NHT       S0007   Early Stage Human Brain       S0010   Human Amygdala       S0015   Kidney medulla       S0022   Human Osteoclastoma Stromal Cells - unamplified       S0026   Stromal cell TF274       S0027   Smooth muscle, serum treated       S0028   Smooth muscle, control       S0031   Spinal cord       S0032   Smooth muscle-ILb induced       S0036   Human Substantia Nigra       S0037   Smooth muscle, IL1b induced       S0038   Human Whole Brain #2 - Oligo dT&gt; 1.5 Kb       S0040   Adipocytes       S0044   Prostate BPH   disease       S0051   Human Hypothalmus, Schizophrenia   disease       S0106   STRIATUM DEPRESSION   disease       S0116   Bone marrow       S0126   Osteoblasts       S0134   Apoptotic T-cell       S0142   Macrophage-oxLDL       S0180   Bone Marrow Stroma, TNF&amp;LPS ind   disease       S0190   Prostate BPH, Lib 2, subtracted       S0196   Synovial IL-1/TNF stimulated       S0208   Messangial cell, frac 1       S0212   Bone Marrow Stromal Cell, untreated       S0216   Neutrophils IL-1 and LPS induced       S0222   H. Frontal cortex, epileptic, re-excision   disease       S0250   Human Osteoblasts II   disease       S0260   Spinal Cord, re-excision       S0276   Synovial hypoxia-RSF subtracted       S0280   Human Adipose Tissue, re-excision       S0282   Brain Frontal Cortex, re-excision       S0298   Bone marrow stroma, treated       S0328   Palate carcinoma   disease       S0330   Palate normal       S0344   Macrophage-oxLDL, re-excision       S0354   Colon Normal II       S0356   Colon Carcinoma   disease       S0358   Colon Normal III       S0360   Colon Tumor II   disease       S0362   Human Gastrocnemius       S0374   Normal colon       S0376   Colon Tumor   disease       S0378   Pancreas normal PCA4 No       S0384   Tongue carcinoma   disease       S0390   Smooth muscle, control, re-excision       S0402   Adrenal Gland, normal       S0406   Rectum tumour       S0408   Colon, normal       S0418   CHME Cell Line, treated 5 hrs       S0420   CHME Cell Line, untreated       S0426   Monocyte activated, re-excision       S0430   Aryepiglottis Normal       S0434   Stomach Normal   disease       S0436   Stomach Tumor   disease       S0438   Liver Normal Met5No       S0440   Liver Tumor Met 5 Tu       S0442   Colon Normal       S0444   Colon Tumor   disease       S0476   Epithelial-TNFa and INF induced       S3014   Smooth muscle, serum induced, re-exc       S6022   H. Adipose Tissue       S6026   Frontal Lobe, Dementia       T0006   Human Pineal Gland       T0068   Normal Ovary, Premenopausal       T0082   Human Adult Retina                    
       [1261]                   TABLE 6                       OMIM           Reference   Description                  103050   Adenylosuccinase deficiency           Autism, succinylpurinemic       107776   Colton blood group, 110450           [Aquaporin-1 deficiency]       109565   Lymphoma, B-cell       115665   Cataract, congenital, Volkmann type       116600   Cataract, posterior polar       120520   Membranous glomerulonephritis, antenatal           [Neutral endopeptidase deficiency]       120550   C1q deficiency, type A       120570   C1q deficiency, type B       120575   C1q deficiency, type C       121300   Coproporphyria           Harderoporphyrinuria       121800   Corneal dystrophy, crystalline, Schnyder       124030   Debrisoquine sensitivity           Parkinsonism, susceptibility to       126453   Dystonia, primary cervical           Blepharospasm, primary benign, 606798       130500   Elliptocytosis-1       138079   Diabetes mellitus, neonatal-onset, 606176           Hyperinsulinism, familial, 602485           MODY, type II, 125851       138140   Glucose transport defect, blood-brain barrier, 606777       138981   Pulmonary alveolar proteinosis, 265120       139191   Growth hormone deficient dwarfism       142461   Dyssegmental dysplasia, Silverman-Handmaker type, 224410           Schwartz-Jampel syndrome, type 1, 255800       142640   Thrombophilia due to HRG deficiency           Thrombophilia due to elevated HRG       142958   Radioulnar synostosis with amegakaryocytic           thrombocytopenia, 605432       142959   Guttmacher syndrome, 176305           Hand-foot-uterus syndrome, 140000       146200   Hypoparathyroidism, familial       153390   SCID due to LCK deficiency       153454   Ehlers-Danlos syndrome, type VI, 225400       153880   Macular dystrophy, dominant cystoid       155600   Malignant melanoma, cutaneous       162080   Retinitis pigmentosa, autosomal dominant       164780   1p36 deletion syndrome       165240   Greig cephalopolysyndactyly syndrome, 175700           Pallister-Hall syndrome, 146510           Polydactyly, postaxial, types A1 and B, 174200           Polydactyly, preaxial, type IV, 174700       167410   Rhabdomyosarcoma, alveolar, 268220       171760   Hypophosphatasia, adult, 146300           Hypophosphatasia, childhood, 241510           Hypophosphatasia, infantile, 241500       172411   Colorectal cancer, resistance to       172430   Enolase deficiency       176000   Porphyria, acute intermittent           Porphyria, acute intermittent, nonerythroid variant       178300   Ptosis, hereditary congenital, 1       180104   Retinitis pigmentosa-9       182380   Glucose/galactose malabsorption, 606824       182600   Spastic paraplegia-3A       185470   Pheochromocytoma, extraadrenal, and cervical           paraganglioma, 115310       186880   Leukemia/lymphoma, T-cell       188826   Sorsby fundus dystrophy, 136900       190040   Dermatofibrosarcoma protuberans           Giant-cell fibroblastoma           Meningioma, SIS-related       190195   Ichthyosiform erythroderma, congenital, 242100           Ichthyosis, lamellar, autosomal recessive, 242300       190300   Tremor, familial essential, 1       203740   Alpha-ketoglutarate dehydrogenase deficiency       210200   3-Methylcrotonylglycinuria I       211420   Breast cancer, ductal       218040   Costello syndrome       228960   [Kininogen deficiency]       236680   Hydrolethalus syndrome       256700   Neuroblastoma       258900   Oroticaciduria       261630   Phenylketonuria due to dihydropteridine reductase deficiency       261640   Phenylketonuria due to PTS deficiency       261670   Myopathy due to phosphoglycerate mutase deficiency       600044   Thrombocythemia, essential, 187950       600243   Temperature-sensitive apoptosis       600423   Hirschsprung disease, cardiac defects,           and autonomic dysfunction       600467   Malignant hyperthermia susceptibility 4       600532   Parkinson disease, susceptibility to, 168600       600593   Craniosynostosis, Adelaide type       600644   Cleft lip/palate ectodermal dysplasia syndrome, 225000           Ectodermal dysplasia, Margarita Island type, 225060           Zlotogora-Ogur syndrome, 225000       600882   Charcot-Marie-Tooth disease, type 2B       600975   Glaucoma 3, primary infantile, B       600994   Deafness, autosomal dominant 5       601472   Charcot-Marie-Tooth neuropathy, type 2D       601583   Wilms tumor susceptibility-5       601990   Neuroblastoma       602023   Bartter syndrome, 241200           Bartter syndrome, antenatal, 601678       602049   Neutrophil immunodeficiency syndrome       602279   Oculopharyngeal muscular dystorphy, 164300           Oculopharyngeal muscular dystrophy, autosomal           recessive, 257950       602322   Dyskeratosis congenita, 127550       602574   Deafness, autosomal dominant 12, 601842           Deafness, autosomal dominant 8, 601543           Deafness, autosomal recessive 21, 603629       602630   Holoprosencephaly-4, 142946       602773   Renal cell carcinoma 4       603023   Leukemia, acute lymphoblastic       603113   Lung cancer, 211980       603273   ADULT syndrome, 103285           Ectrodactyly, ectodermal dysplasia, and cleft           lip/palate syndrome 3, 604292           Hay-Wells syndrome, 106260           Limb-mammary syndrome, 603543           Split-hand/foot malformation, type 4, 605289       603284   Cerebral cavernous malformations-2       603285   Cerebral cavernous malformations-3       603324   Deafness, autosomal dominant 2, 600101           Deafness, autosomal dominant, with peripheral neuropathy           Deafness, autosomal recessive           Erythrokeratodermia variabilis, 133200       603490   XY female       603590   Meningioma       603593   Lysinuric protein intolerance, 222700       603688   Prostate cancer-brain cancer susceptibility       603776   Hypercholesterolemia, familial, 3       603945   Leukoencephalopathy with vanishing white matter, 603896       603959   Hypomagnesemia, primary, 248250       603967   Cramps, familial, potassium-aggravated           Hyperkalemic periodic paralysis, 170500           Hypokalemic periodic paralysis, 170400           Myotonia congenita, atypical, acetazolamide-responsive,           170500           Paramyotonia congenita, 168300       604365   Retinal degeneration, autosomal recessive, prominin-related       604484   Neuropathy, hereditary motor and sensory, Okinawa type       604630   Obesity, mild, early-onset, 601665       604763   Leukemia, acute myeloid       604802   Huntington disease-like 3       604831   Ellis-van Creveld syndrome, 225500           Weyers acrodental dysostosis, 193530       604933   Adenomatous polyposis of the colon, susceptibility to, 175100       605201   Hypoalphalipoproteinemia, primary       605225   Inflammatory bowel disease-7, 266600       605229   Spastic paraplegia 14, autosomal recessive       605389   Hypotrichosis simplex       605425   Erythrokeratodermia variabilis with erythema gyratum           repens, 133200       605441   Adiponectin deficiency       605463   Radiation sensitivity/chromosome instability syndrome,           autosomal dominant       605480   Systemic lupus erythematosus, susceptibility to, 3, 152700       605543   Parkinson disease 4, autosomal dominant, Lewy body       605552   Abdominal obesity-metabolic syndrome       605747   Hypercholesterolemia, familial, autosomal recessive, 603813       605841   Narcolepsy, 161400       605909   Parkinson disease, 168600       605995   Charcot-Marie-Tooth neuropathy, type 2A, 118210       606210   Muscular dystrophy, rigid spine, 1, 602771       606224   Anemia, hemolytic, due to UMPH1 deficiency, 266120       606246   Endometrial stromal tumors       606324   Parkinson disease, 168600       606439   Spastic paraplegia-3A, 182600       606675   Inflammatory bowel disease-4, 266600       606693   Kufor-Rakeb syndrome       606800   Glycogen storage disease II, 232300       606811   Hyperprolinemia, type II, 239510       606860   Angioedema, hereditary, 106100       606928   [Bone mineral density variability 3], 601884       606953   Galactose epimerase deficiency, 230350       606996   Senior-Loken syndrome 4       607037   Peroxisomal bifunctional enzyme deficiency, 261515       607086   Aortic aneurysm, familial thoracic 1       607093   Homocystinuria due to MTHFR deficiency, 236250       607107   Nasopharyngeal carcinoma 1, 161550       607215   Nephronophthisis 4, 606966                    
       [1262] Having generally described the invention, the same will be more readily understood by reference to the following examples, which are provided by way of illustration and are not intended as limiting.  
     
    
    
     EXAMPLES  
     Example 1  
     [1263] Isolation of a Selected cDNA Clone from the Deposited Sample  
     [1264] Each cDNA clone in a cited ATCC deposit is contained in a plasmid vector. Table 1 identifies the vectors used to construct the cDNA library from which each clone was isolated. In many cases, the vector used to construct the library is a phage vector from which a plasmid has been excised. The table immediately below correlates the related plasmid for each phage vector used in constructing the cDNA library. For example, where a particular clone is identified in Table 1 as being isolated in the vector “Lambda Zap,” the corresponding deposited clone is in “pBluescript.” 
                                   Vector Used to Construct Library   Corresponding Deposited Plasmid                  Lambda Zap   pBluescript (pBS)       Uni-Zap XR   pBluescript (pBS)       Zap Express   pBK       lafmid BA   plafmid BA       pSport1   pSport1       pCMVSport 2.0   pCMVSport 2.0       pCMVSport 3.0   pCMVSport 3.0       pCR ®2.1   pCR ®2.1                  
 
     [1265] Vectors Lambda Zap (U.S. Pat. Nos. 5,128,256 and 5,286,636), Uni-Zap XR (U.S. Pat. Nos. 5,128,256 and 5,286,636), Zap Express (U.S. Pat. Nos. 5,128,256 and 5,286,636), pBluescript (pBS) (Short et al.,  Nucleic Acids Res.,  16:7583-7600 (1988); Alting-Mees et al.,  Nucleic Acids Res.,  17:9494 (1989)) and pBK (Alting-Mees et al.,  Strategies,  5:58-61 (1992)) are commercially available from Stratagene Cloning Systems, Inc., 11011 N. Torrey Pines Road, La Jolla, Calif., 92037. pBS contains an ampicillin resistance gene and pBK contains a neomycin resistance gene. Both can be transformed into  E. coli  strain XL-1 Blue, also available from Stratagene. pBS comes in 4 forms SK+, SK−, KS+ and KS. The S and K refers to the orientation of the polylinker to the T7 and T3 primer sequences which flank the polylinker region (“S” is for SacI and “K” is for KpnI which are the first sites on each respective end of the linker). “+” or “−” refer to the orientation of the f1 origin of replication (“ori”), such that in one orientation, single stranded rescue initiated from the f1 ori generates sense strand DNA and in the other, antisense.  
     [1266] Vectors pSport1, pCMVSport 2.0 and pCMVSport 3.0, were obtained from Life Technologies, Inc., P. O. Box 6009, Gaithersburg, Md. 20897. All Sport vectors contain an ampicillin resistance gene and may be transformed into  E. coli  strain DH10B, also available from Life Technologies. (See, for instance, Gruber, C. E., et al., Focus 15:59 (1993)). Vector lafmid BA (Bento Soares, Columbia University, NY) contains an ampicillin resistance gene and can be transformed into  E. coli  strain XL-1 Blue. Vector pCR®2.1, which is available from Invitrogen, 1600 Faraday Avenue, Carlsbad, Calif. 92008, contains an ampicillin resistance gene and may be transformed into  E. coli  strain DH10B, available from Life Technologies. (See, for instance, Clark,  Nuc. Acids Res.,  16:9677-9686 (1988) and Mead et al.,  Bio/Technology,  9 (1991)). Preferably, a polynucleotide of the present invention does not comprise the phage vector sequences identified for the particular clone in Table 1, as well as the corresponding plasmid vector sequences designated above.  
     [1267] The deposited material in the sample assigned the ATCC Deposit Number cited in Table 1 for any given cDNA clone also may contain one or more additional plasmids, each comprising a cDNA clone different from that given clone. Thus, deposits sharing the same ATCC Deposit Number contain at least a plasmid for each cDNA Plasmid:V identified in Table 1. Typically, each ATCC deposit sample cited in Table 1 comprises a mixture of approximately equal amounts (by weight) of about 50 plasmid DNAs, each containing a different cDNA clone; but such a deposit sample may include plasmids for more or less than 50 cDNA clones, up to about 500 cDNA clones.  
     [1268] Two approaches can be used to isolate a particular clone from the deposited sample of plasmid DNAs cited for that clone in Table 1. First, a plasmid is directly isolated by screening the clones using a polynucleotide probe corresponding to SEQ ID NO:X.  
     [1269] Particularly, a specific polynucleotide with 30-40 nucleotides is synthesized using an Applied Biosystems DNA synthesizer according to the sequence reported. The oligonucleotide is labeled, for instance, with  32 P-γ-ATP using T4 polynucleotide kinase and purified according to routine methods. (E.g., Maniatis et al.,  Molecular Cloning: A Laboratory Manual,  Cold Spring Harbor Press, Cold Spring, N.Y. (1982)). The plasmid mixture is transformed into a suitable host, as indicated above (such as XL-1 Blue (Stratagene)) using techniques known to those of skill in the art, such as those provided by the vector supplier or in related publications or patents cited above. The transformants are plated on 1.5% agar plates (containing the appropriate selection agent, e.g., ampicillin) to a density of about 150 transformants (colonies) per plate. These plates are screened using Nylon membranes according to routine methods for bacterial colony screening (e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 2nd Edit., (1989), Cold Spring Harbor Laboratory Press, pages 1.93 to 1.104), or other techniques known to those of skill in the art.  
     [1270] Alternatively, two primers of 17-20 nucleotides derived from both ends of the SEQ ID NO:X (i.e., within the region of SEQ ID NO:X bounded by the 5′ NT and the 3′ NT of the clone defined in Table 1) are synthesized and used to amplify the desired cDNA using the deposited cDNA plasmid as a template. The polymerase chain reaction is carried out under routine conditions, for instance, in 25 μl of reaction mixture with 0.5 ug of the above cDNA template. A convenient reaction mixture is 1.5-5 mM MgCl 2 , 0.01% (w/v) gelatin, 20 μM each of dATP, dCTP, dGTP, dTTP, 25 pmol of each primer and 0.25 Unit of Taq polymerase. Thirty five cycles of PCR (denaturation at 94° C. for 1 min; annealing at 55° C. for 1 min; elongation at 72° C. for 1 min) are performed with a Perkin-Elmer Cetus automated thermal cycler. The amplified product is analyzed by agarose gel electrophoresis and the DNA band with expected molecular weight is excised and purified. The PCR product is verified to be the selected sequence by subcloning and sequencing the DNA product.  
     [1271] Several methods are available for the identification of the 5′ or 3′ non-coding portions of a gene which may not be present in the deposited clone. These methods include but are not limited to, filter probing, clone enrichment using specific probes, and protocols similar or identical to 5′ and 3′ “RACE” protocols which are well known in the art. For instance, a method similar to 5′ RACE is available for generating the missing 5′ end of a desired full-length transcript. (Fromont-Racine et al.,  Nucleic Acids Res.,  21(7):1683-1684 (1993)).  
     [1272] Briefly, a specific RNA oligonucleotide is ligated to the 5′ ends of a population of RNA presumably containing full-length gene RNA transcripts. A primer set containing a primer specific to the ligated RNA oligonucleotide and a primer specific to a known sequence of the gene of interest is used to PCR amplify the 5′ portion of the desired full-length gene. This amplified product may then be sequenced and used to generate the full length gene.  
     [1273] This above method starts with total RNA isolated from the desired source, although poly-A+ RNA can be used. The RNA preparation can then be treated with phosphatase if necessary to eliminate 5′ phosphate groups on degraded or damaged RNA which may interfere with the later RNA ligase step. The phosphatase should then be inactivated and the RNA treated with tobacco acid pyrophosphatase in order to remove the cap structure present at the 5′ ends of messenger RNAs. This reaction leaves a 5′ phosphate group at the 5′ end of the cap cleaved RNA which can then be ligated to an RNA oligonucleotide using T4 RNA ligase.  
     [1274] This modified RNA preparation is used as a template for first strand cDNA synthesis using a gene specific oligonucleotide. The first strand synthesis reaction is used as a template for PCR amplification of the desired 5′ end using a primer specific to the ligated RNA oligonucleotide and a primer specific to the known sequence of the gene of interest. The resultant product is then sequenced and analyzed to confirm that the 5′ end sequence belongs to the desired gene.  
     Example 2  
     [1275] Isolation of Genomic Clones Corresponding to a Polynucleotide  
     [1276] A human genomic P1 library (Genomic Systems, Inc.) is screened by PCR using primers selected for the cDNA sequence corresponding to SEQ ID NO:X., according to the method described in Example 1. (See also, Sambrook.)  
     Example 3  
     [1277] Tissue Distribution of Polypeptide  
     [1278] Tissue distribution of mRNA expression of polynucleotides of the present invention is determined using protocols for Northern blot analysis, described by, among others, Sambrook et al. For example, a cDNA probe produced by the method described in Example 1 is labeled with P 32  using the rediprime™ DNA labeling system (Amersham Life Science), according to manufacturer&#39;s instructions. After labeling, the probe is purified using CHROMA SPIN-100™ column (Clontech Laboratories, Inc.), according to manufacturer&#39;s protocol number PT1200-1. The purified labeled probe is then used to examine various human tissues for mRNA expression.  
     [1279] Multiple Tissue Northern (MTN) blots containing various human tissues (H) or human immune system tissues (IM) (Clontech) are examined with the labeled probe using ExpressHyb™ hybridization solution (Clontech) according to manufacturer&#39;s protocol number PT1190-1. Following hybridization and washing, the blots are mounted and exposed to film at −70° C. overnight, and the films developed according to standard procedures.  
     Example 4  
     [1280] Chromosomal Mapping of the Polynucleotides  
     [1281] An oligonucleotide primer set is designed according to the sequence at the 5′ end of SEQ ID NO:X. This primer preferably spans about 100 nucleotides. This primer set is then used in a polymerase chain reaction under the following set of conditions: 30 seconds, 95° C.; 1 minute, 56° C.; 1 minute, 70° C. This cycle is repeated 32 times followed by one 5 minute cycle at 70° C. Human, mouse, and hamster DNA is used as template in addition to a somatic cell hybrid panel containing individual chromosomes or chromosome fragments (Bios, Inc). The reactions is analyzed on either 8% polyacrylamide gels or 3.5% agarose gels. Chromosome mapping is determined by the presence of an approximately 100 bp PCR fragment in the particular somatic cell hybrid.  
     Example 5  
     [1282] Bacterial Expression of a Polypeptide  
     [1283] A polynucleotide encoding a polypeptide of the present invention is amplified using PCR oligonucleotide primers corresponding to the 5′ and 3′ ends of the DNA sequence, as outlined in Example 1, to synthesize insertion fragments. The primers used to amplify the cDNA insert should preferably contain restriction sites, such as BamHI and XbaI and initiation/stop codons, if necessary, to clone the amplified product into the expression vector. For example, BamHI and XbaI correspond to the restriction enzyme sites on the bacterial expression vector pQE-9. (Qiagen, Inc., Chatsworth, Calif.). This plasmid vector encodes antibiotic resistance (Amp r ), a bacterial origin of replication (ori), an IPTG-regulatable promoter/operator (P/O), a ribosome binding site (RBS), a 6-histidine tag (6-His), and restriction enzyme cloning sites.  
     [1284] The pQE-9 vector is digested with BamHI and XbaI and the amplified fragment is ligated into the pQE-9 vector maintaining the reading frame initiated at the bacterial RBS. The ligation mixture is then used to transform the  E. coli  strain M15/rep4 (Qiagen, Inc.) which contains multiple copies of the plasmid pREP4, which expresses the lacI repressor and also confers kanamycin resistance (Kan r ). Transformants are identified by their ability to grow on LB plates and ampicillin/kanamycin resistant colonies are selected. Plasmid DNA is isolated and confirmed by restriction analysis.  
     [1285] Clones containing the desired constructs are grown overnight (O/N) in liquid culture in LB media supplemented with both Amp (100 ug/ml) and Kan (25 ug/ml). The O/N culture is used to inoculate a large culture at a ratio of 1:100 to 1:250. The cells are grown to an optical density 600 (O.D. 600 ) of between 0.4 and 0.6. IPTG (Isopropyl-B-D-thiogalacto pyranoside) is then added to a final concentration of 1 mM. IPTG induces by inactivating the lacI repressor, clearing the P/O leading to increased gene expression.  
     [1286] Cells are grown for an extra 3 to 4 hours. Cells are then harvested by centrifugation (20 mins at 6000×g). The cell pellet is solubilized in the chaotropic agent 6 Molar Guanidine HCl by stirring for 3-4 hours at 4° C. The cell debris is removed by centrifugation, and the supernatant containing the polypeptide is loaded onto a nickel-nitrilo-tri-acetic acid (“Ni-NTA”) affinity resin column (available from QIAGEN, Inc., supra). Proteins with a 6 x His tag bind to the Ni-NTA resin with high affinity and can be purified in a simple one-step procedure (for details see: The QlAexpressionist (1995) QIAGEN, Inc., supra).  
     [1287] Briefly, the supernatant is loaded onto the column in 6 M guanidine-HCl, pH 8, the column is first washed with 10 volumes of 6 M guanidine-HCl, pH 8, then washed with 10 volumes of 6 M guanidine-HCl pH 6, and finally the polypeptide is eluted with 6 M guanidine-HCl, pH 5.  
     [1288] The purified protein is then renatured by dialyzing it against phosphate-buffered saline (PBS) or 50 mM Na-acetate, pH 6 buffer plus 200 mM NaCl. Alternatively, the protein can be successfully refolded while immobilized on the Ni-NTA column. The recommended conditions are as follows: renature using a linear 6M-1M urea gradient in 500 mM NaCl, 20% glycerol, 20 mM Tris/HCl pH 7.4, containing protease inhibitors. The renaturation should be performed over a period of 1.5 hours or more. After renaturation the proteins are eluted by the addition of 250 mM immidazole. Immidazole is removed by a final dialyzing step against PBS or 50 mM sodium acetate pH 6 buffer plus 200 mM NaCl. The purified protein is stored at 4° C. or frozen at −80° C.  
     [1289] In addition to the above expression vector, the present invention further includes an expression vector comprising phage operator and promoter elements operatively linked to a polynucleotide of the present invention, called pHE4a. (ATCC Accession Number 209645, deposited on Feb. 25, 1998.) This vector contains: 1) a neomycinphosphotransferase gene as a selection marker, 2) an  E. coli  origin of replication, 3) a T5 phage promoter sequence, 4) two lac operator sequences, 5) a Shine-Delgarno sequence, and 6) the lactose operon repressor gene (lacIq). The origin of replication (oriC) is derived from pUC19 (LTI, Gaithersburg, Md.). The promoter sequence and operator sequences are made synthetically.  
     [1290] DNA can be inserted into the pHEa by restricting the vector with NdeI and XbaI, BamHI, XhoI, or Asp718, running the restricted product on a gel, and isolating the larger fragment (the stuffer fragment should be about 310 base pairs). The DNA insert is generated according to the PCR protocol described in Example 1, using PCR primers having restriction sites for NdeI (5′ primer) and XbaI, BamHII, XhoI, or Asp718 (3′ primer). The PCR insert is gel purified and restricted with compatible enzymes. The insert and vector are ligated according to standard protocols.  
     [1291] The engineered vector could easily be substituted in the above protocol to express protein in a bacterial system.  
     Example 6  
     [1292] Purification of a Polypeptide from an Inclusion Body  
     [1293] The following alternative method can be used to purify a polypeptide expressed in  E coli  when it is present in the form of inclusion bodies. Unless otherwise specified, all of the following steps are conducted at 4-10° C.  
     [1294] Upon completion of the production phase of the  E. coli  fermentation, the cell culture is cooled to 4-10° C. and the cells harvested by continuous centrifugation at 15,000 rpm (Heraeus Sepatech). On the basis of the expected yield of protein per unit weight of cell paste and the amount of purified protein required, an appropriate amount of cell paste, by weight, is suspended in a buffer solution containing 100 mM Tris, 50 mM EDTA, pH 7.4. The cells are dispersed to a homogeneous suspension using a high shear mixer.  
     [1295] The cells are then lysed by passing the solution through a microfluidizer (Microfuidics, Corp. or APV Gaulin, Inc.) twice at 4000-6000 psi. The homogenate is then mixed with NaCl solution to a final concentration of 0.5 M NaCl, followed by centrifugation at 7000×g for 15 min. The resultant pellet is washed again using 0.5M NaCl, 100 mM Tris, 50 mM EDTA, pH 7.4.  
     [1296] The resulting washed inclusion bodies are solubilized with 1.5 M guanidine hydrochloride (GuHCl) for 2-4 hours. After 7000×g centrifugation for 15 min., the pellet is discarded and the polypeptide containing supernatant is incubated at 4° C. overnight to allow further GuHCl extraction.  
     [1297] Following high speed centrifugation (30,000×g) to remove insoluble particles, the GuHCl solubilized protein is refolded by quickly mixing the GuHCl extract with 20 volumes of buffer containing 50 mM sodium, pH 4.5, 150 mM NaCl, 2 mM EDTA by vigorous stirring. The refolded diluted protein solution is kept at 4° C. without mixing for 12 hours prior to further purification steps.  
     [1298] To clarify the refolded polypeptide solution, a previously prepared tangential filtration unit equipped with 0.16 μm membrane filter with appropriate surface area (e.g., Filtron), equilibrated with 40 mM sodium acetate, pH 6.0 is employed. The filtered sample is loaded onto a cation exchange resin (e.g., Poros HS-50, Perseptive Biosystems). The column is washed with 40 mM sodium acetate, pH 6.0 and eluted with 250 mM, 500 mM, 1000 mM, and 1500 mM NaCl in the same buffer, in a stepwise manner. The absorbance at 280 nm of the effluent is continuously monitored. Fractions are collected and further analyzed by SDS-PAGE.  
     [1299] Fractions containing the polypeptide are then pooled and mixed with 4 volumes of water. The diluted sample is then loaded onto a previously prepared set of tandem columns of strong anion (Poros HQ-50, Perseptive Biosystems) and weak anion (Poros CM-20, Perseptive Biosystems) exchange resins. The columns are equilibrated with 40 mM sodium acetate, pH 6.0. Both columns are washed with 40 mM sodium acetate, pH 6.0, 200 mM NaCl. The CM-20 column is then eluted using a 10 column volume linear gradient ranging from 0.2 M NaCl, 50 mM sodium acetate, pH 6.0 to 1.0 M NaCl, 50 mM sodium acetate, pH 6.5. Fractions are collected under constant A 280  monitoring of the effluent. Fractions containing the polypeptide (determined, for instance, by 16% SDS-PAGE) are then pooled.  
     [1300] The resultant polypeptide should exhibit greater than 95% purity after the above refolding and purification steps. No major contaminant bands should be observed from Commassie blue stained 16% SDS-PAGE gel when 5 μg of purified protein is loaded. The purified protein can also be tested for endotoxin/LPS contamination, and typically the LPS content is less than 0.1 ng/ml according to LAL assays.  
     Example 7  
     [1301] Cloning and Expression of a Polypeptide in a Baculovirus Expression System  
     [1302] In this example, the plasmid shuttle vector pA2 is used to insert a polynucleotide into a baculovirus to express a polypeptide. This expression vector contains the strong polyhedrin promoter of the  Autographa californica  nuclear polyhedrosis virus (AcMNPV) followed by convenient restriction sites such as BamHI, Xba I and Asp718. The polyadenylation site of the simian virus 40 (“SV40”) is used for Xba I and Asp718. The polyadenylation site of the simian virus 40 (“SV40”) is used for the beta-galactosidase gene from  E coli  under control of a weak Drosophila promoter in the same orientation, followed by the polyadenylation signal of the polyhedrin gene. The inserted genes are flanked on both sides by viral sequences for cell-mediated homologous recombination with wild-type viral DNA to generate a viable virus that express the cloned polynucleotide.  
     [1303] Many other baculovirus vectors can be used in place of the vector above, such as pAc373, pVL941, and pAcIM1, as one skilled in the art would readily appreciate, as long as the construct provides appropriately located signals for transcription, translation, secretion and the like, including a signal peptide and an in-frame AUG as required. Such vectors are described, for instance, in Luckow et al., Virology 170:31-39 (1989).  
     [1304] Specifically, the cDNA sequence contained in the deposited clone is amplified using the PCR protocol described in Example 1 using primers with appropriate restriction sites and initiation/stop codons. If the naturally occurring signal sequence is used to produce the secreted protein, the pA2 vector does not need a second signal peptide. Alternatively, the vector can be modified (pA2 GP) to include a baculovirus leader sequence, using the standard methods described in Summers et al., “A Manual of Methods for Baculovirus Vectors and Insect Cell Culture Procedures,” Texas Agricultural Experimental Station Bulletin NO: 1555 (1987).  
     [1305] The amplified fragment is isolated from a 1% agarose gel using a commercially available kit (“Geneclean,” BIO 101 Inc., La Jolla, Calif.). The fragment then is digested with appropriate restriction enzymes and again purified on a 1% agarose gel.  
     [1306] The plasmid is digested with the corresponding restriction enzymes and optionally, can be dephosphorylated using calf intestinal phosphatase, using routine procedures known in the art. The DNA is then isolated from a 1% agarose gel using a commercially available kit (“Geneclean” BIO 101 Inc., La Jolla, Calif.).  
     [1307] The fragment and the dephosphorylated plasmid are ligated together with T4 DNA ligase.  E. coli  HB101 or other suitable  E. coli  hosts such as XL-1 Blue (Stratagene Cloning Systems, La Jolla, Calif.) cells are transformed with the ligation mixture and spread on culture plates. Bacteria containing the plasmid are identified by digesting DNA from individual colonies and analyzing the digestion product by gel electrophoresis. The sequence of the cloned fragment is confirmed by DNA sequencing.  
     [1308] Five μg of a plasmid containing the polynucleotide is co-transfected with 1.0 μg of a commercially available linearized baculovirus DNA (“BaculoGold™ baculovirus DNA”, Pharmingen, San Diego, Calif.), using the lipofection method described by Felgner et al., Proc. Natl. Acad. Sci. USA 84:7413-7417 (1987). One μg of BaculoGold™ virus DNA and 5 μg of the plasmid are mixed in a sterile well of a microtiter plate containing 50 μl of serum-free Grace&#39;s medium (Life Technologies Inc., Gaithersburg, Md.). Afterwards, 10 μl Lipofectin plus 90 μl Grace&#39;s medium are added, mixed and incubated for 15 minutes at room temperature. Then the transfection mixture is added drop-wise to Sf9 insect cells (ATCC CRL 1711) seeded in a 35 mm tissue culture plate with 1 ml Grace&#39;s medium without serum. The plate is then incubated for 5 hours at 27° C. The transfection solution is then removed from the plate and 1 ml of Grace&#39;s insect medium supplemented with 10% fetal calf serum is added. Cultivation is then continued at 27° C. for four days.  
     [1309] After four days the supernatant is collected and a plaque assay is performed, as described by Summers and Smith, supra. An agarose gel with “Blue Gal” (Life Technologies Inc., Gaithersburg) is used to allow easy identification and isolation of gal-expressing clones, which produce blue-stained plaques. (A detailed description of a “plaque assay” of this type can also be found in the user&#39;s guide for insect cell culture and baculovirology distributed by Life Technologies Inc., Gaithersburg, page 9-10.) After appropriate incubation, blue stained plaques are picked with the tip of a micropipettor (e.g., Eppendorf). The agar containing the recombinant viruses is then resuspended in a microcentrifuge tube containing 200 μl of Grace&#39;s medium and the suspension containing the recombinant baculovirus is used to infect Sf9 cells seeded in 35 mm dishes. Four days later the supernatants of these culture dishes are harvested and then they are stored at 4° C.  
     [1310] To verify the expression of the polypeptide, Sf9 cells are grown in Grace&#39;s medium supplemented with 10% heat-inactivated FBS. The cells are infected with the recombinant baculovirus containing the polynucleotide at a multiplicity of infection (“MOI”) of about 2. If radiolabeled proteins are desired, 6 hours later the medium is removed and is replaced with SF900 II medium minus methionine and cysteine (available from Life Technologies Inc., Rockville, Md.). After 42 hours, 5 μCi of  35 S-methionine and 5 μCi  35 S-cysteine (available from Amersham) are added. The cells are further incubated for 16 hours and then are harvested by centrifugation. The proteins in the supernatant as well as the intracellular proteins are analyzed by SDS-PAGE followed by autoradiography (if radiolabeled).  
     [1311] Microsequencing of the amino acid sequence of the amino terminus of purified protein may be used to determine the amino terminal sequence of the produced protein.  
     Example 8  
     [1312] Expression of a Polypeptide in Mammalian Cells  
     [1313] The polypeptide of the present invention can be expressed in a mammalian cell. A typical mammalian expression vector contains a promoter element, which mediates the initiation of transcription of mRNA, a protein coding sequence, and signals required for the termination of transcription and polyadenylation of the transcript. Additional elements include enhancers, Kozak sequences and intervening sequences flanked by donor and acceptor sites for RNA splicing. Highly efficient transcription is achieved with the early and late promoters from SV40, the long terminal repeats (LTRs) from Retroviruses, e.g., RSV, HTLVI, HIVI and the early promoter of the cytomegalovirus (CMV). However, cellular elements can also be used (e.g., the human actin promoter).  
     [1314] Suitable expression vectors for use in practicing the present invention include, for example, vectors such as pSVL and pMSG (Pharmacia, Uppsala, Sweden), pRSVcat (ATCC 37152), pSV2dhfr (ATCC 37146), pBC12MI (ATCC 67109), pCMVSport 2.0, and pCMVSport 3.0. Mammalian host cells that could be used include, human Hela, 293, H9 and Jurkat cells, mouse NIH3T3 and C127 cells, Cos 1, Cos 7 and CV1, quail QC1-3 cells, mouse L cells and Chinese hamster ovary (CHO) cells.  
     [1315] Alternatively, the polypeptide can be expressed in stable cell lines containing the polynucleotide integrated into a chromosome. The co-transfection with a selectable marker such as dhfr, gpt, neomycin, hygromycin allows the identification and isolation of the transfected cells.  
     [1316] The transfected gene can also be amplified to express large amounts of the encoded protein. The DHFR (dihydrofolate reductase) marker is useful in developing cell lines that carry several hundred or even several thousand copies of the gene of interest. (See, e.g., Alt et al.,  J. Biol. Chem.,  253:1357-1370 (1978); Hamlin et al.,  Biochem. et Biophys. Acta,  1097:107-143 (1990); Page et al.,  Biotechnology,  9:64-68 (1991)). Another useful selection marker is the enzyme glutamine synthase (GS) (Murphy et al.,  Biochem J.,  227:277-279 (1991); Bebbington et al.,  Bio/Technology,  10:169-175 (1992). Using these markers, the mammalian cells are grown in selective medium and the cells with the highest resistance are selected. These cell lines contain the amplified gene(s) integrated into a chromosome. Chinese hamster ovary (CHO) and NSO cells are often used for the production of proteins.  
     [1317] Derivatives of the plasmid pSV2-dhfr (ATCC Accession No.: 37146), the expression vectors pC4 (ATCC Accession No.: 209646) and pC6 (ATCC Accession No.:209647) contain the strong promoter (LTR) of the Rous Sarcoma Virus (Cullen et al.,  Molecular and Cellular Biology,  438-447 (March, 1985)) plus a fragment of the CMV-enhancer (Boshart et al.,  Cell,  41:521-530 (1985)). Multiple cloning sites, e.g., with the restriction enzyme cleavage sites BamHI, XbaI and Asp718, facilitate the cloning of the gene of interest. The vectors also contain the 3′ intron, the polyadenylation and termination signal of the rat preproinsulin gene, and the mouse DHFR gene under control of the SV40 early promoter.  
     [1318] Specifically, the plasmid pC6, for example, is digested with appropriate restriction enzymes and then dephosphorylated using calf intestinal phosphates by procedures known in the art. The vector is then isolated from a 1% agarose gel.  
     [1319] A polynucleotide of the present invention is amplified according to the protocol outlined in Example 1 using primers with appropriate restrictions sites and initiation/stop codons, if necessary. The vector can be modified to include a heterologous signal sequence if necessary for secretion. (See, e.g., WO 96/34891.)  
     [1320] The amplified fragment is isolated from a 1% agarose gel using a commercially available kit (“Geneclean,” BIO 101 Inc., La Jolla, Calif.). The fragment then is digested with appropriate restriction enzymes and again purified on a 1% agarose gel.  
     [1321] The amplified fragment is then digested with the same restriction enzyme and purified on a 1% agarose gel. The isolated fragment and the dephosphorylated vector are then ligated with T4 DNA ligase.  E. coli  HB101 or XL-1 Blue cells are then transformed and bacteria are identified that contain the fragment inserted into plasmid pC6 using, for instance, restriction enzyme analysis.  
     [1322] Chinese hamster ovary cells lacking an active DHFR gene is used for transfection. Five μg of the expression plasmid pC6 is cotransfected with 0.5 μg of the plasmid pSVneo using lipofectin (Felgner et al., supra). The plasmid pSV2-neo contains a dominant selectable marker, the neo gene from Tn5 encoding an enzyme that confers resistance to a group of antibiotics including G418. The cells are seeded in alpha minus MEM supplemented with 1 mg/ml G418. After 2 days, the cells are trypsinized and seeded in hybridoma cloning plates (Greiner, Germany) in alpha minus MEM supplemented with 10, 25, or 50 ng/ml of metothrexate plus 1 mg/ml G418. After about 10-14 days single clones are trypsinized and then seeded in 6-well petri dishes or 10 ml flasks using different concentrations of methotrexate (50 nM, 100 nM, 200 nM, 400 nM, 800 nM). Clones growing at the highest concentrations of methotrexate are then transferred to new 6-well plates containing even higher concentrations of methotrexate (1 μM, 2 μM, 5 μM, 10 mM, 20 mM). The same procedure is repeated until clones are obtained which grow at a concentration of 100-200 μM. Expression of the desired gene product is analyzed, for instance, by SDS-PAGE and Western blot or by reversed phase HPLC analysis.  
     Example 9  
     [1323] Protein Fusions  
     [1324] The polypeptides of the present invention are preferably fused to other proteins. These fusion proteins can be used for a variety of applications. For example, fusion of the present polypeptides to His-tag, HA-tag, protein A, IgG domains, and maltose binding protein facilitates purification. (See Example 5; see also EP A 394,827; Traunecker, et al.,  Nature,  331:84-86 (1988)) The polypeptides can also be fused to heterologous polypeptide sequences to facilitate secretion and intracellular trafficking (e.g., KDEL). Moreover, fusion to IgG-1, IgG-3, and albumin increases the halflife time in vivo. Nuclear localization signals fused to the polypeptides of the present invention can target the protein to a specific subcellular localization, while covalent heterodimer or homodimers can increase or decrease the activity of a fusion protein. Fusion proteins can also create chimeric molecules having more than one function. Finally, fusion proteins can increase solubility and/or stability of the fused protein compared to the non-fused protein. All of the types of fusion proteins described above can be made by modifying the following protocol, which outlines the fusion of a polypeptide to an IgG molecule, or the protocol described in Example 5.  
     [1325] Briefly, the human Fc portion of the IgG molecule can be PCR amplified, using primers that span the 5′ and 3′ ends of the sequence described below. These primers also should have convenient restriction enzyme sites that will facilitate cloning into an expression vector, preferably a mammalian expression vector, and initiation/stop codons, if necessary.  
     [1326] For example, if pC4 (Accession No.: 209646) is used, the human Fc portion can be ligated into the BamHI cloning site. Note that the 3′ BamHI site should be destroyed. Next, the vector containing the human Fc portion is re-restricted with BamHI, linearizing the vector, and a polynucleotide of the present invention, isolated by the PCR protocol described in Example 1, is ligated into this BamHI site. Note that the polynucleotide is cloned without a stop codon, otherwise a fusion protein will not be produced.  
     [1327] If the naturally occurring signal sequence is used to produce the secreted protein, pC4 does not need a second signal peptide. Alternatively, if the naturally occurring signal sequence is not used, the vector can be modified to include a heterologous signal sequence. (See, e.g., WO 96/34891.)  
                          Human IgG Fc region:                         (SEQ ID NO:1)                         GGGATCCGGAGCCCAAATCTTCTGACAAAACTCACACATGCCCACCGTGC                   CCAGCACCTGAATTCGAGGGTGCACCGTCAGTCTTCCTCTTCCCCCCAAA               ACCCAAGGACACCCTCATGATCTCCCGGACTCCTGAGGTCACATGCGTGG               TGGTGGACGTAAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTG               GACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTA               CAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACT               GGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCA               ACCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACC               ACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGG               TCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCAAGCGACATCGCCGTG               GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCC               CGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGG               ACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCAT               GAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGG               TAAATGAGTGCGACGGCCGCGACTCTAGAGGAT          
 
