Patent Publication Number: US-2007124581-A1

Title: Cell adhesion and extracellular matrix proteins

Description:
TECHNICAL FIELD  
      The invention relates to novel nucleic acids, cell adhesion and extracellular matrix proteins encoded by these nucleic acids, and to the use of these nucleic acids and proteins in the diagnosis, treatment, and prevention of immune system disorders, neurological disorders, developmental disorders, connective tissue disorders, and cell proliferative disorders, including cancer. The invention also relates to the assessment of the effects of exogenous compounds on the expression of nucleic acids and cell adhesion and extracellular matrix proteins.  
     BACKGROUND OF THE INVENTION  
      Cell Adhesion Proteins  
      The surface of a cell is rich in transmembrane proteoglycans, glycoproteins, glycolipids, and receptors. These macromolecules mediate adhesion with other cells and with components of the ECM. The interaction of the cell with its surroundings profoundly influences cell shape, strength, flexibility, motility, and adhesion. These dynamic properties are intimately associated with signal transduction pathways controlling cell proliferation and differentiation, tissue construction, and embryonic development. Families of cell adhesion molecules include the cadherins, integrins, lectins, neural cell adhesion proteins, and some members of the proline-rich proteins.  
      Cadherins comprise a family of calcium-dependent glycoproteins that function in mediating cell-cell adhesion in virtually all solid tissues of multicellular organisms. These proteins share multiple repeats of a cadherin-specific motif, and the repeats form the folding units of the cadherin extracellular domain. Cadherin molecules cooperate to form focal contacts, or adhesion plaques, between adjacent epithelial cells. The cadherin family includes the classical cadherins and protocadherins. Classical cadherins include the E-cadherin, N-cadherin, and P-cadherin subfamilies. E-cadherin is present on many types of epithelial cells and is especially important for embryonic development. N-cadherin is present on nerve, muscle, and lens cells and is also critical for embryonic development. P-cadherin is present on cells of the placenta and epidermis. Recent studies report that protocadherins are involved in a variety of cell-cell interactions (Suzuki, S. T. (1996) J. Cell Sci. 109:2609-2611). The intracellular anchorage of cadherins is regulated by their dynamic association with catenins, a family of cytoplasmic signal transduction proteins associated with the actin cytoskeleton. The anchorage of cadherins to the actin cytoskeleton appears to be regulated by protein tyrosine phosphorylation, and the cadherins are the target of phosphorylation-induced junctional disassembly (Aberle, H. et al. (1996) J. Cell. Biochem. 61:514-523).  
      Integrins are ubiquitous transmembrane adhesion molecules that link the ECM to the internal cytoskeleton. Integrins are composed of two noncovalently associated transmembrane glycoprotein subunits called α and β. At least 8 different β subunits (β1-β8) and at least 12 different α subunits have been identified (α1-α8, αL, αM, αX, and αIIb). Individual α subunits are capable of associating with different β subunits, suggesting a possible mechanism for specifying integrin function and ligand binding affinity. Members of the β subunit family are generally of 90-110 kilodaltons (kD) in molecular weight and share about 40-48% amino acid sequence homology. About 56 cysteines distributed among four repeating units are also conserved. Some variation in these conserved features is observed among some of the more divergent β subunit family members. Members of the α subunit family are generally 150-200 kilodaltons in molecular weight and are not as well conserved as the β subunit family. All contain seven repeating domains of 24-45 amino acids spaced about 20-35 amino acids apart. The N-termini each contain 3-4 divalent cation binding sites. (For review, see Pigott, R. and C. Power (1994)  The Adhesion Molecule Facts Book , Academic Press, San Diego, Calif., pp. 9-12.)  
      Integrins function as receptors that specifically recognize and bind to ECM proteins such as fibronectin, fibrinogen, laminin, thrombospondin, vitronectin, von Willebrand factor, and collagen. Some integrins recognize a specific motif, the RGD sequence, at the C-termini of the ECM proteins they bind. For example, binding of integrin to its extracellular ligand may stimulate changes in intracellular calcium levels or protein kinase activity (Sjaastad, M. D. and Nelson, W. J. (1997) BioEssays 19:47-55). At least ten cell surface receptors of the integrin family recognize the ECM component fibronectin, which is involved in many different biological processes including cell migration and embryogenesis (Johansson, S. et al. (1997) Front. Biosci. 2:D126-D146). Integrins also bind to immunoglobulin superfamily proteins such as ICAM-1, -2, and -3 and VCAM-1.  
      Most integrins have been shown to activate focal adhesion kinase (FAK), a protein tyrosine kinase that is linked to Ras signaling pathways that modify the cytoskeleton and stimulate the mitogen-activated protein kinase (MAPK) cascade (Hanks, S. K. and T. R. Polte (1997) BioEssays 19:137-145). Integrins can also influence growth factor signaling through direct interaction with growth factor receptor tyrosine kinases (RTKs) (Miyamoto, S. et al. (1996) J. Cell Biol. 135:1633-1642). Integrins have also been shown to play a vital role in “anoikis,” a term describing programmed cell death caused by loss of cell anchorage (Frisch, S. M. and E. Ruoslahti (1997) Curr. Opin. Cell Biol. 9:701-706).  
      A number of diseases have been attributed to integrin defects. (See Pigott and Power, supra). For example, leukocyte adhesion deficiency (LAD) is an inherited disorder characterized by the impaired migration of neutrophils to sites of extravascular inflammation. LAD is caused by abnormal splicing of and a missense mutation in the RNA encoding the β2 subunit. Additionally, defects in platelet integrin are correlated with Glanzmann&#39;s thrombasthemia, a bleeding disorder characterized by insufficient platelet aggregation.  
      Lectins comprise a ubiquitous family of extracellular glycoproteins which bind cell surface carbohydrates specifically and reversibly, resulting in the agglutination of cells (reviewed in Drickamer, K. and M. E. Taylor (1993) Annu. Rev. Cell Biol. 9:237-264). This function is particularly important for activation of the immune response. Lectins mediate the agglutination and mitogenic stimulation of lymphocytes at sites of inflammation (Lasky, L. A. (1991) J. Cell. Biochem. 45:139-146; Paietta, E. et al. (1989) J. Immunol. 143:2850-2857).  
      Lectins are further classified into subfamilies based on carbohydrate-binding specificity and other criteria. The galectin subfamily, in particular, includes lectins that bind β-galactoside carbohydrate moieties in a thiol-dependent manner (reviewed in Hadari, Y. R. et al. (1998) J. Biol. Chem. 270:3447-3453). Galectins are widely expressed and developmentally regulated. Galectins contain a characteristic carbohydrate recognition domain (CRD). The CRD comprises about 140 amino acids and contains several stretches of about 1-10 amino acids which are highly conserved among all galectins. A particular 6-amino acid motif within the CRD contains conserved tryptophan and arginine residues which are critical for carbohydrate binding. The CRD of some galectins also contains cysteine residues which may be important for disulfide bond formation. Secondary structure predictions indicate that the CRD forms several β-sheets.  
      Galectins play a number of roles in diseases and conditions associated with cell-cell and cell-matrix interactions. For example, certain galectins associate with sites of inflammation and bind to cell surface immunoglobulin E molecules. In addition, galectins may play an important role in cancer metastasis. Galectin overexpression is correlated with the metastatic potential of cancers in humans and mice. Moreover, anti-galectin antibodies inhibit processes associated with cell transformation, such as cell aggregation and anchorage-independent growth (see, for example, Su, Z.-Z. et al. (1996) Proc. Natl. Acad. Sci. USA 93:7252-7257).  
      Selectins, or LEC-CAMs, comprise a specialized lectin subfamily involved primarily in inflammation and leukocyte adhesion (Reviewed in Lasky, supra). Selectins mediate the recruitment of leukocytes from the circulation to sites of acute inflammation and are expressed on the surface of vascular endothelial cells in response to cytokine signaling. Selectins bind to specific ligands on the leukocyte cell membrane and enable the leukocyte to adhere to and migrate along the endothelial surface. Binding of selectin to its ligand leads to polarized rearrangement of the actin cytoskeleton and stimulates signal transduction within the leukocyte (Brenner, B. et al. (1997) Biochem. Biophys. Res. Commun. 231:802-807; Hidari, K. I. et al. (1997) J. Biol. Chem. 272:28750-28756). Members of the selectin family possess three characteristic motifs: a lectin or carbohydrate recognition domain; an epidermal growth factor-like domain; and a variable number of short consensus repeats (scr or “sushi” repeats) which are also present in complement regulatory proteins.  
      Neural cell adhesion proteins (NCAPs) play roles in the establishment of neural networks during development and regeneration of the nervous system (Uyemura, K. et al. (1996) Essays Biochem. 31:37-48; Brummendorf, T., and F. G. Rathjen (1996) Curr. Opin. Neurobiol. 6:584-593). NCAP participates in neuronal cell migration, cell adhesion, neurite outgrowth, axonal fasciculation, pathfinding, synaptic target-recognition, synaptic formation, myelination and regeneration. NCAPs are expressed on the surfaces of neurons associated with learning and memory. Mutations in genes encoding NCAPS are linked with neurological diseases, including hereditary neuropathy, Charcot-Marie-Tooth disease, Dejerine-Sottas disease, X-linked hydrocephalus, MASA syndrome (mental retardation, aphasia, shuffling gait and adducted thumbs), and spastic paraplegia type I. In some cases, expression of NCAP is not restricted to the nervous system. L1, for example, is expressed in melanoma cells and hematopoietic tumor cells where it is implicated in cell spreading and migration, and may play a role in tumor progression (Montgomery, A. M. et al. (1996) J. Cell Biol. 132:475-485).  
      NCAPs have at least one immunoglobulin constant or variable domain (Uyemura et al., supra). They are generally linked to the plasma membrane through a transmembrane domain and/or a glycosyl-phosphatidylinositol (GPI) anchor. The GPI linkage can be cleaved by GPI phospholipase C. Most NCAPs consist of an extracellular region made up of one or more immunoglobulin domains, a membrane spanning domain, and an intracellular region. Many NCAPs contain post-translational modifications including covalently attached oligosaccharide, glucuronic acid, and sulfate. NCAPs fall into three subgroups: simple-type, complex-type, and mixed-type. Simple-type NCAPs contain one or more variable or constant immunoglobulin domains, but lack other types of domains. Members of the simple-type subgroup include Schwann cell myelin protein (SMP), limbic system-associated membrane protein (LAMP), opiate-binding cell-adhesion molecule (OBCAM), and myelin-associated glycoprotein (MAG). The complex-type NCAPs contain fibronectin type III domains in addition to the immunoglobulin domains. The complex-type subgroup includes neural cell-adhesion molecule (NCAM), axonin-1, F11, Bravo, and L1 . Mixed-type NCAPs contain a combination of immunoglobulin domains and other motifs such as tyrosine kinase and epidermal growth factor-like domains. This subgroup includes Trk receptors of nerve growth factors such as nerve growth factor (NGF) and neurotropin 4 (NT4), Neu differentiation factors such as glial growth factor II (GGFII) and acetylcholine receptor-inducing factor (ARIA), and the semaphorin/collapsin family such as semaphorin B and collapsin.  
      Semaphorins are a large group of axonal guidance molecules consisting of at least 30 different members and are found in vertebrates, invertebrates, and even certain viruses. All semaphorins contain the sema domain which is approximately 500 amino acids in length. Neuropilin, a semaphorin receptor, has been shown to promote neurite outgrowth in vitro. The extracellular region of neuropilins consists of three different domains: CUB, discoidin, and MAM domains. The CUB and the MAM motifs of neuropilin have been proposed to have roles in protein-protein interactions and are suggested to be involved in the binding of semaphorins through the sema and the C-terminal domains (reviewed in Raper, J. A. (2000) Curr. Opin. Neurobiol. 10:88-94).  
      An NCAP subfamily, the NCAP-LON subgroup, includes cell adhesion proteins expressed on distinct subpopulations of brain neurons. Members of the NCAP-LON subgroup possess three immunoglobulin domains and bind to cell membranes through GPI anchors. Kilon (a kindred of NCAP-LON), for example, is expressed in the brain cerebral cortex and hippocampus (Funatsu, N. et al. (1999) J. Biol. Chem. 274:8224-8230). Immunostaining localizes Kilon to the dendrites and soma of pyramidal neurons. Kilon has three C2 type immunoglobulin-like domains, six predicted glycosylation sites, and a GPI anchor. Expression of Kilon is developmentally regulated. It is expressed at higher levels in adult brain in comparison to embryonic and early postnatal brains. Confocal microscopy shows the presence of Kilon in dendrites of hypothalamic magnocellular neurons secreting neuropeptides, oxytocin or arginine vasopressin (Miyata, S. et al. (2000) J. Comp. Neurol. 424:74-85). Arginine vasopressin regulates body fluid homeostasis, extracellular osmolarity and intravascular volume. Oxytocin induces contractions of uterine smooth muscle during child birth and of myoepithelial cells in mammary glands during lactation. In magnocellular neurons, Kilon is proposed to play roles in the reorganization of dendritic connections during neuropeptide secretion.  
      The co-ordinated function of effector and accessory cells in the immune system is assisted by adhesion molecules on the cell surface that stabilize interactions between different cell types. Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 which are members of the immunoglobulin superfamily. The interaction of LFA-1 with ICAMs 1 and 2 provides essential accessory adhesion signals in many immune interactions, including those between T and B lymphocytes and cytotoxic T cells and their targets. In addition, both ICAMs are expressed at low levels on resting vascular endothelium. ICAM-1 is strongly upregulated by cytokine stimulation and plays a key role in the arrest of leukocytes in blood vessels at sites of inflammation and injury. A third ligand for LFA-1 expressed in resting leukocytes is ICAM-3. ICAM-3 is closely related to ICAM-1 and is constitutively expressed on all leukocytes. It consists of five immunoglobulin domains and binds LFA-1 through its two N-terminal domains (Fawcett, J. et al. (1992) Nature 360:481-484).  
      Cell adhesion proteins also include some members of the proline-rich proteins (PRPs). PRPs are defined by a high frequency of proline, ranging from 20-50% of the total amino acid content. Some PRPs have short domains which are rich in proline. These proline-rich regions are associated with protein-protein interactions. One family of PRPs are the proline-rich synapse-associated proteins (ProSAPs) which have been shown to bind to members of the postsynaptic density (PSD) protein family and subtypes of the somatostatin receptor (Yao, L. et al. (1999) J. Biol. Chenm 274:  
       27463 -27466; Zitzer, H. et al. (1999) J. Biol. Chem. 274:32997-33001). Members of the ProSAP family contain six to seven ankyrin repeats at the N-terminus, followed by an SH3 domain, a PDZ domain, and seven proline-rich regions and a SAM domain at the C terminus. Several groups of ProSAPs are important structural constituents of synaptic structures in human brain (Zitzer et al., supra). Another member of the PRP family is the HLA-B-associated transcript 2 protein (BAT2) which is rich in proline and includes short tracts of polyproline, polyglycine, and charged amino acids. BAT2 also contains four RGD (Arg-Gly-Asp) motifs typical of integrins (Banerji, J. et al. (1990) Proc. Natl. Acad. Sci. USA 87:2374-2378).  
      Toposome is a cell-adhesion glycoprotein isolated from mesenchyme-blastula embryos. Toposome precursors including vitellogenin promote cell adhesion of dissociated blastula cells.  
      There are additional specific domains characteristic of cell adhesion proteins. One such domain is the MAM domain, a domain of about 170 amino acids found in the extracellular region of diverse proteins. These proteins all share a receptor-like architecture comprising a signal peptide, followed by a large N-terminal extracellular domain, a transmembrane region, and an intracellular domain (PROSITE document PDOC00604 MAM domain signature and profile). MAM domain proteins include zonadhesin, a sperm-specific membrane protein that binds to the zona pellucida of the egg; neuropilin, a cell adhesion molecule that functions during the formation of certain neuronal circuits, and  Xenopus laevis  thyroid hormone induced protein B, which contains four MAM domains and is involved in metamorphosis (Brown, D. D. et al. (1996) Proc. Natl. Acad. Sci. USA 93:1924-1929).  
      The WSC domain was originally found in the yeast WSC (cell-wall integrity and stress response component) proteins which act as sensors of environmental stress. The WSC domains are extracellular and are thought to possess a carbohydrate binding role (Ponting, C. P. et al. (1999) Curr. Biol. 9:S1-S2). A WSC domain has recently been identified in polycystin-1, a human plasma membrane protein. Mutations in polycystin-1 are the cause of the commonest form of autosomal dominant polycystic kidney disease (Ponting, C. P. et al. (1999) Curr. Biol. 9:R585-R588).  
      Leucine rich repeats (LRR) are short motifs found in numerous proteins from a wide range of species. LRR motifs are of variable length, most commonly 20-29 amino acids, and multiple repeats are typically present in tandem. LRR motifs are important for protein/protein interactions and cell adhesion, and LRR proteins are involved in cell/cell interactions, morphogenesis, and development (Kobe, B. and J. Deisenhofer (1995) Curr. Opin. Struct. Biol. 5:409-416). The human ISLR (immunoglobulin superfamily containing leucine-rich repeat) protein contains a C2-type immunoglobulin domain as well as LRR motifs. The ISLR gene is linked to the critical region for Bardet-Biedl syndrome, a developmental disorder of which the most common feature is retinal dystrophy (Nagasawa, A. et al. (1999) Genomics 61:37-43).  
      The sterile alpha motif (SAM) domain is a conserved protein binding domain, approximately 70 amino acids in length, and is involved in the regulation of many developmental processes in eukaryotes. The SAM domain can potentially function as a protein interaction module through its ability to form homo- or hetero-oligomers with other SAM domains (Schultz, J. et al. (1997) Protein Sci. 6:249-253).  
      Extracellular Matrix Proteins  
      The extracellular matrix (ECM) is a complex network of glycoproteins, polysaccharides, proteoglycans, and other macromolecules that are secreted from the cell into the extracellular space. The ECM remains in close association with the cell surface and provides a supportive meshwork that profoundly influences cell shape, motility, strength, flexibility, and adhesion. In fact, adhesion of a cell to its surrounding matrix is required for cell survival except in the case of metastatic tumor cells, which have overcome the need for cell-ECM anchorage. This phenomenon suggests that the ECM plays a critical role in the molecular mechanisms of growth control and metastasis. (Reviewed in Ruoslahti, E. (1996) Sci. Am. 275:72-77.) Furthermore, the ECM determines the structure and physical properties of connective tissue and is particularly important for morphogenesis and other processes associated with embryonic development and pattern formation.  
      The collagens comprise a family of ECM proteins that provide structure to bone, teeth, skin, ligaments, tendons, cartilage, blood vessels, and basement membranes. Multiple collagen proteins have been identified. Three collagen molecules fold together in a triple helix stabilized by interchain disulfide bonds. Bundles of these triple helices then associate to form fibrils. Collagen primary structure consists of hundreds of (Gly-X-Y) repeats where about a third of the X and Y residues are Pro. Glycines are crucial to helix formation as the bulkier amino acid sidechains cannot fold into the triple helical conformation. Because of these strict sequence requirements, mutations in collagen genes have severe consequences. Osteogenesis imperfecta patients have brittle bones that fracture easily; in severe cases patients die in utero or at birth. Ehlers-Danlos syndrome patients have hyperelastic skin, hypermobile joints, and susceptibility to aortic and intestinal rupture. Chondrodysplasia patients have short stature and ocular disorders. Alport syndrome patients have hematuria, sensorineural deafness, and eye lens deformation. (Isselbacher, K. J. et al. (1994)  Harrison&#39;s Principles of Internal Medicine , McGraw-Hill, Inc., New York, N.Y., pp. 2105-2117; and Creighton, T. E. (1984)  Proteins, Structures and Molecular Principles , W.H. Freeman and Company, New York, N.Y., pp. 191-197.)  
      Elastin and related proteins confer elasticity to tissues such as skin, blood vessels, and lungs. Elastin is a highly hydrophobic protein of about 750 amino acids that is rich in proline and glycine residues. Elastin molecules are highly cross-linked, forming an extensive extracellular network of fibers and sheets. Elastin fibers are surrounded by a sheath of microfibrils which are composed of a number of glycoproteins, including fibrillin. Mutations in the gene encoding fibrillin are responsible for Marfan&#39;s syndrome, a genetic disorder characterized by defects in connective tissue. In severe cases, the aortas of afflicted individuals are prone to rupture. (Reviewed in Alberts, B. et al. (1994)  Molecular Biology of the Cell , Garland Publishing, New York, N.Y., pp. 984-986.) The fibulin proteins connect elastic fibers and are though to promote the formation and stabilization of the fiber. Members of the fibulin family contain epidermal growth factor-like motifs as well as an RGD cell attachment sequence (Midwood, K. S. and J. E. Schwarzbauer (2002) Current Biology 12:R279-R281).  
