ENZYMES

Abstract: The invention provides human enzymes (NZMS) and polynucleotides which identify and encode NZMS. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of NZMS.

Description: ENZYMES TECHNICAL FIELD This invention relates to nucleic acid and amino acid sequences of enzymes and to the use of these sequences in the diagnosis, treatment, and prevention of cell proliferative and autoimmune/inflammatory, cardiovascular, gastrointestinal, neurological, pulmonary, reproductive, and eye disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of enzymes. BACKGROUND OF THE INVENTION Hydrolases Hydrolysis is the breaking of a covalent bond in a substrate by introduction of a water molecule. The reaction is catalyzed by a hydrolytic enzyme, or hydrolase, and involves a nucleophilic attack by the water molecule's oxygen atom on a target bond in the substrate. The water molecule is split across the target bond, breaking the bond and generating two product molecules. Hydrolysis reactions form the basis of most metabolic pathways and are present in most biosynthetic pathways. Energy produced in the cell, for example, comes from the hydrolysis of ATP. Hydrolases also participate in reactions essential to functions such as cell signaling, cell proliferation, inflammation, apoptosis, secretion and excretion. Hydrolases are involved in key steps in disease processes involving these functions. Hydrolases may be grouped by substrate specificity into classes including aminohydrolases, phospholipases, carboxyl-esterases, phosphodiesterases, lysozymes, glycosidases, glyoxalases, sulfatases, phosphohydrolases, peptidases, nucleotidases and many others. Serine hydrolases are a functional class of hydrolytic enzymes that contain a serine residue in their active site. This class of enzymes contains proteinases, esterases, and lipases which hydrolyze a variety of substrates and, therefore, have different biological roles. Proteins in this superfamily can be further grouped into subfamilies based on substrate specificity or amino acid similarities (Puente, X.S. and Lopez-Ont, C. (1995) J. Biol. Chem. 270: 12926-12932). DHH phosphoesterases include the prune protein (Aravind, L. and Koonin, E. V. (1998) Trends Biochem. Sci. 23:17-19). Carboxylesterases are proteins that hydrolyze carboxylic esters and are classified into three categories- A, B, and C. Most type-B carboxylesterases are evolutionarily related and are considered to comprise a family of proteins. The type-B carboxylesterase family of proteins includes vertebrate acetylcholinesterase, mammalian liver microsomal carboxylesterase, mammalian bile-salt-activated lipase, and duck fatty acyl-CoA hydrolase. Some members of this protein family are not catalytically active but contain a domain related evolutionarily to other type-B carboxylesterases, such as thyroglobulin and Drosphila protein neuractin. Nucleotidases catalyze the formation of free nucleosides from nucleotides. The cytosolic nucleotidase cN-I (5' nucleotidase-I) cloned from pigeon heart catalyzes the formation of adenosine from AMP generated during ATP hydrolysis (Sala-Newby, G.B. et al. (1999) J. Biol. Chem. 274:17789-17793). Increased adenosine concentration is thought to be a signal of metabolic stress, and adenosine receptors mediate effects including vasodilation, decreased stimulatory neuron firing and ischemic preconditioning in the heart (Schrader, J. ( 1990) Circulation 81:389-391; Rubino, A. et al. (1992) Eur. J. Pharmacol. 220:95-98; de Jong, J.W. et al. (2000) Pharmacol. Ther. 87:141-149). Deficiency of pyrimidine 5 '-nucleotidase can result in hereditary hemolytic anemia (OMEVI Entry 266120). ADP-ribosylation is a reversible post-translational protein modification in which an ADP- ribose moiety is transferred from β-NAD to. a target amino acid such as arginine or cysteine. ADP- ribosylarginine hydrolases regenerate arginine by removing ADP-ribose from the protein, completing the ADP-ribosylation cycle (Moss, J. et al. (1997) Adv. Exp. Med. Biol. 419:25-33). ADP- ribosylation is a well-known reaction among bacterial toxins. Cholera toxin, for example, disrupts the adenylyl cyclase system by ADP-ribosylating the α-subunit of the stimulatory G-protein, causing an increase in intracellular cAMP (Moss, J. and Vaughan, M. (eds) (1990) ADP-ribosylating Toxins and G-Proteins: Insights into Signal Transduction, American Society for Microbiology, Washington, D.C.). ADP-ribosylation may also have a regulatory function in eukaryotes, affecting such processes as cytoskeletal assembly (Zhou, H. et al. (1996) Arch. Biochem. Biophys. 334:214-222) and cell proliferation in cytotoxic T-cells (Wang, J. et al. (1996) J. Immunol. 156:2819-2827). ATPases catalyze the hydrolysis of ATP to ADP in a variety of cellular processes. The ATPases Associated with cellular Activities (AAA) family is characterized by a conserved module of 230 amino acids present in one or two copies in each protein. AAAs function in processes including cell cycle regulation, gene expression in yeast and HN, vesicle-mediated transport, peroxisome assembly, 26S protease function (Confalonieri, F. and Duguet, M. (1995) Bioessays. 17:639-650). SPAF is a AAA-protein specific to early spermatogenesis and malignant conversion (Liu, Y. et al. (2000) Oncogene 19:1579-1588). Sulfatases catalyse the hydrolysis of sulfate ester bonds from a variety of substrates, including glycosaminoglycans, sulfolipids, and steroid sulfates. Sulfatase deficiencies are the cause of several human diseases, primarily lysosomal storage disorders. Other disorders associated with sulfatases include metachromatic leukodystrophy, a neurological disorder resulting from a deficiency of arylsurfatase A, and X-linked recessive chronodysplasia punctata, a disorder of cartilage and bone development due to a deficiency of arylsurfatase E. (See Parenti, G. et al. (1997) Curr. Opin, Genet. Dev. 7:386-391 for review.) Nucleases comprise both enzymes that hydrolyze DNA (DNase) and RNA (RNase). They serve different purposes in nucleic acid metabolism. Nucleases hydrolyze the phosphodiester bonds between adjacent nucleotides either at internal positions (endonucleases) or at the terminal 3' or 5' nucleotide positions (exonucleases). A DNA exonuclease activity in DNA polymerase, for example, serves to remove improperly paired nucleotides attached to the 3 -OH end of the growing DNA strand by the polymerase and thereby serves a "proofreading" function. DNA endonuclease activity is also involved in the excision step of the DNA repair process. RNases also serve a variety of functions. For example, RNase P is a ribonucleoprotein enzyme which cleaves the 5' end of pre-tRNAs as part of their maturation process. RNase H digests the RNA strand of an RNA/DNA hybrid. Such hybrids occur in cells invaded by retroviruses, and RNase H is an important enzyme in the retroviral replication cycle. Pancreatic RNase secreted by the pancreas into the intestine hydrolyzes RNA present in ingested foods. RNase activity in serum and cell extracts is elevated in a variety of cancers and infectious diseases (Schein, CH. (1997) Nat. Biotechnol. 15:529-536). Regulation of RNase activity is being investigated as a means to control tumor angiogenesis, allergic reactions, viral infection and replication, and fungal infections. Lyases Lyases are a class of enzymes that catalyze the cleavage of C-C, C-O, C-N, C-S, C-(halide), P-O, or other bonds without hydrolysis or oxidation to form two molecules, at least one of which contains a double bond (Stryer, L. (1995) Biochemistry, W.H. Freeman and Co., New York NY, p.620). Under the International Classification of Enzymes (Webb, E.C. (1992) Enzyme Nomenclature 1992: Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the Nomenclature and Classification of Enzymes. Academic Press, San Diego CA), lyases form a distinct class designated by the numeral 4 in the first digit of the enzyme number (i.e., EC 4.x.x.x). Further classification of lyases reflects the type of bond cleaved as well as the nature of the cleaved group. The group of C-C lyases includes carboxyl-lyases (decarboxylases), aldehyde-lyases (aldolases), oxo-acid-lyases, and other lyases. The C-O lyase group includes hydro-lyases, lyases acting on polysaccharides, and other lyases. The C-N lyase group includes ammonia-lyases, amidine- lyases, amine-lyases (deaminases), and other lyases. Lyases are critical components of cellular biochemistry, with roles in metabolic energy production, including fatty acid metabolism and the tricarboxylic acid cycle, as well as other diverse enzymatic processes. One important family of lyases are the carbonic anhydrases (CA), also called carbonate dehydratases, which catalyze the hydration of carbon dioxide in the reaction H 2 O + CO 2 ^ HCO 3 ~ + H + . CA accelerates this reaction by a factor of over 10 s by virtue of a zinc ion located in a deep cleft about 15 A below the protein' s surface and co-ordinated to the imidazole groups of three His residues. Water bound to the zinc ion is rapidly converted to HCO 3 ". Eight enzymatic and evolutionarily related forms of carbonic anhydrase are currently known to exist in humans: three cytosolic isozymes (CAI, CAII, and CAHI). two membrane-bound forms (CAIV and GAVE), a mitochondrial form (CAN), a secreted salivary form (CAVT) and a yet uncharacterized isozyme (Prosite PDOC00146 Eukaryotic-type carbonic anhydrases signature). Though the isoenzymes CAI, CAII, and bovine CAiπ have similar secondary structure and polypeptide-chain fold, CAI has 6 tryptophans, CAII has 7 and CADI has 8 (Boren, K. et al. (1996) Protein Sci. 5 :2479-2484). CAII is the predominant CA isoenzyme in the brain of mammals. CAs participate in a variety of physiological processes that involve pH regulation, CO 2 and HCO 3 " transport, ion transport, and water and electrolyte balance. For example, CAII contributes to H + secretion by gastric parietal cells, by renal tubular cells, and by osteoclasts that secrete H + to acidify the bone-resorbing compartment. In addition, CAII promotes HC0 3 " secretion by pancreatic duct cells, cilary body epithelium, choroid plexus, salivary gland acinar cells, and distal colonal epithelium, thus playing a role in the production of pancreatic juice, aqueous humor, cerebrospinal fluid, and saliva, and contributing to electrolyte and water balance. CAII also promotes C0 2 exchange in proximal tubules in the kidney, in erythrocytes, and in lung. CAIV has roles in several tissues: it facilitates HCO 3 " reabsorption in the kidney; promotes CO 2 flux in tissues including brain, skeletal muscle, and heart muscle; and promotes CO 2 exchange from the blood to the alveoli in the lung. CAVI probably plays a role in pH regulation in saliva, along with CAII, and may have a protective effect in the esophagus and stomach. Mitochondrial CAV appears to play important roles in gluconeogenesis and ureagenesis, based on the effects of CA inhibitors on these pathways. (Sly, W.S. and Hu, P.Y. (1995) Ann. Rev. Biochem. 64:375-401.) A number of disease states are marked by variations in CA activity. Mutations in CAII which lead to CAII deficiency are the cause of osteopetrosis with renal tubular acidosis (Online Medelian Inheritance in Man 259730 Osteopetrosis with Renal Tubular Acidosis). The concentration of CAII in the cerebrospinal fluid (CSF) appears to mark disease activity in patients with brain damage. High CA concentrations have been observed in patients with brain infarction. Patients with transient ischemic attack, multiple sclerosis, or epilepsy usually have CAII concentrations in the normal range, but higher CAII levels have been observed in the CSF of those with central nervous system infection, dementia, or trigeminal neuralgia (Parkkila, A.K. et al. (1997) Eur. J. Clin. Invest. 27:392-397). Colonic adenomas and adenocarcinomas have been observed to fail to stain for CA, whereas non- neoplastic controls showed CAI and CAII in the cytoplasm of the columnar cells lining the upper half of colonic crypts. The neoplasms show staining patterns similar to less mature cells lining the base of normal crypts (Gramlich T.L. et al. (1990) Arch. Pathol. Lab. Med. 114:415-419). Therapeutic interventions in a number of diseases involve altering CA activity. CA inhibitors such as acetazolamide are used in the treatment of glaucoma (Stewart, W.C. (1999) Curr. Opin. Opthamol. 10:99-108), essential tremor and Parkinson's disease (Uitti, R.J. (1998) Geriatrics 53:46-48, 53-57), intermittent ataxia (Singhvi, J.P. et al. (2000) Neurology India 48:78-80), and altitude related illnesses (Klocke, D.L. et al. (1998) Mayo Clin. Proc. 73:988-992). CA activity can be particularly useful as an indicator of long-term disease condition, since the enzyme reacts relatively slowly to physiological changes. CAI and zinc concentrations have been observed to decrease in hyperthyroid Graves' disease (Yoshida, K. (1996) Tohoku J. Exp. Med. 178:345-356) and glycosylated CAI is observed in diabetes mellitus (Kondo, T. et al. (1987) Clin. Chim. Acta 166:227-236). A positive correlation has been observed between CAI and CAII reactivity and endometriosis (Brinton, D.A. et al. (1996) Ann. Clin. Lab. Sci. 26:409-420; D'Cruz , O.J. et al. (1996) Fertil. Steril. 66:547-556). Another important member of the lyase family is omithine decarboxylase (ODC), the initial rate-limiting enzyme in polyamine biosynthesis. ODC catalyses the transformation of omithine into putrescine in the reaction L-ornithine ^ putrescine + CO 2 . Polyamines, which include putrescine and the subsequent metabolic pathway products spermidine and spermine, are ubiquitous cell components essential for DNA synthesis, cell differentiation, and proliferation. Thus the polyamines play a key role in tumor proliferation (Medina, M.A. et al. (1999) Biochem. Pharmacol. 57:1341-1344). ODC is a pyridoxal-5'-phosphate (PLP)-dependent enzyme which is active as a homodimer. Conserved residues include those at the PLP binding site and a stretch of glycine residues thought to be part of a substrate binding region (Prosite PDOC00685 Orn/DAP/Arg decarboxylase family 2 signatures). Mammalian ODCs also contain PEST regions, sequence fragments enriched in proline, glutamic acid, serine, and threonine residues that act as signals for intracellular degradation (Medina, supra). Many chemical carcinogens and tumor promoters increase ODC levels and activity. Several known oncogenes may increase ODC levels by enhancing transcription of the ODC gene, and ODC itself may act as an oncogene when expressed at very high levels. A high level of ODC is found in a number of precancerous conditions, and elevation of ODC levels has been used as part of a screen for tumor-promoting compounds (Pegg, A.E. et al. (1995) J. Cell. Biochem. Suppl. 22:132-138). Inhibitors of ODC have been used to treat tumors in animal models and human clinical trials, and have been shown to reduce development of tumors of the bladder, brain, esophagus, gastrointestinal tract, lung, oral cavity, mammary gland, stomach, skin and trachea (Pegg, supra; McCann, P.P. and Pegg, A.E. (1992) Pharmac. Ther. 54:195-215). ODC also shows promise as a target for chemoprevention (Pegg, supra). ODC inhibitors have also been used to treat infections by African trypanosomes , malaria, and Pneumocvstis carinii, and are potentially useful for treatment of autoimmune diseases such as lupus and rheumatoid arthritis (McCann, supra). Another family of pyridoxal-dependent decarboxylases are the group II decarboxylases. This family includes glutamate decarboxylase (GAD) which catalyzes the decarboxylation of glutamate into the neurotransmitter GABA; histidine decarboxylase (HDC), which catalyzes the decarboxylation of histidine to histamine; aromatic-L-amino-acid decarboxylase (DDC), also known as L-dopa decarboxylase or tryptophan decarboxylase, which catalyzes the decarboxylation of tryptophan to tryptamine and also acts on 5-hydroxy-tryptophan and dihydroxyphenylalanine (L-dopa); and cysteine sulfinic acid decarboxylase (CSD), the rate-limiting enzyme in the synthesis of taurine from cysteine (PROSITE PDOC00329 DDC/GAD HDC/TyrDC pyridoxal-phosphate attachment site). Taurine is an abundant sulfonic amino acid in brain and is thought to act as an osmoregulator in brain cells (Bitoun, M. and Tappaz, M. (2000) J. Neurochem. 75:919-924). Phosphatases hydrolytically remove phosphate groups from proteins, an energy-providing step that regulates many cellular processes, including intracellular signaling pathways that in turn control cell growth and differentiation, cell-cell contact, the cell cycle, and oncogenesis. Peptidases, also called proteases, cleave peptide bonds that form the backbone of peptide or protein chains. Proteolytic processing is essential to cell growth, differentiation, remodeling, and homeostasis as well as inflammation and the immune response. Since typical protein half-lives range from hours to a few days, peptidases are continually cleaving precursor proteins to their active form, removing signal sequences from targeted proteins, and degrading aged or defective proteins. Peptidases function in bacterial, parasitic, and viral invasion and replication within a host. Examples of peptidases include trypsin and chymotrypsin, components of the complement cascade and the blood-clotting cascade, lysosomal cathepsins, calpains, pepsin, renin, and chymosin (Beynon, R.J. and J.S. Bond (1994) Proteolytic Enzymes: A Practical Approach. Oxford University Press, New York, NY, pp. 1-5). Lysophospholipases (LPLs) regulate intracellular lipids by catalyzing the hydrolysis of ester bonds to remove an acyl group, a key step in Mpid degradation. Small LPL isoforms, approximately 15-30 kD, function as hydrolases; larger isoforms function both as hydrolases and transacylases. A particular substrate for LPLs, lysophosphatidylcholine, causes lysis of cell membranes. LPL activity is regulated by signaling molecules important in numerous pathways, including the inflammatory response. Thiolester hydrolases, also known as thioesterases, comprise another family of enzymes involved in Mpid metabolism. These enzymes have been found in liver, kidney, heart, lung, testis and white and brown adipose tissues, as well as intestine and adrenal gland tissues. Nomenclature of some members of the thioesterase family is derived from demonstration of their compartmentalization within these tissues in the cytosol (CTE), in peroxisomes (PTE) and in mitochondria (MTE) (Hunt, M.C. et al. (1999) J. Biol. Chem. 274:34317-34326). In general, thioesterases participate in the hydrolysis of long chain fatty acids. Acyl-CoA thioesterases catalyze the hydrolysis of acyl-CoA molecules to free fatty acids and CoA. This enzymatic activity is an intrinsic component of animal fatty acid synthetase and in this context serves to terminate chain elongation (Jones, J.M. et al. (1999) J. Biol. Chem. 274:9216-9223). The ability of thioesterases to regulate acyl-CoA concentration in the cell may provide a mechanism for the control of Mpid metaboMsm (Poupon, V. et al. (1999) J. Biol. Chem. 274:19188-19194). The phosphodiesterases catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. Phosphodiesterases are therefore crucial to a variety of cellular processes. Phosphodiesterases include DNA and RNA endo- and exo-nucleases, which are essential to cell growth and repMcation as well as protein synthesis. Another phosphodiesterase is acid sphingomyeMnase, which hydrolyzes the membrane phosphoMpid sphingomyeMn to ceramide and phosphorylchoMne. PhosphorylchoMne is used in the synthesis of phosphatidylchoMne, which is involved in numerous intracellular signaMng pathways. Ceramide is an essential precursor for the generation of gangMosides, membrane Mpids found in high concentration in neural tissue. Defective acid sphingomyeMnase phosphodiesterase leads to a build-up of sphingomyeMn molecules in lysosomes, resulting in Niemann-Pick disease. Glycosidases catalyze the cleavage of hemiacetyl bonds of glycosides, which are compounds that contain one or more sugar. MammaMan lactase-phlorizin hydrolase, for example, is an intestinal enzyme that spMts lactose. MammaMan beta-galactosidase removes the terminal galactose from gangMosides, glycoproteins, and glycosaminoglycans, and deficiency of this enzyme is associated with a gangMosidosis known as Morquio disease type B. Vertebrate lysosomal alpha-glucosidase, which hydrolyzes glycogen, maltose, and isomaltose, and vertebrate intestinal sucrase-isomaltase, which hydrolyzes sucrose, maltose, and isomaltose, are widely distributed members of this family with highly conserved sequences at their active sites. Phosphoenolpyruvate carboxykinase (ATP) (EC 4.1.1.49) is a lyase involved in gluconeogenesis, the production of glucose from storage compounds in the body. This enzyme catalyzes the decarboxylation of oxaloacetate to form phosphoenolpyruvate, accompanied by hydrolysis of ATP. (See, e.g., Matte, A. et al. (1997) J. Biol. Chem. 272:8105-8108; Medina, N et al. (1990) J. Bacteriol. 172:7151-7156.) L-rhamnose and D-fucose are 6-deoxyhexoses found in complex carbohydrates in bacterial cell walls. One of the steps in the pathways leading to the synthesis of these carbohydrates is the conversion of dTDP-D-glucose to an unstable 4-keto-6-deoxy intermediate, a reaction catalyzed by the lyase dTDP-D-glucose 4,6-dehydratase (EC 4.2.1.46). (See, e.g., Tonetti. M. et al. (1998) Biochimie 80:923-931; Yoshida, Y. et al. (1999) J. Biol. Chem. 274:16933-16939.) Isocitrate lyase (EC 4.1.3.1) is involved in the glyoxylate cycle, a modification of the citric acid cycle. The glyoxylate cycle occurs in bacteria, fungi, and plants. Isocitrate lyase catalyzes the cleavage of isocitrate to yield succinate and glyoxylate. (See, e.g., Beeching, J.R. (1989) Protein Seq. Data Anal. 2:463-466; Atomi, H. et al. (1990) J. Biochem. 107:262-266.) Aldolases are lyases which catalyze aldol condensation reactions. Fructose 1,6-bisphosphate aldolase (FBP-aldolase; EC 4.1.2.13) catalyzes the reversible cleavage of fructose 1,6-bisphosphate to yield dihydroxyacetone phosphate, a ketose, and glyceraldehyde 3-phosphate, an aldose. Class I FBP- aldolases are found in higher organisms, and exist as homotetiamers. Class II FBP-aldolases tend to be dimeric, occur in yeast and bacteria, and have an absolute requirement for a divalent cation for catalytic activity. (See, e.g., Hall, D.R. et al. (1999) J. Mol. Biol. 287:383-394.) Pseudouridine is an isomer of uridine which helps to maintain the specific tertiary structures of certain rRΝAs, tRΝAs, and small nuclear and nucleolar RΝAs. Pseudouridine is not directly incorporated into these RΝAs, but is synthesized by pseudouridine synthases (EC 4.2.1.70), lyases which act on specific uridine residues within these RΝAs. The Rlu family of pseudouridine synthases includes Escherichia coM ribosomal large subunit synthase A, which synthesizes pseudouridine at position 746 in 23 S rRΝA and Escherichia coM ribosomal large subunit synthase C, which synthesizes pseudouridine at positions 955, 2504, and 2580 in 23S rRΝA. (See, e.g., Conrad, J. et al. (1998) J. Biol. Chem. 273:18562-18566.) Fumarate lyases are a group of lyases which share Mmited sequence homology and use fumarate as a substrate. These enzymes include f marase (EC 4.2.1.2), aspartase (EC 4.3.1.1), arginosuccinase (EC 4.3.2.2), and adenylosuccinase (EC 4.3.2.2). (See, e.g., Woods, S.A. et al (1988) Biochim. Biophys. Acta 954:14-26; Woods, S.A. et al. (1988) FEMS Microbiol. Lett. 51:181- 186; Zalkin, H. and J.E. Dixon (1992) Prog. Nucleic Acid Res. Mol. Biol. 42:259-287.) The glyoxylase system is involved in gluconeogenesis, the production of glucose from storage compounds in the body. It consists of glyoxylase I, which catalyzes the formation of S-D- lactoylglutathione from methyglyoxal, a side product of triose-phosphate energy metaboMsm, and glyoxylase EC, which hydrolyzes S-D-lactoylglutathione to D-lactic acid and reduced glutathione. Glyoxylases are involved in hyperglycemia, non-insulin-dependent diabetes mellitus, the detoxification of bacterial toxins, and in the control of cell proMferation and microtubule assembly. A small subclass of hydrolases acting on ether bonds includes the thioether hydrolases. S- adenosyl-L-homocysteine hydrolase, also known as AdoHcyase or SAHH (PROSITE PDOC00603 ; EC 3.3.1.1), is a thioether hydrolase first described in rat Mver extracts as the activity responsible for the reversible hydrolysis of S-adenosyl-L-homocysteine (AdoHcy) to adenosine and homocysteine (Sganga, M.W. et al. (1992) PNAS 89:6328-6332). SAHH is a cytosoMc enzyme that has been found in aU cells that have been tested, with the exception of Escherichia coM and certain related bacteria (Walker, R.D. et al. (1975) Can. J. Biochem. 53:312-319; Shimizu, S. et al. (1988) FEMS Microbiol. Lett. 51:177-180; Shimizu, S. et al. (1984) Eur. J. Biochem. 141:385-392). SAHH activity is dependent on NAD + as a cofactor. Deficiency of SAHH is associated with hypermethioninemia (OnMne MendeMan Inheritance in Man (OMEVI) #180960 Hypermethioninemia), a pathologic condition characterized by neonatal cholestasis, failure to thrive, mental and motor retardation, facial . dysmoφhism with abnormal hair and teeth, and myocaridopathy (Labrune, P. et al. (1990) J. Pediat. 117:220-226). Another subclass of hydrolases includes those enzymes which act on carbon-nitrogen (C-N) bonds other than peptide bonds. To this subclass belong those enzymes hydrolyzing amides, amidines, and other C-N bonds. This subclass is further subdivided on the basis of substrate specificity such as Mnear amides, cycMc amides, Mnear amidines, cycMc amidines, nitriles and other compounds. A hydrolase belonging to the sub-subclass of enzymes acting only on asparagine-oMgosaccharides containing one amino acid is N -(β-N-acetylglucosaminyl)-L-asparaginase, or aspartylglucosylaminidase (AGA; EC 3.5.1.26). AGA is a key enzyme in the cataboMsm of Ν-Mnked oMgosaccharides of glycoproteins. It cleaves the asparagine from the residual Ν-acetylglucosamines as one of the final steps in the lysosomal breakdown of glycoproteins. AGA is an enzyme of lysosomal origin that has been found in worms, rats, mice, pigs, humans, and flavobacteria (ExPASy Enzyme View of ENZYME: 3.5.1.2; SWISS-PROT P20933). A deficiency of AGA causes a lysosomal disease known as aspartylglucosaminuria (AGU) (OnMne MendeMan Inheritance in Man (OMEVI) #208400 Aspartylglucosaminuria; Jenner, FA. et al. (1967) Biochem. J. 103:48P-49P; PolMtt, R.J. et al. (1968) Lancet 11:253-255). Patients with AGU exhibit severe mental retardation, cranial asymmetry, scoMosis, periodic hyperactivity, and vacuolated lymphocytes. AGU in infants is characterized by diarrhea and frequent infections (Palo, J. et al. (1970) J. Ment. Defic. Res. 14:168- 173). It has been shown that AGU stems from genetic mutations in the AGU gene, which probably affects the folding and stabiMty of the AGA molecule (Ikonen, E. et al. (1991) PNAS 88:11222-11226; Ikonen, E. et al. (1991) EMBO J. 10:51-58; Ikonen, E. et al. (1991) Genomics 11:206-211). MetaboMc consequences of AGA deficiency in mice have been found to be associated with defects in neuromotor coordination, including impaired bladder function and severe ataxic gait in older mice (Tenhunen, K. et al. (1995) Genomics 30:244-250; Gonzalez-Gomez, I. et al. (1998) Am. J. Path. 153:1293-1300). Pancreatic ribonucleases (RNase) are pyrimidine-specific endonucleases found in high quantity in the pancreas of certain mammaMan taxa and of some reptiles (Beintema, J.J. et al (1988) Prog. Biophys. Mol. Biol. 51:165-192). Proteins in the mammaMan pancreatic RNase superfamily are noncytosoMc endonucleases that degrade RNA through a two-step transphosphorolytic-hydrolytic reaction (Beintema, J.J. et al. (1986) Mol. Biol. Evol. 3:262-275). Specifically, the enzymes are involved in endonucleolytic cleavage of 3 -phosphomononucleotides and 3 -phosphooMgonucleotides ending in C-P or U-P with 2',3'-cycMc phosphate intermediates. Ribonucleases can unwind the DNA heMx by complexing with single-stranded DNA; the complex arises by an extended multi-site cation-anion interaction between lysine and arginine residues of the enzyme and phosphate groups of the nucleotides. Some of the enzymes belonging to this family appear to play a purely digestive role, whereas others exhibit potent and unusual biological activities (D'Alessio, G. (1993) Trends CeM Biol. 3:106-109). Proteins belonging to the pancreatic RNase family include: bovine seminal vesicle and brain ribonucleases; kidney non-secretory ribonucleases (Beintema, J.J. et al (1986) FEBS Lett. 194:338-343); Mver-type ribonucleases (Rosenberg, H.F. et al. (1989) PNAS U.S.A. 86:4460-4464); angiogenin, which induces vascularisation of normal and maMgnant tissues; eosinophil cationic protein (Hofsteenge, J. et al. (1989) Biochemistry 28:9806-9813), a cytotoxin and helminthotoxin with ribonuclease activity; and frog Mver ribonuclease and frog siaMc acid-binding lectin. The sequences of pancreatic RNases contain 4 conserved disulphide bonds and 3 amino acid residues involved in the catalytic activity. Aconitase (EC 4.2.1.3) is a lyase which carries out a crucial step in the tricarboxyMc acid cycle. Aconitase catalyzes the reversible transformation of citrate into isocitrate through a cis- aconitate intermediate. Two forms of aconitase are found in mammaMan cells, a cytosoMc aconitase (Kennedy, M.C. et al. (1992) Proc. Natl. Acad. Sci. USA 89:11730-11734) and a mitochondrial aconitase (Mirel, D.B. et al. (1998) Gene 213:205-218). Ribulose-l,5-bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) is a lyase which carries out a crucial step in the Calvin cycle during photosynthesis. Rubisco catalyzes the covalent incoφoration of carbon dioxide into the 5-carbon sugar ribulose 1 ,5-bisphosphate along with the simultaneous cleavage of this molecule into two molecules of 3-phosphoglycerate. (See, e.g., Hartman, F.C. and M.R. Haφel (1994) Annu. Rev. Biochem. 63:197-234.) Specific methyltransferases (EC 2.1.1.43) catalyze the methylation of amino groups near the N-termini of the small and large subunits of Rubisco (Ying, Z. et al. (1998) Acta Biol. Hung. 49:173-184; Klein, R.R. and R.L. Houtz (1995) Plant Mol. Biol. 27:249-261). DihydrodipicoMnate synthetase (EC 4.2.1.52) is a lyase involved in lysine biosynthesis. This enzyme catalyzes the condensation of pyruvate and aspartic-β-semialdehyde with the eMmination of water to produce 2,3-dihydrodipicoMnate. Proper regulation of lyases is critical to normal physiolo y. For example, mutation induced deficiencies in the uropoφhyrinogen decarboxylase can lead to photosensitive cutaneous lesions in the geneticaUy-linked disorder famiMal poφhyria cutaneatarda (Mendez, M. et al. (1998) Am. J. Genet. 63:1363-1375). It has also been shown that adenosine deaminase (ADA) deficiency stems from genetic mutations in the ADA gene, resulting in the disorder severe combined immunodeficiency disease (SCID) (Hershfield, M.S. (1998) Semin. Hematol. 