     Example 10  
     [1328] Formulating a Polypeptide  
     [1329] The invention also provides methods of treatment and/or prevention of diseases or disorders (such as, for example, any one or more of the diseases or disorders disclosed herein) by administration to a subject of an effective amount of a Therapeutic. By Therapeutic is meant polynucleotides or polypeptides of the invention (including fragments and variants), agonists or antagonists thereof, and/or antibodies thereto, in combination with a pharmaceutically acceptable carrier type (e.g., a sterile carrier).  
     [1330] The polypeptide composition will be formulated and dosed in a fashion consistent with good medical practice, taking into account the clinical condition of the individual patient (especially the side effects of treatment with the secreted polypeptide alone), the site of delivery, the method of administration, the scheduling of administration, and other factors known to practitioners. The “effective amount” for purposes herein is thus determined by such considerations.  
     [1331] As a general proposition, the total pharmaceutically effective amount of polypeptide administered parenterally per dose will be in the range of about 1 μg/kg/day to 10 mg/kg/day of patient body weight, although, as noted above, this will be subject to therapeutic discretion. More preferably, this dose is at least 0.01 mg/kg/day, and most preferably for humans between about 0.01 and 1 mg/kg/day for the hormone. If given continuously, the polypeptide is typically administered at a dose rate of about 1 μg/kg/hour to about 50 μg/kg/hour, either by 1-4 injections per day or by continuous subcutaneous infusions, for example, using a mini-pump. An intravenous bag solution may also be employed. The length of treatment needed to observe changes and the interval following treatment for responses to occur appears to vary depending on the desired effect.  
     [1332] Pharmaceutical compositions containing the polypeptide of the invention are administered orally, rectally, parenterally, intracistemally, intravaginally, intraperitoneally, topically (as by powders, ointments, gels, drops or transdermal patch), bucally, or as an oral or nasal spray. “Pharmaceutically acceptable carrier” refers to a non-toxic solid, semisolid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type. The term “parenteral” as used herein refers to modes of administration which include intravenous, intramuscular, intraperitoneal, intrastemal, subcutaneous and intraarticular injection and infusion.  
     [1333] The polypeptide is also suitably administered by sustained-release systems. Suitable examples of sustained-release compositions include semi-permeable polymer matrices in the form of shaped articles, e.g., films, or mirocapsules. Sustained-release matrices include polylactides (U.S. Pat. No. 3,773,919, EP 58,481), copolymers of L-glutamic acid and gamma-ethyl-L-glutamate (Sidman et al.,  Biopolymers,  22:547-556 (1983)), poly(2-hydroxyethyl methacrylate) (Langer et al.,  J. Biomed. Mater. Res.  15:167-277 (1981), and Langer,  Chem. Tech.,  12:98-105 (1982)), ethylene vinyl acetate (R. Langer et al.) or poly-D-(−)-3-hydroxybutyric acid (EP 133,988).  
     [1334] In a preferred embodiment, compositions of the invention are formulated in a biodegradable, polymeric drug delivery system, for example as described in U.S. Pat. Nos. 4,938,763; 5,278,201; 5,278,202; 5,324,519; 5,340,849; and 5,487,897 and in International Publication Numbers WO01/35929, WO00/24374, and WO00/06117 which are hereby incorporated by reference in their entirety. In specific preferred embodiments the compositions of the invention are formulated using the ATRIGEL® Biodegradable System of Atrix Laboratories, Inc. (Fort Collins, Colo.).  
     [1335] Examples of biodegradable polymers which can be used in the formulation of compositions of the invention include, but are not limited to, polylactides, polyglycolides, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(amino acids), poly(methyl vinyl ether), poly(maleic anhydride), polyvinylpyrrolidone, polyethylene glycol, polyhydroxycellulose, chitin, chitosan, and copolymers, terpolymers, or combinations or mixtures of the above materials. The preferred polymers are those that have a lower degree of crystallization and are more hydrophobic. These polymers and copolymers are more soluble in the biocompatible solvents than the highly crystalline polymers such as polyglycolide and chitin which also have a high degree of hydrogen-bonding. Preferred materials with the desired solubility parameters are the polylactides, polycaprolactones, and copolymers of these with glycolide in which there are more amorphous regions to enhance solubility. In specific preferred embodiments, the biodegradable polymers which can be used in the formulation of compositions of the invention are poly(lactide-co-glycolides). Polymer properties such as molecular weight, hydrophobicity, and lactide/glycolide ratio may be modified to obtain the desired drug release profile (See, e.g., Ravivarapu et al., Journal of Pharmaceutical Sciences 89:732-741 (2000), which is hereby incorporated by reference in its entirety).  
     [1336] It is also preferred that the solvent for the biodegradable polymer be non-toxic, water miscible, and otherwise biocompatible. Examples of such solvents include, but are not limted to, N-methyl-2-pyrrolidone, 2-pyrrolidone, C2 to C6 alkanols, C1 to C15 alchohols, dils, triols, and tetraols such as ethanol, glycerine propylene glycol, butanol; C3 to C15 alkyl ketones such as acetone, diethyl ketone and methyl ethyl ketone; C3 to C15 esters such as methyl acetate, ethyl acetate, ethyl lactate; alkyl ketones such as methyl ethyl ketone, C1 to C15 amides such as dimethylformamide, dimethylacetamide and caprolactam; C3 to C20 ethers such as tetrahydrofuran, or solketal; tweens, triacetin, propylene carbonate, decylmethylsulfoxide, dimethyl sulfoxide, oleic acid, 1-dodecylazacycloheptan-2-one, Other preferred solvents are benzyl alchohol, benzyl benzoate, dipropylene glycol, tributyrin, ethyl oleate, glycerin, glycofural, isopropyl myristate, isopropyl palmitate, oleic acid, polyethylene glycol, propylene carbonate, and triethyl citrate. The most preferred solvents are N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, triacetin, and propylene carbonate because of the solvating ability and their compatibility.  
     [1337] Additionally, formulations comprising compositions of the invention and a biodegradable polymer may also include release-rate modification agents and/or pore-forming agents. Examples of release-rate modification agents include, but are not limited to, fatty acids, triglycerides, other like hydrophobic compounds, organic solvents, plasticizing compounds and hydrophilic compounds. Suitable release rate modification agents include, for example, esters of mono-, di-, and tricarboxylic acids, such as 2-ethoxyethyl acetate, methyl acetate, ethyl acetate, diethyl phthalate, dimethyl phthalate, dibutyl phthalate, dimethyl adipate, dimethyl succinate, dimethyl oxalate, dimethyl citrate, triethyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, glycerol triacetate, di(n-butyl) sebecate, and the like; polyhydroxy alcohols, such as propylene glycol, polyethylene glycol, glycerin, sorbitol, and the like; fatty acids; triesters of glycerol, such as triglycerides, epoxidized soybean oil, and other epoxidized vegetable oils; sterols, such as cholesterol; alcohols, such as C.sub.6-C.sub.12 alkanols, 2-ethoxyethanol, and the like. The release rate modification agent may be used singly or in combination with other such agents. Suitable combinations of release rate modification agents include, but are not limited to, glycerin/propylene glycol, sorbitol/glycerine, ethylene oxide/propylene oxide, butylene glycol/adipic acid, and the like. Preferred release rate modification agents include, but are not limited to, dimethyl citrate, triethyl citrate, ethyl heptanoate, glycerin, and hexanediol. Suitable pore-forming agents that may be used in the polymer composition include, but are not limited to, sugars such as sucrose and dextrose, salts such as sodium chloride and sodium carbonate, polymers such as hydroxylpropylcellulose, carboxymethylcellulose, polyethylene glycol, and polyvinylpyrrolidone. Solid crystals that will provide a defined pore size, such as salt or sugar, are preferred.  
     [1338] In specific preferred embodiments the compositions of the invention are formulated using the BEMA™ BioErodible Mucoadhesive System, MCA™ MucoCutaneous Absorption System, SMP™ Solvent MicroParticle System, or BCP™ BioCompatible Polymer System of Atrix Laboratories, Inc. (Fort Collins, Colo.).  
     [1339] Sustained-release compositions also include liposomally entrapped polypeptides. Liposomes containing the secreted polypeptide are prepared by methods known per se: DE 3,218,121; Epstein et al.,  Proc. Natl. Acad. Sci. USA,  82:3688-3692 (1985); Hwang et al.,  Proc. Natl. Acad. Sci. USA,  77:4030-4034 (1980); EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP 142,641; Japanese Pat. Appl. 83-118008; U.S. Pat. Nos. 4,485,045 and 4,544,545; and EP 102,324. Ordinarily, the liposomes are of the small (about 200-800 Angstroms) unilamellar type in which the lipid content is greater than about 30 mol. percent cholesterol, the selected proportion being adjusted for the optimal secreted polypeptide therapy.  
     [1340] For parenteral administration, in one embodiment, the polypeptide is formulated generally by mixing it at the desired degree of purity, in a unit dosage injectable form (solution, suspension, or emulsion), with a pharmaceutically acceptable carrier, i.e., one that is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation. For example, the formulation preferably does not include oxidizing agents and other compounds that are known to be deleterious to polypeptides.  
     [1341] Generally, the formulations are prepared by contacting the polypeptide uniformly and intimately with liquid carriers or finely divided solid carriers or both. Then, if necessary, the product is shaped into the desired formulation. Preferably the carrier is a parenteral carrier, more preferably a solution that is isotonic with the blood of the recipient. Examples of such carrier vehicles include water, saline, Ringer&#39;s solution, and dextrose solution. Non-aqueous vehicles such as fixed oils and ethyl oleate are also useful herein, as well as liposomes.  
     [1342] The carrier suitably contains minor amounts of additives such as substances that enhance isotonicity and chemical stability. Such materials are non-toxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, succinate, acetic acid, and other organic acids or their salts; antioxidants such as ascorbic acid; low molecular weight (less than about ten residues) polypeptides, e.g., polyarginine or tripeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids, such as glycine, glutamic acid, aspartic acid, or arginine; monosaccharides, disaccharides, and other carbohydrates including cellulose or its derivatives, glucose, manose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; counterions such as sodium; and/or nonionic surfactants such as polysorbates, poloxamers, or PEG.  
     [1343] The polypeptide is typically formulated in such vehicles at a concentration of about 0.1 mg/ml to 100 mg/ml, preferably 1-10 mg/ml, at a pH of about 3 to 8. It will be understood that the use of certain of the foregoing excipients, carriers, or stabilizers will result in the formation of polypeptide salts.  
     [1344] Any polypeptide to be used for therapeutic administration can be sterile. Sterility is readily accomplished by filtration through sterile filtration membranes (e.g., 0.2 micron membranes). Therapeutic polypeptide compositions generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.  
     [1345] Polypeptides ordinarily will be stored in unit or multi-dose containers, for example, sealed ampoules or vials, as an aqueous solution or as a lyophilized formulation for reconstitution. As an example of a lyophilized formulation, 10-ml vials are filled with 5 ml of sterile-filtered 1% (w/v) aqueous polypeptide solution, and the resulting mixture is lyophilized. The infusion solution is prepared by reconstituting the lyophilized polypeptide using bacteriostatic Water-for-Injection.  
     [1346] The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention. Associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration. In addition, the polypeptides of the present invention may be employed in conjunction with other therapeutic compounds.  
     [1347] The Therapeutics of the invention may be administered alone or in combination with adjuvants. Adjuvants that may be administered with the Therapeutics of the invention include, but are not limited to, alum, alum plus deoxycholate (ImmunoAg), MTP-PE (Biocine Corp.), QS21 (Genentech, Inc.), BCG (e.g., THERACYS®), MPL and nonviable prepartions of  Corynebacterium parvum.  In a specific embodiment, Therapeutics of the invention are administered in combination with alum. In another specific embodiment, Therapeutics of the invention are administered in combination with QS-21. Further adjuvants that may be administered with the Therapeutics of the invention include, but are not limited to, Monophosphoryl lipid immunomodulator, AdjuVax 100a, QS-21, QS-18, CRL1005, Aluminum salts, MF-59, and Virosomal adjuvant technology. Vaccines that may be administered with the Therapeutics of the invention include, but are not limited to, vaccines directed toward protection against MMR (measles, mumps, rubella), polio, varicella, tetanus/diptheria, hepatitis A, hepatitis B, haemophilus influenzae B, whooping cough, pneumonia, influenza, Lyme&#39;s Disease, rotavirus, cholera, yellow fever, Japanese encephalitis, poliomyelitis, rabies, typhoid fever, and pertussis. Combinations may be administered either concomitantly, e.g., as an admixture, separately but simultaneously or concurrently; or sequentially. This includes presentations in which the combined agents are administered together as a therapeutic mixture, and also procedures in which the combined agents are administered separately but simultaneously, e.g., as through separate intravenous lines into the same individual. Administration “in combination” further includes the separate administration of one of the compounds or agents given first, followed by the second.  
     [1348] The Therapeutics of the invention may be administered alone or in combination with other therapeutic agents. In preferred embodiments, therapeutic agents that may be administered in combination with the Therapeutics of the invention, include but not limited to antidiabetic agents (e.g., a biguanide antidiabetic agent, a glitazone antidiabetic agent, and a sulfonylurea antidiabetic agent). In additional embodiments, therapeutic agents that may be administered in combination with the Therapeutics of the invention, include chemotherapeutic agents, antibiotics, steroidal and non-steroidal anti-inflammatories, conventional immunotherapeutic agents, and/or therapeutic treatments described below. Combinations may be administered either concomitantly, e.g., as an admixture, separately but simultaneously or concurrently; or sequentially. This includes presentations in which the combined agents are administered together as a therapeutic mixture, and also procedures in which the combined agents are administered separately but simultaneously, e.g., as through separate intravenous lines into the same individual. Administration “in combination” further includes the separate administration of one of the compounds or agents given first, followed by the second.  
     [1349] In one embodiment, the Therapeutics of the invention are administered in combination with an anticoagulant. Anticoagulants that may be administered with the compositions of the invention include, but are not limited to, heparin, low molecular weight heparin, warfarin sodium (e.g., COUMADIN®)), dicumarol, 4-hydroxycoumarin, anisindione (e.g., MIRADON™), acenocoumarol (e.g., nicoumalone, SINTHROME™), indan-1,3-dione, phenprocoumon (e.g., MARCUMAR™), ethyl biscoumacetate (e.g., TROMEXAN™), and aspirin. In a specific embodiment, compositions of the invention are administered in combination with heparin and/or warfarin. In another specific embodiment, compositions of the invention are administered in combination with warfarin. In another specific embodiment, compositions of the invention are administered in combination with warfarin and aspirin. In another specific embodiment, compositions of the invention are administered in combination with heparin. In another specific embodiment, compositions of the invention are administered in combination with heparin and aspirin.  
     [1350] In another embodiment, the Therapeutics of the invention are administered in combination with thrombolytic drugs. Thrombolytic drugs that may be administered with the compositions of the invention include, but are not limited to, plasminogen, lys-plasminogen, alpha2-antiplasmin, streptokinae (e.g., KABIKINASE™), antiresplace (e.g., EMINASE™), tissue plasminogen activator (t-PA, altevase, ACTIVASE™), urokinase (e.g., ABBOKINASE™), sauruplase, (Prourokinase, single chain urokinase), and aminocaproic acid (e.g., AMICAR™). In a specific embodiment, compositions of the invention are administered in combination with tissue plasminogen activator and aspirin.  
     [1351] In another embodiment, the Therapeutics of the invention are administered in combination with antiplatelet drugs. Antiplatelet drugs that may be administered with the compositions of the invention include, but are not limited to, aspirin, dipyridamole (e.g., PERSANTINE™), and ticlopidine (e.g., TICLID™).  
     [1352] In specific embodiments, the use of anti-coagulants, thrombolytic and/or antiplatelet drugs in combination with Therapeutics of the invention is contemplated for the prevention, diagnosis, and/or treatment of thrombosis, arterial thrombosis, venous thrombosis, thromboembolism, pulmonary embolism, atherosclerosis, myocardial infarction, transient ischemic attack, unstable angina. In specific embodiments, the use of anticoagulants, thrombolytic drugs and/or antiplatelet drugs in combination with Therapeutics of the invention is contemplated for the prevention of occulsion of saphenous grafts, for reducing the risk of periprocedural thrombosis as might accompany angioplasty procedures, for reducing the risk of stroke in patients with atrial fibrillation including nonrheumatic atrial fibrillation, for reducing the risk of embolism associated with mechanical heart valves and or mitral valves disease. Other uses for the therapeutics of the invention, alone or in combination with antiplatelet, anticoagulant, and/or thrombolytic drugs, include, but are not limited to, the prevention of occlusions in extracorporeal devices (e.g., intravascular canulas, vascular access shunts in hemodialysis patients, hemodialysis machines, and cardiopulmonary bypass machines).  
     [1353] In certain embodiments, Therapeutics of the invention are administered in combination with antiretroviral agents, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and/or protease inhibitors (PIs). NRTIs that may be administered in combination with the Therapeutics of the invention, include, but are not limited to, RETROVIR™ (zidovudine/AZT), VIDEX™ (didanosine/ddl), HIVID™ (zalcitabine/ddC), ZERIT™ (stavudine/d4T), EPIVIR™ (lamivudine/3TC), and COMBIVIR™ (zidovudine/lamivudine). NNRTIs that may be administered in combination with the Therapeutics of the invention, include, but are not limited to, VIRAMUNE™ (nevirapine), RESCRIPTOR™ (delavirdine), and SUSTIVA™ (efavirenz). Protease inhibitors that may be administered in combination with the Therapeutics of the invention, include, but are not limited to, CRIXIVAN™ (indinavir), NORVIR™ (ritonavir), INVIRASE™ (saquinavir), and VIRACEPT™ (nelfinavir). In a specific embodiment, antiretroviral agents, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and/or protease inhibitors may be used in any combination with Therapeutics of the invention to treat AIDS and/or to prevent or treat HIV infection.  
     [1354] Additional NRTIs include LODENOSINE™ (F-ddA; an acid-stable adenosine NRTI; Triangle/Abbott; COVIRACIL™ (emtricitabine/FTC; structurally related to lamivudine (3TC) but with 3- to 10-fold greater activity in vitro; Triangle/Abbott); dOTC (BCH-10652, also structurally related to lamivudine but retains activity against a substantial proportion of lamivudine-resistant isolates; Biochem Pharma); Adefovir (refused approval for anti-HIV therapy by FDA; Gilead Sciences); PREVEON® (Adefovir Dipivoxil, the active prodrug of adefovir; its active form is PMEA-pp); TENOFOVIR™ (bis-POC PMPA, a PMPA prodrug; Gilead); DAPD/DXG (active metabolite of DAPD; Triangle/Abbott); D-D4FC (related to 3TC, with activity against AZT/3TC-resistant virus); GW420867X (Glaxo Wellcome); ZIAGEN™ (abacavir/159U89; Glaxo Wellcome Inc.); CS-87 (3′azido-2′,3′-dideoxyuridine; WO 99/66936); and S-acyl-2-thioethyl (SATE)-bearing prodrug forms of β-L-FD4C and β-L-FddC (WO 98/17281).  
     [1355] Additional NNRTIs include COACTINON™ (Emivirine/MKC-442, potent NNRTI of the HEPT class; Triangle/Abbott); CAPRAVIRINE™ (AG-1549/S-1153, a next generation NNRTI with activity against viruses containing the K103N mutation; Agouron); PNU-142721 (has 20- to 50-fold greater activity than its predecessor delavirdine and is active against K103N mutants; Pharmacia &amp; Upjohn); DPC-961 and DPC-963 (second-generation derivatives of efavirenz, designed to be active against viruses with the K103N mutation; DuPont); GW-420867X (has 25-fold greater activity than HBY097 and is active against K103N mutants; Glaxo Wellcome); CALANOLIDE A (naturally occurring agent from the latex tree; active against viruses containing either or both the Y181C and K103N mutations); and Propolis (WO 99/49830).  
     [1356] Additional protease inhibitors include LOPINAVIR™ (ABT378/r; Abbott Laboratories); BMS-232632 (an azapeptide; Bristol-Myres Squibb); TIPRANAVIR™ (PNU-140690, a non-peptic dihydropyrone; Pharmacia &amp; Upjohn); PD-178390 (a nonpeptidic dihydropyrone; Parke-Davis); BMS 232632 (an azapeptide; Bristol-Myers Squibb); L-756,423 (an indinavir analog; Merck); DMP-450 (a cyclic urea compound; Avid &amp; DuPont); AG-1776 (a peptidomimetic with in vitro activity against protease inhibitor-resistant viruses; Agouron); VX-175/GW-433908 (phosphate prodrug of amprenavir; Vertex &amp; Glaxo Welcome); CGP61755 (Ciba); and AGENERASE™ (amprenavir; Glaxo Wellcome Inc.).  
     [1357] Additional antiretroviral agents include fusion inhibitors/gp41 binders. Fusion inhibitors/gp41 binders include T-20 (a peptide from residues 643-678 of the HIV gp41 transmembrane protein ectodomain which binds to gp41 in its resting state and prevents transformation to the fusogenic state; Trimeris) and T-1249 (a second-generation fusion inhibitor; Trimeris).  
     [1358] Additional antiretroviral agents include fusion inhibitors/chemokine receptor antagonists. Fusion inhibitors/chemokine receptor antagonists include CXCR4 antagonists such as AMD 3100 (a bicyclam), SDF-1 and its analogs, and ALX40-4C (a cationic peptide), T22 (an 18 amino acid peptide; Trimeris) and the T22 analogs T134 and T140; CCR5 antagonists such as RANTES (9-68), AOP-RANTES, NNY-RANTES, and TAK-779; and CCR5/CXCR4 antagonists such as NSC 651016 (a distamycin analog). Also included are CCR2B, CCR3, and CCR6 antagonists. Chemokine recpetor agonists such as RANTES, SDF-1, MIP-1α, MIP-1β, etc., may also inhibit fusion.  
     [1359] Additional antiretroviral agents include integrase inhibitors. Integrase inhibitors include dicaffeoylquinic (DFQA) acids; L-chicoric acid (a dicaffeoyltartaric (DCTA) acid); quinalizarin (QLC) and related anthraquinones; ZINTEVIR™ (AR 177, an oligonucleotide that probably acts at cell surface rather than being a true integrase inhibitor; Arondex); and naphthols such as those disclosed in WO 98/50347.  
     [1360] Additional antiretroviral agents include hydroxyurea-like compunds such as BCX-34 (a purine nucleoside phosphorylase inhibitor; Biocryst); ribonucleotide reductase inhibitors such as DIDOX™ (Molecules for Health); inosine monophosphate dehydrogenase (IMPDH) inhibitors sucha as VX-497 (Vertex); and mycopholic acids such as CellCept (mycophenolate mofetil; Roche).  
     [1361] Additional antiretroviral agents include inhibitors of viral integrase, inhibitors of viral genome nuclear translocation such as arylene bis(methylketone) compounds; inhibitors of HIV entry such as AOP-RANTES, NNY-RANTES, RANTES-IgG fusion protein, soluble complexes of RANTES and glycosaminoglycans (GAG), and AMD-3100; nucleocapsid zinc finger inhibitors such as dithiane compounds; targets of HIV Tat and Rev; and pharmacoenhancers such as ABT-378.  
     [1362] Other antiretroviral therapies and adjunct therapies include cytokines and lymphokines such as MIP-1α, MIP-1β, SDF-1α, IL-2, PROLEUKIN™ (aldesleukin/L2-7001; Chiron), IL-4, IL-10, IL-12, and IL-13; interferons such as IFN-α2a; antagonists of TNFs, NFκB, GM-CSF, M-CSF, and IL-10; agents that modulate immune activation such as cyclosporin and prednisone; vaccines such as Remune™ (HIV Immunogen), APL 400-003 (Apollon), recombinant gp120 and fragments, bivalent (B/E) recombinant envelope glycoprotein, rgp120CM235, MN rgp120, SF-2 rgp120, gp120/soluble CD4 complex, Delta JR-FL protein, branched synthetic peptide derived from discontinuous gp120 C3/C4 domain, fusion-competent immunogens, and Gag, Pol, Nef, and Tat vaccines; gene-based therapies such as genetic suppressor elements (GSEs; WO 98/54366), and intrakines (genetically modified CC chemokines targetted to the ER to block surface expression of newly synthesized CCR5 (Yang et al.,  PNAS  94:11567-72 (1997); Chen et al.,  Nat. Med.  3:1110-16 (1997)); antibodies such as the anti-CXCR4 antibody 12G5, the anti-CCR5 antibodies 2D7, 5C7, PA8, PA9, PA10, PA11, PA12, and PA14, the anti-CD4 antibodies Q4120 and RPA-T4, the anti-CCR3 antibody 7B11, the anti-gp120 antibodies 17b, 48d, 447-52D, 257-D, 268-D and 50.1, anti-Tat antibodies, anti-TNF-α antibodies, and monoclonal antibody 33A; aryl hydrocarbon (AH) receptor agonists and antagonists such as TCDD, 3,3′,4,4′,5-pentachlorobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, and α-naphthoflavone (WO 98/30213); and antioxidants such as γ-L-glutamyl-L-cysteine ethyl ester (γ-GCE; WO 99/56764).  
     [1363] In a further embodiment, the Therapeutics of the invention are administered in combination with an antiviral agent. Antiviral agents that may be administered with the Therapeutics of the invention include, but are not limited to, acyclovir, ribavirin, amantadine, and remantidine.  
     [1364] In other embodiments, Therapeutics of the invention may be administered in combination with anti-opportunistic infection agents. Anti-opportunistic agents that may be administered in combination with the Therapeutics of the invention, include, but are not limited to, TRIMETHOPRIM-SULFAMETHOXAZOLE™, DAPSONE™, PENTAMIDINE™, ATOVAQUONE™, ISONIAZID™, RIFAMPIN™, PYRAZINAMIDE™, ETHAMBUTOL™, RIFABUTIN™, CLARITHROMYCIN™, AZITHROMYCIN™, GANCICLOVIR™, FOSCARNET™, CIDOFOVIR™, FLUCONAZOLE™, ITRACONAZOLE™, KETOCONAZOLE™, ACYCLOVIR™, FAMCICOLVIR™, PYRIMETHAMINE™, LEUCOVORIN™, NEUPOGEN™ (filgrastim/G-CSF), and LEUKINE™ (sargramostim/GM-CSF). In a specific embodiment, Therapeutics of the invention are used in any combination with TRIMETHOPRIM-SULFAMETHOXAZOLE™, DAPSONE™, PENTAMIDINE™, and/or ATOVAQUONE™ to prophylactically treat or prevent an opportunistic  Pneumocystis carinii  pneumonia infection. In another specific embodiment, Therapeutics of the invention are used in any combination with ISONIAZID™, RIFAMPIN™, PYRAZINAMIDE™, and/or ETHAMBUTOL™ to prophylactically treat or prevent an opportunistic  Mycobacterium avium  complex infection. In another specific embodiment, Therapeutics of the invention are used in any combination with RIFABUTIN™, CLARITHROMYCIN™, and/or AZITHROMYCIN™ to prophylactically treat or prevent an opportunistic  Mycobacterium tuberculosis  infection. In another specific embodiment, Therapeutics of the invention are used in any combination with GANCICLOVIR™, FOSCARNET™, and/or CIDOFOVIR™ to prophylactically treat or prevent an opportunistic cytomegalovirus infection. In another specific embodiment, Therapeutics of the invention are used in any combination with FLUCONAZOLE™, ITRACONAZOLE™, and/or KETOCONAZOLE™ to prophylactically treat or prevent an opportunistic fungal infection. In another specific embodiment, Therapeutics of the invention are used in any combination with ACYCLOVIR™ and/or FAMCICOLVIR™ to prophylactically treat or prevent an opportunistic herpes simplex virus type I and/or type II infection. In another specific embodiment, Therapeutics of the invention are used in any combination with PYRIMETHAMINE™ and/or LEUCOVORIN™ to prophylactically treat or prevent an opportunistic  Toxoplasma gondii  infection. In another specific embodiment, Therapeutics of the invention are used in any combination with LEUCOVORIN™ and/or NEUPOGEN™ to prophylactically treat or prevent an opportunistic bacterial infection.  
     [1365] In a further embodiment, the Therapeutics of the invention are administered in combination with an antibiotic agent. Antibiotic agents that may be administered with the Therapeutics of the invention include, but are not limited to, amoxicillin, beta-lactamases, aminoglycosides, beta-lactam (glycopeptide), beta-lactamases, Clindamycin, chloramphenicol, cephalosporins, ciprofloxacin, erythromycin, fluoroquinolones, macrolides, metronidazole, penicillins, quinolones, rapamycin, rifampin, streptomycin, sulfonamide, tetracyclines, trimethoprim, trimethoprim-sulfamethoxazole, and vancomycin.  
     [1366] In other embodiments, the Therapeutics of the invention are administered in combination with immunestimulants. Immunostimulants that may be administered in combination with the Therapeutics of the invention include, but are not limited to, levamisole (e.g., ERGAMISOL™), isoprinosine (e.g. INOSIPLEX™), interferons (e.g. interferon alpha), and interleukins (e.g., IL-2).  
     [1367] In other embodiments, Therapeutics of the invention are administered in combination with immunosuppressive agents. Immunosuppressive agents that may be administered in combination with the Therapeutics of the invention include, but are not limited to, steroids, cyclosporine, cyclosporine analogs, cyclophosphamide methylprednisone, prednisone, azathioprine, FK-506, 15-deoxyspergualin, and other immunosuppressive agents that act by suppressing the function of responding T cells. Other immunosuppressive agents that may be administered in combination with the Therapeutics of the invention include, but are not limited to, prednisolone, methotrexate, thalidomide, methoxsalen, rapamycin, leflunomide, mizoribine (BREDININ™), brequinar, deoxyspergualin, and azaspirane (SKF 105685), ORTHOCLONE OKT® 3 (muromonab-CD3), SANDIMMUNE™, NEORAL™, SANGDYA™ (cyclosporine), PROGRAF® (FK506, tacrolimus), CELLCEPT® (mycophenolate motefil, of which the active metabolite is mycophenolic acid), IMURAN™ (azathioprine), glucocorticosteroids, adrenocortical steroids such as DELTASONE™ (prednisone) and HYDELTRASOL™ (prednisolone), FOLEX™ and MEXATE™ (methotrxate), OXSORALEN-ULTRA™ (methoxsalen) and RAPAMUNE™ (sirolimus). In a specific embodiment, immunosuppressants may be used to prevent rejection of organ or bone marrow transplantation.  
     [1368] In an additional embodiment, Therapeutics of the invention are administered alone or in combination with one or more intravenous immune globulin preparations. Intravenous immune globulin preparations that may be administered with the Therapeutics of the invention include, but not limited to, GAMMAR™, IVEEGAM™, SANDOGLOBULIN™, GAMMAGARD S/D™, ATGAM™ (antithymocyte glubulin), and GAMIMUNE™. In a specific embodiment, Therapeutics of the invention are administered in combination with intravenous immune globulin preparations in transplantation therapy (e.g., bone marrow transplant).  
     [1369] In certain embodiments, the Therapeutics of the invention are administered alone or in combination with an anti-inflammatory agent. Anti-inflammatory agents that may be administered with the Therapeutics of the invention include, but are not limited to, corticosteroids (e.g. betamethasone, budesonide, cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, prednisone, and triamcinolone), nonsteroidal anti-inflammatory drugs (e.g., diclofenac, diflunisal, etodolac, fenoprofen, floctafenine, flurbiprofen, ibuprofen, indomethacin, ketoprofen, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, phenylbutazone, piroxicam, sulindac, tenoxicam, tiaprofenic acid, and tolmetin.), as well as antihistamines, aminoarylcarboxylic acid derivatives, arylacetic acid derivatives, arylbutyric acid derivatives, arylcarboxylic acids, arylpropionic acid derivatives, pyrazoles, pyrazolones, salicylic acid derivatives, thiazinecarboxamides, e-acetamidocaproic acid, S-adenosylmethionine, 3-amino-4-hydroxybutyric acid, amixetrine, bendazac, benzydamine, bucolome, difenpiramide, ditazol, emorfazone, guaiazulene, nabumetone, nimesulide, orgotein, oxaceprol, paranyline, perisoxal, pifoxime, proquazone, proxazole, and tenidap.  
     [1370] In an additional embodiment, the compositions of the invention are administered alone or in combination with an anti-angiogenic agent. Anti-angiogenic agents that may be administered with the compositions of the invention include, but are not limited to, Angiostatin (Entremed, Rockville, Md.), Troponin-1 (Boston Life Sciences, Boston, Mass.), anti-Invasive Factor, retinoic acid and derivatives thereof, paclitaxel (Taxol), Suramin, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2, VEGI, Plasminogen Activator Inhibitor-1, Plasminogen Activator Inhibitor-2, and various forms of the lighter “d group” transition metals.  
     [1371] Lighter “d group” transition metals include, for example, vanadium, molybdenum, tungsten, titanium, niobium, and tantalum species. Such transition metal species may form transition metal complexes. Suitable complexes of the above-mentioned transition metal species include oxo transition metal complexes.  
     [1372] Representative examples of vanadium complexes include oxo vanadium complexes such as vanadate and vanadyl complexes. Suitable vanadate complexes include metavanadate and orthovanadate complexes such as, for example, ammonium metavanadate, sodium metavanadate, and sodium orthovanadate. Suitable vanadyl complexes include, for example, vanadyl acetylacetonate and vanadyl sulfate including vanadyl sulfate hydrates such as vanadyl sulfate mono- and trihydrates.  
     [1373] Representative examples of tungsten and molybdenum complexes also include oxo complexes. Suitable oxo tungsten complexes include tungstate and tungsten oxide complexes. Suitable tungstate complexes include ammonium tungstate, calcium tungstate, sodium tungstate dihydrate, and tungstic acid. Suitable tungsten oxides include tungsten (IV) oxide and tungsten (VI) oxide. Suitable oxo molybdenum complexes include molybdate, molybdenum oxide, and molybdenyl complexes. Suitable molybdate complexes include ammonium molybdate and its hydrates, sodium molybdate and its hydrates, and potassium molybdate and its hydrates. Suitable molybdenum oxides include molybdenum (VI) oxide, molybdenum (VI) oxide, and molybdic acid. Suitable molybdenyl complexes include, for example, molybdenyl acetylacetonate. Other suitable tungsten and molybdenum complexes include hydroxo derivatives derived from, for example, glycerol, tartaric acid, and sugars.  
     [1374] A wide variety of other anti-angiogenic factors may also be utilized within the context of the present invention. Representative examples include, but are not limited to, platelet factor 4; protamine sulphate; sulphated chitin derivatives (prepared from queen crab shells), (Murata et al., Cancer Res. 51:22-26, (1991)); Sulphated Polysaccharide Peptidoglycan Complex (SP-PG) (the function of this compound may be enhanced by the presence of steroids such as estrogen, and tamoxifen citrate); Staurosporine; modulators of matrix metabolism, including for example, proline analogs, cishydroxyproline, d,L-3,4-dehydroproline, Thiaproline, alpha,alpha-dipyridyl, aminopropionitrile fumarate; 4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone; Methotrexate; Mitoxantrone; Heparin; Interferons; 2 Macroglobulin-serum; ChIMP-3 (Pavloff et al., J. Bio. Chem. 267:17321-17326, (1992)); Chymostatin (Tomkinson et al., Biochem J. 286:475-480, (1992)); Cyclodextrin Tetradecasulfate; Eponemycin; Camptothecin; Fumagillin (Ingber et al., Nature 348:555-557, (1990)); Gold Sodium Thiomalate (“GST”; Matsubara and Ziff, J. Clin. Invest. 79:1440-1446, (1987)); anticollagenase-serum; alpha2-antiplasmin (Holmes et al., J. Biol. Chem. 262(4):1659-1664, (1987)); Bisantrene (National Cancer Institute); Lobenzarit disodium (N-(2)-carboxyphenyl-4-chloroanthronilic acid disodium or “CCA”; (Takeuchi et al., Agents Actions 36:312-316, (1992)); and metalloproteinase inhibitors such as BB94.  
     [1375] Additional anti-angiogenic factors that may also be utilized within the context of the present invention include Thalidomide, (Celgene, Warren, N.J.); Angiostatic steroid; AGM-1470 (H. Brem and J. Folkman  J Pediatr. Surg.  28:445-51 (1993)); an integrin alpha v beta 3 antagonist (C. Storgard et al.,  J Clin. Invest.  103:47-54 (1999)); carboxynaminolmidazole; Carboxyamidotriazole (CAI) (National Cancer Institute, Bethesda, Md.); Conbretastatin A-4 (CA4P) (OXiGENE, Boston, Mass.); Squalamine (Magainin Pharmaceuticals, Plymouth Meeting, Pa.); TNP-470, (Tap Pharmaceuticals, Deerfield, Ill.); ZD-0101 AstraZeneca (London, UK); APRA (CT2584); Benefin, Byrostatin-1 (SC339555); CGP-41251 (PKC 412); CM101; Dexrazoxane (ICRF187); DMXAA; Endostatin; Flavopridiol; Genestein; GTE; ImmTher; Iressa (ZD1839); Octreotide (Somatostatin); Panretin; Penacillamine; Photopoint; PI-88; Prinomastat (AG-3340) Purlytin; Suradista (FCE26644); Tamoxifen (Nolvadex); Tazarotene; Tetrathiomolybdate; Xeloda (Capecitabine); and 5-Fluorouracil.  
     [1376] Anti-angiogenic agents that may be administed in combination with the compounds of the invention may work through a variety of mechanisms including, but not limited to, inhibiting proteolysis of the extracellular matrix, blocking the function of endothelial cell-extracellular matrix adhesion molecules, by antagonizing the function of angiogenesis inducers such as growth factors, and inhibiting integrin receptors expressed on proliferating endothelial cells. Examples of anti-angiogenic inhibitors that interfere with extracellular matrix proteolysis and which may be administered in combination with the compositons of the invention include, but are not lmited to, AG-3340 (Agouron, La Jolla, Calif.), BAY-12-9566 (Bayer, West Haven, Conn.), BMS-275291 (Bristol Myers Squibb, Princeton, N.J.), CGS-27032A (Novartis, East Hanover, N.J.), Marimastat (British Biotech, Oxford, UK), and Metastat (Aetema, St-Foy, Quebec). Examples of anti-angiogenic inhibitors that act by blocking the function of endothelial cell-extracellular matrix adhesion molecules and which may be administered in combination with the compositons of the invention include, but are not lmited to, EMD-121974 (Merck KcgaA Darmstadt, Germany) and Vitaxin (Ixsys, La Jolla, Calif./Medimmune, Gaithersburg, Md.). Examples of anti-angiogenic agents that act by directly antagonizing or inhibiting angiogenesis inducers and which may be administered in combination with the compositons of the invention include, but are not lmited to, Angiozyme (Ribozyme, Boulder, Colo.), Anti-VEGF antibody (Genentech, S. San Francisco, Calif.), PTK-787/ZK-225846 (Novartis, Basel, Switzerland), SU-101 (Sugen, S. San Francisco, Calif.), SU-5416 (Sugen/Pharmacia Upjohn, Bridgewater, N.J.), and SU-6668 (Sugen). Other anti-angiogenic agents act to indirectly inhibit angiogenesis. Examples of indirect inhibitors of angiogenesis which may be administered in combination with the compositons of the invention include, but are not limited to, IM-862 (Cytran, Kirkland, Wash.), Interferon-alpha, IL-12 (Roche, Nutley, N.J.), and Pentosan polysulfate (Georgetown University, Washington, D.C.).  
     [1377] In particular embodiments, the use of compositions of the invention in combination with anti-angiogenic agents is contemplated for the treatment, prevention, and/or amelioration of an autoimmune disease, such as for example, an autoimmune disease described herein.  
     [1378] In a particular embodiment, the use of compositions of the invention in combination with anti-angiogenic agents is contemplated for the treatment, prevention, and/or amelioration of arthritis. In a more particular embodiment, the use of compositions of the invention in combination with anti-angiogenic agents is contemplated for the treatment, prevention, and/or amelioration of rheumatoid arthritis.  
     [1379] In another embodiment, the polynucleotides encoding a polypeptide of the present invention are administered in combination with an angiogenic protein, or polynucleotides encoding an angiogenic protein. Examples of angiogenic proteins that may be administered with the compositions of the invention include, but are not limited to, acidic and basic fibroblast growth factors, VEGF-1, VEGF-2, VEGF-3, epidermal growth factor alpha and beta, platelet-derived endothelial cell growth factor, platelet-derived growth factor, tumor necrosis factor alpha, hepatocyte growth factor, insulin-like growth factor, colony stimulating factor, macrophage colony stimulating factor, granulocyte/macrophage colony stimulating factor, and nitric oxide synthase.  
     [1380] In additional embodiments, compositions of the invention are administered in combination with a chemotherapeutic agent. Chemotherapeutic agents that may be administered with the Therapeutics of the invention include, but are not limited to alkylating agents such as nitrogen mustards (for example, Mechlorethamine, cyclophosphamide, Cyclophosphamide Ifosfamide, Melphalan (L-sarcolysin), and Chlorambucil), ethylenimines and methylmelamines (for example, Hexamethylmelamine and Thiotepa), alkyl sulfonates (for example, Busulfan), nitrosoureas (for example, Carmustine (BCNU), Lomustine (CCNU), Semustine (methyl-CCNU), and Streptozocin (streptozotocin)), triazenes (for example, Dacarbazine (DTIC; dimethyltriazenoimidazolecarboxamide)), folic acid analogs (for example, Methotrexate (amethopterin)), pyrimidine analogs (for example, Fluorouacil (5-fluorouracil; 5-FU), Floxuridine (fluorodeoxyuridine; FudR), and Cytarabine (cytosine arabinoside)), purine analogs and related inhibitors (for example, Mercaptopurine (6-mercaptopurine; 6-MP), Thioguanine (6-thioguanine; TG), and Pentostatin (2′-deoxycoformycin)), vinca alkaloids (for example, Vinblastine (VLB, vinblastine sulfate)) and Vincristine (vincristine sulfate)), epipodophyllotoxins (for example, Etoposide and Teniposide), antibiotics (for example, Dactinomycin (actinomycin D), Daunorubicin (daunomycin; rubidomycin), Doxorubicin, Bleomycin, Plicamycin (mithramycin), and Mitomycin (mitomycin C), enzymes (for example, L-Asparaginase), biological response modifiers (for example, Interferon-alpha and interferon-alpha-2b), platinum coordination compounds (for example, Cisplatin (cis-DDP) and Carboplatin), anthracenedione (Mitoxantrone), substituted ureas (for example, Hydroxyurea), methylhydrazine derivatives (for example, Procarbazine (N-methylhydrazine; MIH), adrenocorticosteroids (for example, Prednisone), progestins (for example, Hydroxyprogesterone caproate, Medroxyprogesterone, Medroxyprogesterone acetate, and Megestrol acetate), estrogens (for example, Diethylstilbestrol (DES), Diethylstilbestrol diphosphate, Estradiol, and Ethinyl estradiol), antiestrogens (for example, Tamoxifen), androgens (Testosterone proprionate, and Fluoxymesterone), antiandrogens (for example, Flutamide), gonadotropin-releasing horomone analogs (for example, Leuprolide), other hormones and hormone analogs (for example, methyltestosterone, estramustine, estramustine phosphate sodium, chlorotrianisene, and testolactone), and others (for example, dicarbazine, glutamic acid, and mitotane).  
     [1381] In one embodiment, the compositions of the invention are administered in combination with one or more of the following drugs: infliximab (also known as Remicade™ Centocor, Inc.), Trocade (Roche, RO-32-3555), Leflunomide (also known as Arava™ from Hoechst Marion Roussel), Kineret™ (an IL-1 Receptor antagonist also known as Anakinra from Amgen, Inc.)  
     [1382] In a specific embodiment, compositions of the invention are administered in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or combination of one or more of the components of CHOP. In one embodiment, the compositions of the invention are administered in combination with anti-CD20 antibodies, human monoclonal anti-CD20 antibodies. In another embodiment, the compositions of the invention are administered in combination with anti-CD20 antibodies and CHOP, or anti-CD20 antibodies and any combination of one or more of the components of CHOP, particularly cyclophosphamide and/or prednisone. In a specific embodiment, compositions of the invention are administered in combination with Rituximab. In a further embodiment, compositions of the invention are administered with Rituximab and CHOP, or Rituximab and any combination of one or more of the components of CHOP, particularly cyclophosphamide and/or prednisone. In a specific embodiment, compositions of the invention are administered in combination with tositumomab. In a further embodiment, compositions of the invention are administered with tositumomab and CHOP, or tositumomab and any combination of one or more of the components of CHOP, particularly cyclophosphamide and/or prednisone. The anti-CD20 antibodies may optionally be associated with radioisotopes, toxins or cytotoxic prodrugs.  
     [1383] In another specific embodiment, the compositions of the invention are administered in combination Zevalin™. In a further embodiment, compositions of the invention are administered with Zevalin™ and CHOP, or Zevalin™ and any combination of one or more of the components of CHOP, particularly cyclophosphamide and/or prednisone. Zevalin™ may be associated with one or more radisotopes. Particularly preferred isotopes are  90 Y and  111 In.  
     [1384] In an additional embodiment, the Therapeutics of the invention are administered in combination with cytokines. Cytokines that may be administered with the Therapeutics of the invention include, but are not limited to, IL2, IL3, IL4, IL5, IL6, IL7, IL10, IL12, IL13, IL15, anti-CD40, CD40L, IFN-gamma and TNF-alpha. In another embodiment, Therapeutics of the invention may be administered with any interleukin, including, but not limited to, IL-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, IL-20, and IL-21.  
     [1385] In one embodiment, the Therapeutics of the invention are administered in combination with members of the TNF family. TNF, TNF-related or TNF-like molecules that may be administered with the Therapeutics of the invention include, but are not limited to, soluble forms of TNF-alpha, lymphotoxin-alpha (LT-alpha, also known as TNF-beta), LT-beta (found in complex heterotrimer LT-alpha2-beta), OPGL, FasL, CD27L, CD30L, CD40L, 4-1BBL, DcR3, OX40L, TNF-gamma (International Publication No. WO 96/14328), AIM-I (International Publication No. WO 97/33899), endokine-alpha (International Publication No. WO 98/07880), OPG, and neutrokine-alpha (International Publication No. WO 98/18921, OX40, and nerve growth factor (NGF), and soluble forms of Fas, CD30, CD27, CD40 and 4-IBB, TR2 (International Publication No. WO 96/34095), DR3 (International Publication No. WO 97/33904), DR4 (International Publication No. WO 98/32856), TR5 (International Publication No. WO 98/30693), TRANK, TR9 (International Publication No. WO 98/56892),TR10 (International Publication No. WO 98/54202), 312C2 (International Publication No. WO 98/06842), and TR12, and soluble forms CD154, CD70, and CD153.  
     [1386] In an additional embodiment, the Therapeutics of the invention are administered in combination with angiogenic proteins. Angiogenic proteins that may be administered with the Therapeutics of the invention include, but are not limited to, Glioma Derived Growth Factor (GDGF), as disclosed in European Patent Number EP-399816; Platelet Derived Growth Factor-A (PDGF-A), as disclosed in European Patent Number EP-682110; Platelet Derived Growth Factor-B (PDGF-B), as disclosed in European Patent Number EP-282317; Placental Growth Factor (PIGF), as disclosed in International Publication Number WO 92/06194; Placental Growth Factor-2 (PlGF-2), as disclosed in Hauser et al., Growth Factors, 4:259-268 (1993); Vascular Endothelial Growth Factor (VEGF), as disclosed in International Publication Number WO 90/13649; Vascular Endothelial Growth Factor-A (VEGF-A), as disclosed in European Patent Number EP-506477; Vascular Endothelial Growth Factor-2 (VEGF-2), as disclosed in International Publication Number WO 96/39515; Vascular Endothelial Growth Factor B (VEGF-3); Vascular Endothelial Growth Factor B-186 (VEGF-B186), as disclosed in International Publication Number WO 96/26736; Vascular Endothelial Growth Factor-D (VEGF-D), as disclosed in International Publication Number WO 98/02543; Vascular Endothelial Growth Factor-D (VEGF-D), as disclosed in International Publication Number WO 98/07832; and Vascular Endothelial Growth Factor-E (VEGF-E), as disclosed in German Patent Number DE19639601. The above mentioned references are herein incorporated by reference in their entireties.  
     [1387] In an additional embodiment, the Therapeutics of the invention are administered in combination with Fibroblast Growth Factors. Fibroblast Growth Factors that may be administered with the Therapeutics of the invention include, but are not limited to, FGF-1, FGF-2, FGF-3, FGF-4, FGF-5, FGF-6, FGF-7, FGF-8, FGF-9, FGF-10, FGF-11, FGF-12, FGF-13, FGF-14, and FGF-15.  
     [1388] In an additional embodiment, the Therapeutics of the invention are administered in combination with hematopoietic growth factors. Hematopoietic growth factors that may be administered with the Therapeutics of the invention include, but are not limited to, granulocyte macrophage colony stimulating factor (GM-CSF) (sargramostim, LEUKINE™, PROKINE™), granulocyte colony stimulating factor (G-CSF) (filgrastim, NEUPOGEN™), macrophage colony stimulating factor (M-CSF, CSF-1) erythropoietin (epoetin alfa, EPOGEN™, PROCRIT™), stem cell factor (SCF, c-kit ligand, steel factor), megakaryocyte colony stimulating factor, PIXY321 (a GMCSF/IL-3 fusion protein), interleukins, especially any one or more of IL-1 through IL-12, interferon-gamma, or thrombopoietin.  
     [1389] In certain embodiments, Therapeutics of the present invention are administered in combination with adrenergic blockers, such as, for example, acebutolol, atenolol, betaxolol, bisoprolol, carteolol, labetalol, metoprolol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, and timolol.  
     [1390] In another embodiment, the Therapeutics of the invention are administered in combination with an antiarrhythmic drug (e.g., adenosine, amidoarone, bretylium, digitalis, digoxin, digitoxin, diliazem, disopyramide, esmolol, flecainide, lidocaine, mexiletine, moricizine, phenytoin, procainamide, N-acetyl procainamide, propafenone, propranolol, quinidine, sotalol, tocainide, and verapamil).  
     [1391] In another embodiment, the Therapeutics of the invention are administered in combination with diuretic agents, such as carbonic anhydrase-inhibiting agents (e.g., acetazolamide, dichlorphenamide, and methazolamide), osmotic diuretics (e.g., glycerin, isosorbide, mannitol, and urea), diuretics that inhibit Na + -K + -2Cl −  symport (e.g., furosemide, bumetanide, azosemide, piretanide, tripamide, ethacrynic acid, muzolimine, and torsemide), thiazide and thiazide-like diuretics (e.g., bendroflumethiazide, benzthiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, trichormethiazide, chlorthalidone, indapamide, metolazone, and quinethazone), potassium sparing diuretics (e.g., amiloride and triamterene), and mineralcorticoid receptor antagonists (e.g., spironolactone, canrenone, and potassium canrenoate).  
     [1392] In one embodiment, the Therapeutics of the invention are administered in combination with treatments for endocrine and/or hormone imbalance disorders. Treatments for endocrine and/or hormone imbalance disorders include, but are not limited to,  127 I, radioactive isotopes of iodine such as  131 I and  123 I; recombinant growth hormone, such as HUMATROPE™ (recombinant somatropin); growth hormone analogs such as PROTROPIN™ (somatrem); dopamine agonists such as PARLODEL™ (bromocriptine); somatostatin analogs such as SANDOSTATIN™ (octreotide); gonadotropin preparations such as PREGNYL™, A.P.L.™ and PROFASI™ (chorionic gonadotropin (CG)), PERGONAL™ (menotropins), and METRODIN™ (urofollitropin (uFSH)); synthetic human gonadotropin releasing hormone preparations such as FACTREL™ and LUTREPULSE™ (gonadorelin hydrochloride); synthetic gonadotropin agonists such as LUPRON™ (leuprolide acetate), SUPPRELIN™ (histrelin acetate), SYNAREL™ (nafarelin acetate), and ZOLADEX™ (goserelin acetate); synthetic preparations of thyrotropin-releasing hormone such as RELEFACT TRH™ and THYPINONE™ (protirelin); recombinant human TSH such as THYROGEN™; synthetic preparations of the sodium salts of the natural isomers of thyroid hormones such as L-T 4 ™, SYNTHROID™ and LEVOTHROID™ (levothyroxine sodium), L-T 3 ™, CYTOMEL™ and TRIOSTAT™ (liothyroine sodium), and THYROLAR™ (liotrix); antithyroid compounds such as 6-n-propylthiouracil (propylthiouracil), 1-methyl-2-mercaptoimidazole and TAPAZOLE™ (methimazole), NEO-MERCAZOLE™ (carbimazole); beta-adrenergic receptor antagonists such as propranolol and esmolol; Ca 2+  channel blockers; dexamethasone and iodinated radiological contrast agents such as TELEPAQUE™ (iopanoic acid) and ORAGRAFIN™ (sodium ipodate).  
     [1393] Additional treatments for endocrine and/or hormone imbalance disorders include, but are not limited to, estrogens or congugated estrogens such as ESTRACE™ (estradiol), ESTINYL™ (ethinyl estradiol), PREMARIN™, ESTRATAB™, ORTHO-EST™, OGEN™ and estropipate (estrone), ESTROVIS™ (quinestrol), ESTRADERM™ (estradiol), DELESTROGEN™ and VALERGEN™ (estradiol valerate), DEPO-ESTRADIOL CYPIONATE™ and ESTROJECT LA™ (estradiol cypionate); antiestrogens such as NOLVADEX™ (tamoxifen), SEROPHENE™ and CLOMID™ (clomiphene); progestins such as DURALUTIN™ (hydroxyprogesterone caproate), MPA™ and DEPO-PROVERA™ (medroxyprogesterone acetate), PROVERA™ and CYCRIN™ (MPA), MEGACE™ (megestrol acetate), NORLUTIN™ (norethindrone), and NORLUTATE™ and AYGESTIN™ (norethindrone acetate); progesterone implants such as NORPLANT SYSTEM™ (subdermal implants of norgestrel); antiprogestins such as RU 486™ (mifepristone); hormonal contraceptives such as ENOVID™ (norethynodrel plus mestranol), PROGESTASERT™ (intrauterine device that releases progesterone), LOESTRIN™, BREVICON™, MODICON™, GENORA™, NELONA™, NORINYL™, OVACON-35™ and OVACON-50™ (ethinyl estradiol/norethindrone), LEVLEN™, NORDETTE™, TRI-LEVLEN™ and TRIPHASIL-21™ (ethinyl estradiol/levonorgestrel) LO/OVRAL™ and OVRAL™ (ethinyl estradiol/norgestrel), DEMULEN™ (ethinyl estradiol/ethynodiol diacetate), NORINYL™, ORTHO-NOVUM™, NORETHIN™, GENORA™, and NELOVA™ (norethindrone/mestranol), DESOGEN™ and ORTHO-CEPT™ (ethinyl estradiol/desogestrel), ORTHO-CYCLEN™ and ORTHO-TRICYCLEN™ (ethinyl estradiol/norgestimate), MICRONOR™ and NOR-QD™ (norethindrone), and OVRETTE™ (norgestrel).  
     [1394] Additional treatments for endocrine and/or hormone imbalance disorders include, but are not limited to, testosterone esters such as methenolone acetate and testosterone undecanoate; parenteral and oral androgens such as TESTOJECT-50™ (testosterone), TESTEX™ (testosterone propionate), DELATESTRYL™ (testosterone enanthate), DEPO-TESTOSTERONE™ (testosterone cypionate), DANOCRINE™ (danazol), HALOTESTIN™ (fluoxymesterone), ORETON METHYL™, TESTRED™ and VIRILON™ (methyltestosterone), and OXANDRIN™ (oxandrolone); testosterone transdermal systems such as TESTODERM™; androgen receptor antagonist and 5-alpha-reductase inhibitors such as ANDROCUR™ (cyproterone acetate), EULEXIN™ (flutamide), and PROSCAR™ (finasteride); adrenocorticotropic horrnone preparations such as CORTROSYN™ (cosyntropin); adrenocortical steroids and their synthetic analogs such as ACLOVATE™ (alclometasone dipropionate), CYCLOCORT™ (amcinonide), BECLOVENT™ and VANCERIL™ (beclomethasone dipropionate), CELESTONE™ (betamethasone), BENISONE™ and UTICORT™ (betamethasone benzoate), DIPROSONE™ (betamethasone dipropionate), CELESTONE PHOSPHATE™ (betamethasone sodium phosphate), CELESTONE SOLUSPAN™ (betamethasone sodium phosphate and acetate), BETA-VAL™ and VALISONE™ (betamethasone valerate), TEMOVATE™ (clobetasol propionate), CLODERM™ (clocortolone pivalate), CORTEF™ and HYDROCORTONE™ (cortisol (hydrocortisone)), HYDROCORTONE ACETATE™ (cortisol (hydrocortisone) acetate), LOCOID™ (cortisol (hydrocortisone) butyrate), HYDROCORTONE PHOSPHATE™ (cortisol (hydrocortisone) sodium phosphate), A-HYDROCORT™ and SOLU CORTEF™ (cortisol (hydrocortisone) sodium succinate), WESTCORT™ (cortisol (hydrocortisone) valerate), CORTISONE ACETATE™ (cortisone acetate), DESOWEN™ and TRIDESILON™ (desonide), TOPICORT™ (desoximetasone), DECADRON™ (dexamethasone), DECADRON LA™ (dexamethasone acetate), DECADRON PHOSPHATE™ and HEXADROL PHOSPHATE™ (dexamethasone sodium phosphate), FLORONE™ and MAXIFLOR™ (diflorasone diacetate), FLORINEF ACETATE™ (fludrocortisone acetate), AEROBID™ and NASALIDE™ (flunisolide), FLUONID™ and SYNALAR™ (fluocinolone acetonide), LIDEX™ (fluocinonide), FLUOR-OP™ and FML™ (fluorometholone), CORDRAN™ (flurandrenolide), HALOG™ (halcinonide), HMS LIZUIFILM™ (medrysone), MEDROL™ (methylprednisolone), DEPO-MEDROL™ and MEDROL ACETATE™ (methylprednisone acetate), A-METHAPRED™ and SOLUMEDROL™ (methylprednisolone sodium succinate), ELOCON™ (mometasone furoate), HALDRONE™ (paramethasone acetate), DELTA-CORTEF™ (prednisolone), ECONOPRED™ (prednisolone acetate), HYDELTRASOL™ (prednisolone sodium phosphate), HYDELTRA-T.B.A™ (prednisolone tebutate), DELTASONE™ (prednisone), ARISTOCORT™ and KENACORT™ (triamcinolone), KENALOG™ (triameinolone acetonide), ARISTOCORT™ and KENACORT DIACETATE™ (triamcinolone diacetate), and ARISTOSPAN™ (triamcinolone hexacetonide); inhibitors of biosynthesis and action of adrenocortical steroids such as CYTADREN™ (aminoglutethimide), NIZORAL™ (ketoconazole), MODRASTANE™ (trilostane), and METOPIRONE™ (metyrapone);  
     [1395] Additional treatments for endocrine and/or hormone imbalance disorders include, but are not limited to bovine, porcine or human insulin or mixtures thereof; insulin analogs; recombinant human insulin such as HUMULIN™ and NOVOLIN™; oral hypoglycemic agents such as ORAMIDE™ and ORINASE™ (tolbutamide), DIABINESE™ (chlorproparnide), TOLAMIDE™ and TOLINASE™ (tolazamide), DYMELOR™ (acetohexamide), glibenclamide, MICRONASE™, DIBETA™ and GLYNASE™ (glyburide), GLUCOTROL™ (glipizide), and DIAMICRON™ (gliclazide), GLUCOPHAGE™ (metformin), PRECOSE™ (acarbose), AMARYL™ (glimepiride), and ciglitazone; thiazolidinediones (TZDs) such as rosiglitazone, AVANDIA™ (rosiglitazone maleate) ACTOS™ (piogliatazone), and troglitazone; alpha-glucosidase inhibitors; bovine or porcine glucagon; somatostatins such as SANDOSTATIN™ (octreotide); and diazoxides such as PROGLYCEM™ (diazoxide). In still other embodiments, Therapeutics of the invention are administered in combination with one or more of the following: a biguanide antidiabetic agent, a glitazone antidiabetic agent, and a sulfonylurea antidiabetic agent.  
     [1396] In one embodiment, the Therapeutics of the invention are administered in combination with treatments for uterine motility disorders. Treatments for uterine motility disorders include, but are not limited to, estrogen drugs such as conjugated estrogens (e.g., PREMARIN® and ESTRATAB®, estradiols (e.g., CLIMARA® and ALORA®), estropipate, and chlorotrianisene; progestin drugs (e.g., AMEN® (medroxyprogesterone), MICRONOR® (norethidrone acetate), PROMETRIUM® progesterone, and megestrol acetate); and estrogen/progesterone combination therapies such as, for example, conjugated estrogens/medroxyprogesterone (e.g., PREMPRO™ and PREMPHASE®) and norethindrone acetate/ethinyl estsradiol (e.g., FEMHRT™).  
     [1397] In an additional embodiment, the Therapeutics of the invention are administered in combination with drugs effective in treating iron deficiency and hypochromic anemias, including but not limited to, ferrous sulfate (iron sulfate, FEOSOL™), ferrous fumarate (e.g., FEOSTAT™), ferrous gluconate (e.g., FERGON™), polysaccharide-iron complex (e.g., NIFEREX™), iron dextran injection (e.g., INFED™), cupric sulfate, pyroxidine, riboflavin, Vitamin B 12 , cyancobalamin injection (e.g., REDISOL™, RUBRAMIN PC™), hydroxocobalamin, folic acid (e.g., FOLVITE™), leucovorin (folinic acid, 5-CHOH4PteGlu, citrovorum factor) or WELLCOVORIN (Calcium salt of leucovorin), transferrin or ferritin.  
     [1398] In certain embodiments, the Therapeutics of the invention are administered in combination with agents used to treat psychiatric disorders. Psychiatric drugs that may be administered with the Therapeutics of the invention include, but are not limited to, antipsychotic agents (e.g., chlorpromazine, chlorprothixene, clozapine, fluphenazine, haloperidol, loxapine, mesoridazine, molindone, olanzapine, perphenazine, pimozide, quetiapine, risperidone, thioridazine, thiothixene, trifluoperazine, and triflupromazine), antimanic agents (e.g., carbamazepine, divalproex sodium, lithium carbonate, and lithium citrate), antidepressants (e.g., amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, fluvoxamine, fluoxetine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine, protriptyline, sertraline, tranylcypromine, trazodone, trimipramine, and venlafaxine), antianxiety agents (e.g., alprazolam, buspirone, chlordiazepoxide, clorazepate, diazepam, halazepam, lorazepam, oxazepam, and prazepam), and stimulants (e.g., d-amphetamine, methylphenidate, and pemoline).  
     [1399] In other embodiments, the Therapeutics of the invention are administered in combination with agents used to treat neurological disorders. Neurological agents that may be administered with the Therapeutics of the invention include, but are not limited to, antiepileptic agents (e.g., carbamazepine, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproic acid, divalproex sodium, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, zonisamide, diazepam, lorazepam, and clonazepam), antiparkinsonian agents (e.g., levodopa/carbidopa, selegiline, amantidine, bromocriptine, pergolide, ropinirole, pramipexole, benztropine; biperiden; ethopropazine; procyclidine; trihexyphenidyl, tolcapone), and ALS therapeutics (e.g. riluzole).  
     [1400] In another embodiment, Therapeutics of the invention are administered in combination with vasodilating agents and/or calcium channel blocking agents. Vasodilating agents that may be administered with the Therapeutics of the invention include, but are not limited to, Angiotensin Converting Enzyme (ACE) inhibitors (e.g., papaverine, isoxsuprine, benazepril, captopril, cilazapril, enalapril, enalaprilat, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, spirapril, trandolapril, and nylidrin), and nitrates (e.g., isosorbide dinitrate, isosorbide mononitrate, and nitroglycerin). Examples of calcium channel blocking agents that may be administered in combination with the Therapeutics of the invention include, but are not limited to amlodipine, bepridil, diltiazem, felodipine, flunarizine, isradipine, nicardipine, nifedipine, nimodipine, and verapamil.  
     [1401] In certain embodiments, the Therapeutics of the invention are administered in combination with treatments for gastrointestinal disorders. Treatments for gastrointestinal disorders that may be administered with the Therapeutic of the invention include, but are not limited to, H 2  histamine receptor antagonists (e.g., TAGAMET™ (cimetidine), ZANTAC™ (ranitidine), PEPCID™ (famotidine), and AXID™ (nizatidine)); inhibitors of H + , K +  ATPase (e.g., PREVACID™ (lansoprazole) and PPILOSEC™ (omeprazole)); Bismuth compounds (e.g., PEPTO-BISMOL™ (bismuth subsalicylate) and DE-NOL™ (bismuth subcitrate)); various antacids; sucralfate; prostaglandin analogs (e.g. CYTOTEC™ (misoprostol)); muscarinic cholinergic antagonists; laxatives (e.g., surfactant laxatives, stimulant laxatives, saline and osmotic laxatives); antidiarrheal agents (e.g., LOMOTIL™ (diphenoxylate), MOTOFEN™ (diphenoxin), and IMODIUM™ (loperamide hydrochloride)), synthetic analogs of somatostatin such as SANDOSTATIN™ (octreotide), antiemetic agents (e.g., ZOFRAN™ (ondansetron), KYTRIL™ (granisetron hydrochloride), tropisetron, dolasetron, metoclopramide, chlorpromazine, perphenazine, prochlorperazine, promethazine, thiethylperazine, triflupromazine, domperidone, haloperidol, droperidol, trimethobenzamide, dexamethasone, methylprednisolone, dronabinol, and nabilone); D2 antagonists (e.g., metoclopramide, trimethobenzamide and chlorpromazine); bile salts; chenodeoxycholic acid; ursodeoxycholic acid; and pancreatic enzyme preparations such as pancreatin and pancrelipase.  
     [1402] In additional embodiments, the Therapeutics of the invention are administered in combination with other therapeutic or prophylactic regimens, such as, for example, radiation therapy.  
     Example 11  
     [1403] Method of Treating Decreased Levels of the Polypeptide  
     [1404] It will be appreciated that conditions caused by a decrease in the standard or normal expression level of a polypeptide in an individual can be treated by administering the polypeptide of the present invention, preferably in the secreted and/or soluble form. Thus, the invention also provides a method of treatment of an individual in need of an increased level of the polypeptide comprising administering to such an individual a pharmaceutical composition comprising an amount of the polypeptide to increase the activity level of the polypeptide in such an individual.  
     [1405] For example, a patient with decreased levels of a polypeptide receives a daily dose 0.1-100 ug/kg of the polypeptide for six consecutive days. Preferably, the polypeptide is in the secreted form. The exact details of the dosing scheme, based on administration and formulation, are provided in Example 10.  
     Example 12  
     [1406] Method of Treating Increased Levels of the Polypeptide  
     [1407] Antisense technology is used to inhibit production of a polypeptide of the present invention. This technology is one example of a method of decreasing levels of a polypeptide, preferably a secreted form, due to a variety of etiologies, such as cancer.  
     [1408] For example, a patient diagnosed with abnormally increased levels of a polypeptide is administered intravenously antisense polynucleotides at 0.5, 1.0, 1.5, 2.0 and 3.0 mg/kg day for 21 days. This treatment is repeated after a 7-day rest period if the treatment was well tolerated. The antisense polynucleotides of the present invention can be formulated using techniques and formulations described herein (e.g., see Example 10) or otherwise known in the art.  
     Example 13  
     [1409] Method of Treatment Using Gene Therapy—Ex Vivo  
     [1410] One method of gene therapy transplants fibroblasts, which are capable of expressing a polypeptide, onto a patient. Generally, fibroblasts are obtained from a subject by skin biopsy. The resulting tissue is placed in tissue-culture medium and separated into small pieces. Small chunks of the tissue are placed on a wet surface of a tissue culture flask, approximately ten pieces are placed in each flask. The flask is turned upside down, closed tight and left at room temperature over night. After 24 hours at room temperature, the flask is inverted and the chunks of tissue remain fixed to the bottom of the flask and fresh media (e.g., Ham&#39;s F12 media, with 10% FBS, penicillin and streptomycin) is added. The flasks are then incubated at 37° C. for approximately one week.  
     [1411] At this time, fresh media is added and subsequently changed every several days. After an additional two weeks in culture, a monolayer of fibroblasts emerge. The monolayer is trypsinized and scaled into larger flasks.  
     [1412] pMV-7 (Kirschmeier, P. T. et al., DNA, 7:219-25 (1988)), flanked by the long terminal repeats of the Moloney murine sarcoma virus, is digested with EcoRI and HindIII and subsequently treated with calf intestinal phosphatase. The linear vector is fractionated on agarose gel and purified, using glass beads.  
     [1413] The cDNA encoding a polypeptide of the present invention can be amplified using PCR primers which correspond to the 5′ and 3′ end sequences respectively as set forth in Example 1 using primers and having appropriate restriction sites and initiation/stop codons, if necessary. Preferably, the 5′ primer contains an EcoRI site and the 3′ primer includes a HindIII site. Equal quantities of the Moloney murine sarcoma virus linear backbone and the amplified EcoRI and HindIII fragment are added together, in the presence of T4 DNA ligase. The resulting mixture is maintained under conditions appropriate for ligation of the two fragments. The ligation mixture is then used to transform bacteria HB101, which are then plated onto agar containing kanamycin for the purpose of confirming that the vector has the gene of interest properly inserted.  
     [1414] The amphotropic pA317 or GP+am12 packaging cells are grown in tissue culture to confluent density in Dulbecco&#39;s Modified Eagles Medium (DMEM) with 10% calf serum (CS), penicillin and streptomycin. The MSV vector containing the gene is then added to the media and the packaging cells transduced with the vector. The packaging cells now produce infectious viral particles containing the gene (the packaging cells are now referred to as producer cells).  
     [1415] Fresh media is added to the transduced producer cells, and subsequently, the media is harvested from a 10 cm plate of confluent producer cells. The spent media, containing the infectious viral particles, is filtered through a millipore filter to remove detached producer cells and this media is then used to infect fibroblast cells. Media is removed from a sub-confluent plate of fibroblasts and quickly replaced with the media from the producer cells. This media is removed and replaced with fresh media. If the titer of virus is high, then virtually all fibroblasts will be infected and no selection is required. If the titer is very low, then it is necessary to use a retroviral vector that has a selectable marker, such as neo or his. Once the fibroblasts have been efficiently infected, the fibroblasts are analyzed to determine whether protein is produced.  
     [1416] The engineered fibroblasts are then transplanted onto the host, either alone or after having been grown to confluence on cytodex 3 microcarrier beads.  
     Example 14  
     [1417] Gene Therapy Using Endogenous ACRP30-Like Genes  
     [1418] Another method of gene therapy according to the present invention involves operably associating the endogenous ACRP30-Like gene sequence with a promoter via homologous recombination as described, for example, in U.S. Pat. No. 5,641,670, issued Jun. 24, 1997; International Publication NO: WO 96/29411, published Sep. 26, 1996; International Publication NO: WO 94/12650, published Aug. 4, 1994; Koller et al.,  Proc. Natl. Acad. Sci. USA,  86:8932-8935 (1989); and Zijlstra et al.,  Nature,  342:435-438 (1989). This method involves the activation of a gene which is present in the target cells, but which is not expressed in the cells, or is expressed at a lower level than desired.  
     [1419] Polynucleotide constructs are made which contain a promoter and targeting sequences, which are homologous to the 5′ non-coding sequence of the endogenous ACRP30-Like gene, flanking the promoter. The targeting sequence will be sufficiently near the 5′ end of the ACRP30-Like gene so the promoter will be operably linked to the endogenous sequence upon homologous recombination. The promoter and the targeting sequences can be amplified using PCR. Preferably, the amplified promoter contains distinct restriction enzyme sites on the 5′ and 3′ ends. Preferably, the 3′ end of the first targeting sequence contains the same restriction enzyme site as the 5′ end of the amplified promoter and the 5′ end of the second targeting sequence contains the same restriction site as the 3′ end of the amplified promoter.  
     [1420] The amplified promoter and the amplified targeting sequences are digested with the appropriate restriction enzymes and subsequently treated with calf intestinal phosphatase. The digested promoter and digested targeting sequences are added together in the presence of T4 DNA ligase. The resulting mixture is maintained under conditions appropriate for ligation of the two fragments. The construct is size fractionated on an agarose gel then purified by phenol extraction and ethanol precipitation.  
     [1421] In this Example, the polynucleotide constructs are administered as naked polynucleotides via electroporation. However, the polynucleotide constructs may also be administered with transfection-facilitating agents, such as liposomes, viral sequences, viral particles, precipitating agents, etc. Such methods of delivery are known in the art.  
     [1422] Once the cells are transfected, homologous recombination will take place which results in the promoter being operably linked to the endogenous ACRP30-Like gene sequence. This results in the expression of ACRP30-Like polypeptides in the cell. Expression may be detected by immunological staining, or any other method known in the art.  
     [1423] Fibroblasts are obtained from a subject by skin biopsy. The resulting tissue is placed in DMEM+10% fetal calf serum. Exponentially growing or early stationary phase fibroblasts are trypsinized and rinsed from the plastic surface with nutrient medium. An aliquot of the cell suspension is removed for counting, and the remaining cells are subjected to centrifugation. The supernatant is aspirated and the pellet is resuspended in 5 ml of electroporation buffer (20 mM HEPES pH 7.3, 137 mM NaCl, 5 mM KCl, 0.7 mM Na 2  HPO 4 , 6 mM dextrose). The cells are recentrifuged, the supernatant aspirated, and the cells resuspended in electroporation buffer containing 1 mg/ml acetylated bovine serum albumin. The final cell suspension contains approximately 3×10 6  cells/ml. Electroporation should be performed immediately following resuspension.  
     [1424] Plasmid DNA is prepared according to standard techniques. For example, to construct a plasmid for targeting to the ACRP30-Like locus, plasmid pUC18 (MBI Fermentas, Amherst, N.Y.) is digested with HindIII. The CMV promoter is amplified by PCR with an XbaI site on the 5′ end and a BamHI site on the 3′end. Two ACRP30-Like non-coding gene sequences are amplified via PCR: one ACRP30-Like non-coding sequence (ACRP30-Like fragment 1) is amplified with a HindIII site at the 5′ end and an Xba site at the 3′end; the other ACRP30-Like non-coding sequence (ACRP30-Like fragment 2) is amplified with a BamHI site at the 5′end and a HindIII site at the 3′end. The CMV promoter and ACRP30-Like fragments are digested with the appropriate enzymes (CMV promoter—XbaI and BamHI; ACRP30-Like fragment 1—XbaI; ACRP30-Like fragment 2—BamHI) and ligated together. The resulting ligation product is digested with HindIII, and ligated with the HindIII-digested pUC18 plasmid.  
     [1425] Plasmid DNA is added to a sterile cuvette with a 0.4 cm electrode gap (Bio-Rad). The final DNA concentration is generally at least 120 μg/ml. 0.5 ml of the cell suspension (containing approximately 1.5.×10 6  cells) is then added to the cuvette, and the cell suspension and DNA solutions are gently mixed. Electroporation is performed with a Gene-Pulser apparatus (Bio-Rad). Capacitance and voltage are set at 960 μF and 250-300 V, respectively. As voltage increases, cell survival decreases, but the percentage of surviving cells that stably incorporate the introduced DNA into their genome increases dramatically. Given these parameters, a pulse time of approximately 14-20 mSec should be observed.  
     [1426] Electroporated cells are maintained at room temperature for approximately 5 min, and the contents of the cuvette are then gently removed with a sterile transfer pipette. The cells are added directly to 10 ml of prewarmed nutrient media (DMEM with 15% calf serum) in a 10 cm dish and incubated at 37 degree C. The following day, the media is aspirated and replaced with 10 ml of fresh media and incubated for a further 16-24 hours.  
     [1427] The engineered fibroblasts are then injected into the host, either alone or after having been grown to confluence on cytodex 3 microcarrier beads. The fibroblasts now produce the protein product. The fibroblasts can then be introduced into a patient as described above.  
     Example 15  
     [1428] Method of Treatment Using Gene Therapy—In Vivo  
     [1429] Another aspect of the present invention is using in vivo gene therapy methods to treat disorders, diseases and conditions. The gene therapy method relates to the introduction of naked nucleic acid (DNA, RNA, and antisense DNA or RNA) ACRP30-Like sequences into an animal to increase or decrease the expression of the ACRP30-Like polypeptide. The ACRP30-Like polynucleotide may be operatively linked to a promoter or any other genetic elements necessary for the expression of the ACRP30-Like polypeptide by the target tissue. Such gene therapy and delivery techniques and methods are known in the art, see, for example, WO90/11092, WO98/11779; U.S. Pat. Nos. 5,693,622, 5,705,151, 5,580,859; Tabata et al.,  Cardiovasc. Res.  35(3):470-479 (1997), Chao J et al.,  Pharmacol. Res.,  35(6):517-522 (1997), Wolff,  Neuromuscul. Disord.  7(5):314-318 (1997), Schwartz et al.,  Gene Ther.,  3(5):405-411 (1996), Tsurumi Y. et al.,  Circulation,  94(12):3281-3290 (1996) (incorporated herein by reference).  
     [1430] The ACRP30-Like polynucleotide constructs may be delivered by any method that delivers injectable materials to the cells of an animal, such as, injection into the interstitial space of tissues (heart, muscle, skin, lung, liver, intestine and the like). The ACRP30-Like polynucleotide constructs can be delivered in a pharmaceutically acceptable liquid or aqueous carrier.  
     [1431] The term “naked” polynucleotide, DNA or RNA, refers to sequences that are free from any delivery vehicle that acts to assist, promote, or facilitate entry into the cell, including viral sequences, viral particles, liposome formulations, lipofectin or precipitating agents and the like. However, the ACRP30-Like polynucleotides may also be delivered in liposome formulations (such as those taught in Felgner et al.,  Ann. NY Acad. Sci.,  772:126-139 (1995) and Abdallah et al.,  Biol. Cell,  85(1):1-7 (1995)) which can be prepared by methods well known to those skilled in the art.  
     [1432] The ACRP30-Like polynucleotide vector constructs used in the gene therapy method are preferably constructs that will not integrate into the host genome nor will they contain sequences that allow for replication. Any strong promoter known to those skilled in the art can be used for driving the expression of DNA. Unlike other gene therapies techniques, one major advantage of introducing naked nucleic acid sequences into target cells is the transitory nature of the polynucleotide synthesis in the cells. Studies have shown that non-replicating DNA sequences can be introduced into cells to provide production of the desired polypeptide for periods of up to six months.  
     [1433] The polynucleotide constructs can be delivered to the interstitial space of tissues within the an animal, including of muscle, skin, brain, lung, liver, spleen, bone marrow, thymus, heart, lymph, blood, bone, cartilage, pancreas, kidney, gall bladder, stomach, intestine, testis, ovary, uterus, rectum, nervous system, eye, gland, and connective tissue. Interstitial space of the tissues comprises the intercellular fluid, mucopolysaccharide matrix among the reticular fibers of organ tissues, elastic fibers in the walls of vessels or chambers, collagen fibers of fibrous tissues, or that same matrix within connective tissue ensheathing muscle cells or in the lacunae of bone. It is similarly the space occupied by the plasma of the circulation and the lymph fluid of the lymphatic channels. Delivery to the interstitial space of muscle tissue is preferred for the reasons discussed below. They may be conveniently delivered by injection into the tissues comprising these cells. They are preferably delivered to and expressed in persistent, non-dividing cells which are differentiated, although delivery and expression may be achieved in non-differentiated or less completely differentiated cells, such as, for example, stem cells of blood or skin fibroblasts. In vivo muscle cells are particularly competent in their ability to take up and express polynucleotides.  
     [1434] For the naked ACRP30-Like polynucleotide injection, an effective dosage amount of DNA or RNA will be in the range of from about 0.05 g/kg body weight to about 50 mg/kg body weight. Preferably the dosage will be from about 0.005 mg/kg to about 20 mg/kg and more preferably from about 0.05 mg/kg to about 5 mg/kg. Of course, as the artisan of ordinary skill will appreciate, this dosage will vary according to the tissue site of injection. The appropriate and effective dosage of nucleic acid sequence can readily be determined by those of ordinary skill in the art and may depend on the condition being treated and the route of administration. The preferred route of administration is by the parenteral route of injection into the interstitial space of tissues. However, other parenteral routes may also be used, such as, inhalation of an aerosol formulation particularly for delivery to lungs or bronchial tissues, throat or mucous membranes of the nose. In addition, naked ACRP30-Like polynucleotide constructs can be delivered to arteries during angioplasty by the catheter used in the procedure.  
     [1435] The dose response effects of injected ACRP30-Like polynucleotide in muscle in vivo is determined as follows. Suitable ACRP30-Like template DNA for production of mRNA coding for ACRP30-Like polypeptide is prepared in accordance with a standard recombinant DNA methodology. The template DNA, which may be either circular or linear, is either used as naked DNA or complexed with liposomes. The quadriceps muscles of mice are then injected with various amounts of the template DNA.  
     [1436] Five to six week old female and male Balb/C mice are anesthetized by intraperitoneal injection with 0.3 ml of 2.5% Avertin. A 1.5 cm incision is made on the anterior thigh, and the quadriceps muscle is directly visualized. The ACRP30-Like template DNA is injected in 0.1 ml of carrier in a 1 cc syringe through a 27 gauge needle over one minute, approximately 0.5 cm from the distal insertion site of the muscle into the knee and about 0.2 cm deep. A suture is placed over the injection site for future localization, and the skin is closed with stainless steel clips.  
     [1437] After an appropriate incubation time (e.g., 7 days) muscle extracts are prepared by excising the entire quadriceps. Every fifth 15 um cross-section of the individual quadriceps muscles is histochemically stained for ACRP30-Like protein expression. A time course for ACRP30-Like protein expression may be done in a similar fashion except that quadriceps from different mice are harvested at different times. Persistence of ACRP30-Like DNA in muscle following injection may be determined by Southern blot analysis after preparing total cellular DNA and HIRT supernatants from injected and control mice. The results of the above experimentation in mice can be use to extrapolate proper dosages and other treatment parameters in humans and other animals using ACRP30-Like naked DNA.  
     Example 16  
     [1438] Production of an Antibody  
     [1439] a) Hybridoma Technology  
     [1440] The antibodies of the present invention can be prepared by a variety of methods. (See, Current Protocols, Chapter 2.) As one example of such methods, cells expressing ACRP30-Like polypeptide(s) are administered to an animal to induce the production of sera containing polyclonal antibodies. In a preferred method, a preparation of ACRP30-Like polypeptide(s) is prepared and purified to render it substantially free of natural contaminants. Such a preparation is then introduced into an animal in order to produce polyclonal antisera of greater specific activity.  
     [1441] Monoclonal antibodies specific for ACRP30-Like polypeptide(s) are prepared using hybridoma technology. (Kohler et al., Nature 256:495 (1975); Kohler et al., Eur. J. Immunol. 6:511 (1976); Kohler et al., Eur. J. Immunol. 6:292 (1976); Hammerling et al., in: Monoclonal Antibodies and T-Cell Hybridomas, Elsevier, N.Y., pp. 563-681 (1981)). In general, an animal (preferably a mouse) is immunized with ACRP30-Like polypeptide(s) or, more preferably, with a secreted ACRP30-Like polypeptide-expressing cell. Such polypeptide-expressing cells are cultured in any suitable tissue culture medium, preferably in Earle&#39;s modified Eagle&#39;s medium supplemented with 10% fetal bovine serum (inactivated at about 56° C.), and supplemented with about 10 g/l of nonessential amino acids, about 1,000 U/ml of penicillin, and about 100 μg/ml of streptomycin.  
     [1442] The splenocytes of such mice are extracted and fused with a suitable myeloma cell line. Any suitable myeloma cell line may be employed in accordance with the present invention; however, it is preferable to employ the parent myeloma cell line (SP2O), available from the ATCC. After fusion, the resulting hybridoma cells are selectively maintained in HAT medium, and then cloned by limiting dilution as described by Wands et al. (Gastroenterology 80:225-232 (1981)). The hybridoma cells obtained through such a selection are then assayed to identify clones which secrete antibodies capable of binding the ACRP30-Like polypeptide(s).  
     [1443] Alternatively, additional antibodies capable of binding to ACRP30-Like polypeptide(s) can be produced in a two-step procedure using anti-idiotypic antibodies. Such a method makes use of the fact that antibodies are themselves antigens, and therefore, it is possible to obtain an antibody which binds to a second antibody. In accordance with this method, protein specific antibodies are used to immunize an animal, preferably a mouse. The splenocytes of such an animal are then used to produce hybridoma cells, and the hybridoma cells are screened to identify clones which produce an antibody whose ability to bind to the ACRP30-Like protein-specific antibody can be blocked by ACRP30-Like polypeptide(s). Such antibodies comprise anti-idiotypic antibodies to the ACRP30-Like protein-specific antibody and are used to immunize an animal to induce formation of further ACRP30-Like protein-specific antibodies.  
     [1444] For in vivo use of antibodies in humans, an antibody is “humanized”. Such antibodies can be produced using genetic constructs derived from hybridoma cells producing the monoclonal antibodies described above. Methods for producing chimeric and humanized antibodies are known in the art and are discussed herein. (See, for review, Morrison, Science 229:1202 (1985); Oi et al., BioTechniques 4:214 (1986); Cabilly et al., U.S. Pat. No. 4,816,567; Taniguchi et al., EP 171496; Morrison et al., EP 173494; Neuberger et al., WO 8601533; Robinson et al., WO 8702671; Boulianne et al., Nature 312:643 (1984); Neuberger et al., Nature 314:268 (1985)).  
     [1445] b) Isolation of Antibody Fragments Directed Against ACRP30-Like Polypeptide(s) from a Library of scFvs  
     [1446] Naturally occurring V-genes isolated from human PBLs are constructed into a library of antibody fragments which contain reactivities against ACRP30-Like polypeptide(s) to which the donor may or may not have been exposed (see e.g., U.S. Pat. No. 5,885,793 incorporated herein by reference in its entirety).  
     [1447] Rescue of the Library.  
     [1448] A library of scFvs is constructed from the RNA of human PBLs as described in PCT publication WO 92/01047. To rescue phage displaying antibody fragments, approximately 109  E. coli  harboring the phagemid are used to inoculate 50 ml of 2xTY containing 1% glucose and 100 μg/ml of ampicillin (2xTY-AMP-GLU) and grown to an O.D. of 0.8 with shaking. Five ml of this culture is used to innoculate 50 ml of 2xTY-AMP-GLU, 2×108 TU of delta gene 3 helper (M13 delta gene III, see PCT publication WO 92/01047) are added and the culture incubated at 37° C. for 45 minutes without shaking and then at 37° C. for 45 minutes with shaking. The culture is centrifuged at 4000 r.p.m. for 10 min. and the pellet resuspended in 2 liters of 2xTY containing 100 μg/ml ampicillin and 50 μg/ml kanamycin and grown overnight. Phage are prepared as described in PCT publication WO 92/01047.  
     [1449] M13 delta gene III is prepared as follows: M13 delta gene III helper phage does not encode gene III protein, hence the phage(mid) displaying antibody fragments have a greater avidity of binding to antigen. Infectious M13 delta gene III particles are made by growing the helper phage in cells harboring a pUC19 derivative supplying the wild type gene III protein during phage morphogenesis. The culture is incubated for 1 hour at 37° C. without shaking and then for a further hour at 37° C. with shaking. Cells are spun down (IEC-Centra 8,400 r.p.m. for 10 min), resuspended in 300 ml 2xTY broth containing 100 μg ampicillin/ml and 25 μg kanamycin/ml (2xTY-AMP-KAN) and grown overnight, shaking at 37° C. Phage particles are purified and concentrated from the culture medium by two PEG-precipitations (Sambrook et al., 1990), resuspended in 2 ml PBS and passed through a 0.45 μm filter (Minisart NML; Sartorius) to give a final concentration of approximately 1013 transducing units/ml (ampicillin-resistant clones).  
     [1450] Panning of the Library.  
     [1451] Immunotubes (Nunc) are coated overnight in PBS with 4 ml of either 100 μg/ml or 10 μg/ml of a polypeptide of the present invention. Tubes are blocked with 2% Marvel-PBS for 2 hours at 37° C. and then washed 3 times in PBS. Approximately 1013 TU of phage is applied to the tube and incubated for 30 minutes at room temperature tumbling on an over and under turntable and then left to stand for another 1.5 hours. Tubes are washed 10 times with PBS 0.1% Tween-20 and 10 times with PBS. Phage are eluted by adding 1 ml of 100 mM triethylamine and rotating 15 minutes on an under and over turntable after which the solution is immediately neutralized with 0.5 ml of 1.0M Tris-HCl, pH 7.4. Phage are then used to infect 10 ml of mid-log  E. coli  TG1 by incubating eluted phage with bacteria for 30 minutes at 37° C. The  E. coli  are then plated on TYE plates containing 1% glucose and 100 μg/ml ampicillin. The resulting bacterial library is then rescued with delta gene 3 helper phage as described above to prepare phage for a subsequent round of selection. This process is then repeated for a total of 4 rounds of affinity purification with tube-washing increased to 20 times with PBS, 0.1% Tween-20 and 20 times with PBS for rounds 3 and 4.  
     [1452] Characterization of Binders.  
     [1453] Eluted phage from the 3rd and 4th rounds of selection are used to infect  E. coli  HB 2151 and soluble scFv is produced (Marks, et al., 1991) from single colonies for assay. ELISAs are performed with microtitre plates coated with either 10 pg/ml of the polypeptide of the present invention in 50 mM bicarbonate pH 9.6. Clones positive in ELISA are further characterized by PCR fingerprinting (see, e.g., PCT publication WO 92/01047) and then by sequencing. These ELISA positive clones may also be further characterized by techniques known in the art, such as, for example, epitope mapping, binding affinity, receptor signal transduction, ability to block or competitively inhibit antibody/antigen binding, and competitive agonistic or antagonistic activity.  
     Example 17  
     [1454] [ 3 H]-2-Deoxyglucose Uptake Assay  
     [1455] Adipose, skeletal muscle, and liver are insulin-sensitive tissues. Insulin can stimulate glucose uptake/transport into these tissues. In the case of adipose and skeletal muscle, insulin initiates the signal transduction that eventually leads to the translocation of GLUT4, the glucose transporter 4 molecule, from a specialized intracellular compartment to the cell surface. Once on the cell surface, GLUT4 allows for glucose uptake/transport.  
     [1456] A number of adipose and muscle related cell-lines can be used to test for glucose uptake/transport activity in the presence of an ACRP-30 Like polypeptide of the invention. In particular, the 3T3-L1 murine fibroblast cells and the L6 murine skeletal muscle cells can be differentiated into 3T3-L1 adipocytes and into myotubes, respectively, to serve as appropriate in vitro models for the  3 H-2-deoxyglucose uptake assay (Haspel et al., 1999, J Membr Biol, 169 (1): 45-53; Tsakiridis et al., 1995, Endocrinology, 136(10): 4315-22). Briefly, 2×10 5  cells/100 uL of adipocytes or differentiated L6 cells are transferred to 96-well Tissue-Culture, “TC”, treated, i.e. coated with 50 ug/mL of poly-L-lysine, plates for 4 hours at 37° C. The cells are washed once with HEPES buffered saline. Insulin, or an ACRP-30 Like polypeptide, is added at various dilutions (e.g., 5 nM, 10 nM, 100 nM, and 500 nM for insulin) in HEPES buffered saline for 30 min at 37° C. A final concentration of 10 uM cytochalasin B is added to measure the non-specific uptake. The cells are washed three times with HEPES buffered saline. Labeled, i.e. 10 uM of [ 3 H]-2-deoxyglucose, and unlabeled, i.e. 2-deoxyglucose, are added for 10 minutes at room temperature. The cells are washed three times with cold Phosphate Buffered Saline, “PBS”. The cells are lysed upon the addition of 150 uL/well of 0.05 N NaOH and subsequent incubation with shaking for 20 minutes at room temperature. Samples are then transferred to a scintillation vial to which is added 5 mL of scintillation fluid. The vials are counted in a Beta-Scintillation counter. Maximal responses of about 5-fold and 3-fold that of controls for adipocytes and myotubes, respectively, are to be expected.  
     [1457] It will be clear that the invention may be practiced otherwise than as particularly described in the foregoing description and examples. Numerous modifications and variations of the present invention are possible in light of the above teachings and, therefore, are within the scope of the appended claims.  
     [1458] The entire disclosure of each document cited (including patents, patent applications, journal articles, abstracts, laboratory manuals, books, or other disclosures) in the Background of the Invention, Detailed Description, and Examples is hereby incorporated herein by reference. Further, the hard copy of the sequence listing submitted herewith and the corresponding computer readable form are both incorporated herein by reference in their entireties.  
     [1459] Certain ACRP-30-Like polynucleotides and polypeptides of the present invention, including antibodies, were disclosed in U.S. Provisional Application No. 60/328,419, filed Oct. 12, 2001, and International Application No. PCT/US02/32432, filed Oct. 11, 2002, the specification and sequence listing of each of which are herein incorporated by reference in their entireties.  
    