      Fibronectin is a large ECM glycoprotein found in all vertebrates. Fibronectin exists as a dimer of two subunits, each containing about 2,500 amino acids. Each subunit folds into a rod-like structure containing multiple domains. The domains each contain multiple repeated modules, the most common of which is the type III fibronectin repeat. The type III fibronectin repeat is about 90 amino acids in length and is also found in other ECM proteins and in some plasma membrane and cytoplasmic proteins. Furthermore, some type III fibronectin repeats contain a characteristic tripeptide consisting of Arginine-Glycine-Aspartic acid (RGD). The RGD sequence is recognized by the integrin family of cell surface receptors and is also found in other ECM proteins. Disruption of both copies of the gene encoding fibronectin causes early embryonic lethality in mice. The mutant embryos display extensive morphological defects, including defects in the formation of the notochord, somites, heart, blood vessels, neural tube, and extraembryonic structures. (Reviewed in Alberts et al., supra, pp. 986-987.)  
      Laminin is a major glycoprotein component of the basal lamina which underlies and supports epithelial cell sheets. Laminin is one of the first ECM proteins synthesized in the developing embryo. Laminin is an 850 kilodalton protein composed of three polypeptide chains joined in the shape of a cross by disulfide bonds. Laminin is especially important for angiogenesis and, in particular, for guiding the formation of capillaries. (Reviewed in Alberts et al., supra, pp. 990-991.)  
      Many proteinaceous ECM components are proteoglycans. Proteoglycans are composed of unbranched polysaccharide chains (glycosaminoglycans) attached to protein cores. Common proteoglycans include aggrecan, betaglycan, decorin, perlecan, serglycin, and syndecan-1. Some of these molecules not only provide mechanical support, but also bind to extracellular signaling molecules, such as fibroblast growth factor and transforming growth factor β, suggesting a role for proteoglycans in cel-cell communication. (Reviewed in Alberts et al., supra, pp. 973-978.) Likewise, the glycoproteins tenascin-C and tenascin-R are expressed in developing and lesioned neural tissue and provide stimulatory and anti-adhesive (inhibitory) properties, respectively, for axonal growth (Faissner, A. (1997) Cell Tissue Res. 290:331-341).  
      Dentin phosphoryn (DPP) is a major component of the dentin ECM. DPP is a proteoglycan that is synthesized and expressed by odontoblasts (Gu, K. et al. (1998) Eur. J. Oral Sci. 106:1043-1047). DPP is believed to nucleate or modulate the formation of hydroxyapatite crystals.  
      Mucins are highly glycosylated glycoproteins that are the major structural component of the mucus gel. The physiological functions of mucins are cytoprotection, mechanical protection, maintenance of viscosity in secretions, and cellular recognition. MUC6 is a human gastric mucin that is also found in gall bladder, pancreas, seminal vesicles, and female reproductive tract (Toribara, N. W. et al. (1997) J. Biol. Chem. 272:16398-16403). The MUC6 gene has been mapped to human chromosome 11 (Toribara, N. W. et al. (1993) J. Biol. Chem. 268:5879-5885). Hemomucin is a novel  Drosophila  surface mucin that may be involved in the induction of antibacterial effector molecules (Theopold, U. et al. (1996) J. Biol. Chem. 217:12708-12715).  
      Olfactomedin was originally identified as the major component of the mucus layer surrounding the chemosensory dendrites of olfactory neurons. Olfactomedin-related proteins are secreted glycoproteins with conserved C-terminal motifs. The TIGR/myocilin protein, an olfactomedin-related protein expressed in the eye, is associated with the pathogenesis of glaucoma (Kulkarni, N. H. et al. (2000) Genet. Res. 76:41-50).  
      Ankyrin (ANK) repeats mediate protein-protein interactions associated with diverse intracellular functions. ANK repeats are composed of about 33 amino acids that form a helix-turn-helix core preceded by a protruding “tip.” These tips are of variable sequence and may play a role in protein-protein interactions. The helix-turn-helix region of the ANK repeats stack on top of one another and are stabilized by hydrophobic interactions (Yang, Y. et al. (1998) Structure 6:619-626).  
      Sushi repeats, also called short consensus repeats (SCR), are found in a number of proteins that share the common feature of binding to other proteins. For example, in the C-terminal domain of versican, the sushi domain is important for heparin binding. Sushi domains contain basic amino acid residues, which may play a role in binding (Oleszewski, M. et al. (2000) J. Biol. Chem. 275:34478-34485).  
      Link, or X-link, modules are hyaluronan-binding domains found in proteins involved in the assembly of extracellular matrix, cell adhesion, and migration. The Link module superfamily includes CD44, cartilage link protein, and aggrecan. This family also includes BEHAB (brain enriched hyaluronan-binding)/brevican, a component of the brain ECM that is dramatically upregulated in human gliomas, and appears to play a role in determining the invasive potential of brain tumor cells (Gary, S. C. et al. (1998) Curr. Opin. Neurobiol. 8:576-581). There is close similarity between the Link module and the C-type lectin domain, with the predicted hyaluronan-binding site at an analogous position to the carbohydrate-binding pocket in E-selectin (Kohda, D. et al. (1996) Cell 86:767-775).  
      Multidomain or mosaic proteins play an important role in the diverse functions of the extracellular matrix (Engel, J. et al. (1994) Development (Camb.):S35-S42). ECM proteins are frequently characterized by the presence of one or more domains which may contain a number of potential intracellular disulfide bridge motifs. For example, domains which match the epidermal growth factor (EGF) tandem repeat consensus are present within several known extracellular proteins that promote cell growth, development, and cell signaling. This signature sequence is about forty amino acid residues in length and includes six conserved cysteine residues, and a calcium-binding site near the N-terminus of the signature sequence. The main structure is a two-stranded beta-sheet followed by a loop to a C-terminal short two-stranded sheet. Subdomains between the conserved cysteines vary in length (Davis, C. G. (1990) New Biol. 5:410-419). Post-translational hydroxylation of aspartic acid or asparagine residues has been associated with EGF-like domains in several proteins (Prosite PDOC00010).  
      A number of proteins that contain calcium-binding EGF-like domain signature sequences are involved in growth and differentiation. Examples include bone morphogenic protein 1, which induces the formation of cartilage and bone; crumbs, which is a  Drosophila  epithelial development protein; Notch and a number of its homologs, which are involved in neural growth and differentiation, and transforming growth factor beta-1 binding protein (Expasy PROSITE document PDOC00913; Soler, C. and G. Carpenter, in Nicola, N. A. (1994)  The Cytokine Facts Book , Oxford University Press, Oxford, UK, pp. 193-197). EGF-like domains mediate protein-protein interactions for a variety of proteins. For example, EGF-like domains in the ECM glycoprotein fibulin-1 have been shown to mediate both self-association and binding to fibronectin (Tran, H. et al. (1997) J. Biol. Chem. 272:22600-22606). Point mutations in the EGF-like domains of ECM proteins have been identified as the cause of human disorders such as Marfan syndrome and pseudochondroplasia (Maurer, P. et al. (1996) Curr. Opin. Cell Biol. 8:609-617).  
      The CUB domain is an extracellular domain of approximately 110 amino acid residues found mostly in developmentally regulated proteins. The CUB domain contains four conserved cysteine residues and is predicted to have a structure similar to that of immunoglobulins. Vertebrate bone morphogenic protein 1, which induces cartilage and bone formation, and fibropellins I and III from sea urchin, which form the apical lamina component of the ECM, are examples of proteins that contain both CUB and EGF domains (PROSITE PDOC00908).  
      Other ECM proteins are members of the type A domain of von Willebrand factor (vWFA)-like module superfamily, a diverse group of proteins with a module sharing high sequence similarity. The vWFA-like module is found not only in plasma proteins but also in plasma membrane and ECM proteins (Colombatti, A. and P. Bonaldo (1991) Blood 77:2305-2315). Crystal structure analysis of an integrin vWFA-like module shows a classic “Rossmann” fold and suggests a metal ion-dependent adhesion site for binding protein ligands (Lee, J.-O. et al. (1995) Cell 80:631-638). This family includes the protein matrilin-2, an extracellular matrix protein that is expressed in a broad range of mammalian tissues and organs. Matrilin-2 is thought to play a role in ECM assembly by bridging collagen fibrils and the aggrecan network (Deak, F. et al. (1997) J. Biol. Chem. 272:9268-9274).  
      The thrombospondins are multimeric, calcium-binding extracellular glycoproteins found widely in the embryonic extracellular matrix. These proteins are expressed in the developing nervous system or at specific sites in the adult nervous system after injury. Thrombospondins contain multiple EGF-type repeats, as well as a motif known as the thrombospondin type 1 repeat (TSR). The TSR is approximately 60 amino acids in length and contains six conserved cysteine residues. Motifs within TSR domains are involved in mediating cell adhesion through binding to proteoglycans and sulfated glycolipids. Thrombospondin-1 inhibits angiogenesis and modulates endothelial cell adhesion, motility, and growth. TSR domains are found in a diverse group of other proteins, most of which are expressed in the developing nervous system and have potential roles in the guidance of cell and growth cone migration. Proteins that contain TSRs include the F-spondin gene family, the semaphorin 5 family, UNC-5, and SCO-spondin. The TSR superfamily includes the ADAMTS proteins which contain an ADAM (A Disintegrin and Metalloproteinase) domain as well as one or more TSRs. The ADAMTS proteins have roles in regulating the turnover of cartilage matrix, regulation of blood vessel growth, and possibly development of the nervous system. (Reviewed in Adams, J. C. and R. P. Tucker (2000) Dev. Dyn. 218:280-299.)  
      Fibrinogen, the principle protein of vertebrate blood clotting, is a hexamer consisting of two sets of three different chains (alpha, beta, and gamma). The C-terminal domain of the beta and gamma chains comprises about 270 amino acid residues and contains four cysteines involved in two disulfide bonds. This domain has also been found in mammalian tenascin-X, an ECM protein that appears to be involved in cell adhesion (Prosite PDOC00445).  
      Expression Profiling  
      Microarrays are analytical tools used in bioanalysis. A microarray has a plurality of molecules spatially distributed over, and stably associated with, the surface of a solid support. Microarrays of polypeptides, polynucleotides, and/or antibodies have been developed and find use in a variety of applications, such as gene sequencing, monitoring gene expression, gene mapping, bacterial identification, drug discovery, and combinatorial chemistry.  
      One area in particular in which microarrays find use is in gene expression analysis. Array technology can provide a simple way to explore the expression of a single polymorphic gene or the expression profile of a large number of related or unrelated genes. When the expression of a single gene is examined, arrays are employed to detect the expression of a specific gene or its variants. When an expression profile is examined, arrays provide a platform for identifying genes that are tissue specific, are affected by a substance being tested in a toxicology assay, are part of a signaling cascade, carry out housekeeping functions, or are specifically related to a particular genetic predisposition, condition, disease, or disorder.  
      Ovarian Cancer  
      Ovarian cancer is the leading cause of death from a gynecologic cancer. The majority of ovarian cancers are derived from epithelial cells, and 70% of patients with epithelial ovarian cancers present with late-stage disease. As a result, the long-term survival rates for this disease is very low. Identification of early-stage markers for ovarian cancer would significantly increase the survival rate. Genetic variations involved in ovarian cancer development include mutation of p53 and microsatellite instability. Gene expression patterns likely vary when normal ovary is compared to ovarian tumors.  
      Peroxisome Proliferator-activated Receptor Gamma (PPARγ) Agonist  
      Thiazolidinediones (TZDs) act as agonists for the peroxisome-proliferator-activated receptor gamma (PPARγ), a member of the nuclear hormone receptor superfamily. TZDs reduce hyperglycemia, hyperinsulinemia, and hypertension, in part by promoting glucose metabolism and inhibiting gluconeogenesis. Roles for PPARγ and its agonists have been demonstrated in a wide range of pathological conditions including diabetes, obesity, hypertension, atherosclerosis, polycystic ovarian syndrome, and cancers such as breast, prostate, liposarcoma, and colon cancer.  
      The mechanism by which TZDs and other PPARγ agonists enhance insulin sensitivity is not fully understood, but may involve the ability of PPARγ to promote adipogenesis. When ectopically expressed in cultured preadipocytes, PPARγ is a potent inducer of adipocyte differentiation. TZDs, in combination with insulin and other factors, can also enhance differentiation of human preadipocytes in culture (Adams et al. (1997) J. Clin. Invest. 100:3149-3153). The relative potency of different TZDs in promoting adipogenesis in vitro is proportional to both their insulin sensitizing effects in vivo, and their ability to bind and activate PPARγ in vitro. Interestingly, adipocytes derived from omental adipose depots are refractory to the effects of TZDs. It has therefore been suggested that the insulin sensitizing effects of TZDs may result from their ability to promote adipogenesis in subcutaneous adipose depots (Adams et al., supra). Further, dominant negative mutations in the PPARγ gene have been identified in two non-obese subjects with severe insulin resistance, hypertension, and overt non-insulin dependent diabetes mellitus (NIDDM) (Barroso et al. (1998) Nature 402:880-883).  
      NIDDM is the most common form of diabetes mellitus, a chronic metabolic disease that affects 143 million people worldwide. NIDDM is characterized by abnormal glucose and lipid metabolism that result from a combination of peripheral insulin resistance and defective insulin secretion. NHDDM has a complex, progressive etiology and a high degree of heritability. Numerous complications of diabetes including heart disease, stroke, renal failure, retinopathy, and peripheral neuropathy contribute to the high rate of morbidity and mortality.  
      At the molecular level, PPARγ functions as a ligand activated transcription factor. In the presence of ligand, PPARγ forms a heterodimer with the retinoid X receptor (RXR) which then activates transcription of target genes containing one or more copies of a PPARγ response element (PPRE). Many genes important in lipid storage and metabolism contain PPREs and have been identified as PPARγ targets, including PEPCK, aP2, LPL, ACS, and FAT-P (Auwerx, J. (1999) Diabetologia 42:1033-1049). Multiple ligands for PPARγ have been identified. These include a variety of fatty acid metabolites; synthetic drugs belonging to the TZD class, such as Pioglitazone and Rosiglitazone (BRL49653); and certain non-glitazone tyrosine analogs such as GI262570 and GW1929. The prostaglandin derivative 15-dPGJ2 is a potent endogenous ligand for PPARγ.  
      Expression of PPARγ is very high in adipose but barely detectable in skeletal muscle, the primary site for insulin stimulated glucose disposal in the body. PPARγ is also moderately expressed in large intestine, kidney, liver, vascular smooth muscle, hematopoietic cells, and macrophages. The high expression of PPARγ in adipose suggests that the insulin sensitizing effects of TZDs may result from alterations in the expression of one or more PPARγ regulated genes in adipose tissue. Identification of PPARγ target genes will contribute to better drug design and the development of novel therapeutic strategies for diabetes, obesity, and other conditions.  
      Systematic attempts to identify PPARγ target genes have been made in several rodent models of obesity and diabetes (Suzuki et al. (2000) Jpn. J. Pharmacol. 84:113-123; Way et al. (2001) Endocrinology 142:1269-1277). However, a serious drawback of the rodent gene expression studies is that significant differences exist between human and rodent models of adipogenesis, diabetes, and obesity (Taylor (1999) Cell 97:9-12; Gregoire et al. (1998) Physiol. Reviews 78:783-809). Therefore, an unbiased approach to identifying TZD regulated genes in primary cultures of human tissues is necessary to fully elucidate the molecular basis for diseases associated with PPARγ activity.  
      Tangier Disease  
      Tangier disease (TD) is a genetic disorder characterized by near absence of circulating high density lipoprotein (HDL) and the accumulation of cholesterol esters in many tissues, including tonsils, lymph nodes, liver, spleen, thymus, and intestine. Low levels of HDL represent a clear predictor of premature coronary artery disease and homozygous TD correlates with a four- to six-fold increase in cardiovascular disease compared to controls. HDL plays a cardio-protective role in reverse cholesterol transport, the flux of cholesterol from peripheral cells such as tissue macrophages through plasma lipoproteins to the liver. The HDL protein, apolipoprotein A-I, plays a major role in this process, interacting with the cell surface to remove excess cholesterol and phospholipids. This pathway is severely impaired in TD and the defect lies in a specific gene, the ABC1 transporter. This gene is a member of the family of ATP-binding cassette transporters, which utilize ATP hydrolysis to transport a variety of substrates across membranes.  
      Colon Cancer  
      The potential application of gene expression profiling is particularly relevant to improving the diagnosis, prognosis, and treatment of cancers, such as colon cancer and breast cancer. While soft tissue sarcomas are relatively rare, more than 50% of new patients diagnosed with the disease will die from it. The molecular pathways leading to the development of sarcomas are relatively unknown, due to the rarity of the disease and variation in pathology. Colon cancer evolves through a multi-step process whereby pre-malignant colonocytes undergo a relatively defined sequence of events leading to tumor formation. Several factors participate in the process of tumor progression and malignant transformation including genetic factors, mutations, and selection.  
      To understand the nature of gene alterations in colorectal cancer, a number of studies have focused on the inherited syndromes. The first, Familial Adenomatous Polyposis (FAP), is caused by mutations in the Adenomatous Polyposis Coli gene (APC), resulting in truncated or inactive forms of the protein. This tumor suppressor gene has been mapped to chromosome 5q. The second known inherited syndrome is hereditary nonpolyposis colorectal cancer (HNPCC), which is caused by mutations in mismatch repair genes.  
      Although hereditary colon cancer syndromes occur in a small percentage of the population, and most colorectal cancers are considered sporadic, knowledge from studies of the hereditary syndromes can be applied broadly. For instance, somatic mutations in APC occur in at least 80% of sporadic colon tumors. APC mutations are thought to be the initiating event in disease progression. Other mutations occur subsequently. Approximately 50% of colorectal cancers contain activating mutations in ras, while 85% contain inactivating mutations in p53. Changes in all of these genes lead to gene expression changes in colon cancer. Less is understood about downstream targets of these mutations and the role they may play in cancer development and progression.  
      Breast Cancer  
      More than 180,000 new cases of breast cancer are diagnosed each year, and the mortality rate for breast cancer approaches 10% of all deaths in females between the ages of 45-54 (Gish, K. (1999) AWIS Magazine 28:7-10). However the survival rate based on early diagnosis of localized breast cancer is extremely high (97%), compared with the advanced stage of the disease in which the tumor has spread beyond the breast (22%). Current procedures for clinical breast examination are lacking in sensitivity and specificity, and efforts are underway to develop comprehensive gene expression profiles for breast cancer that may be used in conjunction with conventional screening methods to improve diagnosis and prognosis of this disease (Perou, C. M. et al. (2000) Nature 406:747-752).  
      Mutations in two genes, BRCA1 and BRCA2, are known to greatly predispose a woman to breast cancer and may be passed on from parents to children (Gish, supra). However, this type of hereditary breast cancer accounts for only about 5% to 9% of breast cancers, while the vast majority of breast cancer is due to non-inherited mutations that occur in breast epithelial cells.  
      The relationship between expression of epidermal growth factor (EGF) and its receptor, EGFR, to human mammary carcinoma has been particularly well studied. (See Khazaie, K. et al. (1993) Cancer and Metastasis Rev. 12:255-274, and references cited therein for a review of this area.) Overexpression of EGFR, particularly coupled with down-regulation of the estrogen receptor, is a marker of poor prognosis in breast cancer patients. In addition, EGFR expression in breast tumor metastases is frequently elevated relative to the primary tumor, suggesting that EGFR is involved in tumor progression and metastasis. This is supported by accumulating evidence that EGF has effects on cell functions related to metastatic potential, such as cell motility, chemotaxis, secretion and differentiation. Changes in expression of other members of the erbB receptor family, of which EGFR is one, have also been implicated in breast cancer. The abundance of erbB receptors, such as HER-2/neu, HER-3, and HER-4, and their ligands in breast cancer points to their functional importance in the pathogenesis of the disease, and may therefore provide targets for therapy of the disease (Bacus, S. S. et al. (1994) Am. J. Clin. Pathol. 102:S13-S24). Other known markers of breast cancer include a human secreted frizzled protein mRNA that is downregulated in breast tumors; the matrix G1a protein which is overexpressed is human breast carcinoma cells; Drg1 or RTP, a gene whose expression is diminished in colon, breast, and prostate tumors; maspin, a tumor suppressor gene downregulated in invasive breast carcinomas; and CaN19, a member of the S100 protein family, all of which are down regulated in mammary carcinoma cells relative to normal mammary epithelial cells (Zhou, Z. et al. (1998) Int. J. Cancer 78:95-99; Chen, L. et al. (1990) Oncogene 5:1391-1395; Ulrix, W. et al (1999) FEBS Lett 455:23-26; Sager, R. et al. (1996) Curr. Top. Microbiol. Immunol. 213:51-64; and Lee, S. W. et al. (1992) Proc. Natl. Acad. Sci. USA 89:2504-2508).  