35:291-298). The discovery of new enzymes, and the polynucleotides encoding them, satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of ceU proMferative and autoimmune/inflammatory, cardiovascular, gastrointestinal, neurological, pulmonary, reproductive, and eye disorders, and in the assessment of the effects of exogenous compounds on the expression of nucleic acid and amino acid sequences of enzymes. SUMMARY OF THE INVENTION The invention features purified polypeptides, enzymes, referred to collectively as "NZMS" and individually as "NZMS-1," "NZMS-2," "NZMS-3," "NZMS-4," "NZMS-5," "NZMS-6," "NZMS-7," "NZMS-8," "NZMS-9," "NZMS-10," "NZMS-11," "NZMS-12," "NZMS-13," "NZMS-14," "NZMS- 15," "NZMS-16," "NZMS-17," and "NZMS-18." In one aspect, the invention provides an isolated polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, b) a polypeptide comprising a naturaUy occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18. In one alternative, the invention provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:l-l 8. The invention further provides an isolated polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ED NO: 1-18, b) a polypeptide comprising a naturaUy occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:l- 18, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ED NO: 1-18. In one alternative, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO: 1-18. In another alternative, the polynucleotide is selected from the group consisting of SEQ ID NO :19-36. Additionally, the invention provides a recombinant polynucleotide comprising a promoter sequence operably Mnked to a polynucleotide encoding a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, c) a, biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18. In one alternative, the invention provides a cell transformed with the recombinant polynucleotide. In another alternative, the invention provides a transgenic organism comprising the recombinant polynucleotide. The invention also provides a method for producing a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, b) a polypeptide comprising a naturaUy occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, c) a biologicaUy active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 -18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ED NO: 1-18. The method comprises a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide comprising a promoter sequence operably Mnked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed. AdditionaUy, the invention provides an isolated antibody which specificaUy binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, b) a polypeptide comprising a naturaUy occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 1 -18, c) a biologicaUy active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ π> NO:l-18. The invention further provides an isolated polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO: 19-36, b) a polynucleotide comprising a naturaUy occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 19-36, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). In one alternative, the polynucleotide comprises at least 60 contiguous nucleotides. Additionally, the invention provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO :19-36, b) a polynucleotide comprising a naturaUy occurring polynucleotide sequence at least 90% identical to a olynucleoti.de sequence selected from the group consisting of SEQ ED NO:19-36, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and optionaUy, if present, the amount thereof. In one alternative, the probe comprises at least 60 contiguous nucleotides. The invention further provides a method for detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, b) a polynucleotide comprising a naturaUy occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:l 9-36, c) a polynucleotide complementary to the polynucleotide of a), d) a polynucleotide complementary to the polynucleotide of b), and e) an RNA equivalent of a)-d). The method comprises a) ampMfying said target polynucleotide or fragment thereof using polymerase chain reaction ampMfication, and b) detecting the presence or absence of said ampMfied target polynucleotide or fragment thereof, and, optionaUy, if present, the amount thereof. The invention further provides a composition comprising an effective amount of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, b) a polypeptide comprising a naturaUy occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, c) a ' biologicaUy active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ED NO:l-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, and a pharmaceuticaUy acceptable excipient. In one embodiment, the composition comprises an amino acid sequence selected from the group consisting of SEQ ID NO:l-18. The invention additionaUy provides a method of treating a disease or condition associated with decreased expression of functional NZMS, comprising administering to a patient in need of such treatment the composition. The invention also provides a method for screening a compound for effectiveness as an agonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:l -18, c) a biologicaUy active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:l-18. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. In one alternative, the invention provides a composition comprising an agonist compound identified by the method and a pharmaceuticaUy acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with decreased expression of functional NZMS, comprising administering to a patient in need of such treatment the composition. AdditionaUy, the invention provides a method for screening a compound for effectiveness as an antagonist of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, b) a polypeptide comprising a naturaUy occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ED NO:l~18, c) a biologicaUy active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ED NO: 1-18. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. In one alternative, the invention provides a composition comprising an antagonist compound identified by the method and a pharmaceuticaUy acceptable excipient. In another alternative, the invention provides a method of treating a disease or condition associated with overexpression of functional NZMS, comprising administering to a patient in need of such treatment the composition. The invention further provides a method of screening for a compound that specificaUy binds to a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ED NO: 1-18, b) a polypeptide comprising a naturaUy occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO: 1 -18, c) a biologicaUy active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ED NO:l-18. The method comprises a) combining the polypeptide with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide to the test compound, thereby identifying a compound that specificaUy binds to the polypeptide. The invention further provides a method of screening for a compound that modulates the activity of a polypeptide selected from the group consisting of a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:l-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:l -18, c) a biologicaUy active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18. The method comprises a) combining the polypeptide with at least one test compound under conditions permissive for the activity of the polypeptide, b) assessing the activity of the polypeptide in the presence of the test compound, and c) comparing the activity of the polypeptide in the presence of the test compound with the activity of the polypeptide in the absence of the test compound, wherein a change in the activity of the polypeptide in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide. The invention further provides a method for screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a polynucleotide sequence selected from the group consisting of SEQ ID NO: 19-36, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, and b) detecting altered expression of the target polynucleotide. The invention further provides a method for assessing toxicity of a test compound, said method comprising a) treating a biological sample containing nucleic acids with the test compound; b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, ii) a polynucleotide comprising a naturaUy occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:l 9-36, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of M), and v) an RNA equivalent of i)-iv). Hybridization occurs under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide selected from the group consisting of i) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, ii) a polynucleotide comprising a naturaUy occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 19-36, Mi) a polynucleotide complementary to the polynucleotide of i), iv) a polynucleotide complementary to the polynucleotide of M), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide comprises a fragment of a polynucleotide sequence selected from the group consisting of i)-v) above; c) quantifying the amount of hybridization complex; and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound. BRIEF DESCRIPTION OF THE TABLES Table 1 summarizes the nomenclature for the fuU length polynucleotide and polypeptide sequences of the present invention. Table 2 shows the GenBank identification number and annotation of the nearest GenBank homolog, and the PROTEOME database identification numbers and annotations of PROTEOME database homologs, for polypeptides of the invention. The probabihty scores for the matches between each polypeptide and its homolog(s) are also shown. Table 3 shows structural features of polypeptide sequences of the invention, including predicted motifs and domains, along with the methods, algorithms, and searchable databases used for analysis of the polypeptides. Table 4 Msts the cDNA and/or genomic DNA fragments which were used to assemble polynucleotide sequences of the invention. Table 5 shows the representative cDNA Mbrary for polynucleotides of the invention. Table 6 provides an appendix which describes the tissues and vectors used for construction of the cDNA Mbraries shown in Table 5. Table 7 shows the tools, programs, and algorithms used to analyze the polynucleotides and polypeptides of the invention, along with appMcable descriptions, references, and threshold parameters. DESCRIPTION OF THE INVENTION Before the present proteins, nucleotide sequences, and methods are described, it is understood that this invention is not Mmited to the particular machines, materials and methods described, as these may vary. It is also to be understood that the terminology used herein is for the puφose of describing particular embodiments only, and is not intended to Mmit the scope of the present invention which wiU be Mmited only by the appended claims. It must be noted that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a host ceU" includes a pluraUty of such host ceUs, and a reference to "an antibody" is a reference to one or more antibodies and equivalents thereof known to those skiUed in the art, and so forth. Unless defined otherwise, aU technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skiU in the art to which this invention belongs. Although any machines, materials, and methods similar or equivalent to those described herein can be used to practice or test the present invention, the preferred machines, materials and methods are now described. AU pubMcations mentioned herein are cited for the purpose of describing and disclosing the ceU Mnes, protocols, reagents and vectors which are reported in the pubMcations and which might be used in connection with the invention. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. DEFINITIONS "NZMS" refers to the amino acid sequences of substantiaUy purified NZMS obtained from any species, particularly a mammaMan species, including bovine, ovine, porcine, murine, equine, and human, and from any source, whether natural, synthetic, semi-synthetic, or recombinant. The term "agonist" refers to a molecule which intensifies or mimics the biological activity of NZMS. Agonists may include proteins, nucleic acids, carbohydrates, smaU molecules, or any other compound or composition which modulates the activity of NZMS either by directly interacting with NZMS or by acting on components of the biological pathway in which NZMS participates. An "aUeMc variant" is an alternative form of the gene encoding NZMS. AUeMc variants may result from at least one mutation in the nucleic acid sequence and may result in altered mRNAs or in polypeptides whose structure or function may or may not be altered. A gene may have none, one, or many aUeMc variants of its naturaUy occurring form. Common mutational changes which give rise to aUeMc variants are generaUy ascribed to natural deletions, additions, or substitutions of nucleotides. Each of these types of changes may occur alone, or in combination with the others, one or more times in a given sequence. "Altered" nucleic acid sequences encoding NZMS include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as NZMS or a polypeptide. with at least one functional characteristic of NZMS. Included within this definition are polymoφhisms which may or may not be readily detectable using a particular oMgonucleotide probe of the polynucleotide encoding NZMS, and improper or unexpected hybridization to aUeUc variants, with a locus other than the normal chromosomal locus for the polynucleotide sequence encoding NZMS. The encoded protein may also be "altered," and may contain deletions, insertions, or substitutions of amino acid residues which produce a silent change and result in a functionally equivalent NZMS. Dehberate amino acid substitutions may be made on the basis of similarity in polarity, charge, solubiMty, hydrophobicity, hydrophiMcity, and/or the amphipathic nature of the residues, as long as the biological or immunological activity of NZMS is retained. For example, negatively charged amino acids may include aspartic acid and glutamic acid, and positively charged amino acids may include lysine and arginine. Amino acids with uncharged polar side chains having similar hydrophiMcity values may include: asparagine and glutamine; and serine and threonine. Amino acids with uncharged side chains having similar hydrophiMcity values may include: leucine, isoleucine, and vaMne; glycine and alanine; and phenylalanine and tyrosine. The terms "amino acid" and "amino acid sequence" refer to an oMgopeptide, peptide, polypeptide, or protein sequence, or a fragment of any of these, and to naturaMy occurring or synthetic molecules. Where "amino acid sequence" is recited to refer to a sequence of a naturaUy occurring protein molecule, "amino acid sequence" and Mke terms are not meant to Mmit the amino acid sequence to the complete native amino acid sequence associated with the recited protein molecule. "AmpMfication" relates to the production of additional copies of a nucleic acid sequence. AmpMfication is generaUy carried out using polymerase chain reaction (PCR) technologies weU known in the art. The term "antagonist" refers to a molecule which inhibits or attenuates the biological activity of NZMS. Antagonists may include proteins such as antibodies, nucleic acids, carbohydrates, smaU molecules, or any other compound or composition which modulates the activity of NZMS either by directly interacting with NZMS or by acting on components of the biological pathway in which NZMS participates. The term "antibody" refers to intact immunoglobuMn molecules as weU as to fragments thereof, such as Fab, F(ab') 2 , and Fv fragments, which are capable of binding an epitopic determinant. Antibodies that bind NZMS polypeptides can be prepared using intact polypeptides or using fragments containing smaU peptides of interest as the immunizing antigen. The polypeptide or oMgopeptide used to immunize an animal (e.g., a mouse, a rat, or a rabbit) can be derived from the translation of RNA, or synthesized chemically, and can be conjugated to a carrier protein if desired. Commonly used carriers that are chemicaUy coupled to peptides include bovine serum albumin, thyroglobuMn, and keyhole Mmpet hemocyanin (KLH). The coupled peptide is then used to immunize the animal. The term "antigenic determinant" refers to that region of a molecule (i.e., an epitope) that makes contact with a particular antibody. When a protein or a fragment of a protein is used to immunize a host animal, numerous regions of the protein may induce the production of antibodies which bind specificaUy to antigenic determinants (particular regions or three-dimensional structures on the protein). An antigenic determinant may compete with the intact antigen (i.e., the immunogen used to eUcit the immune response) for binding to an antibody. The term "aptamer" refers to a nucleic acid or oMgonucleoti.de molecule that binds to a specific molecular target. Aptamers are derived from an in vitro evolutionary process (e.g., SELEX (Systematic Evolution of Ligands by Exponential Enrichment), described in U.S. Patent No. 5,270,163), which selects for target-specific aptamer sequences from large combinatorial Mbraries. Aptamer compositions may be double-stranded or single-stranded, and may include deoxyribonucleotides, ribonucleotides, nucleotide derivatives, or other nucleotide-Mke molecules. The nucleotide components of an aptamer may have modified sugar groups (e.g., the 2'-OH group of a ribonucleotide may be replaced by 2'-F or -NYL^, which may improve a desired property, e.g., resistance to nucleases or longer Mfetime in blood. Aptamers may be conjugated to other molecules, e.g., a high molecular weight carrier to slow clearance of the aptamer from the circulatory system. Aptamers may be specificaUy cross-Mnked to their cognate Mgands, e.g., by photo-activation of a cross-Mnker. (See, e.g., Brody, E.N. and L. Gold (2000) J. Biotechnol. 74:5-13.) The term "intramer" refers to an aptamer which is expressed in vivo. For example, a vaccinia virus-based RNA expression system has been used to express specific RNA aptamers at high levels in the cytoplasm of leukocytes (BMnd, M. et al. (1999) Proc. Natl Acad. Sci. USA 96:3606-3610). The term "spiegelmer" refers to an aptamer which includes J__-DNA, E.-RNA, or other left- handed nucleotide derivatives or nucleotide-Mke molecules. Aptamers containing left-handed nucleotides are resistant to degradation by naturaUy occurring enzymes, which normaUy act on substrates containing right-handed nucleotides. The term "antisense" refers to any composition capable of base-pairing with the "sense" (coding) strand of a specific nucleic acid sequence. Antisense compositions may include DNA; RNA; peptide nucleic acid (PNA); oMgonucleotides having modified backbone Mnkages such as phosphorothioates, methylphosphonates, or benzylphosphonates; oMgonucleotides having modified sugar groups such as 2'-methoxyethyl sugars or 2'-methoxyethoxy sugars; or oMgonucleotides having modified bases such as 5-methyl cytosine, 2'-deoxyuracil, or 7-deaza-2'-deoxyguanosine. Antisense molecules may be produced by any method including chemical synthesis or transcription. Once introduced into a ceU, the complementary antisense molecule base-pairs with a naturally occurring nucleic acid sequence produced by the ceU to form duplexes which block either transcription or translation. The designation "negative" or "minus" can refer to the antisense strand, and the designation "positive" or "plus" can refer to the sense strand of a reference DNA molecule. The term "biologically active" refers to a protein having structural, regulatory, or biochemical functions of a naturaUy occurring molecule. Likewise, "immunologicaUy active" or "immunogenic" refers to the capabiMty of the natural, recombinant, or synthetic NZMS, or of any oMgopeptide thereof, to induce a specific immune response in appropriate animals or ceUs and to bind with specific antibodies. "Complementary" describes the relationship between two single-stranded nucleic acid sequences that anneal by base-pairing. For example, 5'-AGT-3' pairs with its complement, 3'-TCA-5'. A "composition comprising a given polynucleotide sequence" and a "composition comprising a given amino acid sequence" refer broadly to any composition containing the given polynucleotide or amino acid sequence. The composition may comprise a dry formulation or an aqueous solution. Compositions comprising polynucleotide sequences encoding NZMS or fragments of NZMS may be employed as hybridization probes. The probes may be stored in freeze-dried form and may be associated with a stabiMzing agent such as a carbohydrate. In hybridizations, the probe may be deployed in an aqueous solution containing salts (e.g., NaCl), detergents (e.g., sodium dodecyl sulfate; SDS), and other components (e.g., Denhardt's solution, dry milk, salmon sperm DNA, etc.). "Consensus sequence" refers to a nucleic acid sequence which has been subjected to repeated DNA sequence analysis to resolve uncaUed bases, extended using the XL-PCR kit (AppMed Biosystems, Foster City CA) in the 5' and/or the 3' direction, and resequenced, or which has been assembled from one or more overlapping cDNA, EST, or genomic DNA fragments using a computer program for fragment assembly, such as the GELVIEW fragment assembly system (GCG, Madison WI) or Phrap (University of Washington, Seattle WA). Some sequences have been both extended and assembled to produce the consensus sequence. "Conservative amino acid substitutions" are those substitutions that are predicted to least interfere with the properties of the original protein, i.e., the structure and especiaUy the function of the protein is conserved and not significantly changed by such substitutions. The table below shows amino acids which may be substituted for an original amino acid in a protein and which are regarded as conservative amino acid substitutions. Original Residue Conservative Substitution Ala Gly, Ser Arg His, Lys Asn Asp, Gin, His Asp Asn, Glu Cys Ala, Ser Gin Asn, Glu, His Glu Asp, Gin, His Gly Ala His Asn, Arg, Gin, Glu lie Leu, Val Leu He, Val Lys Arg, Gin, Glu Met Leu, lie Phe His, Met, Leu, Tφ, Tyr Ser Cys, Thr Thr Ser, Val Tφ Phe, Tyr Tyr His, Phe, Tφ Val lie, Leu, Thr Conservative amino acid substitutions generaUy maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha heUcal conformation, (b) the charge or hydrophobicity of the molecule at the site of the substitution, and/or (c) the bulk of the side chain. A "deletion" refers to a change in the amino acid or nucleotide sequence that results in the absence of one or more amino acid residues or nucleotides. The term "derivative" refers to a chemicaUy modified polynucleotide or polypeptide. Chemical modifications of a polynucleotide can include, for example, replacement of hydrogen by an alkyl, acyl, hydroxyl, or amino group. A derivative polynucleotide encodes a polypeptide which retains at least one biological or immunological function of the natural molecule. A derivative polypeptide is one modified by glycosylation, pegylation, or any similar process that retains at least one biological or immunological function of the polypeptide from which it was derived. A "detectable label" refers to a reporter molecule or enzyme that is capable of generating a measurable signal and is covalently or noncovalently joined to a polynucleotide or polypeptide. "Differential expression" refers to increased or upregulated; or decreased, downregulated, or absent gene or protein expression, determined by comparing at least two different samples. Such comparisons may be carried out between, for example, a treated and an untreated sample, or a diseased and a normal sample. "Exon shuffMng" refers to the recombination of different coding regions (exons). Since an exon may represent a structural or functional domain of the encoded protein, new proteins may be assembled through the novel reassortment of stable substructures, thus aUowing acceleration of the evolution of new protein functions. A "fragment" is a unique portion of NZMS or the polynucleotide encoding NZMS which is identical in sequence to but shorter in length than the parent sequence. A fragment may comprise up to the entire length of the defined sequence, minus one nucleotide/amino acid residue. For example, a fragment may comprise from 5 to 1000 contiguous nucleotides or amino acid residues. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other puφoses, may be at least 5, 10, 15, 16, 20, 25, 30, 40, 50, 60, 75, 100, 150, 250 or at least 500 contiguous nucleotides or amino acid residues in length. Fragments may be preferentiaUy selected from certain regions of a molecule. For example, a polypeptide fragment may comprise a certain length of contiguous amino acids selected from the first 250 or 500 amino acids (or first 25% or 50%) of a polypeptide as shown in a certain defined sequence. Clearly these lengths are exemplary, and any length that is supported by the specification, including the Sequence Listing, tables, and figures, may be encompassed by the present embodiments. A fragment of SEQ ID NO: 19-36 comprises a region of unique polynucleotide sequence that specificaUy identifies SEQ ID NO:19-36, for example, as distinct from any other sequence in the genome from which the fragment was obtained. A fragment of SEQ ID NO: 19-36 is useful, for example, in hybridization and ampMfication technologies and in analogous methods that distinguish SEQ ED NO :19-36 from related polynucleotide sequences. The precise length of a fragment of SEQ ID NO: 19-36 and the region of SEQ ED NO: 19-36 to which the fragment corresponds are routinely determinable by one of ordinary skiU in the art based on the intended puφose for the fragment. A fragment of SEQ ID NO:l-18 is encoded by a fragment of SEQ ID NO:19-36. A fragment of SEQ ID NO: 1-18 comprises a region of unique amino acid sequence that specificaUy identifies SEQ ID NO:l-18. For example, a fragment of SEQ ID NO:l-18 is useful as an immunogenic peptide for the development of antibodies that specificaUy recognize SEQ ID NO:l -18. The precise length of a fragment of SEQ ID NO:l-18 and the region of SEQ ID NO:l-18 to which the fragment corresponds are routinely determinable by one of ordinary skiU in the art based on the intended piupose for the fragment. A "fuU length" polynucleotide sequence is one containing at least a translation initiation codon (e.g., methionine) foUowed by an open reading frame and a translation termination codon. A "fuU length" polynucleotide sequence encodes a "fuU length" polypeptide sequence. "Homology" refers to sequence similarity or, interchangeably, sequence identity, between two or more polynucleotide sequences or two or more polypeptide sequences. The terms "percent identity" and "% identity," as apphed to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aMgned using a standardized algorithm. Such an algorithm may insert, in a standardized and reproducible way, gaps in the sequences being compared in order to optimize aMgnment between two sequences, and therefore achieve a more meaningful comparison of the two sequences. Percent identity between polynucleotide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incoφorated into the MEGALIGN version 3.12e sequence aMgnment program. This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison WE). CLUSTAL V is described in Higgins, D.G. and P.M. Shaφ (1989) CABIOS 5:151-153 and in Higgins, D.G. et al. (1992) CABIOS 8:189-191. For pairwise aMgnments of polynucleotide sequences, the default parameters are set as foUows: Ktuple=2, gap penalty=5, window=4, and "diagonals saved"=4. The "weighted" residue weight table is selected as the default. Percent identity is reported by CLUSTAL V as the "percent similarity" between aMgned polynucleotide sequences. Alternatively, a suite of commonly used and freely available sequence comparison algorithms is provided by the National Center for Biotechnology Information (NCBI) Basic Local AMgnment Search Tool (BLAST) (Altschul, S.F. et al. (1990) J. Mol. Biol. 215:403-410), which is available from several sources, including the NCBI, Bethesda, MD, and on the Internet at http://www.ncbi.nlm.nih.gov/BLAST/. The BLAST software suite includes various sequence analysis programs including "blastn," that is used to align a known polynucleotide sequence with other polynucleotide sequences from a variety of databases. Also available is a tool caUed "BLAST 2 Sequences" that is used for direct pairwise comparison of two nucleotide sequences. "BLAST 2 Sequences" can be accessed and used interactively at htφ://www.ncbi.nlm.nih.gov/gorf/bl2.html. The "BLAST 2 Sequences" tool can be used for both blastn and blastp (discussed below). BLAST programs are commonly used with gap and other parameters set to default settings. For example, to compare two nucleotide sequences, one may use blastn with the "BLAST 2 Sequences" tool Version 2.0.12 (April-21-2000) set at default parameters. Such default parameters may be, for example: Matrix: BLOSUM62 Reward for match: 1 Penalty for mismatch: -2 Open Gap: 5 and Extension Gap: 2 penalties Gap x drop-off: 50 Expect: 10 Word Size: 11 Filter: on Percent identity may be measured over the length of an entire defined sequence, for example, as defined by a particular SEQ ID number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined sequence, for instance, a fragment of at least 20, at least 30, at least 40, at least 50, at least 70, at least 100, or at least 200 contiguous nucleotides. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures, or Sequence Listing, may be used to describe a length over which percentage identity may be measured. Nucleic acid sequences that do not show a high degree of identity may nevertheless encode similar amino acid sequences due to the degeneracy of the genetic code. It is understood that changes in a nucleic acid sequence can be made using this degeneracy to produce multiple nucleic acid sequences that aU encode substantiaUy the same protein. The phrases "percent identity" and "% identity," as appMed to polypeptide sequences, refer to the percentage of residue matches between at least two polypeptide sequences aMgned using a standardized algorithm. Methods of polypeptide sequence aMgnment are weU-known. Some aMgnment methods take into account conservative amino acid substitutions. Such conservative substitutions, explained in more detail above, generaUy preserve the charge and_hydrophobicity at the site of substitution, thus preserving the structure (and therefore function) of the polypeptide. Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incoφorated into the MEGALIGN version 3.12e sequence aMgnment program (described and referenced above). For pairwise aMgnments of polypeptide sequences using CLUSTAL V, the default parameters are set as foUows: Ktuple=l, gap penalty=3, window=5, and "diagonals saved"=5. The PAM250 matrix is selected as the default residue weight table. As with polynucleotide aMgnments, the percent identity is reported by CLUSTAL V as the "percent similarity" between aMgned polypeptide sequence pairs. Alternatively the NCBI BLAST software suite may be used. For example, for a pairwise comparison of two polypeptide sequences, one may use the "BLAST 2 Sequences" tool Version 2.0.12 (April-21-2000) with blastp set at default parameters. Such default parameters may be, for example: Matrix: BLOSUM62 Open Gap: 11 and Extension Gap: 1 penalties Gap x drop-off: 50 Expect: 10 Word Size: 3 Filter: on Percent identity may be measured over the length of an entire defined polypeptide sequence, for example, as defined by a particular SEQ ED number, or may be measured over a shorter length, for example, over the length of a fragment taken from a larger, defined polypeptide sequence, for instance, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70 or at least 150 contiguous residues. Such lengths are exemplary only, and it is understood that any fragment length supported by the sequences shown herein, in the tables, figures or Sequence Listing, may be used to describe a length over which percentage identity may be measured. "Human artificial chromosomes" (HACs) are Mnear microchromosomes which may contain DNA sequences of about 6 kb to 10 Mb in size and which contain aU of the elements required for chromosome repMcation, segregation and maintenance. The term "humanized antibody" refers to an antibody molecule in which the amino acid sequence in the non-antigen binding regions has been altered so that the antibody more closely resembles a human antibody, and stiU retains its original binding abiUty. "Hybridization" refers to the process by which a polynucleotide strand anneals with a complementary strand through base pairing under defined hybridization conditions. Specific hybridization is an indication that two nucleic acid sequences share a high degree of complementarity. Specific hybridization complexes form under permissive anneaMng conditions and remain hybridized after the "washing" step(s). The washing step(s) is particularly important in determining the stringency of the hybridization process, with more stringent conditions aUowing less non-specific binding, i.e., binding between pairs of nucleic acid strands that are not perfectly matched. Permissive conditions for anneaMng of nucleic acid sequences are routinely determinable by one of ordinary skiU in the art and may be consistent among hybridization experiments, whereas wash conditions may be varied among experiments to achieve the desired stringency, and therefore hybridization specificity. Permissive anneaMng conditions occur, for example, at 68°C in the presence of about 6 x SSC, about 1% (w/v) SDS, and about 100 μg/ml sheared, denatured salmon sperm DNA. Generally, stringency of hybridization is expressed, in part, with reference to the temperature under which the wash step is carried out. Such wash temperatures are typically selected to be about 5°C to 20°C lower than the thermal melting point (TJ for the specific sequence at a defined ionic strength and pH. The T m is the temperature (under defined ionic strength and pH) at which 50% of the target sequence hybridizes to a perfectly matched probe. An equation for calculating T m and conditions for nucleic acid hybridization are well known and can be found in Sambrook, J. et al. (1989) Molecular Cloning: A Laboratory Manual. 