     
       
         1 
         
           
             107  
           
           
             1  
             733  
             DNA  
             Homo sapiens  
           
            1 

gggatccgga gcccaaatct tctgacaaaa ctcacacatg cccaccgtgc ccagcacctg     60 

aattcgaggg tgcaccgtca gtcttcctct tccccccaaa acccaaggac accctcatga    120 

tctcccggac tcctgaggtc acatgcgtgg tggtggacgt aagccacgaa gaccctgagg    180 

tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca aagccgcggg    240 

aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg caccaggact    300 

ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca acccccatcg    360 

agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac accctgcccc    420 

catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc aaaggcttct    480 

atccaagcga catcgccgtg gagtgggaga gcaatgggca gccggagaac aactacaaga    540 

ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag ctcaccgtgg    600 

acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat gaggctctgc    660 

acaaccacta cacgcagaag agcctctccc tgtctccggg taaatgagtg cgacggccgc    720 

gactctagag gat                                                       733 

 
           
             2  
             3522  
             DNA  
             Homo sapiens  
           
            2 

ggcacgaggt tggaccttcg agcctagctg ctcgcacagg actcggccac ctgcccttcc     60 

tgcaccgact ggccagctca agaggtttgg atatggacct tcttcaattc ctggccttcc    120 

tctttgtcct gcttttgtct gggatgggag ccacaggcac cttgaggacc tccctggacc    180 

caagcctgga gatctacaag aagatgtttg aggtgaagcg gcgggagcag ctgttggcac    240 

tgaagaacct ggcacagctg aacgacatcc accagcagta caagatcctt gatgtcatgc    300 

tcaaggggct ctttaaggtg ctggaggact cccggacagt gctcaccgct gctgatgtgc    360 

tcccagatgg gccctgcccc caggacgaga agctgaagga tgctttctcc cacgtggtgg    420 

agaacacggc cttcttcggc gatgtggtgc tgcgcttccc gaggattgtg cactattact    480 

ttgaccacaa ctccaactgg aacctcctca tccgctgggg tatcagtttc tgcaaccaga    540 

caggcgtctt caaccagggg ccccactcgc ccatcctcag cctgatggcc caggagctgg    600 

ggatcagtga gaaagactcc aacttccaga acccatttaa aatcgaccgc acagagttca    660 

ttcccagcac tgaccctttc cagaaggccc tgagagaaga agagaaacgc cgaaagaaag    720 

aggagaagcg gaaggagatc cgaaaaggcc caaggatctc cagatcccag tctgagttat    780 

agccctggag cagctcaggg ctcagggggc cacaaggagg cagatcggga ggaagaagag    840 

gtggaggtgt ggttgtggtg gagagcacca gctagcccct tccagaaggg gaggccacat    900 

ttgcccggcc ccctggagct gggtctgagc cccagctgaa gggactgagc ctcagatggc    960 

tggattttct ctcaggggcc tcctgctgaa ggggccttca gaggatttta tgctggaaat   1020 

atgaccctgt gcagactgct gggggaggca ggaggatgcc tgcctggacc ctgttggtgg   1080 

ctgaagacct ctggccagct ggcttccgcc cttggtgggg aagcagcaga actaggttct   1140 

gagccacggg tcagggtgcc accctgctgc tggccccact gtgtcacaga gctgcctggc   1200 

acaggtccca gcccctctgc agagacacaa taaaagccag cagacccttt ggaccgacca   1260 

aggctggtgg ggacactgtg aggggaccag ggcccctcag ggatgtagaa acagcttgga   1320 

ggatgcctct gccccaccag gaggggcccc aggccctggc agggcagaga aggaaggggc   1380 

ttggcttggg cctcctggtc ctacgccatc actgcccttg acaaatgatt ggtgttggga   1440 

aaggacctgg aagtgccctg ggacctggga aacatttagc tcaagaagac cttggagcaa   1500 

catgatccct gtcctcagat gtctggggac agtcattgag caagcacagg gaagtcagct   1560 

tgttctctct ggcagcgctg gaagacagtc aacctgtggg tggggggctg cagggggaca   1620 

ggccgcagcc ctgcaggagg ccgtgctccg caatggctgc cctaagctgc atgggtcaga   1680 

cagcttcccg tctcgggagg ccacagggca gggaagctgc agagggcatg tggccctggg   1740 

tagggcagct gcccttcact catgcccctc ccaagcagag gagggaaggg ctttagtgag   1800 

aattctagct ctgcctcttt gaccttgcca agtcaggatc tgcctcttaa aggagcagag   1860 

aaaaccatcc agatcccctc gacacccagc cccctaccac tgacagagca caagtgagat   1920 

ctgagtgtta gcccttcaga tttgctgact ggccttggcc cacccctccc tgtgctgcag   1980 

cttcattggc aaaatgaatt tgatggtatc tgtatcccct gcccagccct aacctgtttc   2040 

tctgaggctg gcctccctac ggggctgcag cagcaaaggg aagccaagcc ttagagaagc   2100 

ctcatggaag ggcccagaac atcctgcacc catcagttac tcggaagtaa ggggacaaga   2160 

agcagctgga agagagctgg gtgtgggggc tgggaggagt gctggagaaa tttccccatc   2220 

agaaggcccc tcactgggca gtggaggcag ggcagtgtgg tgggactgac tcaacagaca   2280 

tagtttcatc tccaccctgc ccttctcagg ttgtgtgacc ccagccacat ggacacccga   2340 

gtctgtgaac taaagggctg gtccatggca ttaacagtgg agggtgtcca ggttcttgat   2400 

gtcttgaaca aagaattggg caaaatgcac aaagcaagga aggaatgaag ggttttactg   2460 

agaatgaaag tatactccac agcatgggag agggcctgag catagggact caaggggccc   2520 

gttacagaat ttttgggagt aaatacccac tagaggattc cattggttac ttgaggtaca   2580 

ccctatgtaa atggaaagga tgaagtaaat ttacaaattc atttacagca tataccctat   2640 

ggggaggata ttccctgtta tagctgaagc gtgaattggc cttatgttcc ctgcctccag   2700 

accctatttt cctgcatcaa cgggaaaggg tcagattcac tggctcagct gtttaacctg   2760 

tcctggtgcc agcagctgga gctgggtgtc aggaccagcc cgcaagctct tccctgccgg   2820 

aaggaccagg ccagtcgctg tccttttcat gctagagagt ggttgtggtt gctgacttag   2880 

cagagaaggt gcttggcttt ccccttaact ggagaaaaaa ctttctaaga accaggcctg   2940 

gttggcagca gacctagctt tcttggggtg gcagggaggc taaagcatac ctcaggacag   3000 

tcagtggtgg gtccagcttc ggctggaggt tctttctact gaataacttc tacgggctct   3060 

gtcattagca ggatttgtat aatttgaagc agagctgggc aactgcagag caatggggaa   3120 

gccagcccag tgtggtggca agacctgggc aacttgggac cagcctgggc tgtctcttgc   3180 

cagctgttgt tatcagaacc aggctcttca cactcagatc cttgggcccc ccatctcaga   3240 

atgcccagtg gttaaaagga tgaaacctgg aatttaagtg acttctcagt gatgtgtgcc   3300 

cttctctgac ggttccttgt tcatcccatg tatttactga ctgcctgcta tatatgcaga   3360 

gccaaagagt ggggcctggt cttgaactat ctcctcatct gccccttctg gcacctcctt   3420 

cctcctgggc tctttcctct aataccgtca tcctctctcc aacctggtta atcctgtcct   3480 

ttctgccctc aaatgggcac cttcaaaaaa aaaaaaaaaa aa                      3522 

 
           
             3  
             2007  
             DNA  
             Homo sapiens  
           
            3 

ccacgcgtcc gcgcgcggag ggcgcctggt gcagcatggg cggcccgcgg gcttgggcgc     60 

tgctctgcct cgggctcctg ctcccgggag gcggcgctgc gtggagcatc ggggcagctc    120 

cgttctccgg acgcaggaac tggtgctcct atgtggtgac ccgcaccatc tcatgccatg    180 

tgcagaatgg cacctacctt cagcgagtgc tgcagaactg cccctggccc atgagctgtc    240 

cggggagcag ctacagaact gtggtgagac ccacatacaa ggtgatgtac aagatagtga    300 

ccgcccgtga gtggaggtgc tgccctgggc actcaggagt gagctgcgag gaagttgcag    360 

cttcctctgc ctccttggag cccatgtggt cgggcagtac catgcggcgg atggcgcttc    420 

ggcccacagc cttctcaggt tgtctcaact gcagcaaagt gtcagagctg acagagcggc    480 

tgaaggtgct ggaggccaag atgaccatgc tgactgtcat agagcagcca gtacctccaa    540 

caccagctac ccctgaggac cctgccccgc tctggggtcc ccctcctgcc cagggcagcc    600 

ccggagatgg aggcctccag gaccaagtcg gtgcttgggg gcttcccggg cccaccggcc    660 

ccaagggaga tgccggcagt cggggcccaa tggggatgag aggcccacca ggtccacagg    720 

gccccccagg gagccctggc cgggctggag ctgtgggcac ccctggagag aggggacctc    780 

ctgggccacc agggcctcct ggcccccctg ggcccccagc ccctgttggg ccaccccatg    840 

cccggatctc ccagcatgga gacccattgc tgtccaacac cttcactgag accaacaacc    900 

actggcccca gggacccact gggcctccag gccctccagg gcccatgggt ccccctgggc    960 

ctcctggccc cacaggtgtc cctgggagtc ctggtcacat aggaccccca ggccccactg   1020 

gacccaaagg aatctctggc cacccaggag agaagggcga gagaggactg cgtggggagc   1080 

ctggccccca aggctctgct gggcagcggg gggaacctgg ccctaaggga gaccctggtg   1140 

agaagagcca ctggaaccag agctggggtc tggggcgggc cctgccggca caggcacccc   1200 

cagcctcctt cggggcaaga ggggcggaca tgcaaccaac taccggatcg tggcccccag   1260 

gagccgggac gagagaggct gagggtggtg gcggcccctg aggcagacca ggccaggctt   1320 

cccctcctac ctggactcgg ccagctgcct ccagggaccg cccgtccata tttattaatg   1380 

tcctcagggt cccttctgcc atctaggcct taggggtaag caggtctcag tcctggcacc   1440 

atgcacatgt ctgaggctga gcaagggctg agaggagagg cttgggcctc agtttccctc   1500 

tgtgaagtgg ggggaggcag gccttcaagg agggatagag gtacaaggct tcgtctcatc   1560 

tgctgtctga gcatccaggc ccaaaggcac tgagggagtc aggagctggg gctcggcaca   1620 

tgcagagatg acagggcagg gggcagtctt cctccccctc cccgaccaaa cctcggggag   1680 

ccctcctgtg cccctccctc cttgttgtcc agtgctgggt tccccacccc gaggtcaggc   1740 

tgcccaatcc tctgactgga tcaccggggg cttcttgcct cagttcttcc ctctgagccc   1800 

ccaggccctc ccgcatctca ggttggggat ggggacatgg agaggaaggg gccgcctact   1860 

cctgcaaatg cttgtgacag atgccaggag gtagatgtgt gctggccaat aaaggcccct   1920 

acctgattcc ccgcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   1980 

aaaaaaaaaa aaaaaaaaaa aaaaaaa                                       2007 

 
           
             4  
             901  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (872)..(872)  
               n equals a,t,g, or c  
             
           
            4 

ccacgcgtcc gccgcccggg ctgctgcagg gtctgagccc cggacagggt gtggtggtag     60 

ctcccaccgg gtcccactgg gcccctcacc tgcttctctc tccccccagc gggatctctt    120 

cggtccccca ggacctccag gtgcagaagt gaccgcggag actctgcttc acgagtttca    180 

ggagctgctg aaagaggcca cggagcgccg gttctcaggg cttctggacc cgctgctgcc    240 

ccagggggcg ggcctgcggc tggtgggcga ggcctttcac tgccggctgc agggtccccg    300 

ccgggtggac aagcggacgc tggtggagct gcatggtttc caggctcctg ctgcccaagg    360 

tgccttcctg cgaggctccg gtctgagcct ggcctcgggt cggttcacgg cccccgtgtc    420 

cggcatcttc cagttctctg ccagtctgca cgtggaccac agtgagctgc agggcaaggc    480 

ccggctgcgg gcccgggacg tggtgtgtgt tctcatctgt attgagtccc tgtgccagcg    540 

ccacacgtgc ctggaggccg tctcaggcct ggagagcaac agcagggtct tcacgctaca    600 

ggtgcagggg ctgctgcagc tgcaggctgg acagtacgct tctgtgtttg tggacaatgg    660 

ctccggggcc gtcctcacca tccaggcggg ctccagcttc tccgggctgc tcctgggcac    720 

gtgagggcgc ccaggggggc tggcgaggag ctgccgccgg atcccgggga ccctcctact    780 

gatgcccgtg gtcaccacaa taaagagccc tccacccyca aaaaaaaaaa aaaaaaaaaa    840 

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa anaaaaaaaa aaaaaaaaaa aaaaaaaaag    900 

g                                                                    901 

 
           
             5  
             1558  
             DNA  
             Homo sapiens  
           
            5 

cgagaaaccg cgcttccgct tctggtcgca gagacctcgg agaccgcgcc ggggagacgg     60 

aggtgctgtg ggtggggggg acctgtggct gctcgtaccg ccccccaccc tcctcttctg    120 

cactgccgtc ctccggaaga ccttttcccc tgctctgttt ccttcaccga gtctgtgcat    180 

cgccccggac ctggccggga ggaggcttgg ccggcgggag atgctctagg ggcggcgcgg    240 

gaggagcggc cggcgggacg gagggcccgg caggaagatg ggctcccgtg gacagggact    300 

cttgctggcg tactgcctgc tccttgcctt tgcctctggc ctggtcctga gtcgcgtgcc    360 

ccatgtccag ggggaacagc aggagtggga ggggactgag gagctgccgt cccctccgga    420 

ccatgccgag agggctgaag aacaacatga aaaatacagg cccagtcagg accaggggct    480 

ccctgcttcc cggtgcttgc gctgctgtga ccccggtacc tccatgtacc cggcgaccgc    540 

cgtgccccag atcaacatca ctatcttgaa aggggagaag ggtgaccgcg gagatcgagg    600 

cctccaaggg aaatatggca aaacaggctc agcaggggcc aggggccaca ctggacccaa    660 

agggcagaag ggctccatgg gggcccctgg ggagcggtgc aagagccact acgccgcctt    720 

ttcggtgggc cggaagaagc ccatgcacag caaccactac taccagacgg tgatcttcga    780 

cacggagttc gtgaacctct acgaccactt caacatgttc accggcaagt tctactgcta    840 

cgtgcccggc ctctacttct tcagcctcaa cgtgcacacc tggaaccaga aggagaccta    900 

cctgcacatc atgaagaacg aggaggaggt ggcgatcttg ttcgcgcagg tgggcgaccg    960 

cagcatcatg caaagccaga gcctgatgct ggagctgcga gagcaggacc aggtgtgggt   1020 

acgcctctac aagggcgaac gtgagaacgc catcttcagc gaggagctgg acacctacat   1080 

caccttcagt ggctacctgg tcaagcacgc caccgagccc tagctggccg gccacctcct   1140 

ttcctctcgc caccttccac ccctgcgctg tgctgacccc agggctcagc accaggctga   1200 

ccccaccgcc tcttccccga tccctggact ccgactccct ggctttggca ttcagtgaga   1260 

cgccctgacc acacagaaag ccaaagcgat cggtgctccc agatcccgca gcctctggag   1320 

agagctgacg gcagatgaaa tcaccagggc ggggcacccg cgagaaccct ctgggacctt   1380 

ccgcggccct ctctgcacac atcctcaagt gaccccgcac ggcgagacgc gggtggcggc   1440 

agggcgtccc agggtgcggc accgcggctc cagtccttgg aaataattag gcaaattcta   1500 

aaggtctcaa aaggagcaaa gtaaaccgtg gaggacaaag aaaaaaaaaa aaaaaaaa     1558 

 
           