      Cell lines derived from human mammary epithelial cells at various stages of breast cancer provide a useful model to study the process of malignant transformation and tumor progression as it has been shown that these cell lines retain many of the properties of their parental tumors for lengthy culture periods (Wistuba, I. I. et al. (1998) Clin. Cancer Res. 4:2931-2938). Such a model is particularly useful for comparing phenotypic and molecular characteristics of human mammary epithelial cells at various stages of malignant transformation.  
      Lung Cancer  
      Lung cancer is the leading cause of cancer death for men and the second leading cause of cancer death for women in the U.S. Lung cancers are divided into four histopathologically distinct groups. Three groups (squamous cell carcinoma, adenocarcinoma, and large cell carcinoma) are classified as non-small cell lung cancers (NSCLCs). The fourth group of cancers is referred to as small cell lung cancer (SCLC). Deletions on chromosome 3 are common in this disease and are thought to indicate the presence of a tumor suppressor gene in this region. Activating mutations in K-ras are commonly found in lung cancer and are the basis of one of the mouse models for the disease.  
      PBMCs  
      Human peripheral blood mononuclear cells (PBMC) can be classified into discrete cellular populations representing the major cellular components of the immune system. PBMCs contain about 52% lymphocytes (12% B lymphocytes, 40% T lymphocytes {25% CD4+ and 15% CD8+}), 20% NK cells, 25% monocytes, and 3% various other cells including dendritic cells and progenitor cells. Glucocorticoids are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. Subsequent to binding, transcription and, ultimately, protein synthesis are affected. The result can include inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid. Beclomethasone is a synthetic glucocorticoid that is used for treating steroid-dependent asthma, relieving symptoms associated with allergic or nonallergic (vasomotor) rhinitis, or preventing recurrent nasal polyps following surgical removal. The anti-inflammatory and vasoconstrictive effects of intranasal beclomethasone are 5000 times greater than those produced by hydrocortisone.  
      Prostate Cancer  
      Prostate cancer is a common malignancy in men over the age of 50, and the incidence increases with age. In the US, there are approximately 132,000 newly diagnosed cases of prostate cancer and more than 33,000 deaths from the disorder each year. Once cancer cells arise in the prostate, they are stimulated by testosterone to a more rapid growth. Thus, removal of the testes can indirectly reduce both rapid growth and metastasis of the cancer. Over 95 percent of prostatic cancers are adenocarcinomas which originate in the prostatic acini. The remaining 5 percent are divided between squamous cell and transitional cell carcinomas, both of which arise in the prostatic ducts or other parts of the prostate gland.  
      As with most tumors, prostate cancer develops through a multistage progression ultimately resulting in an aggressive tumor phenotype. The initial step in tumor progression involves the hyperproliferation of normal luminal and/or basal epithelial cells. Androgen responsive cells become hyperplastic and evolve into early-stage tumors. Although early-stage tumors are often androgen sensitive and respond to androgen ablation, a population of androgen independent cells evolve from the hyperplastic population. These cells represent a more advanced form of prostate tumor that may become invasive and potentially become metastatic to the bone, brain, or lung. A variety of genes may be differentially expressed during tumor progression. For example, loss of heterozygosity (LOH) is frequently observed on chromosome 8p in prostate cancer. Fluorescence in situ hybridization (FISH) revealed a deletion for at least 1 locus on 8p in 29 (69%) tumors, with a significantly higher frequency of the deletion on 8p21.2-p21.1 in advanced prostate cancer than in localized prostate cancer, implying that deletions on 8p22-p21.3 play an important role in tumor differentiation, while 8p21.2-p21.1 deletion plays a role in progression of prostate cancer (Oba, K. et al. (2001) Cancer Genet. Cytogenet. 124: 20-26).  
      A primary diagnostic marker for prostate cancer is prostate specific antigen (PSA). PSA is a tissue-specific serine protease almost exclusively produced by prostatic epithelial cells. The quantity of PSA correlates with the number and volume of the prostatic epithelial cells, and consequently, the levels of PSA are an excellent indicator of abnormal prostate growth. Men with prostate cancer exhibit an early linear increase in PSA levels followed by an exponential increase prior to diagnosis. However, since PSA levels are also influenced by factors such as inflammation, androgen and other growth factors, some scientists maintain that changes in PSA levels are not useful in detecting individual cases of prostate cancer.  
      Current areas of cancer research provide additional prospects for markers as well as potential therapeutic targets for prostate cancer. Several growth factors have been shown to play a critical role in tumor development, growth, and progression. The growth factors Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), and Tumor Growth Factor alpha (TGFα) are important in the growth of normal as well as hyperproliferative prostate epithelial cells, particularly at early stages of tumor development and progression, and affect signaling pathways in these cells in various ways (Lin, J. et al. (1999) Cancer Res. 59:2891-2897; Putz, T. et al. (1999) Cancer Res. 59:227-233). The TGF-β family of growth factors are generally expressed at increased levels in human cancers and the high expression levels in many cases correlates with advanced stages of malignancy and poor survival (Gold, L. I. (1999) Crit. Rev. Oncog. 10:303-360). Finally, there are human cell lines representing both the androgen-dependent stage of prostate cancer (LNCap) as well as the androgen-independent, hormone refractory stage of the disease (PC3 and DU-145) that have proved useful in studying gene expression patterns associated with the progression of prostate cancer, and the effects of cell treatments on these expressed genes (Chung, T. D. (1999) Prostate 15:199-207).  
      Obesity  
      Adipose tissue stores and releases fat during periods of feeding and fasting. White adipose tissue is the major energy reserve in periods of excess energy use. Its primary purpose is mobilization during energy deprivation. Understanding how various molecules regulate adiposity and energy balance in physiological and pathophysiological situations may lead to the development of novel therapeutics for human obesity. Adipose tissue is also one of the important target tissues for insulin. Adipogenesis and insulin resistance in type II diabetes are linked and present intriguing relations. Most patients with type II diabetes are obese and obesity in turn causes insulin resistance.  
      The majority of research in adipocyte biology to date has been done using transformed mouse preadipocyte cell lines. The culture condition which stimulates mouse preadipocyte differentiation is different from that for inducing human primary preadipocyte differentiation. In addition, primary cells are diploid and may therefore reflect the in vivo context better than aneuploid cell lines. Understanding the gene expression profile during adipogenesis in humans will lead to an understanding of the fundamental mechanism of adiposity regulation. Furthermore, through comparing the gene expression profiles of adipogenesis between donor with normal weight and donor with obesity, identification of crucial genes, potential drug targets for obesity and type II diabetes, will be possible.  
      Immune Response  
      The immune system is responsible for coping with trauma caused by a variety of agents. Different specialized immune cells detect and repair damage originating from physical trauma versus foreign agents. For instance, lymphocytes, including T- and B-cells, specifically recognize and respond to foreign pathogens. T-cells fight viral infections and activate other immune cell types, while B-cells secrete antibodies that neutralie bacteria and other microbes. Granulocytes and monocytes are primarily migratory, phagocytic cells that exit the bloodstream to fight infection in tissues. Monocytes, derived from immature pro-monocytes, are capable of differentiating into macrophages that engulf and digest microorganisms as well as damaged or dead cells. Monocytes and macrophages also modulate the immune response by secreting signaling molecules such as growth factors and cytokines, and are recruited to sites of infection and inflammation by signaling proteins secreted by other immune cells. The differentiation of the monocyte blood cell lineage, as well as responses to inflammatory stimuli, can be studied in vitro using cultured cell lines. For example, THP-1 is a human promonocyte cell line, derived from a 1-year-old male with acute monocytic leukemia, that can be induced to differentiate into macrophage-like cells by treatment with both phorbol ester such as phorbol myristate acetate (PMA). Further treatment of these cells with oxidized low density lipids (oxLDL) causes them to acquire a particular “foam” cell morphology that is typically associated with atherosclerosis and the presence of vascular lesions.  
      Monocytes are involved in the initiation and maintenance of inflammatory immune responses. The outer membrane of gram-negative bacteria expresses lipopolysaccharide (LPS) complexes called endotoxins. Toxicity is associated with the lipid component (Lipid A) of LPS, and immunogenicity is associated with the polysaccharide components of LPS. LPS elicits a variety of inflammatory responses, and because it activates complement by the alternative (properdin) pathway, it is often part of the pathology of gram-negative bacterial infections. For the most part, endotoxins remain associated with the cell wall until the bacteria disintegrate. LPS released into the bloodstream by lysing gram-negative bacteria is first bound by certain plasma proteins identified as LPS-binding proteins. The LPS-binding protein complex interacts with CD14 receptors on monocytes, macrophages, B cells, and other types of receptors on endothelial cells. Activation of human B cells with LPS results in mitogenesis as well as immunoglobulin synthesis. In monocytes and macrophages three types of events are triggered during their interaction with LPS: 1) production of cytokines, including IL-1, IL-6, IL-8, TNF-α, and platelet-activating factor, which stimulate production of prostaglandins and leukotrienes that mediate inflammation and septic shock; 2) activation of the complement cascade; and 3) activation of the coagulation cascade.  
      There is a need in the art for new compositions, including nucleic acids and proteins, for the diagnosis, prevention, and treatment of immune system disorders, neurological disorders, developmental disorders, connective tissue disorders, and cell proliferative disorders, including cancer.  
     SUMMARY OF THE INVENTION  
      Various embodiments of the invention provide purified polypeptides, cell adhesion and extracellular matrix proteins, referred to collectively as ‘CADECM’ and individually as ‘CADECM-1,’ ‘CADECM-2,’ ‘CADECM-3,’ ‘CADECM-4,’ ‘CADECM-5,’ ‘CADECM-6,’ ‘CADECM-7,’ ‘CADECM-8,’ ‘CADECM-9,’ ‘CADECM-10,’ ‘CADECM-11,’ ‘CADECM-12,’ ‘CADECM-13,’ ‘CADECM-14,’ ‘CADECM-15,’ ‘CADECM-16,’ ‘CADECM-17,’ ‘CADECM-18,’ ‘CADECM-19,’ ‘CADECM-20,’ ‘CADECM-21,’ ‘CADECM-22,’ ‘CADECM-23,’ ‘CADECM-24,’ ‘CADECM-25,’ ‘CADECM-26,’ ‘CADECM-27,’ ‘CADECM-28,’ ‘CADECM-29,’ ‘CADECM-30,’ and ‘CADECM-31,’ and methods for using these proteins and their encoding polynucleotides for the detection, diagnosis, and treatment of diseases and medical conditions. Embodiments also provide methods for utilizing the purified cell adhesion and extracellular matrix proteins and/or their encoding polynucleotides for facilitating the drug discovery process, including determination of efficacy, dosage, toxicity, and pharmacology. Related embodiments provide methods for utilizing the purified cell adhesion and extracellular matrix proteins and/or their encoding polynucleotides for investigating the pathogenesis of diseases and medical conditions.  
      An embodiment 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. Another embodiment provides an isolated polypeptide comprising an amino acid sequence of SEQ ID NO:1-31.  
      Still another embodiment 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 ID NO:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. In another embodiment, the polynucleotide encodes a polypeptide selected from the group consisting of SEQ ID NO:1-31. In an alternative embodiment, the polynucleotide is selected from the group consisting of SEQ ID NO:32-62.  
      Still another embodiment provides a recombinant polynucleotide comprising a promoter sequence operably linked 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. Another embodiment provides a cell transformed with the recombinant polynucleotide. Yet another embodiment provides a transgenic organism comprising the recombinant polynucleotide.  
      Another embodiment 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. 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 linked to a polynucleotide encoding the polypeptide, and b) recovering the polypeptide so expressed.  
      Yet another embodiment provides an isolated antibody which specifically 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31.  
      Still yet another embodiment 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:32-62, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:32-62, 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 other embodiments, the polynucleotide can comprise at least about 20, 30, 40, 60, 80, or 100 contiguous nucleotides.  
      Yet another embodiment provides a method for detecting a target polynucleotide in a sample, said target polynucleotide being selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:32-62, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:32-62, 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. In a related embodiment, the method can include detecting the amount of the hybridization complex. In still other embodiments, the probe can comprise at least about 20, 30, 40, 60, 80, or 100 contiguous nucleotides.  
      Still yet another embodiment provides a method for detecting a target polynucleotide in a sample, said target polynucleotide being selected from the group consisting of a) a polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO:32-62, b) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:32-62, 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) 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. In a related embodiment, the method can include detecting the amount of the amplified target polynucleotide or fragment thereof.  
      Another embodiment 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and a pharmaceutically acceptable excipient. In one embodiment, the composition can comprise an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. Other embodiments provide a method of treating a disease or condition associated with decreased or abnormal expression of functional CADECM, comprising administering to a patient in need of such treatment the composition.  
      Yet another embodiment 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting agonist activity in the sample. Another embodiment provides a composition comprising an agonist compound identified by the method and a pharmaceutically acceptable excipient. Yet another embodiment provides a method of treating a disease or condition associated with decreased expression of functional CADECM, comprising administering to a patient in need of such treatment the composition.  
      Still yet another embodiment 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. The method comprises a) exposing a sample comprising the polypeptide to a compound, and b) detecting antagonist activity in the sample. Another embodiment provides a composition comprising an antagonist compound identified by the method and a pharmaceutically acceptable excipient. Yet another embodiment provides a method of treating a disease or condition associated with overexpression of functional CADECM, comprising administering to a patient in need of such treatment the composition.  
      Another embodiment provides a method of screening for a compound that specifically 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. 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 specifically binds to the polypeptide.  
      Yet another embodiment 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:1-31, b) a polypeptide comprising a naturally occurring amino acid sequence at least 90% identical or at least about 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:1-31, c) a biologically active fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO: 1-31, and d) an immunogenic fragment of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:1-31. 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.  
      Still yet another embodiment 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:32-62, the method comprising a) exposing a sample comprising the target polynucleotide to a compound, 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.  
      Another embodiment 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:32-62, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:32-62, iii) a polynucleotide having a sequence complementary to i), iv) a polynucleotide complementary to the polynucleotide of ii), 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:32-62, ii) a polynucleotide comprising a naturally occurring polynucleotide sequence at least 90% identical or at least about 90% identical to a polynucleotide sequence selected from the group consisting of SEQ ID NO:32-62, iii) a polynucleotide complementary to the polynucleotide of i), iv) a polynucleotide complementary to the polynucleotide of ii), and v) an RNA equivalent of i)-iv). Alternatively, the target polynucleotide can comprise a fragment of a polynucleotide 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 full length polynucleotide and polypeptide embodiments of the 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 polypeptide embodiments of the invention. The probability scores for the matches between each polypeptide and its homolog(s) are also shown.  
      Table 3 shows structural features of polypeptide embodiments, including predicted motifs and domains, along with the methods, algorithms, and searchable databases used for analysis of the polypeptides.  
      Table 4 lists the cDNA and/or genomic DNA fragments which were used to assemble polynucleotide embodiments, along with selected fragments of the polynucleotides.  
      Table 5 shows representative cDNA libraries for polynucleotide embodiments.  
      Table 6 provides an appendix which describes the tissues and vectors used for construction of the cDNA libraries shown in Table 5.  
      Table 7 shows the tools, programs, and algorithms used to analyze polynucleotides and polypeptides, along with applicable descriptions, references, and threshold parameters.  
      Table 8 shows single nucleotide polymorphisms found in polynucleotide sequences of the invention, along with allele frequencies in different human populations. 
    
    
     DESCRIPTION OF THE INVENTION  
      Before the present proteins, nucleic acids, and methods are described, it is understood that embodiments of the invention are not limited to the particular machines, instruments, materials, and methods described, as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the invention.  
      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 cell” includes a plurality of such host cells, and a reference to “an antibody” is a reference to one or more antibodies and equivalents thereof known to those skilled in the art, and so forth.  
      Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill 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. All publications mentioned herein are cited for the purpose of describing and disclosing the cell lines, protocols, reagents and vectors which are reported in the publications and which might be used in connection with various embodiments of 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  
      “CADECM” refers to the amino acid sequences of substantially purified CADECM obtained from any species, particularly a mammalian 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 CADECM. Agonists may include proteins, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of CADECM either by directly interacting with CADECM or by acting on components of the biological pathway in which CADECM participates.  
      An “allelic variant” is an alternative form of the gene encoding CADECM. Allelic 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 allelic variants of its naturally occurring form. Common mutational changes which give rise to allelic variants are generally 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 CADECM include those sequences with deletions, insertions, or substitutions of different nucleotides, resulting in a polypeptide the same as CADECM or a polypeptide with at least one functional characteristic of CADECM. Included within this definition are polymorphisms which may or may not be readily detectable using a particular oligonucleotide probe of the polynucleotide encoding CADECM, and improper or unexpected hybridization to allelic variants, with a locus other than the normal chromosomal locus for the polynucleotide encoding CADECM. 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 CADECM. Deliberate amino acid substitutions may be made on the basis of one or more similarities in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues, as long as the biological or immunological activity of CADECM 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 hydrophilicity values may include: asparagine and glutamine; and serine and threonine. Amino acids with uncharged side chains having similar hydrophilicity values may include: leucine, isoleucine, and valine; glycine and alanine; and phenylalanine and tyrosine.  
      The terms “amino acid” and “amino acid sequence” can refer to an oligopeptide, a peptide, a polypeptide, or a protein sequence, or a fragment of any of these, and to naturally occurring or synthetic molecules. Where “amino acid sequence” is recited to refer to a sequence of a naturally occurring protein molecule, “amino acid sequence” and like terms are not meant to limit the amino acid sequence to the complete native amino acid sequence associated with the recited protein molecule.  
      “Amplification” relates to the production of additional copies of a nucleic acid. Amplification may be carried out using polymerase chain reaction (PCR) technologies or other nucleic acid amplification technologies well known in the art.  
      The term “antagonist” refers to a molecule which inhibits or attenuates the biological activity of CADECM. Antagonists may include proteins such as antibodies, anticalins, nucleic acids, carbohydrates, small molecules, or any other compound or composition which modulates the activity of CADECM either by directly interacting with CADECM or by acting on components of the biological pathway in which CADECM participates.  
      The term “antibody” refers to intact immunoglobulin molecules as well as to fragments thereof, such as Fab, F(ab′) 2 , and Fv fragments, which are capable of binding an epitopic determinant. Antibodies that bind CADECM polypeptides can be prepared using intact polypeptides or using fragments containing small peptides of interest as the immunizing antigen. The polypeptide or oligopeptide 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 chemically coupled to peptides include bovine serum albumin, thyroglobulin, and keyhole limpet 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 specifically 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 elicit the immune response) for binding to an antibody.  
      The term “aptamer” refers to a nucleic acid or oligonucleotide 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. Pat. No. 5,270,163), which selects for target-specific aptamer sequences from large combinatorial libraries. Aptamer compositions may be double-stranded or single-stranded, and may include deoxyribonucleotides, ribonucleotides, nucleotide derivatives, or other nucleotide-like 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 2′-NH 2 ), which may improve a desired property, e.g., resistance to nucleases or longer lifetime 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 specifically cross-linked to their cognate ligands, e.g., by photo-activation of a cross-linker (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 (Blind, M. et al. (1999) Proc. Natl. Acad. Sci. USA 96:3606-3610).  
      The term “spiegelmer” refers to an aptamer which includes L-DNA, L-RNA, or other left-handed nucleotide derivatives or nucleotide-like molecules. Aptamers containing left-handed nucleotides are resistant to degradation by naturally occurring enzymes, which normally 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 polynucleotide having a specific nucleic acid sequence. Antisense compositions may include DNA; RNA; peptide nucleic acid (PNA); oligonucleotides having modified backbone linkages such as phosphorothioates, methylphosphonates, or benzylphosphonates; oligonucleotides having modified sugar groups such as 2′-methoxyethyl sugars or 2′-methoxyethoxy sugars; or oligonucleotides 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 cell, the complementary antisense molecule base-pairs with a naturally occurring nucleic acid sequence produced by the cell 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 naturally occurring molecule. Likewise, “immunologically active” or “immunogenic” refers to the capability of the natural, recombinant, or synthetic CADECM, or of any oligopeptide thereof, to induce a specific immune response in appropriate animals or cells 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” and a “composition comprising a given polypeptide” can refer to any composition containing the given polynucleotide or polypeptide. The composition may comprise a dry formulation or an aqueous solution. Compositions comprising polynucleotides encoding CADECM or fragments of CADECM may be employed as hybridization probes. The probes may be stored in freeze-dried form and may be associated with a stabilizing 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&#39;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 uncalled bases, extended using the XL-PCR kit (Applied Biosystems, Foster City Calif.) 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 (Accelrys, Burlington Mass.) or Phrap (University of Washington, Seattle Wash.). 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 especially 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, Gln, His           Asp   Asn, Glu           Cys   Ala, Ser           Gln   Asn, Glu, His           Glu   Asp, Gln, His           Gly   Ala           His   Asn, Arg, Gln, Glu           Ile   Leu, Val           Leu   Ile, Val           Lys   Arg, Gln, Glu           Met   Leu, Ile           Phe   His, Met, Leu, Trp, Tyr           Ser   Cys, Thr           Thr   Ser, Val           Trp   Phe, Tyr           Tyr   His, Phe, Trp           Val   Ile, Leu, Thr                      
 
 Conservative amino acid substitutions generally maintain (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a beta sheet or alpha helical 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 chemically 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 shuffling” 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 allowing acceleration of the evolution of new protein functions.  