2 nd ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; specificaUy see volume 2, chapter 9. High stringency conditions for hybridization between polynucleotides of the present invention include wash conditions of 68°C in the presence of about 0.2 x SSC and about 0.1% SDS, for 1 hour. Alternatively, temperatures of about 65°C, 60°C, 55°C, or 42°C may be used. SSC concentration may be varied from about 0.1 to 2 x SSC, with SDS being present at about 0.1%. TypicaUy, blocking reagents are used to block non-specific hybridization. Such blocking reagents include, for instance, sheared and denatured salmon sperm DNA at about 100-200 μg/ml. Organic solvent, such as formamide at a concentration of about 35-50% v/v, may also be used under particular circumstances, such as for RNA:DNA hybridizations. Useful variations on these wash conditions will be readily apparent to those of ordinary skiU in the art. Hybridization, particularly under high stringency conditions, may be suggestive of evolutionary similarity between the nucleotides. Such similarity is strongly indicative of a similar role for the nucleotides and their encoded polypeptides. The term "hybridization complex" refers to a complex formed between two nucleic acid sequences by virtue of the formation of hydrogen bonds between complementary bases. A hybridization complex may be formed in solution (e.g., C 0 t or R 0 t analysis) or formed between one nucleic acid sequence present in solution and another nucleic acid sequence immobilized on a soMd support (e.g., paper, membranes, filters, chips, pins or glass sMdes, or any other appropriate substrate l to which ceUs or their nucleic acids have been fixed). The words "insertion" and "addition" refer to changes in an amino acid or nucleotide sequence resulting in the addition of one or more amino acid residues or nucleotides, respectively. "Immune response" can refer to conditions associated with inflammation, trauma, immune disorders, or infectious or genetic disease, etc. These conditions can be characterized by expression of various factors, e.g., cytokines, chemokines, and other signaMng molecules, which may affect ceUular and systemic defense systems. An "immunogenic fragment" is a polypeptide or oMgopeptide fragment of NZMS which is capable of eMciting an immune response when introduced into a Mving organism, for example, a mammal. The term "immunogenic fragment" also includes any polypeptide or oMgopeptide fragment of NZMS which is useful in any of the antibody production methods disclosed herein or known in the art. The term "microarray" refers to an arrangement of a pluraMty of polynucleotides, polypeptides, or other chemical compounds on a substrate. The terms "element" and "array element" refer to a polynucleotide, polypeptide, or other chemical compound having a unique and defined position on a microarray. The term "modulate" refers to a change in the activity of NZMS. For example, modulation may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of NZMS. The phrases "nucleic acid" and "nucleic acid sequence" refer to a nucleotide, oMgonucleotide, polynucleotide, or any fragment thereof. These phrases also refer to DNA or RNA of genomic or synthetic origin which may be single-stranded or double-stranded and may represent the sense or the antisense strand, to peptide nucleic acid (PNA), or to any DNA-Mke or RNA-Mke material. "Operably Mnked" refers to the situation in which a first nucleic acid sequence is placed in a functional relationship with a second nucleic acid sequence. For instance, a promoter is operably Mnked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Operably Mnked DNA sequences may be in close proximity or contiguous and, where necessary to join two protein coding regions, in the same reading frame. "Peptide nucleic acid" (PNA) refers to an antisense molecule or anti-gene agent which comprises an oMgonucleotide of at least about 5 nucleotides in length Mnked to a peptide backbone of amino acid residues ending in lysine. The terminal lysine confers solubiMty to the composition. PNAs preferentiaUy bind complementary single stranded DNA or RNA and stop transcript elongation, and may be pegylated to extend their Mfespan in the ceU. "Post-translational modification" of an NZMS may involve Mpidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur syntheticaUy or biochemically. Biochemical modifications wiU vary by ceU type depending on the enzymatic miUeu of NZMS. "Probe" refers to nucleic acid sequences encoding NZMS, their complements, or fragments thereof, which are used to detect identical, aUehc or related nucleic acid sequences. Probes are isolated oMgonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, Mgands, chemiluminescent agents, and enzymes. "Primers" are short nucleic acids, usually DNA oMgonucleotides, which may be annealed to a target polynucleotide by complementary base-pairing. The primer may then be extended along the target DNA strand by a DNA polymerase enzyme. Primer pairs can be used for ampMfication (and identification) of a nucleic acid sequence, e.g., by the polymerase chain reaction (PCR). Probes and primers as used in the present invention typicaUy comprise at least 15 contiguous nucleotides of a known sequence. In order to enhance specificity, longer probes and primers may also be employed, such as probes and primers that comprise at least 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, or at least 150 consecutive nucleotides of the disclosed nucleic acid sequences. Probes and primers may be considerably longer than these examples, and it is understood that any length supported by the specification, including the tables, figures, and Sequence Listing, may be used. Methods for preparing and using probes and primers are described in the references, for example Sambrook, J. et al. (1989) Molecular Cloning: A Laboratory Manual. 2 nd ed., vol. 1-3, Cold Spring Harbor Press, Plainview NY; Ausubel, F.M. et al. (1987) Current Protocols in Molecular Biology, Greene Publ. Assoc. & Wiley-Intersciences, New York NY; Innis, M. et al. (1990) PCR Protocols, A Guide to Methods and AppMcations, Academic Press, San Diego CA. PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that puφose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge MA). OMgonucleotides for use as primers are selected using software known in the art for such puφose. For example, OLIGO 4.06 software is useful for the selection of PCR primer pairs of up to 100 nucleotides each, and for the analysis of oMgonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases. Similar primer selection programs have incoφorated additional features for expanded capabiMties. For example, the PrimOU primer selection program (available to the pubMc from the Genome Center at University of Texas South West Medical Center, DaUas TX) is capable of choosing specific primers from megabase sequences and is thus useful for designing primers on a genome-wide scope. The Primer3 primer selection program (available to the pubMc from the Whitehead Institute/MIT Center for Genome Research, Cambridge MA) aUows the user to input a "mispriming Mbrary," in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oMgonucleotides for microarrays. (The source code for the latter two primer selection programs may also be obtained from their respective sources and modified to meet the user's specific needs.) The PrimeGen program (available to the pubMc from the UK Human Genome Mapping Project Resource Centre, Cambridge UK) designs primers based on multiple sequence aMgnments, thereby aUowing selection of primers that hybridize to either the most conserved or least conserved regions of aMgned nucleic acid sequences. Hence, this program, is useful for identification of both unique and conserved oMgonucleotides and polynucleotide fragments. The oMgonucleotides and polynucleotide fragments identified by any of the above selection methods are useful in hybridization technologies, for example, as PCR or sequencing primers, microarray elements, or specific probes to identify fuUy or partiaUy complementary polynucleotides in a sample of nucleic acids. Methods of oMgonucleotide selection are not Mmited to those described above. A "recombinant nucleic acid" is a sequence that is not naturaUy occurring or has a sequence that is made by an artificial combination of two or more otherwise separated segments of sequence. This artificial combination is often accompMshed by chemical synthesis or, more commonly, by the artificial manipulation of isolated segments of nucleic acids, e.g., by genetic engineering techniques such as those described in Sambrook, supra. The term recombinant includes nucleic acids that have been altered solely by addition, substitution, or deletion of a portion of the nucleic acid. Frequently, a recombinant nucleic acid may include a nucleic acid sequence operably Mnked to a promoter sequence. Such a recombinant nucleic acid may be part of a vector that is used, for example, to transform a ceU. Alternatively, such recombinant nucleic acids may be part of a viral vector, e.g., based on a vaccinia vims, that could be use to vaccinate a mammal wherein the recombinant nucleic acid is expressed, inducing a protective immunological response in the mammal. A "regulatory element" refers to a nucleic acid sequence usuaUy derived from untranslated regions of a gene and includes enhancers, promoters, introns, and 5' and 3' untranslated regions (UTRs). Regulatory elements interact with host or viral proteins which control transcription, translation, or RNA stabiUty. "Reporter molecules" are chemical or biochemical moieties used for labeMng a nucleic acid, amino acid, or antibody. Reporter molecules include radionucMdes; enzymes; fluorescent, chemiluminescent, or chromogenic agents; substrates; cofactors; inhibitors; magnetic particles; and other moieties known in the art. An "RNA equivalent," in reference to a DNA sequence, is composed of the same Mnear sequence of nucleotides as the reference DNA sequence with the exception that aU occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose. The term "sample" is used in its broadest sense. A sample suspected of containing NZMS, nucleic acids encoding NZMS, or fragments thereof may comprise a bodily fluid; an extract from a ceU, chromosome, organeUe, or membrane isolated from a ceU; a ceU; genomic DNA, RNA, or cDNA, in solution or bound to a substrate; a tissue; a tissue print; etc. The terms "specific binding" and "specifically binding" refer to that interaction between a protein or peptide and an agonist, an antibody, an antagonist, a small molecule, or any natural or synthetic binding composition. The interaction is dependent upon the presence of a particular stmcture of the protein, e.g., the antigenic determinant or epitope, recognized by the binding molecule. For example, if an antibody is specific for epitope "A," the presence of a polypeptide comprising the epitope A, or the presence of free unlabeled A, in a reaction containing free labeled A and the antibody will reduce the amount of labeled A that binds to the antibody. The term "substantially purified" refers to nucleic acid or amino acid sequences that are removed from their natural environment and are isolated or separated, and are at least 60% free, preferably at least 75% free, and most preferably at least 90% free from other components with which they are naturaUy associated. A "substitution" refers to the replacement of one or more amino acid residues or nucleotides by different amino acid residues or nucleotides, respectively. "Substrate" refers to any suitable rigid or semi-rigid support including membranes, filters, chips, sMdes, wafers, fibers, magnetic or nonmagnetic beads, gels, tubing, plates, polymers, microparticles and capiUaries. The substrate can have a variety of surface forms, such as weUs, trenches, pins, channels and pores, to which polynucleotides or polypeptides are bound. A "transcript image" or "expression profile" refers to the coUective pattern of gene expression by a particular ceU type or tissue under given conditions at a given time. "Transformation" describes a process by which exogenous DNA is introduced into a recipient cell. Transformation may occur under natural or artificial conditions according to various methods weU known in the art, and may rely on any known method for the insertion of foreign nucleic acid sequences into a prokaryotic or eukaryotic host ceU. The method for transformation is selected based on the type of host ceU being transformed and may include, but is not Mmited to, bacteriophage or viral infection, electroporation, heat shock, Mpofection, and particle bombardment. The term "transformed ceUs" includes stably transformed ceUs in which the inserted DNA is capable of repMcation either as an autonomously repMcating plasmid or as part of the host chromosome, as weU as transiently transformed ceUs which express the inserted DNA or RNA for Mmited periods of time. A "transgenic organism," as used herein, is any organism, including but not Mmited to animals and plants, in which one or more of the ceUs of the organism contains heterologous nucleic acid introduced by way of human intervention, such as by transgenic techniques well known in the art. The nucleic acid is introduced into the ceU, directly or indirectly by introduction into a precursor of the ceU, by way of dehberate genetic manipulation, such as by microinjection or by infection with a recombinant vims. The term genetic manipulation does not include classical cross-breeding, or in vitro fertiUzation, but rather is directed to the introduction of a recombinant DNA molecule. The transgenic organisms contemplated in accordance with the present invention include bacteria, cyanobacteria, fungi, plants and animals. The isolated DNA of the present invention can be introduced into the host by methods known in the art, for example infection, fransfection, transformation or transconjugation. Techniques for transferring the DNA of the present invention into such organisms are widely known and provided in references such as Sambrook et al. (1989), supra. A "variant" of a particular nucleic acid sequence is defined as a nucleic acid sequence having at least 40% sequence identity to the particular nucleic acid sequence over a certain length of one of the nucleic acid sequences using blastn with the "BLAST 2 Sequences" tool Version 2.0.9 (May-07- 1999) set at default parameters. Such a pair of nucleic acids may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length. A variant may be described as, for example, an "aUeMc" (as defined above), "spMce," "species," or "polymoφhic" variant. A spMce variant may have significant identity to a reference molecule, but wiU generaUy have a greater or lesser number of polynucleotides due to alternate spMcing of exons during mRNA processing. The corresponding polypeptide may possess additional functional domains or lack domains that are present in the reference molecule. Species variants are polynucleotide sequences that vary from one species to another. The resulting polypeptides wiU generaUy have significant amino acid identity relative to each other. A polymoφhic variant is a variation in the polynucleotide sequence of a particular gene between individuals of a given species. Polymoφhic variants also may encompass "single nucleotide polymoφhisms" (SNPs) in which the polynucleotide sequence varies by one nucleotide base. The presence of SNPs may be indicative of, for example, a certain population, a disease state, or a propensity for a disease state. A "variant" of a particular polypeptide sequence is defined as a polypeptide sequence having at least 40% sequence identity to the particular polypeptide sequence over a certain length of one of the polypeptide sequences using blastp with the "BLAST 2 Sequences" tool Version 2.0.9 (May-07- 1999) set at default parameters. Such a pair of polypeptides may show, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% or greater sequence identity over a certain defined length of one of the polypeptides. THE INVENTION The invention is based on the discovery of new human enzymes (NZMS), the polynucleotides encoding NZMS, and the use of these compositions for the diagnosis, treatment, or prevention of ceU proMferative and autoimmune/inflammatory, cardiovascular, gastrointestinal, neurological, pufmonary, reproductive, and eye disorders. Table 1 summarizes the nomenclature for the full length polynucleotide and polypeptide sequences of the invention. Each polynucleotide and its corresponding polypeptide are correlated to a single Incyte project identification number (Incyte Project ID). Each polypeptide sequence is denoted by both a polypeptide sequence identification number (Polypeptide SEQ ID NO:) and an Incyte polypeptide sequence number (Incyte Polypeptide ED) as shown. Each polynucleotide sequence is denoted by both a polynucleotide sequence identification number (Polynucleotide SEQ ED NO:) and an Incyte polynucleotide consensus sequence number (Incyte Polynucleotide ID) as shown. Table 2 shows sequences with homology to the polypeptides of the invention as identified by BLAST analysis against the GenBank protein (genpept) database and the PROTEOME database. Columns 1 and 2 show the polypeptide sequence identification number (Polypeptide SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ED) for polypeptides of the invention. Column 3 shows the GenBank identification number (GenBank ED NO:) of the nearest GenBank homolog and the PROTEOME database identification numbers (PROTEOME ID NO:) of the nearest PROTEOME database homologs. Column 4 shows the probabiUty scores for the matches between each polypeptide and its homolog(s). Column 5 shows the annotation of the GenBank and PROTEOME database homolog(s) along with relevant citations where appMcable, aU of which are expressly incoφorated by reference herein. Table 3 shows various structural features of the polypeptides of the invention. Columns 1 and 2 show the polypeptide sequence identification number (SEQ ID NO:) and the corresponding Incyte polypeptide sequence number (Incyte Polypeptide ED) for each polypeptide of the invention. Column 3 shows the number of amino acid residues in each polypeptide. Column 4 shows potential phosphorylation sites, and column 5 shows potential glycosylation sites, as determined by the MOTIFS program of the GCG sequence analysis software package (Genetics Computer Group, Madison WI). Column 6 shows amino acid residues comprising signature sequences, domains, and motifs. Column 7 shows analytical methods for protein structure/function analysis and in some cases, searchable databases to which the analytical methods were appMed. Together, Tables 2 and 3 summarize the properties of polypeptides of the invention, and these properties estabMsh that the claimed polypeptides are enzymes. For example, SEQ ID NO:l is 59% identical to human carbonic anhydrase I (GenBank ID gl79793) as determined by the Basic Local AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 6.5e-87, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ED NO:l also contains a eukaryotic-type carbonic anhydrase domain as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFTLESCAN analyses provide further corroborative evidence that SEQ ID NO:l is a carbonic anhydrase. As another example, SEQ ID NO:3 is 34% identical to Halobacterium dihydrodipicoMnate synthase (GenBank ID gl 0580053) as determined by the Basic I_ocal AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 6.0e-29, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ID NO:3 also contains a dihydrodipicoMnate synthetase family domain as determined by searching for statisticaUy significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFTLESCAN analyses provide further corroborative evidence that SEQ ED NO:3 is a dihydrodipicoMnate synthase. As another example, SEQ ID NO:4 is 98% identical to Rattus norvegicus S-adenosyl-L- homocysteine hydrolase (GenBank ID gl 185363) as determined by the Basic Local AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 2.1e-230, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ID NO:4 also contains an S-adenosyl-L-homocysteine hydrolase signature pattern as determined by searching for statisticaUy significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from additional BLAST and MOTIFS analyses provide further corroborative evidence that SEQ ID NO:4 is an S-adenosyl-L-homocysteine hydrolase. As another example, SEQ ID NO:7 is 59% identical to Sanguinus oedipus ribonuclease k6 precursor (GenBank ID g2745760) as determined by the Basic I_ocal AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 5.3e-44, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ID NO:7 also contains a pancreatic ribonuclease domain as determined, by searching for statisticaUy significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFILESCAN analyses provide further corroborative evidence that SEQ ID NO:7 is a pancreatic ribonuclease. As another example, SEQ ID NO:10 is 55% identical to human arylsulfatase B precursor (GenBank ID gl79077) as determined by the Basic Local AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 1.9e-144, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ID NO: 10 also contains a sulfatase domain as determined by searching for statisticaUy significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFILESCAN analyses provide further corroborative evidence that SEQ ID NO:10 is a sulfatase. As another example, SEQ ID NO:13 is 55% identical to feUne arylsulfatase B (ARSB) (GenBank ID g258856) as determined by the Basic Local AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 3.1e-144, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ED NO: 13 also contains a sulfatase domain as determined by searching for statisticaUy significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFILESCAN analyses provide further corroborative evidence that SEQ ED NO:13 is a sulfatase. As another example, SEQ ID NO:14 is 80% identical from residues N200 to K362 to human S-adenosylhomocysteine hydrolase (GenBank ID gl78279) as determined by the Basic Local AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 5.6e-83, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ID NO:14 also contains an S-adenosyl-L-homocysteine hydrolase domain as determined by searching for statisticaUy significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS, MOTIFS, and additional BLAST analyses provide further corroborative evidence that SEQ ED NO:14 is an S-adenosyl-L- homocysteine hydrolase. The algorithms and parameters for the analysis of SEQ ED NO:l are described in Table 7. As another example, SEQ ED NO:15 is 56% identical to Mus musculus spermatogenesis associated ATPase (GenBank ID g4105619) as determined by the Basic E >cal AMgnment Search Tool (BLAST). (See Table 2.) The BLAST probabiMty score is 8.6e-144, which indicates the probabiMty of obtaining the observed polypeptide sequence aMgnment by chance. SEQ ID NO:l 5 also contains an AAA ATPase domain as determined by searching for statisticaUy significant matches in the hidden Markov model (HMM)-based PFAM database of conserved protein family domains. (See Table 3.) Data from BLIMPS and MOTIFS analyses provide further corroborative evidence that SEQ ID NO: 15 is an AAA ATPase. SEQ ID NO:2, SEQ ID NO:5-6, SEQ ID NO:8-9, SEQ ID NO:ll-12 and SEQ ED NO.16-18 were analyzed and annotated in a similar manner. The algorithms and parameters for the analysis of SEQ ED NO.1-18 are described in Table 7. As shown in Table 4, the fuU length polynucleotide sequences of the present invention were assembled using cDNA sequences or coding (exon) sequences derived from genomic DNA, or any combination of these two types of sequences. Column 1 Msts the polynucleotide sequence identification number (Polynucleotide SEQ ID NO:), the corresponding Incyte polynucleotide consensus sequence number (Incyte ID) for each polynucleotide of the invention, and the length of each polynucleotide sequence in basepairs. Column 2 shows the nucleotide start (5') and stop (3') positions of the cDNA and/or genomic sequences used to assemble the fuU length polynucleotide sequences of the invention, and of fragments of the polynucleotide sequences which are useful, for example, in hybridization or ampMfication technologies that identify SEQ ID NO:19-36 or that distinguish between SEQ ID NO: 19-36 and related polynucleotide sequences. The polynucleotide fragments described in Column 2 of Table 4 may refer specifically, for example, to Incyte cDNAs derived from tissue-specific cDNA Mbraries or from pooled cDNA Mbraries. Alternatively, the polynucleotide fragments described in column 2 may refer to GenBank cDNAs or ESTs which contributed to the assembly of the fuU length polynucleotide sequences. In addition, the polynucleotide fragments described in column 2 may identify sequences derived from the ENSEMBL (The Sanger Centre, Cambridge, UK) database (i.e., those sequences including the designation "ENST"). Alternatively, the polynucleotide fragments described in column 2 may be derived from the NCBI RefSeq Nucleotide Sequence Records Database (i.e., those sequences including the designation "NM" or "NT") or the NCBI RefSeq Protein Sequence Records (i.e., those sequences including the designation "NP"). Alternatively, the polynucleotide fragments described in column 2 may refer to assemblages of both cDNA and Genscan-predicted exons brought together by an "exon stitching" algorithm. For example, a polynucleotide sequence identified as VL_XXXXXX_N 1 _N 2 _YYYYY_N 3 _N 4 represents a "stitched" sequence in which XXXXXX is the identification number of the cluster of sequences to which the algorithm was appMed, and YYYYY is the number of the prediction generated by the algorithm, and N ι 3m , if present, represent specific exons that may have been manuaUy edited during analysis (See Example V). Alternatively, the polynucleotide fragments in column 2 may refer to assemblages of exons brought together by an "exon-stretching" algorithm. For example, a polynucleotide sequence identified as ¥ XXXXXX_gAAAAA_gBBBBB_l_N is a "stretched" sequence, with XXXXXX being the Incyte project identification number, gAAAAA being the GenBank identification number of the human genomic sequence to which the "exon-stretching" algorithm was appMed, gBBBBB being the GenBank identification number or NCBI RefSeq identification number of the nearest GenBank protein homolog, and N referring to specific exons (See Example V). In instances where a RefSeq sequence was used as a protein homolog for the "exon-stretching" algorithm, a RefSeq identifier (denoted by "NM," "NP," or "NT") may be used in place of the GenB ank identifier (i. e. , gBBBBB) . Alternatively, a prefix identifies component sequences that were hand-edited, predicted from genomic DNA sequences, or derived from a combination of sequence analysis methods. The foUowing Table Msts examples of component sequence prefixes and corresponding sequence analysis methods associated with the prefixes (see Example IV and Example V). In some cases, Incyte cDNA coverage redundant with the sequence coverage shown in column 2 was obtained to confirm the final consensus polynucleotide sequence, but the relevant Incyte cDNA identification numbers are not shown. Table 5 shows the representative cDNA Mbraries for those full length polynucleotide sequences which were assembled using Incyte cDNA sequences. The representative cDNA Mbrary is the Incyte cDNA Mbrary which is most frequently represented by the Incyte cDNA sequences which were used to assemble and confirm the above polynucleotide sequences. The tissues and vectors which were used to constmct the cDNA Mbraries shown in Table 5 are described in Table 6. The invention also encompasses NZMS variants. A preferred NZMS variant is one which has at least about 80%, or alternatively at least about 90%, or even at least about 95% amino acid sequence identity to the NZMS amino acid sequence, and which contains at least one functional or structural characteristic of NZMS. The invention also encompasses polynucleotides which encode NZMS. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO: 19-36, which encodes NZMS. The polynucleotide sequences of SEQ ID NO:l 9-36, as presented in the Sequence listing, embrace tiie equivalent RNA sequences, wherein occurrences of the nitrogenous base thymine are replaced with uracil, and the sugar backbone is composed of ribose instead of deoxyribose. The invention also encompasses a variant of a polynucleotide sequence encoding NZMS. In particular, such a variant polynucleotide sequence wiU have at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to the polynucleotide sequence encoding NZMS. A particular aspect of the invention encompasses a variant of a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:l 9- 36 which has at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID NO:19-36. Any one of the polynucleotide variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of NZMS. In addition, or in the alternative, a polynucleotide variant of the invention is a spMce variant of a polynucleotide sequence encoding NZMS. A spMce variant may have portions which have significant sequence identity to the polynucleotide sequence encoding NZMS, but wiU generaUy have a greater or lesser number of polynucleotides due to additions or deletions of blocks of sequence arising from alternate spMcing of exons during mRNA processing. A spMce variant may have less than about 70%, or alternatively less than about 60%, or alternatively less than about 50% polynucleotide sequence identity to the polynucleotide sequence encoding NZMS over its entire length; however, portions of the spMce variant wiU have at least about 70%, or alternatively at least about 85%, or alternatively at least about 95%, or alternatively 100% polynucleotide sequence identity to portions of the polynucleotide sequence encoding NZMS. For example, a polynucleotide comprising a sequence of SEQ ED NO:35 is a spMce variant of a polynucleotide comprising a sequence of SEQ ID NO:36. Any one of the spMce variants described above can encode an amino acid sequence which contains at least one functional or structural characteristic of NZMS. It wiU be appreciated by those skiUed in the art that as a result of the degeneracy of the genetic code, a multitude of polynucleotide sequences encoding NZMS, some bearing minimal similarity to the polynucleotide sequences of any known and naturaUy occurring gene, may be produced. Thus, the invention contemplates each and every possible variation of polynucleotide sequence that could be made by selecting combinations based on possible codon choices. These combinations are made in accordance with the standard triplet genetic code as appMed to the polynucleotide sequence of naturaUy occurring NZMS, and aU such variations are to be considered as being specificaUy disclosed. Although nucleotide sequences which encode NZMS and its variants are generaUy capable of hybridizing to the nucleotide sequence of the naturaUy occurring NZMS under appropriately selected conditions of stringency, it may be advantageous to produce nucleotide sequences encoding NZMS or its derivatives possessing a substantiaUy different codon usage, e.g., inclusion of non-naturaUy occurring codons. Codons may be selected to increase the rate at which expression of the peptide occurs in a particular prokaryotic or eukaryotic host in accordance with the frequency with which particular codons are utiMzed by the host. Other reasons for substantiaUy altering the nucleotide sequence encoding NZMS and its derivatives without altering the encoded amino acid sequences include the production of RNA transcripts having more desirable properties, such as a greater half-Mfe, than transcripts produced from the naturaUy occurring sequence. The invention also encompasses production of DNA sequences which encode NZMS and NZMS derivatives, or fragments thereof, entirely by synthetic chemistry. After production, the synthetic sequence may be inserted into any of the many available expression vectors and ceU systems using reagents well known in the art. Moreover, synthetic chemistry may be used to introduce mutations into a sequence encoding NZMS or any fragment thereof. Also encompassed by the invention are polynucleotide sequences that are capable of hybridizing to the claimed polynucleotide sequences, and, in particular, to those shown in SEQ ID NO:l 9-36 and fragments thereof under various conditions of stringency. (See, e.g., Wahl, G.M. and S.L. Berger (1987) Methods Enzymol. 152:399-407; Kimmel, A.R. (1987) Methods Enzymol. 152:507- 511.) Hybridization conditions, including anneaMng and wash conditions, are described in "Definitions." Methods for DNA sequencing are weU known in the art and may be used to practice any of the embodiments of the invention. The methods may employ such enzymes as the Klenow fragment of DNA polymerase I, SEQUENASE (US Biochemical, Cleveland OH), Taq polymerase (AppMed Biosystems), thermostable T7 polymerase (Amersham Pharmacia Biotech, Piscataway NJ), or combinations of polymerases and proofreading exonucleases such as those found in the ELONGASE ampMfication system (Life Technologies, Gaithersburg MD). Preferably, sequence preparation is automated with machines such as the MICROLAB 2200 Mquid transfer system (Hamilton, Reno NN), PTC200 thermal cycler (MJ Research, Watertown MA) and ABI CATALYST 800 thermal cycler (AppMed Biosystems). Sequencing is then carried out using either the ABI 373 or 377 DΝA sequencing system (AppMed Biosystems), the MEGABACE 1000 DΝA sequencing system (Molecular Dynamics, Sunnyvale CA), or other systems known in the art. The resulting sequences are analyzed using a variety of algorithms which are weU known in the art. (See, e.g., Ausubel, F.M. (1997) Short Protocols in Molecular Biology, John Wiley & Sons, New York NY, unit 7.7; Meyers, R.A. (1995) Molecular Biology and Biotechnology. Wiley VCH, New York NY, pp. 856-853.) The nucleic acid sequences encoding NZMS may be extended utilizing a partial nucleotide sequence and employing various PCR-based methods known in the art to detect upstream sequences, such as promoters and regulatory elements. For example, one method which may be employed, restriction-site PCR, uses universal and nested primers to ampMfy unknown sequence from genomic DNA within a cloning vector. (See, e.g., Sarkar, G. (1993) PCR Methods AppMc. 2:318-322.) Another method, inverse PCR, uses primers that extend in divergent directions to ampMfy unknown sequence from a circularized template. The template is derived from restriction fragments comprising a known genomic locus and surrounding sequences. (See, e.g., TrigMa, T. et al. (1988) Nucleic Acids Res. 16:8186.) A third method, capture PCR, involves PCR ampMfication of DNA fragments adjacent to known sequences in human and yeast artificial chromosome DNA. (See, e.g., Lagerstrom, M. et al. (1991) PCR Methods AppMc. 