             6  
             1313  
             DNA  
             Homo sapiens  
           
            6 

ggcacgagcc tagagagggc agactatcag ggtgccggcg gtgagaatcc agggagagga     60 

gcggaaacag aagaggggca gaagaccggg gcacttgtgg gttgcagagc ccctcagcca    120 

tgttgggagc caagccacac tggctaccag gtcccctaca cagtcccggg ctgcccttgg    180 

ttctggtgct tctggccctg ggggccgggt gggcccagga ggggtcagag cccgtcctgc    240 

tggaggggga gtgcctggtg gtctgtgagc ctggccgagc tgctgcaggg gggcccgggg    300 

gagcagccct gggagaggca ccccctgggc gagtggcatt tgctgcggtc cgaagccacc    360 

accatgagcc agcaggggaa accggcaatg gcaccagtgg ggccatctac ttcgaccagg    420 

tcctggtgaa cgagggcggt ggctttgacc gggcctctgg ctccttcgta gcccctgtcc    480 

ggggtgtcta cagcttccgg ttccatgtgg tgaaggtgta caaccgccaa actgtccagg    540 

tgagcctgat gctgaacacg tggcctgtca tctcagcctt tgccaatgat cctgacgtga    600 

cccgggaggc agccaccagc tctgtgctac tgcccttgga ccctggggac cgagtgtctc    660 

tgcgcctgcg tcgggggaat ctactgggtg gttggaaata ctcaagtttc tctggcttcc    720 

tcatcttccc tctctgagga cccaagtctt tcaagcacaa gaatccagcc cctgacaact    780 

ttcttctgcc ctctcttgcc ccagaaacag cagaggcagg agagagactc cctctggctc    840 

ctatcccacc tctttgcatg ggaccctgtg ccaaacaccc aagtttaaga gaagagcaga    900 

gctgagagca ggtatacaga gctggaagtg gaccatggaa aacatcgata accatgcatc    960 

ctcttgcttg gccacctcct gaaactgctc cacctttgaa gtttgaactt tagtccctcc   1020 

acactctgac tgctgcctcc ttcctcccag ctctctcact gagttatctt cactgtacct   1080 

gttccagcat atccccacta tctctctttc tcctgatctg tgctgtctta ttctcctcct   1140 

taggcttcct attacctggg attccatgat tcattccttc agaccctctc ctgccagtat   1200 

gctaaaccct ccctctctct ttcttatccc gctgacccat tggcccagcc tggatgaatc   1260 

tatcaataaa acaactagag aatggtgaaa aaaaaaaaaa aaaaaaaaaa aaa          1313 

 
           
             7  
             1312  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (27)..(27)  
               n equals a,t,g, or c  
             
           
            7 

gctggccctg ctgttgctgc tactgcncgc ctgctgcccc gtgcgggcgc agaacgacac     60 

ggagcccatc gtgctggagg gcaagtgcct ggtggtgtgc gactccagcc cgtcggcgga    120 

cggcgccgtc acctcctccc taggcatctc cgtgcgctcc ggcagcgcca aggtggcctt    180 

ctccgccacg cggagcacca accacgagcc gtccgagatg agcaaccgca ccatgaccat    240 

ctatttcgac caggtattag taaatattgg caaccacttt gatcttgctt ccagtatatt    300 

tgtagcaccg agaaaaggga tttatagctt cagcttccac gtggtcaaag tgtataacag    360 

acaaaccatc caggtcagtt taatgcagaa tggctaccca gtgatctcgg cctttgcagg    420 

agaccaggat gtcaccagag aagctgctag caatggcgtg ctgctgctca tggaaaggga    480 

agacaaagtg catctcaaac ttgagagagg caacctcatg gggggctgga aatactccac    540 

attctcgggc ttcttggtgt ttcctctata aacacagagc cccctagatg gtgggggaat    600 

ggcaaactgg acccaggact ccgcccttta aaacaccctg aacttactgg aattggacac    660 

cttgtttcca acctccgtca gactgttgca gtagaagaat gatttccttt gaaacctcca    720 

gtacttttkt ttttgttttt tggaatactg acaattcctc gggaacctgg cctctaatta    780 

gttttagatg acaaggtctt aaggagaaat gaaattatcg atttgagcaa tttgtacctg    840 

tgattgtaaa gtcaatatcg gattttattg ttgggaccat ggacctcttt tgtttgtatg    900 

ttgtattgtc gtcccaacgg aaggagagct cctgactcca ggatgggctg caggttgcag    960 

tcagggcttg aagtaggagc ccagcaaaga accacctgct ggacagtcct tgacatgtgt   1020 

tctgtgtgtg tctgtatagc cttaagaaaa agaatggctt cactttcatt ctgtattctt   1080 

ccccccacca tgtggctggg aggacttggg agggggatgg ggacattggg gaacctgttc   1140 

aagaagtgct ttatccagag aagcaaattt ttgcacgatt gggactgcaa ttttgttttt   1200 

gtanttgttt gtgttttttc cttgnaaaag ctttactttt cctttccaca ctcagctctt   1260 

ccctcctcaa ccccattttt aatttttcct tgccgggggt tgaaggagag aa           1312 

 
           
             8  
             1022  
             DNA  
             Homo sapiens  
           
            8 

gcagccaggg cttgccgggc cgcgatggcc gcgacggccg cgacggcgcg cccggggctc     60 

cgggagagaa aggcgagggc gggaggccgg gactgccggg acctcgaggg gaccccgggc    120 

cgcgaggaga ggcgggaccc gcggggccca ccgggcctgc cggggagtgc tcggtgcctc    180 

cgcgatccgc cttcagcgcc aagcgctccg agagccgggt gcctccgccg tctgacgcac    240 

ccttgccctt cgaccgcgtg ctggtgaacg agcagggaca ttacgacgcc gtcaccggca    300 

agttcacctg ccaggtgcct ggggtctact acttcgccgt ccatgccacc gtctaccggg    360 

ccagcctgca gtttgatctg gtgaagaatg gcgaatccat tgcctctttc ttccagtttt    420 

tcggggggtg gcccaagcca gcctcgctct cggggggggc catggtgagg ctggagcctg    480 

aggaccaagt gtgggtgcag gtgggtgtgg gtgactacat tggcatctat gccagcatca    540 

agacagacag caccttctcc ggatttctgg tgtactccga ctggcacagc tccccagtct    600 

ttgcttagtg cccactgcaa agtgagctca tgctctcact cctagaagga gggtgtgagg    660 

ctgacaacca ggtcatccag gagggctggc ccccctggaa tattgtgaat gactagggag    720 

gtggggtaga gcactctccg tcctgctgct ggcaaggaat gggaacagtg gctgtctgcg    780 

atcaggtctg gcagcatggg gcagtggctg gatttctgcc caagaccaga ggagtgtgct    840 

gtgctggcaa gtgtaagtcc cccagttgct ctggtccagg agcccacggt ggggtgctct    900 

cttcctggtc ctctgcttct ctggatcctc cccaccccct cctgctcctg gggccggccc    960 

ttttctcaga gatcactcaa taaacctaag aaccctcaaa aaaaaaaaaa aaaaaaaaaa   1020 

aa                                                                  1022 

 
           
             9  
             1254  
             DNA  
             Homo sapiens  
           
            9 

acgcgtccga gcagatctga ggacatctct gtgccaggcc agaaaccgcc cacctgcagt     60 

tccttctccg ggatggacgt ggggcccagc tccctgcccc accttgggct gaagctgctg    120 

ctgctcctgc tgctgctgcc cctcaggggc caagccaaca caggctgcta cgggatccca    180 

gggatgcccg gcctgcccgg ggcaccaggg aaggatgggt acgacggact gccggggccc    240 

aagggggagc caggaatccc agccattccc gggatccgag gacccaaagg gcagaaggga    300 

gaacccggct tacccggcca tcctgggaaa aatggcccca tgggaccccc tgggatgcca    360 

ggggtgcccg gccccatggg catccctgga gagccaggtg aggagggcag atacaagcag    420 

aaattccagt cagtgttcac ggtcactcgg cagacccacc agccccctgc acccaacagc    480 

ctgatcagat tcaacgcggt cctcaccaac ccgcagggag attatgacac gagcactggc    540 

aagttcacct gcaaagtccc cggcctctac tactttgtct accacgcgtc gcatacagcc    600 

aacctgtgcg tgctgctgta ccgcagcggc gtcaaagtgg tcaccttctg tggccacacg    660 

tccaaaacca atcaggtcaa ctcgggcggt gtgctgctga ggttgcaggt gggcgaggag    720 

gtgtggctgg ctgtcaatga ctactacgac atggtgggca tccagggctc tgacagcgtc    780 

ttctccggct tcctgctctt ccccgactag ggcgggcaga tgcgctcgag ccccacgggc    840 

cttccacctc cctcagcttc ctgcatggac ccaccttact ggccagtctg catccttgcc    900 

tagaccattc tccccaccag atggacttct cctccaggga gcccaccctg acccaccccc    960 

actgcacccc ctccccatgg gttctctcct tcctctgaac ttctttagga gtcactgctt   1020 

gtgtggttcc tgggacactt aaccaatgcc ttctggtact gccattcttt tttttttttt   1080 

ttttcaagta ttggaagggg tggggagata tataaataaa tcatgaaatc aataaaaaaa   1140 

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   1200 

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa         1254 

 
           
             10  
             1618  
             DNA  
             Homo sapiens  
           
            10 

ccacgcgtcc gcaaggagcc agaggccatg cagtggctca gggtccgtga gtcgcctggg     60 

gaggccacag gacacagggt caccatgggg acagccgccc tgggtcccgt ctgggcagcg    120 

ctcctgctct ttctcctgat gtgtgagatc cctatggtgg agctcacctt tgacagagct    180 

gtggccagcg actgccaacg gtgctgtgac tctgaggacc ccctggatcc tgcccatgta    240 

tcctcagcct cttcctccgg ccgcccccac gccctgcctg agatcagacc ctacattaat    300 

atcaccatcc tgaagggtga caaaggggac ccaggcccaa tgggcctgcc agggtacatg    360 

ggcagggagg gtccccaagg ggagcctggc cctcagggca gcaagggtga caagggggag    420 

atgggcagcc ccggcgcccc gtgccagaag cgcttcttcg ccttctcagt gggccgcaag    480 

acggccctgc acagcggcga ggacttccag acgctgctct tcgaaagggt ctttgtgaac    540 

cttgatgggt gctttgacat ggcgaccggc cagtttgctg ctcccctgcg tggcatctac    600 

ttcttcagcc tcaatgtgca cagctggaat tacaaggaga cgtacgtgca cattatgcat    660 

aaccagaaag aggctgtcat cctgtacgcg cagcccagcg agcgcagcat catgcagagc    720 

cagagtgtga tgctggacct ggcctacggg gaccgcgtct gggtgcggct cttcaagcgc    780 

cagcgcgaga acgccatcta cagcaacgac ttcgacacct acatcacctt cagcggccac    840 

ctcatcaagg ccgaggacga ctgagggcct ctgggccacc ctcccggctg gagagctcag    900 

ctgatacggc atcctgcgag aagacctgcc ctcctcactg ggatcccctt cctgcctcct    960 

cccagggctc tgccagggcc ttgctcagtc ccttccacca aagtcatctg aacttccgtt   1020 

tcccagggcc tccagctgcc ctcagacact gatgtctgtc cccaggtgct ctctgcccct   1080 

catgcccctc tcaccggccc agtgccccga ctctccaggc tttatcaagg tgctaaggcc   1140 

cgggtgggca gctcctcgtc tcagagccct cctccggcct ggtgctgcct ttacaaacac   1200 

ctgcaggaga agggccacgg aagccccagg ctttagagcc ctcagcaggt ctggggagct   1260 

agagcaaagg agggacctca ggccttccgt ttcttcttcc agggtggggt ggcctggtgt   1320 

tcccctagcc ttccaaaccc aggtggcctg cccttctccc cagagggagg cggcctccgc   1380 

ccattggtgc tcatgcagac tctggggctg aggtgccccg gggggtgatc tctggtgctc   1440 

acagtcgagg gagccgtggc tccatggcca gatgacggaa acagggtctg accaagtgcc   1500 

aggaagacct gtgctataaa ccaccctgcc tgatcctgcc cctgcctgac cccgccacgc   1560 

cctgccgtcc agcatgatta aagaatgctg tctcctcttg gaaaaaaaaa aaaaaaaa     1618 

 
           
             11  
             1336  
             DNA  
             Homo sapiens  
           
            11 

ggcacgagct ggtaccaaag caagtttttc actgagctct catgaaagat cctcagtctc     60 

ttgtggattt agaatcctgc agcagcccac catctaagag caagagccaa agatgtttgt    120 

cttgctctat gttacaagtt ttgccatttg tgccagtgga caaccccggg gtaatcagtt    180 

gaaaggagag aactactccc ccaggtatat ctgcagcatt cctggcttgc ctggacctcc    240 

agggccccct ggagcaaatg gttcccctgg gccccatggt cgcatcggcc ttccaggaag    300 

agatggtaga gacggcagga aaggagagaa aggtgaaaag ggaactgcag gtttgagagg    360 

taagactgga ccgctaggtc ttgccggtga gaaaggggac caaggagaga ctgggaagaa    420 

aggacccata ggaccagagg gagagaaagg agaagtaggt ccaattggtc ctcctggacc    480 

aaagggagac agaggagaac aaggggaccc ggggctgcct ggagtttgca gatgtggaag    540 

catcgtgctc aaatccgcct tttctgttgg catcacaacc agctacccag aagaaagact    600 

acctattata tttaacaagg tcctcttcaa cgagggagag cactacaacc ctgccacagg    660 

gaagttcatc tgtgctttcc cagggatcta ttacttttct tatgatatca cattggctaa    720 

taagcatctg gcaatcggac tggtacacaa tgggcaatac cggataaaga ccttcgacgc    780 

caacacagga aaccatgatg tggcttcggg gtccacagtc atctatctgc agccagaaga    840 

tgaagtctgg ctggagattt tcttcacaga ccagaatggc ctcttctcag acccaggttg    900 

ggcagacagc ttattctccg ggtttctctt atacgttgac acagattacc tagattccat    960 

atcagaagat gatgaattgt gatcaggacc aagatccctg tggtaaacac tctgattgaa   1020 

tctggggttc cagaaggtgg aacaagcagg aatgggatcc aaagagactc ccactcagat   1080 

tctaaagcat ttaaagacaa ttctagcaga atttatcaaa acaagatgaa acacagaaaa   1140 

gttgaaacca caacaaaatg aattctatta aagaatagcc ccagatataa attctcttga   1200 

aagcaatgtt cataaatatt taagcaaatt aaagacaatg ttaacaaatt ttctattaaa   1260 

tgccctgagt gataaaacca gttggcaata atattgcctt attaaatctt caaaaaataa   1320 

aaaaaaaaaa aaaaaa                                                   1336 

 
           
             12  
             1114  
             DNA  
             Homo sapiens  
           
            12 

ggcacgagga gcttctttgc tccggacgcc cctggacgtg gcgggcagcc gcgagggtaa     60 

ccaccatgat cccctgggtg ctcctggcct gtgccctccc ctgtgctgct gacccactgc    120 

ttggcgcctt tgctcgcagg gacttccgga aaggctcccc tcaactggtc tgcagcctgc    180 

ctggccccca gggcccaccc ggccccccag gagccccagg gccctcagga atgatgggac    240 

gaatgggctt tcctggcaaa gacggccaag atggacacga cggcgaccgg ggggacagcg    300 

gagaggaagg tccacctggc cggacaggta accggggaaa gccaggacca aagggcaaag    360 

ccggggccat tgggcgggct ggcccccgtg gccccaaggg ggtcaacggt acccccggga    420 

agcatggcac accaggcaag aaggggccca agggcaagaa gggggagcca ggcctcccag    480 

gcccctgcag ctgtggcagt ggccatacca agtcagcttt ctcggtggca gtgaccaaga    540 

gctacccacg ggagcggctg cccatcaagt ttgacaagat tctgatgaac gagggtggcc    600 

actacaatgc ttccagcggc aagttcgtct gcggcgtgcc tgggatctac tacttcacct    660 

acgacatcac gctggccaac aagcacctgg ccatcggcct ggtgcacaac ggccagtacc    720 

gcatccggac ctttgatgcc aacaccggca accacgatgt ggcctcaggc tccaccatcc    780 

tggctctcaa gcagggtgac gaagtttggc tgcagatctt ctactcagag cagaacgggc    840 

tcttctatga cccttactgg acagacagcc tctttacggg cttcctaatc tatgccgacc    900 

aggatgaccc caacgaggta tagacatgcc acggcggtcc tccaggcagg gaacaagctt    960 

ctggacttgg gcttacagag caagacccca caactgtagg ctgggggtgg ggggtcgagt   1020 

gagcggttct agcctcaggc tcacctcctc tgcctctttt tttccccttc attaaatcca   1080 

aaccttttta ttcatcaaaa aaaaaaaaaa aaaa                               1114 

 
           
             13  
             659  
             DNA  
             Homo sapiens  
           
            13 

ggcacagcac gcgcagcttg gtgggctcgg acgctggccc cgggccgcgg caccaaccac     60 

tcgccttcga caccgagttc gtcaacattg gcggcgactt cgacgcggcg gccggcgtgt    120 

tccgctgccg tctgcccggc gcctacttct tctccttcac gctgggcaag ctgccgcgta    180 

agacgctgtc ggttaagctg atgaagaacc gcgacgaggt gcaggccatg atttacgacg    240 

acggcgcgtc gcggcgccgc gagatgcaga gccagagcgt gatgctggcc ctgcggcgcg    300 

gcgacgccgt ctggctgctc agccacgacc acgacggcta cggcgcctac agcaaccacg    360 

gcaagtacat caccttctcc ggcttcctgg tgtaccccga cctcgccccc gccgccccgc    420 

cgggcctcgg ggcctcggag ctactgtgag ccccgggcca gagaagagcc cgggagggcc    480 

aggggcgtgc atgccaggcc gggcccgagg ctcgaaagtc ccgcgcgagc gccacggcct    540 

ccgggcgcgc ctggactctg ccaataaagc ggaaagcggg cacgcgcagc gcccggcagc    600 

ccaggaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa     659 

 
           
             14  
             1195  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (1147)..(1147)  
               n equals a,t,g, or c  
             
           
            14 

cccacgcgtc cgggggacag tgaggggacg ggaaaggggc cagcctgctg gkccatggga     60 

ggggaccgtc aggggaaagc ccttcccgcc tctggggaag ggaacttccg cttcggaccg    120 

agggcagtag gctctcggct cctggtccca ctgctgctca gcccagtggc ctcacaggac    180 

accagcttcc caggaggcgt ctgacacagt atgatgatga agatcccatg gggcagcatc    240 

ccagtactga tgttgctcct gctcctgggc ctaatcgata tctcccaggc ccagctcagc    300 

tgcaccgggc ccccagccat ccctggcatc ccgggtatcc ctgggacacc tggccccgat    360 

ggccaacctg ggaccccagg gataaaagga gagaaagggc ttccagggct ggctggagac    420 

catggtgagt tcggagagaa gggagaccca gggattcctg ggaatccagg aaaagtcggc    480 

cccaagggcc ccatgggccc taaaggtggc ccaggggccc ctggagcccc aggccccaaa    540 

ggtgaatcgg gagactacaa ggccacccag aaaatcgcct tctctgccac aagaaccatc    600 

aacgtccccc tgcgccggga ccagaccatc cgcttcgacc acgtgatcac caacatgaac    660 

aacaattatg agccccgcag tggcaagttc acctgcaagg tgcccggtct ctactacttc    720 

acctaccacg ccagctctcg agggaacctg tgcgtgaacc tcatgcgtgg ccgggagcgt    780 

gcacagaagg tggtcacctt ctgtgactat gcctacaaca ccttccaggt caccaccggt    840 

ggcatggtcc tcaagctgga gcagggggag aacgtcttcc tgcaggccac cgacaagaac    900 

tcactactgg gcatggaggg tgccaacagc atcttttccg ggttcctgct ctttccagat    960 

atggaggcct gacctgtggg ctgcttcaca tccaccccgg ctccccctgc cagcaacgct   1020 

cactctaccc ccaacaccac cccttgccca gccaatgcac acagtagggc ttggtgaatg   1080 

ctgctgagtg aatgagtaaa taaactcttc aaggccaaaa aaaaaaaaag cacttaagta   1140 

ttcatcnaac aatcacccag tagcggtgat ccagactgaa aagatgcgag acgcc        1195 

 
           
             15  
             3951  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (3871)..(3871)  
               n equals a,t,g, or c  
             
           
            15 

gagctccacc gcggtggcgg ccgctctaga actagtggat cccccgggct gcaggawttc     60 

ggcacgagag ctgctccgtg ctggagggaa gtgagagttt tattcaggct cagtacaact    120 

gtgcctggaa ccagatgccc tgtccgtcgg cgctggtgta tcgagtgaac ttcagaccta    180 

gatatgtcac taggtataag acagtgacac agttggaatg gaggtgctgt cctggcttta    240 

gagggggaga ttgccaagaa ggtcccaaag accccgtgaa gaccctccgc cccacgccgg    300 

ctcggcctcg aaacagcttg aagaaagcca cagataatga acccagccaa ttctcagagc    360 

ccaggaagac tttgtcccca actggtacag cacaaccaag ctggggggta gatccaaaag    420 

aggggcctca ggaacttcag gaaaagaaga tacaggtgct agaggagaag gttcttcgac    480 

tcacaaggac ggttcttgac ctccagtctt cccttgctgg agtgagtgaa aatctcaaac    540 

atgccactca ggatgatgcc agtagaacac gggcaccagg gctcagcagc cagcacccca    600 

agcctgacac cactgttagt ggagacacag aaacgggcca gagtcctggt gtcttcaaca    660 

ctaaggaatc tggcatgaag gacatcaagt ctgaattggc tgaagtcaaa gatactctaa    720 

agaacaaaag tgacaagctg gaagagctgg atggaaaagt gaagggctac gaagggcagc    780 

tcagacagct ccaggaagca gctcagggcc cgacggtgac catgacaacc aacgaactct    840 

accaagccta tgtggacagt aagatcgacg ccctgagaga ggagctcatg gagggcatgg    900 

acagaaagct ggctgacctg aaaaactcat gtgagtacaa gctcactggc ctccagcagc    960 

agtgtgatga ctatgggagc agctacctgg gagtgataga gctcataggg gagaaggaaa   1020 

caagcctgag aaaagaaata aataacctcc gagcccggct acaggagcct tcagcccagg   1080 

caaattgctg cgacagtgaa aagaatggtg acattggtca acagatcaag acattggacc   1140 

agaaaatcga gagagttgct gaagccacca gaatgctgaa tggaagactg gacaatgagt   1200 

ttgaccgcct tatagttcca gagccagatg tggattttga tgcaaaatgg aatgaactcg   1260 

atgcaaggat caatgtgacg gagaagaacg ctgaagaaca ttgcttttac attgaggaaa   1320 

cccttcgggg cgccattaat ggagaggtgg gtgacttgaa gcagcttgtt gatcagaaaa   1380 

tacagtctct ggaagaccgt ctggggagcg ttctcctaca gatgaccaat aacactggtg   1440 

cagagctcag tcccccaggg gcagcagccc tgccaggagt gtcagggtca ggagatgaac   1500 

gggtcatgat ggaattaaac cacctgaagg acaaagttca agttgttgaa gacatttgcc   1560 

tgctgaacat ccagggaaag cctcatggga tggaaggtgc cttgccaaac agggaagacc   1620 

gcgcagtacg cgacagcctg caccttttga aatctctcaa cgacacgatg cacaggaagt   1680 

ttcaagaaac cgaacaaacc atccagaaac ttcaacagga ttttagtttt ctttattctc   1740 

aattaaacca cacagaaaat gatgtgactc atcttcaaaa ggaaatgagc aattgtagag   1800 

caggtgaaaa cgctggcatg ggtaggttca ctaaggtggg tgagcaagaa aggacagtgg   1860 

acaccctgcc gtccccccag caccccgtgg ctcattgctg cagtcagctg gaggagaggt   1920 

ggcagaggtt gcagagccag gtcatctcgg agctggatgc ttgtaaggaa tgcacgcagg   1980 

gggtccagag ggaggtctcc atggtggagg gcagggtgtc tcatatggag aaaacttgca   2040 

gcaagctgga ctctatctca ggaaatcttc agaggatcaa ggaggggctc aacaagcatg   2100 

tcagcagcct gtggaactgt gtcaggcaga tgaacggaac gctcaggtcg cattccagag   2160 

acatttctgg cctgaagaat tcagtccagc agttctacag ccacgtcttc cagatttcta   2220 

ctgatttgca agatctggtc aaatttcagc catcagcaaa ggcgccctcg cccccgccgc   2280 

ccgcagaggc cccgaaggag ccgctgcagc ccgagcccgc cccgccgagg cccagcggcc   2340 

ccgcaaccgc agaggaccct gggcgacggc ccgtcctgcc ccagcggccc cccgaggaga   2400 

ggccgcccca gccgccaggc tccaccgggg tcatcgcgga gacgggccag gccgggcccc   2460 

ccgcaggcgc aggcgtgtct gggcggggtc tgccgcgggg cgtggacggc cagaccggga   2520 

gcggcaccgt ccccggcgca gaaggcttcg cgggcgcacc aggatacccg aagtcacctc   2580 

ctgtagcttc cccaggagct ccggtgcctt ctctggtgtc tttttctgcg gggctcaccc   2640 

agaagccttt ccccagtgat gggggcgttg tcctctttaa caaagtgctg gtgaacgacg   2700 

gggatgttta caaccccagc accggggtct tcacggctcc ttatgatggg cgctacctga   2760 

tcacggccac cctcaccccc gagagagacg cctacgtgga agcagtgctg tcggtctcca   2820 

acgccagcgt ggcccagctg cataccgctg ggtacaggag agagttcctg gaataccacc   2880 

gccctccagg agctttgcat acctgcgggg gcccgggggc attccacctc atcgtgcacc   2940 

tgaaggcggg agatgcagtc aacgtcgtgg tgactggggg caagctggct cacacagact   3000 

ttgatgaaat gtactccaca tttagtgggg ttttcttata tcctttcctt tcccacctct   3060 

aaggtggctg gggagatgtc aggggaaaga yagatagttg taaaaactct aaagctttaa   3120 

tatattcggt ttgtatgtaa tggaagcacg gggctagagt ttccacatag gccccaacat   3180 

aaaggccttc cctcgctgtt gaggccacca tgccttactg catccagcca ggctgcagrg   3240 

agtgaggcac acggtgaaca tggccactga cttttctgcc actctaactg gacaactgga   3300 

agacttggaa aggcctccac ctgtatctac actctgaggg ccctggactg ggcctgagct   3360 

tgccacagag gctccgtctg actgtgggct gggaggaggg aggcagggga gagccggtca   3420 

cggtggctgg tctttactgc agggcagcac tgtggccagc tgtctgtctt tacactgcat   3480 

gcagaagttt aaacactgaa gtgccgaagt ggcccgtgcc gccgcacaga gaccccgact   3540 

ttagtttggg ctgttccacg cttggctcac cattgccgcc tgggacttaa cctgctcagg   3600 

cgggccttcg cccagctgca aatagggatg cgttagagac tgttcccaaa gcttgttggg   3660 

ctccttaaat ggcatgtaca atttaagtgc aaagacaggg agtgtcaata aagatggaaa   3720 

gccatttcca gttaaaaaaa aaaaaaaact cgaggggggg cccggtaccc aattcgccct   3780 

atagtgagtc gtattacaat tcactggccg tcgttttaca acgtcgtgac tgggaaaacc   3840 

ctggcgttac ccaacttaat cgccttgcag nacatccccc tttcgccagc tggcgtaata   3900 

acnaaaaagc ccgcaccgat cgcccttccc aacaggttgc gcaacctgaa t            3951 

 
           
             16  
             1280  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (81)..(82)  
               n equals a,t,g, or c  
             
           
            16 

ttacaaaaag ctatttaggt gacactatag aaggtacgcc tgcaggtacc ggtccggaat     60 

tcccgggtcg acccacgcgt nngggttttg atacttatag aggactccct tcaatttcca    120 

atggaaatta tagccagctg cagttccaag ctagagagta ttctggagca ccttattccc    180 

aaagggataa tttccagcag tgttataagc gaggagggac atctggtggt ccacgagcaa    240 

attcgagagc taactgcttc attatgagaa actcactgtt gctaataaaa cagcagggtg    300 

gagtgattct tctcaggtga gcagcccaga aagagacaac gaaaccttta acagtggtga    360 

ctctggacaa ggagactccc gtagcatgac ccctgtggat gtgccagtga caaatccagc    420 

agccaccata ctgccagtac acgtctaccc tctgcctcag cagatgcgag ttgccttctc    480 

agcagccaga acctctaatc tggcccctgg aactttagac caacctattg tgtttgatct    540 

tcttctgaac aacttaggag aaacttttga tcttcagctt ggtagattta attgcccagt    600 

gaatggcact tacgttttca tttttcacat gctaaagctg gcagtgaatg tgccactgta    660 

tgtcaacctc atgaagaatg aagaggtctt ggtatcagcc tatgccaatg atggtgctcc    720 

agaccatgaa actgctagca atcatgcaat tcttcagctc ttccagggag accagatatg    780 

gttacgtctg cacaggggag caatttatgg aagtagctgg aaatattcta cgttttcagg    840 

ctatcttctt tatcaagatt gaaagtcagt acagtattga caataaaagg atggtgttct    900 

aattagtggg attgaaggaa aagtagtctt tgccctcatg actgattggt ttaggaaaat    960 

gtttttgttc ctagagggag gaggtcctta cttttttgtt ttccttcctg aggtgaaaaa   1020 

tcaagctgaa tgacaattag cactaatctg gcactttata aattgtgatg tagcctcgct   1080 

agtcaagctg tgaatgtata ttgtttgcac ttaatcctta actgtattaa cgttcagctt   1140 

actaaactga ctgcctcaag tccaggcaag ttacaatgcc ttgttgtgcc tcaataaaaa   1200 

agttacatgc aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   1260 

aaaaaaaaaa ngggggggnc                                               1280 

 
           
             17  
             3764  
             DNA  
             Homo sapiens  
           
            17 

ctgatactat ttaaggtacg cctgcaggta ccggtccgga attcgcggcc gcgtcgaccg     60 

atcctctccg tgggagccag cgagcctctc tccctgatct tacgtgctca aggatccagt    120 

ttcacctatg gaatgagaaa gttggggaag aagtcatcta gcgtcttgct actcaaagtg    180 

tggtccatgg accagcagca tcagcatcac ctgggatctt cttggaagaa atgtagaaac    240 

tcaggcctca ccccagaatc tgccttttta taagaccccc agaagctgtt gtgaaggcag    300 

agcagcatct gctgaagaga cagaaaccag ccccagaggt gtcacaggaa gtcaccagca    360 

aggacattgg tctttgattt gattcagcag tcctgtcaag tataaatgtg atggctgtgc    420 

tgcctggccc tctgcagctg ctgggagtgc tgcttaccat ttccctgagt tccatcaggc    480 

tcattcaggc tggtgcctac tatgggatca agccgctgcc acctcaaatt cctcctcaga    540 

tgccaccaca aattccacaa taccagcccc tgggtcagca agtacctcac atgcctttgg    600 

ccaaagatgg ccttgccatg ggcaaggaga tgccccactt gcagtatggc aaagagtatc    660 

cacacctacc ccaatatatg aaggaaattc aaccggcgcc aagaatgggc aaggaagccg    720 

tacccaagaa aggcaaagaa ataccattag ccagtttacg aggggaacaa ggtccccgtg    780 

gagagcctgg cccaagagga ccacctgggc cccctggttt gccaggtcat gggatacctg    840 

gaattaaagg aaaaccaggg ccacagggat atccaggagt tggaaagcca ggtatgcctg    900 

gaatgccagg ggaagccagg agccatgggc atgcctgggg caaaaggaga aattggacag    960 

aaaggggaaa ttgggcctat ggggatccca ggaccacaag gacctccagg gcctcatgga   1020 

cttcctggca ttgggaagcc aggtgggcca gggttaccag ggcaaccagg accaaagggt   1080 

gatcgaggac ccaaaggact accaggacct caaggccttc ggggtcctaa aggagacaag   1140 

ggcttcggga tgccaggtgc gccaggtgta aaggggcctc cagggatgca cggccctccc   1200 

ggccctgttg gactgccagg agtgggcaaa ccaggagtga caggcttccc tgggccccag   1260 

ggccccctgg gaaagccagg ggctccagga gaacctgggc cacaaggccc tattggggta   1320 

ccgggggttc aaggacctcc tgggataccc ggaattggaa agccaggcca ggatgggatc   1380 

ccaggccagc caggatttcc aggtggcaaa ggggagcaag gactgccagg gctaccagga   1440 

cccccaggcc ttccagggat tgggaaacca ggcttcccag gacccaaagg tgaccggggc   1500 

atgggaggtg ttcctggggc tcttggacca agaggggaga aaggaccaat aggtgcccca   1560 

ggaatagggg gtcctccagg agagccaggc ctgcctggaa tcccaggtcc tatgggccct   1620 

ccaggtgcta ttggttttcc tggacccaaa ggagaaggtg ggattgtagg gccacagggg   1680 

ccaccaggtc ccaagggtga gccagggctt caaggcttcc caggaaagcc aggtttcctt   1740 

ggtgaagtag ggcctcctgg catgaggggt ttgccaggtc ccatagggcc caagggggaa   1800 

gctgggcaaa aaggtgtacc aggactccct ggtgttccag ggcttctcgg acctaaggga   1860 

gagccaggaa tcccagggga tcagggttta cagggccccc caggtatccc agggattggg   1920 

ggccctagtg gccccattgg accacctggg attccaggcc ccaaagggga gccgggcctc   1980 

ccagggcccc ctgggttccc tggtataggg aaacccggag tggcaggact tcatggcccc   2040 

ccagggaagc ctggtgccct tggtcctcaa ggccagcctg gccttccagg acccccaggc   2100 

cctccaggac ctccaggacc cccagctgtg atgcccccta caccaccacc ccagggagag   2160 

tatctgccag atatggggct gggaattgat ggcgtgaaac ccccccatgc ctacggggct   2220 

aagaaaggca agaatggagg gccagcctat gagatgcctg catttaccgc cgagctaacc   2280 

gcacctttcc caccggtggg ggccccagtg aagtttaaca aactgctgta taacggcaga   2340 

cagaactaca acccgcagac aggcatcttc acctgtgagg tccctggtgt ctactacttt   2400 

gcataccacg ttcactgcaa ggggggcaac gtgtgggttg ctctattcaa gaacaacgag   2460 

cccgtgatgt acacgtacga cgagtacaaa aagggcttcc tggaccaggc atctgggagt   2520 

gcagtgctgc tgctcaggcc cggagaccgg gtgttcctcc agatgccctc agaacaggct   2580 

gcaggactgt atgccgggca gtatgtccac tcctcctttt caggatattt attgtatccc   2640 

atgtaaaaac aaaaaaacaa aaaacaaaga aaagaaagag attttataga agaaaatgac   2700 

acaccaaaaa atccaaatga aaaacataat tgcttcaaaa cacttacaca gttggaaagt   2760 

tatatgtaag tgaaaatttg gaccattgtg tacaaataaa aactaagatg catgtttaat   2820 

actccacaca gcagcctgta attgcgaatg atgggataga gttatgtatc aagtactgac   2880 

acttggttgt acccactgga atcatattag ctgttttatg ttatatgctt ccacagtaac   2940 

ctgcttattc agatcagtca aaatatatca gtatgaaaga tcatagctaa tgaaaggcac   3000 

tcactcatat tgtttacttt aaaatattta taaatatgcc ttaaagaaat acaaatgata   3060 

acaattacat accgtattta cttgcttaat ttcctctgta tttgtgtaga tactttgaca   3120 

tggaatatat ggtggggaga cccgtagtgt taccgcccca gtgggagggg gccctgggga   3180 

ccctggtaat gctttagtca aagggatatc tctcttgtat cagaggctgt gtcttttagt   3240 

aacaggagtc ctcgtcagaa ttgcgtgtct gttgtctcta aaagaatggg tgaaccaatc   3300 

ggcctttgtg aatttattca gtgccttctc tgtaccaagc actgggtaag gcacttttgt   3360 

ggagcattag acagtaaccc tcaaggagct agagaaccgg atgggagaca tgagcggtaa   3420 

ttaactcact tgttccccag agtttctatt tgttttgatt ttctttttct gtgacttatt   3480 

ttcctatttt ctttcctcca tgtaattttc actatggccc aactaatata aacacctgga   3540 

aattacaagg aaaaaaaatt cttcctctaa taactttcca aatttgtgga atatttattt   3600 

gtaatagcag ttatcagtta tgcttatata gcattaaaaa ttctcctcct ttgactacac   3660 

acacaaccac agtgtggttc taatcatgga gatatcagta atttttagta actgaatttt   3720 

gaggacattt ctctgtttag catgtatgca aactgatatg taat                    3764 

 
           
             18  
             2485  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (2388)..(2388)  
               n equals a,t,g, or c  
             
           
            18 

aggggtccct ggctcccctg gaatacgggc cctccggggc ctcccgggcc cccgggaccc     60 

cctggtgccc ctggggcctt cgatgagact ggcatcgcag gcttgcacct gcccaacggy    120 

ggtgtggagg gtgccgtgct gggcaagggg ggcaagccac agtttgggct gggcgagctg    180 

tctgcccatg ccacaccggc cttcactgcg gtgctcacct cgcccttccc cgcctcgggc    240 

atgcccgtga aatttgaccg gactctctac aatggccaca gcggctacaa cccagccact    300 

ggcatcttca cctgccctgt gggcggcgtc tactactttg cttaccatgt gcacgtcaag    360 

ggcaccaacg tgtgggtggc cctgtacaag aacaacgtgc cggccaccta tacctacgat    420 

gagtacaaga agggctacct ggaccaggca tctggtgggg ccgtgctcca gctgcggccc    480 

aacgaccagg tctgggtgca gatgccgtcg gaccaggcca acggcctcta ctccacggag    540 

tacatccact cctccttttc aggattcttg ctctgcccca cataacccgc ggggggtgtc    600 

ctgctgccct ggcctcctcc cctttagtgg tagagcgacc ttttcaatta caaagaacct    660 

cctggaaaaa aaaacaaaag ctgaacagag gcggccgtgg ccttggcccg aggagactaa    720 

cttgctttct ccctgcatgc aggctgagat tgtttctgga aggggctggc ctgagtttct    780 

ttcccccaaa tgtctgtgca gtgtcagggc tgcaccccat aggccctgag gcacacagcc    840 

cagccccttg tgagtcctgg cctctgctgg gccctgaagg agctgagagg gagctcaact    900 

ccccaccccg ccacgtgggg agacagccct tcccactggc tccctgatgg cacctgctgg    960 

aggaaagggg cacggcctcc ctcacagccc ttggctgggg ctcctccagc tccccctggg   1020 

acctccagca tatgacagtg gactaaggac tgtggggttt tcctccaagg ggaagggaga   1080 

agaggggacc atcgaggtgg cgagtgtgga caccctgcca ggactgcagc ccccatggtg   1140 

atgctgtggc atcagacatg tccgtggtgg gcacagtgcc tgttgccctg ggaaagggca   1200 

acctcccttt cactgctcca gtggcagcca tggggaaggc agtttgtgag ggcttggggc   1260 

acagacctgg ggcaggaggc agctcttcac gttcatccct gtctctcccg ggctgccccc   1320 

gccagctctg gctgtttagc ttgagggcag cacagaggcc cctgggacac ctacaggcca   1380 

gaaagatcaa cctctgtgaa gtgtctagaa gtatctagtg cagatggtgg cggaggcaga   1440 

atcgaccatc agcaaacatg agcactcttc cctttctccc cttccacctg ctgcgggctg   1500 

ggctggtttt ctcaatacaa aattgtaaga ggatccttgt caccccagcc aggtatcccc   1560 

aaggcagagc acctctcgtt tggccctctg aacaaggtgc acgcgagctg ggggatgaag   1620 

acggctccca cttccttttc cttaataaga accatatggt gggtgtatgt gtgtacaaga   1680 

ggggttcatc tgtgggggct tcctctcctt ccaccctctg gttccaattt cctgttctaa   1740 

gcaggactag ggcccaggag gctaaggctg ggagagaaag ggtgccaaca ggtcccttgg   1800 

gaatgagttg gctctggacg tttctgccct gttccccgat cagagctcct ctgcaggaaa   1860 

caggcaggat gcccctccca acccctcagt ccctacgtca agcggagtgg ataaggctga   1920 

gatgagtgct gggagtggtg gacattcctg ctcgtgcaaa gatggccact ttccccgcag   1980 

ctgcagggcc tcgcgctcgg ccctcgccag gccagcccca ctccttgtac caagtgtgaa   2040 

ctggggtcat tcggtctgtg atctcgttgc actgctccaa gtctggctgt gtccaggcgg   2100 

tccatgttga aaatggagga tggctgctga cttctgactg gctgagcagt gggttccttc   2160 

aggttccttg ccaaccctcc tcccctgccc acaacttctc caaacaaagc aggctgtttg   2220 

ctcacttctt caaaaggagg aatgataacc caaatctgcc caagtgacac ttgagaaggt   2280 

tttggctggg gttcctggtg grrtttctta ctacctaacg cccaaggaaa accaactaag   2340 

ggactctcaa accaytacct gggtgggggg ttttttcggt tcaacctntt tctttcccta   2400 

gggttcaaag gccantattc atctngatgt tgtttagggg atggggtttc ttgatttggg   2460 

caggaaattt aattcaggtt nccca                                         2485 

 
           
             19  
             1550  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (1547)..(1547)  
               n equals a,t,g, or c  
             
           
            19 

ctgcagtctg tggttctgat tccataccag aggggctcag gatgctgttg ctgggagctg     60 

ttctactgct attagctctg cccggtcatg accaggaaac cacgactcaa gggcccggag    120 

tcctgcttcc cctgcccaag ggggcctgca caggttggat ggcgggcatc ccagggcatc    180 

cgggccataa tggggcccca ggccgtgatg gcagagatgg cacccctggt gagaagggtg    240 

agaaaggaga tccaggtctt attggtccta agggagacat cggtgaaacc ggagtacccg    300 

gggctgaagg tccccgaggc tttccgggaa tccaaggcag gaaaggagaa cctggagaag    360 

gtgcctatgt ataccgctca gcattcagtg tgggattgga gacttacgtt actatcccca    420 

acatgcccat tcgctttacc aagatcttct acaatcagca aaaccactat gatggctcca    480 

ctggtaaatt ccactgcaac attcctgggc tgtactactt tgcctaccac atcacagtct    540 

atatgaagga tgtgaaggtc agcctcttca agaaggacaa ggctatgctc ttcacctatg    600 

atcagtacca ggaaaataat gtggaccagg cctccggctc tgtgctcctg catctggagg    660 

tgggcgacca agtctggctc caggtgtatg gggaaggaga gcgtaatgga ctctatgctg    720 

ataatgacaa tgactccacc ttcacaggct ttcttctcta ccatgacacc aactgatcac    780 

cactaactca gagcctccty caggccaaac agccccaaag tcaattaaag gctttcagta    840 

cggttaggaa gttgattatt atttagttgg aggcctttag atattattca ttcatttact    900 

cattcattta ttcattcatt catcaagtaa ctttaaaaaa atcatatgct atgttcccag    960 

tcctggggag cttcacaaac atgaccagat aactgactag aaagaagtag ttgacagtgc   1020 

tattttgtgc ccactgtctc tcctgatgct catatcaatc ctataaggca cagggaacaa   1080 

gcattctcct gtttttacag attgtatcct gaggctgaga gagttaagtg aatgtctaag   1140 

gtcacacaag tattaagtga cagtgctaga aatcaaaccc agagctgtgg actttgttca   1200 

ctagactgtg cccttttata gaggtacatg ttctctttgg agtgttggta ggtgtctgtt   1260 

tcccacctca cctgagagcc attgaatttg ccttcctcat gaattaaaac ctcccccaag   1320 

cagagcttcc tcagagaaag tggttctatg atgaagtcct gtcttggaag gactactact   1380 

caatggyccc tgcactactc tacttcctct tacctatgtc ccttctcatg cctttccctc   1440 

caacggggaa agccaactcc atctctaagt gctgaactca tccctgttcc tcaaggccac   1500 

ctggccagga gcttctctga tgtgatatcc actttttttt ttttttnaaa              1550 

 
           
             20  
             1518  
             DNA  
             Homo sapiens  
           
            20 

ccacgcgtcc ggactcactg aatgagctcc agaccactgt ggagggccag ggcgctgatc     60 

tggctgacct gggggcaacc aaggaccgta tcatttctga gattaacagg ctgcagcagg    120 

aggccacaga gcatgctaca gagagtgaag agcgcttccg aggcctagag gagggacaag    180 

cacaggccgg ccagtgcccc agcttagagg ggcgattggg ccgtcttgag ggtgtctgtg    240 

aacggttgga cactgtggct gggggactgc agggcctgcg cgagggcctt tccagacacg    300 

tggctgggct ctgggctggg ctccgggaaa ccaacaccac cagccagatg caggcagccc    360 

tgctggagaa gctggtcggg ggacaggcgg gcctgggcag gcggctgggt gcccttaaca    420 

gctccctgca gctcctggag gaccgtctgc accagctcag cctgaaggac ctcactgggc    480 

ctgcaggaga ggctgggccc ccagggcctc ctgggctgca gggaccccca ggccctgctg    540 

gacctccagg atcaccaggc aaggacgggc aagagggccc catcgggcca ccaggtcctc    600 

aaggtgaaca gggagtggag ggggcaccag cagcccctgt gccccaagtg gcattttcag    660 

ctgctctgag tttgccccgg tctgaaccag gcacggtccc cttcgacaga gtcctgctca    720 

atgatggagg ctattatgat ccagagacag gcgtgttcac agcgccactg gctggacgct    780 

acttgctgag cgcggtgctg actgggcacc ggcacgagaa agtggaggcc gtgctgtccc    840 

gctccaacca gggcgtggcc cgcgtagact ccggtggcta cgagcctgag ggcctggaga    900 

ataagccggt ggccgagagc cagcccagcc cgggcaccct gggcgtcttc agcctcatcc    960 

tgccgctgca ggccggggac acggtctgcg tcgacctggt catggggcag ctggcgcact   1020 

cggaggagcc gctcaccatc ttcagcgggg ccctgctcta tggggaccca gagcttgaac   1080 

acgcgtagac tggggtcccg cccgacgtgt ctacgtcggc tgaagagaca gcgggggcgg   1140 

cgggctcctg gggtctcgcc tgagacgggg cacctagccc tgggcgagcg ccgcacccgg   1200 

gcccgcagcg gcaccgcgcc cagagcggcc tctccccacg cccggggcgc gccggctcag   1260 

ggaggctcgg ggccgcccat gcagactttt ggcctggcgc gatcccccaa gaacccctcc   1320 

agggccggcc tgcggaggag ccgatcctcg caccctccgc tccctccact ggccctccag   1380 

gtcgattccc tgggctccag gctcccccgc gcgggcgccg cccgccgcca tactaaacga   1440 

tcgaggaata aagacacttg gtttttctaa aaaaaactaa aaaaaaaaaa aaaaaaaaaa   1500 

aaaaaaaaaa aaaaaaaa                                                 1518 

 
           
             21  
             1545  
             DNA  
             Homo sapiens  
           
            21 

ccacgcgtcc ggtggctcca tgtataggag acagtgaaag agatgggggt ggcattttct     60 

tccaggagag ttgtggggag atgaccgtta ggtcataagc gcgcccctac tctgcactgg    120 

cgagaccagc aaagctggag tgaacccagc tgaacctggg ccgcagcagc cccggaggct    180 

ggaggcgctg cagtcgggaa acaccaggag gatggagccc ttttccctgt aagcaggagg    240 

ccaggatcct gattcctgag ccggcttccc acggacccca ggccccggca gggtcctggc    300 

gggaggaaga acccacggat tcagagtctg tcatctgaac catgaggatc tggtggcttc    360 

tgcttgccat tgaaatctgc acagggaaca taaactcaca ggacacctgc aggcaagggc    420 

accctggaat ccctgggaac cccggtcaca atggtctgcc tggaagagat ggacgagacg    480 

gagcgaaggg tgacaaaggc gatgcaggag aaccaggacg tcctggcagc ccggggaagg    540 

atgggacgag tggagagaag ggagaacgag gagcagatgg aaaagttgaa gcaaaaggca    600 

tcaaaggtga tcaaggctca agaggatccc caggaaaaca tggccccaag gggcttgcag    660 

ggcccatggg agagaaaggc ctccgaggag agactgggcc tcaggggcag aaggggaata    720 

agggtgacgt gggtcccact ggtcctgagg ggccaagggg caacattggg cctttgggcc    780 

caactggttt accgggcccc atgggcccta ttggaaagcc tggtcccaag ggagaagctg    840 

gacccacggg gccccagggt gagccaggag tccggggaat aagaggctgg aaaggagatc    900 

gaggagagaa agggaaaatc ggtgagactc tagtcttgcc aaaaagtgct ttcactgtgg    960 

ggctcacggt gctgagcaag tttccttctt cagatgtgcc cattaaattt gataagatcc   1020 

tgtataacga attcaaccat tatgatacag cagcggggaa attcacgtgc cacattgctg   1080 

gggtctatta cttcacctac cacatcactg ttttctccag gaatgttcag gtgtctttgg   1140 

tcaaaaatgg agtaaaaata ctgcacacca aagatgctta catgagctct gaggaccagg   1200 

cctctggcgg cattgtcctg cagctgaagc tcggggatga ggtgtggctg caggtgacag   1260 

gaggagagag gttcaatggc ttgtttgctg atgaggacga tgacacaact ttcacagggt   1320 

tccttctgtt cagcagcccg tgacagagga gagtttaaaa atccgccaca ccatccatca   1380 

gaatcagctt gggatgaact tattcagatg gttttacttt attaattcct ccaattatta   1440 

caataatcat aaaaaggtga aaatggaaaa gttattccca aaactgattc tgtgtaactt   1500 

actatttttc caggagtaaa tatttaaaat aaaaaaaaaa aaaaa                   1545 

 
           
             22  
             3543  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (3)..(3)  
               n equals a,t,g, or c  
             