      A “fragment” is a unique portion of CADECM or a polynucleotide encoding CADECM which can be 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 about 5 to about 1000 contiguous nucleotides or amino acid residues. A fragment used as a probe, primer, antigen, therapeutic molecule, or for other purposes, 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 preferentially 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:32-62 can comprise a region of unique polynucleotide sequence that specifically identifies SEQ ID NO:32-62, for example, as distinct from any other sequence in the genome from which the fragment was obtained. A fragment of SEQ ID NO:32-62 can be employed in one or more embodiments of methods of the invention, for example, in hybridization and amplification technologies and in analogous methods that distinguish SEQ ID NO:32-62 from related polynucleotides. The precise length of a fragment of SEQ ID NO:32-62 and the region of SEQ ID NO:32-62 to which the fragment corresponds are routinely determinable by one of ordinary skill in the art based on the intended purpose for the fragment.  
      A fragment of SEQ ID NO:1-31 is encoded by a fragment of SEQ ID NO:32-62. A fragment of SEQ ID NO:1-31 can comprise a region of unique amino acid sequence that specifically identifies SEQ ID NO:1-31. For example, a fragment of SEQ ID NO:1-31 can be used as an immunogenic peptide for the development of antibodies that specifically recognize SEQ ID NO:1-31. The precise length of a fragment of SEQ ID NO:1-31 and the region of SEQ ID NO:1-31 to which the fragment corresponds can be determined based on the intended purpose for the fragment using one or more analytical methods described herein or otherwise known in the art.  
      A “full length” polynucleotide is one containing at least a translation initiation codon (e.g., methionine) followed by an open reading frame and a translation termination codon. A “full length” polynucleotide sequence encodes a “full length” polypeptide sequence.  
      “Homology” refers to sequence similarity or, alternatively, sequence identity, between two or more polynucleotide sequences or two or more polypeptide sequences.  
      The terms “percent identity” and “% identity,” as applied to polynucleotide sequences, refer to the percentage of identical nucleotide matches between at least two polynucleotide sequences aligned 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 alignment between two sequences, and therefore achieve a more meaningful comparison of the two sequences.  
      Percent identity between polynucleotide sequences may be determined using one or more computer algorithms or programs known in the art or described herein. For example, percent identity can be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program This program is part of the LASERGENE software package, a suite of molecular biological analysis programs (DNASTAR, Madison Wis.). CLUSTAL V is described in Higgins, D. G. and P. M. Sharp (1989; CABIOS 5:151-153) and in Higgins, D. G. et al. (1992; CABIOS 8:189-191). For pairwise alignments of polynucleotide sequences, the default parameters are set as follows: Ktuple=2, gap penalty=5, window=4, and “diagonals saved”=4. The “weighted” residue weight table is selected as the default.  
      Alternatively, a suite of commonly used and freely available sequence comparison algorithms which can be used is provided by the National Center for Biotechnology Information (NCBI) Basic Local Alignment 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 called “BLAST 2 Sequences” that is used for direct pairwise comparison of two nucleotide sequences. “BLAST 2 Sequences” can be accessed and used interactively at http://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 (Apr. 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×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 all encode substantially the same protein.  
      The phrases “percent identity” and “% identity,” as applied to polypeptide sequences, refer to the percentage of identical residue matches between at least two polypeptide sequences aligned using a standardized algorithm. Methods of polypeptide sequence alignment are well-known. Some alignment methods take into account conservative amino acid substitutions. Such conservative substitutions, explained in more detail above, generally preserve the charge and hydrophobicity at the site of substitution, thus preserving the structure (and therefore function) of the polypeptide. The phrases “percent similarity” and “% similarity,” as applied to polypeptide sequences, refer to the percentage of residue matches, including identical residue matches and conservative substitutions, between at least two polypeptide sequences aligned using a standardized algorithm. In contrast, conservative substitutions are not included in the calculation of percent identity between polypeptide sequences.  
      Percent identity between polypeptide sequences may be determined using the default parameters of the CLUSTAL V algorithm as incorporated into the MEGALIGN version 3.12e sequence alignment program (described and referenced above). For pairwise alignments of polypeptide sequences using CLUSTAL V, the default parameters are set as follows: Ktuple=1, gap penalty=3, window=5, and “diagonals saved”=5. The PAM250 matrix is selected as the default residue weight table.  
      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 (Apr. 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×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 ID 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 linear microchromosomes which may contain DNA sequences of about 6 kb to 10 Mb in size and which contain all of the elements required for chromosome replication, 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 still retains its original binding ability.  
      “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 annealing 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 allowing less non-specific binding, i.e., binding between pairs of nucleic acid strands that are not perfectly matched. Permissive conditions for annealing of nucleic acid sequences are routinely determinable by one of ordinary skill 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 annealing conditions occur, for example, at 68° C. in the presence of about 6×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 (T m ) 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. and D. W. Russell (2001 ; Molecular Cloning: A Laboratory Manual,  3rd ed., vol. 1-3, Cold Spring Harbor Press, Cold Spring Harbor N.Y., ch. 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×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×SSC, with SDS being present at about 0.1%. Typically, 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 skill 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 acids by virtue of the formation of hydrogen bonds between complementary bases. A hybridization complex may be formed in solution (e.g., C o t or R o t analysis) or formed between one nucleic acid present in solution and another nucleic acid immobilized on a solid support (e.g., paper, membranes, filters, chips, pins or glass slides, or any other appropriate substrate to which cells or their nucleic acids have been fixed).  
      The words “insertion” and “addition” refer to changes in an amino acid or polynucleotide 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 signaling molecules, which may affect cellular and systemic defense systems.  
      An “immunogenic fragment” is a polypeptide or oligopeptide fragment of CADECM which is capable of eliciting an immune response when introduced into a living organism, for example, a mammal. The term “immunogenic fragment” also includes any polypeptide or oligopeptide fragment of CADECM 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 plurality of polynucleotides, polypeptides, antibodies, or other chemical compounds on a substrate.  
      The terms “element” and “array element” refer to a polynucleotide, polypeptide, antibody, or other chemical compound having a unique and defined position on a microarray.  
      The term “modulate” refers to a change in the activity of CADECM. For example, modulation may cause an increase or a decrease in protein activity, binding characteristics, or any other biological, functional, or immunological properties of CADECM.  
      The phrases “nucleic acid” and “nucleic acid sequence” refer to a nucleotide, oligonucleotide, 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-like or RNA-like material.  
      “Operably linked” 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 linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Operably linked 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 oligonucleotide of at least about 5 nucleotides in length linked to a peptide backbone of amino acid residues ending in lysine. The terminal lysine confers solubility to the composition. PNAs preferentially bind complementary single stranded DNA or RNA and stop transcript elongation, and may be pegylated to extend their lifespan in the cell.  
      “Post-translational modification” of an CADECM may involve lipidation, glycosylation, phosphorylation, acetylation, racemization, proteolytic cleavage, and other modifications known in the art. These processes may occur synthetically or biochemically. Biochemical modifications will vary by cell type depending on the enzymatic milieu of CADECM.  
      “Probe” refers to nucleic acids encoding CADECM, their complements, or fragments thereof, which are used to detect identical, allelic or related nucleic acids. Probes are isolated oligonucleotides or polynucleotides attached to a detectable label or reporter molecule. Typical labels include radioactive isotopes, ligands, chemiluminescent agents, and enzymes. “Primers” are short nucleic acids, usually DNA oligonucleotides, 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 amplification (and identification) of a nucleic acid, e.g., by the polymerase chain reaction (PCR).  
      Probes and primers as used in the present invention typically 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, for example, Sambrook, J. and D. W. Russell (2001 ; Molecular Cloning: A Laboratory Manual,  3rd ed., vol. 1-3, Cold Spring Harbor Press, Cold Spring Harbor N.Y.), Ausubel, F. M. et al. (1999 ; Short Protocols in Molecular Biology,  4 th  ed., John Wiley &amp; Sons, New York N.Y.), and Innis, M. et al. (1990 ; PCR Protocols, A Guide to Methods and Applications , Academic Press, San Diego Calif.). PCR primer pairs can be derived from a known sequence, for example, by using computer programs intended for that purpose such as Primer (Version 0.5, 1991, Whitehead Institute for Biomedical Research, Cambridge Mass.).  
      Oligonucleotides for use as primers are selected using software known in the art for such purpose. 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 oligonucleotides and larger polynucleotides of up to 5,000 nucleotides from an input polynucleotide sequence of up to 32 kilobases. Similar primer selection programs have incorporated additional features for expanded capabilities. For example, the PrimOU primer selection program (available to the public from the Genome Center at University of Texas South West Medical Center, Dallas Tex.) 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 public from the Whitehead Institute/MIT Center for Genome Research, Cambridge Mass.) allows the user to input a “mispriming library,” in which sequences to avoid as primer binding sites are user-specified. Primer3 is useful, in particular, for the selection of oligonucleotides 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&#39;s specific needs.) The PrimeGen program (available to the public from the UK Human Genome Mapping Project Resource Centre, Cambridge UK) designs primers based on multiple sequence alignments, thereby allowing selection of primers that hybridize to either the most conserved or least conserved regions of aligned nucleic acid sequences. Hence, this program is useful for identification of both unique and conserved oligonucleotides and polynucleotide fragments. The oligonucleotides 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 fully or partially complementary polynucleotides in a sample of nucleic acids. Methods of oligonucleotide selection are not limited to those described above.  
      A “recombinant nucleic acid” is a nucleic acid that is not naturally 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 accomplished 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 and Russell (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 linked to a promoter sequence. Such a recombinant nucleic acid may be part of a vector that is used, for example, to transform a cell.  
      Alternatively, such recombinant nucleic acids may be part of a viral vector, e.g., based on a vaccinia virus, 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 usually 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 stability.  
      “Reporter molecules” are chemical or biochemical moieties used for labeling a nucleic acid, amino acid, or antibody. Reporter molecules include radionuclides; 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 molecule, is composed of the same linear sequence of nucleotides as the reference DNA molecule with the exception that all 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 CADECM, nucleic acids encoding CADECM, or fragments thereof may comprise a bodily fluid; an extract from a cell, chromosome, organelle, or membrane isolated from a cell; a cell; 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 structure 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 about 60% free; preferably at least about 75% free, and most preferably at least about 90% free from other components with which they are naturally 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, slides, wafers, fibers, magnetic or nonmagnetic beads, gels, tubing, plates, polymers, microparticles and capillaries. The substrate can have a variety of surface forms, such as wells, trenches, pins, channels and pores, to which polynucleotides or polypeptides are bound.  
      A “transcript image” or “expression profile” refers to the collective pattern of gene expression by a particular cell 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 well 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 cell. The method for transformation is selected based on the type of host cell being transformed and may include, but is not limited to, bacteriophage or viral infection, electroporation, heat shock, lipofection, and particle bombardment. The term “transformed cells” includes stably transformed cells in which the inserted DNA is capable of replication either as an autonomously replicating plasmid or as part of the host chromosome, as well as transiently transformed cells which express the inserted DNA or RNA for limited periods of time.  
      A “transgenic organism,” as used herein, is any organism, including but not limited to animals and plants, in which one or more of the cells 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 cell, directly or indirectly by introduction into a precursor of the cell, by way of deliberate genetic manipulation, such as by microinjection or by infection with a recombinant virus. In another embodiment, the nucleic acid can be introduced by infection with a recombinant viral vector, such as a lentiviral vector (Lois, C. et al. (2002) Science 295:868-872). The term genetic manipulation does not include classical cross-breeding, or in vitro fertilization, 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, transfection, 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 and Russell (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 7, 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 “allelic” (as defined above), “splice,” “species,” or “polymorphic” variant. A splice variant may have significant identity to a reference molecule, but will generally have a greater or lesser number of polynucleotides due to alternate splicing during mRNA processing. The corresponding polypeptide may possess additional functional domains or lack domains that are present in the reference molecule. Species variants are polynucleotides that vary from one species to another. The resulting polypeptides will generally have significant amino acid identity relative to each other. A polymorphic variant is a variation in the polynucleotide sequence of a particular gene between individuals of a given species. Polymorphic variants also may encompass “single nucleotide polymorphisms” (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 or sequence similarity 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 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 or sequence similarity over a certain defined length of one of the polypeptides.  
      The Invention  
      Various embodiments of the invention include new human cell adhesion and extracellular matrix proteins (CADECM), the polynucleotides encoding CADECM, and the use of these compositions for the diagnosis, treatment, or prevention of immune system disorders, neurological disorders, developmental disorders, connective tissue disorders, and cell proliferative disorders, including cancer.  
      Table 1 summarizes the nomenclature for the full length polynucleotide and polypeptide embodiments 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 ID) as shown. Each polynucleotide sequence is denoted by both a polynucleotide sequence identification number (Polynucleotide SEQ ID NO:) and an Incyte polynucleotide consensus sequence number (Incyte Polynucleotide ID) as shown. Column 6 shows the Incyte ID numbers of physical, full length clones corresponding to the polypeptide and polynucleotide sequences of the invention. The full length clones encode polypeptides which have at least 95% sequence identity to the polypeptide sequences shown in column 3.  
      Table 2 shows sequences with homology to polypeptide embodiments 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 ID) for polypeptides of the invention. Column 3 shows the GenBank identification number (GenBank ID 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 probability 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 applicable, all of which are expressly incorporated 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 ID) 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 (Accelrys, Burlington Mass.). 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 applied.  
      Together, Tables 2 and 3 summarize the properties of polypeptides of the invention, and these properties establish that the claimed polypeptides are cell adhesion and extracellular matrix proteins. For example, SEQ ID NO:1 is 91% identical, from residue L15 to residue V989, to human NrCAM protein (GenBank ID g2511666) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 2.0e-301, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:1 also has homology to neuronal cell adhesion molecule, a member of the immunoglobulin superfamily predicted to have a role in neuronal cell adhesion, as determined by BLAST analysis using the PROTEOME database. SEQ ID NO:1 also contains a fibronectin type III domain as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM and SMARTs databases and an Ig superfamily from SCOP domain as determined by a search of the HMM-based INCY database. (See Table 3.) Data from MOTIFS analyses, and BLAST analyses against the PRODOM and DOMO databases, provide further corroborative evidence that SEQ ID NO:1 is a cell adhesion molecule. In another example, SEQ ID NO:9 is 96% identical, from residue M1 to residue P673, and 99% identical from residue G643 to residue S752 to human LI-adherin (GenBank ID g854175) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 0.0, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:9 also has homology to proteins that are localized to the plasma membrane, mediate calcium-dependent cell to cell adhesion, are expressed in gastric intestinal metaplasia and andenocarcinomas, and are liver-intestine cadherins, as determined by BLAST analysis using the PROTEOME database. SEQ ID NO:9 also contains cadherin domains as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM and SMART databases of conserved protein families/domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFILESCAN analyses, and BLAST analyses against the PRODOM and DOMO databases, provide further corroborative evidence that SEQ ID NO:9 is a cadherin. In another example, SEQ ID NO:16 is 99% identical, from residue M1 to residue Q947, to human platelet glycoprotein IIb, a member of the integrin family that functions as a receptor for fibrinogen (GenBank ID g386753) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 0.0, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:16 also has homology to integrin alpha 2b, a subunit of the fibrinogen receptor that is involved in hemostasis, blood coagulation, platelet aggregation, cell adhesion and actin reoganization, and is associated with immune thrombocytopenic purpura and Glanzmann thrombasthenia, as determined by BLAST analysis using the PROTEOME database. SEQ ID NO:16 also contains an integrin alpha domain as well as FG-GAP repeats as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM and SMART databases of conserved protein families/domains. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFILESCAN analyses, and BLAST analyses against the PRODOM and DOMO databases, provide further corroborative evidence that SEQ ID NO:16 is an integrin alpha subunit. In another example, SEQ ID NO:24 is 92% identical from residue M1 to residue V4560, to  Rattus norvegicus  fat3 (GenBank ID g19773543) as determined by the Basic Local Alignment Search Tool (BLAST). (See Table 2.) The BLAST probability score is 0.0, which indicates the probability of obtaining the observed polypeptide sequence alignment by chance. SEQ ID NO:24 also has homology to FAT tumor suppressor homolog, a member of the cadherin superfamily, as determined by BLAST analysis using the PROTEOME database. SEQ ID NO:24 also contains epidermal growth factor (EGF)-like domains, cadherin repeats, calcium-binding EGF domains, and a laminin G domain as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based SMART database of conserved protein families/domains, as well as an epidermal growth factor (EGF)-like domain and a laminin G domain as determined by searching for statistically significant matches in the hidden Markov model (HMM)-based PFAM database. (See Table 3.) Data from BLIMPS, MOTIFS, and PROFILESCAN analyses, and BLAST analyses against the PRODOM and DOMO databases, provide further corroborative evidence that SEQ ID NO:24 is a cadherin. SEQ ID NO:2-8, SEQ ID NO:10-15, SEQ ID NO:17-23, and SEQ ID NO:25-31 were analyzed and annotated in a similar manner. The algorithms and parameters for the analysis of SEQ ID NO:1-31 are described in Table 7.  
      As shown in Table 4, the full length polynucleotide embodiments were assembled using cDNA sequences or coding (exon) sequences derived from genomic DNA, or any combination of these two types of sequences. Column 1 lists 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 full length polynucleotide embodiments, and of fragments of the polynucleotides which are useful, for example, in hybridization or amplification technologies that identify SEQ ID NO:32-62 or that distinguish between SEQ ID NO:32-62 and related polynucleotides.  
      The polynucleotide fragments described in Column 2 of Table 4 may refer specifically, for example, to Incyte cDNAs derived from tissue-specific cDNA libraries or from pooled cDNA libraries. Alternatively, the polynucleotide fragments described in column 2 may refer to GenBank cDNAs or ESTs which contributed to the assembly of the full length polynucleotides. 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 FL_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 applied, and YYYYY is the number of the prediction generated by the algorithm, and N 1,2,3 . . .  , if present, represent specific exons that may have been manually 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 FLXXXXXX_gAAAAA_gBBBBB — 1_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 applied, 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 GenBank 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 following Table lists examples of component sequence prefixes and corresponding sequence analysis methods associated with the prefixes (see Example IV and Example V).  
                                   Prefix   Type of analysis and/or examples of programs                  GNN, GFG,   Exon prediction from genomic sequences using,       ENST   for example, GENSCAN (Stanford University,           CA, USA) or FGENES (Computer Genomics Group,           The Sanger Centre, Cambridge, UK).       GBI   Hand-edited analysis of genomic sequences.       FL   Stitched or stretched genomic sequences (see Example V).       INCY   Full length transcript and exon prediction from mapping           of EST sequences to the genome. Genomic location           and EST composition data are combined to predict           the exons and resulting transcript.                  
 
      In some cases, Incyte cDNA coverage redundant with the sequence coverage shown in Table 4 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 libraries for those full length polynucleotides which were assembled using Incyte cDNA sequences. The representative cDNA library is the Incyte cDNA library which is most frequently represented by the Incyte cDNA sequences which were used to assemble and confirm the above polynucleotides. The tissues and vectors which were used to construct the cDNA libraries shown in Table 5 are described in Table 6.  
      Table 8 shows single nucleotide polymorphisms (SNPs) found in polynucleotide sequences of the invention, along with allele frequencies in different human populations. Columns 1 and 2 show the polynucleotide sequence identification number (SEQ ID NO:) and the corresponding Incyte project identification number (PID) for polynucleotides of the invention. Column 3 shows the Incyte identification number for the EST in which the SNP was detected (EST ID), and column 4 shows the identification number for the SNP (SNP ID). Column 5 shows the position within the EST sequence at which the SNP is located (EST SNP), and column 6 shows the position of the SNP within the full-length polynucleotide sequence (CB 1 SNP). Column 7 shows the allele found in the EST sequence. Columns 8 and 9 show the two alleles found at the SNP site. Column 10 shows the amino acid encoded by the codon including the SNP site, based upon the allele found in the EST. Columns 11-14 show the frequency of allele 1 in four different human populations. An entry of n/d (not detected) indicates that the frequency of allele 1 in the population was too low to be detected, while n/a (not available) indicates that the allele frequency was not determined for the population.  
      The invention also encompasses CADECM variants. Various embodiments of CADECM variants can have at least about 80%, at least about 90%, or at least about 95% amino acid sequence identity to the CADECM amino acid sequence, and can contain at least one functional or structural characteristic of CADECM.  