1:111-119.) In this method, multiple restriction enzyme digestions and Mgations may be used to insert an engineered double-stranded sequence into a region of unknown sequence before performing PCR. Other methods which may be used to retrieve unknown sequences are known in the art. (See, e.g., Parker, J.D. et al. (1991) Nucleic Acids Res. 19:3055-3060). AdditionaUy, one may use PCR, nested primers, and PROMOTERF1NDER Mbraries (Clontech, Palo Alto CA) to walk genomic DNA. This procedure avoids the need to screen Mbraries and is useful in finding intron/exon junctions. For aU PCR-based methods, primers may be designed using commerciaUy available software, such as OLIGO 4.06 primer analysis software (National Biosciences, Plymouth MN) or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the template at temperatures of about 68°C to 72°C. When screening for fuU length cDNAs, it is preferable to use Mbraries that have been size-selected to include larger cDNAs. In addition, random-primed Mbraries, which often include sequences containing the 5' regions of genes, are preferable for situations in which an oMgo d(T) Mbrary does not yield a fuU-length cDNA. Genomic Mbraries may be useful for extension of sequence into 5' non-transcribed regulatory regions. CapiUary electrophoresis systems which are commerciaUy available may be used to analyze the size or confirm the nucleotide sequence of sequencing or PCR products. In particular, capiUary sequencing may employ flowable polymers for electrophoretic separation, four different nucleotide- specific, laser-stimulated fluorescent dyes, and a charge coupled device camera for detection of the emitted wavelengths. Output/Mght intensity may be converted to electrical signal using appropriate software (e.g., GENOTYPER and SEQUENCE NAVIGATOR, AppMed Biosystems), and the entire process from loading of samples to computer analysis and electronic data display may be computer controUed. CapiUary electrophoresis is especially preferable for sequencing smaU DNA fragments which may be present in Mmited amounts in a particular sample. In another embodiment of the invention, polynucleotide sequences or fragments thereof which encode NZMS may be cloned in recombinant DNA molecules that direct expression of NZMS, or fragments or functional equivalents thereof, in appropriate host ceUs. Due to the inherent degeneracy of the genetic code, other DNA sequences which encode substantiaUy the same or a functionally equivalent amino acid sequence may be produced and used to express NZMS. The nucleotide sequences of the present invention can be engineered using methods generaUy known in the art in order to alter NZMS-encoding sequences for a variety of pmposes including, but not Mmited to, modification of the cloning, processing, and/or expression of the gene product. DNA shuffling by random fragmentation and PCR reassembly of gene fragments and synthetic oMgonucleotides may be used to engineer the nucleotide sequences. For example, oMgonucleotide- mediated site-directed mutagenesis may be used to introduce mutations that create new restriction sites, alter glycosylation patterns, change codon preference, produce spMce variants, and so forth. The nucleotides of the present invention may be subjected to DNA shuffling techniques such as MOLECULARBREEDING (Maxygen Inc., Santa Clara CA; described in U.S. Patent No. 5,837,458; Chang, C-C. et al. (1999) Nat. Biotechnol. 17:793-797; Christians, F.C. et al. (1999) Nat. Biotechnol. 17:259-264; and Crameri, A. et al. (1996) Nat. Biotechnol. 14:315-319) to alter or improve the biological properties of NZMS, such as its biological or enzymatic activity or its abiMty to bind to other molecules or compounds. DNA shuffling is a process by which a Mbrary of gene variants is produced using PCR-mediated recombination of gene fragments. The Mbrary is then subjected to selection or screening procedures that identify those gene variants with the desired properties. These preferred variants may then be pooled and further subjected to recursive rounds of DNA shuffling and selection/screening. Thus, genetic diversity is created through "artificial" breeding and rapid molecular evolution. For example, fragments of a single gene containing random point mutations may be recombined, screened, and then reshuffled until the desired properties are optimized. Alternatively, fragments of a given gene may be recombined with fragments of homologous genes in the same gene family, either from the same or different species, thereby maximizing the genetic diversity of multiple naturaUy occurring genes in a directed and controllable manner. In another embodiment, sequences encoding NZMS may be synthesized, in whole or in part, using chemical methods weU known in the art. (See, e.g., Camthers, M.H. et al. (1980) Nucleic Acids Symp. Ser. 7:215-223; and Horn, T. et al. (1980) Nucleic Acids Symp. Ser. 7:225-232.) Alternatively, NZMS itself or a fragment thereof may be synthesized using chemical methods. For example, peptide synthesis can be performed using various solution-phase or soMd-phase techniques. (See, e.g., Creighton, T. (1984) Proteins, Stmctures and Molecular Properties. WH Freeman, New York NY, pp. 55-60; and Roberge, J.Y. et al. (1995) Science 269:202-204.) Automated synthesis may be achieved using the ABI 431 A peptide synthesizer (AppMed Biosystems). Additionally, the amino acid sequence of NZMS, or any part theleof, may be altered during direct synthesis and/or combined with sequences from other proteins, or any part thereof, to produce a variant polypeptide or a polypeptide having a sequence of a naturaUy occurring polypeptide. The peptide may be substantiaUy purified by preparative high performance Mquid chromatography. (See, e.g., Chiez, R.M. and F.Z. Regnier (1990) Methods Enzymol. 182:392-421.) The composition of the synthetic peptides may be confirmed by amino acid analysis or by sequencing. (See, e.g., Creighton, supra, pp. 28-53.) In order to express a biologicaUy active NZMS, the nucleotide sequences encoding NZMS or derivatives thereof may be inserted into an appropriate expression vector, i.e., a vector which contains the necessary elements for transcriptional and translational control of the inserted coding sequence in a suitable host. These elements include regulatory sequences, such as enhancers, constitutive and inducible promoters, and 5' and 3' untranslated regions in the vector and in polynucleotide sequences encoding NZMS. Such elements may vary in their strength and specificity. Specific initiation signals may also be used to achieve more efficient translation of sequences encoding NZMS. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where sequences encoding NZMS and its initiation codon and upstream regulatory sequences are inserted into the appropriate expression vector, no additional transcriptional or translational control signals may be needed. However, in cases where only coding sequence, or a fragment thereof, is inserted, exogenous translational control signals including an in-frame ATG initiation codon should be provided by the vector. Exogenous translational elements and initiation codons may be of various origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of enhancers appropriate for the particular host ceU system used. (See, e.g., Scharf, D. et al. (1994) Results Probl. CeU Differ. 20:125-162.) Methods which are weU known to those skiUed in the art may be used to constmct expression vectors containing sequences encoding NZMS and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. (See, e.g., Sambrook, J. et al. (1989) Molecular Cloning, A Laboratory Manual. Cold Spring Harbor Press, Plainview NY, ch. 4, 8, and 16-17; Ausubel, F.M. et al. (1995) Current Protocols in Molecular Biology, John Wiley & Sons, New York NY, ch. 9, 13, and 16.) A variety of expression vector/host systems may be utiMzed to contain and express sequences encoding NZMS. These include, but are not Mmited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors; yeast transformed with yeast expression vectors; insect ceU systems infected with viral expression vectors (e.g., baculovims); plant ceU systems transformed with viral expression vectors (e.g., cauMflower mosaic vims, CaMV, or tobacco mosaic vims, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal ceU systems. (See, e.g., Sambrook, supra; Ausubel, supra; Van Heeke, G. and S.M. Schuster (1989) J. Biol. Chem. 264:5503-5509; Engelhard, E.K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945; Takamatsu, N. (1987) EMBO J. 6:307-311; The McGraw HiU Yearbook of Science and Technology (1992) McGraw HiU, New York NY, pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659; and Harrington, J.J. et al. (1997) Nat. Genet. 15:345-355.) Expression vectors derived from refrovimses, adenoviruses, or heφes or vaccinia vimses, or from various bacterial plasmids, may be used for deUvery of nucleotide sequences to the targeted organ, tissue, or ceU population. (See, e.g., Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5(6):350-356; Yu, M. et al. (1993) Proc. Natl. Acad. Sci. USA 90(13):6340-6344; BuUer, R.M. et al. (1985) Nature 317(6040):813-815; McGregor, D.P. et al. (1994) Mol. Immunol. 31(3):219-226; and Verma, I.M. and N. Somia (1997) Nature 389:239-242.) The invention is not Mmited by the host cell employed. In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotide sequences encoding NZMS. For example, routine cloning, subcloning, and propagation of polynucleotide sequences encoding NZMS can be achieved using a multifunctional E. coM vector such as PBLUESCRIPT (Sfratagene, La JoUa CA) or PSPORT1 plasmid (life Technologies). Ligation of sequences encoding NZMS into the vector's multiple cloning site dismpts the lacL gene, aUowing a colorimetric screening procedure for identification of fransformed bacteria containing recombinant molecules. In addition, these vectors may be useful for in vifro transcription, dideoxy sequencing, single strand rescue with helper phage, and creation of nested deletions in the cloned sequence. (See, e.g., Van Heeke, G. and S.M. Schuster (1989) J. Biol. Chem. 264:5503-5509.) When large quantities of NZMS are needed, e.g. for the production of antibodies, vectors which direct high level expression of NZMS may be used. For example, vectors containing the strong, inducible SP6 or T7 bacteriophage promoter may be used. Yeast expression systems may be used for production of NZMS. A number of vectors containing constitutive or inducible promoters, such as alpha factor, alcohol oxidase, and PGH promoters, may be used in the yeast Saccharomyces cerevisiae or Pichia pastoris. In addition, such vectors direct either the secretion or intraceUular retention of expressed proteins and enable integration of foreign sequences into the host genome for stable propagation. (See, e.g., Ausubel, 1995, supra; Bitter, G.A. et al. (1987) Methods Enzymol. 153:516-544; and Scorer, CA. et al. (1994) Bio/Technology 12:181-184.) Plant systems may also be used for expression of NZMS. Transcription of sequences encoding NZMS may be driven by viral promoters, e.g., the 35S and 19S promoters of CaMV used alone or in combination with the omega leader sequence from TMV (Takamatsu, N. (1987) EMBO J. 6:307-311). Alternatively, plant promoters such as the small subunit of RUBISCO or heat shock promoters may be used. (See, e.g., Comzzi, G. et al. (1984) EMBO J. 3:1671-1680; BrogUe, R. et al. (1984) Science 224:838-843; and Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105.) These constmcts can be introduced into plant ceUs by direct DNA transformation or pathogen-mediated fransfection. (See, e.g.. The McGraw HiU Yearbook of Science and Technology (1992) McGraw HiU, New YorkNY, pp. 191-196.) In mammaMan ceUs, a number of viral-based expression systems may be utiMzed. In cases where an adenovirus is used as an expression vector, sequences encoding NZMS may be Mgated into an adenovims transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a non-essential El or E3 region of the viral genome may be used to obtain infective vims which expresses NZMS in host ceUs. (See, e.g., I_ogan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659.) In addition, transcription enhancers, such as the Rous sarcoma vims (RSV) enhancer, may be used to increase expression in mammaMan host ceUs. SN40 or EB V- based vectors may also be used for high-level protein expression. Human artificial chromosomes (HACs) may also be employed to deMver larger fragments of DNA than can be contained in and expressed from a plasmid. HACs of about 6 kb to 10 Mb are constmcted and deMvered via conventional deMvery methods (Mposomes, polycationic amino polymers, or vesicles) for therapeutic puφoses. (See, e.g., Harrington, J.J. et al. (1997) Nat. Genet. 15:345- 355.) For long term production of recombinant proteins in mammaMan systems, stable expression of NZMS in ceU Mnes is preferred. For example, sequences encoding NZMS can be transformed into ceU Mnes using expression vectors which may contain viral origins of repMcation and/or endogenous expression elements and a selectable marker gene on the same or on a separate vector. FoUowing the introduction of the vector, ceUs may be aUowed to grow for about 1 to 2 days in enriched media before being switched to selective media. The puφose of the selectable marker is to confer resistance to a selective agent, and its presence aUows growth and recovery of ceUs which successfully express the introduced sequences. Resistant clones of stably fransformed cells may be propagated using tissue culture techniques appropriate to the cell type. Any number of selection systems may be used to recover fransformed ceU Mnes. These include, but are not Mmited to, the heφes simplex vims thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk and apr ceUs, respectively. (See, e.g., Wigler, M. et al. (1977) Cell 11:223-232; Lowy, I. et al. (1980) CeU 22:817-823.) Also, antimetaboMte, antibiotic, or herbicide resistance can be used as the basis for selection. For example, dhfr confers resistance to methotrexate; neo confers resistance to the aminoglycosides neomycin and G-418; and als and pat confer resistance to chlorsulfuron and phosphinofricin acetyltransferase, respectively. (See, e.g., Wigler, M. et al. (1980) Proc. Natl. Acad. Sci. USA 77:3567-3570; Colbere-Garapin, F. et al. (1981) J. Mol. Biol. 150:1-14.) Additional selectable genes have been described, e.g., trpB and hisD, which alter ceUular requirements for metaboMtes. (See, e.g., Hartman, S.C. and R.C. MulMgan (1988) Proc. Natl. Acad. Sci. USA 85:8047-8051.) Visible markers, e.g., anthocyanins, green fluorescent proteins (GFP; Clontech), β glucuronidase and its substrate β-glucuronide, or luciferase and its substrate luciferin may be used. These markers can be used not only to identify transformants, but also to quantify the amount of transient or stable protein expression attributable to a specific vector system. (See, e.g., Rhodes, CA. (1995) Methods Mol. Biol. 55:121-131.) Although the presence/absence of marker gene expression suggests that the gene of interest is also present, the presence and expression of the gene may need to be confirmed. For example, if the sequence encoding NZMS is inserted within a marker gene sequence, transformed ceUs containing sequences encoding NZMS can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding NZMS under the control of a single promoter. Expression of the marker gene in response to induction or selection usuaUy indicates expression of the tandem gene as weU. In general, host ceUs that contain the nucleic acid sequence encoding NZMS and that express NZMS may be identified by a variety of procedures known to those of skiU in the art. These procedures include, but are not Mmited to, DNA-DNA or DNA-RNA hybridizations, PCR ampMfication, and protein bioassay or immunoassay techniques which include membrane, solution, or chip based technologies for the detection and/or quantification of nucleic acid or protein sequences. Immunological methods for detecting and measuring the expression of NZMS using either specific polyclonal or monoclonal antibodies are known in the art. Examples of such techniques include enzyme-Mnked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), and fluorescence activated ceU sorting (FACS). A two-site, monoclonal-based immunoassay utiMzing monoclonal antibodies reactive to two non-interfering epitopes on NZMS is preferred, but a competitive binding assay may be employed. These and other assays are well known in the art. (See, e.g., Hampton, R. et al. (1 90) Serological Methods, a Laboratory Manual, APS Press, St. Paul MN, Sect. IV; CoMgan, J.E. et al. (1997) Current Protocols in Immunology, Greene Pub. Associates and Wiley-Interscience, New York NY; and Pound, J.D. (1998) Immunochemical Protocols, Humana Press, Totowa NJ.) A wide variety of labels and conjugation techniques are known by those skiUed in the art and may be used in various nucleic acid and amino acid assays. Means for producing labeled hybridization or PCR probes for detecting sequences related to polynucleotides encoding NZMS include oMgolabeMng, nick translation, end-labeMng, or PCR ampMfication using a labeled nucleotide. Alternatively, the sequences encoding NZMS, or any fragments thereof, may be cloned into a vector for the production of an mRNA probe. Such vectors are known in the art, are commercially available, and may be used to synthesize RNA probes in vitro by addition of an appropriate RNA polymerase such as T7, T3, or SP6 and labeled nucleotides. These procedures may be conducted using a variety of commerciaUy available kits, such as those provided by Amersham Pharmacia Biotech, Promega (Madison WI), and US Biochemical. Suitable reporter molecules or labels which may be used for ease of detection include radionucMdes, enzymes, fluorescent, chemiluminescent, or chromogenic agents, as well as substrates, cofactors, inhibitors, magnetic particles, and the Mke. Host ceUs transformed with nucleotide sequences encoding NZMS may be cultured under conditions suitable for the expression and recovery of the protein from ceU culture. The protein produced by a transformed ceU may be secreted or retained intraceUularly depending on the sequence and/or the vector used. As wiU be understood by those of skiU in the art, expression vectors containing polynucleotides which encode NZMS may be designed to contain signal sequences which direct secretion of NZMS through a prokaryotic or eukaryotic ceU membrane. En addition, a host ceU strain may be chosen for its abiUty to modulate expression of the inserted sequences or to process the expressed protein in the desired fashion. Such modifications of the polypeptide include, but are not Mmited to, acetylation, carboxylation, glycosylation, phosphorylation Mpidation, and acylation. Post-translational processing which cleaves a "prepro" or "pro" form of the protein may also be used to specify protein targeting, folding, and/or activity. Different host ceUs which have specific ceUular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and WE38) are available from the American Type Culture CoUection (ATCC, Manassas VA) and may be chosen to ensure the correct modification and processing of the foreign protein. In another embodiment of the invention, natural, modified, or recombinant nucleic acid sequences encoding NZMS may be Mgated to a heterologous sequence resulting in translation of a fusion protein in any of the aforementioned host systems. For example, a chimeric NZMS protein containing a heterologous moiety that can be recognized by a commercially available antibody may faciUtate the screening of peptide Mbraries for inhibitors of NZMS activity. Heterologous protein and peptide moieties may also faciMtate purification of fusion proteins using commerciaUy available affinity matrices. Such moieties include, but are not Mmited to, glutathione S-transferase (GST), maltose binding protein (MBP), thioredoxin (Trx), calmoduMn binding peptide (CBP), 6-His, FLAG, c-myc, and hemagglutinin (HA). GST, MBP, Trx, CBP, and 6-His enable purification of their cognate fusion , proteins on immobiMzed glutathione, maltose, phenylarsine oxide, calmoduMn, and metal-chelate resins, respectively. FLAG, c-myc, and hemagglutinin (HA) enable immunoaffinity purification of fusion proteins using commerciaUy available monoclonal and polyclonal antibodies that specificaUy recognize these epitope tags. A fusion protein may also be engineered to contain a proteolytic cleavage site located between the NZMS encoding sequence and the heterologous protein sequence, so that NZMS may be cleaved away from the heterologous moiety foUowing purification. Methods for fusion protein expression and purification are discussed in Ausubel (1995, supra, ch. 10). A variety of commerciaUy available kits may also be used to faciMtate expression and purification of fusion proteins. In a further embodiment of the invention, synthesis of radiolabeled NZMS may be achieved in vitro using the TNT rabbit reticulocyte lysate or wheat germ extract system (Promega). These systems couple transcription and translation of protein-coding sequences operably associated with the T7, T3, or SP6 promoters. Translation takes place in the presence of a radiolabeled amino acid precursor, for example, 35 S-methionine. NZMS of the present invention or fragments thereof may be used to screen for compounds that specificaUy bind to NZMS. At least one and up to a pluraUty of test compounds may be screened for specific binding to NZMS. Examples of test compounds include antibodies, oMgonucleotides, proteins (e.g., receptors), or smaU molecules. In one embodiment, the compound thus identified is closely related to the natural Mgand of NZMS, e.g., a Mgand or fragment thereof, a natural substrate, a structural or functional mimetic, or a natural binding partner. (See, e.g., CoMgan, J.E. et al. (1991) Current Protocols in Immunology 1(2): Chapter 5.) Similarly, the compound can be closely related to the natural receptor to which NZMS binds, or to at least a fragment of the receptor, e.g., the Mgand binding site. In either case, the compound can be rationaUy designed using known techniques. In one embodiment, screening for these compounds involves producing appropriate ceUs which express NZMS, either as a secreted protein or on the ceU membrane. Preferred ceUs include cells from mammals, yeast, Drosophila, or E. coM. Cells expressing NZMS or ceU membrane fractions which contain NZMS are then contacted with a test compound and binding, stimulation, or inhibition of activity of either NZMS or the compoun. is analyzed. An assay may simply test binding of a test compound to the polypeptide, wherein binding is detected by a fluorophore, radioisotope, enzyme conjugate, or other detectable label. For example, the assay may comprise the steps of combining at least one test compound with NZMS, either in solution or affixed to a soMd support, and detecting the binding of NZMS to the compound. Alternatively, the assay may detect or measure binding of a test compound in the presence of a labeled competitor. AdditionaUy, the assay may be carried out using ceU-free preparations, chemical Mbraries, or natural product mixtures, and the test compound(s) may be free in solution or affixed to a soMd support. NZMS of the present invention or fragments thereof may be used to screen for compounds that modulate the activity of NZMS. Such compounds may include agonists, antagonists, or partial or inverse agonists. In one embodiment, an assay is performed under conditions permissive for NZMS activity, wherein NZMS is combined with at least one test compound, and the activity of NZMS in the presence of a test compound is compared with the activity of NZMS in the absence of the test compound. A change in the activity of NZMS in the presence of the test compound is indicative of a compound that modulates the activity of NZMS. Alternatively, a test compound is combined with an in vitro or ceU-free system comprising NZMS under conditions suitable for NZMS activity, and the assay is performed. In either of these assays, a test compound which modulates the activity of NZMS may do so indirectly and need not come in direct contact with the test compound. At least one and up to a pluraUty of test compounds may be screened. In another embodiment, polynucleotides encoding NZMS or their mammaMan homologs may be "knocked out" in an animal model system using homologous recombination in embryonic stem (ES) ceUs. Such techniques are weU known in the art and are useful for the generation of animal models of human disease. (See, e.g., U.S. Patent No. 5,175,383 and U.S. Patent No. 5,767,337.) For example, mouse ES ceUs, such as the mouse 129/SvJ ceU Mne, are derived from the early mouse embryo and grown in culture. The ES ceUs are fransformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphofransferase gene (neo; Capecchi, M.R. (1989) Science 244:1288-1292). The vector integrates into the corresponding region of the host genome by homologous recombination. Alternatively, homologous recombination takes place using the Cre-loxP system to knockout a gene of interest in a tissue- or developmental stage-specific manner (Marth, J.D. (1996) CMn. Invest. 97:1999-2002; Wagner, K.U. et al. (1997) Nucleic Acids Res. 25:4323-4330). Transformed ES ceUs are identified and microinjected into mouse ceU blastocysts such as those from the C57BL/6 mouse strain. The blastocysts are surgicaUy transferred to pseudopregnant dams, and the resulting chimeric progeny are genotyped and bred to produce heterozygous or homozygous strains. Transgenic animals thus generated may be tested with potential therapeutic or toxic agents. Polynucleotides encoding NZMS may also be manipulated in vitro in ES ceUs derived from human blastocysts. Human ES ceUs have the potential to differentiate into at least eight separate ceU Mneages including endoderm, mesoderm, and ectodermal ceU types. These ceU Mneages differentiate into, for example, neural cells, hematopoietic Mneages, and cardiomyocytes (Thomson, J.A. et al. (1998) Science 282:1145-1147). Polynucleotides encoding NZMS can also be used to create "knockin" humanized animals (pigs) or transgenic animals (mice or rats) to model human disease. With knockin technology, a region of a polynucleotide encoding NZMS is injected into animal ES ceUs, and the injected sequence integrates into the animal ceU genome. Transformed ceUs are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred Mnes are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease. Alternatively, a mammal inbred to overexpress NZMS, e.g., by secreting NZMS in its milk, may also serve as a convenient source of that protein (Janne, J. et al. (1998) Biotechnol. Annu. Rev. 4:55-74). THERAPEUTICS Chemical and structural similarity, e.g., in the context of sequences and motifs, exists between regions of NZMS and enzymes. In addition, the expression of NZMS is closely associated with brain tissue, breast tissue, bronchial smooth muscle tissue, endometrial tissue, kidney tissue, Mver tissue, lung tissue, pituitary tissue, prostate tissue, smaU intestine tissue, THP-1 promonocyte ceUs, and thymus tissue. Therefore, NZMS appears to play a role in ceU proMferative and autoimmune/inflammatory, cardiovascular, gastrointestinal, neurological, pulmonary, reproductive, and eye disorders. In the treatment of disorders associated with increased NZMS expression or activity, it is desirable to decrease the expression or activity of NZMS. In the treatment of disorders associated with decreased NZMS expression or activity, it is desirable to increase the expression or activity of NZMS. Therefore, in one embodiment, NZMS or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of NZMS. Examples of such disorders include, but are not Mmited to, a ceU proMferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancers of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, gangMa, gastrointestinal tract, heart, kidney, Mver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, saMvary glands, skin, spleen, testis, thymus, thyroid, and utems; an autoimmune/inflammatory disorder such as acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory distress syndrome, aUergies, ankylosing spondyhtis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), bronchitis, cholecystitis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes melMtus, emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosis fetaMs, erythema nodosum, afrophic gastritis, glomemlonephritis, Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis, hypereosinophiMa, irritable bowel syndrome, multiple sclerosis, myasthenia gravis, mvocardial or pericardial inflammation, osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjogren's syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, thrombocytopenic pmpura, ulcerative coMtis, uveitis, Werner syndrome, compMcations of cancer, hemodialysis, and extracoφoreal circulation, viral, bacterial, fungal, parasitic, protozoal, and helminthic infections, and trauma X-Mnked agammaglobinemia of Braton, common variable immunodeficiency (CVI), DiGeorge's syndrome (thymic hypoplasia), thymic dysplasia, isolated IgA deficiency, severe combined immunodeficiency disease (SCID), immunodeficiency with thrombocytopenia and eczema (Wiskott-Aldrich syndrome), Chediak-Higashi syndrome, chronic granulomatous diseases, hereditary angioneurotic edema, and immunodeficiency associated with Cushing's disease; a cardiovascular disorder such as arteriovenous fistula, atherosclerosis, hypertension, vascuMtis, Raynaud's disease, aneurysms, arterial dissections, varicose veins, thrombophlebitis and phlebothrombosis, vascular tumors, and compMcations of thrombolysis, baUoon angioplasty, vascular replacement, and coronary artery bypass graft surgery , congestive heart failure, ischemic heart disease, angina pectoris, myocardial infarction, hypertensive heart disease, degenerative valvular heart disease, calcific aortic valve stenosis, congenitaUy bicuspid aortic valve, mitral annular calcification, mitral valve prolapse, rheumatic fever and rheumatic heart disease, infective endocarditis, nonbacterial thrombotic endocarditis, endocarditis of systemic lupus erythematosus, carcinoid heart disease, cardiomyopathy, myocarditis, pericarditis, neoplastic heart disease, congenital heart disease, and compMcations of cardiac transplantation, congenital lung anomaMes, atelectasis, pulmonary congestion and edema, pulmonary emboMsm, puMnonary hemorrhage, puMnonary infarction, pulmonary hypertension, vascular sclerosis, obstructive pulmonary disease, restrictive pulmonary disease, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, bronchial asthma, broncbiectasis, bacterial pneumonia, viral and mycoplasmal pneumonia, lung abscess, pulmonary tuberculosis, diffuse interstitial diseases, pneumoconioses, sarcoidosis, idiopathic pulmonary fibrosis, desquamative interstitial pneumonitis, hypersensitivity pneumonitis, pulmonary eosinophiMa bronchioMtis obUterans-organizing pneumonia, diffuse pulmonary hemorrhage syndromes, Goodpasture's syndromes, idiopathic pulmonary hemosiderosis, pulmonary involvement in coUagen- vascular disorders, pulmonary alveolar proteinosis, lung tumors, inflammatory and noninflammatory pleural effusions, pneumothorax, pleural tumors, drug- induced lung disease, radiation-induced lung disease, and compMcations of lung transplantation; a gastrointestinal disorder such as dysphagia, peptic esophagitis, esophageal spasm, esophageal stricture, esophageal carcinoma, dyspepsia, indigestion, gastritis, gastric carcinoma, anorexia, nausea, emesis, gasfroparesis, anfral or pyloric edema, abdominal angina, pyrosis, gastroenteritis, intestinal obstmction, infections of the intestinal tract, peptic ulcer, choleMthiasis, cholecystitis, cholestasis, pancreatitis, pancreatic carcinoma, biMary tract disease, hepatitis, hyperbiMrubinemia, cirrhosis, passive congestion of the Mver, hepatoma, infectious coMtis, ulcerative coMtis, ulcerative proctitis, Crohn's disease, Whipple's disease, MaUory-Weiss syndrome, colonic carcinoma, colonic obstruction, irritable bowel syndrome, short bowel syndrome, diarrhea, constipation, gastrointestinal hemorrhage, acquired immunodeficiency syndrome (AIDS) enteropathy, jaundice, hepatic encephalopathy, hepatorenal syndrome, hepatic steatosis, hemochromatosis, Wilson's disease, alpha^antitrypsin deficiency, Reye's syndrome, primary sclerosing cholangitis, Mver infarction, portal vein obstruction and thrombosis, centrilobular necrosis, peMosis hepatis, hepatic vein thrombosis, veno-occlusive disease, preeclampsia, eclampsia, acute fatty Mver of pregnancy, intrahepatic cholestasis of pregnancy, and hepatic tumors including nodular hypeφlasias, adenomas, and carcinomas; a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington's disease, dementia, Parkinson's disease and other exfrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyeMnating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative infracranial thrombophlebitis, myeMtis and radicuMtis, viral central nervous system disease, prion diseases including kura, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal famiMal insomnia, nutritional and metaboMc diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebeUoretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system including Down syndrome, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis, inherited, metaboMc, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postheφetic neuralgia, Tourette's disorder, progressive supranuclear palsy, corticobasal degeneration, and famiMal frontotemporal dementia; a pulmonary disorder, such as congenital lung anomaMes, atelectasis, pulmonary congestion and edema, pulmonary emboMsm, pulmonary hemorrhage, pulmonary infarction, pulmonary hypertension, vascular sclerosis, obstructive pulmonary disease, restrictive pulmonary disease, chronic obstructive pulmonary disease, emphysema, chronic bronchitis, bronchial asthma, bronchiectasis, bacterial pneumonia, viral and