           
            22 

ttnctgcagg aattcggcac gaggttggac cttcgagcct agctgctcgc acaggactcg     60 

gccacctgcc cttcctgcac cgactggcca gctcaagagg tttggatatg gaccttcttc    120 

aattcctggc cttcctcttt gtcctgcttt tgtctgggat gggagccaca ggcaccttga    180 

ggacctccct ggacccaagc ctggagatct acaagaagat gtttgaggtg aagcggcggg    240 

agcagctgtt ggcactgaag aacctggcac agctgaacga catccaccag cagtacaaga    300 

tccttgatgt catgctcaag gggctcttta aggtgctgga ggactcccgg acagtgctca    360 

ccgctgctga tgtgctccca gatgggccct tcccccagga cgagaagctg aaggatgctt    420 

tctcccacgt ggtggagaac acggccttct tcggcgatgt ggtgctgcgc ttcccgagga    480 

ttgtgcacta ttactttgac cacaactcca actggaacct cctcatccgc tggggtatca    540 

gtttctgcaa ccagacaggc gtcttcaacc aggggcccca ctcgcccatc ctcagcctga    600 

tggcccagga gctggggatc agtgagaaag actccaactt ccagaaccca tttaaaatcg    660 

accgcacaga gttcattccc agcactgacc ctttccagaa ggccctgaga gaagaagaga    720 

aacgccgaaa gaaagaggag aagcggaagg agatccgaaa aggcccaagg atctccagat    780 

cccagtctga gttatagccc tggagcagct cagggctcag ggggccacaa ggaggcagrt    840 

cgggaggaag aagaggtgga ggtgtggttg tggtggagag caccagctag ccccttccag    900 

aaggggaggc cacatttgcc cggccccctg gagctgggtc tgagccccag ctgaagggac    960 

tgagcctcag atggctggat tttctctcag gggcctcctg ctgaaggggc cttcagagga   1020 

ttttatgctg gaaatatgac cctgtgcaga ctgctggggg aggcaggagg atgcctgcct   1080 

ggaccctgtt ggtggctgaa gacctctggc cagctggctt ccgcccttgg tggggaagca   1140 

gcagaactag gttctgagcc acgggtcagg gtgccaccct gctgctggcc ccactgtgtc   1200 

acagagctgc ctggcacagg tcccagcccc tctgcagaga cacaataaaa gccagcagac   1260 

cctttggacc gaccaaggct ggtggggaca ctgtgagggg accagggccc ctcagggatg   1320 

tagaaacagc ttggaggatg cctctgcccc accaggaggg gccccaggcc ctggcagggc   1380 

agagaaggaa ggggcttggc ttgggcctcc tggtcctacg ccatcactgc ccttgacaaa   1440 

tgattggtgt tgggaaagga cctggaagtg ccctgggacc tgggaaacat ttagctcaag   1500 

aagaccttgg agcaacatga tccctgtcct cagatgtctg gggacagtca ttgagcaagc   1560 

acagggaagt cagcttgttc tctctggcag cgctggaaga cagtcaacct gtgggtgggg   1620 

ggctgcaggg ggacaggccg cagccctgca ggaggccgtg ctccgcaatg gctgccctaa   1680 

gctgcatggg tcagacagct tcccgtctcg ggaggccaca gggcagggaa gctgcagagg   1740 

gcatgtggcc ctgggtaggg cagctgccct tcactcatgc ccctcccaag cagaggaggg   1800 

aagggcttta gtgagaattc tagctctgcc tctttgacct tgccaagtca ggatctgcct   1860 

cttaaaggag cagagaaaac catyccagat cccctcgaca cccagccccc taccactgac   1920 

agagcacaag tgagatctga rtgktagccc ttcaratttg ctgactggcc ttggcccacc   1980 

cctycctgtg ctgcagcttc attggcaaaa tgaatttgat ggtatctgta tcccctgccc   2040 

agccctaacc tgtttctctg aggctggcct ycctacgggg ctgcagcagc aaagggaagc   2100 

caagccttag agaagcctca tggaagggcc cagaacatcc tgcacccatc agttactcgg   2160 

aagtaagggg acaagaagca gctggaagag agctgggtgt gggggctggg argagtgctg   2220 

ragaaatttc cccatcagaa ggcccctcac tgggcagtgr aggcaggsca gtgtggtggg   2280 

actgactcaa cagacatagt ttcatctcca ccctgccctt ctcaggttgt gtgaccccag   2340 

ccacatggac acccgagtct gtgaactaaa gggctggtcc atggcattam cagtgraggg   2400 

tgtccaggtt cttgatgtct tgaacaaaga attgggcaaa atgcacaaag caaggaagga   2460 

atgaagggtt ttactgagaa tgaaagtata ctccacagca tgggagaggg cctgagcata   2520 

gggactcaag gggcccgtta cagaattttt gggagtaaat acccactaga ggattccatt   2580 

ggttacttga ggtacaccct atgtaaatgg aaaggatgaa gtaaatttac aaattcattt   2640 

acagcatata ccctatgggg aggatattcc ctgttatagc tgaagcgtga attggcctta   2700 

tgttccctgc ctccagaccc tattttcctg catcaacggg aaagggtcag attcactggc   2760 

tcagctgttt aacctgtcct ggtgccagca gctggagctg ggtgtcagga ccagcccgca   2820 

agctcttccc tgccggaagg accaggccag tcgctgtcct tttcatgcta gagagtggtt   2880 

gtggttgctg acttagcaga gaaggtgctt ggctttcccc ttaactggag aaaaaacttt   2940 

ctaagaacca ggcctggttg gcagcagacc tagctttctt ggggtggcag ggaggctaaa   3000 

gcatacctca ggacagtcag tggtgggtcc agcttcggct ggaggttctt tctactgaat   3060 

aacttctacg ggctctgtca ttagcaggat ttgtataatt tgaagcagag ctgggcaact   3120 

gcagagcaat ggggaagcca gcccagtgtg gtggcaagac ctgggcaact tgggaccagc   3180 

ctgggctgtc tcttgccagc tgttgttatc agaaccaggc tcttcacact cagatccttg   3240 

ggccccccat ctcagaatgc ccagtggtta aaaggatgaa acctggaatt taagtgactt   3300 

ctcagtgatg tgtgcccttc tctgacggtt ccttgttcat cccatgtatt tactgactgc   3360 

ctgctatata tgcagagcca aagagtgggg cctggtcttg aactatctcc tcatctgccc   3420 

cttctggcac ctccttcctc ctgggctctt tcctctaata ccgtcatcct ctctccaacc   3480 

tggttaatcc tgtcctttct gccctcaaat gggcaccttc aaaaaaaaaa aaaaaaaact   3540 

cga                                                                 3543 

 
           
             23  
             3522  
             DNA  
             Homo sapiens  
           
            23 

ggcacgaggt tggaccttcg agcctagctg ctcgcacagg actcggccac ctgcccttcc     60 

tgcaccgact ggccagctca agaggtttgg atatggacct tcttcaattc ctggccttcc    120 

tctttgtcct gcttttgtct gggatgggag ccacaggcac cttgaggacc tccctggacc    180 

caagcctgga gatctacaag aagatgtttg aggtgaagcg gcgggagcag ctgttggcac    240 

tgaagaacct ggcacagctg aacgacatcc accagcagta caagatcctt gatgtcatgc    300 

tcaaggggct ctttaaggtg ctggaggact cccggacagt gctcaccgct gctgatgtgc    360 

tcccagatgg gccctgcccc caggacgaga agctgaagga tgctttctcc cacgtggtgg    420 

agaacacggc cttcttcggc gatgtggtgc tgcgcttccc gaggattgtg cactattact    480 

ttgaccacaa ctccaactgg aacctcctca tccgctgggg tatcagtttc tgcaaccaga    540 

caggcgtctt caaccagggg ccccactcgc ccatcctcag cctgatggcc caggagctgg    600 

ggatcagtga gaaagactcc aacttccaga acccatttaa aatcgaccgc acagagttca    660 

ttcccagcac tgaccctttc cagaaggccc tgagagaaga agagaaacgc cgaaagaaag    720 

aggagaagcg gaaggagatc cgaaaaggcc caaggatctc cagatcccag tctgagttat    780 

agccctggag cagctcaggg ctcagggggc cacaaggagg cagatcggga ggaagaagag    840 

gtggaggtgt ggttgtggtg gagagcacca gctagcccct tccagaaggg gaggccacat    900 

ttgcccggcc ccctggagct gggtctgagc cccagctgaa gggactgagc ctcagatggc    960 

tggattttct ctcaggggcc tcctgctgaa ggggccttca gaggatttta tgctggaaat   1020 

atgaccctgt gcagactgct gggggaggca ggaggatgcc tgcctggacc ctgttggtgg   1080 

ctgaagacct ctggccagct ggcttccgcc cttggtgggg aagcagcaga actaggttct   1140 

gagccacggg tcagggtgcc accctgctgc tggccccact gtgtcacaga gctgcctggc   1200 

acaggtccca gcccctctgc agagacacaa taaaagccag cagacccttt ggaccgacca   1260 

aggctggtgg ggacactgtg aggggaccag ggcccctcag ggatgtagaa acagcttgga   1320 

ggatgcctct gccccaccag gaggggcccc aggccctggc agggcagaga aggaaggggc   1380 

ttggcttggg cctcctggtc ctacgccatc actgcccttg acaaatgatt ggtgttggga   1440 

aaggacctgg aagtgccctg ggacctggga aacatttagc tcaagaagac cttggagcaa   1500 

catgatccct gtcctcagat gtctggggac agtcattgag caagcacagg gaagtcagct   1560 

tgttctctct ggcagcgctg gaagacagtc aacctgtggg tggggggctg cagggggaca   1620 

ggccgcagcc ctgcaggagg ccgtgctccg caatggctgc cctaagctgc atgggtcaga   1680 

cagcttcccg tctcgggagg ccacagggca gggaagctgc agagggcatg tggccctggg   1740 

tagggcagct gcccttcact catgcccctc ccaagcagag gagggaaggg ctttagtgag   1800 

aattctagct ctgcctcttt gaccttgcca agtcaggatc tgcctcttaa aggagcagag   1860 

aaaaccatcc agatcccctc gacacccagc cccctaccac tgacagagca caagtgagat   1920 

ctgagtgtta gcccttcaga tttgctgact ggccttggcc cacccctccc tgtgctgcag   1980 

cttcattggc aaaatgaatt tgatggtatc tgtatcccct gcccagccct aacctgtttc   2040 

tctgaggctg gcctccctac ggggctgcag cagcaaaggg aagccaagcc ttagagaagc   2100 

ctcatggaag ggcccagaac atcctgcacc catcagttac tcggaagtaa ggggacaaga   2160 

agcagctgga agagagctgg gtgtgggggc tgggaggagt gctggagaaa tttccccatc   2220 

agaaggcccc tcactgggca gtggaggcag ggcagtgtgg tgggactgac tcaacagaca   2280 

tagtttcatc tccaccctgc ccttctcagg ttgtgtgacc ccagccacat ggacacccga   2340 

gtctgtgaac taaagggctg gtccatggca ttaacagtgg agggtgtcca ggttcttgat   2400 

gtcttgaaca aagaattggg caaaatgcac aaagcaagga aggaatgaag ggttttactg   2460 

agaatgaaag tatactccac agcatgggag agggcctgag catagggact caaggggccc   2520 

gttacagaat ttttgggagt aaatacccac tagaggattc cattggttac ttgaggtaca   2580 

ccctatgtaa atggaaagga tgaagtaaat ttacaaattc atttacagca tataccctat   2640 

ggggaggata ttccctgtta tagctgaagc gtgaattggc cttatgttcc ctgcctccag   2700 

accctatttt cctgcatcaa cgggaaaggg tcagattcac tggctcagct gtttaacctg   2760 

tcctggtgcc agcagctgga gctgggtgtc aggaccagcc cgcaagctct tccctgccgg   2820 

aaggaccagg ccagtcgctg tccttttcat gctagagagt ggttgtggtt gctgacttag   2880 

cagagaaggt gcttggcttt ccccttaact ggagaaaaaa ctttctaaga accaggcctg   2940 

gttggcagca gacctagctt tcttggggtg gcagggaggc taaagcatac ctcaggacag   3000 

tcagtggtgg gtccagcttc ggctggaggt tctttctact gaataacttc tacgggctct   3060 

gtcattagca ggatttgtat aatttgaagc agagctgggc aactgcagag caatggggaa   3120 

gccagcccag tgtggtggca agacctgggc aacttgggac cagcctgggc tgtctcttgc   3180 

cagctgttgt tatcagaacc aggctcttca cactcagatc cttgggcccc ccatctcaga   3240 

atgcccagtg gttaaaagga tgaaacctgg aatttaagtg acttctcagt gatgtgtgcc   3300 

cttctctgac ggttccttgt tcatcccatg tatttactga ctgcctgcta tatatgcaga   3360 

gccaaagagt ggggcctggt cttgaactat ctcctcatct gccccttctg gcacctcctt   3420 

cctcctgggc tctttcctct aataccgtca tcctctctcc aacctggtta atcctgtcct   3480 

ttctgccctc aaatgggcac cttcaaaaaa aaaaaaaaaa aa                      3522 

 
           
             24  
             1969  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (996)..(996)  
               n equals a,t,g, or c  
             
           
            24 

ccacgcgtcc gcgcgcggag ggcgcctggt gcagcatggg cggcccgcgg gcttgggcgc     60 

tgctctgcct cgggctcctg ctcccgggag gcggcgctgc gtggagcatc ggggcagctc    120 

cgttctccgg acgcaggaac tggtgctcct atgtggtgac ccgcaccatc tcatgccatg    180 

tgcagaatgg cacctacctt cagcgagtgc tgcagaactg cccctggccc atgagctgtc    240 

cggggagcag ctacagaact gtggtgagac ccacatacaa ggtgatgtac aagatagtga    300 

ccgcccgtga gtggaggtgc tgccctgggc actcaggagt gagctgcgag gaagttgcag    360 

cttcctctgc ctccttggag cccatgtggt cgggcagtac catgcggcgg atggcgcttc    420 

ggcccacagc cttctcaggt tgtctcaact gcagcaaagt gtcagagctg acagagcggc    480 

tgaaggtgct ggaggccaag atgaccatgc tgactgtcat agagcagcca gtacctccaa    540 

caccagctac ccctgaggac cctgccccgc tctggggtcc ccctcctgcc cagggcagcc    600 

ccggagatgg aggcctccag gaccaagtcg gtgcttgggg gcttcccggg cccaccggcc    660 

ccaagggaga tgccggcagt cggggcccaa tggggatgag aggcccacca ggtccacagg    720 

gccccccagg gagccctggc cgggctggag ctgtgggcac ccctggagag aggggacctc    780 

ctgggccacc agggcctcct ggcccccctg ggcccccagc ccctgttggg ccaccccatg    840 

cccggatctc ccagcatgga gacccattgc tgtccaacac cttcactgag accaacaacc    900 

actggcccca gggacccact gggcctccag gccctccagg gcccatgggt ccccctgggc    960 

ctcctggccc cacaggtgtc cctgggagtc ctggtnacat aggaccccca ggccccactg   1020 

gacccaaagg aatctctggn cacccaggag agaagggnga gaagaaanga ctgcgtgggg   1080 

agcctggccc ccaaggctct gctgggcagc ggggggaacc tggccctaag ggagaccctg   1140 

gtgagaagag ccactggaac cagagctggg gtctgggcgg gccctgccgg cacaggcacc   1200 

cccagcctcc ttcggggcaa gagggcggac atgcaaccaa ctaccgggat cgtggccccc   1260 

aggagccggg acgagagagg ctgagggtgg tggcggcccc tgaggcagac caggccaggc   1320 

ttcccctcct acctggactc ggccagctgc ctccagggac cgcccgtcca tatttattaa   1380 

tgtcctcagg gtcccttctg ccatctaggc cttaggggta agcaggtctc agtcctggca   1440 

ccatgcacat gtctgaggct gagcaagggc tgagaggaga ggcttgggcc tcagtttccc   1500 

tctgtgaagt ggggggaggc aggccttcaa ggagggatag aggtacaagg cttcgtctca   1560 

tctgctgtct gagcatccag gcccaaaggc actgagggag tcaggagctg gggctcggca   1620 

catgcagaga tgacagggca gggggcagtc ttcctccccc tccccgacca aacctcgggg   1680 

agccctcctg tgcccctccc tccttgttgt ccagtgctgg gttccccacc ccgaggtcag   1740 

gctgcccaat cctctgactg gatcaccggg ggcttcttgc ctcagttctt ccctctgagc   1800 

ccccaggccc tcccgcatct caggttgggg atggggacat ggagaggaag gggccgccta   1860 

ctcctgcaaa tgcttgtgac agatgccagg aggtagatgt gtgctggcca ataaaggccc   1920 

ctacctgatt ccccgcaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaa               1969 

 
           
             25  
             2189  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (2)..(2)  
               n equals a,t,g, or c  
             
           
            25 

gnancgnggt acgactcact atagggaaag ctggtacgcc tgcaggtacc ggtccggaat     60 

tcccgggtcg acccacgcgt ccgcgcgcgg agggcgcctg gtgcagcatg ggcggcccgc    120 

gggcttgggc gctgctctgc ctcgggctcc tgctcccggg aggcggcgct gcgtggagca    180 

tcggggcagc tccgttctcc ggacgcagga actggtgctc ctatgtggtg acccgcacca    240 

tctcatgcca tgtgcagaat ggcacctacc ttcagcgagt gctgcagaac tgcccctggc    300 

ccatgagctg tccggggagc agctacagaa ctgtggtgag acccacatac aaggtgatgt    360 

acaagatagt gaccgcccgt gagtggaggt gctgccctgg gcactcagga gtgagctgcg    420 

aggaagttgc agcttcctct gcctccttgg agcccatgtg gtcgggcagt accatgcggc    480 

ggatggcgct tcggcccaca gccttctcag gttgtctcaa ctgcagcaaa gtgtcagagc    540 

tgacagagcg gctgaaggtg ctggaggcca agatgaccat gctgactgtc atagagcagc    600 

cagtacctcc aacaccagct acccctgagg accctgcccc gctctggggt ccccctcctg    660 

cccagggcag ccccggagat ggaggcctcc aggaccaagt cggtgcttgg gggcttcccg    720 

ggcccaccgg ccccaaggga gatgccggca gtcggggccc aatggggatg agaggcccac    780 

caggtccaca gggcccccca gggagccctg gccgggctgg agctgtgggc acccctggag    840 

agaggggacc tcctgggcca ccagggcctc ctggcccccc tgggccccca gcccctgttg    900 

ggccacccca tgcccggatc tcccagcatg gagacccatt gctgtccaac accttcactg    960 

agaccaacaa ccactggccc cagggaccca ctgggcctcc aggccctcca gggcccatgg   1020 

gtccccctgg gcctcctggc cccacaggtg tccctgggag tcctggtcac ataggacccc   1080 

caggccccac tggacccaaa ggaatctctg gccacccagg agagaagggc gagagaggac   1140 

tgcgtgggga gcctggcccc caaggctctg ctgggcagcg gggggaacct ggccctaagg   1200 

gagaccctgg tgagaagagc cactgggggg aggggttgca ccagctacgc gaggctttga   1260 

agattttagc tgagagggtt ttaatcttgg aaacaatgat tgggctctat gaaccagagc   1320 

tggggtctgg ggcgggccct gccggcacag gcacccccag cctccttcgg ggcaagaggg   1380 

gcggacatgc aaccaactac cggatcgtgg cccccaggag ccgggacgag agaggctgag   1440 

ggtggtggcg gcccctgagg cagaccaggc caggcttccc ctcctacctg gactcggcca   1500 

gctgcctcca gggaccgccc gtccatattt attaatgtcc tcagggtccc ttctgccatc   1560 

taggccttag gggtaagcag gtctcagtcc tggcaccatg cacatgtctg aggctgagca   1620 

agggctgaga ggagaggctt gggcctcagt ttccctctgt gaagtggggg gaggcaggcc   1680 

ttcaaggagg gatagaggta caaggcttcg tctcatctgc tgtctgagca tccaggccca   1740 

aaggcactga gggagtcagg agctggggct cggcacatgc agagatgaca gggcaggggg   1800 

cagtcttcct ccccctcccc gaccaaacct cggggagccc tcctgtgccc ctccctcctt   1860 

gttgtccagt gctgggttcc ccaccccgag gtcaggctgc ccaatcctct gactggatca   1920 

ccgggggctt cttgcctcag ttcttccctc tgagccccca ggccctcccg catctcaggt   1980 

tggggatggg gacatggaga ggaaggggcc gcctactcct gcaaatgctt gtgacagatg   2040 

ccaggaggta gatgtgtgct ggccaataaa ggcccctacc tgattccccg caaaaaaaaa   2100 

aaaaaaaaaa aaaaaaaaaa aaaagggcgg ccgctctaga ggatccaagc ttacgtacgc   2160 

gtgcaygcgr gtcatagctc ttctatagc                                     2189 

 
           
             26  
             1236  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (1)..(1)  
               n equals a,t,g, or c  
             
           
            26 

ncgggnggca gaangaaaat ataaagnaaa ttttcctgng cattcggcac ctaccctcag     60 

cgagtgctgc agaactgccc ctggcccatg agctgtccgg ggagcatcta cagaactgtg    120 

gtgagaccca catacaaggt gatgtacaag atagtgaccg cccgtgagtg gaggtgctgc    180 

cctgggcact caggagtgag ctgcgaggaa gttgcagctt cctctgcctc cttggagccc    240 

atgtggtcgg gcagtaccat gcggcggatg gcgcttcggc ccacagcctt ctcaggttgt    300 

ctcaactgca gcaaagtgtc agagctgaca gagcggctga aggtgctgga ggccaagatg    360 

accatgctga ctgtcataga gcagccagta cctccaacac cagctacccc tgaggaccct    420 

gccccgctct ggggtccccc tcctgcccag ggcagccccg gagatggagg cctccaggac    480 

caagtcggtg cttgggggct tcccgggccc accggcccca agggagatgc cggcagtcgg    540 

ggcccaatgg ggatgagagg cccaccaggt ccacagggcc ccccagggag ccctggccgg    600 

gctggagctg tgggcacccc tggagagagg ggacctcckg ggccaccagg gcctcctggc    660 

ccccctgggc ccccagcccc tgttgggcca ccccatgccc ggatctccca gcatggagac    720 

ccattgctgt ccaacacctt cactgagacc aacaaccact ggccccaggg acccactggg    780 

cctccaggcc ctccagggcc catgggtccc cctgggcctc ctggccccac aggtgtccct    840 

gggagtcctg gtcacatagg acccccaggc cccactggac ccaaaggaat ctctggccac    900 

ccaggagaga agggcgagag aggactgcgt ggggagcctg gcccccaagg ctctgctggg    960 

cagcgggggg aacctggccc taagggagac cctggtgaga agagccactg ggctcctagc   1020 

ttacagagct tcctgcagca gcaggctcag ctggagctcc tggccagamg ggtcamcctc   1080 

ctggaagcca tcatctggcc agaaccagag ctgggggtct ggggcggccc tgccggcama   1140 

ggacccccag cytcttcggg gcaagagggg cggacatgca accaaactac cggatcgtgg   1200 

gccccaagaa cccgggacga agagaagctn annggn                             1236 

 
           
             27  
             832  
             DNA  
             Homo sapiens  
           
            27 

ctgctgggca gcggggggaa cctggcccta aggaagaccc tggtgagaag accctggaac     60 

cagagctggg gtctggggcg ggccctgccg gcacaggcac ccccagcctc cttcggggca    120 

agaggggcgg acatgcaacc aactaccgga tcgtggcccc caggagccgg gacgagagag    180 

gctgagggtg gtggcggccc ctgaggcaga ccaggccagg cttcccctcc tacctggact    240 

cggccagctg cctccaggga ccgcccgtcc atatttatta atgtcctcag ggtcccttct    300 

gccatctagg ccttaggggt aagcaggtct cagtcctggc accatgcaca tgtctgaggc    360 

tgagcaaggg ctgagaggag aggcttgggc ctcagtttcc ctctgtgaag tggggggagg    420 

caggccttca aggagggata gaggtacaag gcttcgtctc atctgctgtc tgagcatcca    480 

ggcccaaagg cactgaggga gtcaggagct ggggctcggc acatgcagag atgacagggc    540 

agggggcagt cttcctcccc ctccccgacc aaacctcggg gagccctcct gtgcccctcc    600 

ctccttgttg tccagtgctg ggttccccac cccgaggtca ggctgcccaa tcctctgact    660 

ggatcaccgg gggcttcttg cctcagttct tccctctgag cccccaggcc ctcccgcatc    720 

tcaggttggg gatggggaca tggagaggaa ggggccgcct actcctgcaa atgcttgtga    780 

cagatgccag gaggtagatg ctgtctctta tacacatctc aaccatcatc ga            832 

 
           
             28  
             1967  
             DNA  
             Homo sapiens  
           
            28 

ccacgcgtcc gcgcgcggag ggcgcctggt gcagcatggg cggcccgcgg gcttgggcgc     60 

tgctctgcct cgggctcctg ctcccgggag gcggcgctgc gtggagcatc ggggcagctc    120 

cgttctccgg acgcaggaac tggtgctcct atgtggtgac ccgcaccatc tcatgccatg    180 

tgcagaatgg cacctacctt cagcgagtgc tgcagaactg cccctggccc atgagctgtc    240 

cggggagcag ctacagaact gtggtgagac ccacatacaa ggtgatgtac aagatagtga    300 

ccgcccgtga gtggaggtgc tgccctgggc actcaggagt gagctgcgag gaagttgcag    360 

cttcctctgc ctccttggag cccatgtggt cgggcagtac catgcggcgg atggcgcttc    420 

ggcccacagc cttctcaggt tgtctcaact gcagcaaagt gtcagagctg acagagcggc    480 

tgaaggtgct ggaggccaag atgaccatgc tgactgtcat agagcagcca gtaccttcaa    540 

caccagctac ccctgaggac cctgccccgc tctggggtcc ccctcctgcc cagggcagcc    600 

ccggagatgg aggcctccag gaccaagtcg gtgcttgggg gcttcccggg cccaccggcc    660 

ccaagggaga tgccggcagt cggggcccaa tggggatgag aggcccacca ggtccacagg    720 

gccccccagg gagccctggc cgggctggag ctgtgggcac ccctggagag aggggacctc    780 

ctgggccacc agggcctcct ggcccccctg ggcccccagc ccctgttggg ccaccccatg    840 

cccggatctc ccagcatgga gacccattgc tgtccaacac cttcactgag accaacaacc    900 

actggcccca gggacccact gggcctccag gccctccagg gcccatgggt ccccctgggc    960 

ctcctggccc cacaggtgtc cctgggagtc ctggtcacat aggaccccca ggccccactg   1020 

gacccaaagg aatctctggc cacccaggag agaagggcga gagaggactg cgtggggagc   1080 

ctggccccca aggctctgct gggcagcggg gggaacctgg ccctaaggga gaccctggtg   1140 

agaagagcca ctggaaccag agctggggtc tggggcgggc cctgccggca caggcacccc   1200 

cagcctcctt cggggcaaga ggggcggaca tgcaaccaac taccggatcg tggcccccag   1260 

gagccgggac gagagaggct gagggtggtg gcggcccctg aggcagacca ggccaggctt   1320 

cccctcctac ctggactcgg ccagctgcct ccagggaccg cccgtccata tttattaatg   1380 

tcctcagggt cccttctgcc atctaggcct taggggtaag caggtctcag tcctggcacc   1440 

atgcacatgt ctgaggctga gcaagggctg agaggagagg cttgggcctc agtttccctc   1500 

tgtgaagtgg ggggaggcag gccttcaagg agggatagag gtacaaggct tcgtctcatc   1560 

tgctgtctga gcatccaggc ccaaaggcac tgagggagtc aggagctggg gctcggcaca   1620 

tgcagagatg acagggcagg gggcagtctt cctccccctc cccgaccaaa cctcggggag   1680 

ccctcctgtg cccctccctc cttgttgtcc agtgctgggt tccccacccc gaggtcaggc   1740 

tgcccaatcc tctgactgga tcaccggggg cttcttgcct cagttcttcc ctctgagccc   1800 

ccaggccctc ccgcatctca ggttggggat ggggacatgg agaggaaggg gccgcctact   1860 

cctgcaaatg cttgtgacag atgccaggag gtagatgtgt gctggccaat aaaggcccct   1920 

acctgattcc ccgcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa                 1967 

 
           
             29  
             1967  
             DNA  
             Homo sapiens  
           
            29 

ccacgcgtcc gcgcgcggag ggcgcctggt gcagcatggg cggcccgcgg gcttgggcgc     60 

tgctctgcct cgggctcctg ctcccgggag gcggcgctgc gtggagcatc ggggcagctc    120 

cgttctccgg acgcaggaac tggtgctcct atgtggtgac ccgcaccatc tcatgccatg    180 

tgcagaatgg cacctacctt cagcgagtgc tgcagaactg cccctggccc atgagctgtc    240 

cggggagcag ctacagaact gtggtgagac ccacatacaa ggtgatgtac aagatagtga    300 

ccgcccgtga gtggaggtgc tgccctgggc actcaggagt gagctgcgag gaagttgcag    360 

cttcctctgc ctccttggag cccatgtggt cgggcagtac catgcggcgg atggcgcttc    420 

ggcccacagc cttctcaggt tgtctcaact gcagcaaagt gtcagagctg acagagcggc    480 

tgaaggtgct ggaggccaag atgaccatgc tgactgtcat agagcagcca gtacctccaa    540 

caccagctac ccctgaggac cctgccccgc tctggggtcc ccctcctgcc cagggcagcc    600 

ccggagatgg aggcctccag gaccaagtcg gtgcttgggg gcttcccggg cccaccggcc    660 

ccaagggaga tgccggcagt cggggcccaa tggggatgag aggcccacca ggtccacagg    720 

gccccccagg gagccctggc cgggctggag ctgtgggcac ccctggagag aggggacctc    780 

ctgggccacc agggcctcct ggcccccctg ggcccccagc ccctgttggg ccaccccatg    840 

cccggatctc ccagcatgga gacccattgc tgtccaacac cttcactgag accaacaacc    900 

actggcccca gggacccact gggcctccag gccctccagg gcccatgggt ccccctgggc    960 

ctcctggccc cacaggtgtc cctgggagtc ctggtcacat aggaccccca ggccccactg   1020 

gacccaaagg aatctctggc cacccaggag agaagggcga gagaggactg cgtggggagc   1080 

ctggccccca aggctctgct gggcagcggg gggaacctgg ccctaaggga gaccctggtg   1140 

agaagagcca ctggaaccag agctggggtc tggggcgggc cctgccggca caggcacccc   1200 

cagcctcctt cggggcaaga ggggcggaca tgcaaccaac taccggatcg tggcccccag   1260 

gagccgggac gagagaggct gagggtggtg gcggcccctg aggcagacca ggccaggctt   1320 

cccctcctac ctggactcgg ccagctgcct ccagggaccg cccgtccata tttattaatg   1380 

tcctcagggt cccttctgcc atctaggcct taggggtaag caggtctcag tcctggcacc   1440 

atgcacatgt ctgaggctga gcaagggctg agaggagagg cttgggcctc agtttccctc   1500 

tgtgaagtgg ggggaggcag gccttcaagg agggatagag gtacaaggct tcgtctcatc   1560 

tgctgtctga gcatccaggc ccaaaggcac tgagggagtc aggagctggg gctcggcaca   1620 

tgcagagatg acagggcagg gggcagtctt cctccccctc cccgaccaaa cctcggggag   1680 

ccctcctgtg cccctccctc cttgttgtcc agtgctgggt tccccacccc gaggtcaggc   1740 

tgcccaatcc tctgactgga tcaccggggg cttcttgcct cagttcttcc ctctgagccc   1800 

ccaggccctc ccgcatctca ggttggggat ggggacatgg agaggaaggg gccgcctact   1860 

cctgcaaatg cttgtgacag atgccaggag gtagatgtgt gctggccaat aaaggcccct   1920 

acctgattcc ccgcaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa                 1967 

 
           
             30  
             2006  
             DNA  
             Homo sapiens  
           
            30 

ccacgcgtcc gcgcgcggag ggcgcctggt gcagcatggg cggcccgcgg gcttgggcgc     60 

tgctctgcct cgggctcctg ctcccgggag gcggcgctgc gtggagcatc ggggcagctc    120 

cgttctccgg acgcaggaac tggtgctcct atgtggtgac ccgcaccatc tcatgccatg    180 

tgcagaatgg cacctacctt cagcgagtgc tgcagaactg cccctggccc atgagctgtc    240 

cggggagcag ctacagaact gtggtgagac ccacatacaa ggtgatgtac aagatagtga    300 

ccgcccgtga gtggaggtgc tgccctgggc actcaggagt gagctgcgag gaagttgcag    360 

cttcctctgc ctccttggag cccatgtggt cgggcagtac catgcggcgg atggcgcttc    420 

ggcccacagc cttctcaggt tgtctcaact gcagcaaagt gtcagagctg acagagcggc    480 

tgaaggtgct ggaggccaag atgaccatgc tgactgtcat agagcagcca gtacctccaa    540 

caccagctac ccctgaggac cctgccccgc tctggggtcc ccctcctgcc cagggcagcc    600 

ccggagatgg aggcctccag gaccaagtcg gtgcttgggg gcttcccggg cccaccggcc    660 

ccaagggaga tgccggcagt cggggcccaa tggggatgag aggcccacca ggtccacagg    720 

gccccccagg gagccctggc cgggctggag ctgtgggcac ccctggagag aggggacctc    780 

ctgggccacc agggcctcct ggcccccctg ggcccccagc ccctgttggg ccaccccatg    840 

cccggatctc ccagcatgga gacccattgc tgtccaacac cttcactgag accaacaacc    900 

actggcccca gggacccact gggcctccag gccctccagg gcccatgggt ccccctgggc    960 

ctcctggccc cacaggtgtc cctgggagtc ctggtcacat aggaccccca ggccccactg   1020 

gacccaaagg aatctctggc cacccaggag agaagggcga gagaggactg cgtggggagc   1080 

ctggccccca aggctctgct gggcagcggg gggaacctgg ccctaaggga gaccctggtg   1140 

agaagagcca ctggaaccag agctggggtc tgggcgggcc ctgccggcac aggcaccccc   1200 

agcctccttc ggggcaagag ggcggacatg caaccaacta ccgggatcgt ggcccccagg   1260 

agccgggacg agagaggctg agggtggtgg cggcccctga ggcagaccag gccaggcttc   1320 

ccctcctacc tggactcggc cagctgcctc cagggaccgc ccgtccatat ttattaatgt   1380 

cctcagggtc ccttctgcca tctaggcctt aggggtaagc aggtctcagt cctggcacca   1440 

tgcacatgtc tgaggctgag caagggctga gaggagaggc ttgggcctca gtttccctct   1500 

gtgaagtggg gggaggcagg ccttcaagga gggatagagg tacaaggctt cgtctcatct   1560 

gctgtctgag catccaggcc caaaggcact gagggagtca ggagctgggg ctcggcacat   1620 

gcagagatga cagggcaggg ggcagtcttc ctccccctcc ccgaccaaac ctcggggagc   1680 

cctcctgtgc ccctccctcc ttgttgtcca gtgctgggtt ccccaccccg aggtcaggct   1740 

gcccaatcct ctgactggat caccgggggc ttcttgcctc agttcttccc tctgagcccc   1800 

caggccctcc cgcatctcag gttggggatg gggacatgga gaggaagggg ccgcctactc   1860 

ctgcaaatgc ttgtgacaga tgccaggagg tagatgtgtg ctggccaata aaggccccta   1920 

cctgattccc cgcaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   1980 

aaaaaaaaaa aaaaaaaaaa aaaaaa                                        2006 

 
           
             31  
             897  
             DNA  
             Homo sapiens  
           
            31 

ccacgcgtcc gccgcccggg ctgctgcagg gtctgagccc cggacagggt gtggtggtag     60 

ctcccaccgg gtcccactgg gcccctcacc tgcttctctc tccccccagc gggatctctt    120 

cggtccccca ggacctccag gtgcagaagt gaccgcggag actctgcttc acgagtttca    180 

ggagctgctg aaagaggcca cggagcgccg gttctcaggg cttctggacc cgctgctgcc    240 

ccagggggcg ggcctgcggc tggtgggcga ggcctttcac tgccggctgc agggtccccg    300 

ccgggtggac aagcggacgc tggtggagct gcatggtttc caggctcctg ctgcccaagg    360 

tgccttcctg cgaggctccg gtctgagcct ggcctcgggt cggttcacgg cccccgtgtc    420 

cggcatcttc cagttctctg ccagtctgca cgtggaccac agtgagctgc agggcaaggc    480 

ccggctgcgg gcccgggacg tggtgtgtgt tctcatctgt attgagtccc tgtgccagcg    540 

ccacacgtgc ctggaggccg tctcaggcct ggagagcaac agcagggtct tcacgctaca    600 

ggtgcagggg ctgctgcagc tgcaggctgg acagtacgct tctgtgtttg tggacaatgg    660 

ctccggggcc gtcctcacca tccaggcggg ctccagcttc tccgggctgc tcctgggcac    720 

gtgagggcgc ccaggggggc tggcgaggag ctgccgccgg atcccgggga ccctcctact    780 

gatgcccgtg gtcaccacaa taaagagccc tccaccctca aaaaaaaaaa aaaaaaaaaa    840 

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaa       897 

 
           
             32  
             990  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (751)..(751)  
               n equals a,t,g, or c  
             
           
            32 

ggggaactgc agtgacagca ggagtaagag tgggaggcag gacagagctg ggacacaggt     60 

atggagaggg ggttcagcga gcctagagag ggcagactat cagggtgccg gcggtgagaa    120 

tccagggaga ggagcggaaa cagaagaggg gcagaagacc ggggcacttg tgggttgcag    180 

agcccctcag ccatgttggg agccaagcca cactggctac caggtcccct acacagtccc    240 

gggctgccct tggttctggt gcttctggcc ctgggggccg ggtgggccca ggaggggtca    300 

gagcccgtcc tgctggaggg ggagtgcctg gtggtctgtg agcctggccg agctgctgca    360 

ggggggcccg ggggagcagc cctgggagag gcaccccctg ggcgagtggc atttgytgcg    420 

gtccgaagcc accaccatga gccagcaggg gaaaccggca atggcaccag tggggccatc    480 

tacttcgacc aggtcctggt gaacgagggc ggtggctttg accgggcctc tggctccttc    540 

gtagcccctg tccggggtgt ctacagcttc cggttccatg tggtgaaggt gtacaaccgc    600 

caaactgtcc aggtgagcct gatgctgaac acgtggcctg tcatctcagc ctttgccaat    660 

gatcctgacg tgacccggga ggcagccacc agctctgtgc tactgccctt ggaccctggg    720 

gaccgagtgt ctctgcgcct gcgtcggggg naatctactg ggtggttgga aatactcaag    780 

tttctctggc ttcctcatct tccctctctg aaggacccaa gtctttcaag cacaagaatc    840 

cagcccctga caactttctt ctgccctctc ttgccccana aacagcanaa gcagganana    900 

nactccctct ggctcctatc ccacctcttt gcatgggaac ctgtgccaaa cacccaagtt    960 

taagaaaaaa ataaaactgt ggcatctcca                                     990 

 
           
             33  
             1384  
             DNA  
             Homo sapiens  
           
            33 

tcgagttttt tttttttttt tttgaccacc attctctagt tgttttattg atagattcat     60 

ccaggctggg ccaatgggac agcgggataa gaaagagaga gggagggttt agcatactgg    120 

caggagaggg tctgaaggaa tgaatcatgg aatcccaggt aataggaagc ctaaggagga    180 

gaataagaca gcacagatca ggagaaagag agatagtggg gatatgctgg aacaggtaca    240 

gtgaarataa ctcagtgaga gagctgggag gaaggaggca gcagtcagag tktggaggga    300 

ctaaagttca aacttcaaag gtggacagtt tcaggaggtg gccaagcaag argatgcatg    360 

gttatcsatg ttttccatgg tccacttcca gctctgtata cctgccwcag ytytrytytt    420 

ytcttaaact tgggtgtttg gcacaggktc ccatgcaaag argtgggata ggarccagag    480 

ggagtctctc tcctgcctct gctgtttctg gggcaagaga gggcagaaga aagttgtcag    540 

gggctggatt cttgtgcttg aaaracttgg gtcctcagag agggaagatg aggaagccag    600 

agaaacttga gtatttccaa ccacccagta gattcccccg acgcaggcgc agagacactc    660 

ggtccccagg gtccaagggc agtagcacag agctggtggc tgcctcccgg gtcacgtcag    720 

gatcattggc aaaggctgag atgacaggcc acgtgttcag catcaggctc acctggacag    780 

tttggcggtt gtacaccttc accacatgga accggaagct gtagacaccc cggacagggg    840 

ctacgaagga gccagaggcc cggtcaaagc caccgccctc gttcaccagg acctggtcga    900 

agtagatggc cccamtggtg ccattgccgg tttcccctgc tggctcatgg tgktggcttc    960 

ggaccgcagc aaatgccact cgcccagggg gtgcctctcc cagggctgct cccccgggcc   1020 

cccctgcagc agctcggcca ggctcacaga ccaccaggca ctccccctcc agcaggacgg   1080 

gctctgaccc ctcctgggcc cacccggccc ccagggccag aagcaccaga accaagggca   1140 

gcccgggact gtgtagggga cctggtagcc agtgtggctt ggctcccaac atggctgagg   1200 

ggctctgcaa cccacaagtg ccccggtctt ctgcccctct tctgtttccg ctcctctccc   1260 

tggattctca ccgccggcac cctgatagtc tgccctctct aggctcgctg aaccccctct   1320 

ccatacctgt gtcccagctc tgtcctgcct cccactctta ctcctgctgt cactgcagtt   1380 

cccc                                                                1384 

 
           
             34  
             809  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (307)..(307)  
               n equals a,t,g, or c  
             
           
            34 

cgcctgctgc cccgtgcggg cgcagaacga cacggagccc atcgtgctgg agggcaagtg     60 

cctggtggtg tgcgactcca gcccgtcggc ggacggcgcc gtcacctcct ccctaggcat    120 

ctccgtgcgc tccggcagcg ccaaggtggc cttctccgcc acgcggagca ccaaccacga    180 

gccgtccgag atgagcaacc gcaccatgac catctatttc gaccaggtat tagtaaatat    240 

tggcaaccac tttgatcttg cttccagtat atttgtagca ccgagaaaag ggatttatag    300 

cttcagnttc cacgtggtca aagtgtataa cagacaaacc atccaggtca gtttaatgca    360 

gaatggctac ccagtgatct cggcctttgc aggagaccag gatgtcacca gagaagctgc    420 

tagcaatggc gtgctgctgc tcatggaaag ggaagacaaa gtgcatctca aacttgagag    480 

aggcaacctc atggggggct ggaaatactc cacattctcg ggcttcttgg tgtttcctct    540 

ataaacacag agccccctag atggtggggg aatggcaaac tggacccagg actccgccct    600 

ttaaaacacc ctggaactta ctggaattgg acaccttgtt tccaacctcc gttcagactg    660 

tttgcagtag gaaggaatga tttcctttgg aaacctccag tacttttgtt ttgttttttg    720 

ggattattga catttcctcg ggaaccgggc ntttanttag tttttagatg gacaaggtct    780 

ttaagggaga attgaatttt tcgntttga                                      809 

 
           
             35  
             1215  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (1212)..(1212)  
               n equals a,t,g, or c  
             
           
            35 

gcggccgcag ctccagctcc cggtgtccgg gactcgggtc tcccgccagg gggcgccact     60 

ccccgcgctt tgcagccctg agcgggggag gggcccaggc ggcgggagcc cccttggcca    120 

gccccccaga tctgccctgc gggaaggggt ggaggaggta cccgtgcggg aggaggcgct    180 

ggccgaagct caggcagggg cggggagggg tacggtgacc ttagagtcgc cgccccgctg    240 

cgggctgagc cgccgctact ctcamcctgc cgccccgctt accccgcagg actgccggga    300 

cctcgagggg accccgggcc gcgaggagag gcgggacccg cggggcccac cgggcctgcc    360 

ggggagtgct cggtgcctcc gcgatccgcc ttcagcgcca agcgctccga gagccgggtg    420 

cctccgccgt ctgacgcacc cttgcccttc gaccgcgtgc tggtgaacga gcagggacat    480 

tacgacgccg tcaccggcaa gttcacctgc caggtgcctg gggtctacta cttcgccgtc    540 

catgccaccg tctaccgggc cagcctgcag tttgatctgg tgaagaatgg cgaatccatt    600 

gcctctttct tccagttttt cggggggtgg cccaagccag cctcgctctc ggkgggggcc    660 

atggtgaggc tggagcctga ggaccaagtg tgggtgcagg tgggtgtggg tgactacatt    720 

ggcatctatg ccagcatcaa gacagacagc accttctccg gatttctggt gtactccgac    780 

tggcacagct ccccagtctt tgcttagtgc ccactgcaaa gtgagctcat gctctcactc    840 

ctagaaggag ggtgtgaggc tgacaaccag gtcatccagg agggctggcc cccctggaat    900 

attgtgaatg actagggagg tggggtagag cactctccgt cctgctgctg gcaaggaatg    960 

ggaacagtgg ctgtctgcga tcaggtctgg cagcatgggg cagtggctgg atttctgccc   1020 

aagaccagag gagtgtgctg tgctggcaag tgtaagtccc ccagttgctc tggtccagga   1080 

gcccacggtg gggtgctctc ttcctggtcc tctgcttctc tggatcctcc ccaccccctc   1140 

ctgctcctgg ggccggccct tttctcagag atcactcaat aaacctaaga accctcaaaa   1200 

aaaaaaaaaa anggg                                                    1215 

 
           
             36  
             1311  
             DNA  
             Homo sapiens  
           
            36 

ggtcgaccca cgcgtccgca ctcagacacc gtgtcctctt gcctgggaga ggggaagcag     60 

atctgaggac atctctgtgc caggccagaa accgcccacc tgcagttcct tctccgggat    120 

ggacgtgggg cccagctccc tgccccacct tgggctgaag ctgctgctgc tcctgctgct    180 

gctgcccctc aggggccaag ccaacacagg ctgctacggg atcccaggga tgcccggcct    240 

gcccggggca ccagggaagg atgggtacga cggactgccg gggcccaagg gggagccagg    300 

aatcccagcc attcccggga tccgaggacc caaagggcag aagggagaac ccggcttacc    360 

cggccatcct gggaaaaatg gccccatggg accccctggg atgccagggg tgcccggccc    420 

catgggcatc cctggagagc caggtgagga gggcagatac aagcagaaat tccagtcagt    480 

gttcacggtc actcggcaga cccaccagcc ccctgcaccc aacagcctga tcagattcaa    540 

cgcggtcctc accaacccgc agggagatta tgacacgagc actggcaagt tcacctgcaa    600 

agtccccggc ctctactact ttgtctacca cgcgtcgcat acagccaacc tgtgcgtgct    660 

gctgtaccgc agcggcgtca aagtggtcac cttctgtggc cacacgtcca aaaccaatca    720 

ggtcaactcg ggcggtgtgc tgctgaggtt gcaggtgggc gaggaggtgt ggctggctgt    780 

caatgactac tacgacatgg tgggcatcca gggctctgac agcgtcttct ccggcttcct    840 

gctcttcccc gactagggcg ggcagatgcg ctcgagcccc acgggccttc cacctccctc    900 

agcttcctgc atggacccac cttactggcc agtctgcatc cttgcctaga ccattctccc    960 

caccagatgg acttctcctc cagggagccc accctgaccc acccccactg caccccctcc   1020 

ccatgggttc tctccttcct ctgaacttct ttaggagtca ctgcttgtgt ggttcctggg   1080 

acacttaacc aatgccttct ggtactgcca ttcttttttt tttttttttc aagtattgga   1140 

aggggtgggg agatatataa ataaatcatg aaatcaatac awaaaaaaaa aaaaaaaaaa   1200 

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   1260 

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a            1311 

 
           
             37  
             350  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (4)..(4)  
               n equals a,t,g, or c  
             
           
            37 

gggnatnang cttcctgctc ttccccgact agggcgggca gatgcgctcg agacccacgg     60 

gccttccacc tccctcagct tcctgcatgg acccacctta ctggccagtc tgcatccttg    120 

cctagaccat tctcccctcc agggagccca ccctgaccca cccccactgc accccctccc    180 

catgggttct ctccttcctc tgaacttctt taggagtcac tgcttgtgtg gttcctggga    240 

cacttaacca atgccttctg gtactgccat tctttttttt tttttttcaa gtattggaag    300 

gggtggggag atatataaat aaatcatgaa atcaaaaaaa aaaaaaaaag               350 

 
           
             38  
             622  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (316)..(316)  
               n equals a,t,g, or c  
             
           
            38 

ggggagcaga tctgaggaca tctctgtgcc aggccagaaa ccgcccacct gcagttcctt     60 

ctccgggatg gacgtggggc ccagctccct gccccacctt gggctgaagc tgctgctgct    120 

cctgctgctg ctgcccctca ggggccaagc caacacaggc tgctacggga tcccagggat    180 

gcccggcctg ccyggggcac cagggaagga tgggtacgac ggactgccgg ggcccaaggg    240 

ggagccagga atccagccat tccgggatcc gaggacccaa arggcagaag ggagaacccg    300 

gcttacccgg ccatcntggg aaaawtggyc catggkaccc cctgggatgc caggggtgcc    360 

ggcccatggg catccctgga gagcaggtga gragggcaga tacaagcaga aattccagtc    420 

aktgtcacgg cactcggaga ccacagcccc tgacccaaca gctgatagat caacgcggtc    480 

taacaaccga aggagatata cacgacactg naagtcactg aaagnccggc ttacacttgc    540 

tacacgcgtg ataagcaact ggctgtgtga cgaacggnta angggcactt tgggcaacnc    600 

aaacataggc aatngcgggg ct                                             622 

 
           
             39  
             1333  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (485)..(486)  
               n equals a,t,g, or c  
             
           
            39 

agctggtacc aaagcaagtt tttcactgag ctctcatgaa agatcctcag tctcttgtgg     60 

atttagaatc ctgcagcagc ccaccatcta agagcaagar ccaaagatgt ttgtcttgct    120 

ctatgttaca agttttgcca tttgtgccag tggacaaccc cggggtaatc agttgaaagg    180 

agagaactac tcccccaggt atatctgcag cattcctggc ttgcctggac ctccagggcc    240 

ccctggagca aatggttccc ctgggcccca tggtcgcatc ggccttccag gaagagatgg    300 

tagagacggc aggaaaggag agaaaggtga aaagggaact gcaggtttga gaggtaagac    360 

tggaccgcta ggtcttgccg gtgagaaagg ggaccaagga gagactggga agaaaggacc    420 

cataggacca gagggagaga aaggagaagt aggtccaatt ggtcctcctg gaccaaaggg    480 

agacnnatga tanctntggg acccggggct gcctggagtt tgcagatgtg gaagcatcgt    540 

gctcaaatcc gccttttctg ttggcatcac aaccagctac ccagaanaaa gactacctat    600 

tatatttaac aaggtcctcc ttccacgagg ganagcacta caaccctgcc acaggggaag    660 

ttcatctgtg ctttcccagg ggatctatta cttttcttat gatatcacat tggctaataa    720 

gcatctggca atcggactgg tacacaatgg gcaataccgg ataaagacct tcgacgccaa    780 

cacaggaaac catgatgtgg cttcggggtc cacagtcatc tatctgcagc cagaagatga    840 

agtctggctg gagattttct tcacagacca gaatggcctc ttctcagacc caggttgggc    900 

agacagctta ttctccgggt ttctcttata cgttgacaca gattacctag attccatatc    960 

agaagatgat gaattgtgat caggaccaag atccctgtgg taaacactct gattgaatct   1020 

ggggttccag aaggtggaac aagcaggaat gggatccaaa gagactccca ctcagattct   1080 

aaagcattta aagacaattc tagcagaatt tatcaaaaca agatgaaaca cagaaaagtt   1140 

gaaaccacaa caaaatgaat tctattaaag aatagcccca gatataaatt ctcttgaaag   1200 

caatgttcat aaatatttaa gcaaattaaa gacaatgtta acaaattttc tattaaatgc   1260 

cctgagtgat aaaaccagtt ggcaataata ttgccttatt aaatcttcaa aaaataaaaa   1320 

aaattaaaan aaa                                                      1333 

 
           