      Various embodiments also encompass polynucleotides which encode CADECM. In a particular embodiment, the invention encompasses a polynucleotide sequence comprising a sequence selected from the group consisting of SEQ ID NO:32-62, which encodes CADECM. The polynucleotide sequences of SEQ ID NO:32-62, as presented in the Sequence Listing, embrace the 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 variants of a polynucleotide encoding CADECM. In particular, such a variant polynucleotide will have at least about 70%, or alternatively at least about 85%, or even at least about 95% polynucleotide sequence identity to a polynucleotide encoding CADECM. A particular aspect of the invention encompasses a variant of a polynucleotide comprising a sequence selected from the group consisting of SEQ ID NO:32-62 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:32-62. Any one of the polynucleotide variants described above can encode a polypeptide which contains at least one functional or structural characteristic of CADECM.  
      In addition, or in the alternative, a polynucleotide variant of the invention is a splice variant of a polynucleotide encoding CADECM. A splice variant may have portions which have significant sequence identity to a polynucleotide encoding CADECM, but will generally have a greater or lesser number of polynucleotides due to additions or deletions of blocks of sequence arising from alternate splicing during mRNA processing. A splice variant may have less than about 70%, or alternatively less than about 60%, or alternatively less than about 50% polynucleotide sequence identity to a polynucleotide encoding CADECM over its entire length; however, portions of the splice variant will 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 encoding CADECM. For example, a polynucleotide comprising a sequence of SEQ ID NO:33 and a polynucleotide comprising a sequence of SEQ ID NO:34 are splice variants of each other; and a polynucleotide comprising a sequence of SEQ ID NO:35 and a polynucleotide comprising a sequence of SEQ ID NO:36 are splice variants of each other; a polynucleotide comprising a sequence of SEQ ID NO:39 and a polynucleotide comprising a sequence of SEQ ID NO:46 are splice variants of each other; a polynucleotide comprising a sequence of SEQ ID NO:51 and a polynucleotide comprising a sequence of SEQ ID NO:57 are splice variants of each other; and a polynucleotide comprising a sequence of SEQ ID NO:59 and a polynucleotide comprising a sequence of SEQ ID NO:60 are splice variants of each other. Any one of the splice variants described above can encode a polypeptide which contains at least one functional or structural characteristic of CADECM.  
      It will be appreciated by those skilled in the art that as a result of the degeneracy of the genetic code, a multitude of polynucleotide sequences encoding CADECM, some bearing minimal similarity to the polynucleotide sequences of any known and naturally 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 applied to the polynucleotide sequence of naturally occurring CADECM, and all such variations are to be considered as being specifically disclosed.  
      Although polynucleotides which encode CADECM and its variants are generally capable of hybridizing to polynucleotides encoding naturally occurring CADECM under appropriately selected conditions of stringency, it may be advantageous to produce polynucleotides encoding CADECM or its derivatives possessing a substantially different codon usage, e.g., inclusion of non-naturally 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 utilized by the host. Other reasons for substantially altering the nucleotide sequence encoding CADECM 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-life, than transcripts produced from the naturally occurring sequence.  
      The invention also encompasses production of polynucleotides which encode CADECM and CADECM derivatives, or fragments thereof, entirely by synthetic chemistry. After production, the synthetic polynucleotide may be inserted into any of the many available expression vectors and cell, systems using reagents well known in the art. Moreover, synthetic chemistry may be used to introduce mutations into a polynucleotide encoding CADECM or any fragment thereof.  
      Embodiments of the invention can also include polynucleotides that are capable of hybridizing to the claimed polynucleotides, and, in particular, to those having the sequences shown in SEQ ID NO:32-62 and fragments thereof, under various conditions of stringency (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 annealing and wash conditions, are described in “Definitions.” 
      Methods for DNA sequencing are well 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 Ohio), Taq polymerase (Applied Biosystems), thermostable T7 polymerase (Amersham Biosciences, Piscataway N. J.), or combinations of polymerases and proofreading exonucleases such as those found in the ELONGASE amplification system (Invitrogen, Carlsbad Calif.). Preferably, sequence preparation is automated with machines such as the MICROLAB 2200 liquid transfer system (Hamilton, Reno Nev.), PTC200 thermal cycler (MJ Research, Watertown Mass.) and ABI CATALYST 800 thermal cycler (Applied Biosystems). Sequencing is then carried out using either the ABI 373 or 377 DNA sequencing system (Applied Biosystems), the MEGABACE 1000 DNA sequencing system (Amersham Biosciences), or other systems known in the art. The resulting sequences are analyzed using a variety of algorithms which are well known in the art (Ausubel et al., supra, ch. 7; Meyers, R. A. (1995)  Molecular Biology and Biotechnology , Wiley VCH, New York N.Y., pp. 856-853).  
      The nucleic acids encoding CADECM 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 amplify unknown sequence from genomic DNA within a cloning vector (Sarkar, G. (1993) PCR Methods Applic. 2:318-322). Another method, inverse PCR, uses primers that extend in divergent directions to amplify unknown sequence from a circularized template. The template is derived from restriction fragments comprising a known genomic locus and surrounding sequences (Triglia, T. et al. (1988) Nucleic Acids Res. 16:8186). A third method, capture PCR, involves PCR amplification of DNA fragments adjacent to known sequences in human and yeast artificial chromosome DNA (Lagerstrom, M. et al. (1991) PCR Methods Applic. 1:111-119). In this method, multiple restriction enzyme digestions and ligations 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 (Parker, J. D. et al. (1991) Nucleic Acids Res. 19:3055-3060). Additionally, one may use PCR, nested primers, and PROMOTERFINDER libraries (Clontech, Palo Alto Calif.) to walk genomic DNA. This procedure avoids the need to screen libraries and is useful in finding intron/exon junctions. For all PCR-based methods, primers may be designed using commercially available software, such as OLIGO 4.06 primer analysis software (National Biosciences, Plymouth Minn.) 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 full length cDNAs, it is preferable to use libraries that have been size-selected to include larger cDNAs. In addition, random-primed libraries, which often include sequences containing the 5′ regions of genes, are preferable for situations in which an oligo d(T) library does not yield a full-length cDNA. Genomic libraries may be useful for extension of sequence into 5′ non-transcribed regulatory regions.  
      Capillary electrophoresis systems which are commercially available may be used to analyze the size or confirm the nucleotide sequence of sequencing or PCR products. In particular, capillary 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/light intensity may be converted to electrical signal using appropriate software (e.g., GENOTYPER and SEQUENCE NAVIGATOR, Applied Biosystems), and the entire process from loading of samples to computer analysis and electronic data display may be computer controlled. Capillary electrophoresis is especially preferable for sequencing small DNA fragments which may be present in limited amounts in a particular sample.  
      In another embodiment of the invention, polynucleotides or fragments thereof which encode CADECM may be cloned in recombinant DNA molecules that direct expression of CADECM, or fragments or functional equivalents thereof, in appropriate host cells. Due to the inherent degeneracy of the genetic code, other polynucleotides which encode substantially the same or a functionally equivalent polypeptides may be produced and used to express CADECM.  
      The polynucleotides of the invention can be engineered using methods generally known in the art in order to alter CADECM-encoding sequences for a variety of purposes including, but not limited 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 oligonucleotides may be used to engineer the nucleotide sequences. For example, oligonucleotide-mediated site-directed mutagenesis may be used to introduce mutations that create new restriction sites, alter glycosylation patterns, change codon preference, produce splice variants, and so forth.  
      The nucleotides of the present invention may be subjected to DNA shuffling techniques such as MOLECULARBREEDING (Maxygen Inc., Santa Clara Calif.; described in U.S. Pat. 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 CADECM, such as its biological or enzymatic activity or its ability to bind to other molecules or compounds. DNA shuffling is a process by which a library of gene variants is produced using PCR-mediated recombination of gene fragments. The library 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 naturally occurring genes in a directed and controllable manner.  
      In another embodiment, polynucleotides encoding CADECM may be synthesized, in whole or in part, using one or more chemical methods well known in the art (Caruthers, M. H. et al. (1980) Nucleic Acids Symp. Ser. 7:215-223; Horn, T. et al. (1980) Nucleic Acids Symp. Ser. 7:225-232). Alternatively, CADECM itself or a fragment thereof may be synthesized using chemical methods known in the art. For example, peptide synthesis can be performed using various solution-phase or solid-phase techniques (Creighton, T. (1984)  Proteins, Structures and Molecular Properties , WH Freeman, New York N.Y., pp. 55-60; Roberge, J. Y. et al. (1995) Science 269:202-204). Automated synthesis may be achieved using the ABI 431A peptide synthesizer (Applied Biosystems). Additionally, the amino acid sequence of CADECM, or any part thereof, 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 naturally occurring polypeptide.  
      The peptide may be substantially purified by preparative high performance liquid chromatography (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 (Creighton, supra, pp. 28-53).  
      In order to express a biologically active CADECM, the polynucleotides encoding CADECM 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 polynucleotides encoding CADECM. Such elements may vary in their strength and specificity. Specific initiation signals may also be used to achieve more efficient translation of polynucleotides encoding CADECM. Such signals include the ATG initiation codon and adjacent sequences, e.g. the Kozak sequence. In cases where a polynucleotide sequence encoding CADECM 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 cell system used (Scharf, D. et al. (1994) Results Probl. Cell Differ. 20:125-162).  
      Methods which are well known to those skilled in the art may be used to construct expression vectors containing polynucleotides encoding CADECM and appropriate transcriptional and translational control elements. These methods include in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination (Sambrook and Russell, supra, ch. 1-4, and 8; Ausubel et al., supra, ch. 1, 3, and 15).  
      A variety of expression vector/host systems may be utilized to contain and express polynucleotides encoding CADECM. These include, but are not limited to, microorganisms such as bacteria transformed with recombinant bacteriophage, plasmid, or cosmid DNA expression vectors; yeast transformed with yeast expression vectors; insect cell systems infected with viral expression vectors (e.g., baculovirus); plant cell systems transformed with viral expression vectors (e.g., cauliflower mosaic virus, CaMV, or tobacco mosaic virus, TMV) or with bacterial expression vectors (e.g., Ti or pBR322 plasmids); or animal cell systems (Sambrook and Russell, supra; Ausubel et al., 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 Hill Yearbook of Science and Technology  (1992) McGraw Hill, New York N.Y., pp. 191-196; Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659; Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355). Expression vectors derived from retroviruses, adenoviruses, or herpes or vaccinia viruses, or from various bacterial plasmids, may be used for delivery of polynucleotides to the targeted organ, tissue, or cell population (Di Nicola, M. et al. (1998) Cancer Gen. Ther. 5:350-356; Yu, M. et al. (1993) Proc. Natl. Acad. Sci. USA 90:6340-6344; Buller, R. M. et al. (1985) Nature 317:813-815; McGregor, D. P. et al. (1994) Mol. Immunol. 31:219-226; Verma, I. M. and N. Sornia (1997) Nature 389:239-242). The invention is not limited by the host cell employed.  
      In bacterial systems, a number of cloning and expression vectors may be selected depending upon the use intended for polynucleotides encoding CADECM. For example, routine cloning, subcloning, and propagation of polynucleotides encoding CADECM can be achieved using a multifunctional  E. coli  vector such as PBLUESCRIPT (Stratagene, La Jolla Calif.) or PSPORT1 plasmid (Invitrogen). Ligation of polynucleotides encoding CADECM into the vector&#39;s multiple cloning site disrupts the lacZ gene, allowing a colorimetric screening procedure for identification of transformed bacteria containing recombinant molecules. In addition, these vectors may be useful for in vitro transcription, dideoxy sequencing, single strand rescue with helper phage, and creation of nested deletions in the cloned sequence (Van Heeke, G. and S. M. Schuster (1989) J. Biol. Chem. 264:5503-5509). When large quantities of CADECM are needed, e.g. for the production of antibodies, vectors which direct high level expression of CADECM 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 CADECM. 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 intracellular retention of expressed proteins and enable integration of foreign polynucleotide sequences into the host genome for stable propagation (Ausubel et al., supra; Bitter, G. A. et al. (1987) Methods Enzymol. 153:516-544; Scorer, C. A. et al. (1994) Bio/Technology 12:181-184).  
      Plant systems may also be used for expression of CADECM. Transcription of polynucleotides encoding CADECM 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 (Coruzzi, G. et al. (1984) EMBO J. 3:1671-1680; Broglie, R. et al. (1984) Science 224:838-843; Winter, J. et al. (1991) Results Probl. Cell Differ. 17:85-105). These constructs can be introduced into plant cells by direct DNA transformation or pathogen-mediated transfection ( The McGraw Hill Yearbook of Science and Technology  (1992) McGraw Hill, New York N.Y., pp. 191-196).  
      In mammalian cells, a number of viral-based expression systems may be utilized. In cases where an adenovirus is used as an expression vector, polynucleotides encoding CADECM may be ligated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a non-essential E1 or E3 region of the viral genome may be used to obtain infective virus-which expresses CADECM in host cells (Logan, J. and T. Shenk (1984) Proc. Natl. Acad. Sci. USA 81:3655-3659). In addition, transcription enhancers, such as the Rous sarcoma virus (RSV) enhancer, may be used to increase expression in mammalian host cells. SV40 or EBV-based vectors may also be used for high-level protein expression.  
      Human artificial chromosomes (HACs) may also be employed to deliver larger fragments of DNA than can be contained in and expressed from a plasmid. HACs of about 6 kb to 10 Mb are constructed and delivered via conventional delivery methods (liposomes, polycationic amino polymers, or vesicles) for therapeutic purposes (Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355).  
      For long term production of recombinant proteins in mammalian systems, stable expression of CADECM in cell lines is preferred. For example, polynucleotides encoding CADECM can be transformed into cell lines using expression vectors which may contain viral origins of replication and/or endogenous expression elements and a selectable marker gene on the same or on a separate vector. Following the introduction of the vector, cells may be allowed to grow for about 1 to 2 days in enriched media before being switched to selective media. The purpose of the selectable marker is to confer resistance to a selective agent, and its presence allows growth and recovery of cells which successfully express the introduced sequences. Resistant clones of stably transformed cells may be propagated using tissue culture techniques appropriate to the cell type.  
      Any number of selection systems may be used to recover transformed cell lines. These include, but are not limited to, the herpes simplex virus thymidine kinase and adenine phosphoribosyltransferase genes, for use in tk −  and apr −  cells, respectively (Wigler, M. et al. (1977) Cell 11:223-232; Lowy, I. et al. (1980) Cell 22:817-823). Also, antimetabolite, 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 G418; and als and pat confer resistance to chlorsulfuron and phosphinotricin acetyltransferase, respectively (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 cellular requirements for metabolites (Hartnan, S. C. and R. C. Mulligan (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 (Rhodes, C. A. (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 CADECM is inserted within a marker gene sequence, transformed cells containing polynucleotides encoding CADECM can be identified by the absence of marker gene function. Alternatively, a marker gene can be placed in tandem with a sequence encoding CADECM under the control of a single promoter. Expression of the marker gene in response to induction or selection usually indicates expression of the tandem gene as well.  
      In general, host cells that contain the polynucleotide encoding CADECM and that express CADECM may be identified by a variety of procedures known to those of skill in the art. These procedures include, but are not limited to, DNA-DNA or DNA-RNA hybridizations, PCR amplification, 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 CADECM using either specific polyclonal or monoclonal antibodies are known in the art. Examples of such techniques include enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), and fluorescence activated cell sorting (FACS). A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering epitopes on CADECM is preferred, but a competitive binding assay may be employed. These and other assays are well known in the art (Hampton, R. et al. (1990)  Serological Methods, a Laboratory Manual , APS Press, St. Paul Minn., Sect. IV; Coligan, J. E. et al. (1997)  Current Protocols in Immunology , Greene Pub. Associates and Wiley-Interscience, New York N.Y.; Pound, J. D. (1998)  Immunochemical Protocols , Humana Press, Totowa N.J.).  
      A wide variety of labels and conjugation techniques are known by those skilled 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 CADECM include oligolabeling, nick translation, end-labeling, or PCR amplification using a labeled nucleotide. Alternatively, polynucleotides encoding CADECM, 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 commercially available kits, such as those provided by Amersham Biosciences, Promega (Madison Wis.), and US Biochemical. Suitable reporter molecules or labels which may be used for ease of detection include radionuclides, enzymes, fluorescent, chemiluminescent, or chromogenic agents, as well as substrates, cofactors, inhibitors, magnetic particles, and the like.  
      Host cells transformed with polynucleotides encoding CADECM may be cultured under conditions suitable for the expression and recovery of the protein from cell culture. The protein produced by a transformed cell may be secreted or retained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors containing polynucleotides which encode CADECM may be designed to contain signal sequences which direct secretion of CADECM through a prokaryotic or eukaryotic cell membrane.  
      In addition, a host cell strain may be chosen for its ability to modulate expression of the inserted polynucleotides or to process the expressed protein in the desired fashion. Such modifications of the polypeptide include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, 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 cells which have specific cellular machinery and characteristic mechanisms for post-translational activities (e.g., CHO, HeLa, MDCK, HEK293, and WI38) are available from the American Type Culture Collection (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 polynucleotides encoding CADECM may be ligated to a heterologous sequence resulting in translation of a fusion protein in any of the aforementioned host systems. For example, a chimeric CADECM protein containing a heterologous moiety that can be recognized by a commercially available antibody may facilitate the screening of peptide libraries for inhibitors of CADECM activity. Heterologous protein and peptide moieties may also facilitate purification of fusion proteins using commercially available affinity matrices. Such moieties include, but are not limited to, glutathione S-transferase (GST), maltose binding protein (MBP), thioredoxin (Trx), calmodulin 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 immobilized glutathione, maltose, phenylarsine oxide, calmodulin, and metal-chelate resins, respectively. FLAG, c-myc, and hemagglutinin(HA) enable immunoaffinity purification of fusion proteins using commercially available monoclonal and polyclonal antibodies that specifically recognize these epitope tags. A fusion protein may also be engineered to contain a proteolytic cleavage site located between the CADECM encoding sequence and the heterologous protein sequence, so that CADECM may be cleaved away from the heterologous moiety following purification. Methods for fusion protein expression and purification are discussed in Ausubel et al. (supra, ch. 10 and 16). A variety of commercially available kits may also be used to facilitate expression and purification of fusion proteins.  
      In another embodiment, synthesis of radiolabeled CADECM 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.  
      CADECM, fragments of CADECM, or variants of CADECM may be used to screen for compounds that specifically bind to CADECM. One or more test compounds may be screened for specific binding to CADECM. In various embodiments, 1, 2, 3, 4, 5, 10, 20, 50, 100, or 200 test compounds can be screened for specific binding to CADECM. Examples of test compounds can include antibodies, anticalins, oligonucleotides, proteins (e.g., ligands or receptors), or small molecules.  
      In related embodiments, variants of CADECM can be used to screen for binding of test compounds, such as antibodies, to CADECM, a variant of CADECM, or a combination of CADECM and/or one or more variants CADECM. In an embodiment, a variant of CADECM can be used to screen for compounds that bind to a variant of CADECM, but not to CADECM having the exact sequence of a sequence of SEQ ID NO:1-31. CADECM variants used to perform such screening can have a range of about 50% to about 99% sequence identity to CADECM, with various embodiments having 60%, 70%, 75%, 80%, 85%, 90%, and 95% sequence identity.  
      In an embodiment, a compound identified in a screen for specific binding to CADECM can be closely related to the natural ligand of CADECM, e.g., a ligand or fragment thereof, a natural substrate, a structural or functional mimetic, or a natural binding partner (Coligan, J. E. et al. (1991)  Current Protocols in Immunology  1(2):Chapter 5). In another embodiment, the compound thus identified can be a natural ligand of a receptor CADECM (Howard, A. D. et al. (2001) Trends Pharmacol. Sci.22:132-140; Wise, A. et al. (2002) Drug Discovery Today 7:235-246).  
      In other embodiments, a compound identified in a screen for specific binding to CADECM can be closely related to the natural receptor to which CADECM binds, at least a fragment of the receptor, or a fragment of the receptor including all or a portion of the ligand binding site or binding pocket. For example, the compound may be a receptor for CADECM which is capable of propagating a signal, or a decoy receptor for CADECM which is not capable of propagating a signal (Ashkenazi, A. and V. M. Divit (1999) Curr. Opin. Cell Biol. 11:255-260; Mantovani, A. et al. (2001) Trends Immunol. 22:328-336). The compound can be rationally designed using known techniques. Examples of such techniques include those used to construct the compound etanercept (ENBREL; Amgen Inc., Thousand Oaks Calif.), which is efficacious for treating rheumatoid arthritis in humans. Etanercept is an engineered p75 tumor necrosis factor (TNF) receptor dimer linked to the Fc portion of human IgG 1  (Taylor, P. C. et al. (2001) Curr. Opin. Immunol. 13:611-616).  
      In one embodiment, two or more antibodies having similar or, alternatively, different specificities can be screened for specific binding to CADECM, fragments of CADECM, or variants of CADECM. The binding specificity of the antibodies thus screened can thereby be selected to identify particular fragments or variants of CADECM. In one embodiment, an antibody can be selected such that its binding specificity allows for preferential identification of specific fragments or variants of CADECM. In another embodiment, an antibody can be selected such that its binding specificity allows for preferential diagnosis of a specific disease or condition having increased, decreased, or otherwise abnormal production of CADECM.  