mycoplasmal pneumonia, lung abscess, pulmonary tuberculosis, diffuse interstitial diseases, pneumoconioses, sarcoidosis, idiopathic pulmonary fibrosis, desquamative interstitial pneumonitis, hypersensitivity pneumonitis, pulmonary eosinophiMa bronchioMtis obMterans-organizing pneumonia, diffuse pulmonary hemorrhage syndromes, Goodpasture's syndromes, idiopathic pulmonary hemosiderosis, puMnonary involvement in coUagen-vascular disorders, pulmonary alveolar proteinosis, lung tumors, inflammatory and noninflammatory pleural effusions, pneumothorax, pleural tumors, drag- induced lung disease, radiation-induced lung disease, and compMcations of lung transplantation; a reproductive disorder such as a disorder of prolactin production, infertiUty, including tubal disease, ovulatoiy defects, and endometriosis, a disruption of the estrous cycle, a disruption of the menstrual cycle, polycystic ovary syndrome, ovarian hyperstimulation syndrome, an endometrial or ovarian tumor, a uterine fibroid, autoimmune disorders, an ectopic pregnancy, and teratogenesis; cancer of the breast, fibrocystic breast disease, and galactorrhea; a disruption of spermatogenesis, abnormal sperm physiology, cancer of the testis, cancer of the prostate, benign prostatic hypeφlasia, prostatitis, Peyronie's disease, impotence, carcinoma of the male breast, and gynecomastia; and an eye disorder such as ocular hypertension and glaucoma. In another embodiment, a vector capable of expressing NZMS or a fragment or derivative thereof may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of NZMS including, but not Mmited to, those described above. In a further embodiment, a composition comprising a substantiaUy purified NZMS in conjunction with a suitable pharmaceutical carrier may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of NZMS including, but not Mmited to, those provided above. In stiU another embodiment, an agonist which modulates the activity of NZMS may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of NZMS including, but not Mmited to, those Msted above. In a further embodiment, an antagonist of NZMS may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of NZMS. Examples of such disorders include, but are not Mmited to, those ceU proMferative and autoimmune/inflammatory, cardiovascular, gastrointestinal, neurological, pulmonary, reproductive, and eye disorders described above. In one aspect, an antibody which specifically binds NZMS may be used directly as an antagonist or indirectly as a targeting or deUvery mechanism for bringing a pharmaceutical agent to ceUs or tissues which express NZMS. In an additional embodiment, a vector expressing the complement of the polynucleotide encoding NZMS may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of NZMS including, but not Mmited to, those described above. In other embodiments, any of the proteins, antagonists, antibodies, agonists, complementary sequences, or vectors of the invention may be administered in combination with other appropriate therapeutic agents. Selection of the appropriate agents for use in combination therapy may be made by one of ordinary skiU in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergisticaUy to effect the treatment or prevention of the various disorders described above. Using this approach, one may be able to achieve therapeutic efficacy with lower dosages of each agent, thus reducing the potential for adverse side effects. An antagonist of NZMS may be produced using methods which are generaUy known in the art. In particular, purified NZMS may be used to produce antibodies or to screen Mbraries of pharmaceutical agents to identify those which specificaUy bind NZMS. Antibodies to NZMS may also be generated using methods that are weU known in the art. Such antibodies may include, but are not Mmited to, polyclonal, monoclonal, chimeric, and single chain antibodies, Fab fragments, and fragments produced by a Fab expression Mbrary. NeutraMzing antibodies (i.e., those which inhibit dimer formation) are generaUy preferred for therapeutic use. For the production of antibodies, various hosts including goats, rabbits, rats, mice, humans, and others may be immunized by injection with NZMS or with any fragment or oMgopeptide thereof which has immunogenic properties. Depending on the host species, various adjuvants may be used to increase immunological response. Such adjuvants include, but are not Mmited to, Freund's, mineral gels such as aluminum hydroxide, and surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, KLH, and dinitrophenol. Among adjuvants used in humans, BCG (bacilli Calmette-Guerin) and Corvnebacterium parvum are especiaUy preferable. It is preferred that the oMgopeptides, peptides, or fragments used to induce antibodies to NZMS have an amino acid sequence consisting of at least about 5 amino acids, and generaUy wiU consist of at least about 10 amino acids. It is also preferable that these oMgopeptides, peptides, or fragments are identical to a portion of the amino acid sequence of the natural protein. Short stretches of NZMS amino acids may be fused with those of another protein, such as KLH, and antibodies to the chimeric molecule may be produced. Monoclonal antibodies to NZMS may be prepared using any technique which provides for the production of antibody molecules by continuous ceU Mnes in culture. These include, but are not Mmited to, the hybridoma technique, the human B-ceU hybridoma technique, and the EBV-hybridoma technique. (See, e.g., Kohler, G. et al. (1975) Nature 256:495-497; Kozbor, D. et al. (1985) J. Immunol. Methods 81 :31-42; Cote, R.J. et al. (1983) Proc. Natl. Acad. Sci. USA 80:2026-2030; and Cole, S.P. et al. (1984) Mol. CeU Biol. 62:109-120.) In addition, techniques developed for the production of "chimeric antibodies," such as the spMcing of mouse antibody genes to human antibody genes to obtain a molecule with appropriate antigen specificity and biological activity, can be used. (See, e.g., Morrison, S.L. et al. (1984) Proc. Natl. Acad. Sci. USA 81 :6851-6855; Neuberger, M.S. et al. (1984) Nature 312:604-608; and Takeda, S. et al. (1985) Nature 314:452-454.) Alternatively, techniques described for the production of single chain antibodies may be adapted, using methods known in the art, to produce NZMS-specific single chain antibodies. Antibodies with related specificity, but of distinct idiotypic composition, may be generated by chain shuffling from random combinatorial immunoglobuMn Mbraries. (See, e.g., Burton, D.R. (1991) Proc. Natl. Acad. Sci. USA 88:10134-10137.) Antibodies may also be produced by inducing in vivo production in the lymphocyte population or by screening immunoglobuMn Mbraries or panels of highly specific binding reagents as disclosed in the Mterature. (See, e.g., Orlandi, R. et al. (1989) Proc. Natl. Acad. Sci. USA 86:3833-3837; Winter, G. et al. (1991) Nature 349:293-299.) Antibody fragments which contain specific binding sites for NZMS may also be generated. For example, such fragments include, but are not Mmited to, F(ab ! ) 2 fragments produced by pepsin digestion of the antibody molecule and Fab fragments generated by reducing the disulfide bridges of the F(ab')2 fragments. Alternatively, Fab expression Mbraries may be constmcted to aUow rapid and easy identification of monoclonal Fab fragments with the desired specificity. (See, e.g., Huse, W.D. et al. (1989) Science 246:1275-1281.) Various immunoassays may be used for screening to identify antibodies having the desired specificity. Numerous protocols for competitive binding or immunoradiometric assays using either polyclonal or monoclonal antibodies with estabhshed specificities are weU known in the art. Such immunoassays typically involve the measurement of complex formation between NZMS and its specific antibody. A two-site, monoclonal-based immunoassay utiMzing monoclonal antibodies reactive to two non-interfering NZMS epitopes is generaUy used, but a competitive binding assay may also be • employed (Pound, supra). Various methods such as Scatchard analysis in conjunction with radioimmunoassay techniques may be used to assess the affinity of antibodies for NZMS. Affinity is expressed as an association constant, K a , which is defined as the molar concentration of NZMS-antibody complex divided by the molar concentrations of free antigen and free antibody under equiUbrium conditions. The K, determined for a preparation of polyclonal antibodies, which are heterogeneous in their affinities for multiple NZMS epitopes, represents the average affinity, or avidity, of the antibodies for NZMS. The K, determined for a preparation of monoclonal antibodies, which are monospecific for a particular NZMS epitope, represents a true measure of affinity. High-affinity antibody preparations with K^ ranging from about 10 9 to IO 12 L/mole are preferred for use in immunoassays in which the NZMS- antibody complex must withstand rigorous manipulations. Eow-affinity antibody preparations with K^ ranging from about 10 s to IO 7 L/mole are preferred for use in immunopurification and similar procedures which ultimately require dissociation of NZMS, preferably in active form, from the antibody (Catty, D. (1988) Antibodies, Volume I: A Practical Approach, ERL Press, Washington DC; Liddell, J.E. and A. Cryer (1991) A Practical Guide to Monoclonal Antibodies, John Wiley & Sons, New York NY). The titer and avidity of polyclonal antibody preparations may be further evaluated to determine the quaMty and suitabiMty of such preparations for certain downstream appMcations. For example, a polyclonal antibody preparation containing at least 1-2 mg specific antibody/ml, preferably 5-10 mg specific antibody/ml, is generaUy employed in procedures requiring precipitation of NZMS-antibody complexes. Procedures for evaluating antibody specificity, titer, and avidity, and guideMnes for antibody quaMty and usage in various appMcations, are generaUy available. (See, e.g., Catty, supra, and CoMgan et al. supra.) En another embodiment of the invention, the polynucleotides encoding NZMS, or any fragment or complement thereof, may be used for therapeutic puφoses. In one aspect, modifications of gene expression can be achieved by designing complementary sequences or antisense molecules (DNA, RNA, PNA, or modified oMgonucleotides) to the coding or regulatory regions of the gene encoding NZMS. Such technology is well known in the art, and antisense oMgonucleotides or larger fragments can be designed from various locations along the coding or confrol regions of sequences encoding NZMS. (See, e.g., Agrawal, S., ed. (1996) Antisense Therapeutics, Humana Press Inc., Totawa NJ.) In therapeutic use, any gene deMvery system suitable for introduction of the antisense sequences into appropriate target ceUs can be used. Antisense sequences can be deMvered infraceUularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the ceUular sequence encoding the target protein. (See, e.g., Slater, J.E. et al. (1998) J. Allergy CMn. Immunol. 102(3):469-475; and Scanlon, K.J. et al. (1995) 9(13):1288-1296.) Antisense sequences can also be introduced infraceUularly through the use of viral vectors, such as retrovirus and adeno-associated vims vectors. (See, e.g., MiUer, A.D. (1990) Blood 76:271; Ausubel, supra; Uckert, W. and W. Walther (1994) Pharmacol. Ther. 63(3):323-347.) Other gene deMvery mechanisms include Mposome-derived systems, artificial viral envelopes, and other systems known in the art. (See, e.g., Rossi, J.J. (1995) Br. Med. Bull. 51(l):217-225; Boado, R.J. et al. (1998) J. Pharm. Sci. 87(11):1308-1315; and Morris, M.C. et al. (1997) Nucleic Acids Res. 25(14):2730-2736.) In another embodiment of the invention, polynucleotides encoding NZMS may be used for somatic or germline gene therapy. Gene therapy may be performed to (i) correct a genetic deficiency (e.g., in the cases of severe combined immunodeficiency (SCED)-Xl disease characterized by X- Mnked inheritance (Cavazzana-Calvo, M. et al. (2000) Science 288:669-672), severe combined immunodeficiency syndrome associated with an inherited adenosine deaminase (ADA) deficiency (Blaese, R.M. et al. (1995) Science 270:475-480; Bordignon, C et al. (1995) Science 270:470-475), cystic fibrosis (Zabner, J. et al. (1993) CeU 75:207-216; Crystal, R.G. et al. (1995) Hum. Gene Therapy 6:643-666; Crystal, R.G. et al (1995) Hum. Gene Therapy 6:667-703), thalassamias, famiMal hypercholesterolemia, and hemopbiUa resulting from Factor VUI or Factor EX deficiencies (Crystal, R.G. (1995) Science 270:404-410; Verma, I.M. and N. So ia (1997) Nature 389:239-242)), (ii) express a conditionaUy lethal gene product (e.g., in the case of cancers which result from unregulated ceU proMferation), or (iii) express a protein which affords protection against infraceUular parasites (e.g., against human refrovimses, such as human immunodeficiency vims (HIV) (Baltimore, D. (1988) Nature 335:395-396; Poeschla, E. et al. (1996) Proc. Natl. Acad. Sci. USA. 93:11395-11399), hepatitis B or C vims (HBN HCV); fungal parasites, such as Candida albicans and Paracoccidioides brasiMensis; and protozoan parasites such as Plasmodium falciparum and Trypanosoma cruzi). In the case where a genetic deficiency in ΝZMS expression or regulation causes disease, the expression of ΝZMS from an appropriate population of transduced ceUs may aUeviate the cMnical manifestations caused by the genetic deficiency. In a further embodiment of the invention, diseases or disorders caused by deficiencies in ΝZMS are treated by constructing mammaMan expression vectors encoding ΝZMS and introducing these vectors by mechanical means into ΝZMS-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vifro include (i) direct DΝA microinjection into individual cells, (ii) balMstic gold particle deMvery, (iii) Mposome-mediated fransfection, (iv) receptor-mediated gene fransfer, and (v) the use of DΝA transposons (Morgan, R.A. and W.F. Anderson (1993) Annu. Rev. Biochem. 62:191-217; Ivies, Z. (1997) CeU 91:501-510; Boulay, J-L. and H. Recipon (1998) Curr. Opin. Biotechnol. 9:445-450). Expression vectors that may be effective for the expression of ΝZMS include, but are not Mmited to, the PCDΝA 3.1, EPITAG, PRCCMV2, PREP, PVAX, PCR2-TOPOTA vectors (Invifrogen, Carlsbad CA), PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La JoUa CA), and PTET-OFF, PTET-OΝ, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto CA). ΝZMS may be expressed using (i) a constitutively active promoter, (e.g., from cytomegalovims (CMV), Rous sarcoma vims (RSV), SV40 vims, thymidine kinase (TK), or β-actin genes), (n) an inducible promoter (e.g., the tetracycMne-regulated promoter (Gossen, M. and H. Bujard (1992) Proc. Νatl. Acad. Sci. USA 89:5547-5551; Gossen, M. et al. (1995) Science 268:1766-1769; Rossi, F.M.N and H.M. Blau (1998) Curr. Opin. Biotechnol. 9:451-456), commerciaUy available in the T-REX plasmid (Invifrogen)); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PEΝD; Invifrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter (Rossi, F.M.N. and H.M. Blau, supra)), or (ui) a tissue-specific promoter or the native promoter of the endogenous gene encoding ΝZMS from a normal individual. CommerciaUy available Mposome transformation kits (e.g., the PERFECT LIPED TRANSFECTION KIT, available from Invifrogen) aUow one with ordinary skiU in the art to dehver polynucleotides to target ceUs in culture and require minimal effort to optimize experimental parameters. In the alternative, transformation is performed using the calcium phosphate method (Graham, F.L. and A.J. Eb (1973) Virology 52:456-467), or by electroporation (Neumann, E. et al. (1982) EMBO J. 1:841-845). The introduction of DNA to primary ceUs requires modification of these standardized mammaMan fransfection protocols. In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to NZMS expression are treated by constructing a refrovirus vector consisting of (i) the polynucleotide encoding NZMS under the confrol of an independent promoter or the retro vims long terminal repeat (LTR) promoter, (ti) appropriate RNA packaging signals, and (ui) a Rev-responsive element (RRE) along with additional refrovirus cώ-acting RNA sequences and coding sequences required for efficient vector propagation. Refrovirus vectors (e.g., PFB and PFBNEO) are commerciaUy available (Stratagene) and are based on pubMshed data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. USA 92:6733-6737), incoφorated by reference herein. The vector is propagated in an appropriate vector producing ceU Mne (VPCL) that expresses an envelope gene with a tropism for receptors on the target ceUs or a promiscuous envelope protein such as VSVg (Armentano, D. et al. (1987) J. Virol. 61:1647-1650; Bender, M.A. et al. (1987) J. Virol. 61:1639-1646; Adam, M.A. and A.D. MiUer (1988) J. Virol. 62:3802-3806; DuU, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey, R.,e1 al. (1998) J. Virol. 72:9873-9880). U.S. Patent No. 5,910,434 to Rigg ("Method for obtaining refrovirus packaging ceU Mnes producing high transducing efficiency retroviral supernatant") discloses a method for obtaining refrovirus packaging cell Mnes and is hereby incoiporated by reference. Propagation of retrovirus vectors, transduction of a population of ceUs (e.g., CD4 + T-ceUs), and the return of transduced cells to a patient are procedures well known to persons skiUed in the art of gene therapy and have been ' well documented (Ranga, U. et al. (1997) J. Virol. 71:7020-7029; Bauer, G. et al. (1997) Blood 89:2259-2267; Bonyhadi, M.L (1997) J. Virol. 71:4707-4716; Ranga, U. et al. (1998) Proc. Natl. Acad. Sci. USA 95:1201-1206; Su, L. (1997) Blood 89:2283-2290). In the alternative, an adenovims-based gene therapy deMvery system is used to deMver polynucleotides encoding NZMS to ceUs which have one or more genetic abnormaUties with respect to the expression of NZMS. The construction and packaging of adenovirus-based vectors are weU known to those with ordinary skiU in the art. RepMcation defective adenovims vectors have proven to be versatile for importing genes encoding immunoregulatory proteins into intact islets in the pancreas (Csete, M.E. et al. (1995) Transplantation 27:263-268). PqtentiaUy useful adenoviral vectors are described in U.S. Patent No. 5,707,618 to Armentano ("Adenovirus vectors for gene therapy"), hereby incoφorated by reference. For adenoviral vectors, see also Antinozzi, P. A. et al. (1999) Annu. Rev. Nutr. 19:511-544 and Verma, I.M. and N. Somia (1997) Nature 18:389:239-242, both incoφorated by reference herein. In another alternative, a heφes-based, gene therapy deMvery system is used to deMver polynucleotides encoding NZMS to target ceUs which have one or more genetic abnormaUties with respect to the expression of NZMS. The use of heφes simplex vims (HSV)-based vectors may be especially valuable for introducing NZMS to ceUs of the central nervous system, for which HSV has a fropism. The construction and packaging of heφes-based vectors are weU known to those with ordinary skiU in the art. A repMcation-competent heφes simplex vims (HSV) type 1 -based vector has been used to deMver a reporter gene to the eyes of primates (Liu, X. et al. (1999) Exp. Eye Res. 169:385-395). The construction of a HSV-1 vims vector has also been disclosed in detail in U.S. Patent No. 5,804,413 to DeLuca ("Heipes simplex vims strains for gene transfer"), which is hereby incoφorated by reference. U.S. Patent No. 5,804,413 teaches the use of recombinant HSV d92 which consists of a genome containing at least one exogenous gene to be transferred to a ceU under the control of the appropriate promoter for pmposes including human gene therapy. Also taught by this patent are the construction and use of recombinant HSV strains deleted for ICP4, ICP27 and ICP22. For HSV vectors, see also Goins, W.F. et al. (1999) J. Virol. 73:519-532 and Xu, H. et al. (1994) Dev. Biol. 163 : 152-161 , hereby incoφorated by reference. The manipulation of cloned heφesvirus sequences, the generation of recombinant vims foUowing the fransfection of multiple plasmids containing different segments of the large heφesvirus genomes, the growth and propagation of heφesvirus, and the infection of ceUs with heφesvirus are techniques weU known to those of ordinary sktil in the art. In another alternative, an alphavirus (positive, single-stranded RNA vims) vector is used to deMver polynucleotides encoding NZMS to target ceUs. The biology of the prototypic alphavirus, SemMki Forest Vims (SFV), has been studied extensively and gene transfer vectors have been based on the SFV genome (Garoff, H. and K.-J. Li (1998) Curr. Opin. Biotechnol. 9:464-469). During alphavirus RNA repMcation, a subgenomic RNA is generated that normaUy encodes the viral capsid proteins. This subgenomic RNA repMcates to higher levels than the fuU length genomic RNA, resulting in the oveφroduction of capsid proteins relative to the viral proteins with enzymatic activity (e.g., protease and polymerase). Similarly, inserting the coding sequence for NZMS into the alphavirus genome in place of the capsid-coding region results in the production of a large number of NZMS-coding RNAs and the synthesis of high levels of NZMS in vector transduced ceUs. While alphavims infection is typicaUy associated with ceU lysis within a few days, the ability to estabMsh a persistent infection in hamster normal kidney ceUs (BHK-21) with a variant of Sindbis vims (SEN) indicates that the lytic repMcation of alphaviruses can be altered to suit the needs of the gene therapy appMcation (Dryga, S.A. et al. (1997) Virology 228:74-83). The wide host range of alphaviruses wiU aUow the introduction of NZMS into a variety of cell types. The specific transduction of a subset of ceUs in a population may require the sorting of ceUs prior to transduction. The methods of manipulating infectious cDNA clones of alphaviruses, performing alphavims cDNA and RNA fransfections, and performing alphavims infections, are weU known to those with ordinary skiU in the art. OMgonucleotides derived from the transcription initiation site, e.g., between about positions -10 and +10 from the start site, may also be employed to inhibit gene expression. Similarly, inhibition can be achieved using triple heMx base-pairing methodology. Triple heMx pairing is useful because it causes inhibition of the abiMty of the double heMx to open sufficiently for the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described in the Mterature. (See, e.g., Gee, J.E. et al. (1994) in Huber, B.E. and B.I. Carr, Molecular and Immunologic Approaches, Futura PubMshing, Mt. Kisco NY, pp. 163-177.) A complementary sequence or antisense molecule may also be designed to block translation of mRNA by preventing the transcript from binding to ribosomes. Ribozymes, enzymatic RNA molecules, may also be used to catalyze the specific cleavage of RNA. The mechanism of ribozyme action involves sequence-specific hybridization of the ribozyme molecule to complementary target RNA, foUowed by endonucleolytic cleavage. For example, engineered hammerhead motif ribozyme molecules may specificaUy and efficiently catalyze endonucleolytic cleavage of sequences encoding NZMS. Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites, including the foUowing sequences: GUA, GUU, and GUC Once identified, short RNA sequences of between 15 and 20 ribonucleotides, corresponding to the region of the target gene containing the cleavage site, may be evaluated for secondary structural features which may render the oMgonucleotide inoperable. The suitabihty of candidate targets may also be evaluated by testing accessibiMty to hybridization with complementary oMgonucleotides using ribonuclease protection assays. Complementary ribonucleic acid molecules and ribozymes of the invention may be prepared by any method known in the art for the synthesis of nucleic acid molecules. These include techniques for chemicaUy synthesizing oMgonucleotides such as soMd phase phosphoramidite chemical synthesis. Alternatively, RNA molecules may be generated by in vitro and in vivo transcription of DNA sequences encoding NZMS. Such DNA sequences may be incoφorated into a wide variety of vectors with suitable RNA polymerase promoters such as T7 or SP6. Alternatively, these cDNA constmcts that synthesize complementary RNA, constitutively or inducibly, can be infroduced into ceU Mnes, ceUs, or tissues. RNA molecules may be modified to increase infraceUular stabiUty and half-Ufe. Possible modifications include, but are not Mmited to, the addition of flanking sequences at the 5' and/or 3' ends of the molecule, or the use of phosphorothioate or 2' O-methyl rather than phosphodiesterase Mnkages within the backbone of the molecule. This concept is inherent in the production of PNAs and can be extended in all of these molecules by the inclusion of nonfraditional bases such as mosine, queosine, and wybutosine, as weU as acetyl-, methyl-, thio-, and similarly modified forms of adenine, cytidine, guanine, thymine, and uridine which are not as easily recognized by endogenous endonucleases. An additional embodiment of the invention encompasses a method for screening for a compound which is effective in altering expression of a polynucleotide encoding NZMS. Compounds which may be effective in altering expression of a specific polynucleotide may include, but are not Mmited to, oMgonucleotides, antisense oMgonucleotides, triple heMx-forming oMgonucleotides, transcription factors and other polypeptide transcriptional regulators, and non-macromolecular chemical entities which are capable of interacting with specific polynucleotide sequences. Effective compounds may alter polynucleotide expression by acting as either inhibitors or promoters of polynucleotide expression. Thus, in the treatment of disorders associated with increased NZMS expression or activity, a compound which specificaUy inhibits expression of the polynucleotide encoding NZMS may be therapeutically useful, and in the treatment of disorders associated with decreased NZMS expression or activity, a compound which specifically promotes expression of the polynucleotide encoding NZMS may be therapeuticaUy useful. At least one, and up to a pluraUty, of test compounds may be screened for effectiveness in altering expression of a specific polynucleotide. A test compound may be obtained by any method commonly known in the art, including chemical modification of a compound known to be effective in altering polynucleotide expression; selection from an existing, commerciaUy-available or proprietary Mbrary of naturaUy-occurring or non-natural chemical compounds; rational design of a compound based on chemical and/or structural properties of the target polynucleotide; and selection from a Mbrary of chemical compounds created combinatoriaUy or randomly. A sample comprising a polynucleotide encoding NZMS is exposed to at least one test compound thus obtained. The sample may comprise, for example, an intact or permeabiMzed ceU, or an in vifro ceU-free or reconstituted biochemical system. Alterations in the expression of a polynucleotide encoding NZMS are assayed by any method commonly known in the art. TypicaUy, the expression of a specific nucleotide is detected by hybridization with a probe having a nucleotide sequence complementary to the sequence of the polynucleotide encoding NZMS. The amount of hybridization may be quantified, thus forming the basis for a comparison of the expression of the polynucleotide both with and without exposure to one or more test compounds. Detection of a change in the expression of a polynucleotide exposed to a test compound indicates that the test compound is effective in altering the expression of the polynucleotide. A screen for a compound effective in altering expression of a specific polynucleotide can be carried out, for example, using a Schizosaccharomyces pombe gene expression system (Atkins, D. et al. (1999) U.S. Patent No. 5,932,435; Amdt, G.M. et al. (2000) Nucleic Acids Res. 28:E15) or a human ceU Mne such as HeLa ceU (Clarke, M.L. et al. (2000) Biochem. Biophys. Res. Commun. 268:8-13). A particular embodiment of the present invention involves screening a combinatorial Mbrary of oMgonucleotides (such as deoxyribonucleotides, ribonucleotides, peptide nucleic acids, and modified oMgonucleotides) for antisense activity against a specific polynucleotide sequence (Bruice, T.W. et al. (1997) U.S. Patent No. 5,686,242; Bruice, T.W. et al. (2000) U.S. Patent No. 6,022,691). Many methods for introducing vectors into ceUs or tissues are available and equaUy suitable for use in vivo, in vitro, and ex vivo. For ex vivo therapy, vectors may be introduced into stem cells taken from the patient and clonally propagated for autologous transplant back into that same patient. DeMvery by fransfection, by Mposome injections, or by polycationic amino polymers may be achieved using methods which are well known in the art. (See, e.g., Goldman, C.K. et al. (1997) Nat. Biotechnol. 15:462-466.) Any of the therapeutic methods described above may be appMed to any subject in need of such therapy, including, for example, mammals such as humans, dogs, cats, cows, horses, rabbits, and monkeys. An additional embodiment of the invention relates to the administration of a composition which generaUy comprises an active ingredient formulated with a pharmaceuticaUy acceptable excipient. Excipients may include, for example, sugars, starches, ceUuloses, gums, and proteins. Various formulations are commonly known and are thoroughly discussed in the latest edition of Remington's Pharmaceutical Sciences (Maack PubMshing, Easton PA). Such compositions may consist of NZMS, antibodies to NZMS, and mimetics, agonists, antagonists, or inhibitors of NZMS. The compositions utiMzed in this invention may be administered by any number of routes including, but not Mmited to, oral, intravenous, intramuscular, infra-arterial, inframeduUary, infrathecal, intravenfricular, pulmonary, transdermal, subcutaneous, intraperitoneal, infranasal, enteral, topical, subUngual, or rectal means. Compositions for pulmonary administration may be prepared in Mquid or dry powder form. These compositions are generaUy aerosoMzed immediately prior to inhalation by the patient. In the case of smaU molecules (e.g. traditional low molecular weight organic drags), aerosol deMvery of fast- acting formulations is weU-known in the art. In the case of macromolecules (e.g. larger peptides and proteins), recent developments in the field of pulmonary deMvery via the alveolar region of the lung have enabled the practical deMvery of drags such as insuMn to blood circulation (see, e.g., Patton, J.S. et al., U.S. Patent No. 5,997,848). Pulmonary deMvery has the advantage of administration without needle injection, and obviates the need for potentiaUy toxic penetration enhancers. Compositions suitable for use in the invention include compositions wherein the active ingredients are contained in an effective amount to achieve the intended puφose. The determination of an effective dose is weU within the capabiMty of those skiUed in the art. SpeciaMzed forms of compositions may be prepared for direct infraceUular deMvery of macromolecules comprising NZMS or fragments thereof. For example, Mposome preparations containing a ceU-impermeable macromolecule may promote ceU fusion and infraceUular deMvery of the macromolecule. Alternatively, NZMS or a fragment thereof may be joined to a short cationic N- terminal portion from the HEV Tat-1 protein. Fusion proteins thus generated have been found to transduce into the cells of aU tissues, including the brain, in a mouse model system (Schwarze, S.R. et al. (1999) Science 285:1569-1572). For any compound, the therapeutically effective dose can be estimated initiaUy either in cell culture assays, e.g., of neoplastic ceUs, or in animal models such as mice, rats, rabbits, dogs, monkeys, or pigs. An animal model may also be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans. A therapeutically effective dose refers to that amount of active ingredient, for example NZMS or fragments thereof, antibodies of NZMS, and agonists, antagonists or inhibitors of NZMS, which ameUorates the symptoms or condition. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in ceU cultures or with experimental animals, such as by calculating the ED 50 (the dose therapeutically effective in 50% of the population) or LD 50 (the dose lethal to 50% of the population) statistics. The dose ratio of toxic to therapeutic effects is the therapeutic index, which can be expressed as the LD 50 /ED 50 ratio. Compositions which exhibit large therapeutic indices are preferred. The data obtained from ceU culture assays and animal studies are used to formulate a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that includes the ED 50 with Mttle or no toxicity. The dosage varies within this range depending upon the dosage form employed, the sensitivity of the patient, and the route of administration. The exact dosage wiU be determined by the practitioner, in Mght of factors related to the subject requiring freatment. Dosage and adminisfration are adjusted to provide sufficient levels of the active moiety or to maintain the desired effect. Factors which may be taken into account include the severity of the disease state, the general health of the subject, the age, weight, and gender of the subject, time and frequency of administration, drag combination(s), reaction sensitivities, and response to therapy. Long-acting compositions may be administered every 3 to 4 days, every week, or biweekly depending on the half-Mfe and clearance rate of the particular formulation. Normal dosage amounts may vary from about 0.1 μg to 100,000 μg, up to a total dose of about 1 gram, depending upon the route of administration. Guidance as to particular dosages and methods of deMvery is provided in the Mterature and generaUy available to practitioners in the art. Those skilled in the art wiU employ different formulations for nucleotides than for proteins or their inhibitors. Similarly, deMvery of polynucleotides or polypeptides wiU be specific to particular ceUs, conditions, locations, etc. DIAGNOSTICS In another embodiment, antibodies which specificaUy bind NZMS may be used for the diagnosis of disorders characterized by expression of NZMS, or in assays to monitor patients being treated with NZMS or agonists, antagonists, or inhibitors of NZMS. Antibodies useful for diagnostic puφoses may be prepared in the same manner as described above for therapeutics. Diagnostic assays for NZMS include methods which utiMze the antibody and a label to detect NZMS in human body fluids or in extracts of cells or tissues. The antibodies may be used with or without modification, and may be labeled by covalent or non-covalent attachment of a reporter molecule. A wide variety of reporter molecules, several of which are described above, are known in the art and may be used. A variety of protocols for measuring NZMS, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of NZMS expression. Normal or standard values for NZMS expression are estabhshed by combining body fluids or ceU extracts taken from normal mammaMan subjects, for example, human subjects, with antibodies to NZMS under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of NZMS expressed in subject, confrol, and disease samples from biopsied tissues are compared with the standard values. Deviation between standard and subject values estabMshes the parameters for diagnosing disease. In another embodiment of the invention, the polynucleotides encoding NZMS may be used for diagnostic puφoses. The polynucleotides which may be used include oMgonucleotide sequences, complementary RNA and DNA molecules, and PNAs. The polynucleotides may be used to detect and quantify gene expression in biopsied tissues in which expression of NZMS may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of NZMS, and to monitor regulation of NZMS levels during therapeutic intervention. In one aspect, hybridization with PCR probes which are capable of detecting polynucleotide sequences, including genomic sequences, encoding NZMS or closely related molecules may be used to identify nucleic acid sequences which encode NZMS. The specificity of the probe, whether it is made from a highly specific region, e.g., the 5' regulatory region, or from a less specific region, e.g., a conserved motif, and the stringency of the hybridization or ampMfication wiU determine whether the probe identifies only naturaUy occurring sequences encoding NZMS, aUeMc variants, or related sequences. Probes may also be used for the detection of related sequences, and may have at least 50% sequence identity to any of the NZMS encoding sequences. The hybridization probes of the subject invention may be DNA or RNA and may be derived from the sequence of SEQ ID NO: 19-36 or from genomic sequences including promoters, enhancers, and introns of the NZMS gene. Means for producing specific hybridization probes for DNAs encoding NZMS include the cloning of polynucleotide sequences encoding NZMS or NZMS derivatives into vectors for the production of mRNA probes. Such vectors are known in the art, are commerciaUy available, and may be used to synthesize RNA probes in vitro by means of the addition of the appropriate RNA polymerases and the appropriate labeled nucleotides. Hybridization probes may be labeled by a variety of reporter groups, for example, by radionucMdes such as 32 P or 35 S, or by enzymatic labels, such as alkaMne phosphatase coupled to the probe via avidin/biotin coupMng systems, and the Mke. Polynucleotide sequences encoding NZMS may be used for the diagnosis of disorders associated with expression of NZMS. Examples of such disorders include, but are not Mmited to, a cell proMferative disorder such as actinic keratosis, arteriosclerosis, atherosclerosis, bursitis, cirrhosis, hepatitis, mixed connective tissue disease (MCTD), myelofibrosis, paroxysmal nocturnal hemoglobinuria, polycythemia vera, psoriasis, primary thrombocythemia, and cancers including adenocarcinoma, leukemia, lymphoma, melanoma, myeloma, sarcoma, teratocarcinoma, and, in particular, cancers of the adrenal gland, bladder, bone, bone marrow, brain, breast, cervix, gall bladder, gangMa, gastrointestinal tract, heart, kidney, Mver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, saMvary glands, skin, spleen, testis, thymus, thyroid, and uterus; an autoimmune/inflammatory disorder such as acquired immunodeficiency syndrome (AIDS), Addison's disease, adult respiratory ' distress syndrome, aUergies, ankylosing spondyMtis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyendocrinopathy-candidiasis- ectodermal dystrophy (APECED), bronchitis, cholecystitis, contact dermatitis, Crohn's disease, atopic dermatitis, dermatomyositis, diabetes melMtus, emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosis feta s, erythema nodosum, afrophic gastritis, glomerulonephritis, Goodpasture's syndrome, gout, Graves' disease, Hashimoto's thyroiditis, hypereosinophiUa, irritable bowel syndrome, multiple sclerosis, myasthenia gravis, mvocardial or pericardial inflammation, •osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis, Reiter's syndrome, rheumatoid arthritis, scleroderma, Sjδgren's syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, thrombocytopenic puφura, ulcerative coMtis, uveitis, Werner syndrome, compMcations of cancer, hemodialysis, and extracoφoreal circulation, viral, bacterial, fungal, parasitic, protozoal, and helminthic infections, and trauma; a neurological disorder such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer's disease, Pick's disease, Huntington' s disease, dementia, Parkinson's disease and other extrapyramidal disorders, amyotrophic lateral sclerosis and other motor neuron disorders, progressive neural muscular atrophy, retinitis pigmentosa, hereditary ataxias, multiple sclerosis and other demyeMnating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myeMtis and radicuMtis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt- Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal famiMal insomnia, nutritional and metaboMc diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebeUoretinal hemangioblastomatosis, encephalotrigeminal syndrome, mental retardation and other developmental disorders of the central nervous system including Down syndrome, cerebral palsy, neuroskeletal disorders, autonomic nervous system disorders, cranial nerve disorders, spinal cord diseases, muscular dystrophy and other neuromuscular disorders, peripheral nervous system disorders, dermatomyositis and polymyositis, inherited, metaboMc, endocrine, and toxic myopathies, myasthenia gravis, periodic paralysis, mental disorders including mood, anxiety, and schizophrenic disorders, seasonal affective disorder (SAD), akathesia, amnesia, catatonia, diabetic neuropathy, tardive dyskinesia, dystonias, paranoid psychoses, postheφetic neuralgia, Tourette's disorder, progressive supranuclear palsy, corticobasal degeneration, and famiMal frontotemporal dementia; and an eye disorder such as ocular hypertension and glaucoma. The polynucleotide sequences encoding NZMS may be used in Southern or northern analysis, dot blot, or other membrane-based technologies; in PCR technologies; in dipstick, pin, and multiformat ELISA-Mke assays; and in microarrays utiMzing fluids or tissues from patients to detect altered NZMS expression. Such quaUtative or quantitative methods are weU known in the art. In a particular aspect, the nucleotide sequences encoding NZMS may be useful in assays that detect the presence of associated disorders, particularly those mentioned above. The nucleotide sequences encoding NZMS may be labeled by standard methods and added to a fluid or tissue sample from a patient under conditions suitable for the formation of hybridization complexes. After a suitable incubation period, the sample is washed and the signal is quantified and compared with a standard value. If the amount of signal in the patient sample is significantly altered in comparison to a confrol sample then the presence of altered levels of nucleotide sequences encoding NZMS in the sample indicates the presence of the associated disorder. Such assays may also be used to evaluate the efficacy of a particular therapeutic treatment regimen in animal studies, in cMnical trials, or to monitor the treatment of an individual patient. In order to provide a basis for the diagnosis of a disorder associated with expression of NZMS, a normal or standard profile for expression is estabMshed. This may be accompMshed by combining body fluids or ceU extracts taken from normal subjects, either animal or human, with a sequence, or a fragment thereof, encoding NZMS, under conditions suitable for hybridization or ampMfication. Standard hybridization may be quantified by comparing the values obtained from normal subjects with values from an experiment in which a known amount of a substantiaUy purified polynucleotide is used. Standard values obtained in this manner may be compared with values obtained from samples from patients who are symptomatic for a disorder. Deviation from standard values is used to estabMsh the presence of a disorder. Once the presence of a disorder is estabMshed and a treatment protocol is initiated, hybridization assays may be repeated on a regular basis to determine if the level of expression in the patient begins to approximate that which is observed in the normal subject. The results obtained from successive assays may be used to show the efficacy of treatment over a period ranging from several days to months. With respect to cancer, the presence of an abnormal amount of transcript (either under- or overexpressed) 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 cMnical symptoms. A more definitive diagnosis of this type may aUow health professionals to employ preventative measures or aggressive treatment earher thereby preventing the development or further progression of the cancer. Additional diagnostic uses for oMgonucleotides designed from the sequences encoding NZMS may involve the use of PCR. These oMgomers may be chemicaUy synthesized, generated enzymaticaUy, or produced in vitro. OMgomers wiU preferably contain a fragment of a polynucleotide encoding NZMS, or a fragment of a polynucleotide complementary to the polynucleotide encoding NZMS, and wiU be employed under optimized conditions for identification of a specific gene or condition. OMgomers may also be employed under less stringent conditions for detection or quantification of closely related DNA or RNA sequences. In a particular aspect, oMgonucleotide primers derived from the polynucleotide sequences encoding NZMS may be used to detect single nucleotide polymoφhisms (SNPs). SNPs are substitutions, insertions and deletions that are a frequent cause of inherited or acquired genetic disease in humans. Methods of SNP detection include, but are not Mmited to, single-sfranded conformation polymoφhism (SSCP) and fluorescent SSCP (fSSCP) methods. In SSCP, oMgonucleotide primers derived from the polynucleotide sequences encoding NZMS are used to ampMfy DNA using the polymerase chain reaction (PCR). The DNA may be derived, for example, from diseased or normal tissue, biopsy samples, bodily fluids, and the Mke. SNPs in the DNA cause differences in the secondary and tertiary stractures of PCR products in single-sfranded form, and these differences are detectable using gel electrophoresis in non-denaturing gels. In fSCCP, the oMgonucleotide primers are fluorescently labeled, which aUows detection of the ampMmers in high-throughput equipment such as DNA sequencing machines. AdditionaUy, sequence database analysis methods, termed in siMco SNP (isSNP), are capable of identifying polymoφhisms by comparing the sequence of individual overlapping DNA fragments which assemble into a common consensus sequence. These computer- based methods filter out sequence variations due to laboratory preparation of DNA and sequencing errors using statistical models and automated analyses of DNA sequence chromatograms. In the alternative, SNPs may be detected and characterized by mass spectrometry using, for example, the high throughput MASSARRAY system (Sequenom, Inc., San Diego CA). Methods which may also be used to quantify the expression of NZMS include radiolabeMng or biotinylating nucleotides, coampMfication of a confrol nucleic acid, and inteφolating results from standard curves. (See, e.g., Melby, P.C et al. (1993) J. Immunol. Methods 159:235-244; Duplaa, C. et al. (1993) Anal. Biochem. 212:229-236.) The speed of quantitation of multiple samples may be accelerated by running the- assay in a high-throughput format where the oMgomer or polynucleotide of interest is presented in various dilutions and a specfrophotomefric or colorimetric response gives rapid quantitation. In further embodiments, oMgonucleotides or longer fragments derived from any of the polynucleotide sequences described herein may be used as elements on a microarray. The microarray can be used in transcript imaging techniques which monitor the relative expression levels of large numbers of genes simultaneously as described below. The microarray may also be used to identify genetic variants, mutations, and polymoφhisms. This information may be used to determine gene function, to understand the genetic basis of a disorder, to diagnose a disorder, to monitor progression regression of disease as a function of gene expression, and to develop and monitor the activities of therapeutic agents in the freatment of disease. In particular, this information may be used to develop a pharmacogenomic profile of a patient in order to select the most appropriate and effective treatment regimen for that patient. For example, therapeutic agents which are highly effective and display the fewest side effects may be selected for a patient based on his her pharmacogenomic profile. In another embodiment, NZMS, fragments of NZMS, or antibodies specific for NZMS may be used as elements on a microarray. The microarray may be used to monitor or measure protein- protein interactions, drug-target interactions, and gene expression profiles, as described above. A particular embodiment relates to the use of the polynucleotides of the present invention to generate a transcript image of a tissue or cell type. A franscript image represents the global pattern of gene expression by a particular tissue or ceU type. Global gene expression patterns are analyzed by quantifying the number of expressed genes and their relative abundance under given conditions and at a given time. (See Seilhamer et al., "Comparative Gene Transcript Analysis," U.S. Patent No. 5,840,484, expressly incoφorated by reference herein.) Thus a transcript image may be generated by hybridizing the polynucleotides of the present invention or their complements to the totaUty of transcripts or reverse transcripts of a particular tissue or cell type. In one embodiment, the hybridization takes place in high-throughput format, wherein the polynucleotides of the present invention or their complements comprise a subset of a pluraUty of elements on a microarray. The resultant transcript image would provide a profile of gene activity. Transcript images may be generated using transcripts isolated from tissues, ceU Mnes, biopsies, or other biological samples. The transcript image may thus reflect gene expression in vivo, as in the case of a tissue or biopsy sample, or in vifro, as in the case of a ceU Mne. Transcript images which profile the expression of the polynucleotides of the present invention may also be used in conjunction with in vitro model systems and precMnical evaluation of pharmaceuticals, as weU as toxicological testing of industrial and naturaUy-occurring environmental compounds. AU compounds induce characteristic gene expression patterns, frequently termed molecular fingeφrints or toxicant signatures, which are indicative of mechanisms of action and toxicity (Nuwaysir, E.F. et al. (1999) Mol. Carcinog. 24:153-159; Steiner, S. and N.L. Anderson (2000) Toxicol. I_ett. 112-113:467-471, expressly incoφorated by reference herein). If a test compound has a signature similar to that of a compound with known toxicity, it is Mkely to share those toxic properties. These fingeφrints or signatures are most useful and refined when they contain expression information from a large number of genes and gene famiMes. IdeaUy, a genome-wide measurement of expression provides the highest quaMty signature. Even genes whose expression is not altered by any tested compounds are important as weU, as the levels of expression of these genes are used to normaUze the rest of the expression data. The normaMzation procedure is useful for comparison of expression data after freatment with different compounds. While the assignment of gene function to elements of a toxicant signature aids in inteφretation of toxicity mechanisms, knowledge of gene function is not necessary for the statistical matching of signatures which leads to prediction of toxicity. (See, for example, Press Release 00-02 from the National Institute of Environmental Health Sciences, released February 29, 2000, available at http://www.niehs.nih.gov/oc/news/toxchip.htm.) Therefore, it is important and desirable in toxicological screening using toxicant signatures to include aU expressed gene sequences. En one embodiment, the toxicity of a test compound is assessed by treating a biological sample containing nucleic acids with the test compound. Nucleic acids that are expressed in the treated biological sample are hybridized with one or more probes specific to the polynucleotides of the present invention, so that transcript levels corresponding to the polynucleotides of the present invention may be quantified. The transcript levels in the treated biological sample are compared with levels in an untreated biological sample. Differences in the transcript levels between the two samples are indicative of a toxic response caused by the test compound in the treated sample. Another particular embodiment relates to the use of the polypeptide sequences of the present invention to analyze the proteome of a tissue or ceU type. The term proteome refers to the global pattern of protein expression in a particular tissue or cell type. Each protein component of a proteome can be subjected individuaUy to further analysis. Proteome expression patterns, or profiles, are analyzed by quantifying the number of expressed proteins and their relative abundance under given conditions and at a given time. A profile of a ceU's proteome may thus be generated by separating and analyzing the polypeptides of a particular tissue or ceU type. En one embodiment, the separation is achieved using two-dimensional gel electrophoresis, in which proteins from a sample are separated by isoelecfric focusing in the first dimension, and then according to molecular weight by sodium dodecyl sulfate slab gel electrophoresis in the second dimension (Steiner and Anderson, supra). The proteins are visuaMzed in the gel as discrete and uniquely positioned spots, typicaUy by staining the gel with an agent such as Coomassie Blue or silver or fluorescent stains. The optical density of each protein spot is generaUy proportional to the level of the protein in the sample. The optical densities of equivalently positioned protein spots from different samples, for example, from biological samples either freated or untreated with a test compound or therapeutic agent, are compared to identify any changes in protein spot density related to the freatment. The proteins in the spots are partiaUy sequenced using, for example, standard methods employing chemical or enzymatic cleavage foUowed by mass spectrometry. The identity of the protein in a spot may be determined by comparing its partial sequence, preferably of at least 5 contiguous amino acid residues, to the polypeptide sequences of the present invention. In some cases, further sequence data may be obtained for definitive protein identification. A proteomic profile may also be generated using antibodies specific for NZMS to quantify the levels of NZMS expression. In one embodiment, the antibodies are used as elements on a microarray, and protein expression levels are quantified by exposing the microarray to the sample and detecting the levels of protein bound to each array element (Lueking, A. et al. (1999) Anal. Biochem. 270:103- ll l; Mendoze, L.G. et al. (1999) Biotechniques 27:778-788). Detection may be performed by a variety of methods known in the art, for example, by reacting the proteins in the sample with a thiol- or amino-reactive fluorescent compound and detecting the amount of fluorescence bound at each array element. Toxicant signatures at the proteome level are also useful for toxicological screening, and should be analyzed in paraUel with toxicant signatures at the franscript level. There is a poor correlation between franscript and protein abundances for some proteins in some tissues (Anderson, N.L. and J. Seilhamer (1997) Electrophoresis 18:533-537), so proteome toxicant signatures may be useful in the analysis of compounds which do not significantly affect the franscript image, but which alter the proteomic profile. In addition, the analysis of transcripts in body fluids is difficult, due to rapid degradation of mRNA, so proteomic profiling may be more reMable and informative in such cases. In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins that are expressed in the treated biological sample are separated so that the amount of each protein can be quantified. The amount of each protein is compared to the amount of the corresponding protein in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample. Individual proteins are identified by sequencing the amino acid residues of the individual proteins and comparing these partial sequences to the polypeptides of the present invention. In another embodiment, the toxicity of a test compound is assessed by treating a biological sample containing proteins with the test compound. Proteins from the biological sample are incubated with antibodies specific to the polypeptides of the present invention. The amount of protein recognized by the antibodies is quantified. The amount of protein in the treated biological sample is compared with the amount in an untreated biological sample. A difference in the amount of protein between the two samples is indicative of a toxic response to the test compound in the treated sample. Microarrays may be prepared, used, and analyzed using methods known in the art. (See, e.g., Brennan, T.M. et al. (1995) U.S. Patent No. 5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA 93:10614-10619; Baldeschweiler et al. (1995) PCT appMcation W095/251116; Shalon, D. et al. (1995) PCT appMcation WO95/35505; HeUer, R.A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150-2155; and Heller, M.J. et al. (1997) U.S. Patent No. 5,605,662.) Various types of microarrays are weU known and thoroughly described in DNA Microarrays: A Practical Approach, M. Schena, ed. (1999) Oxford University Press, I-ondon, hereby expressly incoφorated by reference. In another embodiment of the invention, nucleic acid sequences encoding NZMS may be used to generate hybridization probes useful in mapping the naturaUy occurring genomic sequence. Either coding or noncoding sequences may be used, and in some instances, noncoding sequences may be preferable over coding sequences. For example, conservation of a coding sequence among members of a multi-gene family may potentially cause undesired cross hybridization during chromosomal mapping. The sequences may be mapped to a particular chromosome, to a specific region of a chromosome, or to artificial chromosome constructions, e.g., human artificial chromosomes (HACs), yeast artificial chromosomes (YACs), bacterial artificial chromosomes (BACs), bacterial PI constructions, or single chromosome cDNA Mbraries. (See, e.g., Harrington, J.J. et al. (1997) Nat. Genet. 15:345-355; Price, CM. (1993) Blood Rev. 7:127-134; and Trask, BJ. (1991) Trends Genet. 7:149-154.) Once mapped, the nucleic acid sequences of the invention may be used to develop genetic Mnkage maps, for example, which correlate the inheritance of a disease state with the inheritance of a particular chromosome region or restriction fragment length polymoφhism (RFLP). (See, for example, Lander, E.S. and D. Botstein (1986) Proc. Natl. Acad. Sci. USA 83:7353-7357.) Fluorescent in situ hybridization (FISH) may be correlated with other physical and genetic map data. (See, e.g., Heinz-Ulrich, et al. (1995) in Meyers, supra, pp. 965-968.) Examples of genetic map data can be found in various scientific journals or at the OnMne MendeMan Inheritance in Man (OMEvI) World Wide Web site. Correlation between the location of the gene encoding NZMS on a physical map and a specific disorder, or a predisposition to a specific disorder, may help define the region of DNA associated with that disorder and thus may further positional cloning efforts. In situ hybridization of chromosomal preparations and physical mapping techniques, such as Mnkage analysis using estabMshed chromosomal markers, may be used for extending genetic maps. Often the placement of a gene on the chromosome of another mammaMan species, such as mouse, may reveal associated markers even if the exact chromosomal locus is not known. This information is valuable to investigators searching for disease genes using positional cloning or other gene discovery techniques. Once the gene or genes responsible for a disease or syndrome have been crudely locaMzed by genetic Mnkage to a particular genomic region, e.g., ataxia-telangiectasia to 1 lq22-23, any sequences mapping to that area may represent associated or regulatory genes for further investigation. (See, e.g., Gatti, R.A. et al. (1988) Nature 336:577-580.) The nucleotide sequence of the instant invention may also be used to detect differences in the chromosomal location due to franslocation, inversion, etc., among normal, carrier, or affected individuals. In another embodiment of the invention, NZMS, its catalytic or immunogenic fragments, or oMgopeptides thereof can be used for screening Mbraries of compounds in any of a variety of drug screening techniques. The fragment employed in such screening may be free in solution, affixed to a soMd support, borne on a ceU surface, or located infraceUularly. The formation of binding complexes between NZMS and the agent being tested may be measured. Another technique for drag screening provides for high throughput screening of compounds having suitable binding affinity to the protein of interest. (See, e.g., Geysen, et al. (1984) PCT appMcation WO84/03564.) In this method, large numbers of different smaU test compounds are synthesized on a soMd substrate. The test compounds are reacted with NZMS, or fragments thereof, and washed. Bound NZMS is then detected by methods weU known in the art. Purified NZMS can also be coated directly onto plates for use in the aforementioned drag screening techniques. Alternatively, non-neutraUzing antibodies can be used to capture the peptide and immobilize it on a soMd support. In another embodiment, one may use competitive drag screening assays in which neutraMzing antibodies capable of binding NZMS specificaUy compete with a test compound for binding NZMS. In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with NZMS. In additional embodiments, the nucleotide sequences which encode NZMS may be used in any molecular biology techniques that have yet to be developed, provided the new techniques rely on properties of nucleotide sequences that are currently known, including, but not Mmited to, such properties as the triplet genetic code and specific base pair interactions. Without further elaboration, it is beMeved that one skiUed in the art can, using the preceding description, utiMze the present invention to its fuUest extent. The foUowing preferred specific embodiments are, therefore, to be construed as merely illustrative, and not Mmitative of the remainder of the disclosure in any way whatsoever. The disclosures of aU patents, appMcations, and pubMcations mentioned above and below, including U.S. Ser. No. 60/251,824, U.S. Ser. No. 60/255,773, U.S. Ser. No. 60/254,312, U.S. Ser. No. 60/256,188, U.S. Ser. No. 60/257,488, U.S. Ser. No. 60/262,839, U.S. Ser. No. 60/264,402, U.S. Ser. No. 60/255,940, and U.S. Ser. No. [Attorney Docket No. PF-1245 P, filed October 19, 2001] are hereby expressly incoφorated by reference. EXAMPLES I. Construction of cDNA Libraries Incyte cDNAs were derived from cDNA Mbraries described in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto CA) and shown in Table 4, column 2. Some tissues were homogenized and lysed in guanidinium isothiocyanate, while others were homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TREZOL (Life Technologies), a monophasic solution of phenol and guanidine isothiocyanate. The resulting lysates were cenfrifuged over CsCl cushions or extracted with chloroform. RNA was precipitated from the lysates with either isopropanol or sodium acetate and ethanol, or by other routine methods. Phenol extraction and precipitation of RNA were repeated as necessary to increase RNA purity. In some cases, RNA was treated with DNase. For most Mbraries, poly(A)+ RNA was isolated using oMgo d(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles (QIAGEN, Chatsworth CA), or an OLIGOTEX mRNA purification kit (QIAGEN). Alternatively, RNA was isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA purification kit (Ambion, Austin TX). In some cases, Sfratagene was provided with RNA and constmcted the corresponding cDNA Mbraries. Otherwise, cDNA was synthesized and cDNA Mbraries were constructed with the UNIZAP vector system (Sfratagene) or SUPERSCRIPT plasmid system (Life Technologies), using the recommended procedures or similar methods known in the art. (See, e.g., Ausubel, 1997, supra, units 5.1-6.6.) Reverse transcription was initiated using oMgo d(T) or random primers. Synthetic oMgonucleotide adapters were Mgated to double stranded cDNA, and the cDNA was digested with the appropriate restriction enzyme or enzymes. For most Mbraries, the cDNA was size-selected (300- 1000 bp) using SEPHACRYL S1000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Pharmacia Biotech) or preparative agarose gel electrophoresis. cDNAs were Mgated into compatible restriction enzyme sites of the polyMnker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Sfratagene), PSPORT1 plasmid (Life Technologies), PCDNA2.1 plasmid (Invifrogen, Carlsbad CA), PBK-CMV plasmid (Sfratagene), PCR2-TOPOTA plasmid (ftivittogen), PCMV-ICIS plasmid (Sfratagene), pIGEN (Incyte Genomics, Palo Alto CA), or pESfCY (Incyte Genomics), or derivatives thereof. Recombinant plasmids were fransformed into competent E. coM ceUs including XLI -Blue, XLl-BlueMRF, or SOLR from Sfratagene or DH5α, DH10B, or ElectroMAX DH10B from Life Technologies. II. Isolation of cDNA Clones Plasmids obtained as described in Example I were recovered from host ceUs by in vivo excision using the UNIZAP vector system (Sfratagene) or by ceU lysis. Plasmids were purified using at least one of the foUowing: a Magic or WIZARD Minipreps DNA purification system (Promega); an AGTC Miniprep purification kit (Edge Biosystems, Gaithersburg MD); and QIAWELL 8 Plasmid, QIAWELL 8 Plus Plasmid, QIAWELL 8 Ultra Plasmid purification systems or the R.E.A.L. PREP 96 plasmid purification kit from QIAGEN. FoUowing precipitation, plasmids were resuspended in 0.1 ml of distiUed water and stored, with or without lyophiMzation, at 4°C Alternatively, plasmid DNA was ampMfied from host ceU lysates using direct Mnk PCR in a high-throughput format (Rao, V.B. (1994) Anal. Biochem. 