             40  
             1211  
             DNA  
             Homo sapiens  
           
            40 

tcgagttttt tttttttttt tttgatgaat aaaaaggttt ggatttaatg aaggggaaaa     60 

aaagaggcrg aggaggtgag cctgaggcta gaaccgctca ctcgaccccc cacccccagc    120 

ctacagttgt ggggtcttgc tctgtaagcc caagtccaga agcttgttcc ctgcctggag    180 

gaccgccgtg gcatgtctat acctcgttgg ggtcatcctg gtcggcatag attaggaagc    240 

ccgtaaagag gctgtctgtc cagtaagggt catagaagag cccgttctgc tctgagtaga    300 

agatctgcag ccaaacttcg tcaccctgct tgagagccag gatggtggag cctgaggcca    360 

catcgtggtt gccggtgttg gcatcaaagg tccggatgcg gtactggccg ttgtgcacca    420 

ggccgatggc caggtgcttg ttggccagcg tgatgtcgta ggtgaagtag tagatcccag    480 

gcacgccgca gacgaacttg ccgctggaag cattgtagtg gccaccctcg ttcatcagaa    540 

tcttgtcaaa cttgatgggc agccgctccc gtgggtagct cttggtcact gccaccgaga    600 

aagctgactt ggtatggcca ctgccacagc tgcaggggcc tgggaggcct ggctccccct    660 

tcttgccctt gggccccttc ttgcctggtg tgccatgctt cccgggggta ccgttgaccc    720 

ccttggggcc acgggggcca gcccgcccaa tggccccggc tttgcccttt ggtcctggct    780 

ttccccggtt acctgtccgg ccaggtggac cttcctctcc gctgtccccc cggtcgccgt    840 

cgtgtccatc ttggccgtct ttgccaggaa agcccattcg tcccatcatt cctgagggcc    900 

ctggggctcc tggggggccg ggtgggccct gggggccagg caggctgcag accagttgag    960 

gggagccttt ccggaagtcc ctgcgagcaa aggcgccaag cagtgggtca gcagcacagg   1020 

ggagggcaca ggccaggagc acccagggga tcatggtggt taccctcgcg gctgcccgcc   1080 

acgtccaggg gcgtccggag caaagaagct cctcgtgccg aattcctgca gcccggggga   1140 

tccactagtt ctagagcggc cgccaccgcg gtggagctcc agcttttgtt cccwttagga   1200 

ggaagattcc c                                                        1211 

 
           
             41  
             616  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (262)..(262)  
               n equals a,t,g, or c  
             
           
            41 

ggcacagcgc acgcaacttg gtgggctcgg acgctggccc cgggcgcggc accaaccact     60 

cgccttcgac accgagttcg tcaacattgg cggcgacttc gacgcgrcgg ccggcgtgtt    120 

ccgctgccgt ctgcccggcg cctacttctt ctccttcacg ctgggcaagc tgccgcgtaa    180 

gacgctgtcg gttaagctga tgaagaaccg cgacgaggtg caggccatga tttacgacga    240 

cggcgcgtcg cggcgccgcg angatgcaga gccagagcgt gatgctggcc ctgcggcgcg    300 

gcgacgyctc tggctgctca gccacgacca cgacggctac ggcgcctaca gcaaccacgg    360 

caagtacatc accttctccg gcttcctggt gtaccccgac ctcgcccccg ccgcccgccg    420 

ggcctcgggg cctcggagct actgtgagcc ccgggccaga gaagagcccg ggagggccag    480 

gggcgtgcat gccaggccgg gcccgaggct cgaaagtccc gcgcgagcgc cacggnctcc    540 

gggcgcgcct ggactctgcc aataaagcgg aaagcgggca cggcaggccc ggmagcccag    600 

gmaaaaaaaa aaaaaa                                                    616 

 
           
             42  
             1161  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (1113)..(1113)  
               n equals a,t,g, or c  
             
           
            42 

gccagcctgc tggtccatgg gaggggaccg tcaggggaaa gcccttcccg cctctgggga     60 

agggaacttc cgcttcggac cgagggcagt aggctctcgg ctcctggtcc cactgctgct    120 

cagcccagtg gcctcacagg acaccagctt cccaggaggc gtctgacaca gtatgatgat    180 

gaagatccca tggggcagca tcccagtact gatgttgctc ctgctcctgg gcctaatcga    240 

tatctcccag gcccagctca gctgcaccgg gcccccagcc atccctggca tcccgggtat    300 

ccctgggaca cctggccccg atggccaacc tgggacccca gggataaaag gagagaaagg    360 

gcttccaggg ctggctggag accatggtga gttcggagag aagggagacc cagggattcc    420 

tgggaatcca ggaaaagtcg gccccaaggg ccccatgggc cctaaaggtg gcccaggggc    480 

ccctggagcc ccaggcccca aaggtgaatc gggagactac aaggccaccc agaaaatcgc    540 

cttctctgcc acaagaacca tcaacgtccc cctgcgccgg gaccagacca tccgcttcga    600 

ccacgtgatc accaacatga acaacaatta tgagccccgc agtggcaagt tcacctgcaa    660 

ggtgcccggt ctctactact tcacctacca cgccagctct cgagggaacc tgtgcgtgaa    720 

cctcatgcgt ggccgggagc gtgcacagaa ggtggtcacc ttctgtgact atgcctacaa    780 

caccttccag gtcaccaccg gtggcatggt cctcaagctg gagcaggggg agaacgtctt    840 

cctgcaggcc accgacaaga actcactact gggcatggag ggtgccaaca gcatcttttc    900 

cgggttcctg ctctttccag atatggaggc ctgacctgtg ggctgcttca catccacccc    960 

ggctccccct gccagcaacg ctcactctac ccccaacacc accccttgcc cagccaatgc   1020 

acacagtagg gcttggtgaa tgctgctgag tgaatgagta aataaactct tcaaggccaa   1080 

aaaaaaaaaa aaaaagcact taagtattca tcnaacaatc acccagtagc ggtgatccag   1140 

actgaaaaga tgcgagacgc c                                             1161 

 
           
             43  
             687  
             DNA  
             Homo sapiens  
           
            43 

ccggggcccc cccccgagtt tttttttttt tttttggcct tgaaragttt atttactcat     60 

tcactcagca gcattcacca agccctactg kgtgcattgg ctgggcaagg ggkggkgttg    120 

ggggtagagk gagcgttgct ggcaggggga gccggggtgg atgtgaagca gcccacaggt    180 

caggcctcca tatctggaaa gagcaggaac ccggaaaaga tgctgttggc accctccatg    240 

cccagtagtg agttcttgtc ggtggcctgc aggaagacgt tctccccctg ctccagcttg    300 

aggaccatgc caccggtggt gacctggaag gtgttgtagg catagtcaca gaaggtgacc    360 

accttctgtg cacgctcccg gccacgcatg aggttcacgc acaggttccc tcgagagctg    420 

gcgtggtagg tgaagtakta ragaccgggc accttgcagg tgaacttgcc actgcggggc    480 

tcataattgt tgktcatgtt ggkgatcacg tggtcsaagc ggatggtctg gtcccsgcgc    540 

agggggacgt tgatggktct tgtggcarar aaaggcattt tctgggkggc ctgagtctcc    600 

cgattcacct ttgggctggg ggcttcgggc ccctgggcaa ccttaggccc atgggggcct    660 

tggggccgcc ttttcctgat tccagga                                        687 

 
           
             44  
             1194  
             DNA  
             Homo sapiens  
           
            44 

ttggtccatg ggaggggacc gtcaggggaa agcccttccc gcctctgggg aaggraactt     60 

ccgcttcgga ccgagggcag taggctctcg gctcctggtc ccactgctgc tcagcccagt    120 

ggcctcacag gacaccagct tcccaggagg cgtctgacac agtatgatga tgaagatccc    180 

atggggcagc atcccagtac tgatgttgct cctgctcctg ggcctaatcg atatctccca    240 

ggcccagctc agctgcaccg ggcccccagc catccctggc atcccgggta tccctgggac    300 

acctggcccc gatggccaac ctgggacccc agggataaaa ggagagaaag ggcttccagg    360 

gctggctgga gaccatggtg agttcggaga gaagggagac ccagggattc ctgggaatcc    420 

aggaaaagtc ggccccaagg gccccatggg ccctaaaggt ggcccagggg cccctggagc    480 

cccaggcccc aaaggtgaat cgggagacta caaggccacc cagaaaatcg ccttctctgc    540 

cacaagaacc atcaacgtcc ccctgcgccg ggaccagacc atccgcttcg accacgtgat    600 

caccaacatg aacaacaatt atgagccccg cagtggcaag ttcacctgca aggtgcccgg    660 

tctctactac ttcacctacc acgccagctc tcgagggaac ctgtgcgtga acctcatgcg    720 

tggccgggag cgtgcacaga aggtggtcac cttctgtgac tatgcctaca acaccttcca    780 

ggtcaccacc ggtggcatgg tcctcaagct ggagcagggg gagaacgtct tcctgcaggc    840 

caccgacaag aactcactac tgggcatgga gggtgccaac agcatctttt ccgggttcct    900 

gctctttcca gatatggagg cctgacctgt gggctgcttc acatccaccc cggctccccc    960 

tgccagcaac gctcactcta cccccaacac caccccttgc ccagccaatg cacacagtag   1020 

ggcttggtga atgctgctga gtgaatgagt aaataaactc ttcaaggcca agggacagtg   1080 

gtctaattca actctgtgtc ccagcacctg gcacaccaga agtgccatgc tcagaaatgt   1140 

tggttacatg aatgaatgaa ccatgaatga atgaaaaaaa aaaaaaaaaa aaaa         1194 

 
           
             45  
             1792  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (19)..(19)  
               n equals a,t,g, or c  
             
           
            45 

tccgccccat tgccgcaant ggccggtags cgtgtacggt ggaaggtcta tataascaga     60 

gcttcgttta gtaaccgtca gatcgctgga agcgccatcc acgctgtttt gacctccata    120 

gaagacccgg gnccgatcca gcytccggac tctagcttag cccgcggacg gataccawtt    180 

tcacncagga accagctatg accactaggc ttttgcaaaa agctatttag gtgacactat    240 

agaaggtacg cctgcaggta ccggtccgga attcccgggt cgacccacgc gtccggtcct    300 

gccccagcgg ccccccgagg agaggccgcc ccagccgcca ggctccaccg gggtcatcgc    360 

ggagacgggc caggccgggc cccccgcagg cgcaggcgtg tctgggcggg gtctgccgcg    420 

gggcgtggac ggccagaccg ggagcggcac cgtccccggc gcagaaggct tcgcgggcgc    480 

accaggatac ccgaagtcac ctcctgtagc ttccccagga gctccggtgc cttctctggt    540 

gtctttttct gcggggctca cccagaagcc tttccccagt gatgggggcg ttgtcctctt    600 

taacaaagtg ctggtgaacg acggggatgt ttacaacccc agcaccgggg tcttcacggc    660 

tccttatgat gggcgctacc tgatcacggc caccctcacc cccgagagag acgcctacgt    720 

ggaagcagtg ctgtcggtct ccaacgccag cgtggcccag ctgcataccg ctgggtacag    780 

gagagagttc ctggaatacc accgccctcc aggagctttg catacctgcg ggggcccggg    840 

ggcattccac ctcatcgtgc acctgaaggc gggagatgca gtcaacgtcg tggtgactgg    900 

gggcaagctg gctcacacag actttgatga aatgtactcc acatttagtg gggttttctt    960 

atatcctttc ctttcccacc tctaaggtgg ctggggagat gtcaggggaa agayagatag   1020 

ttgtaaaaac tctaaagctt taatatattc ggtttgtatg taatggaagc acggggctag   1080 

agtttccaca taggccccaa cataaaggcc ttccctcgct gttgaggcca ccatgcctta   1140 

ctgcatccag ccaggctgca grgagtgagg cacacggtga acatggccac tgacttttct   1200 

gccactctaa ctggacaact ggaagacttg gaaaggcctc cacctgtatc tacactctga   1260 

gggccctgga ctgggcctga gcttgccaca gaggctccgt ctgactgtgg gctgggagga   1320 

gggaggcagg ggagagccgg tcacggtggc tggtctttac tgcagggcag cactgtggcc   1380 

agctgtctgt ctttacactg catgcagaag tttaaacact gaagtgccga agtggcccgt   1440 

gccgccgcac agagaccccg actttagttt gggctgttcc acgcttggct caccattgcc   1500 

gcctgggact taacctgctc aggcgggcct tcgcccagct gcaaataggg atgcgttaga   1560 

gactgttccc aaagcttgtt gggctcctta aatggcatgt acaatttaag tgcaaagaca   1620 

gggagtgtca ataaagatgg aaagccattt ccagttaaaa aaaaaaaaaa aaaaaaaaaa   1680 

aaaaaaaaaa aaaaaagggc ggccgctcta gaggatccct cgaggggccc aagcttacgc   1740 

gtgcatgcga cgtcatagct ctctccctat agtagtcgta ttataagtag ct           1792 

 
           
             46  
             1412  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (1363)..(1363)  
               n equals a,t,g, or c  
             
           
            46 

ccacgcgtcc ggtcctgccc cagcggcccc ccgaggagag gccgccccag ccgccaggct     60 

ccaccggggt catcgcggag acgggccagg ccgggccccc cgcaggcgca ggcgtgtctg    120 

ggcggggtct gccgcggggc gtggacggcc agaccgggag cggcaccgtc cccggcgcag    180 

aaggcttcgc gggcgcacca ggatacccga agtcacctcc tgtagcttcc ccaggagctc    240 

cggtgccttc tctggtgtct ttttctgcgg ggctcaccca gaagcctttc cccagtgatg    300 

ggggcgttgt cctctttaac aaagtgctgg tgaacgacgg ggatgtttac aaccccagca    360 

ccggggtctt cacggctcct tatgatgggc gctacctgat cacggccacc ctcacccccg    420 

agagagacgc ctacgtggaa gcagtgctgt cggtctccaa cgccagcgtg gcccagctgc    480 

ataccgctgg gtacaggaga gagttcctgg aataccaccg ccctccagga gctttgcata    540 

cctgcggggg cccgggggca ttccacctca tcgtgcacct gaaggcggga gatgcagtca    600 

acgtcgtggt gactgggggc aagctggctc acacagactt tgatgaaatg tactccacat    660 

ttagtggggt tttcttatat cctttccttt cccacctcta aggtggctgg ggagatgtca    720 

ggggaaagac agatagttgt aaaaactcta aagctttaat atattcggtt tgtatgtaat    780 

ggaagcacgg ggctagagtt tccacatagg ccccaacata aaggccttcc ctcgctgttg    840 

aggccaccat gccttactgc atccagccag gctgcagaga gtgaggcaca cggtgaacat    900 

ggccactgac ttttctgcca ctctaactgg acaactggaa gacttggaaa ggcctccacc    960 

tgtatctaca ctctgagggc cctggactgg gcctgagctt gccacagagg ctccgtctga   1020 

ctgtgggctg ggaggaggga ggcaggggag agccggtcac ggtggctggt ctttactgca   1080 

gggcagcact gtggccagct gtctgtcttt acactgcatg cagaagttta aacactgaag   1140 

tgccgaagtg gcccgtgccg ccgcacagag accccgactt tagtttgggc tgttccacgc   1200 

ttggctcacc attgccgcct gggacttaac ctgctcaggc gggccttcgc ccagctgcaa   1260 

atagggatgc gttagagact gttcccaaag cttgttgggc tccttaaatg gcatgtacaa   1320 

tttaagtgca aagacaggga gtgtcaataa agatggaaag ccntttccag ttaaaaaaaa   1380 

aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa                                 1412 

 
           
             47  
             646  
             DNA  
             Homo sapiens  
           
            47 

cgatcctctc cgtgggagcc agcgagcctc tctccctgat cttacgtgct caaggatcca     60 

gtttcaccta tggaatgaga aagttgggga agaagtcatc tagcgtcttg ctactcaaag    120 

tgtggtccat ggaccagcag catcagcatc acctgggatc ttcttggaag aaatgtagaa    180 

actcaggcct caccccagaa tctgcctttt tataagaccc ccagaagctg ttgtgaaggc    240 

agagcagcat ctgctgaaga gacagaaacc agccccagag gtgtcacagg aagtcaccag    300 

caaggacatt ggtctttgat ttgattcagc agtcctgtca agtataaatg tgatggctgt    360 

gctgcctggc cctctgcagc tgctgggagt gctgcttacc atttccctga gttccatcag    420 

gctcattcag gctggtgcct actatgggat caagccgctg ccacctcaaa ttcctcctca    480 

gatgccacca caaattccac aataccagcc cctgggtcag caagtacctc acatgccttt    540 

ggccaaagat ggccttgcca tgggcaagga gatgccccac ttgcagtatg gcaaagagta    600 

tccacaccta ccccaatata tgaaggaaat tcaaccggcg gtcgac                   646 

 
           
             48  
             2536  
             DNA  
             Homo sapiens  
             
               misc_feature  
               (2)..(3)  
               n equals a,t,g, or c  
             
           
            48 

gnntgacacc cagcgcctgc gagcgatgga gaagctgctg gcctcggtgg aggagcggtt     60 

cggcacctcg cagggctggc ggtgggccgc aggccccctc aggaatgctg ctctccagag    120 

ctgggccggc gactggcaga gctggagcgc aggctggatg tcgtggccgg ctcagtgaca    180 

gtgctgagtg ggcggcgagg cacagagctg ggaggagccg cggggcaggg aggccacccc    240 

ccaggctaca ccagcttggc ctcccgcctg tctcgcctgg aggaccgctt caactccacc    300 

ctgggccctt cggaggagca ggaggagagc tggcctgggg ctcctggggg gctgagccac    360 

tggctgcctg ctgcccgggg ccgactagag cagttggggg ggctgctggc caatgtgagc    420 

gggkagctgg gggggcggtt ggatctgttg gaggagcagg tggcaggggc catgcaggca    480 

tgcgggcagc tctgctctgg ggcccctggg gagcaggact ctcaagtcag cgagatcctc    540 

agtgccttgg agcgcagggt gctggacagt gaggggcagc tgcggctggt gggctccggc    600 

ctgcacacgg tggaagcagc gggggaggcc cggcaggcca cgctggaggg attacaagag    660 

gttgtgggcc ggctccagga tcgtgtggat gcccaggatg agacagctgc agagttcaca    720 

ctacggctga atctcactgc ggcccggcta ggccaactgg aggggctgct gcaggcccat    780 

ggggatgagg gctgtggggc ctgtggcgga gtccaagagg aactaggccg ccttcgggat    840 

ggtgtggagc gctgctcctg ccccctgttg cctcctcggg gtcctggggc tggtccaggt    900 

gttgggggcc caagccgtgg gcccctggac ggcttcagcg tgtttggggg cagctcaggc    960 

tcagccctgc aggccctgca aggagagctc tctgaggtta ttctcagctt cagctccctc   1020 

aatgactcac tgaatgagct ccagaccact gtggagggcc agggcgctga tctggctgac   1080 

ctgggggcaa ccaaggaccg tatcatttct gagattaaca ggctgcagca ggaggccaca   1140 

gagcatgcta cagagagtga agagcgcttc cgaggcctag aggagggaca agcacaggcc   1200 

ggccagtgcc ccagcttaga ggggcgattg ggccgtcttg agggtgtctg tgaacggttg   1260 

gacactgtgg ctgggggact gcagggcctg cgcgagggcc tttccagaca cgtggctggg   1320 

ctctgggctg ggctccggga aaccaacacc accagccaga tgcaggcagc cctgctggag   1380 

aagctggtcg ggggacaggc gggcctgggc aggcggctgg gtgcccttaa cagctccctg   1440 

cagctcctgg aggaccgtct gcaccagctc agcctgaagg acctcactgg gcctgcagga   1500 

gaggctgggc ccccagggcc tcctgggctg cagggacccc caggccctgc tggacctcca   1560 

ggatcaccag gcaaggacgg gcaagagggc cccatcgggc caccaggtcc tcaaggtgaa   1620 

cagggagtgg agggggcacc agcagcccct gtgccccaag tggcattttc agctgctctg   1680 

agtttgcccc ggtctgaacc aggcacggtc cccttcgaca gagtcctgct caatgatgga   1740 

ggctattatg atccagagac aggcgtgttc acagcgccac tggctggacg ctacttgctg   1800 

agcgcggtgc tgactgggca ccggcacgag aaagtggagg ccgtgctgtc ccgctccaac   1860 

cagggcgtgg cccgcgtaga ctccggtggc tacgagcctg agggcctgga gaataagccg   1920 

gtggccgaga gccagcccag cccgggcacc ctgggcgtct tcagcctcat cctgccgctg   1980 

caggccgggg acacggtctg cgtcgacctg gtcatggggc agctggcgca ctcggaggag   2040 

ccgctcacca tcttcagcgg ggccctgctc tatggggacc cagagcttga acacgcgtag   2100 

actggggtcc cgcccgacgt gtctacgtcg gctgaagaga cagcgggggc ggcgggctcc   2160 

tggggtctcg cctgagacgg ggcacctagc cctgggcgag cgccgcaccc gggcccgcag   2220 

cggcaccgcg cccagagcgg cctctcccca cgcccggggc gcgccggctc agggaggctc   2280 

ggggccgccc atgcagactt ttggcctggc gcgatccccc aagaacccct ccagggccgg   2340 

cctgcggagg agccgatcct cgcaccctcc gctccctcca ctggccctcc aggtcgattc   2400 

cctgggctcc aggctccccc gcgcgggcgc cgcccaccgc catactaaac gatcgaggaa   2460 

taaagacact tggtttttct aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   2520 

aaaaaaaggc ggccgc                                                   2536 

 
           
             49  
             1530  
             DNA  
             Homo sapiens  
           
            49 

tccatgtata ggagacagtg aaagagatgg gggtggcatt ttcttccagg agagttgtgg     60 

ggagatgacc gttaggtcat aagcgcgccc ctactctgca ctggcgagac cagcaaagct    120 

ggagtgaacc cagctgaacc tgggccgcag cagccccgga ggctggaggc gctgcagtcg    180 

ggaaacacca ggaggatgga gcccttttcc ctgtaagcag gaggccagga tcctgattcc    240 

tgagccggct tcccacggac cccaggcccc ggcagggtcc tggcgggagg aagaacccac    300 

ggattcagag tctgtcatct gaaccatgag gatctggtgg cttctgcttg ccattgaaat    360 

ctgcacaggg aacataaact cacaggacac ctgcaggcaa gggcaccctg gaatccctgg    420 

gaaccccggt cacaatggtc tgcctggaag agatggacga gacggagcga agggtgacaa    480 

aggcgatgca ggagaaccag gacgtcctgg cagcccgggg aaggatggga cgagtggaga    540 

gaagggagaa cgaggagcag atggaaaagt tgaagcaaaa ggcatcaaag gtgatcaagg    600 

ctcaagagga tccccaggaa aacatggccc caaggggctt gcagggccca tgggagagaa    660 

aggcctccga ggagagactg ggcctcaggg gcagaagggg aataagggtg acgtgggtcc    720 

cactggtcct gaggggccaa ggggcaacat tgggcctttg ggcccaactg gtttaccggg    780 

ccccatgggc cctattggaa agcctggtcc caagggagaa gctggaccca cggggcccca    840 

gggtgagcca ggagtccggg gaataagagg ctggaaagga gatcgaggag agaaagggaa    900 

aatcggtgag actctagtct tgccaaaaag tgctttcact gtggggctca cggtgctgag    960 

caagtttcct tcttcagatg tgcccattaa atttgataag atcctgtata acgaattcaa   1020 

ccattatgat acagcagcgg ggaaattcac gtgccacatt gctggggtct attacttcac   1080 

ctaccacatc actgttttct ccaggaatgt tcaggtgtct ttggtcaaaa atggagtaaa   1140 

aatactgcac accaaagatg cttacatgag ctctgaggac caggcctctg gcggcattgt   1200 

cctgcagctg aagctcgggg atgaggtgtg gctgcaggtg acaggaggag agaggttcaa   1260 

tggcttgttt gctgatgagg acgatgacac aactttcaca gggttccttc tgttcagcag   1320 

cccgtgacag aggagagttt aaaaatccgc cacaccatcc atcagaatca gcttgggatg   1380 

aacttattca gatggtttta ctttattaat tcctccaatt attacaataa tcataaaaag   1440 

gtgaaaatgg aaaagttatt cccaaaactg attctgtgta acttactatt tttccaggag   1500 

taaatattta aaataaaaaa aaaaaaaaag                                    1530 

 
           
             50  
             229  
             PRT  
             Homo sapiens  
           
            50 

Met Asp Leu Leu Gln Phe Leu Ala Phe Leu Phe Val Leu Leu Leu Ser 
  1               5                  10                  15 

Gly Met Gly Ala Thr Gly Thr Leu Arg Thr Ser Leu Asp Pro Ser Leu 
             20                  25                  30 

Glu Ile Tyr Lys Lys Met Phe Glu Val Lys Arg Arg Glu Gln Leu Leu 
         35                  40                  45 

Ala Leu Lys Asn Leu Ala Gln Leu Asn Asp Ile His Gln Gln Tyr Lys 
     50                  55                  60 

Ile Leu Asp Val Met Leu Lys Gly Leu Phe Lys Val Leu Glu Asp Ser 
 65                  70                  75                  80 

Arg Thr Val Leu Thr Ala Ala Asp Val Leu Pro Asp Gly Pro Cys Pro 
                 85                  90                  95 

Gln Asp Glu Lys Leu Lys Asp Ala Phe Ser His Val Val Glu Asn Thr 
            100                 105                 110 

Ala Phe Phe Gly Asp Val Val Leu Arg Phe Pro Arg Ile Val His Tyr 
        115                 120                 125 

Tyr Phe Asp His Asn Ser Asn Trp Asn Leu Leu Ile Arg Trp Gly Ile 
    130                 135                 140 

Ser Phe Cys Asn Gln Thr Gly Val Phe Asn Gln Gly Pro His Ser Pro 
145                 150                 155                 160 

Ile Leu Ser Leu Met Ala Gln Glu Leu Gly Ile Ser Glu Lys Asp Ser 
                165                 170                 175 

Asn Phe Gln Asn Pro Phe Lys Ile Asp Arg Thr Glu Phe Ile Pro Ser 
            180                 185                 190 

Thr Asp Pro Phe Gln Lys Ala Leu Arg Glu Glu Glu Lys Arg Arg Lys 
        195                 200                 205 

Lys Glu Glu Lys Arg Lys Glu Ile Arg Lys Gly Pro Arg Ile Ser Arg 
    210                 215                 220 

Ser Gln Ser Glu Leu 
225 

 
           
             51  
             421  
             PRT  
             Homo sapiens  
           
            51 

Met Gly Gly Pro Arg Ala Trp Ala Leu Leu Cys Leu Gly Leu Leu Leu 
  1               5                  10                  15 

Pro Gly Gly Gly Ala Ala Trp Ser Ile Gly Ala Ala Pro Phe Ser Gly 
             20                  25                  30 

Arg Arg Asn Trp Cys Ser Tyr Val Val Thr Arg Thr Ile Ser Cys His 
         35                  40                  45 

Val Gln Asn Gly Thr Tyr Leu Gln Arg Val Leu Gln Asn Cys Pro Trp 
     50                  55                  60 

Pro Met Ser Cys Pro Gly Ser Ser Tyr Arg Thr Val Val Arg Pro Thr 
 65                  70                  75                  80 

Tyr Lys Val Met Tyr Lys Ile Val Thr Ala Arg Glu Trp Arg Cys Cys 
                 85                  90                  95 

Pro Gly His Ser Gly Val Ser Cys Glu Glu Val Ala Ala Ser Ser Ala 
            100                 105                 110 

Ser Leu Glu Pro Met Trp Ser Gly Ser Thr Met Arg Arg Met Ala Leu 
        115                 120                 125 

Arg Pro Thr Ala Phe Ser Gly Cys Leu Asn Cys Ser Lys Val Ser Glu 
    130                 135                 140 

Leu Thr Glu Arg Leu Lys Val Leu Glu Ala Lys Met Thr Met Leu Thr 
145                 150                 155                 160 

Val Ile Glu Gln Pro Val Pro Pro Thr Pro Ala Thr Pro Glu Asp Pro 
                165                 170                 175 

Ala Pro Leu Trp Gly Pro Pro Pro Ala Gln Gly Ser Pro Gly Asp Gly 
            180                 185                 190 

Gly Leu Gln Asp Gln Val Gly Ala Trp Gly Leu Pro Gly Pro Thr Gly 
        195                 200                 205 

Pro Lys Gly Asp Ala Gly Ser Arg Gly Pro Met Gly Met Arg Gly Pro 
    210                 215                 220 

Pro Gly Pro Gln Gly Pro Pro Gly Ser Pro Gly Arg Ala Gly Ala Val 
225                 230                 235                 240 

Gly Thr Pro Gly Glu Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 
                245                 250                 255 

Pro Pro Gly Pro Pro Ala Pro Val Gly Pro Pro His Ala Arg Ile Ser 
            260                 265                 270 

Gln His Gly Asp Pro Leu Leu Ser Asn Thr Phe Thr Glu Thr Asn Asn 
        275                 280                 285 

His Trp Pro Gln Gly Pro Thr Gly Pro Pro Gly Pro Pro Gly Pro Met 
    290                 295                 300 

Gly Pro Pro Gly Pro Pro Gly Pro Thr Gly Val Pro Gly Ser Pro Gly 
305                 310                 315                 320 

His Ile Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Ile Ser Gly His 
                325                 330                 335 

Pro Gly Glu Lys Gly Glu Arg Gly Leu Arg Gly Glu Pro Gly Pro Gln 
            340                 345                 350 

Gly Ser Ala Gly Gln Arg Gly Glu Pro Gly Pro Lys Gly Asp Pro Gly 
        355                 360                 365 

Glu Lys Ser His Trp Asn Gln Ser Trp Gly Leu Gly Arg Ala Leu Pro 
    370                 375                 380 

Ala Gln Ala Pro Pro Ala Ser Phe Gly Ala Arg Gly Ala Asp Met Gln 
385                 390                 395                 400 

Pro Thr Thr Gly Ser Trp Pro Pro Gly Ala Gly Thr Arg Glu Ala Glu 
                405                 410                 415 

Gly Gly Gly Gly Pro 
            420 

 
           
             52  
             240  
             PRT  
             Homo sapiens  
           
            52 

His Ala Ser Ala Ala Arg Ala Ala Ala Gly Ser Glu Pro Arg Thr Gly 
  1               5                  10                  15 

Cys Gly Gly Ser Ser His Arg Val Pro Leu Gly Pro Ser Pro Ala Ser 
             20                  25                  30 

Leu Ser Pro Gln Arg Asp Leu Phe Gly Pro Pro Gly Pro Pro Gly Ala 
         35                  40                  45 

Glu Val Thr Ala Glu Thr Leu Leu His Glu Phe Gln Glu Leu Leu Lys 
     50                  55                  60 

Glu Ala Thr Glu Arg Arg Phe Ser Gly Leu Leu Asp Pro Leu Leu Pro 
 65                  70                  75                  80 

Gln Gly Ala Gly Leu Arg Leu Val Gly Glu Ala Phe His Cys Arg Leu 
                 85                  90                  95 

Gln Gly Pro Arg Arg Val Asp Lys Arg Thr Leu Val Glu Leu His Gly 
            100                 105                 110 

Phe Gln Ala Pro Ala Ala Gln Gly Ala Phe Leu Arg Gly Ser Gly Leu 
        115                 120                 125 

Ser Leu Ala Ser Gly Arg Phe Thr Ala Pro Val Ser Gly Ile Phe Gln 
    130                 135                 140 

Phe Ser Ala Ser Leu His Val Asp His Ser Glu Leu Gln Gly Lys Ala 
145                 150                 155                 160 

Arg Leu Arg Ala Arg Asp Val Val Cys Val Leu Ile Cys Ile Glu Ser 
                165                 170                 175 

Leu Cys Gln Arg His Thr Cys Leu Glu Ala Val Ser Gly Leu Glu Ser 
            180                 185                 190 

Asn Ser Arg Val Phe Thr Leu Gln Val Gln Gly Leu Leu Gln Leu Gln 
        195                 200                 205 

Ala Gly Gln Tyr Ala Ser Val Phe Val Asp Asn Gly Ser Gly Ala Val 
    210                 215                 220 

Leu Thr Ile Gln Ala Gly Ser Ser Phe Ser Gly Leu Leu Leu Gly Thr 
225                 230                 235                 240 

 
           
             53  
             281  
             PRT  
             Homo sapiens  
           
            53 

Met Gly Ser Arg Gly Gln Gly Leu Leu Leu Ala Tyr Cys Leu Leu Leu 
  1               5                  10                  15 

Ala Phe Ala Ser Gly Leu Val Leu Ser Arg Val Pro His Val Gln Gly 
             20                  25                  30 

Glu Gln Gln Glu Trp Glu Gly Thr Glu Glu Leu Pro Ser Pro Pro Asp 
         35                  40                  45 

His Ala Glu Arg Ala Glu Glu Gln His Glu Lys Tyr Arg Pro Ser Gln 
     50                  55                  60 

Asp Gln Gly Leu Pro Ala Ser Arg Cys Leu Arg Cys Cys Asp Pro Gly 
 65                  70                  75                  80 

Thr Ser Met Tyr Pro Ala Thr Ala Val Pro Gln Ile Asn Ile Thr Ile 
                 85                  90                  95 

Leu Lys Gly Glu Lys Gly Asp Arg Gly Asp Arg Gly Leu Gln Gly Lys 
            100                 105                 110 

Tyr Gly Lys Thr Gly Ser Ala Gly Ala Arg Gly His Thr Gly Pro Lys 
        115                 120                 125 

Gly Gln Lys Gly Ser Met Gly Ala Pro Gly Glu Arg Cys Lys Ser His 
    130                 135                 140 

Tyr Ala Ala Phe Ser Val Gly Arg Lys Lys Pro Met His Ser Asn His 
145                 150                 155                 160 

Tyr Tyr Gln Thr Val Ile Phe Asp Thr Glu Phe Val Asn Leu Tyr Asp 
                165                 170                 175 

His Phe Asn Met Phe Thr Gly Lys Phe Tyr Cys Tyr Val Pro Gly Leu 
            180                 185                 190 

Tyr Phe Phe Ser Leu Asn Val His Thr Trp Asn Gln Lys Glu Thr Tyr 
        195                 200                 205 

Leu His Ile Met Lys Asn Glu Glu Glu Val Ala Ile Leu Phe Ala Gln 
    210                 215                 220 

Val Gly Asp Arg Ser Ile Met Gln Ser Gln Ser Leu Met Leu Glu Leu 
225                 230                 235                 240 

Arg Glu Gln Asp Gln Val Trp Val Arg Leu Tyr Lys Gly Glu Arg Glu 
                245                 250                 255 

Asn Ala Ile Phe Ser Glu Glu Leu Asp Thr Tyr Ile Thr Phe Ser Gly 
            260                 265                 270 

Tyr Leu Val Lys His Ala Thr Glu Pro 
        275                 280 

 
           
             54  
             205  
             PRT  
             Homo sapiens  
           
            54 

Met Leu Gly Ala Lys Pro His Trp Leu Pro Gly Pro Leu His Ser Pro 
  1               5                  10                  15 

Gly Leu Pro Leu Val Leu Val Leu Leu Ala Leu Gly Ala Gly Trp Ala 
             20                  25                  30 

Gln Glu Gly Ser Glu Pro Val Leu Leu Glu Gly Glu Cys Leu Val Val 
         35                  40                  45 

Cys Glu Pro Gly Arg Ala Ala Ala Gly Gly Pro Gly Gly Ala Ala Leu 
     50                  55                  60 

Gly Glu Ala Pro Pro Gly Arg Val Ala Phe Ala Ala Val Arg Ser His 
 65                  70                  75                  80 

His His Glu Pro Ala Gly Glu Thr Gly Asn Gly Thr Ser Gly Ala Ile 
                 85                  90                  95 

Tyr Phe Asp Gln Val Leu Val Asn Glu Gly Gly Gly Phe Asp Arg Ala 
            100                 105                 110 

Ser Gly Ser Phe Val Ala Pro Val Arg Gly Val Tyr Ser Phe Arg Phe 
        115                 120                 125 

His Val Val Lys Val Tyr Asn Arg Gln Thr Val Gln Val Ser Leu Met 
    130                 135                 140 

Leu Asn Thr Trp Pro Val Ile Ser Ala Phe Ala Asn Asp Pro Asp Val 
145                 150                 155                 160 

Thr Arg Glu Ala Ala Thr Ser Ser Val Leu Leu Pro Leu Asp Pro Gly 
                165                 170                 175 

Asp Arg Val Ser Leu Arg Leu Arg Arg Gly Asn Leu Leu Gly Gly Trp 
            180                 185                 190 

Lys Tyr Ser Ser Phe Ser Gly Phe Leu Ile Phe Pro Leu 
        195                 200                 205 

 
           
             55  
             189  
             PRT  
             Homo sapiens  
             
               SITE  
               (9)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            55 

Leu Ala Leu Leu Leu Leu Leu Leu Xaa Ala Cys Cys Pro Val Arg Ala 
  1               5                  10                  15 

Gln Asn Asp Thr Glu Pro Ile Val Leu Glu Gly Lys Cys Leu Val Val 
             20                  25                  30 

Cys Asp Ser Ser Pro Ser Ala Asp Gly Ala Val Thr Ser Ser Leu Gly 
         35                  40                  45 

Ile Ser Val Arg Ser Gly Ser Ala Lys Val Ala Phe Ser Ala Thr Arg 
     50                  55                  60 

Ser Thr Asn His Glu Pro Ser Glu Met Ser Asn Arg Thr Met Thr Ile 
 65                  70                  75                  80 

Tyr Phe Asp Gln Val Leu Val Asn Ile Gly Asn His Phe Asp Leu Ala 
                 85                  90                  95 

Ser Ser Ile Phe Val Ala Pro Arg Lys Gly Ile Tyr Ser Phe Ser Phe 
            100                 105                 110 

His Val Val Lys Val Tyr Asn Arg Gln Thr Ile Gln Val Ser Leu Met 
        115                 120                 125 

Gln Asn Gly Tyr Pro Val Ile Ser Ala Phe Ala Gly Asp Gln Asp Val 
    130                 135                 140 

Thr Arg Glu Ala Ala Ser Asn Gly Val Leu Leu Leu Met Glu Arg Glu 
145                 150                 155                 160 

Asp Lys Val His Leu Lys Leu Glu Arg Gly Asn Leu Met Gly Gly Trp 
                165                 170                 175 

Lys Tyr Ser Thr Phe Ser Gly Phe Leu Val Phe Pro Leu 
            180                 185 

 
           
             56  
             201  
             PRT  
             Homo sapiens  
           
            56 

Ser Gln Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Arg Asp Gly Ala 
  1               5                  10                  15 

Pro Gly Ala Pro Gly Glu Lys Gly Glu Gly Gly Arg Pro Gly Leu Pro 
             20                  25                  30 

Gly Pro Arg Gly Asp Pro Gly Pro Arg Gly Glu Ala Gly Pro Ala Gly 
         35                  40                  45 

Pro Thr Gly Pro Ala Gly Glu Cys Ser Val Pro Pro Arg Ser Ala Phe 
     50                  55                  60 

Ser Ala Lys Arg Ser Glu Ser Arg Val Pro Pro Pro Ser Asp Ala Pro 
 65                  70                  75                  80 

Leu Pro Phe Asp Arg Val Leu Val Asn Glu Gln Gly His Tyr Asp Ala 
                 85                  90                  95 

Val Thr Gly Lys Phe Thr Cys Gln Val Pro Gly Val Tyr Tyr Phe Ala 
            100                 105                 110 

Val His Ala Thr Val Tyr Arg Ala Ser Leu Gln Phe Asp Leu Val Lys 
        115                 120                 125 

Asn Gly Glu Ser Ile Ala Ser Phe Phe Gln Phe Phe Gly Gly Trp Pro 
    130                 135                 140 

Lys Pro Ala Ser Leu Ser Gly Gly Ala Met Val Arg Leu Glu Pro Glu 
145                 150                 155                 160 

Asp Gln Val Trp Val Gln Val Gly Val Gly Asp Tyr Ile Gly Ile Tyr 
                165                 170                 175 

Ala Ser Ile Lys Thr Asp Ser Thr Phe Ser Gly Phe Leu Val Tyr Ser 
            180                 185                 190 

Asp Trp His Ser Ser Pro Val Phe Ala 
        195                 200 

 
           
             57  
             245  
             PRT  
             Homo sapiens  
           
            57 

Met Asp Val Gly Pro Ser Ser Leu Pro His Leu Gly Leu Lys Leu Leu 
  1               5                  10                  15 

Leu Leu Leu Leu Leu Leu Pro Leu Arg Gly Gln Ala Asn Thr Gly Cys 
             20                  25                  30 

Tyr Gly Ile Pro Gly Met Pro Gly Leu Pro Gly Ala Pro Gly Lys Asp 
         35                  40                  45 

Gly Tyr Asp Gly Leu Pro Gly Pro Lys Gly Glu Pro Gly Ile Pro Ala 
     50                  55                  60 

Ile Pro Gly Ile Arg Gly Pro Lys Gly Gln Lys Gly Glu Pro Gly Leu 
 65                  70                  75                  80 

Pro Gly His Pro Gly Lys Asn Gly Pro Met Gly Pro Pro Gly Met Pro 
                 85                  90                  95 

Gly Val Pro Gly Pro Met Gly Ile Pro Gly Glu Pro Gly Glu Glu Gly 
            100                 105                 110 

Arg Tyr Lys Gln Lys Phe Gln Ser Val Phe Thr Val Thr Arg Gln Thr 
        115                 120                 125 

His Gln Pro Pro Ala Pro Asn Ser Leu Ile Arg Phe Asn Ala Val Leu 
    130                 135                 140 

Thr Asn Pro Gln Gly Asp Tyr Asp Thr Ser Thr Gly Lys Phe Thr Cys 
145                 150                 155                 160 

Lys Val Pro Gly Leu Tyr Tyr Phe Val Tyr His Ala Ser His Thr Ala 
                165                 170                 175 

Asn Leu Cys Val Leu Leu Tyr Arg Ser Gly Val Lys Val Val Thr Phe 
            180                 185                 190 

Cys Gly His Thr Ser Lys Thr Asn Gln Val Asn Ser Gly Gly Val Leu 
        195                 200                 205 

Leu Arg Leu Gln Val Gly Glu Glu Val Trp Leu Ala Val Asn Asp Tyr 
    210                 215                 220 

Tyr Asp Met Val Gly Ile Gln Gly Ser Asp Ser Val Phe Ser Gly Phe 
225                 230                 235                 240 

Leu Leu Phe Pro Asp 
                245 

 
           
             58  
             278  
             PRT  
             Homo sapiens  
           
            58 

Met Gln Trp Leu Arg Val Arg Glu Ser Pro Gly Glu Ala Thr Gly His 
  1               5                  10                  15 

Arg Val Thr Met Gly Thr Ala Ala Leu Gly Pro Val Trp Ala Ala Leu 
             20                  25                  30 

Leu Leu Phe Leu Leu Met Cys Glu Ile Pro Met Val Glu Leu Thr Phe 
         35                  40                  45 

Asp Arg Ala Val Ala Ser Asp Cys Gln Arg Cys Cys Asp Ser Glu Asp 
     50                  55                  60 

Pro Leu Asp Pro Ala His Val Ser Ser Ala Ser Ser Ser Gly Arg Pro 
 65                  70                  75                  80 

His Ala Leu Pro Glu Ile Arg Pro Tyr Ile Asn Ile Thr Ile Leu Lys 
                 85                  90                  95 

Gly Asp Lys Gly Asp Pro Gly Pro Met Gly Leu Pro Gly Tyr Met Gly 
            100                 105                 110 

Arg Glu Gly Pro Gln Gly Glu Pro Gly Pro Gln Gly Ser Lys Gly Asp 
        115                 120                 125 

Lys Gly Glu Met Gly Ser Pro Gly Ala Pro Cys Gln Lys Arg Phe Phe 
    130                 135                 140 

Ala Phe Ser Val Gly Arg Lys Thr Ala Leu His Ser Gly Glu Asp Phe 
145                 150                 155                 160 

Gln Thr Leu Leu Phe Glu Arg Val Phe Val Asn Leu Asp Gly Cys Phe 
                165                 170                 175 

Asp Met Ala Thr Gly Gln Phe Ala Ala Pro Leu Arg Gly Ile Tyr Phe 
            180                 185                 190 

Phe Ser Leu Asn Val His Ser Trp Asn Tyr Lys Glu Thr Tyr Val His 
        195                 200                 205 

Ile Met His Asn Gln Lys Glu Ala Val Ile Leu Tyr Ala Gln Pro Ser 
    210                 215                 220 

Glu Arg Ser Ile Met Gln Ser Gln Ser Val Met Leu Asp Leu Ala Tyr 
225                 230                 235                 240 

Gly Asp Arg Val Trp Val Arg Leu Phe Lys Arg Gln Arg Glu Asn Ala 
                245                 250                 255 

Ile Tyr Ser Asn Asp Phe Asp Thr Tyr Ile Thr Phe Ser Gly His Leu 
            260                 265                 270 

Ile Lys Ala Glu Asp Asp 
        275 

 
           
             59  
             289  
             PRT  
             Homo sapiens  
           
            59 

Met Phe Val Leu Leu Tyr Val Thr Ser Phe Ala Ile Cys Ala Ser Gly 
  1               5                  10                  15 

Gln Pro Arg Gly Asn Gln Leu Lys Gly Glu Asn Tyr Ser Pro Arg Tyr 
             20                  25                  30 

Ile Cys Ser Ile Pro Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Ala 
         35                  40                  45 

Asn Gly Ser Pro Gly Pro His Gly Arg Ile Gly Leu Pro Gly Arg Asp 
     50                  55                  60 

Gly Arg Asp Gly Arg Lys Gly Glu Lys Gly Glu Lys Gly Thr Ala Gly 
 65                  70                  75                  80 

Leu Arg Gly Lys Thr Gly Pro Leu Gly Leu Ala Gly Glu Lys Gly Asp 
                 85                  90                  95 

Gln Gly Glu Thr Gly Lys Lys Gly Pro Ile Gly Pro Glu Gly Glu Lys 
            100                 105                 110 

Gly Glu Val Gly Pro Ile Gly Pro Pro Gly Pro Lys Gly Asp Arg Gly 
        115                 120                 125 

Glu Gln Gly Asp Pro Gly Leu Pro Gly Val Cys Arg Cys Gly Ser Ile 
    130                 135                 140 

Val Leu Lys Ser Ala Phe Ser Val Gly Ile Thr Thr Ser Tyr Pro Glu 
145                 150                 155                 160 

Glu Arg Leu Pro Ile Ile Phe Asn Lys Val Leu Phe Asn Glu Gly Glu 
                165                 170                 175 

His Tyr Asn Pro Ala Thr Gly Lys Phe Ile Cys Ala Phe Pro Gly Ile 
            180                 185                 190 

Tyr Tyr Phe Ser Tyr Asp Ile Thr Leu Ala Asn Lys His Leu Ala Ile 
        195                 200                 205 

Gly Leu Val His Asn Gly Gln Tyr Arg Ile Lys Thr Phe Asp Ala Asn 
    210                 215                 220 

Thr Gly Asn His Asp Val Ala Ser Gly Ser Thr Val Ile Tyr Leu Gln 
225                 230                 235                 240 

Pro Glu Asp Glu Val Trp Leu Glu Ile Phe Phe Thr Asp Gln Asn Gly 
                245                 250                 255 

Leu Phe Ser Asp Pro Gly Trp Ala Asp Ser Leu Phe Ser Gly Phe Leu 
            260                 265                 270 

Leu Tyr Val Asp Thr Asp Tyr Leu Asp Ser Ile Ser Glu Asp Asp Glu 
        275                 280                 285 

Leu 

 
           
             60  
             285  
             PRT  
             Homo sapiens  
           
            60 

Met Ile Pro Trp Val Leu Leu Ala Cys Ala Leu Pro Cys Ala Ala Asp 
  1               5                  10                  15 

Pro Leu Leu Gly Ala Phe Ala Arg Arg Asp Phe Arg Lys Gly Ser Pro 
             20                  25                  30 

Gln Leu Val Cys Ser Leu Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro 
         35                  40                  45 

Gly Ala Pro Gly Pro Ser Gly Met Met Gly Arg Met Gly Phe Pro Gly 
     50                  55                  60 

Lys Asp Gly Gln Asp Gly His Asp Gly Asp Arg Gly Asp Ser Gly Glu 
 65                  70                  75                  80 

Glu Gly Pro Pro Gly Arg Thr Gly Asn Arg Gly Lys Pro Gly Pro Lys 
                 85                  90                  95 

Gly Lys Ala Gly Ala Ile Gly Arg Ala Gly Pro Arg Gly Pro Lys Gly 
            100                 105                 110 

Val Asn Gly Thr Pro Gly Lys His Gly Thr Pro Gly Lys Lys Gly Pro 
        115                 120                 125 

Lys Gly Lys Lys Gly Glu Pro Gly Leu Pro Gly Pro Cys Ser Cys Gly 
    130                 135                 140 

Ser Gly His Thr Lys Ser Ala Phe Ser Val Ala Val Thr Lys Ser Tyr 
145                 150                 155                 160 

Pro Arg Glu Arg Leu Pro Ile Lys Phe Asp Lys Ile Leu Met Asn Glu 
                165                 170                 175 

Gly Gly His Tyr Asn Ala Ser Ser Gly Lys Phe Val Cys Gly Val Pro 
            180                 185                 190 

Gly Ile Tyr Tyr Phe Thr Tyr Asp Ile Thr Leu Ala Asn Lys His Leu 
        195                 200                 205 

Ala Ile Gly Leu Val His Asn Gly Gln Tyr Arg Ile Arg Thr Phe Asp 
    210                 215                 220 

Ala Asn Thr Gly Asn His Asp Val Ala Ser Gly Ser Thr Ile Leu Ala 
225                 230                 235                 240 

Leu Lys Gln Gly Asp Glu Val Trp Leu Gln Ile Phe Tyr Ser Glu Gln 
                245                 250                 255 

Asn Gly Leu Phe Tyr Asp Pro Tyr Trp Thr Asp Ser Leu Phe Thr Gly 
            260                 265                 270 

Phe Leu Ile Tyr Ala Asp Gln Asp Asp Pro Asn Glu Val 
        275                 280                 285 

 
           
             61  
             146  
             PRT  
             Homo sapiens  
           
            61 

Thr Arg Ser Leu Val Gly Ser Asp Ala Gly Pro Gly Pro Arg His Gln 
  1               5                  10                  15 

Pro Leu Ala Phe Asp Thr Glu Phe Val Asn Ile Gly Gly Asp Phe Asp 
             20                  25                  30 

Ala Ala Ala Gly Val Phe Arg Cys Arg Leu Pro Gly Ala Tyr Phe Phe 
         35                  40                  45 

Ser Phe Thr Leu Gly Lys Leu Pro Arg Lys Thr Leu Ser Val Lys Leu 
     50                  55                  60 

Met Lys Asn Arg Asp Glu Val Gln Ala Met Ile Tyr Asp Asp Gly Ala 
 65                  70                  75                  80 

Ser Arg Arg Arg Glu Met Gln Ser Gln Ser Val Met Leu Ala Leu Arg 
                 85                  90                  95 

Arg Gly Asp Ala Val Trp Leu Leu Ser His Asp His Asp Gly Tyr Gly 
            100                 105                 110 

Ala Tyr Ser Asn His Gly Lys Tyr Ile Thr Phe Ser Gly Phe Leu Val 
        115                 120                 125 

Tyr Pro Asp Leu Ala Pro Ala Ala Pro Pro Gly Leu Gly Ala Ser Glu 
    130                 135                 140 