      In an embodiment, anticalins can be screened for specific binding to CADECM, fragments of CADECM, or variants of CADECM. Anticalins are ligand-binding proteins that have been constructed based on a lipocalin scaffold (Weiss, G. A. and H. B. Lowman (2000) Chem. Biol. 7:R177-R184; Skerra, A. (2001) J. Biotechnol. 74:257-275). The protein architecture of lipocalins can include a beta-barrel having eight antiparallel beta-strands, which supports four loops at its open end. These loops form the natural ligand-binding site of the lipocalins, a site which can be re-engineered in vitro by amino acid substitutions to impart novel binding specificities. The amino acid substitutions can be made using methods known in the art or described herein, and can include conservative substitutions (e.g., substitutions that do not alter binding specificity) or substitutions that modestly, moderately, or significantly alter binding specificity.  
      In one embodiment, screening for compounds which specifically bind to, stimulate, or inhibit CADECM involves producing appropriate cells which express CADECM, either as a secreted protein or on the cell membrane. Preferred cells can include cells from mammals, yeast,  Drosophila , or  E. coli . Cells expressing CADECM or cell membrane fractions which contain CADECM are then contacted with a test compound and binding, stimulation, or inhibition of activity of either CADECM or the compound 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 CADECM, either in solution or affixed to a solid support, and detecting the binding of CADECM to the compound. Alternatively, the assay may detect or measure binding of a test compound in the presence of a labeled competitor. Additionally, the assay may be carried out using cell-free preparations, chemical libraries, or natural product mixtures, and the test compound(s) may be free in solution or affixed to a solid support.  
      An assay can be used to assess the ability of a compound to bind to its natural ligand and/or to inhibit the binding of its natural ligand to its natural receptors. Examples of such assays include radio-labeling assays such as those described in U.S. Pat. No. 5,914,236 and U.S. Pat. No. 6,372,724. In a related embodiment, one or more amino acid substitutions can be introduced into a polypeptide compound (such as a receptor) to improve or alter its ability to bind to its natural ligands (Matthews, D. J. and J. A. Wells. (1994) Chem. Biol. 1:25-30). In another related embodiment, one or more amino acid substitutions can be introduced into a polypeptide compound (such as a ligand) to improve or alter its ability to bind to its natural receptors (Cunningham, B. C. and J. A. Wells (1991) Proc. Natl. Acad. Sci. USA 88:3407-3411; Lowman, H. B. et al. (1991) J. Biol. Chem. 266:10982-10988).  
      CADECM, fragments of CADECM, or variants of CADECM may be used to screen for compounds that modulate the activity of CADECM. Such compounds may include agonists, antagonists, or partial or inverse agonists. In one embodiment, an assay is performed under conditions permissive for CADECM activity, wherein CADECM is combined with at least one test compound, and the activity of CADECM in the presence of a test compound is compared with the activity of CADECM in the absence of the test compound. A change in the activity of CADECM in the presence of the test compound is indicative of a compound that modulates the activity of CADECM. Alternatively, a test compound is combined with an in vitro or cell-free system comprising CADECM under conditions suitable for CADECM activity, and the assay is performed. In either of these assays, a test compound which modulates the activity of CADECM may do so indirectly and need not come in direct contact with the test compound. At least one and up to a plurality of test compounds may be screened.  
      In another embodiment, polynucleotides encoding CADECM or their mammalian homologs may be “knocked out” in an animal model system using homologous recombination in embryonic stem (ES) cells. Such techniques are well known in the art and are useful for the generation of animal models of human disease (see, e.g., U.S. Pat. No. 5,175,383 and U.S. Pat. No. 5,767,337). For example, mouse ES cells, such as the mouse 129/SvJ cell line, are derived from the early mouse embryo and grown in culture. The ES cells are transformed with a vector containing the gene of interest disrupted by a marker gene, e.g., the neomycin phosphotransferase 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) Clin. Invest. 97:1999-2002; Wagner, K. U. et al. (1997) Nucleic Acids Res. 25:4323-4330). Transformed ES cells are identified and microinjected into mouse cell blastocysts such as those from the C57BL/6 mouse strain. The blastocysts are surgically 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 CADECM may also be manipulated in vitro in ES cells derived from human blastocysts. Human ES cells have the potential to differentiate into at least eight separate cell lineages including endoderm, mesoderm, and ectodermal cell types. These cell lineages differentiate into, for example, neural cells, hematopoietic lineages, and cardiomyocytes (Thomson, J. A. et al. (1998) Science 282:1145-1147).  
      Polynucleotides encoding CADECM 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 CADECM is injected into animal ES cells, and the injected sequence integrates into the animal cell genome. Transformed cells are injected into blastulae, and the blastulae are implanted as described above. Transgenic progeny or inbred lines are studied and treated with potential pharmaceutical agents to obtain information on treatment of a human disease. Alternatively, a mammal inbred to overexpress CADECM, e.g., by secreting CADECM 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 CADECM and cell adhesion and extracellular matrix proteins. In addition, examples of tissues expressing CADECM can be found in Table 6 and can also be found in Example XI. Therefore, CADECM appears to play a role in immune system disorders, neurological disorders, developmental disorders, connective tissue disorders, and cell proliferative disorders, including cancer. In the treatment of disorders associated with increased CADECM expression or activity, it is desirable to decrease the expression or activity of CADECM. In the treatment of disorders associated with decreased CADECM expression or activity, it is desirable to increase the expression or activity of CADECM.  
      Therefore, in one embodiment, CADECM 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 CADECM. Examples of such disorders include, but are not limited to, an immune system disorder, such as acquired immunodeficiency syndrome (AIDS), X-linked agammaglobinemia of Bruton, common variable immunodeficiency (CVI), DiGeorge&#39;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, immunodeficiency associated with Cushing&#39;s disease, Addison&#39;s disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), bronchitis, cholecystitis, contact dermatitis, Crohn&#39;s disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture&#39;s syndrome, gout, Graves&#39; disease, Hashimoto&#39;s thyroiditis, hypereosinophilia, irritable bowel syndrome, multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis, Reiter&#39;s syndrome, rheumatoid arthritis, scleroderma, Sjögren&#39;s syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, viral, bacterial, fungal, parasitic, protozoal, and helminthic infections, and trauma; a neurological disorder, such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer&#39;s disease, Pick&#39;s disease, Huntington&#39;s disease, dementia, Parkinson&#39;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 demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal 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, metabolic, 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, postherpetic neuralgia, Tourette&#39;s disorder, progressive supranuclear palsy, corticobasal degeneration, and familial frontotemporal dementia; a developmental disorder, such as renal tubular acidosis, anemia, Cushing&#39;s syndrome, achondroplastic dwarfism, Duchenne and Becker muscular dystrophy, epilepsy, gonadal dysgenesis, WAGR syndrome (Wilms&#39; tumor, aniridia, genitourinary abnormalities, and mental retardation), Smith-Magenis syndrome, myelodysplastic syndrome, hereditary mucoepithelial dysplasia, hereditary keratodermas, hereditary neuropathies such as Charcot-Marie-Tooth disease and neurofibromatosis, hypothyroidism, hydrocephalus, seizure disorders such as Syndenham&#39;s chorea and cerebral palsy, spina bifida, anencephaly, craniorachischisis, congenital glaucoma, cataract, and sensorineural hearing loss; a connective tissue disorder, such as osteogenesis imperfecta, Ehlers-Danlos syndrome, chondrodysplasias, Marfan syndrome, Alport syndrome, familial aortic aneurysm, achondroplasia, mucopolysaccharidoses, osteoporosis, osteopetrosis, Paget&#39;s disease, rickets, osteomalacia, hyperparathyroidism, renal osteodystrophy, osteonecrosis, osteomyelitis, osteoma, osteoid osteoma, osteoblastoma, osteosarcoma, osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma, chondrosarcoma, fibrous cortical defect, nonossifying fibroma, fibrous dysplasia, fibrosarcoma, malignant fibrous histiocytoma, Ewing&#39;s sarcoma, primitive neuroectodermal tumor, giant cell tumor, osteoarthritis, rheumatoid arthritis, ankylosing spondyloarthritis, Reiter&#39;s syndrome, psoriatic arthritis, enteropathic arthritis, infectious arthritis, gout, gouty arthritis, calcium pyrophosphate crystal deposition disease, ganglion, synovial cyst, villonodular synovitis, systemic sclerosis, Dupuytren&#39;s contracture, hepatic fibrosis, lupus erythematosus, mixed connective tissue disease, epidermolysis bullosa simplex, bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis), non-epidermolytic and epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, pachyonychia congenita, and white sponge nevus; and a cell proliferative 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, colon, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus.  
      In another embodiment, a vector capable of expressing CADECM 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 CADECM including, but not limited to, those described above.  
      In a further embodiment, a composition comprising a substantially purified CADECM 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 CADECM including, but not limited to, those provided above.  
      In still another embodiment, an agonist which modulates the activity of CADECM may be administered to a subject to treat or prevent a disorder associated with decreased expression or activity of CADECM including, but not limited to, those listed above.  
      In a further embodiment, an antagonist of CADECM may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of CADECM. Examples of such disorders include, but are not limited to, those immune system disorders, neurological disorders, developmental disorders, connective tissue disorders, and cell proliferative disorders, including cancer described above. In one aspect, an antibody which specifically binds CADECM may be used directly as an antagonist or indirectly as a targeting or delivery mechanism for bringing a pharmaceutical agent to cells or tissues which express CADECM.  
      In an additional embodiment, a vector expressing the complement of the polynucleotide encoding CADECM may be administered to a subject to treat or prevent a disorder associated with increased expression or activity of CADECM including, but not limited to, those described above.  
      In other embodiments, any protein, agonist, antagonist, antibody, complementary sequence, or vector embodiments 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 skill in the art, according to conventional pharmaceutical principles. The combination of therapeutic agents may act synergistically 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 CADECM may be produced using methods which are generally known in the art. In particular, purified CADECM may be used to produce antibodies or to screen libraries of pharmaceutical agents to identify those which specifically bind CADECM. Antibodies to CADECM may also be generated using methods that are well known in the art. Such antibodies may include, but are not limited to, polyclonal, monoclonal, chimeric, and single chain antibodies, Fab fragments, and fragments produced by a Fab expression library. In an embodiment, neutralizing antibodies (i.e., those which inhibit dimer formation) can be used therapeutically. Single chain antibodies (e.g., from camels or llamas) may be potent enzyme inhibitors and may have application in the design of peptide mimetics, and in the development of immuno-adsorbents and biosensors (Muyldermans, S. (2001) J. Biotechnol. 74:277-302).  
      For the production of antibodies, various hosts including goats, rabbits, rats, mice, camels, dromedaries, llamas, humans, and others may be immunized by injection with CADECM or with any fragment or oligopeptide 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 limited to, Freund&#39;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  Corynebacterium parvum  are especially preferable.  
      It is preferred that the oligopeptides, peptides, or fragments used to induce antibodies to CADECM have an amino acid sequence consisting of at least about 5 amino acids, and generally will consist of at least about 10 amino acids. It is also preferable that these oligopeptides, peptides, or fragments are substantially identical to a portion of the amino acid sequence of the natural protein. Short stretches of CADECM 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 CADECM may be prepared using any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique, the human B-cell hybridoma technique, and the EBV-hybridoma technique (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; Cole, S. P. et al. (1984) Mol. Cell Biol. 62:109-120).  
      In addition, techniques developed for the production of “chimeric antibodies,” such as the splicing of mouse antibody genes to human antibody genes to obtain a molecule with appropriate antigen specificity and biological activity, can be used (Morrison, S. L. et al. (1984) Proc. Natl. Acad. Sci. USA 81:6851-6855; Neuberger, M. S. et al. (1984) Nature 312:604-608; 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 CADECM-specific single chain antibodies. Antibodies with related specificity, but of distinct idiotypic composition, may be generated by chain shuffling from random combinatorial immunoglobulin libraries (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 immunoglobulin libraries or panels of highly specific binding reagents as disclosed in the literature (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 CADECM may also be generated. For example, such fragments include, but are not limited 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 libraries may be constructed to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity (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 established specificities are well known in the art. Such immunoassays typically involve the measurement of complex formation between CADECM and its specific antibody. A two-site, monoclonal-based immunoassay utilizing monoclonal antibodies reactive to two non-interfering CADECM epitopes is generally 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 CADECM. Affinity is expressed as an association constant, K a , which is defined as the molar concentration of CADECM-antibody complex divided by the molar concentrations of free antigen and free antibody under equilibrium conditions. The K a  determined for a preparation of polyclonal antibodies, which are heterogeneous in their affinities for multiple CADECM epitopes, represents the average affinity, or avidity, of the antibodies for CADECM. The K a  determined for a preparation of monoclonal antibodies, which are monospecific for a particular CADECM epitope, represents a true measure of affinity. High-affinity antibody preparations with K a  ranging from about 10 9  to 10 12  L/mole are preferred for use in immunoassays in which the CADECM-antibody complex must withstand rigorous manipulations. Low-affinity antibody preparations with K a  ranging from about 10 6  to 10 7  L/mole are preferred for use in immunopurification and similar procedures which ultimately require dissociation of CADECM, preferably in active form, from the antibody (Catty, D. (1988)  Antibodies Volume I: A Practical Approach , IRL Press, Washington D.C.; Liddell, J. E. and A. Cryer (1991)  A Practical Guide to Monoclonal Antibodies , John Wiley &amp; Sons, New York N.Y.).  
      The titer and avidity of polyclonal antibody preparations may be further evaluated to determine the quality and suitability of such preparations for certain downstream applications. For example, a polyclonal antibody preparation containing at least 1-2 mg specific antibody/ml, preferably 5-10 mg specific antibody/ml, is generally employed in procedures requiring precipitation of CADECM-antibody complexes. Procedures for evaluating antibody specificity, titer, and avidity, and guidelines for antibody quality and usage in various applications, are generally available (Catty, supra; Coligan et al., supra).  
      In another embodiment of the invention, polynucleotides encoding CADECM, or any fragment or complement thereof, may be used for therapeutic purposes. In one aspect, modifications of gene expression can be achieved by designing complementary sequences or antisense molecules (DNA, RNA, PNA, or modified oligonucleotides) to the coding or regulatory regions of the gene encoding CADECM. Such technology is well known in the art, and antisense oligonucleotides or larger fragments can be designed from various locations along the coding or control regions of sequences encoding CADECM (Agrawal, S., ed. (1996)  Antisense Therapeutics , Humana Press, Totawa N.J.).  
      In therapeutic use, any gene delivery system suitable for introduction of the antisense sequences into appropriate target cells can be used. Antisense sequences can be delivered intracellularly in the form of an expression plasmid which, upon transcription, produces a sequence complementary to at least a portion of the cellular sequence encoding the target protein (Slater, J. E. et al. (1998) J. Allergy Clin. Immunol. 102:469-475; Scanlon, K. J. et al. (1995) FASEB J. 9:1288-1296). Antisense sequences can also be introduced intracellularly through the use of viral vectors, such as retrovirus and adeno-associated virus vectors (Miller, A. D. (1990) Blood 76:271-278; Ausubel et al., supra; Uckert, W. and W. Walther (1994) Pharmacol. Ther. 63:323-347). Other gene delivery mechanisms include liposome-derived systems, artificial viral envelopes, and other systems known in the art (Rossi, J. J. (1995) Br. Med. Bull. 51:217-225; Boado, R. J. et al. (1998) J. Pharm. Sci. 87:1308-1315; Morris, M. C. et al. (1997) Nucleic Acids Res. 25:2730-2736).  
      In another embodiment of the invention, polynucleotides encoding CADECM 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 (SCID)-X1 disease characterized by X-linked 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) Cell 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, familial hypercholesterolemia, and hemophilia resulting from Factor VIII or Factor IX deficiencies (Crystal, R. G. (1995) Science 270:404-410; Verma, I. M. and N. Somia (1997) Nature 389:239-242)), (ii) express a conditionally lethal gene product (e.g., in the case of cancers which result from unregulated cell proliferation), or (iii) express a protein which affords protection against intracellular parasites (e.g., against human retroviruses, such as human immunodeficiency virus (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 virus (HBV, HCV); fungal parasites, such as  Candida albicans  and  Paracoccidioides brasiliensis ; and protozoan parasites such as  Plasmodium falciparum  and  Trypanosoma cruzi ). In the case where a genetic deficiency in CADECM expression or regulation causes disease, the expression of CADECM from an appropriate population of transduced cells may alleviate the clinical manifestations caused by the genetic deficiency.  
      In a further embodiment of the invention, diseases or disorders caused by deficiencies in CADECM are treated by constructing mammalian expression vectors encoding CADECM and introducing these vectors by mechanical means into CADECM-deficient cells. Mechanical transfer technologies for use with cells in vivo or ex vitro include (i) direct DNA microinjection into individual cells, (ii) ballistic gold particle delivery, (iii) liposome-mediated transfection, (iv) receptor-mediated gene transfer, and (v) the use of DNA transposons (Morgan, R. A. and W. F. Anderson (1993) Annu. Rev. Biochen. 62:191-217; Ivics, Z. (1997) Cell 91:501-510; Boulay, J.-L. and H. Récipon (1998) Curr. Opin. Biotechnol. 9:445-450).  
      Expression vectors that may be effective for the expression of CADECM include, but are not limited to, the PCDNA 3.1, EPITAG, PRCCMV2, PREP, PVAX, PCR2-TOPOTA vectors (Invitrogen, Carlsbad Calif.), PCMV-SCRIPT, PCMV-TAG, PEGSH/PERV (Stratagene, La Jolla Calif.), and PTET-OFF, PTET-ON, PTRE2, PTRE2-LUC, PTK-HYG (Clontech, Palo Alto Calif.). CADECM may be expressed using (i) a constitutively active promoter, (e.g., from cytomegalovirus (CMV), Rous sarcoma virus (RSV), SV40 virus, thymidine kinase (TK), or β-actin genes), (ii) an inducible promoter (e.g., the tetracycline-regulated promoter (Gossen, M. and H. Bujard (1992) Proc. Natl. Acad. Sci. USA 89:5547-5551; Gossen, M. et al. (1995) Science 268:1766-1769; Rossi, F. M. V. and H. M. Blau (1998) Curr. Opin. Biotechnol. 9:451-456), commercially available in the T-REX plasmid (Invitrogen)); the ecdysone-inducible promoter (available in the plasmids PVGRXR and PIND; Invitrogen); the FK506/rapamycin inducible promoter; or the RU486/mifepristone inducible promoter (Rossi, F. M. V. and H. M. Blau, supra)), or (iii) a tissue-specific promoter or the native promoter of the endogenous gene encoding CADECM from a normal individual.  
      Commercially available liposome transformation kits (e.g., the PERFECT LIPID TRANSFECTION KIT, available from Invitrogen) allow one with ordinary skill in the art to deliver polynucleotides to target cells 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 cells requires modification of these standardized mammalian transfection protocols.  
      In another embodiment of the invention, diseases or disorders caused by genetic defects with respect to CADECM expression are treated by constructing a retrovirus vector consisting of (i) the polynucleotide encoding CADECM under the control of an independent promoter or the retrovirus long terminal repeat (LTR) promoter, (ii) appropriate RNA packaging signals, and (iii) a Rev-responsive element (RRE) along with additional retrovirus cis-acting RNA sequences and coding sequences required for efficient vector propagation. Retrovirus vectors (e.g., PFB and PFBNEO) are commercially available (Stratagene) and are based on published data (Riviere, I. et al. (1995) Proc. Natl. Acad. Sci. USA 92:6733-6737), incorporated by reference herein. The vector is propagated in an appropriate vector producing cell line (VPCL) that expresses an envelope gene with a tropism for receptors on the target cells 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. Miller (1988) J. Virol. 62:3802-3806; Dull, T. et al. (1998) J. Virol. 72:8463-8471; Zufferey, R. et al. (1998) J. Virol. 72:9873-9880). U.S. Pat. No. 5,910,434 to Rigg (“Method for obtaining retrovirus packaging cell lines producing high transducing efficiency retroviral supernatant”) discloses a method for obtaining retrovirus packaging cell lines and is hereby incorporated by reference. Propagation of retrovirus vectors, transduction of a population of cells (e.g., CD4 +  T-cells), and the return of transduced cells to a patient are procedures well known to persons skilled 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 an embodiment, an adenovirus-based gene therapy delivery system is used to deliver polynucleotides encoding CADECM to cells which have one or more genetic abnormalities with respect to the expression of CADECM. The construction and packaging of adenovirus-based vectors are well known to those with ordinary skill in the art. Replication defective adenovirus 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). Potentially useful adenoviral vectors are described in U.S. Pat. No. 5,707,618 to Armentano (“Adenovirus vectors for gene therapy”), hereby incorporated 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).  