216:1-14). Host ceU lysis and thermal cycMng steps were carried out in a single reaction mixture. Samples were processed and stored in 384- well plates, and the concentration of ampMfied plasmid DNA was quantified fluorometricaUy using PICOGREEN dye (Molecular Probes, Eugene OR) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland). III. Sequencing and Analysis Incyte cDNA recovered in plasmids as described in Example II were sequenced as foUows. Sequencing reactions were processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 (AppMed Biosystems) thermal cycler or the PTC-200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific) or the MICROLAB 2200 (Hamilton) Mquid fransfer system. cDNA sequencing reactions were prepared using reagents provided by Amersham Pharmacia Biotech or suppMed in ABI sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (AppMed Biosystems). Elecfrophoretic separation of cDNA sequencing reactions and detection of labeled polynucleotides were carried out using the MEGABACE 1000 DNA sequencing system (Molecular Dynamics); the ABI PRISM 373 or 377 sequencing system (AppMed Biosystems) in conjunction with standard ABI protocols and base calling software; or other sequence analysis systems known in the art. Reading frames within the cDNA sequences were identified using standard methods (reviewed in Ausubel, 1997, supra, unit 7.7). Some of the cDNA sequences were selected for extension using the techniques disclosed in Example VUI. The polynucleotide sequences derived from Incyte cDNAs were vaMdated by removing vector, Mnker, and poly(A) sequences and by masking ambiguous bases, using algorithms and programs based on BLAST, dynamic programming, and dinucleotide nearest neighbor analysis. The Incyte cDNA sequences or translations thereof were then queried against a selection of pubMc databases such as the GenBank primate, rodent, mammaMan, vertebrate, and eukaryote databases, and BLOCKS, PRINTS, DOMO, PRODOM; PROTEOME databases with sequences from Homo sapiens, Rattus norvegicus, Mus musculus, Caenorhabditis elegans, Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Candida albicans (Incyte Genomics, Palo Alto CA); and hidden Markov model (HMM)-based protein family databases such as PFAM. (HMM is a probabiMstic approach which analyzes consensus primary structures of gene famiMes. See, for example, Eddy, S.R. (1996) Curr. Opin. Struct. Biol. 6:361-365.) The queries were performed using programs based on BLAST, FASTA, BLIMPS, and HMMER. The Incyte cDNA sequences were assembled to produce full length polynucleotide sequences. Alternatively, GenBank cDNAs, GenBank ESTs, stitched sequences, stretched sequences, or Genscan-predicted coding sequences (see Examples IV and V) were used to extend Incyte cDNA assemblages to full length. Assembly was performed using programs based on Phred, Phrap, and Consed, and cDNA assemblages were screened for open reading frames using programs based on GeneMark, BLAST, and FASTA. The fuU length polynucleotide sequences were translated to derive the corresponding fuU length polypeptide sequences. Alternatively, a polypeptide of the invention may begin at any of the methionine residues of the full length translated polypeptide. Full length polypeptide sequences were subsequently analyzed by querying against databases such as the GenBank protein databases (genpept), SwissProt, the PROTEOME databases, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, and hidden Markov model (HMM)-based protein family databases such as PFAM. FuU length polynucleotide sequences are also analyzed using MACDNASIS PRO software (Hitachi Software Engineering, South San Francisco CA) and LASERGENE software (DNASTAR). Polynucleotide and polypeptide sequence aMgnments are generated using default parameters specified by the CLUSTAL algorithm as incoφorated into the MEGALIGN multisequence aMgnment program (DNASTAR), which also calculates the percent identity between aMgned sequences. Table 7 summarizes the tools, programs, and algorithms used for the analysis and assembly of Incyte cDNA and fuU length sequences and provides appMcable descriptions, references, and threshold parameters. The first column of Table 7 shows the tools, programs, and algorithms used, the second column provides brief descriptions thereof, the third column presents appropriate references, aU of which are incoφorated by reference herein in their entirety, and the fourth column presents, where appMcable, the scores, probabiMty values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score or the lower the probabiMty value, the greater the identity between two sequences). The programs described above for the assembly and analysis of fuU length polynucleotide and polypeptide sequences were also used to identify polynucleotide sequence fragments from SEQ ID NO: 19-36. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and ampMfication technologies are described in Table 4, column 2. IV. Identification and Editing of Coding Sequences from Genomic DNA Putative enzymes were initially identified by running the Genscan gene identification program against pubMc genomic sequence databases (e.g., gbpri and gbhtg). Genscan is a general-purpose gene identification program which analyzes genomic DNA sequences from a variety of organisms (See Burge, C and S. KarMn (1997) J. Mol. Biol. 268:78-94, and Burge, C. and S. KarMn (1998) Curr. Opin. Struct. Biol. 8:346-354). The program concatenates predicted exons to form an assembled cDNA sequence extending from a methionine to a stop codon. The output of Genscan is a FASTA , database of polynucleotide and polypeptide sequences. The maximum range of sequence for Genscan to analyze at once was set to 30 kb. To determine which of these Genscan predicted cDNA sequences encode enzymes, the encoded polypeptides were analyzed by querying against PFAM models for enzymes. Potential enzymes were also identified by homology to Incyte cDNA sequences that had been annotated as enzymes. These selected Genscan-predicted sequences were then compared by BLAST analysis to the genpept and gbpri pubMc databases. Where necessary, the Genscan-predicted sequences were then edited by comparison to the top BLAST hit from genpept to correct errors in the sequence predicted by Genscan, such as extra or omitted exons. BLAST analysis was also used to find any Incyte cDNA or pubMc cDNA coverage of the Genscan-predicted sequences, thus providing evidence for transcription. When Incyte cDNA coverage was available, this information was used to correct or confirm the Genscan predicted sequence. FuU length polynucleotide sequences were obtained by assembhng Genscan-predicted coding sequences with Incyte cDNA sequences and/or pubMc cDNA sequences using the assembly process described in Example H. Alternatively, fuU length polynucleotide sequences were derived entirely from edited or unedited Genscan-predicted coding sequences. V. Assembly of Genomic Sequence Data with cDNA Sequence Data "Stitched" Sequences Partial cDNA sequences were extended with exons predicted by the Genscan gene identification program described in Example IV. Partial cDNAs assembled as described in Example HI were mapped to genomic DNA and parsed into clusters containing related cDNAs and Genscan exon predictions from one or more genomic sequences. Each cluster was analyzed using an algorithm based on graph theory and dynamic programming to integrate cDNA and genomic information, generating possible spMce variants that were subsequently confirmed, edited, or extended to create a fuU length sequence. Sequence intervals in which the entire length of the interval was present on more than one sequence in the cluster were identified, and intervals thus identified were considered to be equivalent by transitivity. For example, if an interval was present on a cDNA and two genomic sequences, then aU three intervals were considered to be equivalent. This process allows unrelated but consecutive genomic sequences to be brought together, bridged by cDNA sequence. Intervals thus identified were then "stitched" together by the stitching algorithm in the order that they appear along their parent sequences to generate the longest possible sequence, as weU as sequence variants. Linkages between intervals which proceed along one type of parent sequence (cDNA to cDNA or genomic sequence to genomic sequence) were given preference over Unkages which change parent type (cDNA to genomic sequence). The resultant stitched sequences were translated and compared , by BLAST analysis to the genpept and gbpri pubMc databases. Incorrect exons predicted by Genscan were corrected by comparison to the top BLAST hit from genpept. Sequences were further extended with additional cDNA sequences, or by inspection of genomic DNA, when necessary. "Stretched" Sequences Partial DNA sequences were extended to full length with an algorithm based on BLAST analysis. First, partial cDNAs assembled as described in Example III were queried against pubMc databases such as the GenBank primate, rodent, mammaMan, vertebrate, and eukaryote databases using the BLAST program. The nearest GenBank protein homolog was then compared by BLAST analysis to either Incyte cDNA sequences or GenScan exon predicted sequences described in Example IV. A chimeric protein was generated by using the resultant high-scoring segment pairs (HSPs) to map the translated sequences onto the GenBank protein homolog. Insertions or deletions may occur in the chimeric protein with respect to the original GenBank protein homolog. The GenBank protein homolog, the chimeric protein, or both were used as probes to search for homologous genomic sequences from the pubMc human genome databases. Partial DNA sequences were therefore "stretched" or extended by the addition of homologous genomic sequences. The resultant stretched sequences were examined to determine whether it contained a complete gene. VI. Chromosomal Mapping of NZMS Encoding Polynucleotides The sequences which were used to assemble SEQ ID NO: 19-36 were compared with sequences from the Incyte LIFESEQ database and pubMc domain databases using BLAST and other implementations of the Smith- Waterman algorithm. Sequences from these databases that matched SEQ ID NO :19-36 were assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as Phrap (Table 7). Radiation hybrid and genetic mapping data available from pubMc resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome Research (WIGR), and Genethon were used to determine if any of the clustered sequences had been previously mapped. Inclusion of a mapped sequence in a cluster resulted in the assignment of aU sequences of that cluster, including its particular SEQ ID NO:, to that map location. Map locations are represented by ranges, or intervals, of human chromosomes. The map position of an interval, in centiMorgans, is measured relative to the terminus of the chromosome's p- arm. (The centiMorgan (cM) is a unit of measurement based on recombination frequencies between chromosomal markers. On average, 1 cM is roughly equivalent to 1 megabase (Mb) of DNA in humans, although this can vary widely due to hot and cold spots of recombination.) The cM distances are based on genetic markers mapped by Genethon which provide boundaries for radiation hybrid markers whose sequences were included in each of the clusters. Human genome maps and other resources available to the pubMc, such as the NCBI "GeneMap'99" World Wide Web site (http://www.ncbi.nlm.nih.gov/genemap/), can be employed to determine if previously identified disease genes map within or in proximity to the intervals indicated above. In this manner, SEQ ID NO:31 was mapped to chromosome 8 within the interval from 64.60 to 78.80 centiMorgans. In this manner, SEQ ID NO:32 was mapped to chromosome 11 within the interval from 92.50 to 96.20 centiMorgans. VII. Analysis of Polynucleotide Expression Northern analysis is a laboratory technique used to detect the presence of a franscript of a gene and involves the hybridization of a labeled nucleotide sequence to a membrane on which RNAs from a particular ceU type or tissue have been bound. (See, e.g., Sambrook, supra, ch. 7; Ausubel (1995) supra, ch. 4 and 16.) Analogous computer techniques applying BLAST were used to search for identical or related molecules in cDNA databases such as GenBank or LIFESEQ (Incyte Genomics). This analysis is much faster than multiple membrane-based hybridizations. In addition, the sensitivity of the computer search can be modified to determine whether any particular match is categorized as exact or similar. The basis of the search is the product score, which is defined as: BLAST Score x Percent Identity 5 x minimum {length(Seq. 1), length(Seq. 2)} The product score takes into account both the degree of similarity between two sequences and the length of the sequence match. The product score is a normaMzed value between 0 and 100, and is calculated as foUows: the BLAST score is multipMed by the percent nucleotide identity and the product is divided by (5 times the length of the shorter of the two sequences). The BLAST score is calculated by assigning a score of +5 for every base that matches in a high-scoring segment pair (HSP), and -4 for every mismatch. Two sequences may share more than one HSP (separated by gaps). If there is more than one HSP, then the pair with the highest BLAST score is used to calculate the product score. The product score represents a balance between fractional overlap and quaMty in a BLAST aMgnment. For example, a product score of 100 is produced only for 100% identity over the entire length of the shorter of the two sequences being compared. A product score of 70 is produced either by 100% identity and 70% overlap at one end, or by 88% identity and 100% overlap at the other. A product score of 50 is produced either by 100% identity and 50% overlap at one end, or 79% identity and 100% overlap. Alternatively, polynucleotide sequences encoding NZMS are analyzed with respect to the tissue sources from which they were derived. For example, some fuU length sequences are assembled, at least in part, with overlapping Incyte cDNA sequences (see Example IH). Each cDNA sequence is derived from a cDNA Mbrary constructed from a human tissue. Each human tissue is classified into one of the foUowing organ/tissue categories: cardiovascular system; connective tissue; digestive system; embryonic structures; endocrine system; exocrine glands; genitaUa, female; genitaMa, male; germ cells; hemic and immune system; Mver; musculoskeletal system; nervous system; pancreas; respiratory system; sense organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. The number of Mbraries in each category is counted and divided by the total number of Mbraries across aU categories. Similarly, each human tissue is classified into one of the foUowing disease/condition categories: cancer, ceU Mne, developmental, inflammation, neurological, trauma, cardiovascular, pooled, and other, and the number of Mbraries in each category is counted and divided by the total number of Mbraries across aU categories. The resulting percentages reflect the tissue- and disease-specific expression of cDNA encoding NZMS. cDNA sequences and cDNA Mbraiy/tissue information are found in the LIFESEQ GOLD database (Incyte Genomics, Palo Alto CA). VIII. Extension of NZMS Encoding Polynucleotides FuU length polynucleotide sequences were also produced by extension of an appropriate fragment of the full length molecule using oMgonucleotide primers designed from this fragment. One primer was synthesized to initiate 5' extension of the known fragment, and the other primer was synthesized to initiate 3 ' extension of the known fragment. The initial primers were designed using OLIGO 4.06 software (National Biosciences), or another appropriate program, to be about 22 to 30 nucleotides in length, to have a GC content of about 50% or more, and to anneal to the target sequence at temperatures of about 68 ° C to about 72 ° C Any stretch of nucleotides which would result in haiφin stractures and primer-primer dimerizations was avoided. Selected human cDNA Mbraries were used to extend the sequence. If more than one extension was necessary or desired, additional or nested sets of primers were designed. High fideMty ampMfication was obtained by PCR using methods weU known in the art. PCR was performed in 96-weU plates using the PTC-200 thermal cycler (MJ Research, Inc.). The reaction mix contained DNA template, 200 nmol of each primer, reaction buffer containing Mg 2+ , (NH 4 ) 2 S0 4 , and 2-mercaptoethanol, Taq DNA polymerase (Amersham Pharmacia Biotech), ELONGASE enzyme (Life Technologies), and Pfu DNA polymerase (Sfratagene), with the foUowing parameters for primer pair PCI A and PCI B: Step 1 : 94°C, 3 min; Step 2: 94°C, 15 sec; Step 3: 60°C, 1 min; Step 4: 68°C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68°C, 5 min; Step 7: storage at 4°C In the alternative, the parameters for primer pair T7 and SK+ were as foUows: Step 1 : 94 °C, , 3 min; Step 2: 94°C, 15 sec; Step 3: 57°C, 1 min; Step 4: 68°C, 2 min; Step 5: Steps 2, 3, and 4 repeated 20 times; Step 6: 68 °C, 5 min; Step 7: storage at 4°C The concentration of DNA in each weU was determined by dispensing 100 μl PICOGREEN quantitation reagent (0.25% (v/v) PICOGREEN; Molecular Probes, Eugene OR) dissolved in IX TE and 0.5 μl of undiluted PCR product into each weU of an opaque fluorimeter plate (Corning Costar, Acton MA), aUowing the DNA to bind to the reagent. The plate was scanned in a Fluoroskan U (Labsystems Oy, Helsinki, Finland) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 l to 10 μl aUquot of the reaction mixture was analyzed by electrophoresis on a 1 % agarose gel to determine which reactions were successful in extending the sequence. The extended nucleotides were desalted and concentrated, transferred to 384-weU plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison WI), and sonicated or sheared prior to reUgation into pUC 18 vector (Amersham Pharmacia Biotech). For shotgun sequencing, the digested nucleotides were separated on low concentration (0.6 to 0.8%) agarose gels, fragments were excised, and agar digested with Agar ACE (Promega). Extended clones were reMgated using T4 Mgase (New England Biolabs, Beverly MA) into pUC 18 vector (Amersham Pharmacia Biotech), freated with Pfu DNA polymerase (Sfratagene) to fill-in restriction site overhangs, and transfected into competent E. coM ceUs. Transformed ceUs were selected on antibiotic-containing media, and individual colonies were picked and cultured overnight at 37 °C in 384- weU plates in LB/2x carb Mquid media. The ceUs were lysed, and DNA was ampMfied by PCR using Taq DNA polymerase (Amersham Pharmacia Biotech) and Pfu DNA polymerase (Sfratagene) with the foUowing parameters: Step 1: 94°C, 3 min; Step 2: 94°C, 15 sec; Step 3: 60°C, 1 min; Step 4: 72°C, 2 min; Step 5: steps 2, 3, and 4 repeated 29 times; Step 6: 72°C, 5 min; Step 7: storage at 4°C DNA was quantified by PICOGREEN reagent (Molecular Probes) as described above. Samples with low DNA recoveries were reampMfied using the same conditions as described above. Samples were diluted with 20% dimethysulfoxide (1 :2, v/v), and sequenced using DYENAMIC energy fransfer sequencing primers and the DYENAMIC DIRECT kit (Amersham Pharmacia Biotech) or the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (AppMed Biosystems). In Mke manner, full length polynucleotide sequences are verified using the above procedure or are used to obtain 5' regulatory sequences using the above procedure along with oMgonucleotides designed for such extension, and an appropriate genomic Mbrary. IX. Labeling and Use of Individual Hybridization Probes Hybridization probes derived from SEQ ED NO :19-36 are employed to screen cDNAs, genomic DNAs, or mRNAs. Although the labehng of oMgonucleotides, consisting of about 20 base pairs, is specificaUy described, essentiaUy the same procedure is used with larger nucleotide fragments. OMgonucleotides are designed using state-of-the-art software such as OLIGO 4.06 software (National Biosciences) and labeled by combining 50 pmol of each oMgomer, 250 μCi of [γ- 32 P] adenosine triphosphate (Amersham Pharmacia Biotech), and T4 polynucleotide kinase (DuPont NEN, Boston MA). The labeled oMgonucleotides are substantiaUy purified using a SEPHADEX G-25 superfine size exclusion dextran bead column (Amersham Pharmacia Biotech). An aUquot containing IO 7 counts per minute of the labeled probe is used in a typical membrane-based hybridization analysis of human genomic DNA digested with one of the foUowing endonucleases: Ase I, Bgl H, Eco RI, Pst I, Xba I, or Pvu H (DuPont NEN). The DNA from each digest is fractionated on a 0.7% agarose gel and transferred to nylon membranes (Nytran Plus, Schleicher & SchueU, Durham NH). Hybridization is carried out for 16 hours at 40 °C To remove nonspecific signals, blots are sequentiaUy washed at room temperature under conditions of up to, for example, 0.1 x saMne sodium citrate and 0.5% sodium dodecyl sulfate. Hybridization patterns are visuaMzed using autoradiography or an alternative imaging means and compared. X. Microarrays The Mnkage or synthesis of array elements upon a microarray can be achieved utiMzing photoMthography, piezoelectric printing (ink-jet printing, See, e.g., Baldeschweiler, supra.), mechanical microspotting technologies, and derivatives thereof. The substrate in each of the aforementioned technologies should be uniform and soMd with a non-porous surface (Schena (1999), supra). Suggested substrates include siMcon, siMca, glass sMdes, glass chips, and siMcon wafers. Alternatively, a procedure analogous to a dot or slot blot may also be used to arrange and Mnk elements to the surface of a substrate using thermal, UV, chemical, or mechanical bonding procedures. A typical array may be produced using available methods and machines weU known to those of ordinary skiU in the art and may contain any appropriate number of elements. (See, e.g., Schena, M. et al. (1995) Science 270:467-470; Shalon, D. et al. (1996) Genome Res. 6:639-645; MarshaU, A. and J. Hodgson (1998) Nat. Biotechnol. 16:27-31.) FuU length cDNAs, Expressed Sequence Tags (ESTs), or fragments or oMgomers thereof may comprise the elements of the microarray. Fragments or oMgomers suitable for hybridization can be selected using software well known in the art such as LASERGENE software (DNASTAR). The array elements are hybridized with polynucleotides in a biological sample. The polynucleotides in the biological sample are conjugated to a fluorescent label or other molecular tag for ease of detection. After hybridization, nonhybridized nucleotides from the biological sample are removed, and a fluorescence scanner is used to detect hybridization at each array element. Alternatively, laser desorbtion and mass spectrometry may be used for detection of hybridization. The degree of complementarity and the relative abundance of each polynucleotide which hybridizes to an element on the microarray may be assessed. In one embodiment, microarray preparation and usage is described in detail below. Tissue or Cell Sample Preparation Total RNA is isolated from tissue samples using the guanidinium thiocyanate method and poly(A) + RNA is purified using the oMgo-(dT) ceUulose method. Each poly(A) + RNA sample is reverse franscribed using MMLV reverse-franscriptase, 0.05 pg/μl oUgo-(dT) primer (21mer), IX first strand buffer, 0.03 units/μl RNase inhibitor, 500 μM dATP, 500 μM dGTP, 500 μM dTTP, 40 μM dCTP, 40 μM dCTP-Cy3 (BDS) or dCTP-Cy5 (Amersham Pharmacia Biotech). The reverse transcription reaction is performed in a 25 ml volume containing 200 ng poly(A) + RNA with GEMB RIGHT kits (Incyte). Specific confrol poly(A) + RNAs are synthesized by in vifro transcription from non-coding yeast genomic DNA. After incubation at 37° C for 2 hr, each reaction sample (one with Cy3 and another with Cy5 labeMng) is freated with 2.5 ml of 0.5M sodium hydroxide and incubated for 20 minutes at 85° C to the stop the reaction and degrade the RNA. Samples are purified using two successive CHROMA SPIN 30 gel filtration spin columns (CLONTECH Laboratories, Inc. (CLONTECH), Palo Alto CA) and after combining, both reaction samples are ethanol precipitated using 1 ml of glycogen (1 mg/ml), 60 ml sodium acetate, and 300 ml of 100% ethanol. The sample is then dried to completion using a SpeedVAC (Savant Instruments Inc., HolbrookNY) and resuspended in 14 μl 5X SSC/0.2% SDS. Microarray Preparation Sequences of the present invention are used to generate array elements. Each array element is ampMfied from bacterial ceUs containing vectors with cloned cDNA inserts. PCR ampMfication uses primers complementary to the vector sequences flanking the cDNA insert. Array elements are ampMfied in thirty cycles of PCR from an initial quantity of 1-2 ng to a final quantity greater than 5 μg. AmpMfied array elements are then pmified using SEPHACRYL-400 (Amersham Pharmacia Biotech). Purified array elements are immobiMzed on polymer-coated glass sMdes. Glass microscope sMdes (Corning) are cleaned by ultrasound in 0.1 % SDS and acetone, with extensive distilled water washes between and after treatments. Glass sMdes are etched in 4% hydrofluoric acid (VWR Scientific Products Coφoration (VWR), West Chester PA), washed extensively in distiUed water, and coated with 0.05% aminopropyl silane (Sigma) in 95% ethanol. Coated sMdes are cured in a 110°C oven. Array elements are appMed to the coated glass substrate using a procedure described in U.S. Patent No. 5,807,522, incoφorated herein by reference. 1 μl of the array element DNA, at an average concentration of 100 ng/μl, is loaded into the open capillary printing element by a high-speed robotic apparatus. The apparatus then deposits about 5 nl of array element sample per sMde. Microarrays are UV-crossMnked using a STRATALINKER UV-crossMnker (Sfratagene). Microarrays are washed at room temperature once in 0.2% SDS and three times in distiUed water. Non-specific binding sites are blocked by incubation of microarrays in 0.2% casein in phosphate buffered saUne (PBS) (Tropix, Inc., Bedford MA) for 30 minutes at 60° C foUowed by washes in 0.2% SDS and distiUed water as before. Hybridization Hybridization reactions contain 9 μl of sample mixture consisting of 0.2 μg each of Cy3 and Cy5 labeled cDNA synthesis products in 5X SSC, 0.2% SDS hybridization buffer. The sample mixture is heated to 65° C for 5 minutes and is aUquoted onto the microarray surface and covered with an 1.8 cm 2 coversMp. The arrays are transferred to a wateφroof chamber having a cavity just sMghtly larger than a microscope sMde. The chamber is kept at 100% humidity intemaUy by the addition of 140 μl of 5X SSC in a comer of the chamber. The chamber containing the arrays is incubated for about 6.5 hours at 60° C. The arrays are washed for 10 min at 45° C in a first wash buffer (IX SSC, 0.1 % SDS), three times for 10 minutes each at 45° C in a second wash buffer (O.lX SSC), and dried. Detection Reporter-labeled hybridization complexes are detected with a microscope equipped with an Innova 70 mixed gas 10 W laser (Coherent, Inc., Santa Clara CA) capable of generating spectral Mnes at 488 nm for excitation of Cy3 and at 632 nm for excitation of Cy5. The excitation laser Mght is focused on the array using a 20X microscope objective (Nikon, Inc., MelviUe NY). The sMde containing the array is placed on a computer-confroUed X-Y stage on the microscope and raster- scanned past the objective. The 1.8 cm x 1.8 cm array used in the present example is scanned with a resolution of 20 micrometers. In two separate scans, a mixed gas multiUne laser excites the two fluorophores sequentiaUy. Emitted Mght is spMt, based on wavelength, into two photomultipMer tube detectors (PMT R1477, Hamamatsu Photonics Systems, Bridgewater NJ) corresponding to the two fluorophores. Appropriate filters positioned between the array and the photomultipMer tubes are used to filter the signals. The emission maxima of the fluorophores used are 565 nm for Cy3 and 650 nm for Cy5. Each array is typicaUy scanned twice, one scan per fluorophore using the appropriate filters at the laser source, although the apparatus is capable of recording the spectra from both fluorophores simultaneously. The sensitivity of the scans is typically caUbrated using the signal intensity generated by a cDNA control species added to the sample mixture at a known concentration. A specific location on the array contains a complementary DNA sequence, aUowing the intensity of the signal at that location to be correlated with a weight ratio of hybridizing species of 1 : 100,000. When two samples from different sources (e.g., representing test and control ceUs), each labeled with a different fluorophore, are hybridized to a single array for the pvupose of identifying genes that are differentiaUy expressed, the caUbration is done by labeMng samples of the caMbrating cDNA with the two fluorophores and adding identical amounts of each to the hybridization mixture. The output of the photomultipMer tube is digitized using a 12-bit RTI-835H analog-to-digital (AID) conversion board (Analog Devices, Inc., Norwood MA) instaUed in an EBM-compatible PC computer. The digitized data are displayed as an image where the signal intensity is mapped using a Mnear 20-color transformation to a pseudocolor scale ranging from blue (low signal) to red (high signal). The data is also analyzed quantitatively. Where two different fluorophores are excited and measured simultaneously, the data are first corrected for optical crosstalk (due to overlapping emission spectra) between the fluorophores using each fluorophore's emission spectrum. A grid is superimposed over the fluorescence signal image such that the signal from each spot is centered in each element of the grid. The fluorescence signal within each element is then integrated to obtain a numerical value corresponding to the average intensity of the signal. The software used for signal analysis is the GEMTOOLS gene expression analysis program (Incyte). XL Complementary Polynucleotides Sequences complementary to the NZMS-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturaUy occurring NZMS. Although use of oMgonucleotides comprising from about 15 to 30 base pairs is described, essentiaUy the same procedure is used with smaller or with larger sequence fragments. Appropriate oMgonucleotides are designed using OLIGO 4.06 software (National Biosciences) and the coding sequence of NZMS. To inhibit transcription, a complementary oMgonucleotide is designed from the most unique 5' sequence and used to prevent promoter binding to the coding sequence. To inhibit franslation, a complementary oMgonucleotide is designed to prevent ribosomal binding to the NZMS-encoding transcript. XII. Expression of NZMS Expression and purification of NZMS is achieved using bacterial or virus-based expression systems. For expression of NZMS in bacteria, cDNA is subcloned into an appropriate vector containing an antibiotic resistance gene and an inducible promoter that directs high levels of cDNA transcription. Examples of such promoters include, but are not Mmited to, the trp-lac (tac) hybrid promoter and the T5 or T7 bacteriophage promoter in conjunction with the lac operator regulatory element. Recombinant vectors are transformed into suitable bacterial hosts, e.g., BL21(DE3). Antibiotic resistant bacteria express NZMS upon induction with isopropyl beta-D- thiogalactopyranoside (EPTG). Expression of NZMS in eukaryotic cells is achieved by infecting insect or mammaMan ceU Mnes with recombinant Autographica caMfornica nuclear polyhedrosis vims (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding NZMS by either homologous recombination or bacterial-mediated transposition involving transfer plasmid intermediates. Viral infectivity is maintained and the strong polyhedrin promoter drives high levels of cDNA transcription. Recombinant baculovirus is used to infect Spodoptera frugiperda (Sf9) insect ceUs in most cases, or human hepatocytes, in some cases. Infection of the latter requires additional genetic modifications to baculovirus. (See Engelhard, E.K. et al. (1994) Proc. Natl. Acad. Sci. USA 91:3224-3227; Sandig, V. et al. (1996) Hum. Gene Ther. 7:1937-1945.) In most expression systems, NZMS is synthesized as a fusion protein with, e.g., glutathione S- fransferase (GST) or a peptide epitope tag, such as FLAG or 6-His, permitting rapid, single-step, affinity-based purification of recombinant fusion protein from crude cell lysates. GST, a 26-kilodalton enzyme from Schistosoma iaponicum, enables the purification of fusion proteins on immobiMzed glutathione under conditions that maintain protein activity and antigenicity (Amersham Pharmacia Biotech). FoUowing purification, the GST moiety can be proteolyticaUy cleaved from NZMS at specificaUy engineered sites. FLAG, an 8-amino acid peptide, enables immunoaffinity purification using commercially available monoclonal and polyclonal anti-FLAG antibodies (Eastman Kodak). 6- His, a stretch of six consecutive histidine residues, enables purification on metal-chelate resins (QIAGEN). Methods for protein expression and purification are discussed in Ausubel (1995, supra, ch. 10 and 16). Purified NZMS obtained by these methods can be used directly in the assays shown in Examples XVI, XVII, and XVJH, etc. where appMcable. XIII. Functional Assays NZMS function is assessed by expressing the sequences encoding NZMS at physiologicaUy elevated levels in mammaMan cell culture systems. cDNA is subcloned into a mammaMan expression vector containing a strong promoter that drives high levels of cDNA expression. Vectors of choice . include PCMV SPORT (Life Technologies) and PCR3.1 (Invifrogen, Carlsbad CA), both of which « contain the cytomegalovims promoter. 5-10 μg of recombinant vector are transiently transfected into a human ceU Mne, for example, an endotheMal or hematopoietic cell Une, using either Mposome formulations or electroporation. 1-2 μg of an additional plasmid containing sequences encoding a marker protein are co-transfected. Expression of a marker protein provides a means to distinguish transfected ceUs from nontransfected cells and is a rehable predictor of cDNA expression from the recombinant vector. Marker proteins of choice include, e.g., Green Fluorescent Protein (GFP; Clontech), CD64, or a CD64-GFP fusion protein. Flow cytometry (FCM), an automated, laser optics- based technique, is used to identify transfected ceUs expressing GFP or CD64-GFP and to evaluate the apoptotic state of the ceUs and other ceUular properties. FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding or coincident with ceU death. These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in ceU size and granularity as measured by forward Mght scatter and 90 degree side Mght scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of ceU surface and infraceUular proteins as measured by reactivity with specific antibodies; and alterations in plasma membrane composition as measured by the binding of fluorescein-conjugated Annexin V protein to the ceU surface. Methods in flow cytometry are discussed in Ormerod, M.G. (1994) Flow Cytometry, Oxford, New York NY. The influence of NZMS on gene expression can be assessed using highly purified populations of ceUs fransfected with sequences encoding NZMS and either CD64 or CD64-GFP. CD64 and CD64-GFP are expressed on the surface of fransfected ceUs and bind to conserved regions of human immunoglobuMn G (IgG). Transfected ceUs are efficiently separated from nonfransfected ceUs using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Lake Success NY). mRNA can be purified from the ceUs using methods weU known by those of skiU in the art. Expression of mRNA encoding NZMS and other genes of interest can be analyzed by northern analysis or microarray techniques. XIV. Production of NZMS Specific Antibodies NZMS substantiaUy purified using polyacrylamide gel electrophoresis (PAGE; see, e.g., Harrington, M.G. (1990) Methods Enzymol. 