Leu Leu 
145 

 
           
             62  
             251  
             PRT  
             Homo sapiens  
           
            62 

Met Lys Ile Pro Trp Gly Ser Ile Pro Val Leu Met Leu Leu Leu Leu 
  1               5                  10                  15 

Leu Gly Leu Ile Asp Ile Ser Gln Ala Gln Leu Ser Cys Thr Gly Pro 
             20                  25                  30 

Pro Ala Ile Pro Gly Ile Pro Gly Ile Pro Gly Thr Pro Gly Pro Asp 
         35                  40                  45 

Gly Gln Pro Gly Thr Pro Gly Ile Lys Gly Glu Lys Gly Leu Pro Gly 
     50                  55                  60 

Leu Ala Gly Asp His Gly Glu Phe Gly Glu Lys Gly Asp Pro Gly Ile 
 65                  70                  75                  80 

Pro Gly Asn Pro Gly Lys Val Gly Pro Lys Gly Pro Met Gly Pro Lys 
                 85                  90                  95 

Gly Gly Pro Gly Ala Pro Gly Ala Pro Gly Pro Lys Gly Glu Ser Gly 
            100                 105                 110 

Asp Tyr Lys Ala Thr Gln Lys Ile Ala Phe Ser Ala Thr Arg Thr Ile 
        115                 120                 125 

Asn Val Pro Leu Arg Arg Asp Gln Thr Ile Arg Phe Asp His Val Ile 
    130                 135                 140 

Thr Asn Met Asn Asn Asn Tyr Glu Pro Arg Ser Gly Lys Phe Thr Cys 
145                 150                 155                 160 

Lys Val Pro Gly Leu Tyr Tyr Phe Thr Tyr His Ala Ser Ser Arg Gly 
                165                 170                 175 

Asn Leu Cys Val Asn Leu Met Arg Gly Arg Glu Arg Ala Gln Lys Val 
            180                 185                 190 

Val Thr Phe Cys Asp Tyr Ala Tyr Asn Thr Phe Gln Val Thr Thr Gly 
        195                 200                 205 

Gly Met Val Leu Lys Leu Glu Gln Gly Glu Asn Val Phe Leu Gln Ala 
    210                 215                 220 

Thr Asp Lys Asn Ser Leu Leu Gly Met Glu Gly Ala Asn Ser Ile Phe 
225                 230                 235                 240 

Ser Gly Phe Leu Leu Phe Pro Asp Met Glu Ala 
                245                 250 

 
           
             63  
             975  
             PRT  
             Homo sapiens  
           
            63 

Met Pro Cys Pro Ser Ala Leu Val Tyr Arg Val Asn Phe Arg Pro Arg 
  1               5                  10                  15 

Tyr Val Thr Arg Tyr Lys Thr Val Thr Gln Leu Glu Trp Arg Cys Cys 
             20                  25                  30 

Pro Gly Phe Arg Gly Gly Asp Cys Gln Glu Gly Pro Lys Asp Pro Val 
         35                  40                  45 

Lys Thr Leu Arg Pro Thr Pro Ala Arg Pro Arg Asn Ser Leu Lys Lys 
     50                  55                  60 

Ala Thr Asp Asn Glu Pro Ser Gln Phe Ser Glu Pro Arg Lys Thr Leu 
 65                  70                  75                  80 

Ser Pro Thr Gly Thr Ala Gln Pro Ser Trp Gly Val Asp Pro Lys Glu 
                 85                  90                  95 

Gly Pro Gln Glu Leu Gln Glu Lys Lys Ile Gln Val Leu Glu Glu Lys 
            100                 105                 110 

Val Leu Arg Leu Thr Arg Thr Val Leu Asp Leu Gln Ser Ser Leu Ala 
        115                 120                 125 

Gly Val Ser Glu Asn Leu Lys His Ala Thr Gln Asp Asp Ala Ser Arg 
    130                 135                 140 

Thr Arg Ala Pro Gly Leu Ser Ser Gln His Pro Lys Pro Asp Thr Thr 
145                 150                 155                 160 

Val Ser Gly Asp Thr Glu Thr Gly Gln Ser Pro Gly Val Phe Asn Thr 
                165                 170                 175 

Lys Glu Ser Gly Met Lys Asp Ile Lys Ser Glu Leu Ala Glu Val Lys 
            180                 185                 190 

Asp Thr Leu Lys Asn Lys Ser Asp Lys Leu Glu Glu Leu Asp Gly Lys 
        195                 200                 205 

Val Lys Gly Tyr Glu Gly Gln Leu Arg Gln Leu Gln Glu Ala Ala Gln 
    210                 215                 220 

Gly Pro Thr Val Thr Met Thr Thr Asn Glu Leu Tyr Gln Ala Tyr Val 
225                 230                 235                 240 

Asp Ser Lys Ile Asp Ala Leu Arg Glu Glu Leu Met Glu Gly Met Asp 
                245                 250                 255 

Arg Lys Leu Ala Asp Leu Lys Asn Ser Cys Glu Tyr Lys Leu Thr Gly 
            260                 265                 270 

Leu Gln Gln Gln Cys Asp Asp Tyr Gly Ser Ser Tyr Leu Gly Val Ile 
        275                 280                 285 

Glu Leu Ile Gly Glu Lys Glu Thr Ser Leu Arg Lys Glu Ile Asn Asn 
    290                 295                 300 

Leu Arg Ala Arg Leu Gln Glu Pro Ser Ala Gln Ala Asn Cys Cys Asp 
305                 310                 315                 320 

Ser Glu Lys Asn Gly Asp Ile Gly Gln Gln Ile Lys Thr Leu Asp Gln 
                325                 330                 335 

Lys Ile Glu Arg Val Ala Glu Ala Thr Arg Met Leu Asn Gly Arg Leu 
            340                 345                 350 

Asp Asn Glu Phe Asp Arg Leu Ile Val Pro Glu Pro Asp Val Asp Phe 
        355                 360                 365 

Asp Ala Lys Trp Asn Glu Leu Asp Ala Arg Ile Asn Val Thr Glu Lys 
    370                 375                 380 

Asn Ala Glu Glu His Cys Phe Tyr Ile Glu Glu Thr Leu Arg Gly Ala 
385                 390                 395                 400 

Ile Asn Gly Glu Val Gly Asp Leu Lys Gln Leu Val Asp Gln Lys Ile 
                405                 410                 415 

Gln Ser Leu Glu Asp Arg Leu Gly Ser Val Leu Leu Gln Met Thr Asn 
            420                 425                 430 

Asn Thr Gly Ala Glu Leu Ser Pro Pro Gly Ala Ala Ala Leu Pro Gly 
        435                 440                 445 

Val Ser Gly Ser Gly Asp Glu Arg Val Met Met Glu Leu Asn His Leu 
    450                 455                 460 

Lys Asp Lys Val Gln Val Val Glu Asp Ile Cys Leu Leu Asn Ile Gln 
465                 470                 475                 480 

Gly Lys Pro His Gly Met Glu Gly Ala Leu Pro Asn Arg Glu Asp Arg 
                485                 490                 495 

Ala Val Arg Asp Ser Leu His Leu Leu Lys Ser Leu Asn Asp Thr Met 
            500                 505                 510 

His Arg Lys Phe Gln Glu Thr Glu Gln Thr Ile Gln Lys Leu Gln Gln 
        515                 520                 525 

Asp Phe Ser Phe Leu Tyr Ser Gln Leu Asn His Thr Glu Asn Asp Val 
    530                 535                 540 

Thr His Leu Gln Lys Glu Met Ser Asn Cys Arg Ala Gly Glu Asn Ala 
545                 550                 555                 560 

Gly Met Gly Arg Phe Thr Lys Val Gly Glu Gln Glu Arg Thr Val Asp 
                565                 570                 575 

Thr Leu Pro Ser Pro Gln His Pro Val Ala His Cys Cys Ser Gln Leu 
            580                 585                 590 

Glu Glu Arg Trp Gln Arg Leu Gln Ser Gln Val Ile Ser Glu Leu Asp 
        595                 600                 605 

Ala Cys Lys Glu Cys Thr Gln Gly Val Gln Arg Glu Val Ser Met Val 
    610                 615                 620 

Glu Gly Arg Val Ser His Met Glu Lys Thr Cys Ser Lys Leu Asp Ser 
625                 630                 635                 640 

Ile Ser Gly Asn Leu Gln Arg Ile Lys Glu Gly Leu Asn Lys His Val 
                645                 650                 655 

Ser Ser Leu Trp Asn Cys Val Arg Gln Met Asn Gly Thr Leu Arg Ser 
            660                 665                 670 

His Ser Arg Asp Ile Ser Gly Leu Lys Asn Ser Val Gln Gln Phe Tyr 
        675                 680                 685 

Ser His Val Phe Gln Ile Ser Thr Asp Leu Gln Asp Leu Val Lys Phe 
    690                 695                 700 

Gln Pro Ser Ala Lys Ala Pro Ser Pro Pro Pro Pro Ala Glu Ala Pro 
705                 710                 715                 720 

Lys Glu Pro Leu Gln Pro Glu Pro Ala Pro Pro Arg Pro Ser Gly Pro 
                725                 730                 735 

Ala Thr Ala Glu Asp Pro Gly Arg Arg Pro Val Leu Pro Gln Arg Pro 
            740                 745                 750 

Pro Glu Glu Arg Pro Pro Gln Pro Pro Gly Ser Thr Gly Val Ile Ala 
        755                 760                 765 

Glu Thr Gly Gln Ala Gly Pro Pro Ala Gly Ala Gly Val Ser Gly Arg 
    770                 775                 780 

Gly Leu Pro Arg Gly Val Asp Gly Gln Thr Gly Ser Gly Thr Val Pro 
785                 790                 795                 800 

Gly Ala Glu Gly Phe Ala Gly Ala Pro Gly Tyr Pro Lys Ser Pro Pro 
                805                 810                 815 

Val Ala Ser Pro Gly Ala Pro Val Pro Ser Leu Val Ser Phe Ser Ala 
            820                 825                 830 

Gly Leu Thr Gln Lys Pro Phe Pro Ser Asp Gly Gly Val Val Leu Phe 
        835                 840                 845 

Asn Lys Val Leu Val Asn Asp Gly Asp Val Tyr Asn Pro Ser Thr Gly 
    850                 855                 860 

Val Phe Thr Ala Pro Tyr Asp Gly Arg Tyr Leu Ile Thr Ala Thr Leu 
865                 870                 875                 880 

Thr Pro Glu Arg Asp Ala Tyr Val Glu Ala Val Leu Ser Val Ser Asn 
                885                 890                 895 

Ala Ser Val Ala Gln Leu His Thr Ala Gly Tyr Arg Arg Glu Phe Leu 
            900                 905                 910 

Glu Tyr His Arg Pro Pro Gly Ala Leu His Thr Cys Gly Gly Pro Gly 
        915                 920                 925 

Ala Phe His Leu Ile Val His Leu Lys Ala Gly Asp Ala Val Asn Val 
    930                 935                 940 

Val Val Thr Gly Gly Lys Leu Ala His Thr Asp Phe Asp Glu Met Tyr 
945                 950                 955                 960 

Ser Thr Phe Ser Gly Val Phe Leu Tyr Pro Phe Leu Ser His Leu 
                965                 970                 975 

 
           
             64  
             158  
             PRT  
             Homo sapiens  
           
            64 

Met Thr Pro Val Asp Val Pro Val Thr Asn Pro Ala Ala Thr Ile Leu 
  1               5                  10                  15 

Pro Val His Val Tyr Pro Leu Pro Gln Gln Met Arg Val Ala Phe Ser 
             20                  25                  30 

Ala Ala Arg Thr Ser Asn Leu Ala Pro Gly Thr Leu Asp Gln Pro Ile 
         35                  40                  45 

Val Phe Asp Leu Leu Leu Asn Asn Leu Gly Glu Thr Phe Asp Leu Gln 
     50                  55                  60 

Leu Gly Arg Phe Asn Cys Pro Val Asn Gly Thr Tyr Val Phe Ile Phe 
 65                  70                  75                  80 

His Met Leu Lys Leu Ala Val Asn Val Pro Leu Tyr Val Asn Leu Met 
                 85                  90                  95 

Lys Asn Glu Glu Val Leu Val Ser Ala Tyr Ala Asn Asp Gly Ala Pro 
            100                 105                 110 

Asp His Glu Thr Ala Ser Asn His Ala Ile Leu Gln Leu Phe Gln Gly 
        115                 120                 125 

Asp Gln Ile Trp Leu Arg Leu His Arg Gly Ala Ile Tyr Gly Ser Ser 
    130                 135                 140 

Trp Lys Tyr Ser Thr Phe Ser Gly Tyr Leu Leu Tyr Gln Asp 
145                 150                 155 

 
           
             65  
             605  
             PRT  
             Homo sapiens  
           
            65 

Met Gly Tyr Leu Glu Leu Lys Glu Asn Gln Gly His Arg Asp Ile Gln 
  1               5                  10                  15 

Glu Leu Glu Ser Gln Val Cys Leu Glu Cys Gln Gly Lys Pro Gly Ala 
             20                  25                  30 

Met Gly Met Pro Gly Ala Lys Gly Glu Ile Gly Gln Lys Gly Glu Ile 
         35                  40                  45 

Gly Pro Met Gly Ile Pro Gly Pro Gln Gly Pro Pro Gly Pro His Gly 
     50                  55                  60 

Leu Pro Gly Ile Gly Lys Pro Gly Gly Pro Gly Leu Pro Gly Gln Pro 
 65                  70                  75                  80 

Gly Pro Lys Gly Asp Arg Gly Pro Lys Gly Leu Pro Gly Pro Gln Gly 
                 85                  90                  95 

Leu Arg Gly Pro Lys Gly Asp Lys Gly Phe Gly Met Pro Gly Ala Pro 
            100                 105                 110 

Gly Val Lys Gly Pro Pro Gly Met His Gly Pro Pro Gly Pro Val Gly 
        115                 120                 125 

Leu Pro Gly Val Gly Lys Pro Gly Val Thr Gly Phe Pro Gly Pro Gln 
    130                 135                 140 

Gly Pro Leu Gly Lys Pro Gly Ala Pro Gly Glu Pro Gly Pro Gln Gly 
145                 150                 155                 160 

Pro Ile Gly Val Pro Gly Val Gln Gly Pro Pro Gly Ile Pro Gly Ile 
                165                 170                 175 

Gly Lys Pro Gly Gln Asp Gly Ile Pro Gly Gln Pro Gly Phe Pro Gly 
            180                 185                 190 

Gly Lys Gly Glu Gln Gly Leu Pro Gly Leu Pro Gly Pro Pro Gly Leu 
        195                 200                 205 

Pro Gly Ile Gly Lys Pro Gly Phe Pro Gly Pro Lys Gly Asp Arg Gly 
    210                 215                 220 

Met Gly Gly Val Pro Gly Ala Leu Gly Pro Arg Gly Glu Lys Gly Pro 
225                 230                 235                 240 

Ile Gly Ala Pro Gly Ile Gly Gly Pro Pro Gly Glu Pro Gly Leu Pro 
                245                 250                 255 

Gly Ile Pro Gly Pro Met Gly Pro Pro Gly Ala Ile Gly Phe Pro Gly 
            260                 265                 270 

Pro Lys Gly Glu Gly Gly Ile Val Gly Pro Gln Gly Pro Pro Gly Pro 
        275                 280                 285 

Lys Gly Glu Pro Gly Leu Gln Gly Phe Pro Gly Lys Pro Gly Phe Leu 
    290                 295                 300 

Gly Glu Val Gly Pro Pro Gly Met Arg Gly Leu Pro Gly Pro Ile Gly 
305                 310                 315                 320 

Pro Lys Gly Glu Ala Gly Gln Lys Gly Val Pro Gly Leu Pro Gly Val 
                325                 330                 335 

Pro Gly Leu Leu Gly Pro Lys Gly Glu Pro Gly Ile Pro Gly Asp Gln 
            340                 345                 350 

Gly Leu Gln Gly Pro Pro Gly Ile Pro Gly Ile Gly Gly Pro Ser Gly 
        355                 360                 365 

Pro Ile Gly Pro Pro Gly Ile Pro Gly Pro Lys Gly Glu Pro Gly Leu 
    370                 375                 380 

Pro Gly Pro Pro Gly Phe Pro Gly Ile Gly Lys Pro Gly Val Ala Gly 
385                 390                 395                 400 

Leu His Gly Pro Pro Gly Lys Pro Gly Ala Leu Gly Pro Gln Gly Gln 
                405                 410                 415 

Pro Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly Pro Pro 
            420                 425                 430 

Ala Val Met Pro Pro Thr Pro Pro Pro Gln Gly Glu Tyr Leu Pro Asp 
        435                 440                 445 

Met Gly Leu Gly Ile Asp Gly Val Lys Pro Pro His Ala Tyr Gly Ala 
    450                 455                 460 

Lys Lys Gly Lys Asn Gly Gly Pro Ala Tyr Glu Met Pro Ala Phe Thr 
465                 470                 475                 480 

Ala Glu Leu Thr Ala Pro Phe Pro Pro Val Gly Ala Pro Val Lys Phe 
                485                 490                 495 

Asn Lys Leu Leu Tyr Asn Gly Arg Gln Asn Tyr Asn Pro Gln Thr Gly 
            500                 505                 510 

Ile Phe Thr Cys Glu Val Pro Gly Val Tyr Tyr Phe Ala Tyr His Val 
        515                 520                 525 

His Cys Lys Gly Gly Asn Val Trp Val Ala Leu Phe Lys Asn Asn Glu 
    530                 535                 540 

Pro Val Met Tyr Thr Tyr Asp Glu Tyr Lys Lys Gly Phe Leu Asp Gln 
545                 550                 555                 560 

Ala Ser Gly Ser Ala Val Leu Leu Leu Arg Pro Gly Asp Arg Val Phe 
                565                 570                 575 

Leu Gln Met Pro Ser Glu Gln Ala Ala Gly Leu Tyr Ala Gly Gln Tyr 
            580                 585                 590 

Val His Ser Ser Phe Ser Gly Tyr Leu Leu Tyr Pro Met 
        595                 600                 605 

 
           
             66  
             194  
             PRT  
             Homo sapiens  
           
            66 

Arg Gly Pro Trp Leu Pro Trp Asn Thr Gly Pro Pro Gly Pro Pro Gly 
  1               5                  10                  15 

Pro Pro Gly Pro Pro Gly Ala Pro Gly Ala Phe Asp Glu Thr Gly Ile 
             20                  25                  30 

Ala Gly Leu His Leu Pro Asn Gly Gly Val Glu Gly Ala Val Leu Gly 
         35                  40                  45 

Lys Gly Gly Lys Pro Gln Phe Gly Leu Gly Glu Leu Ser Ala His Ala 
     50                  55                  60 

Thr Pro Ala Phe Thr Ala Val Leu Thr Ser Pro Phe Pro Ala Ser Gly 
 65                  70                  75                  80 

Met Pro Val Lys Phe Asp Arg Thr Leu Tyr Asn Gly His Ser Gly Tyr 
                 85                  90                  95 

Asn Pro Ala Thr Gly Ile Phe Thr Cys Pro Val Gly Gly Val Tyr Tyr 
            100                 105                 110 

Phe Ala Tyr His Val His Val Lys Gly Thr Asn Val Trp Val Ala Leu 
        115                 120                 125 

Tyr Lys Asn Asn Val Pro Ala Thr Tyr Thr Tyr Asp Glu Tyr Lys Lys 
    130                 135                 140 

Gly Tyr Leu Asp Gln Ala Ser Gly Gly Ala Val Leu Gln Leu Arg Pro 
145                 150                 155                 160 

Asn Asp Gln Val Trp Val Gln Met Pro Ser Asp Gln Ala Asn Gly Leu 
                165                 170                 175 

Tyr Ser Thr Glu Tyr Ile His Ser Ser Phe Ser Gly Phe Leu Leu Cys 
            180                 185                 190 

Pro Thr 

 
           
             67  
             244  
             PRT  
             Homo sapiens  
           
            67 

Met Leu Leu Leu Gly Ala Val Leu Leu Leu Leu Ala Leu Pro Gly His 
  1               5                  10                  15 

Asp Gln Glu Thr Thr Thr Gln Gly Pro Gly Val Leu Leu Pro Leu Pro 
             20                  25                  30 

Lys Gly Ala Cys Thr Gly Trp Met Ala Gly Ile Pro Gly His Pro Gly 
         35                  40                  45 

His Asn Gly Ala Pro Gly Arg Asp Gly Arg Asp Gly Thr Pro Gly Glu 
     50                  55                  60 

Lys Gly Glu Lys Gly Asp Pro Gly Leu Ile Gly Pro Lys Gly Asp Ile 
 65                  70                  75                  80 

Gly Glu Thr Gly Val Pro Gly Ala Glu Gly Pro Arg Gly Phe Pro Gly 
                 85                  90                  95 

Ile Gln Gly Arg Lys Gly Glu Pro Gly Glu Gly Ala Tyr Val Tyr Arg 
            100                 105                 110 

Ser Ala Phe Ser Val Gly Leu Glu Thr Tyr Val Thr Ile Pro Asn Met 
        115                 120                 125 

Pro Ile Arg Phe Thr Lys Ile Phe Tyr Asn Gln Gln Asn His Tyr Asp 
    130                 135                 140 

Gly Ser Thr Gly Lys Phe His Cys Asn Ile Pro Gly Leu Tyr Tyr Phe 
145                 150                 155                 160 

Ala Tyr His Ile Thr Val Tyr Met Lys Asp Val Lys Val Ser Leu Phe 
                165                 170                 175 

Lys Lys Asp Lys Ala Met Leu Phe Thr Tyr Asp Gln Tyr Gln Glu Asn 
            180                 185                 190 

Asn Val Asp Gln Ala Ser Gly Ser Val Leu Leu His Leu Glu Val Gly 
        195                 200                 205 

Asp Gln Val Trp Leu Gln Val Tyr Gly Glu Gly Glu Arg Asn Gly Leu 
    210                 215                 220 

Tyr Ala Asp Asn Asp Asn Asp Ser Thr Phe Thr Gly Phe Leu Leu Tyr 
225                 230                 235                 240 

His Asp Thr Asn 

 
           
             68  
             361  
             PRT  
             Homo sapiens  
           
            68 

Thr Arg Pro Asp Ser Leu Asn Glu Leu Gln Thr Thr Val Glu Gly Gln 
  1               5                  10                  15 

Gly Ala Asp Leu Ala Asp Leu Gly Ala Thr Lys Asp Arg Ile Ile Ser 
             20                  25                  30 

Glu Ile Asn Arg Leu Gln Gln Glu Ala Thr Glu His Ala Thr Glu Ser 
         35                  40                  45 

Glu Glu Arg Phe Arg Gly Leu Glu Glu Gly Gln Ala Gln Ala Gly Gln 
     50                  55                  60 

Cys Pro Ser Leu Glu Gly Arg Leu Gly Arg Leu Glu Gly Val Cys Glu 
 65                  70                  75                  80 

Arg Leu Asp Thr Val Ala Gly Gly Leu Gln Gly Leu Arg Glu Gly Leu 
                 85                  90                  95 

Ser Arg His Val Ala Gly Leu Trp Ala Gly Leu Arg Glu Thr Asn Thr 
            100                 105                 110 

Thr Ser Gln Met Gln Ala Ala Leu Leu Glu Lys Leu Val Gly Gly Gln 
        115                 120                 125 

Ala Gly Leu Gly Arg Arg Leu Gly Ala Leu Asn Ser Ser Leu Gln Leu 
    130                 135                 140 

Leu Glu Asp Arg Leu His Gln Leu Ser Leu Lys Asp Leu Thr Gly Pro 
145                 150                 155                 160 

Ala Gly Glu Ala Gly Pro Pro Gly Pro Pro Gly Leu Gln Gly Pro Pro 
                165                 170                 175 

Gly Pro Ala Gly Pro Pro Gly Ser Pro Gly Lys Asp Gly Gln Glu Gly 
            180                 185                 190 

Pro Ile Gly Pro Pro Gly Pro Gln Gly Glu Gln Gly Val Glu Gly Ala 
        195                 200                 205 

Pro Ala Ala Pro Val Pro Gln Val Ala Phe Ser Ala Ala Leu Ser Leu 
    210                 215                 220 

Pro Arg Ser Glu Pro Gly Thr Val Pro Phe Asp Arg Val Leu Leu Asn 
225                 230                 235                 240 

Asp Gly Gly Tyr Tyr Asp Pro Glu Thr Gly Val Phe Thr Ala Pro Leu 
                245                 250                 255 

Ala Gly Arg Tyr Leu Leu Ser Ala Val Leu Thr Gly His Arg His Glu 
            260                 265                 270 

Lys Val Glu Ala Val Leu Ser Arg Ser Asn Gln Gly Val Ala Arg Val 
        275                 280                 285 

Asp Ser Gly Gly Tyr Glu Pro Glu Gly Leu Glu Asn Lys Pro Val Ala 
    290                 295                 300 

Glu Ser Gln Pro Ser Pro Gly Thr Leu Gly Val Phe Ser Leu Ile Leu 
305                 310                 315                 320 

Pro Leu Gln Ala Gly Asp Thr Val Cys Val Asp Leu Val Met Gly Gln 
                325                 330                 335 

Leu Ala His Ser Glu Glu Pro Leu Thr Ile Phe Ser Gly Ala Leu Leu 
            340                 345                 350 

Tyr Gly Asp Pro Glu Leu Glu His Ala 
        355                 360 

 
           
             69  
             333  
             PRT  
             Homo sapiens  
           
            69 

Met Arg Ile Trp Trp Leu Leu Leu Ala Ile Glu Ile Cys Thr Gly Asn 
  1               5                  10                  15 

Ile Asn Ser Gln Asp Thr Cys Arg Gln Gly His Pro Gly Ile Pro Gly 
             20                  25                  30 

Asn Pro Gly His Asn Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Ala 
         35                  40                  45 

Lys Gly Asp Lys Gly Asp Ala Gly Glu Pro Gly Arg Pro Gly Ser Pro 
     50                  55                  60 

Gly Lys Asp Gly Thr Ser Gly Glu Lys Gly Glu Arg Gly Ala Asp Gly 
 65                  70                  75                  80 

Lys Val Glu Ala Lys Gly Ile Lys Gly Asp Gln Gly Ser Arg Gly Ser 
                 85                  90                  95 

Pro Gly Lys His Gly Pro Lys Gly Leu Ala Gly Pro Met Gly Glu Lys 
            100                 105                 110 

Gly Leu Arg Gly Glu Thr Gly Pro Gln Gly Gln Lys Gly Asn Lys Gly 
        115                 120                 125 

Asp Val Gly Pro Thr Gly Pro Glu Gly Pro Arg Gly Asn Ile Gly Pro 
    130                 135                 140 

Leu Gly Pro Thr Gly Leu Pro Gly Pro Met Gly Pro Ile Gly Lys Pro 
145                 150                 155                 160 

Gly Pro Lys Gly Glu Ala Gly Pro Thr Gly Pro Gln Gly Glu Pro Gly 
                165                 170                 175 

Val Arg Gly Ile Arg Gly Trp Lys Gly Asp Arg Gly Glu Lys Gly Lys 
            180                 185                 190 

Ile Gly Glu Thr Leu Val Leu Pro Lys Ser Ala Phe Thr Val Gly Leu 
        195                 200                 205 

Thr Val Leu Ser Lys Phe Pro Ser Ser Asp Val Pro Ile Lys Phe Asp 
    210                 215                 220 

Lys Ile Leu Tyr Asn Glu Phe Asn His Tyr Asp Thr Ala Ala Gly Lys 
225                 230                 235                 240 

Phe Thr Cys His Ile Ala Gly Val Tyr Tyr Phe Thr Tyr His Ile Thr 
                245                 250                 255 

Val Phe Ser Arg Asn Val Gln Val Ser Leu Val Lys Asn Gly Val Lys 
            260                 265                 270 

Ile Leu His Thr Lys Asp Ala Tyr Met Ser Ser Glu Asp Gln Ala Ser 
        275                 280                 285 

Gly Gly Ile Val Leu Gln Leu Lys Leu Gly Asp Glu Val Trp Leu Gln 
    290                 295                 300 

Val Thr Gly Gly Glu Arg Phe Asn Gly Leu Phe Ala Asp Glu Asp Asp 
305                 310                 315                 320 

Asp Thr Thr Phe Thr Gly Phe Leu Leu Phe Ser Ser Pro 
                325                 330 

 
           
             70  
             229  
             PRT  
             Homo sapiens  
           
            70 

Met Asp Leu Leu Gln Phe Leu Ala Phe Leu Phe Val Leu Leu Leu Ser 
  1               5                  10                  15 

Gly Met Gly Ala Thr Gly Thr Leu Arg Thr Ser Leu Asp Pro Ser Leu 
             20                  25                  30 

Glu Ile Tyr Lys Lys Met Phe Glu Val Lys Arg Arg Glu Gln Leu Leu 
         35                  40                  45 

Ala Leu Lys Asn Leu Ala Gln Leu Asn Asp Ile His Gln Gln Tyr Lys 
     50                  55                  60 

Ile Leu Asp Val Met Leu Lys Gly Leu Phe Lys Val Leu Glu Asp Ser 
 65                  70                  75                  80 

Arg Thr Val Leu Thr Ala Ala Asp Val Leu Pro Asp Gly Pro Phe Pro 
                 85                  90                  95 

Gln Asp Glu Lys Leu Lys Asp Ala Phe Ser His Val Val Glu Asn Thr 
            100                 105                 110 

Ala Phe Phe Gly Asp Val Val Leu Arg Phe Pro Arg Ile Val His Tyr 
        115                 120                 125 

Tyr Phe Asp His Asn Ser Asn Trp Asn Leu Leu Ile Arg Trp Gly Ile 
    130                 135                 140 

Ser Phe Cys Asn Gln Thr Gly Val Phe Asn Gln Gly Pro His Ser Pro 
145                 150                 155                 160 

Ile Leu Ser Leu Met Ala Gln Glu Leu Gly Ile Ser Glu Lys Asp Ser 
                165                 170                 175 

Asn Phe Gln Asn Pro Phe Lys Ile Asp Arg Thr Glu Phe Ile Pro Ser 
            180                 185                 190 

Thr Asp Pro Phe Gln Lys Ala Leu Arg Glu Glu Glu Lys Arg Arg Lys 
        195                 200                 205 

Lys Glu Glu Lys Arg Lys Glu Ile Arg Lys Gly Pro Arg Ile Ser Arg 
    210                 215                 220 

Ser Gln Ser Glu Leu 
225 

 
           
             71  
             229  
             PRT  
             Homo sapiens  
           
            71 

Met Asp Leu Leu Gln Phe Leu Ala Phe Leu Phe Val Leu Leu Leu Ser 
  1               5                  10                  15 

Gly Met Gly Ala Thr Gly Thr Leu Arg Thr Ser Leu Asp Pro Ser Leu 
             20                  25                  30 

Glu Ile Tyr Lys Lys Met Phe Glu Val Lys Arg Arg Glu Gln Leu Leu 
         35                  40                  45 

Ala Leu Lys Asn Leu Ala Gln Leu Asn Asp Ile His Gln Gln Tyr Lys 
     50                  55                  60 

Ile Leu Asp Val Met Leu Lys Gly Leu Phe Lys Val Leu Glu Asp Ser 
 65                  70                  75                  80 

Arg Thr Val Leu Thr Ala Ala Asp Val Leu Pro Asp Gly Pro Cys Pro 
                 85                  90                  95 

Gln Asp Glu Lys Leu Lys Asp Ala Phe Ser His Val Val Glu Asn Thr 
            100                 105                 110 

Ala Phe Phe Gly Asp Val Val Leu Arg Phe Pro Arg Ile Val His Tyr 
        115                 120                 125 

Tyr Phe Asp His Asn Ser Asn Trp Asn Leu Leu Ile Arg Trp Gly Ile 
    130                 135                 140 

Ser Phe Cys Asn Gln Thr Gly Val Phe Asn Gln Gly Pro His Ser Pro 
145                 150                 155                 160 

Ile Leu Ser Leu Met Ala Gln Glu Leu Gly Ile Ser Glu Lys Asp Ser 
                165                 170                 175 

Asn Phe Gln Asn Pro Phe Lys Ile Asp Arg Thr Glu Phe Ile Pro Ser 
            180                 185                 190 

Thr Asp Pro Phe Gln Lys Ala Leu Arg Glu Glu Glu Lys Arg Arg Lys 
        195                 200                 205 

Lys Glu Glu Lys Arg Lys Glu Ile Arg Lys Gly Pro Arg Ile Ser Arg 
    210                 215                 220 

Ser Gln Ser Glu Leu 
225 

 
           
             72  
             459  
             PRT  
             Homo sapiens  
             
               SITE  
               (321)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            72 

Met Gly Gly Pro Arg Ala Trp Ala Leu Leu Cys Leu Gly Leu Leu Leu 
  1               5                  10                  15 

Pro Gly Gly Gly Ala Ala Trp Ser Ile Gly Ala Ala Pro Phe Ser Gly 
             20                  25                  30 

Arg Arg Asn Trp Cys Ser Tyr Val Val Thr Arg Thr Ile Ser Cys His 
         35                  40                  45 

Val Gln Asn Gly Thr Tyr Leu Gln Arg Val Leu Gln Asn Cys Pro Trp 
     50                  55                  60 

Pro Met Ser Cys Pro Gly Ser Ser Tyr Arg Thr Val Val Arg Pro Thr 
 65                  70                  75                  80 

Tyr Lys Val Met Tyr Lys Ile Val Thr Ala Arg Glu Trp Arg Cys Cys 
                 85                  90                  95 

Pro Gly His Ser Gly Val Ser Cys Glu Glu Val Ala Ala Ser Ser Ala 
            100                 105                 110 

Ser Leu Glu Pro Met Trp Ser Gly Ser Thr Met Arg Arg Met Ala Leu 
        115                 120                 125 

Arg Pro Thr Ala Phe Ser Gly Cys Leu Asn Cys Ser Lys Val Ser Glu 
    130                 135                 140 

Leu Thr Glu Arg Leu Lys Val Leu Glu Ala Lys Met Thr Met Leu Thr 
145                 150                 155                 160 

Val Ile Glu Gln Pro Val Pro Pro Thr Pro Ala Thr Pro Glu Asp Pro 
                165                 170                 175 

Ala Pro Leu Trp Gly Pro Pro Pro Ala Gln Gly Ser Pro Gly Asp Gly 
            180                 185                 190 

Gly Leu Gln Asp Gln Val Gly Ala Trp Gly Leu Pro Gly Pro Thr Gly 
        195                 200                 205 

Pro Lys Gly Asp Ala Gly Ser Arg Gly Pro Met Gly Met Arg Gly Pro 
    210                 215                 220 

Pro Gly Pro Gln Gly Pro Pro Gly Ser Pro Gly Arg Ala Gly Ala Val 
225                 230                 235                 240 

Gly Thr Pro Gly Glu Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 
                245                 250                 255 

Pro Pro Gly Pro Pro Ala Pro Val Gly Pro Pro His Ala Arg Ile Ser 
            260                 265                 270 

Gln His Gly Asp Pro Leu Leu Ser Asn Thr Phe Thr Glu Thr Asn Asn 
        275                 280                 285 

His Trp Pro Gln Gly Pro Thr Gly Pro Pro Gly Pro Pro Gly Pro Met 
    290                 295                 300 

Gly Pro Pro Gly Pro Pro Gly Pro Thr Gly Val Pro Gly Ser Pro Gly 
305                 310                 315                 320 

Xaa Ile Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Ile Ser Gly His 
                325                 330                 335 

Pro Gly Glu Lys Gly Glu Lys Lys Xaa Leu Arg Gly Glu Pro Gly Pro 
            340                 345                 350 

Gln Gly Ser Ala Gly Gln Arg Gly Glu Pro Gly Pro Lys Gly Asp Pro 
        355                 360                 365 

Gly Glu Lys Ser His Trp Asn Gln Ser Trp Gly Leu Gly Gly Pro Cys 
    370                 375                 380 

Arg His Arg His Pro Gln Pro Pro Ser Gly Gln Glu Gly Gly His Ala 
385                 390                 395                 400 

Thr Asn Tyr Arg Asp Arg Gly Pro Gln Glu Pro Gly Arg Glu Arg Leu 
                405                 410                 415 

Arg Val Val Ala Ala Pro Glu Ala Asp Gln Ala Arg Leu Pro Leu Leu 
            420                 425                 430 

Pro Gly Leu Gly Gln Leu Pro Pro Gly Thr Ala Arg Pro Tyr Leu Leu 
        435                 440                 445 

Met Ser Ser Gly Ser Leu Leu Pro Ser Arg Pro 
    450                 455 

 
           
             73  
             443  
             PRT  
             Homo sapiens  
           
            73 

Met Gly Gly Pro Arg Ala Trp Ala Leu Leu Cys Leu Gly Leu Leu Leu 
  1               5                  10                  15 

Pro Gly Gly Gly Ala Ala Trp Ser Ile Gly Ala Ala Pro Phe Ser Gly 
             20                  25                  30 

Arg Arg Asn Trp Cys Ser Tyr Val Val Thr Arg Thr Ile Ser Cys His 
         35                  40                  45 

Val Gln Asn Gly Thr Tyr Leu Gln Arg Val Leu Gln Asn Cys Pro Trp 
     50                  55                  60 

Pro Met Ser Cys Pro Gly Ser Ser Tyr Arg Thr Val Val Arg Pro Thr 
 65                  70                  75                  80 

Tyr Lys Val Met Tyr Lys Ile Val Thr Ala Arg Glu Trp Arg Cys Cys 
                 85                  90                  95 

Pro Gly His Ser Gly Val Ser Cys Glu Glu Val Ala Ala Ser Ser Ala 
            100                 105                 110 

Ser Leu Glu Pro Met Trp Ser Gly Ser Thr Met Arg Arg Met Ala Leu 
        115                 120                 125 

Arg Pro Thr Ala Phe Ser Gly Cys Leu Asn Cys Ser Lys Val Ser Glu 
    130                 135                 140 

Leu Thr Glu Arg Leu Lys Val Leu Glu Ala Lys Met Thr Met Leu Thr 
145                 150                 155                 160 

Val Ile Glu Gln Pro Val Pro Pro Thr Pro Ala Thr Pro Glu Asp Pro 
                165                 170                 175 

Ala Pro Leu Trp Gly Pro Pro Pro Ala Gln Gly Ser Pro Gly Asp Gly 
            180                 185                 190 

Gly Leu Gln Asp Gln Val Gly Ala Trp Gly Leu Pro Gly Pro Thr Gly 
        195                 200                 205 

Pro Lys Gly Asp Ala Gly Ser Arg Gly Pro Met Gly Met Arg Gly Pro 
    210                 215                 220 

Pro Gly Pro Gln Gly Pro Pro Gly Ser Pro Gly Arg Ala Gly Ala Val 
225                 230                 235                 240 

Gly Thr Pro Gly Glu Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 
                245                 250                 255 

Pro Pro Gly Pro Pro Ala Pro Val Gly Pro Pro His Ala Arg Ile Ser 
            260                 265                 270 

Gln His Gly Asp Pro Leu Leu Ser Asn Thr Phe Thr Glu Thr Asn Asn 
        275                 280                 285 

His Trp Pro Gln Gly Pro Thr Gly Pro Pro Gly Pro Pro Gly Pro Met 
    290                 295                 300 

Gly Pro Pro Gly Pro Pro Gly Pro Thr Gly Val Pro Gly Ser Pro Gly 
305                 310                 315                 320 

His Ile Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Ile Ser Gly His 
                325                 330                 335 

Pro Gly Glu Lys Gly Glu Arg Gly Leu Arg Gly Glu Pro Gly Pro Gln 
            340                 345                 350 

Gly Ser Ala Gly Gln Arg Gly Glu Pro Gly Pro Lys Gly Asp Pro Gly 
        355                 360                 365 

Glu Lys Ser His Trp Gly Glu Gly Leu His Gln Leu Arg Glu Ala Leu 
    370                 375                 380 

Lys Ile Leu Ala Glu Arg Val Leu Ile Leu Glu Thr Met Ile Gly Leu 
385                 390                 395                 400 

Tyr Glu Pro Glu Leu Gly Ser Gly Ala Gly Pro Ala Gly Thr Gly Thr 
                405                 410                 415 

Pro Ser Leu Leu Arg Gly Lys Arg Gly Gly His Ala Thr Asn Tyr Arg 
            420                 425                 430 

Ile Val Ala Pro Arg Ser Arg Asp Glu Arg Gly 
        435                 440 

 
           
             74  
             12  
             PRT  
             Homo sapiens  
           
            74 

Gly Arg Pro Arg Pro Pro Ala Leu Val Leu Ala Arg 
  1               5                  10 

 
           
             75  
             19  
             PRT  
             Homo sapiens  
           
            75 

Gly Thr Ala Arg Pro Tyr Leu Leu Met Ser Ser Gly Ser Leu Leu Pro 
  1               5                  10                  15 

Ser Arg Pro 

 
           
             76  
             421  
             PRT  
             Homo sapiens  
           
            76 

Met Gly Gly Pro Arg Ala Trp Ala Leu Leu Cys Leu Gly Leu Leu Leu 
  1               5                  10                  15 

Pro Gly Gly Gly Ala Ala Trp Ser Ile Gly Ala Ala Pro Phe Ser Gly 
             20                  25                  30 

Arg Arg Asn Trp Cys Ser Tyr Val Val Thr Arg Thr Ile Ser Cys His 
         35                  40                  45 

Val Gln Asn Gly Thr Tyr Leu Gln Arg Val Leu Gln Asn Cys Pro Trp 
     50                  55                  60 

Pro Met Ser Cys Pro Gly Ser Ser Tyr Arg Thr Val Val Arg Pro Thr 
 65                  70                  75                  80 

Tyr Lys Val Met Tyr Lys Ile Val Thr Ala Arg Glu Trp Arg Cys Cys 
                 85                  90                  95 

Pro Gly His Ser Gly Val Ser Cys Glu Glu Val Ala Ala Ser Ser Ala 
            100                 105                 110 

Ser Leu Glu Pro Met Trp Ser Gly Ser Thr Met Arg Arg Met Ala Leu 
        115                 120                 125 

Arg Pro Thr Ala Phe Ser Gly Cys Leu Asn Cys Ser Lys Val Ser Glu 
    130                 135                 140 

Leu Thr Glu Arg Leu Lys Val Leu Glu Ala Lys Met Thr Met Leu Thr 
145                 150                 155                 160 

Val Ile Glu Gln Pro Val Pro Ser Thr Pro Ala Thr Pro Glu Asp Pro 
                165                 170                 175 

Ala Pro Leu Trp Gly Pro Pro Pro Ala Gln Gly Ser Pro Gly Asp Gly 
            180                 185                 190 

Gly Leu Gln Asp Gln Val Gly Ala Trp Gly Leu Pro Gly Pro Thr Gly 
        195                 200                 205 

Pro Lys Gly Asp Ala Gly Ser Arg Gly Pro Met Gly Met Arg Gly Pro 
    210                 215                 220 

Pro Gly Pro Gln Gly Pro Pro Gly Ser Pro Gly Arg Ala Gly Ala Val 
225                 230                 235                 240 

Gly Thr Pro Gly Glu Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 
                245                 250                 255 

Pro Pro Gly Pro Pro Ala Pro Val Gly Pro Pro His Ala Arg Ile Ser 
            260                 265                 270 

Gln His Gly Asp Pro Leu Leu Ser Asn Thr Phe Thr Glu Thr Asn Asn 
        275                 280                 285 

His Trp Pro Gln Gly Pro Thr Gly Pro Pro Gly Pro Pro Gly Pro Met 
    290                 295                 300 

Gly Pro Pro Gly Pro Pro Gly Pro Thr Gly Val Pro Gly Ser Pro Gly 
305                 310                 315                 320 

His Ile Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Ile Ser Gly His 
                325                 330                 335 

Pro Gly Glu Lys Gly Glu Arg Gly Leu Arg Gly Glu Pro Gly Pro Gln 
            340                 345                 350 

Gly Ser Ala Gly Gln Arg Gly Glu Pro Gly Pro Lys Gly Asp Pro Gly 
        355                 360                 365 

Glu Lys Ser His Trp Asn Gln Ser Trp Gly Leu Gly Arg Ala Leu Pro 
    370                 375                 380 

Ala Gln Ala Pro Pro Ala Ser Phe Gly Ala Arg Gly Ala Asp Met Gln 
385                 390                 395                 400 

Pro Thr Thr Gly Ser Trp Pro Pro Gly Ala Gly Thr Arg Glu Ala Glu 
                405                 410                 415 

Gly Gly Gly Gly Pro 
            420 

 
           
             77  
             421  
             PRT  
             Homo sapiens  
           
            77 

Met Gly Gly Pro Arg Ala Trp Ala Leu Leu Cys Leu Gly Leu Leu Leu 
  1               5                  10                  15 

Pro Gly Gly Gly Ala Ala Trp Ser Ile Gly Ala Ala Pro Phe Ser Gly 
             20                  25                  30 

Arg Arg Asn Trp Cys Ser Tyr Val Val Thr Arg Thr Ile Ser Cys His 
         35                  40                  45 

Val Gln Asn Gly Thr Tyr Leu Gln Arg Val Leu Gln Asn Cys Pro Trp 
     50                  55                  60 

Pro Met Ser Cys Pro Gly Ser Ser Tyr Arg Thr Val Val Arg Pro Thr 
 65                  70                  75                  80 

Tyr Lys Val Met Tyr Lys Ile Val Thr Ala Arg Glu Trp Arg Cys Cys 
                 85                  90                  95 

Pro Gly His Ser Gly Val Ser Cys Glu Glu Val Ala Ala Ser Ser Ala 
            100                 105                 110 

Ser Leu Glu Pro Met Trp Ser Gly Ser Thr Met Arg Arg Met Ala Leu 
        115                 120                 125 

Arg Pro Thr Ala Phe Ser Gly Cys Leu Asn Cys Ser Lys Val Ser Glu 
    130                 135                 140 

Leu Thr Glu Arg Leu Lys Val Leu Glu Ala Lys Met Thr Met Leu Thr 
145                 150                 155                 160 

Val Ile Glu Gln Pro Val Pro Pro Thr Pro Ala Thr Pro Glu Asp Pro 
                165                 170                 175 

Ala Pro Leu Trp Gly Pro Pro Pro Ala Gln Gly Ser Pro Gly Asp Gly 
            180                 185                 190 

Gly Leu Gln Asp Gln Val Gly Ala Trp Gly Leu Pro Gly Pro Thr Gly 
        195                 200                 205 

Pro Lys Gly Asp Ala Gly Ser Arg Gly Pro Met Gly Met Arg Gly Pro 
    210                 215                 220 

Pro Gly Pro Gln Gly Pro Pro Gly Ser Pro Gly Arg Ala Gly Ala Val 
225                 230                 235                 240 

Gly Thr Pro Gly Glu Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 
                245                 250                 255 

Pro Pro Gly Pro Pro Ala Pro Val Gly Pro Pro His Ala Arg Ile Ser 
            260                 265                 270 

Gln His Gly Asp Pro Leu Leu Ser Asn Thr Phe Thr Glu Thr Asn Asn 
        275                 280                 285 

His Trp Pro Gln Gly Pro Thr Gly Pro Pro Gly Pro Pro Gly Pro Met 
    290                 295                 300 

Gly Pro Pro Gly Pro Pro Gly Pro Thr Gly Val Pro Gly Ser Pro Gly 
305                 310                 315                 320 

His Ile Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Ile Ser Gly His 
                325                 330                 335 

Pro Gly Glu Lys Gly Glu Arg Gly Leu Arg Gly Glu Pro Gly Pro Gln 
            340                 345                 350 

Gly Ser Ala Gly Gln Arg Gly Glu Pro Gly Pro Lys Gly Asp Pro Gly 
        355                 360                 365 

Glu Lys Ser His Trp Asn Gln Ser Trp Gly Leu Gly Arg Ala Leu Pro 
    370                 375                 380 

Ala Gln Ala Pro Pro Ala Ser Phe Gly Ala Arg Gly Ala Asp Met Gln 
385                 390                 395                 400 

Pro Thr Thr Gly Ser Trp Pro Pro Gly Ala Gly Thr Arg Glu Ala Glu 
                405                 410                 415 

Gly Gly Gly Gly Pro 
            420 

 
           
             78  
             458  
             PRT  
             Homo sapiens  
           
            78 

Met Gly Gly Pro Arg Ala Trp Ala Leu Leu Cys Leu Gly Leu Leu Leu 
  1               5                  10                  15 

Pro Gly Gly Gly Ala Ala Trp Ser Ile Gly Ala Ala Pro Phe Ser Gly 
             20                  25                  30 

Arg Arg Asn Trp Cys Ser Tyr Val Val Thr Arg Thr Ile Ser Cys His 
         35                  40                  45 

Val Gln Asn Gly Thr Tyr Leu Gln Arg Val Leu Gln Asn Cys Pro Trp 
     50                  55                  60 

Pro Met Ser Cys Pro Gly Ser Ser Tyr Arg Thr Val Val Arg Pro Thr 
 65                  70                  75                  80 

Tyr Lys Val Met Tyr Lys Ile Val Thr Ala Arg Glu Trp Arg Cys Cys 
                 85                  90                  95 

Pro Gly His Ser Gly Val Ser Cys Glu Glu Val Ala Ala Ser Ser Ala 
            100                 105                 110 

Ser Leu Glu Pro Met Trp Ser Gly Ser Thr Met Arg Arg Met Ala Leu 
        115                 120                 125 

Arg Pro Thr Ala Phe Ser Gly Cys Leu Asn Cys Ser Lys Val Ser Glu 
    130                 135                 140 

Leu Thr Glu Arg Leu Lys Val Leu Glu Ala Lys Met Thr Met Leu Thr 
145                 150                 155                 160 

Val Ile Glu Gln Pro Val Pro Pro Thr Pro Ala Thr Pro Glu Asp Pro 
                165                 170                 175 

Ala Pro Leu Trp Gly Pro Pro Pro Ala Gln Gly Ser Pro Gly Asp Gly 
            180                 185                 190 

Gly Leu Gln Asp Gln Val Gly Ala Trp Gly Leu Pro Gly Pro Thr Gly 
        195                 200                 205 

Pro Lys Gly Asp Ala Gly Ser Arg Gly Pro Met Gly Met Arg Gly Pro 
    210                 215                 220 

Pro Gly Pro Gln Gly Pro Pro Gly Ser Pro Gly Arg Ala Gly Ala Val 
225                 230                 235                 240 

Gly Thr Pro Gly Glu Arg Gly Pro Pro Gly Pro Pro Gly Pro Pro Gly 
                245                 250                 255 

Pro Pro Gly Pro Pro Ala Pro Val Gly Pro Pro His Ala Arg Ile Ser 
            260                 265                 270 

Gln His Gly Asp Pro Leu Leu Ser Asn Thr Phe Thr Glu Thr Asn Asn 
        275                 280                 285 

His Trp Pro Gln Gly Pro Thr Gly Pro Pro Gly Pro Pro Gly Pro Met 
    290                 295                 300 

Gly Pro Pro Gly Pro Pro Gly Pro Thr Gly Val Pro Gly Ser Pro Gly 
305                 310                 315                 320 