      In another embodiment, a herpes-based, gene therapy delivery system is used to deliver polynucleotides encoding CADECM to target cells which have one or more genetic abnormalities with respect to the expression of CADECM. The use of herpes simplex virus (HSV)-based vectors may be especially valuable for introducing CADECM to cells of the central nervous system, for which HSV has a tropism. The construction and packaging of herpes-based vectors are well known to those with ordinary skill in the art. A replication-competent herpes simplex virus (HSV) type 1-based vector has been used to deliver 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 virus vector has also been disclosed in detail in U.S. Pat. No. 5,804,413 to DeLuca (“Herpes simplex virus strains for gene transfer”), which is hereby incorporated by reference. U.S. Pat. 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 cell under the control of the appropriate promoter for purposes 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). The manipulation of cloned herpesvirus sequences, the generation of recombinant virus following the transfection of multiple plasmids containing different segments of the large herpesvirus genomes, the growth and propagation of herpesvirus, and the infection of cells with herpesvirus are techniques well known to those of ordinary skill in the art.  
      In another embodiment, an alphavirus (positive, single-stranded RNA virus) vector is used to deliver polynucleotides encoding CADECM to target cells. The biology of the prototypic alphavirus, Seinliki Forest Virus (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 replication, a subgenomic RNA is generated that normally encodes the viral capsid proteins. This subgenomic RNA replicates to higher levels than the full length genomic RNA, resulting in the overproduction of capsid proteins relative to the viral proteins with enzymatic activity (e.g., protease and polymerase). Similarly, inserting the coding sequence for CADECM into the alphavirus genome in place of the capsid-coding region results in the production of a large number of CADECM-coding RNAs and the synthesis of high levels of CADECM in vector transduced cells. While alphavirus infection is typically associated with cell lysis within a few days, the ability to establish a persistent infection in hamster normal kidney cells (BHK-21) with a variant of Sindbis virus (SIN) indicates that the lytic replication of alphaviruses can be altered to suit the needs of the gene therapy application (Dryga, S. A. et al. (1997) Virology 228:74-83). The wide host range of alphaviruses will allow the introduction of CADECM into a variety of cell types. The specific transduction of a subset of cells in a population may require the sorting of cells prior to transduction. The methods of manipulating infectious cDNA clones of alphaviruses, performing alphavirus cDNA and RNA transfections, and performing alphavirus infections, are well known to those with ordinary skill in the art.  
      Oligonucleotides 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 helix base-pairing methodology. Triple helix pairing is useful because it causes inhibition of the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described in the literature (Gee, J. E. et al. (1994) in Huber, B. E. and B. I. Carr,  Molecular and Immunologic Approaches , Futura Publishing, Mt. Kisco N.Y., 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, followed by endonucleolytic cleavage. For example, engineered hammerhead motif ribozyme molecules may specifically and efficiently catalyze endonucleolytic cleavage of RNA molecules encoding CADECM.  
      Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites, including the following 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 oligonucleotide inoperable. The suitability of candidate targets may also be evaluated by testing accessibility to hybridization with complementary oligonucleotides using ribonuclease protection assays.  
      Complementary ribonucleic acid molecules and ribozymes may be prepared by any method known in the art for the synthesis of nucleic acid molecules. These include techniques for chemically synthesizing oligonucleotides such as solid phase phosphoramidite chemical synthesis. Alternatively, RNA molecules may be generated by in vitro and in vivo transcription of DNA molecules encoding CADECM. Such DNA sequences may be incorporated into a wide variety of vectors with suitable RNA polymerase promoters such as T7 or SP6. Alternatively, these cDNA constructs that synthesize complementary RNA, constitutively or inducibly, can be introduced into cell lines, cells, or tissues.  
      RNA molecules may be modified to increase intracellular stability and half-life. Possible modifications include, but are not limited 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 linkages 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 nontraditional bases such as inosine, queosine, and wybutosine, as well as acetyl-, methyl-, thio-, and similarly modified forms of adenine, cytidine, guanine, thymine, and uridine which are not as easily recognized by endogenous endonucleases.  
      In other embodiments of the invention, the expression of one or more selected polynucleotides of the present invention can be altered, inhibited, decreased, or silenced using RNA interference (RNAi) or post-transcriptional gene silencing (PTGS) methods known in the art. RNAi is a post-transcriptional mode of gene silencing in which double-stranded RNA (dsRNA) introduced into a targeted cell specifically suppresses the expression of the homologous gene (i.e., the gene bearing the sequence complementary to the dsRNA). This effectively knocks out or substantially reduces the expression of the targeted gene. PTGS can also be accomplished by use of DNA or DNA fragments as well. RNAi methods are described by Fire, A. et al. (1998; Nature 391:806-811) and Gura, T. (2000; Nature 404:804-808). PTGS can also be initiated by introduction of a complementary segment of DNA into the selected tissue using gene delivery and/or viral vector delivery methods described herein or known in the art.  
      RNAi can be induced in mammalian cells by the use of small interfering RNA also known as siRNA. siRNA are shorter segments of dsRNA (typically about 21 to 23 nucleotides in length) that result in vivo from cleavage of introduced dsRNA by the action of an endogenous ribonuclease. siRNA appear to be the mediators of the RNAi effect in mammals. The most effective siRNAs appear to be 21 nucleotide dsRNAs with 2 nucleotide 3′ overhangs. The use of siRNA for inducing RNAi in mammalian cells is described by Elbashir, S. M. et al. (2001; Nature 411:494-498).  
      siRNA can be generated indirectly by introduction of dsRNA into the targeted cell. Alternatively, siRNA can be synthesized directly and introduced into a cell by transfection methods and agents described herein or known in the art (such as liposome-mediated transfection, viral vector methods, or other polynucleotide delivery/introductory methods). Suitable siRNAs can be selected by examining a transcript of the target polynucleotide (e.g., mRNA) for nucleotide sequences downstream from the AUG start codon and recording the occurrence of each nucleotide and the 3′ adjacent 19 to 23 nucleotides as potential siRNA target sites, with sequences having a 21 nucleotide length being preferred. Regions to be avoided for target siRNA sites include the 5′ and 3′ untranslated regions (UTRs) and regions near the start codon (within 75 bases), as these may be richer in regulatory protein binding sites. UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP endonuclease complex. The selected target sites for siRNA can then be compared to the appropriate genome database (e.g., human, etc.) using BLAST or other sequence comparison algorithms known in the art. Target sequences with significant homology to other coding sequences can be eliminated from consideration. The selected siRNAs can be produced by chemical synthesis methods known in the art or by in vitro transcription using commercially available methods and kits such as the SILENCER siRNA construction kit (Ambion, Austin Tex.).  
      In alternative embodiments, long-term gene silencing and/or RNAi effects can be induced in selected tissue using expression vectors that continuously express siRNA. This can be accomplished using expression vectors that are engineered to express hairpin RNAs (shRNAs) using methods known in the art (see, e.g., Brummelkamp, T. R. et al. (2002) Science 296:550-553; and Paddison, P. J. et al. (2002) Genes Dev. 16:948-958). In these and related embodiments, shRNAs can be delivered to target cells using expression vectors known in the art. An example of a suitable expression vector for delivery of siRNA is the PSILENCER1.0-U6 (circular) plasmid (Ambion). Once delivered to the target tissue, shRNAs are processed in vivo into siRNA-like molecules capable of carrying out gene-specific silencing.  
      In various embodiments, the expression levels of genes targeted by RNAi or PTGS methods can be determined by assays for mRNA and/or protein analysis. Expression levels of the mRNA of a targeted gene can be determined, for example, by northern analysis methods using the NORTHERNMAX-GLY kit (Ambion); by microarray methods; by PCR methods; by real time PCR methods; and by other RNA/polynucleotide assays known in the art or described herein. Expression levels of the protein encoded by the targeted gene can be determined, for example, by microarray methods; by polyacrylamide gel electrophoresis; and by Western analysis using standard techniques known in the art.  
      An additional embodiment of the invention encompasses a method for screening for a compound which is effective in altering expression of a polynucleotide encoding CADECM. Compounds which may be effective in altering expression of a specific polynucleotide may include, but are not limited to, oligonucleotides, antisense oligonucleotides, triple helix-forming oligonucleotides, 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 CADECM expression or activity, a compound which specifically inhibits expression of the polynucleotide encoding CADECM may be therapeutically useful, and in the treatment of disorders associated with decreased CADECM expression or activity, a compound which specifically promotes expression of the polynucleotide encoding CADECM may be therapeutically useful.  
      In various embodiments, one or more 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, commercially-available or proprietary library of naturally-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 library of chemical compounds created combinatorially or randomly. A sample comprising a polynucleotide encoding CADECM is exposed to at least one test compound thus obtained. The sample may comprise, for example, an intact or permeabilized cell, or an in vitro cell-free or reconstituted biochemical system. Alterations in the expression of a polynucleotide encoding CADECM are assayed by any method commonly known in the art. Typically, 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 CADECM. 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. Pat. No. 5,932,435; Arndt, G. M. et al. (2000) Nucleic Acids Res. 28:E15) or a human cell line such as HeLa cell (Clarke, M. L. et al. (2000) Biochem. Biophys. Res. Commun. 268:8-13). A particular embodiment of the present invention involves screening a combinatorial library of oligonucleotides (such as deoxyribonucleotides, ribonucleotides, peptide nucleic acids, and modified oligonucleotides) for antisense activity against a specific polynucleotide sequence (Bruice, T. W. et al. (1997) U.S. Pat. No. 5,686,242; Bruice, T. W. et al. (2000) U.S. Pat. No. 6,022,691).  
      Many methods for introducing vectors into cells or tissues are available and equally 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. Delivery by transfection, by liposome injections, or by polycationic amino polymers may be achieved using methods which are well known in the art (Goldman, C. K. et al. (1997) Nat. Biotechnol. 15:462-466).  
      Any of the therapeutic methods described above may be applied 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 generally comprises an active ingredient formulated with a pharmaceutically acceptable excipient. Excipients may include, for example, sugars, starches, celluloses, gums, and proteins. Various formulations are commonly known and are thoroughly discussed in the latest edition of  Remington&#39;s Pharmaceutical Sciences  (Maack Publishing, Easton Pa.). Such compositions may consist of CADECM, antibodies to CADECM, and mimetics, agonists, antagonists, or inhibitors of CADECM.  
      In various embodiments, the compositions described herein, such as pharmaceutical compositions, may be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or rectal means.  
      Compositions for pulmonary administration may be prepared in liquid or dry powder form. These compositions are generally aerosolized immediately prior to inhalation by the patient. In the case of small molecules (e.g. traditional low molecular weight organic drugs), aerosol delivery of fast-acting formulations is well-known in the art. In the case of macromolecules (e.g. larger peptides and proteins), recent developments in the field of pulmonary delivery via the alveolar region of the lung have enabled the practical delivery of drugs such as insulin to blood circulation (see, e.g., Patton, J. S. et al., U.S. Pat. No. 5,997,848). Pulmonary delivery allows administration without needle injection, and obviates the need for potentially 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 purpose. The determination of an effective dose is well within the capability of those skilled in the art.  
      Specialized forms of compositions may be prepared for direct intracellular delivery of macromolecules comprising CADECM or fragments thereof. For example, liposome preparations containing a cell-impermeable macromolecule may promote cell fusion and intracellular delivery of the macromolecule. Alternatively, CADECM or a fragment thereof may be joined to a short cationic N-terminal portion from the HIV Tat-1 protein. Fusion proteins thus generated have been found to transduce into the cells of all 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 initially either in cell culture assays, e.g., of neoplastic cells, 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 CADECM or fragments thereof, antibodies of CADECM, and agonists, antagonists or inhibitors of CADECM, which ameliorates the symptoms or condition. Therapeutic efficacy and toxicity may be determined by standard pharmaceutical procedures in cell 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 cell 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 little 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 will be determined by the practitioner, in light of factors related to the subject requiring treatment. Dosage and administration 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, drug 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-life 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 delivery is provided in the literature and generally available to practitioners in the art. Those skilled in the art will employ different formulations for nucleotides than for proteins or their inhibitors. Similarly, delivery of polynucleotides or polypeptides will be specific to particular cells, conditions, locations, etc.  
      Diagnostics  
      In another embodiment, antibodies which specifically bind CADECM may be used for the diagnosis of disorders characterized by expression of CADECM, or in assays to monitor patients being treated with CADECM or agonists, antagonists, or inhibitors of CADECM. Antibodies useful for diagnostic purposes may be prepared in the same manner as described above for therapeutics. Diagnostic assays for CADECM include methods which utilize the antibody and a label to detect CADECM 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 CADECM, including ELISAs, RIAs, and FACS, are known in the art and provide a basis for diagnosing altered or abnormal levels of CADECM expression. Normal or standard values for CADECM expression are established by combining body fluids or cell extracts taken from normal mammalian subjects, for example, human subjects, with antibodies to CADECM under conditions suitable for complex formation. The amount of standard complex formation may be quantitated by various methods, such as photometric means. Quantities of CADECM expressed in subject, control, and disease samples from biopsied tissues are compared with the standard values. Deviation between standard and subject values establishes the parameters for diagnosing disease.  
      In another embodiment of the invention, polynucleotides encoding CADECM may be used for diagnostic purposes. The polynucleotides which may be used include oligonucleotides, 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 CADECM may be correlated with disease. The diagnostic assay may be used to determine absence, presence, and excess expression of CADECM, and to monitor regulation of CADECM levels during therapeutic intervention.  
      In one aspect, hybridization with PCR probes which are capable of detecting polynucleotides, including genomic sequences, encoding CADECM or closely related molecules may be used to identify nucleic acid sequences which encode CADECM. 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 amplification will determine whether the probe identifies only naturally occurring sequences encoding CADECM, allelic 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 CADECM 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:32-62 or from genomic sequences including promoters, enhancers, and introns of the CADECM gene.  
      Means for producing specific hybridization probes for polynucleotides encoding CADECM include the cloning of polynucleotides encoding CADECM or CADECM derivatives into vectors for the production of mRNA probes. Such vectors are known in the art, are commercially 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 radionuclides such as  32 P or  35 S, or by enzymatic labels, such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems, and the like.  
      Polynucleotides encoding CADECM may be used for the diagnosis of disorders associated with expression of CADECM. Examples of such disorders include, but are not limited to, an immune system disorder, such as acquired immunodeficiency syndrome (AIDS), X-linked agammaglobinemia of Bruton, common variable immunodeficiency (CVI), DiGeorge&#39;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, immunodeficiency associated with Cushing&#39;s disease, Addison&#39;s disease, adult respiratory distress syndrome, allergies, ankylosing spondylitis, amyloidosis, anemia, asthma, atherosclerosis, autoimmune hemolytic anemia, autoimmune thyroiditis, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), bronchitis, cholecystitis, contact dermatitis, Crohn&#39;s disease, atopic dermatitis, dermatomyositis, diabetes mellitus, emphysema, episodic lymphopenia with lymphocytotoxins, erythroblastosis fetalis, erythema nodosum, atrophic gastritis, glomerulonephritis, Goodpasture&#39;s syndrome, gout, Graves&#39; disease, Hashimoto&#39;s thyroiditis, hypereosinophilia, irritable bowel syndrome, multiple sclerosis, myasthenia gravis, myocardial or pericardial inflammation, osteoarthritis, osteoporosis, pancreatitis, polymyositis, psoriasis, Reiter&#39;s syndrome, rheumatoid arthritis, scleroderma, Sjögren&#39;s syndrome, systemic anaphylaxis, systemic lupus erythematosus, systemic sclerosis, thrombocytopenic purpura, ulcerative colitis, uveitis, Werner syndrome, complications of cancer, hemodialysis, and extracorporeal circulation, viral, bacterial, fungal, parasitic, protozoal, and helminthic infections, and trauma; a neurological disorder, such as epilepsy, ischemic cerebrovascular disease, stroke, cerebral neoplasms, Alzheimer&#39;s disease, Pick&#39;s disease, Huntington&#39;s disease, dementia, Parkinson&#39;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 demyelinating diseases, bacterial and viral meningitis, brain abscess, subdural empyema, epidural abscess, suppurative intracranial thrombophlebitis, myelitis and radiculitis, viral central nervous system disease, prion diseases including kuru, Creutzfeldt-Jakob disease, and Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, nutritional and metabolic diseases of the nervous system, neurofibromatosis, tuberous sclerosis, cerebelloretinal 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, metabolic, 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, postherpetic neuralgia, Tourette&#39;s disorder, progressive supranuclear palsy, corticobasal degeneration, and familial frontotemporal dementia; a developmental disorder, such as renal tubular acidosis, anemia, Cushing&#39;s syndrome, achondroplastic dwarfism, Duchenne and Becker muscular dystrophy, epilepsy, gonadal dysgenesis, WAGR syndrome (Wilms&#39; tumor, aniridia, genitourinary abnormalities, and mental retardation), Smith-Magenis syndrome, myelodysplastic syndrome, hereditary mucoepithelial dysplasia, hereditary keratodermas, hereditary neuropathies such as Charcot-Marie-Tooth disease and neurofibromatosis, hypothyroidism, hydrocephalus, seizure disorders such as Syndenham&#39;s chorea and cerebral palsy, spina bifida, anencephaly, craniorachischisis, congenital glaucoma, cataract, and sensorineural hearing loss; a connective tissue disorder, such as osteogenesis imperfecta, Ehlers-Danlos syndrome, chondrodysplasias, Marfan syndrome, Alport syndrome, familial aortic aneurysm, achondroplasia, mucopolysaccharidoses, osteoporosis, osteopetrosis, Paget&#39;s disease, rickets, osteomalacia, hyperparathyroidism, renal osteodystrophy, osteonecrosis, osteomyelitis, osteoma, osteoid osteoma, osteoblastoma, osteosarcoma, osteochondroma, chondroma, chondroblastoma, chondromyxoid fibroma, chondrosarcoma, fibrous cortical defect, nonossifying fibroma, fibrous dysplasia, fibrosarcoma, malignant fibrous histiocytoma, Ewing&#39;s sarcoma, primitive neuroectodermal tumor, giant cell tumor, osteoarthritis, rheumatoid arthritis, ankylosing spondyloarthritis, Reiter&#39;s syndrome, psoriatic arthritis, enteropathic arthritis, infectious arthritis, gout, gouty arthritis, calcium pyrophosphate crystal deposition disease, ganglion, synovial cyst, villonodular synovitis, systemic sclerosis, Dupuytren&#39;s contracture, hepatic fibrosis, lupus erythematosus, mixed connective tissue disease, epidermolysis bullosa simplex, bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis), non-epidermolytic and epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, pachyonychia congenita, and white sponge nevus; and a cell proliferative 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, colon, gall bladder, ganglia, gastrointestinal tract, heart, kidney, liver, lung, muscle, ovary, pancreas, parathyroid, penis, prostate, salivary glands, skin, spleen, testis, thymus, thyroid, and uterus. Polynucleotides encoding CADECM may be used in Southern or northern analysis, dot blot, or other membrane-based technologies; in PCR technologies; in dipstick, pin, and multiformat ELISA-like assays; and in microarrays utilizing fluids or tissues from patients to detect altered CADECM expression. Such qualitative or quantitative methods are well known in the art.  
      In a particular embodiment, polynucleotides encoding CADECM may be used in assays that detect the presence of associated disorders, particularly those mentioned above. Polynucleotides complementary to sequences encoding CADECM 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 control sample then the presence of altered levels of polynucleotides encoding CADECM 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 clinical 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 CADECM, a normal or standard profile for expression is established. This may be accomplished by combining body fluids or cell extracts taken from normal subjects, either animal or human, with a sequence, or a fragment thereof, encoding CADECM, under conditions suitable for hybridization or amplification. 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 substantially 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 establish the presence of a disorder.  
      Once the presence of a disorder is established 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 clinical symptoms. A more definitive diagnosis of this type may allow health professionals to employ preventative measures or aggressive treatment earlier, thereby preventing the development or further progression of the cancer.  
      Additional diagnostic uses for oligonucleotides designed from the sequences encoding CADECM may involve the use of PCR. These oligomers may be chemically synthesized, generated enzymatically, or produced in vitro. Oligomers will preferably contain a fragment of a polynucleotide encoding CADECM, or a fragment of a polynucleotide complementary to the polynucleotide encoding CADECM, and will be employed under optimized conditions for identification of a specific gene or condition. Oligomers may also be employed under less stringent conditions for detection or quantification of closely related DNA or RNA sequences.  
      In a particular aspect, oligonucleotide primers derived from polynucleotides encoding CADECM may be used to detect single nucleotide polymorphisms (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 limited to, single-stranded conformation polymorphism (SSCP) and fluorescent SSCP (fSSCP) methods. In SSCP, oligonucleotide primers derived from polynucleotides encoding CADECM are used to amplify 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 like. SNPs in the DNA cause differences in the secondary and tertiary structures of PCR products in single-stranded form, and these differences are detectable using gel electrophoresis in non-denaturing gels. In fSCCP, the oligonucleotide primers are fluorescently labeled, which allows detection of the amplimers in high-throughput equipment such as DNA sequencing machines. Additionally, sequence database analysis methods, termed in silico SNP (isSNP), are capable of identifying polymorphisms 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 Calif.).  