182:488-495), or other purification techniques, is used to immunize rabbits and to produce antibodies using standard protocols. Alternatively, the NZMS amino acid sequence is analyzed using LASERGENE software (DNASTAR) to determine regions of high immunogenicity, and a corresponding oMgopeptide is synthesized and used to raise antibodies by means known to those of skill in the art. Methods for > selection of appropriate epitopes, such as those near the C-terminus or in hydrophiUc regions are well described in the art. (See, e.g., Ausubel, 1995, supra, ch. 11.) TypicaUy, oMgopeptides of about 15 residues in length are synthesized using an ABI 431 A peptide synthesizer (AppMed Biosystems) using FMOC chemistry and coupled to KLH (Sigma- Aldrich, St. Louis MO) by reaction with N-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) to increase immunogenicity. (See, e.g., Ausubel, 1995, supra.) Rabbits are immunized with the oMgopeptide- KLH complex in complete Freund's adjuvant. Resulting antisera are tested for antipeptide and anti-NZMS activity by, for example, binding the peptide or NZMS to a substrate, blocking with 1 % BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG. XV. Purification of Naturally Occurring NZMS Using Specific Antibodies NaturaUy occurring or recombinant NZMS is substantiaUy purified by immunoaffinity chromatography using antibodies specific for NZMS. An immunoaffinity column is constracted by covalently coupMng anti-NZMS antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Pharmacia Biotech). After the coupMng, the resin is blocked and washed according to the manufacturer's instructions. Media containing NZMS are passed over the immunoaffinity column, and the column is washed under conditions that aUow the preferential absorbance of NZMS (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/NZMS binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaofrope, such as urea or thiocyanate ion), and NZMS is coUected. XVI. Identification of Molecules Which Interact with NZMS NZMS, or biologicaUy active fragments thereof, are labeled with 125 I Bolton-Hunter reagent. (See, e.g., Bolton, A.E. and W.M. Hunter (1973) Biochem. J. 133:529-539.) Candidate molecules previously arrayed in the wells of a multi-weU plate are incubated with the labeled NZMS, washed, and any weUs with labeled NZMS complex are assayed. Data obtained using different concenfrations of NZMS are used to calculate values for the number, affinity, and association of NZMS with the candidate molecules. Alternatively, molecules interacting with NZMS are analyzed using the yeast two-hybrid system as described in Fields, S. and O. Song (1989) Nature 340:245-246, or using commercially available kits based on the two-hybrid system, such as the MATCHMAKER system (Clontech). NZMS may also be used in the PATHCALLING process (CuraGen Corp., New Haven CT) which employs the yeast two-hybrid system in a high-throughput manner to determine aU interactions between the proteins encoded by two large Mbraries of genes (Nandabalan, K. et al. (2000) U.S. Patent No. 6,057,101). XVII. Demonstration of NZMS activity Lyase activity of NZMS is demonstrated through a variety of specific enzyme assays. In general, NZMS is incubated with its subsfrate(s) under conditions suitable for the enzymatic reaction being assayed. After a suitable period of time, the reaction is terminated, and the formation of the product(s) are monitored spectrophotometricaUy, chromatographically, fluorometricaUy, or by some other appropriate method. Lyase activity is proportional to the amount of product(s) formed, or the rate of product formation. Some examples of specific lyase activity assays are described below. Glyoxalase activity of NZMS is measured spectrophotometricaUy as described (Ridderstrom, M. et al. (1996) J. Biol. Chem. 271:319-323). NZMS is added to a 1 ml reaction volume containing 900 μM S-D-lactoylglutathione and 200 μM 5,5'-dithiobis(2-nitrobenzoate) in 100 mM MOPS, pH 7.2, at 37 C. The formation of glutathione is monitored spectrophotometricaUy at 412 nm. Glyoxalase I activity of NZMS is measured by monitoring the formation of glutathione thioester from methylglyoxal and glutathione. NZMS is incubated with 2mM methylglyoxal and 2 mM reduced glutathione in 0.1 M sodium phosphate, pH 7.0, at 30°C Formation of the glutathione thioester is monitored spectrophotometricaUy at a wavelength of 240 nm. Glyoxalase I activity of NZMS is proportional to the rate of formation of the glutathione thioester. (See, e.g., Riddersfrom, M. et al. (1998) J. Biol. Chem. 273:21623-21628.) dTDP-D-glucose 4,6-dehydratase activity of NZMS is measured by monitoring the formation of dTDP-4-keto-6-deoxy-D-glucose from dTDP-D-glucose. NZMS is incubated with 50 mM Tris- HCl, pH 7.6, 12 mM MgCl 2 , 4 mM dTDP-D-glucose, 0.9 unit of inorganic pyrophosphatase, and 8 mM NADPH for 3 hours at 37 °C. The sugar components in the mixture are coupled with 2- aminopyridine and then analyzed chromatographicaUy using an anion-exchange column. Dehydratase activity is proportional to the amount of dTDP-4-keto-6-deoxy-D-glucose formed. (See, e.g., Yoshida, 1999, supra.) Aconitase activity of NZMS is measured in an assay coupled to isocitric dehydrogenase. NZMS is incubated with isocitric dehydrogenase, NADP, and citrate, and the reduction of NADP is monitored fluorometricaUy. Aconitase activity is proportional to the rate of NADP reduction. (See, e.g., Costello, L.C et al. (1997) J. Biol. Chem. 272:28875-28881 ; CosteUo, L.C. et al. (1996) Urology 48:654-659.) DihydrodipicoMnate synthase activity of NZMS is measured using the o-aminobenzaldehyde method (Yugari, Y. and C Gilvarg (1965) J. Biol. Chem. 240:4710-4716; Karchi, H. et al. (1994) Proc. Natl. Acad. Sci. USA 91:2577-2581). Alternatively, dihydrodipicoMnate synthase activity of NZMS is measured as described by Frisch and coworkers (Frisch, D.A. et al. (1 91) Plant Physiol. 96:444-452; Shaver, J.M. et al. (1996) Proc. Natl. Acad. Sci. USA 93 ; 1962-1966). Sulfatase activity of NZMS is measured by incubating NZMS with the synthetic substrate p- nitrocatechol sulfate and monitoring the release of free p-nifrocatechol after the addition of base. The activity of NZMS is proportional to the amount of free p-nifrocatechol released, as measured spectrophotometricaUy at 515 nm. Ribonuclease activity of NZMS can be measured spectrophotometricaUy by determining the amount of solubiMzed RNA that is produced as a result of incubation of RNA substrate with NZMS. 5 μl (20 μg) of a 4 mg/ml solution of yeast tRNA (Sigma) is added to 0.8 ml of 40 mM sodium phosphate, pH 7.5, containing NZMS. The reaction is incubated at 25 °C for 15 minutes. The reaction is stopped by addition of 0.5 ml of an ice-cold fresh solution of 20 mM lanthanum nitrate plus 3% perchloric acid. The stopped reaction is incubated on ice for at least 15 min, and the insoluble tRNA is removed by cenfrifugation for 5 min at 10,000 g. SolubiMzed tRNA is determined as UV absorbance (260 nm) of the remaining supernatant, with A 260 of 1.0 corresponding to 40 μg of solubiMzed RNA (Rosenberg, H.F. et al. (1996) Nucleic Acids Research 24:3507-3513). An assay for carbonic anhydrase activity of NZMS uses the fluorescent pH indicator 8- hydroxypyrene-l,3,6-frisulfonate (pyranine) in combination with stopped-flow fluorometry to measure carbonic anhydrase activity (Shingles, et al. 1997, Anal. Biochem. 252: 190-197). A pH 6.0 solution is mixed with a pH 8.0 solution and the initial rate of bicarbonate dehydration is measured. Addition of carbonic anhydrase to the pH 6.0 solution enables the measurement of the initial rate of activity at physiological temperatures with resolution times of 2 ms. Shingles et al. used this assay to resolve differences in activity and sensitivity to sulfonamides by comparing mammaMan carbonic anhydrase isoforms. The fluorescent technique' s sensitivity aUows the determination of initial rates with a protein concentration as Mttle as 65 ng/ml. Decarboxylase activity of NZMS is measured as the release of C0 2 from labeled subsfrate. For example, omithine decarboxylase activity of NZMS is assayed by measuring the release of C0 2 fromL-[l- 1 C]-orr_ithine (Reddy, S.G et al. (1996) J. Biol. Chem. 271:24945-24953). Activity is measured in 200 μl assay buffer (50 mM Tris/HCl, pH 7.5, 0.1 mM EDTA, 2 mM dithiothreitol, 5 mM NaF, 0.1% Brij35, 1 mM PMSF, 60 μM pyridoxal-5-phosphate) containing 0.5 mM L-ornithine plus 0.5 μCi L-tl- 1 C]ornithine. The reactions are stopped after 15-30 minutes by addition of 1 M cifric acid, and the 1 C0 2 evolved is trapped on a paper disk filter saturated with 20 μl of 2 N NaOH. The radioactivity on the disks is determined by Mquid scintiUatibn spectography. The amount of 14 C0 2 released is proportional to omithine decarboxylase activity of NZMS. Protein phosphatase activity can be measured by the hydrolysis of p-nifrophenyl phosphate (PNPP). NZMS is incubated together with PNPP in HEPES buffer pH 7.5, in the presence of 0.1 % β-mercaptoethanol at 37° C for 60 min. The reaction is stopped by the addition of 6 ml of 10 N NaOH (Diamond, R.H. et al. (1994) Mol. Cell. Biol. 14:3752-62). Alternatively, acid phosphatase activity of NZMS is demonstrated by incubating NZMS containing extract with 100 μl of 10 mM PNPP in 0.1 M sodium citrate, pH 4.5, and 50 μl of 40 mM NaCl at 37 °C for 20 min. The reaction is stopped by the addition of 0.5 ml of 0.4 M glycine/NaOH, pH 10.4 (Saftig, P. et al. (1997) J. Biol. Chem. 272:18628-18635). The increase in Mght absorbance at 410 nm resulting from the hydrolysis of PNPP is measured using a specfrophotometer. The increase in Mght absorbance is proportional to the activity of NZMS in the assay. In the alternative, NZMS activity is determined by measuring the amount of phosphate removed from a phosphorylated protein subsfrate. Reactions are performed with 2 or 4 nM NZMS in a final volume of 30 μl containing 60 mM Tris, pH 7.6, 1 mM EDTA, 1 mM EGTA, 0.1% 2-mercaptoethanol and 10 μM subsfrate, 32 P-labeled on serine/threonine or tyrosine, as appropriate. Reactions are initiated with substrate and incubated at 30° C for 10-15 min. Reactions are quenched with 450 μl of 4% (w/v) activated charcoal in 0.6 M HCl, 90 mM Na 4 P 2 0 7 , and 2 mM NaH 2 P0 4 , then centrifuged at 12,000 x g for 5 min. Acid-soluble 32 Pi is quantified by Mquid scintiUation counting (Sinclair, C et al. (1999) J. Biol. Chem. 274:23666-23672). AdditionaUy, NZMS activity can be determined by measuring the amount of sulfate removed from a suUonated protein substrate. Reactions are performed in 50 mM Tris-HCl buffer, pH 8.0 containing 5 mM 4-nitrocatechol sulfate and 5 μl crude supernatant protein extracted from ceUs expressing NZMS. The reaction is incubated at 37 °C for 30 minutes (HaUmann, A. et al. (1994) Eur. J. Biochem. 221 :143-150.) The increase in Mght absorbance at 410 nm resulting from the hydrolysis of the phenol sulfate substrate is measured using a spectrophotometer. The increase in Mght absorbance is proportional to the activity of NZMS in the assay. NZMS activity can be measured by determining the amount of free adenosine produced by the hydrolysis of AMP, as described by Sala-Newby et al. supra. Briefly, NZMS is incubated with AMP in a suitable buffer for 10 minutes at 37 °C. Free adenosine is separated from AMP and measured by reverse phase HPLC. Alternatively, NZMS activity is measured by the NZMSolysis of ADP-ribosylarginine (KonczaUk, P. and J. Moss (1999) J. Biol. Chem. 274:16736-16740). 50 ng of NZMS are incubated with 100 μM ADP-ribosyl-[ 14 C]arginine (78,000 cpm) in 50 mM potassium phosphate, pH 7.5, 5 mM dithiothreitol, 10 mM MgCl 2 in a final volume of 100 μl. After 1 h at 37° C, 90 μl of the sample is appMed to a column (0.5 x 4 cm) of Affi-Gel 601 (boronate) equiMbrated and eluted with five 1-ml portions of 0.1 M glycine, pH 9.0, 0.1 M NaCl, and 10 mM MgCl 2 . Free 14 C-Arg in the total eluate is measured by Mquid scintillation counting. NZMS hydrolytic activity is measured in the hydrolytic direction spectroscopicaUy by measuring the rate of the product (homocysteine) formed by reaction with 5,5'-Dithiobis(2-nifrobenzoic acid) (DTNB). To 800 μl of an enzyme solution containing 4.7 μg of NZMS and 4 units of adenosine deaminase in 50 mM potassium phosphate buffer, pH 7.2, containing 1 mM EDTA (buffer A), is added 200 μl of S-Adenosyl-L-homocysteine (500 μM) containing 250 μM DTNB in buffer A. The reaction mixture is incubated at 37 °C for 2 minutes. Hydrolytic activity is monitored at 412 nm continuously using a diode array UV spectrophotometer. Enzyme activity is defined as the amount of enzyme that can hydrolyze 1 μmol of S-Adenosyl-L-homocysteine/minute (Yuan, C-S et al. (1996) J. Biol. Chem. 271:28009-28015). NZMS hydrolytic activity is measured in the synthetic direction as the production of S- adenosyl homocysteine using 3-deazaadenosine as a subsfrate (Sganga, M.W. et al. supra). Briefly, NZMS is incubated in a 100 μl volume containing 0.1 mM 3-deazaadenosine, 5 mM homocysteine, 20 mM Hepes (pH 7.2). The assay mixture is incubated at 37 °C for 15 minutes. The reaction is terminated by the addition of 10 μl of 3 M perchloric acid. After incubation on ice for 15 minutes, the mixture is centrifuged for 5 minutes at 18,000 x g in a microcentrifuge at 4°C The supernatant is removed, neutraMzed by the addition of 1 M potassium carbonate, and centrifuged again. A 50 μl aMquot of supernatant is then chromatographed on an Altex Ulfrasphere ODS column (5 μm particles, 4.6 x 250 mm) by isocratic elution with 0.2 M ammonium dihydrogen phosphate (Aldrich) at a flow rate of 1 ml/min. Protein is determined by the bicinchoninic acid assay (Pierce). Alternatively, NZMS hydrolyase activity can be measured in the synthetic direction by a TLC method (Hershfield, M.S. et al. (1979) J. Biol. Chem. 254:22-25). In a preincubation step, 50 μM [8- 14 C]adenosine is incubated with 5 molar equivalents of NAD + for 15 minutes at 22 °C. Assay samples containing NZMS in a 50 μl final volume of 50 mM potassium phosphate buffer, pH 7.4, 1 mM DTT, and 5 mM homocysteine, are mixed with the preincubated [8- 1 C]adenosine/NAD + to initiate the reaction. The reaction is incubated at 37 °C, and 1 μl samples are spotted on TLC plates at 5 minute intervals for 30 minutes. The chromatograms are developed in butanol-1 /glacial acetic acid/water (12:3:5, v/v) and dried. Standards are used to identify substrate and products under ultraviolet Mght. The complete spots containing [ 1 C]adenosine and [ 1 C]SAH are then detected by exposing x-ray film to the TLC plate. The radiolabeled subsfrate and product are then cut from the chromatograms and counted by Mquid scintillation spectrometry. Specific activity of the enzyme is determined from the Mnear least squares slopes of the product vs time plots and the milMgrams of protein in the sample (Bethin, K.E. et al. (1995) J. Biol. Chem. 270:20698-20702). XVIII. Identification of NZMS Agonists and Antagonists Agonists or antagonists of NZMS activation or inhibition may be tested using the assay described in section XVII. Agonists cause an increase in NZMS activity and antagonists cause a decrease in NZMS activity. Various modifications and variations of the described methods and systems of the invention wiU be apparent to those skiUed in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with certain embodiments, it should be understood that the invention as claimed should not be unduly Mmited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skiUed in molecular biology or related fields are intended to be within the scope of the foUowing claims. Table 2 VO ■P-- Table 2 Table 2 VO ON Table 3 Table 3 Table 3 Table 3 o o Table 3 Table 3 Table 3 o ω Table 3 o -rt Table 3 Table 3 o ON Table 3 Table 3 Table 3 Table 3 Table 4 Table 4 Table 4 Table 4 Table 4 <- ι Table 4 CTN Table 5 Table 6 Table 6 Table 6 t o Table 7 Table 7 Table 7

Claims: What is claimed is: 1. An isolated polypeptide selected from the group consisting of: a) a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ED NO:l-18, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NOrl-17, c) a polypeptide comprising a naturally occurring amino acid sequence at least 94% identical to the amino acid sequence of SEQ ID NO:18, d) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, and e) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18. 2. An isolated polypeptide of claim 1 comprising an amino acid sequence selected from the group consisting of SEQ ID NO.1-18. 3. An isolated polynucleotide encoding a polypeptide of claim 1. 4. An isolated polynucleotide encoding a polypeptide of claim 2. 5. An isolated polynucleotide of claim 4 comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO: 19-36. 6. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of claim 3. 7. A cell transformed with a recombinant polynucleotide of claim 6. 8. A transgenic organism comprising a recombinant polynucleotide of claim 6. 9. A method of producing a polypeptide of claim 1 , the method comprising: a) culturing a cell under conditions suitable for expression of the polypeptide, wherein said cell is transformed with a recombinant polynucleotide, and said recombinant polynucleotide comprises a promoter sequence operably linked to a polynucleotide encoding the polypeptide of claim 1 , and b) recovering the polypeptide so expressed. 10. A method of claim 9, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18. 11. An isolated antibody which specifically binds to a polypeptide of claim 1. 12. An isolated polynucleotide selected from the group consisting of: a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:19-36, c) a polynucleotide complementary to a polynucleotide of a), d) a polynucleotide complementary to a polynucleotide of b), and e) an RNA equivalent of a)-d). 13. An isolated polynucleotide comprising at least 60 contiguous nucleotides of a polynucleotide of claim 12. 14. A method of detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 12, the method comprising: a) hybridizing the sample with a probe comprising at least 20 contiguous nucleotides comprising a sequence complementary to said target polynucleotide in the sample, and which probe specifically hybridizes to said target polynucleotide, under conditions whereby a hybridization complex is formed between said probe and said target polynucleotide or fragments thereof, and b) detecting the presence or absence of said hybridization complex, and, optionally, if present, the amount thereof. 15. A method of claim 14, wherein the probe comprises at least 60 contiguous nucleotides. 16. A method of detecting a target polynucleotide in a sample, said target polynucleotide having a sequence of a polynucleotide of claim 12, the method comprising: a) amplifying said target polynucleotide or fragment thereof using polymerase chain reaction amplification, and b) detecting the presence or absence of said amplified target polynucleotide or fragment thereof, and, optionally, if present, the amount thereof . 17. A composition comprising a polypeptide of claim 1 and a pharmaceutically acceptable excipient. 18. A composition of claim 17, wherein the polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18. 19. A method for treating a disease or condition associated with decreased expression of functional NZMS, comprising administering to a patient in need of such treatment the composition of claim 17. 20. A method of screening a compound for effectiveness as an agonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting agonist activity in the sample. 21. A composition comprising an agonist compound identified by a method of claim 20 and a pharmaceutically acceptable excipient. 22. A method for treating a disease or condition associated with decreased expression of functional NZMS, comprising administering to a patient in need of such treatment a composition of claim 21. 23. A method of screening a compound for effectiveness as an antagonist of a polypeptide of claim 1, the method comprising: a) exposing a sample comprising a polypeptide of claim 1 to a compound, and b) detecting antagonist activity in the sample. 24. A composition comprising an antagonist compound identified by a method of claim 23 and a pharmaceutically acceptable excipient. 25. A method for treating a disease or condition associated with overexpression of functional NZMS, comprising administering to a patient in need of such treatment a composition of claim 24. 26. A method of screening for a compound that specifically binds to the polypeptide of claim 1, the method comprising: a) combining the polypeptide of claim 1 with at least one test compound under suitable conditions, and b) detecting binding of the polypeptide of claim 1 to the test compound, thereby identifying a compound that specifically binds to the polypeptide of claim 1. 27. A method of screening for a compound that modulates the activity of the polypeptide of claim 1, the method comprising: a) combining the polypeptide of claim 1 with at least one test compound under conditions permissive for the activity of the polypeptide of claim 1 , b) assessing the activity of the polypeptide of claim 1 in the presence of the test compound, and c) comparing the activity of the polypeptide of claim 1 in the presence of the test compound with the activity of the polypeptide of claim 1 in the absence of the test compound, wherein a change in the activity of the polypeptide of claim 1 in the presence of the test compound is indicative of a compound that modulates the activity of the polypeptide of claim 1. 28. A method of screening a compound for effectiveness in altering expression of a target polynucleotide, wherein said target polynucleotide comprises a sequence of claim 5, the method comprising: a) exposing a sample comprising the target polynucleotide to a compound, under conditions suitable for the expression of the target polynucleotide, b) detecting altered expression of the target polynucleotide, and c) comparing the expression of the target polynucleotide in the presence of varying amounts of the compound and in the absence of the compound. 29. A method of assessing toxicity of a test compound, the method comprising: a) treating a biological sample containing nucleic acids with the test compound, b) hybridizing the nucleic acids of the treated biological sample with a probe comprising at least 20 contiguous nucleotides of a polynucleotide of claim 12 under conditions whereby a specific hybridization complex is formed between said probe and a target polynucleotide in the biological sample, said target polynucleotide comprising a polynucleotide sequence of a polynucleotide of claim 12 or fragment thereof, c) quantifying the amount of hybridization complex, and d) comparing the amount of hybridization complex in the treated biological sample with the amount of hybridization complex in an untreated biological sample, wherein a difference in the amount of hybridization complex in the treated biological sample is indicative of toxicity of the test compound. 30. A diagnostic test for a condition or disease associated with the expression of NZMS in a biological sample, the method comprising: a) combining the biological sample with an antibody of claim 11 , under conditions suitable for the antibody to bind the polypeptide and form an antibody:polypeptide complex, and b) detecting the complex, wherein the presence of the complex correlates with the presence of the polypeptide in the biological sample. 31. The antibody of claim 11 , wherein the antibody is: a) a chimeric antibody, b) a single chain antibody, c) a Fab fragment, d) a F(ab') 2 fragment, or e) a humanized antibody. 32. A composition comprising an antibody of claim 11 and an acceptable excipient. 33. A method of diagnosing a condition or disease associated with the expression of NZMS in a subject, comprising administering to said subject an effective amount of the composition of claim 32. 34. A composition of claim 32, wherein the antibody is labeled. 35. A method of diagnosing a condition or disease associated with the expression of NZMS in a subject, comprising administering to said subject an effective amount of the composition of claim 34. 36. A method of preparing a polyclonal antibody with the specificity of the antibody of claim 11 , the method comprising: a) immunizing an animal with a polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, or an immunogenic fragment thereof, under conditions to elicit an antibody response, b) isolating antibodies from said animal, and c) screening the isolated antibodies with the polypeptide, thereby identifying a polyclonal antibody which binds specifically to a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18. 37. A polyclonal antibody produced by a method of claim 36. 38. A composition comprising the polyclonal antibody of claim 37 and a suitable carrier. 39. A method of making a monoclonal antibody with the specificity of the antibody of claim 11, the method comprising: a) immunizing an animal with a polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18, or an immunogenic fragment thereof, under conditions to elicit an antibody response, b) isolating antibody producing cells from the animal, c) fusing the antibody producing cells with immortalized cells to form monoclonal antibody-producing hybridoma cells, d) culturing the hybridoma cells, and e) isolating from the culture monoclonal antibody which binds specifically to a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:l-18. 40. A monoclonal antibody produced by a method of claim 39. 41. A composition comprising the monoclonal . antibody of claim 40 and a suitable carrier. 42. The antibody of claim 11, wherein the antibody is produced by screening a Fab expression library. 43. The antibody of claim 11 , wherein the antibody is produced by screening a recombinant immunoglobuMn library. 44. A method of detecting a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1-18 in a sample, the method comprising: a) incubating the antibody of claim 11 with a sample under conditions to allow specific binding of the antibody and the polypeptide, and b) detecting specific binding, wherein specific binding indicates the presence of a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ED NO:l -18 in the sample. 45. A method of purifying a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:l-18 from a sample, the method comprising: a) incubating the antibody of claim 11 with a sample under conditions to allow specific binding of the antibody and the polypeptide, and b) separating the antibody from the sample and obtaining the purified polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:l-18. 46. A microarray wherem at least one element of the microarray is a polynucleotide of claim 13. 47. A method of generating an expression profile of a sample which contains polynucleotides, the method comprising: a) labeling the polynucleotides of the sample, b) contacting the elements of the microarray of claim 46 with the labeled polynucleotides of the sample under conditions suitable for the formation of a hybridization complex, and c) quantifying the expression of the polynucleotides in the sample. 48. An array comprising different nucleotide molecules affixed in distinct physical locations on a solid substrate, wherem at least one of said nucleotide molecules comprises a first oligonucleotide or polynucleotide sequence specifically hybridizable with at least 30 contiguous nucleotides of a target polynucleotide, and wherein said target polynucleotide is a polynucleotide of claim 12. 49. An array of claim 48, wherein said first oligonucleotide or polynucleotide sequence is completely complementary to at least 30 contiguous nucleotides of said target polynucleotide. 50. An array of claim 48, wherein said first oligonucleotide or polynucleotide sequence is completely complementary to at least 60 contiguous nucleotides of said target polynucleotide. 51. An array of claim 48, wherein said first oligonucleotide or polynucleotide sequence is completely complementary to said target polynucleotide. 52. An array of claim 48, which is a microarray. 53. An array of claim 48, further comprising said target polynucleotide hybridized to a nucleotide molecule comprising said first oligonucleotide or polynucleotide sequence. 54. An array of claim 48, wherein a linker joins at least one of said nucleotide molecules to said solid substrate. 55. An array of claim 48, wherein each distinct physical location on the substrate contains multiple nucleotide molecules, and the multiple nucleotide molecules at any single distinct physical location have the same sequence, and each distinct physical location on the substrate contains nucleotide molecules having a sequence which differs from the sequence of nucleotide molecules at another distinct physical location on the substrate. 56. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:l. 57. A polypeptide of claim 1 , comprising the amino acid sequence of SEQ ED NO:2. 58. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:3. 59. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:4. 60. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:5. 61. A polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO:6. 62. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ED NO:7. 63. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:8. 64. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:9. 65. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:10. 66. A polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO:l 1. 67. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ED NO: 12. 68. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:13. 69. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ED NO:14. 70. A polypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:15. 71. Apolypeptide of claim 1, comprising the amino acid sequence of SEQ ID NO:16. 72. A polypeptide of claim 1 , comprising the amino acid sequence of SEQ ED NO:17. 73. A polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO : 18. 74. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO: 19. 75. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:20. 76. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:21. 77. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:22. 78. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:23. 79. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:24. 80. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:25. 81. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:26. 82. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:27. 83. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:28. 84. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:29. 85. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:30. 86. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:31. 87. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:32. 88. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:33. 89. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ED NO:34. 90. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:35. 91. A polynucleotide of claim 12, comprising the polynucleotide sequence of SEQ ID NO:36.

Inventors: ARVIZU CHANDRA, BAUGHN MARIAH R, DING LI, DUGGAN BRENDAN M, GANDHI AMEENA R, GRIFFIN JENNIFER A, HILLMAN JENNIFER L, LEE ERNESTINE A, LEE SALLY, LU DYUNG AINA M, LU YAN, RAMKUMAR JAYALAXMI, SANJANWALA MADHU M, TANG Y TOM, TRIBOULEY CATHERINE M, WALIA NARINDER K, WARREN BRIDGET A, YAO MONIQUE G, YUE HENRY, ARVIZU, CHANDRA, BAUGHN, MARIAH, R., DING, LI, DUGGAN, BRENDAN, M., GANDHI, AMEENA, R., GRIFFIN, JENNIFER, A., HILLMAN, JENNIFER, L., LEE, ERNESTINE, A., LEE, SALLY, LU, DYUNG, AINA, M., LU, YAN, RAMKUMAR, JAYALAXMI, SANJANWALA, MADHU, M., TANG, Y., TOM, TRIBOULEY, CATHERINE, M., WALIA, NARINDER, K., WARREN, BRIDGET, A., YAO, MONIQUE, G., YUE, HENRY
Applicants: ARVIZU CHANDRA, BAUGHN MARIAH R, DING LI, DUGGAN BRENDAN M, GANDHI AMEENA R, GRIFFIN JENNIFER A, HILLMAN JENNIFER L, INCYTE GENOMICS INC, LEE ERNESTINE A, LEE SALLY, LU DYUNG AINA M, LU YAN, RAMKUMAR JAYALAXMI, SANJANWALA MADHU M, TANG Y TOM, TRIBOULEY CATHERINE M, WALIA NARINDER K, WARREN BRIDGET A, YAO MONIQUE G, YUE HENRY, ARVIZU, CHANDRA, BAUGHN, MARIAH, R., DING, LI, DUGGAN, BRENDAN, M., GANDHI, AMEENA, R., GRIFFIN, JENNIFER, A., HILLMAN, JENNIFER, L., INCYTE GENOMICS, INC., LEE, ERNESTINE, A., LEE, SALLY, LU, DYUNG, AINA, M., LU, YAN, RAMKUMAR, JAYALAXMI, SANJANWALA, MADHU, M., TANG, Y., TOM, TRIBOULEY, CATHERINE, M., WALIA, NARINDER, K., WARREN, BRIDGET, A., YAO, MONIQUE, G., YUE, HENRY
Application year: 2001
Main classification: C12N9
IPC codes: A61K38, A61K45, A61K49, A61P1, A61P9, A61P11, A61P15, A61P25, A61P27, A61P29, A61P35, A61P37, C07K16, C12N1, C12N5, C12N9, C12N15, C12P21, C12Q1, G01N33, G01N37