His Ile Gly Pro Pro Gly Pro Thr Gly Pro Lys Gly Ile Ser Gly His 
                325                 330                 335 

Pro Gly Glu Lys Gly Glu Arg Gly Leu Arg Gly Glu Pro Gly Pro Gln 
            340                 345                 350 

Gly Ser Ala Gly Gln Arg Gly Glu Pro Gly Pro Lys Gly Asp Pro Gly 
        355                 360                 365 

Glu Lys Ser His Trp Asn Gln Ser Trp Gly Leu Gly Gly Pro Cys Arg 
    370                 375                 380 

His Arg His Pro Gln Pro Pro Ser Gly Gln Glu Gly Gly His Ala Thr 
385                 390                 395                 400 

Asn Tyr Arg Asp Arg Gly Pro Gln Glu Pro Gly Arg Glu Arg Leu Arg 
                405                 410                 415 

Val Val Ala Ala Pro Glu Ala Asp Gln Ala Arg Leu Pro Leu Leu Pro 
            420                 425                 430 

Gly Leu Gly Gln Leu Pro Pro Gly Thr Ala Arg Pro Tyr Leu Leu Met 
        435                 440                 445 

Ser Ser Gly Ser Leu Leu Pro Ser Arg Pro 
    450                 455 

 
           
             79  
             240  
             PRT  
             Homo sapiens  
           
            79 

His Ala Ser Ala Ala Arg Ala Ala Ala Gly Ser Glu Pro Arg Thr Gly 
  1               5                  10                  15 

Cys Gly Gly Ser Ser His Arg Val Pro Leu Gly Pro Ser Pro Ala Ser 
             20                  25                  30 

Leu Ser Pro Gln Arg Asp Leu Phe Gly Pro Pro Gly Pro Pro Gly Ala 
         35                  40                  45 

Glu Val Thr Ala Glu Thr Leu Leu His Glu Phe Gln Glu Leu Leu Lys 
     50                  55                  60 

Glu Ala Thr Glu Arg Arg Phe Ser Gly Leu Leu Asp Pro Leu Leu Pro 
 65                  70                  75                  80 

Gln Gly Ala Gly Leu Arg Leu Val Gly Glu Ala Phe His Cys Arg Leu 
                 85                  90                  95 

Gln Gly Pro Arg Arg Val Asp Lys Arg Thr Leu Val Glu Leu His Gly 
            100                 105                 110 

Phe Gln Ala Pro Ala Ala Gln Gly Ala Phe Leu Arg Gly Ser Gly Leu 
        115                 120                 125 

Ser Leu Ala Ser Gly Arg Phe Thr Ala Pro Val Ser Gly Ile Phe Gln 
    130                 135                 140 

Phe Ser Ala Ser Leu His Val Asp His Ser Glu Leu Gln Gly Lys Ala 
145                 150                 155                 160 

Arg Leu Arg Ala Arg Asp Val Val Cys Val Leu Ile Cys Ile Glu Ser 
                165                 170                 175 

Leu Cys Gln Arg His Thr Cys Leu Glu Ala Val Ser Gly Leu Glu Ser 
            180                 185                 190 

Asn Ser Arg Val Phe Thr Leu Gln Val Gln Gly Leu Leu Gln Leu Gln 
        195                 200                 205 

Ala Gly Gln Tyr Ala Ser Val Phe Val Asp Asn Gly Ser Gly Ala Val 
    210                 215                 220 

Leu Thr Ile Gln Ala Gly Ser Ser Phe Ser Gly Leu Leu Leu Gly Thr 
225                 230                 235                 240 

 
           
             80  
             256  
             PRT  
             Homo sapiens  
             
               SITE  
               (75)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            80 

Met Leu Gly Ala Lys Pro His Trp Leu Pro Gly Pro Leu His Ser Pro 
  1               5                  10                  15 

Gly Leu Pro Leu Val Leu Val Leu Leu Ala Leu Gly Ala Gly Trp Ala 
             20                  25                  30 

Gln Glu Gly Ser Glu Pro Val Leu Leu Glu Gly Glu Cys Leu Val Val 
         35                  40                  45 

Cys Glu Pro Gly Arg Ala Ala Ala Gly Gly Pro Gly Gly Ala Ala Leu 
     50                  55                  60 

Gly Glu Ala Pro Pro Gly Arg Val Ala Phe Xaa Ala Val Arg Ser His 
 65                  70                  75                  80 

His His Glu Pro Ala Gly Glu Thr Gly Asn Gly Thr Ser Gly Ala Ile 
                 85                  90                  95 

Tyr Phe Asp Gln Val Leu Val Asn Glu Gly Gly Gly Phe Asp Arg Ala 
            100                 105                 110 

Ser Gly Ser Phe Val Ala Pro Val Arg Gly Val Tyr Ser Phe Arg Phe 
        115                 120                 125 

His Val Val Lys Val Tyr Asn Arg Gln Thr Val Gln Val Ser Leu Met 
    130                 135                 140 

Leu Asn Thr Trp Pro Val Ile Ser Ala Phe Ala Asn Asp Pro Asp Val 
145                 150                 155                 160 

Thr Arg Glu Ala Ala Thr Ser Ser Val Leu Leu Pro Leu Asp Pro Gly 
                165                 170                 175 

Asp Arg Val Ser Leu Arg Leu Arg Arg Gly Xaa Ser Thr Gly Trp Leu 
            180                 185                 190 

Glu Ile Leu Lys Phe Leu Trp Leu Pro His Leu Pro Ser Leu Lys Asp 
        195                 200                 205 

Pro Ser Leu Ser Ser Thr Arg Ile Gln Pro Leu Thr Thr Phe Phe Cys 
    210                 215                 220 

Pro Leu Leu Pro Xaa Lys Gln Xaa Lys Gln Xaa Xaa Xaa Ser Leu Trp 
225                 230                 235                 240 

Leu Leu Ser His Leu Phe Ala Trp Glu Pro Val Pro Asn Thr Gln Val 
                245                 250                 255 

 
           
             81  
             205  
             PRT  
             Homo sapiens  
             
               SITE  
               (80)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            81 

Met Leu Gly Ala Lys Pro His Trp Leu Pro Gly Pro Leu His Ser Pro 
  1               5                  10                  15 

Gly Leu Pro Leu Val Leu Val Leu Leu Ala Leu Gly Ala Gly Trp Ala 
             20                  25                  30 

Gln Glu Gly Ser Glu Pro Val Leu Leu Glu Gly Glu Cys Leu Val Val 
         35                  40                  45 

Cys Glu Pro Gly Arg Ala Ala Ala Gly Gly Pro Gly Gly Ala Ala Leu 
     50                  55                  60 

Gly Glu Ala Pro Pro Gly Arg Val Ala Phe Ala Ala Val Arg Ser Xaa 
 65                  70                  75                  80 

His His Glu Pro Ala Gly Glu Thr Gly Asn Gly Thr Xaa Gly Ala Ile 
                 85                  90                  95 

Tyr Phe Asp Gln Val Leu Val Asn Glu Gly Gly Gly Phe Asp Arg Ala 
            100                 105                 110 

Ser Gly Ser Phe Val Ala Pro Val Arg Gly Val Tyr Ser Phe Arg Phe 
        115                 120                 125 

His Val Val Lys Val Tyr Asn Arg Gln Thr Val Gln Val Ser Leu Met 
    130                 135                 140 

Leu Asn Thr Trp Pro Val Ile Ser Ala Phe Ala Asn Asp Pro Asp Val 
145                 150                 155                 160 

Thr Arg Glu Ala Ala Thr Ser Ser Val Leu Leu Pro Leu Asp Pro Gly 
                165                 170                 175 

Asp Arg Val Ser Leu Arg Leu Arg Arg Gly Asn Leu Leu Gly Gly Trp 
            180                 185                 190 

Lys Tyr Ser Ser Phe Ser Gly Phe Leu Ile Phe Pro Leu 
        195                 200                 205 

 
           
             82  
             180  
             PRT  
             Homo sapiens  
             
               SITE  
               (102)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            82 

Ala Cys Cys Pro Val Arg Ala Gln Asn Asp Thr Glu Pro Ile Val Leu 
  1               5                  10                  15 

Glu Gly Lys Cys Leu Val Val Cys Asp Ser Ser Pro Ser Ala Asp Gly 
             20                  25                  30 

Ala Val Thr Ser Ser Leu Gly Ile Ser Val Arg Ser Gly Ser Ala Lys 
         35                  40                  45 

Val Ala Phe Ser Ala Thr Arg Ser Thr Asn His Glu Pro Ser Glu Met 
     50                  55                  60 

Ser Asn Arg Thr Met Thr Ile Tyr Phe Asp Gln Val Leu Val Asn Ile 
 65                  70                  75                  80 

Gly Asn His Phe Asp Leu Ala Ser Ser Ile Phe Val Ala Pro Arg Lys 
                 85                  90                  95 

Gly Ile Tyr Ser Phe Xaa Phe His Val Val Lys Val Tyr Asn Arg Gln 
            100                 105                 110 

Thr Ile Gln Val Ser Leu Met Gln Asn Gly Tyr Pro Val Ile Ser Ala 
        115                 120                 125 

Phe Ala Gly Asp Gln Asp Val Thr Arg Glu Ala Ala Ser Asn Gly Val 
    130                 135                 140 

Leu Leu Leu Met Glu Arg Glu Asp Lys Val His Leu Lys Leu Glu Arg 
145                 150                 155                 160 

Gly Asn Leu Met Gly Gly Trp Lys Tyr Ser Thr Phe Ser Gly Phe Leu 
                165                 170                 175 

Val Phe Pro Leu 
            180 

 
           
             83  
             241  
             PRT  
             Homo sapiens  
             
               SITE  
               (62)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            83 

Ala Gly Glu Gly Pro Arg Arg Arg Glu Pro Pro Trp Pro Ala Pro Gln 
  1               5                  10                  15 

Ile Cys Pro Ala Gly Arg Gly Gly Gly Gly Thr Arg Ala Gly Gly Gly 
             20                  25                  30 

Ala Gly Arg Ser Ser Gly Arg Gly Gly Glu Gly Tyr Gly Asp Leu Arg 
         35                  40                  45 

Val Ala Ala Pro Leu Arg Ala Glu Pro Pro Leu Leu Ser Xaa Cys Arg 
     50                  55                  60 

Pro Ala Tyr Pro Ala Gly Leu Pro Gly Pro Arg Gly Asp Pro Gly Pro 
 65                  70                  75                  80 

Arg Gly Glu Ala Gly Pro Ala Gly Pro Thr Gly Pro Ala Gly Glu Cys 
                 85                  90                  95 

Ser Val Pro Pro Arg Ser Ala Phe Ser Ala Lys Arg Ser Glu Ser Arg 
            100                 105                 110 

Val Pro Pro Pro Ser Asp Ala Pro Leu Pro Phe Asp Arg Val Leu Val 
        115                 120                 125 

Asn Glu Gln Gly His Tyr Asp Ala Val Thr Gly Lys Phe Thr Cys Gln 
    130                 135                 140 

Val Pro Gly Val Tyr Tyr Phe Ala Val His Ala Thr Val Tyr Arg Ala 
145                 150                 155                 160 

Ser Leu Gln Phe Asp Leu Val Lys Asn Gly Glu Ser Ile Ala Ser Phe 
                165                 170                 175 

Phe Gln Phe Phe Gly Gly Trp Pro Lys Pro Ala Ser Leu Ser Xaa Gly 
            180                 185                 190 

Ala Met Val Arg Leu Glu Pro Glu Asp Gln Val Trp Val Gln Val Gly 
        195                 200                 205 

Val Gly Asp Tyr Ile Gly Ile Tyr Ala Ser Ile Lys Thr Asp Ser Thr 
    210                 215                 220 

Phe Ser Gly Phe Leu Val Tyr Ser Asp Trp His Ser Ser Pro Val Phe 
225                 230                 235                 240 

Ala 

 
           
             84  
             245  
             PRT  
             Homo sapiens  
           
            84 

Met Asp Val Gly Pro Ser Ser Leu Pro His Leu Gly Leu Lys Leu Leu 
  1               5                  10                  15 

Leu Leu Leu Leu Leu Leu Pro Leu Arg Gly Gln Ala Asn Thr Gly Cys 
             20                  25                  30 

Tyr Gly Ile Pro Gly Met Pro Gly Leu Pro Gly Ala Pro Gly Lys Asp 
         35                  40                  45 

Gly Tyr Asp Gly Leu Pro Gly Pro Lys Gly Glu Pro Gly Ile Pro Ala 
     50                  55                  60 

Ile Pro Gly Ile Arg Gly Pro Lys Gly Gln Lys Gly Glu Pro Gly Leu 
 65                  70                  75                  80 

Pro Gly His Pro Gly Lys Asn Gly Pro Met Gly Pro Pro Gly Met Pro 
                 85                  90                  95 

Gly Val Pro Gly Pro Met Gly Ile Pro Gly Glu Pro Gly Glu Glu Gly 
            100                 105                 110 

Arg Tyr Lys Gln Lys Phe Gln Ser Val Phe Thr Val Thr Arg Gln Thr 
        115                 120                 125 

His Gln Pro Pro Ala Pro Asn Ser Leu Ile Arg Phe Asn Ala Val Leu 
    130                 135                 140 

Thr Asn Pro Gln Gly Asp Tyr Asp Thr Ser Thr Gly Lys Phe Thr Cys 
145                 150                 155                 160 

Lys Val Pro Gly Leu Tyr Tyr Phe Val Tyr His Ala Ser His Thr Ala 
                165                 170                 175 

Asn Leu Cys Val Leu Leu Tyr Arg Ser Gly Val Lys Val Val Thr Phe 
            180                 185                 190 

Cys Gly His Thr Ser Lys Thr Asn Gln Val Asn Ser Gly Gly Val Leu 
        195                 200                 205 

Leu Arg Leu Gln Val Gly Glu Glu Val Trp Leu Ala Val Asn Asp Tyr 
    210                 215                 220 

Tyr Asp Met Val Gly Ile Gln Gly Ser Asp Ser Val Phe Ser Gly Phe 
225                 230                 235                 240 

Leu Leu Phe Pro Asp 
                245 

 
           
             85  
             76  
             PRT  
             Homo sapiens  
           
            85 

Ala Leu Pro Arg Leu Gly Arg Ala Asp Ala Leu Glu Thr His Gly Pro 
  1               5                  10                  15 

Ser Thr Ser Leu Ser Phe Leu His Gly Pro Thr Leu Leu Ala Ser Leu 
             20                  25                  30 

His Pro Cys Leu Asp His Ser Pro Leu Gln Gly Ala His Pro Asp Pro 
         35                  40                  45 

Pro Pro Leu His Pro Leu Pro Met Gly Ser Leu Leu Pro Leu Asn Phe 
     50                  55                  60 

Phe Arg Ser His Cys Leu Cys Gly Ser Trp Asp Thr 
 65                  70                  75 

 
           
             86  
             185  
             PRT  
             Homo sapiens  
             
               SITE  
               (72)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            86 

Met Asp Val Gly Pro Ser Ser Leu Pro His Leu Gly Leu Lys Leu Leu 
  1               5                  10                  15 

Leu Leu Leu Leu Leu Leu Pro Leu Arg Gly Gln Ala Asn Thr Gly Cys 
             20                  25                  30 

Tyr Gly Ile Pro Gly Met Pro Gly Leu Pro Gly Ala Pro Gly Lys Asp 
         35                  40                  45 

Gly Tyr Asp Gly Leu Pro Gly Pro Lys Gly Glu Pro Gly Ile Gln Pro 
     50                  55                  60 

Phe Arg Asp Pro Arg Thr Gln Xaa Ala Glu Gly Arg Thr Arg Leu Thr 
 65                  70                  75                  80 

Arg Pro Ser Trp Glu Xaa Trp Xaa Met Xaa Pro Pro Gly Met Pro Gly 
                 85                  90                  95 

Val Pro Ala His Gly His Pro Trp Arg Ala Gly Glu Xaa Gly Arg Tyr 
            100                 105                 110 

Lys Gln Lys Phe Gln Ser Xaa Ser Arg His Ser Glu Thr Thr Ala Pro 
        115                 120                 125 

Asp Pro Thr Ala Asp Arg Ser Thr Arg Ser Asn Asn Arg Arg Arg Tyr 
    130                 135                 140 

Thr Arg His Xaa Lys Ser Leu Lys Xaa Arg Leu Thr Leu Ala Thr Arg 
145                 150                 155                 160 

Val Ile Ser Asn Trp Leu Cys Asp Glu Arg Xaa Xaa Gly Thr Leu Gly 
                165                 170                 175 

Asn Xaa Asn Ile Gly Asn Xaa Gly Ala 
            180                 185 

 
           
             87  
             127  
             PRT  
             Homo sapiens  
             
               SITE  
               (127)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            87 

Met Phe Val Leu Leu Tyr Val Thr Ser Phe Ala Ile Cys Ala Ser Gly 
  1               5                  10                  15 

Gln Pro Arg Gly Asn Gln Leu Lys Gly Glu Asn Tyr Ser Pro Arg Tyr 
             20                  25                  30 

Ile Cys Ser Ile Pro Gly Leu Pro Gly Pro Pro Gly Pro Pro Gly Ala 
         35                  40                  45 

Asn Gly Ser Pro Gly Pro His Gly Arg Ile Gly Leu Pro Gly Arg Asp 
     50                  55                  60 

Gly Arg Asp Gly Arg Lys Gly Glu Lys Gly Glu Lys Gly Thr Ala Gly 
 65                  70                  75                  80 

Leu Arg Gly Lys Thr Gly Pro Leu Gly Leu Ala Gly Glu Lys Gly Asp 
                 85                  90                  95 

Gln Gly Glu Thr Gly Lys Lys Gly Pro Ile Gly Pro Glu Gly Glu Lys 
            100                 105                 110 

Gly Glu Val Gly Pro Ile Gly Pro Pro Gly Pro Lys Gly Asp Xaa 
        115                 120                 125 

 
           
             88  
             285  
             PRT  
             Homo sapiens  
           
            88 

Met Ile Pro Trp Val Leu Leu Ala Cys Ala Leu Pro Cys Ala Ala Asp 
  1               5                  10                  15 

Pro Leu Leu Gly Ala Phe Ala Arg Arg Asp Phe Arg Lys Gly Ser Pro 
             20                  25                  30 

Gln Leu Val Cys Ser Leu Pro Gly Pro Gln Gly Pro Pro Gly Pro Pro 
         35                  40                  45 

Gly Ala Pro Gly Pro Ser Gly Met Met Gly Arg Met Gly Phe Pro Gly 
     50                  55                  60 

Lys Asp Gly Gln Asp Gly His Asp Gly Asp Arg Gly Asp Ser Gly Glu 
 65                  70                  75                  80 

Glu Gly Pro Pro Gly Arg Thr Gly Asn Arg Gly Lys Pro Gly Pro Lys 
                 85                  90                  95 

Gly Lys Ala Gly Ala Ile Gly Arg Ala Gly Pro Arg Gly Pro Lys Gly 
            100                 105                 110 

Val Asn Gly Thr Pro Gly Lys His Gly Thr Pro Gly Lys Lys Gly Pro 
        115                 120                 125 

Lys Gly Lys Lys Gly Glu Pro Gly Leu Pro Gly Pro Cys Ser Cys Gly 
    130                 135                 140 

Ser Gly His Thr Lys Ser Ala Phe Ser Val Ala Val Thr Lys Ser Tyr 
145                 150                 155                 160 

Pro Arg Glu Arg Leu Pro Ile Lys Phe Asp Lys Ile Leu Met Asn Glu 
                165                 170                 175 

Gly Gly His Tyr Asn Ala Ser Ser Gly Lys Phe Val Cys Gly Val Pro 
            180                 185                 190 

Gly Ile Tyr Tyr Phe Thr Tyr Asp Ile Thr Leu Ala Asn Lys His Leu 
        195                 200                 205 

Ala Ile Gly Leu Val His Asn Gly Gln Tyr Arg Ile Arg Thr Phe Asp 
    210                 215                 220 

Ala Asn Thr Gly Asn His Asp Val Ala Ser Gly Ser Thr Ile Leu Ala 
225                 230                 235                 240 

Leu Lys Gln Gly Asp Glu Val Trp Leu Gln Ile Phe Tyr Ser Glu Gln 
                245                 250                 255 

Asn Gly Leu Phe Tyr Asp Pro Tyr Trp Thr Asp Ser Leu Phe Thr Gly 
            260                 265                 270 

Phe Leu Ile Tyr Ala Asp Gln Asp Asp Pro Asn Glu Val 
        275                 280                 285 

 
           
             89  
             205  
             PRT  
             Homo sapiens  
             
               SITE  
               (5)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            89 

Phe Phe Phe Phe Xaa Pro Gly Leu Pro Gly Leu Pro Cys Pro Leu Ser 
  1               5                  10                  15 

Ala Leu Leu Ala Glu Ser Arg Arg Ala Arg Xaa Pro Trp Arg Ser Arg 
             20                  25                  30 

Gly Thr Phe Glu Pro Arg Ala Arg Pro Gly Met His Ala Pro Gly Pro 
         35                  40                  45 

Pro Gly Leu Phe Ser Gly Pro Gly Leu Thr Val Ala Pro Arg Pro Arg 
     50                  55                  60 

Gly Pro Ala Gly Gly Gly Gly Glu Val Gly Val His Gln Glu Ala Gly 
 65                  70                  75                  80 

Glu Gly Asp Val Leu Ala Val Val Ala Val Gly Ala Val Ala Val Val 
                 85                  90                  95 

Val Val Ala Glu Gln Pro Glu Xaa Ser Pro Arg Arg Arg Ala Ser Ile 
            100                 105                 110 

Thr Leu Trp Leu Cys Ile Xaa Ala Ala Pro Arg Arg Ala Val Val Val 
        115                 120                 125 

Asn His Gly Leu His Leu Val Ala Val Leu His Gln Leu Asn Arg Gln 
    130                 135                 140 

Arg Leu Thr Arg Gln Leu Ala Gln Arg Glu Gly Glu Glu Val Gly Ala 
145                 150                 155                 160 

Gly Gln Thr Ala Ala Glu His Ala Gly Arg Arg Val Glu Val Ala Ala 
                165                 170                 175 

Asn Val Asp Glu Leu Gly Val Glu Gly Glu Trp Leu Val Pro Arg Pro 
            180                 185                 190 

Gly Pro Ala Ser Glu Pro Thr Lys Leu Arg Ala Leu Cys 
        195                 200                 205 

 
           
             90  
             251  
             PRT  
             Homo sapiens  
           
            90 

Met Lys Ile Pro Trp Gly Ser Ile Pro Val Leu Met Leu Leu Leu Leu 
  1               5                  10                  15 

Leu Gly Leu Ile Asp Ile Ser Gln Ala Gln Leu Ser Cys Thr Gly Pro 
             20                  25                  30 

Pro Ala Ile Pro Gly Ile Pro Gly Ile Pro Gly Thr Pro Gly Pro Asp 
         35                  40                  45 

Gly Gln Pro Gly Thr Pro Gly Ile Lys Gly Glu Lys Gly Leu Pro Gly 
     50                  55                  60 

Leu Ala Gly Asp His Gly Glu Phe Gly Glu Lys Gly Asp Pro Gly Ile 
 65                  70                  75                  80 

Pro Gly Asn Pro Gly Lys Val Gly Pro Lys Gly Pro Met Gly Pro Lys 
                 85                  90                  95 

Gly Gly Pro Gly Ala Pro Gly Ala Pro Gly Pro Lys Gly Glu Ser Gly 
            100                 105                 110 

Asp Tyr Lys Ala Thr Gln Lys Ile Ala Phe Ser Ala Thr Arg Thr Ile 
        115                 120                 125 

Asn Val Pro Leu Arg Arg Asp Gln Thr Ile Arg Phe Asp His Val Ile 
    130                 135                 140 

Thr Asn Met Asn Asn Asn Tyr Glu Pro Arg Ser Gly Lys Phe Thr Cys 
145                 150                 155                 160 

Lys Val Pro Gly Leu Tyr Tyr Phe Thr Tyr His Ala Ser Ser Arg Gly 
                165                 170                 175 

Asn Leu Cys Val Asn Leu Met Arg Gly Arg Glu Arg Ala Gln Lys Val 
            180                 185                 190 

Val Thr Phe Cys Asp Tyr Ala Tyr Asn Thr Phe Gln Val Thr Thr Gly 
        195                 200                 205 

Gly Met Val Leu Lys Leu Glu Gln Gly Glu Asn Val Phe Leu Gln Ala 
    210                 215                 220 

Thr Asp Lys Asn Ser Leu Leu Gly Met Glu Gly Ala Asn Ser Ile Phe 
225                 230                 235                 240 

Ser Gly Phe Leu Leu Phe Pro Asp Met Glu Ala 
                245                 250 

 
           
             91  
             168  
             PRT  
             Homo sapiens  
             
               SITE  
               (34)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            91 

Pro Gly Ile Arg Lys Arg Arg Pro Gln Gly Pro His Gly Pro Lys Val 
  1               5                  10                  15 

Ala Gln Gly Pro Glu Ala Pro Ser Pro Lys Val Asn Arg Glu Thr Gln 
             20                  25                  30 

Ala Xaa Gln Lys Met Pro Phe Xaa Ala Thr Arg Xaa Ile Asn Val Pro 
         35                  40                  45 

Leu Arg Xaa Asp Gln Thr Ile Arg Xaa Asp His Val Ile Xaa Asn Met 
     50                  55                  60 

Xaa Asn Asn Tyr Glu Pro Arg Ser Gly Lys Phe Thr Cys Lys Val Pro 
 65                  70                  75                  80 

Gly Leu Xaa Tyr Phe Thr Tyr His Ala Ser Ser Arg Gly Asn Leu Cys 
                 85                  90                  95 

Val Asn Leu Met Arg Gly Arg Glu Arg Ala Gln Lys Val Val Thr Phe 
            100                 105                 110 

Cys Asp Tyr Ala Tyr Asn Thr Phe Gln Val Thr Thr Gly Gly Met Val 
        115                 120                 125 

Leu Lys Leu Glu Gln Gly Glu Asn Val Phe Leu Gln Ala Thr Asp Lys 
    130                 135                 140 

Asn Ser Leu Leu Gly Met Glu Gly Ala Asn Ser Ile Phe Ser Gly Phe 
145                 150                 155                 160 

Leu Leu Phe Pro Asp Met Glu Ala 
                165 

 
           
             92  
             255  
             PRT  
             Homo sapiens  
           
            92 

His Ser Met Met Met Lys Ile Pro Trp Gly Ser Ile Pro Val Leu Met 
  1               5                  10                  15 

Leu Leu Leu Leu Leu Gly Leu Ile Asp Ile Ser Gln Ala Gln Leu Ser 
             20                  25                  30 

Cys Thr Gly Pro Pro Ala Ile Pro Gly Ile Pro Gly Ile Pro Gly Thr 
         35                  40                  45 

Pro Gly Pro Asp Gly Gln Pro Gly Thr Pro Gly Ile Lys Gly Glu Lys 
     50                  55                  60 

Gly Leu Pro Gly Leu Ala Gly Asp His Gly Glu Phe Gly Glu Lys Gly 
 65                  70                  75                  80 

Asp Pro Gly Ile Pro Gly Asn Pro Gly Lys Val Gly Pro Lys Gly Pro 
                 85                  90                  95 

Met Gly Pro Lys Gly Gly Pro Gly Ala Pro Gly Ala Pro Gly Pro Lys 
            100                 105                 110 

Gly Glu Ser Gly Asp Tyr Lys Ala Thr Gln Lys Ile Ala Phe Ser Ala 
        115                 120                 125 

Thr Arg Thr Ile Asn Val Pro Leu Arg Arg Asp Gln Thr Ile Arg Phe 
    130                 135                 140 

Asp His Val Ile Thr Asn Met Asn Asn Asn Tyr Glu Pro Arg Ser Gly 
145                 150                 155                 160 

Lys Phe Thr Cys Lys Val Pro Gly Leu Tyr Tyr Phe Thr Tyr His Ala 
                165                 170                 175 

Ser Ser Arg Gly Asn Leu Cys Val Asn Leu Met Arg Gly Arg Glu Arg 
            180                 185                 190 

Ala Gln Lys Val Val Thr Phe Cys Asp Tyr Ala Tyr Asn Thr Phe Gln 
        195                 200                 205 

Val Thr Thr Gly Gly Met Val Leu Lys Leu Glu Gln Gly Glu Asn Val 
    210                 215                 220 

Phe Leu Gln Ala Thr Asp Lys Asn Ser Leu Leu Gly Met Glu Gly Ala 
225                 230                 235                 240 

Asn Ser Ile Phe Ser Gly Phe Leu Leu Phe Pro Asp Met Glu Ala 
                245                 250                 255 

 
           
             93  
             258  
             PRT  
             Homo sapiens  
           
            93 

Ala Phe Ala Lys Ser Tyr Leu Gly Asp Thr Ile Glu Gly Thr Pro Ala 
  1               5                  10                  15 

Gly Thr Gly Pro Glu Phe Pro Gly Arg Pro Thr Arg Pro Val Leu Pro 
             20                  25                  30 

Gln Arg Pro Pro Glu Glu Arg Pro Pro Gln Pro Pro Gly Ser Thr Gly 
         35                  40                  45 

Val Ile Ala Glu Thr Gly Gln Ala Gly Pro Pro Ala Gly Ala Gly Val 
     50                  55                  60 

Ser Gly Arg Gly Leu Pro Arg Gly Val Asp Gly Gln Thr Gly Ser Gly 
 65                  70                  75                  80 

Thr Val Pro Gly Ala Glu Gly Phe Ala Gly Ala Pro Gly Tyr Pro Lys 
                 85                  90                  95 

Ser Pro Pro Val Ala Ser Pro Gly Ala Pro Val Pro Ser Leu Val Ser 
            100                 105                 110 

Phe Ser Ala Gly Leu Thr Gln Lys Pro Phe Pro Ser Asp Gly Gly Val 
        115                 120                 125 

Val Leu Phe Asn Lys Val Leu Val Asn Asp Gly Asp Val Tyr Asn Pro 
    130                 135                 140 

Ser Thr Gly Val Phe Thr Ala Pro Tyr Asp Gly Arg Tyr Leu Ile Thr 
145                 150                 155                 160 

Ala Thr Leu Thr Pro Glu Arg Asp Ala Tyr Val Glu Ala Val Leu Ser 
                165                 170                 175 

Val Ser Asn Ala Ser Val Ala Gln Leu His Thr Ala Gly Tyr Arg Arg 
            180                 185                 190 

Glu Phe Leu Glu Tyr His Arg Pro Pro Gly Ala Leu His Thr Cys Gly 
        195                 200                 205 

Gly Pro Gly Ala Phe His Leu Ile Val His Leu Lys Ala Gly Asp Ala 
    210                 215                 220 

Val Asn Val Val Val Thr Gly Gly Lys Leu Ala His Thr Asp Phe Asp 
225                 230                 235                 240 

Glu Met Tyr Ser Thr Phe Ser Gly Val Phe Leu Tyr Pro Phe Leu Ser 
                245                 250                 255 

His Leu 

 
           
             94  
             232  
             PRT  
             Homo sapiens  
           
            94 

Thr Arg Pro Val Leu Pro Gln Arg Pro Pro Glu Glu Arg Pro Pro Gln 
  1               5                  10                  15 

Pro Pro Gly Ser Thr Gly Val Ile Ala Glu Thr Gly Gln Ala Gly Pro 
             20                  25                  30 

Pro Ala Gly Ala Gly Val Ser Gly Arg Gly Leu Pro Arg Gly Val Asp 
         35                  40                  45 

Gly Gln Thr Gly Ser Gly Thr Val Pro Gly Ala Glu Gly Phe Ala Gly 
     50                  55                  60 

Ala Pro Gly Tyr Pro Lys Ser Pro Pro Val Ala Ser Pro Gly Ala Pro 
 65                  70                  75                  80 

Val Pro Ser Leu Val Ser Phe Ser Ala Gly Leu Thr Gln Lys Pro Phe 
                 85                  90                  95 

Pro Ser Asp Gly Gly Val Val Leu Phe Asn Lys Val Leu Val Asn Asp 
            100                 105                 110 

Gly Asp Val Tyr Asn Pro Ser Thr Gly Val Phe Thr Ala Pro Tyr Asp 
        115                 120                 125 

Gly Arg Tyr Leu Ile Thr Ala Thr Leu Thr Pro Glu Arg Asp Ala Tyr 
    130                 135                 140 

Val Glu Ala Val Leu Ser Val Ser Asn Ala Ser Val Ala Gln Leu His 
145                 150                 155                 160 

Thr Ala Gly Tyr Arg Arg Glu Phe Leu Glu Tyr His Arg Pro Pro Gly 
                165                 170                 175 

Ala Leu His Thr Cys Gly Gly Pro Gly Ala Phe His Leu Ile Val His 
            180                 185                 190 

Leu Lys Ala Gly Asp Ala Val Asn Val Val Val Thr Gly Gly Lys Leu 
        195                 200                 205 

Ala His Thr Asp Phe Asp Glu Met Tyr Ser Thr Phe Ser Gly Val Phe 
    210                 215                 220 

Leu Tyr Pro Phe Leu Ser His Leu 
225                 230 

 
           
             95  
             98  
             PRT  
             Homo sapiens  
           
            95 

Met Ala Val Leu Pro Gly Pro Leu Gln Leu Leu Gly Val Leu Leu Thr 
  1               5                  10                  15 

Ile Ser Leu Ser Ser Ile Arg Leu Ile Gln Ala Gly Ala Tyr Tyr Gly 
             20                  25                  30 

Ile Lys Pro Leu Pro Pro Gln Ile Pro Pro Gln Met Pro Pro Gln Ile 
         35                  40                  45 

Pro Gln Tyr Gln Pro Leu Gly Gln Gln Val Pro His Met Pro Leu Ala 
     50                  55                  60 

Lys Asp Gly Leu Ala Met Gly Lys Glu Met Pro His Leu Gln Tyr Gly 
 65                  70                  75                  80 

Lys Glu Tyr Pro His Leu Pro Gln Tyr Met Lys Glu Ile Gln Pro Ala 
                 85                  90                  95 

Val Asp 

 
           
             96  
             542  
             PRT  
             Homo sapiens  
           
            96 

Met Gln Ala Cys Gly Gln Leu Cys Ser Gly Ala Pro Gly Glu Gln Asp 
  1               5                  10                  15 

Ser Gln Val Ser Glu Ile Leu Ser Ala Leu Glu Arg Arg Val Leu Asp 
             20                  25                  30 

Ser Glu Gly Gln Leu Arg Leu Val Gly Ser Gly Leu His Thr Val Glu 
         35                  40                  45 

Ala Ala Gly Glu Ala Arg Gln Ala Thr Leu Glu Gly Leu Gln Glu Val 
     50                  55                  60 

Val Gly Arg Leu Gln Asp Arg Val Asp Ala Gln Asp Glu Thr Ala Ala 
 65                  70                  75                  80 

Glu Phe Thr Leu Arg Leu Asn Leu Thr Ala Ala Arg Leu Gly Gln Leu 
                 85                  90                  95 

Glu Gly Leu Leu Gln Ala His Gly Asp Glu Gly Cys Gly Ala Cys Gly 
            100                 105                 110 

Gly Val Gln Glu Glu Leu Gly Arg Leu Arg Asp Gly Val Glu Arg Cys 
        115                 120                 125 

Ser Cys Pro Leu Leu Pro Pro Arg Gly Pro Gly Ala Gly Pro Gly Val 
    130                 135                 140 

Gly Gly Pro Ser Arg Gly Pro Leu Asp Gly Phe Ser Val Phe Gly Gly 
145                 150                 155                 160 

Ser Ser Gly Ser Ala Leu Gln Ala Leu Gln Gly Glu Leu Ser Glu Val 
                165                 170                 175 

Ile Leu Ser Phe Ser Ser Leu Asn Asp Ser Leu Asn Glu Leu Gln Thr 
            180                 185                 190 

Thr Val Glu Gly Gln Gly Ala Asp Leu Ala Asp Leu Gly Ala Thr Lys 
        195                 200                 205 

Asp Arg Ile Ile Ser Glu Ile Asn Arg Leu Gln Gln Glu Ala Thr Glu 
    210                 215                 220 

His Ala Thr Glu Ser Glu Glu Arg Phe Arg Gly Leu Glu Glu Gly Gln 
225                 230                 235                 240 

Ala Gln Ala Gly Gln Cys Pro Ser Leu Glu Gly Arg Leu Gly Arg Leu 
                245                 250                 255 

Glu Gly Val Cys Glu Arg Leu Asp Thr Val Ala Gly Gly Leu Gln Gly 
            260                 265                 270 

Leu Arg Glu Gly Leu Ser Arg His Val Ala Gly Leu Trp Ala Gly Leu 
        275                 280                 285 

Arg Glu Thr Asn Thr Thr Ser Gln Met Gln Ala Ala Leu Leu Glu Lys 
    290                 295                 300 

Leu Val Gly Gly Gln Ala Gly Leu Gly Arg Arg Leu Gly Ala Leu Asn 
305                 310                 315                 320 

Ser Ser Leu Gln Leu Leu Glu Asp Arg Leu His Gln Leu Ser Leu Lys 
                325                 330                 335 

Asp Leu Thr Gly Pro Ala Gly Glu Ala Gly Pro Pro Gly Pro Pro Gly 
            340                 345                 350 

Leu Gln Gly Pro Pro Gly Pro Ala Gly Pro Pro Gly Ser Pro Gly Lys 
        355                 360                 365 

Asp Gly Gln Glu Gly Pro Ile Gly Pro Pro Gly Pro Gln Gly Glu Gln 
    370                 375                 380 

Gly Val Glu Gly Ala Pro Ala Ala Pro Val Pro Gln Val Ala Phe Ser 
385                 390                 395                 400 

Ala Ala Leu Ser Leu Pro Arg Ser Glu Pro Gly Thr Val Pro Phe Asp 
                405                 410                 415 

Arg Val Leu Leu Asn Asp Gly Gly Tyr Tyr Asp Pro Glu Thr Gly Val 
            420                 425                 430 

Phe Thr Ala Pro Leu Ala Gly Arg Tyr Leu Leu Ser Ala Val Leu Thr 
        435                 440                 445 

Gly His Arg His Glu Lys Val Glu Ala Val Leu Ser Arg Ser Asn Gln 
    450                 455                 460 

Gly Val Ala Arg Val Asp Ser Gly Gly Tyr Glu Pro Glu Gly Leu Glu 
465                 470                 475                 480 

Asn Lys Pro Val Ala Glu Ser Gln Pro Ser Pro Gly Thr Leu Gly Val 
                485                 490                 495 

Phe Ser Leu Ile Leu Pro Leu Gln Ala Gly Asp Thr Val Cys Val Asp 
            500                 505                 510 

Leu Val Met Gly Gln Leu Ala His Ser Glu Glu Pro Leu Thr Ile Phe 
        515                 520                 525 

Ser Gly Ala Leu Leu Tyr Gly Asp Pro Glu Leu Glu His Ala 
    530                 535                 540 

 
           
             97  
             333  
             PRT  
             Homo sapiens  
           
            97 

Met Arg Ile Trp Trp Leu Leu Leu Ala Ile Glu Ile Cys Thr Gly Asn 
  1               5                  10                  15 

Ile Asn Ser Gln Asp Thr Cys Arg Gln Gly His Pro Gly Ile Pro Gly 
             20                  25                  30 

Asn Pro Gly His Asn Gly Leu Pro Gly Arg Asp Gly Arg Asp Gly Ala 
         35                  40                  45 

Lys Gly Asp Lys Gly Asp Ala Gly Glu Pro Gly Arg Pro Gly Ser Pro 
     50                  55                  60 

Gly Lys Asp Gly Thr Ser Gly Glu Lys Gly Glu Arg Gly Ala Asp Gly 
 65                  70                  75                  80 

Lys Val Glu Ala Lys Gly Ile Lys Gly Asp Gln Gly Ser Arg Gly Ser 
                 85                  90                  95 

Pro Gly Lys His Gly Pro Lys Gly Leu Ala Gly Pro Met Gly Glu Lys 
            100                 105                 110 

Gly Leu Arg Gly Glu Thr Gly Pro Gln Gly Gln Lys Gly Asn Lys Gly 
        115                 120                 125 

Asp Val Gly Pro Thr Gly Pro Glu Gly Pro Arg Gly Asn Ile Gly Pro 
    130                 135                 140 

Leu Gly Pro Thr Gly Leu Pro Gly Pro Met Gly Pro Ile Gly Lys Pro 
145                 150                 155                 160 

Gly Pro Lys Gly Glu Ala Gly Pro Thr Gly Pro Gln Gly Glu Pro Gly 
                165                 170                 175 

Val Arg Gly Ile Arg Gly Trp Lys Gly Asp Arg Gly Glu Lys Gly Lys 
            180                 185                 190 

Ile Gly Glu Thr Leu Val Leu Pro Lys Ser Ala Phe Thr Val Gly Leu 
        195                 200                 205 

Thr Val Leu Ser Lys Phe Pro Ser Ser Asp Val Pro Ile Lys Phe Asp 
    210                 215                 220 

Lys Ile Leu Tyr Asn Glu Phe Asn His Tyr Asp Thr Ala Ala Gly Lys 
225                 230                 235                 240 

Phe Thr Cys His Ile Ala Gly Val Tyr Tyr Phe Thr Tyr His Ile Thr 
                245                 250                 255 

Val Phe Ser Arg Asn Val Gln Val Ser Leu Val Lys Asn Gly Val Lys 
            260                 265                 270 

Ile Leu His Thr Lys Asp Ala Tyr Met Ser Ser Glu Asp Gln Ala Ser 
        275                 280                 285 

Gly Gly Ile Val Leu Gln Leu Lys Leu Gly Asp Glu Val Trp Leu Gln 
    290                 295                 300 

Val Thr Gly Gly Glu Arg Phe Asn Gly Leu Phe Ala Asp Glu Asp Asp 
305                 310                 315                 320 

Asp Thr Thr Phe Thr Gly Phe Leu Leu Phe Ser Ser Pro 
                325                 330 

 
           
             98  
             159  
             PRT  
             Homo sapiens  
             
               SITE  
               (43)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            98 

Gln Glu Gly Ser Glu Pro Val Leu Leu Glu Gly Glu Cys Leu Val Val 
  1               5                  10                  15 

Cys Glu Pro Gly Arg Ala Ala Ala Gly Gly Pro Gly Gly Ala Ala Leu 
             20                  25                  30 

Gly Glu Ala Pro Pro Gly Arg Val Ala Phe Xaa Ala Val Arg Ser His 
         35                  40                  45 

His His Glu Pro Ala Gly Glu Thr Gly Asn Gly Thr Ser Gly Ala Ile 
     50                  55                  60 

Tyr Phe Asp Gln Val Leu Val Asn Glu Gly Gly Gly Phe Asp Arg Ala 
 65                  70                  75                  80 

Ser Gly Ser Phe Val Ala Pro Val Arg Gly Val Tyr Ser Phe Arg Phe 
                 85                  90                  95 

His Val Val Lys Val Tyr Asn Arg Gln Thr Val Gln Val Ser Leu Met 
            100                 105                 110 

Leu Asn Thr Trp Pro Val Ile Ser Ala Phe Ala Asn Asp Pro Asp Val 
        115                 120                 125 

Thr Arg Glu Ala Ala Thr Ser Ser Val Leu Leu Pro Leu Asp Pro Gly 
    130                 135                 140 

Asp Arg Val Ser Leu Arg Leu Arg Arg Gly Xaa Ser Thr Gly Trp 
145                 150                 155 

 
           
             99  
             27  
             DNA  
             Homo sapiens  
           
            99 

gcggcaagct ttttgcaaag cctaggc                                         27 

 
           
             100  
             287  
             PRT  
             Homo sapiens  
           
            100 

Pro Arg Val Arg Lys Glu Pro Glu Ala Met Gln Trp Leu Arg Val Arg 
  1               5                  10                  15 

Glu Ser Pro Gly Glu Ala Thr Gly His Arg Val Thr Met Gly Thr Ala 
             20                  25                  30 

Ala Leu Gly Pro Val Trp Ala Ala Leu Leu Leu Phe Leu Leu Met Cys 
         35                  40                  45 

Glu Ile Pro Met Val Glu Leu Thr Phe Asp Arg Ala Val Ala Ser Asp 
     50                  55                  60 

Cys Gln Arg Cys Cys Asp Ser Glu Asp Pro Leu Asp Pro Ala His Val 
 65                  70                  75                  80 

Ser Ser Ala Ser Ser Ser Gly Arg Pro His Ala Leu Pro Glu Ile Arg 
                 85                  90                  95 

Pro Tyr Ile Asn Ile Thr Ile Leu Lys Gly Asp Lys Gly Asp Pro Gly 
            100                 105                 110 

Pro Met Gly Leu Pro Gly Tyr Met Gly Arg Glu Gly Pro Gln Gly Glu 
        115                 120                 125 

Pro Gly Pro Gln Gly Ser Lys Gly Asp Lys Gly Glu Met Gly Ser Pro 
    130                 135                 140 

Gly Ala Pro Cys Gln Lys Arg Phe Phe Ala Phe Ser Val Gly Arg Lys 
145                 150                 155                 160 

Thr Ala Leu His Ser Gly Glu Asp Phe Gln Thr Leu Leu Phe Glu Arg 
                165                 170                 175 

Val Phe Val Asn Leu Asp Gly Cys Phe Asp Met Ala Thr Gly Gln Phe 
            180                 185                 190 

Ala Ala Pro Leu Arg Gly Ile Tyr Phe Phe Ser Leu Asn Val His Ser 
        195                 200                 205 

Trp Asn Tyr Lys Glu Thr Tyr Val His Ile Met His Asn Gln Lys Glu 
    210                 215                 220 

Ala Val Ile Leu Tyr Ala Gln Pro Ser Glu Arg Ser Ile Met Gln Ser 
225                 230                 235                 240 

Gln Ser Val Met Leu Asp Leu Ala Tyr Gly Asp Arg Val Trp Val Arg 
                245                 250                 255 

Leu Phe Lys Arg Gln Arg Glu Asn Ala Ile Tyr Ser Asn Asp Phe Asp 
            260                 265                 270 

Thr Tyr Ile Thr Phe Ser Gly His Leu Ile Lys Ala Glu Asp Asp 
        275                 280                 285 

 
           
             101  
             162  
             PRT  
             Homo sapiens  
             
               SITE  
               (1)  
               Xaa equals any of the naturally occurring 
      L-amino acids  
             
           
            101 

Xaa Leu Trp Asp Pro Gly Leu Pro Gly Val Cys Arg Cys Gly Ser Ile 
  1               5                  10                  15 

Val Leu Lys Ser Ala Phe Ser Val Gly Ile Thr Thr Ser Tyr Pro Glu 
             20                  25                  30 

Xaa Arg Leu Pro Ile Ile Phe Asn Lys Val Leu Leu Pro Arg Gly Xaa 
         35                  40                  45 

Ala Leu Gln Pro Cys His Arg Gly Ser Ser Ser Val Leu Ser Gln Gly 
     50                  55                  60 

Ile Tyr Tyr Phe Ser Tyr Asp Ile Thr Leu Ala Asn Lys His Leu Ala 
 65                  70                  75                  80 

Ile Gly Leu Val His Asn Gly Gln Tyr Arg Ile Lys Thr Phe Asp Ala 
                 85                  90                  95 

Asn Thr Gly Asn His Asp Val Ala Ser Gly Ser Thr Val Ile Tyr Leu 
            100                 105                 110 

Gln Pro Glu Asp Glu Val Trp Leu Glu Ile Phe Phe Thr Asp Gln Asn 
        115                 120                 125 

Gly Leu Phe Ser Asp Pro Gly Trp Ala Asp Ser Leu Phe Ser Gly Phe 
    130                 135                 140 

Leu Leu Tyr Val Asp Thr Asp Tyr Leu Asp Ser Ile Ser Glu Asp Asp 
145                 150                 155                 160 

Glu Leu 

 
           
             102  
             15  
             PRT  
             Homo sapiens  
           
            102 

Gly Ser Ile Val Leu Lys Ser Ala Phe Ser Val Gly Ile Thr Thr 
  1               5                  10                  15 

 
           
             103  
             14  
             PRT  
             Homo sapiens  
           
            103 

Gly Ile Tyr Tyr Phe Ser Tyr Asp Ile Thr Leu Ala Asn Lys 
  1               5                  10 

 
           
             104  
             13  
             PRT  
             Homo sapiens  
           
            104 

Asp Ser Leu Phe Ser Gly Phe Leu Leu Tyr Val Asp Thr 
  1               5                  10 

 
           
             105  
             13  
             PRT  
             Homo sapiens  
           
            105 

Asn His Asp Val Ala Ser Gly Ser Thr Val Ile Tyr Leu 
  1               5                  10 

 
           
             106  
             126  
             PRT  
             Homo sapiens  
           
            106 

Ser Ala Phe Thr Val Ile Leu Ser Lys Ala Tyr Pro Ala Val Gly Ala 
  1               5                  10                  15 

Pro Ile Pro Phe Asp Glu Ile Leu Tyr Asn Arg Gln Gln His Tyr Asp 
             20                  25                  30 

Pro Arg Ser Gly Ile Phe Thr Cys Lys Ile Pro Gly Ile Tyr Tyr Phe 
         35                  40                  45 

Ser Tyr His Ile His Val Lys Gly Thr His Val Trp Val Gly Leu Tyr 
     50                  55                  60 

Lys Asn Gly Thr Pro Thr Met Tyr Thr Tyr Asp Glu Tyr Ser Lys Gly 
 65                  70                  75                  80 

Tyr Leu Asp Gln Ala Ser Gly Ser Ala Ile Met Glu Leu Thr Glu Asn 
                 85                  90                  95 

Asp Gln Val Trp Leu Gln Leu Pro Asn Ala Glu Ser Asn Gly Leu Tyr 
            100                 105                 110 

Ser Ser Glu Tyr Val His Ser Ser Phe Ser Gly Phe Leu Val 
        115                 120                 125 

 
           
             107  
             126  
             PRT  
             Homo sapiens  
           
            107 

Ser Ala Phe Ser Val Ala Val Thr Lys Ser Tyr Pro Arg Glu Arg Leu 
  1               5                  10                  15 

Pro Ile Lys Phe Asp Lys Ile Leu Met Asn Glu Gly Gly His Tyr Asn 
             20                  25                  30 

Ala Ser Ser Gly Lys Phe Val Cys Gly Val Pro Gly Ile Tyr Tyr Phe 
         35                  40                  45 

Thr Tyr Asp Ile Thr Leu Ala Asn Lys His Leu Ala Ile Gly Leu Val 
     50                  55                  60 

His Asn Gly Gln Tyr Arg Ile Arg Thr Phe Asp Ala Asn Thr Gly Asn 
 65                  70                  75                  80 

His Asp Val Ala Ser Gly Ser Thr Ile Leu Ala Leu Lys Gln Gly Asp 
                 85                  90                  95 

Glu Val Trp Leu Gln Ile Phe Tyr Ser Glu Gln Asn Gly Leu Phe Tyr 
            100                 105                 110 

Asp Pro Tyr Trp Thr Asp Ser Leu Phe Thr Gly Phe Leu Ile 
        115                 120                 125