      SNPs may be used to study the genetic basis of human disease. For example, at least 16 common SNPs have been associated with non-insulin-dependent diabetes mellitus. SNPs are also useful for examining differences in disease outcomes in monogenic disorders, such as cystic fibrosis, sickle cell anemia, or chronic granulomatous disease. For example, variants in the mannose-binding lectin, MBL2, have been shown to be correlated with deleterious pulmonary outcomes in cystic fibrosis. SNPs also have utility in pharmacogenomics, the identification of genetic variants that influence a patient&#39;s response to a drug, such as life-threatening toxicity. For example, a variation in N-acetyl transferase is associated with a high incidence of peripheral neuropathy in response to the anti-tuberculosis drug isoniazid, while a variation in the core promoter of the ALOX5 gene results in diminished clinical response to treatment with an anti-asthma drug that targets the 5-lipoxygenase pathway. Analysis of the distribution of SNPs in different populations is useful for investigating genetic drift, mutation, recombination, and selection, as well as for tracing the origins of populations and their migrations (Taylor, J. G. et al. (2001) Trends Mol. Med. 7:507-512; Kwok, P.-Y. and Z. Gu (1999) Mol. Med. Today 5:538-543; Nowotny, P. et al. (2001) Curr. Opin. Neurobiol. 11:637-641).  
      Methods which may also be used to quantify the expression of CADECM include radiolabeling or biotinylating nucleotides, coamplification of a control nucleic acid, and interpolating results from standard curves (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 oligomer or polynucleotide of interest is presented in various dilutions and a spectrophotometric or colorimetric response gives rapid quantitation.  
      In further embodiments, oligonucleotides or longer fragments derived from any of the polynucleotides 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 polymorphisms. 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 treatment 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, CADECM, fragments of CADECM, or antibodies specific for CADECM 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 transcript image represents the global pattern of gene expression by a particular tissue or cell 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 (Seilhamer et al., “Comparative Gene Transcript Analysis,” U.S. Pat. No. 5,840,484; hereby expressly incorporated by reference herein). Thus a transcript image may be generated by hybridizing the polynucleotides of the present invention or their complements to the totality 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 plurality 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, cell lines, 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 vitro, as in the case of a cell line.  
      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 preclinical evaluation of pharmaceuticals, as well as toxicological testing of industrial and naturally-occurring environmental compounds. All compounds induce characteristic gene expression patterns, frequently termed molecular fingerprints 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. Lett. 112-113:467-471). If a test compound has a signature similar to that of a compound with known toxicity, it is likely to share those toxic properties. These fingerprints or signatures are most useful and refined when they contain expression information from a large number of genes and gene families. Ideally, a genome-wide measurement of expression provides the highest quality signature. Even genes whose expression is not altered by any tested compounds are important as well, as the levels of expression of these genes are used to normalize the rest of the expression data. The normalization procedure is useful for comparison of expression data after treatment with different compounds. While the assignment of gene function to elements of a toxicant signature aids in interpretation 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 Feb. 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 all expressed gene sequences.  
      In an embodiment, the toxicity of a test compound can be 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 embodiment relates to the use of the polypeptides disclosed herein to analyze the proteome of a tissue or cell 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 individually 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 cell&#39;s proteome may thus be generated by separating and analyzing the polypeptides of a particular tissue or cell type. In one embodiment, the separation is achieved using two-dimensional gel electrophoresis, in which proteins from a sample are separated by isoelectric 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 visualized in the gel as discrete and uniquely positioned spots, typically by staining the gel with an agent such as Coomassie Blue or silver or fluorescent stains. The optical density of each protein spot is generally 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 treated or untreated with a test compound or therapeutic agent, are compared to identify any changes in protein spot density related to the treatment. The proteins in the spots are partially sequenced using, for example, standard methods employing chemical or enzymatic cleavage followed 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 interest. In some cases, further sequence data may be obtained for definitive protein identification.  
      A proteomic profile may also be generated using antibodies specific for CADECM to quantify the levels of CADECM 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. 270:103-111; 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 parallel with toxicant signatures at the transcript level. There is a poor correlation between transcript 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 transcript 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 reliable 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 (Brennan, T. M. et al. (1995) U.S. Pat. No. 5,474,796; Schena, M. et al. (1996) Proc. Natl. Acad. Sci. USA 93:10614-10619; Baldeschweiler et al. (1995) PCT application WO95/25116; Shalon, D. et al. (1995) PCT application WO95/35505; Heller, R. A. et al. (1997) Proc. Natl. Acad. Sci. USA 94:2150-2155; Heller, M. J. et al. (1997) U.S. Pat. No. 5,605,662). Various types of microarrays are well known and thoroughly described in Schena, M., ed. (1999 ; DNA Microarrays: A Practical Aproach , Oxford University Press, London).  
      In another embodiment of the invention, nucleic acid sequences encoding CADECM may be used to generate hybridization probes useful in mapping the naturally 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 P1 constructions, or single chromosome cDNA libraries (Harrington, J. J. et al. (1997) Nat. Genet. 15:345-355; Price, C. M. (1993) Blood Rev. 7:127-134; Trask, B. J. (1991) Trends Genet. 7:149-154). Once mapped, the nucleic acid sequences may be used to develop genetic linkage maps, for example, which correlate the inheritance of a disease state with the inheritance of a particular chromosome region or restriction fragment length polymorphism (RFLP) (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 (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 Online Mendelian Inheritance in Man (OMIM) World Wide Web site. Correlation between the location of the gene encoding CADECM 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 linkage analysis using established chromosomal markers, may be used for extending genetic maps. Often the placement of a gene on the chromosome of another mammalian 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 localized by genetic linkage to a particular genomic region, e.g., ataxia-telangiectasia to 11q22-23, any sequences mapping to that area may represent associated or regulatory genes for further investigation (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 translocation, inversion, etc., among normal, carrier, or affected individuals.  
      In another embodiment of the invention, CADECM, its catalytic or immunogenic fragments, or oligopeptides thereof can be used for screening libraries 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 solid support, borne on a cell surface, or located intracellularly. The formation of binding complexes between CADECM and the agent being tested may be measured.  
      Another technique for drug screening provides for high throughput screening of compounds having suitable binding affinity to the protein of interest (Geysen, et al. (1984) PCT application WO84/03564). In this method, large numbers of different small test compounds are synthesized on a solid substrate. The test compounds are reacted with CADECM, or fragments thereof, and washed. Bound CADECM is then detected by methods well known in the art. Purified CADECM can also be coated directly onto plates for use in the aforementioned drug screening techniques. Alternatively, non-neutralizing antibodies can be used to capture the peptide and immobilize it on a solid support.  
      In another embodiment, one may use competitive drug screening assays in which neutralizing antibodies capable of binding CADECM specifically compete with a test compound for binding CADECM. In this manner, antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with CADECM.  
      In additional embodiments, the nucleotide sequences which encode CADECM 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 limited to, such properties as the triplet genetic code and specific base pair interactions.  
      Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.  
      The disclosures of all patents, applications, and publications mentioned above and below, including U.S. Ser. No. 60/379,840, U.S. Ser. No. 60/381,291, U.S. Ser. No. 60/383,183, and U.S. Ser. No. 60/394,146, are hereby expressly incorporated by reference.  
     EXAMPLES  
      I. Construction of cDNA Libraries  
      Incyte cDNAs are derived from cDNA libraries described in the LIFESEQ database (Incyte, Palo Alto Calif.). Some tissues are homogenized and lysed in guanidinium isothiocyanate, while others are homogenized and lysed in phenol or in a suitable mixture of denaturants, such as TRIZOL (Invitrogen), a monophasic solution of phenol and guanidine isothiocyanate. The resulting lysates are centrifuged over CsCl cushions or extracted with chloroform RNA is precipitated from the lysates with either isopropanol or sodium acetate and ethanol, or by other routine methods.  
      Phenol extraction and precipitation of RNA are repeated as necessary to increase RNA purity. In some cases, RNA is treated with DNase. For most libraries, poly(A)+ RNA is isolated using oligo d(T)-coupled paramagnetic particles (Promega), OLIGOTEX latex particles (QIAGEN, Chatsworth Calif.), or an OLIGOTEX mRNA purification kit (QIAGEN). Alternatively, RNA is isolated directly from tissue lysates using other RNA isolation kits, e.g., the POLY(A)PURE mRNA purification kit (Ambion, Austin Tex.).  
      In some cases, Stratagene is provided with RNA and constructs the corresponding cDNA libraries. Otherwise, cDNA is synthesized and cDNA libraries are constructed with the UNIZAP vector system (Stratagene) or SUPERSCRIPT plasmid system (Invitrogen), using the recommended procedures or similar methods known in the art (Ausubel et al., supra, ch. 5). Reverse transcription is initiated using oligo d(T) or random primers. Synthetic oligonucleotide adapters are ligated to double stranded cDNA, and the cDNA is digested with the appropriate restriction enzyme or enzymes. For most libraries, the cDNA is size-selected (300-1000 bp) using SEPHACRYL S1000, SEPHAROSE CL2B, or SEPHAROSE CL4B column chromatography (Amersham Biosciences) or preparative agarose gel electrophoresis. cDNAs are ligated into compatible restriction enzyme sites of the polylinker of a suitable plasmid, e.g., PBLUESCRIPT plasmid (Stratagene), PSPORT1 plasmid (Invitrogen, Carlsbad Calif.), PCDNA2.1 plasmid (Invitrogen), PBK-CMV plasmid (Stratagene), PCR2-TOPOTA plasmid (Invitrogen), PCMV-ICIS plasmid (Stratagene), pIGEN (Incyte, Palo Alto Calif.), pRARE (Incyte), or pINCY (Incyte), or derivatives thereof. Recombinant plasmids are transformed into competent  E. coli  cells including XL1-Blue, XL1-BlueMRF, or SOLR from Stratagene or DH5α, DH10B, or ElectroMAX DH10B from Invitrogen.  
      II. Isolation of cDNA Clones  
      Plasmids obtained as described in Example I are recovered from host cells by in vivo excision using the UNIZAP vector system (Stratagene) or by cell lysis. Plasmids are purified using at least one of the following: 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. Following precipitation, plasmids are resuspended in 0.1 ml of distilled water and stored, with or without lyophilization, at 4° C.  
      Alternatively, plasmid DNA is amplified from host cell lysates using direct link PCR in a high-throughput format (Rao, V. B. (1994) Anal. Biochem. 216:1-14). Host cell lysis and thermal cycling steps are carried out in a single reaction mixture. Samples are processed and stored in 384-well plates, and the concentration of amplified plasmid DNA is quantified fluorometrically using PICOGREEN dye (Molecular Probes, Eugene Oreg.) and a FLUOROSKAN II fluorescence scanner (Labsystems Oy, Helsinki, Finland).  
      III. Sequencing and Analysis  
      Incyte cDNA recovered in plasmids as described in Example II are sequenced as follows. Sequencing reactions are processed using standard methods or high-throughput instrumentation such as the ABI CATALYST 800 (Applied Biosystems) thermal cycler or the PTC-200 thermal cycler (MJ Research) in conjunction with the HYDRA microdispenser (Robbins Scientific) or the MICROLAB 2200 (Hamilton) liquid transfer system. cDNA sequencing reactions are prepared using reagents provided by Amersham Biosciences or supplied in ABI sequencing kits such as the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems). Electrophoretic separation of cDNA sequencing reactions and detection of labeled polynucleotides are carried out using the MEGABACE 1000 DNA sequencing system (Amersham Biosciences); the ABI PRISM 373 or 377 sequencing system (Applied 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 are identified using standard methods (Ausubel et al., supra, ch. 7). Some of the cDNA sequences are selected for extension using the techniques disclosed in Example VIII.  
      Polynucleotide sequences derived from Incyte cDNAs are validated by removing vector, linker, 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 are then queried against a selection of public databases such as the GenBank primate, rodent, mammalian, 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, Palo Alto Calif.); hidden Markov model (HMM)-based protein family databases such as PFAM, INCY, and TIGRFAM (Haft, D. H. et al. (2001) Nucleic Acids Res. 29:41-43); and HMM-based protein domain databases such as SMART (Schultz, J. et al. (1998) Proc. Natl. Acad. Sci. USA 95:5857-5864; Letunic, I. et al. (2002) Nucleic Acids Res. 30:242-244). (HMM is a probabilistic approach which analyzes consensus primary structures of gene families; see, for example, Eddy, S. R. (1996) Curr. Opin. Struct. Biol. 6:361-365.) The queries are performed using programs based on BLAST, FASTA, BLIMPS, and HMMER. The Incyte cDNA sequences are 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) are used to extend Incyte cDNA assemblages to full length. Assembly is performed using programs based on Phred, Phrap, and Consed, and cDNA assemblages are screened for open reading frames using programs based on GeneMark, BLAST, and FASTA. The full length polynucleotide sequences are translated to derive the corresponding full length polypeptide sequences. Alternatively, a polypeptide may begin at any of the methionine residues of the full length translated polypeptide. Full length polypeptide sequences are subsequently analyzed by querying against databases such as the GenBank protein databases (genpept), SwissProt, the PROTEOME databases, BLOCKS, PRINTS, DOMO, PRODOM, Prosite, hidden Markov model (HMM)-based protein family databases such as PFAM, INCY, and TIGRFAM; and HMM-based protein domain databases such as SMART. Full length polynucleotide sequences are also analyzed using MACDNASIS PRO software (MiraiBio, Alameda Calif.) and LASERGENE software (DNASTAR). Polynucleotide and polypeptide sequence alignments are generated using default parameters specified by the CLUSTAL algorithm as incorporated into the MEGALIGN multisequence alignment program (DNASTAR), which also calculates the percent identity between aligned sequences.  
      Table 7 summarizes tools, programs, and algorithms used for the analysis and assembly of Incyte cDNA and full length sequences and provides applicable 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, all of which are incorporated by reference herein in their entirety, and the fourth column presents, where applicable, the scores, probability values, and other parameters used to evaluate the strength of a match between two sequences (the higher the score or the lower the probability value, the greater the identity between two sequences).  
      The programs described above for the assembly and analysis of full length polynucleotide and polypeptide sequences are also used to identify polynucleotide sequence fragments from SEQ ID NO:32-62. Fragments from about 20 to about 4000 nucleotides which are useful in hybridization and amplification technologies are described in Table 4, column 2.  
      IV. Identification and Editing of Coding Sequences from Genomic DNA  
      Putative cell adhesion and extracellular matrix proteins are initially identified by running the Genscan gene identification program against public 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 (Burge, C. and S. Karlin (1997) J. Mol. Biol. 268:78-94; Burge, C. and S. Karlin (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 is set to 30 kb. To determine which of these Genscan predicted cDNA sequences encode cell adhesion and extracellular matrix proteins, the encoded polypeptides are analyzed by querying against PFAM models for cell adhesion and extracellular matrix proteins. Potential cell adhesion and extracellular matrix proteins are also identified by homology to Incyte cDNA sequences that have been annotated as cell adhesion and extracellular matrix proteins. These selected Genscan-predicted sequences are then compared by BLAST analysis to the genpept and gbpri public databases. Where necessary, the Genscan-predicted sequences are 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 is also used to find any Incyte cDNA or public cDNA coverage of the Genscan-predicted sequences, thus providing evidence for transcription. When Incyte cDNA coverage is available, this information is used to correct or confirm the Genscan predicted sequence. Full length polynucleotide sequences are obtained by assembling Genscan-predicted coding sequences with Incyte cDNA sequences and/or public cDNA sequences using the assembly process described in Example III. Alternatively, full length polynucleotide sequences are 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 are extended with exons predicted by the Genscan gene identification program described in Example IV. Partial cDNAs assembled as described in Example III are mapped to genomic DNA and parsed into clusters containing related cDNAs and Genscan exon predictions from one or more genomic sequences. Each cluster is analyzed using an algorithm based on graph theory and dynamic programming to integrate cDNA and genomic information, generating possible splice variants that are subsequently confirmed, edited, or extended to create a full length sequence. Sequence intervals in which the entire length of the interval is present on more than one sequence in the cluster are identified, and intervals thus identified are considered to be equivalent by transitivity., For example, if an interval is present on a cDNA and two genomic sequences, then all three intervals are considered to be equivalent. This process allows unrelated but consecutive genomic sequences to be brought together, bridged by cDNA sequence. Intervals thus identified are then “stitched” together by the stitching algorithm in the order that they appear along their parent sequences to generate the longest possible sequence, as well as sequence variants. Linkages between intervals which proceed along one type of parent sequence (cDNA to cDNA or genomic sequence to genomic sequence) are given preference over linkages which change parent type (cDNA to genomic sequence). The resultant stitched sequences are translated and compared by BLAST analysis to the genpept and gbpri public databases. Incorrect exons predicted by Genscan are corrected by comparison to the top BLAST hit from genpept. Sequences are further extended with additional cDNA sequences, or by inspection of genomic DNA, when necessary.  
      “Stretched” Sequences  
      Partial DNA sequences are extended to full length with an algorithm based on BLAST analysis. First, partial cDNAs assembled as described in Example III are queried against public databases such as the GenBank primate, rodent, mammalian, vertebrate, and eukaryote databases using the BLAST program. The nearest GenBank protein homolog is then compared by BLAST analysis to either Incyte cDNA sequences or GenScan exon predicted sequences described in Example IV. A chimeric protein is 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 are used as probes to search for homologous genomic sequences from the public human genome databases. Partial DNA sequences are therefore “stretched” or extended by the addition of homologous genomic sequences. The resultant stretched sequences are examined to determine whether they contain a complete gene.  
      VI. Chromosomal Mapping of CADECM Encoding Polynucleotides  
      The sequences used to assemble SEQ ID NO:32-62 are compared with sequences from the Incyte LIFESEQ database and public domain databases using BLAST and other implementations of the Smith-Waterman algorithm. Sequences from these databases that matched SEQ ID NO:32-62 are assembled into clusters of contiguous and overlapping sequences using assembly algorithms such as Phrap (Table 7). Radiation hybrid and genetic mapping data available from public resources such as the Stanford Human Genome Center (SHGC), Whitehead Institute for Genome Research (WIGR), and Généthon are used to determine if any of the clustered sequences have been previously mapped. Inclusion of a mapped sequence in a cluster results in the assignment of all 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&#39;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 Généthon 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 public, such as the NCBI “(GeneMap&#39;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.  
      VII. Analysis of Polynucleotide Expression  
      Northern analysis is a laboratory technique used to detect the presence of a transcript of a gene and involves the hybridization of a labeled nucleotide sequence to a membrane on which RNAs from a particular cell type or tissue have been bound (Sambrook and Russell, supra, ch. 7; Ausubel et al., supra, ch. 4).  
      Analogous computer techniques applying BLAST are used to search for identical or related molecules in databases such as GenBank or LIEESEQ (Incyte). 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   ×   Percent   ⁢           ⁢   Identity       5   ×   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 normalized value between 0 and 100, and is calculated as follows: the BLAST score is multiplied 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 quality in a BLAST aligmnent. 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, polynucleotides encoding CADECM are analyzed with respect to the tissue sources from which they are derived. For example, some full length sequences are assembled, at least in part, with overlapping Incyte cDNA sequences (see Example III). Each cDNA sequence is derived from a cDNA library constructed from a human tissue. Each human tissue is classified into one of the following organ/tissue categories: cardiovascular system; connective tissue; digestive system, embryonic structures; endocrine system; exocrine glands; genitalia, female; genitalia, male; germ cells; hemic and immune system; liver; musculoskeletal system; nervous system; pancreas; respiratory system; sense organs; skin; stomatognathic system; unclassified/mixed; or urinary tract. The number of libraries in each category is counted and divided by the total number of libraries across all categories. Similarly, each human tissue is classified into one of the following disease/condition categories: cancer, cell line, developmental, inflammation, neurological, trauma, cardiovascular, pooled, and other, and the number of libraries in each category is counted and divided by the total number of libraries across all categories. The resulting percentages reflect the tissue- and disease-specific expression of cDNA encoding CADECM. cDNA sequences and cDNA library/tissue information are found in the LIFESEQ database (Incyte, Palo Alto Calif.).  
      VIII. Extension of CADECM Encoding Polynucleotides  
      Full length polynucleotides are produced by extension of an appropriate fragment of the full length molecule using oligonucleotide primers designed from this fragment. One primer is synthesized to initiate 5′ extension of the known fragment, and the other primer is synthesized to initiate 3′ extension of the known fragment. The initial primers are 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 hairpin structures and primer-primer dimerizations is avoided.  
      Selected human cDNA libraries are used to extend the sequence. If more than one extension is necessary or desired, additional or nested sets of primers are designed.  
      High fidelity amplification is obtained by PCR using methods well known in the art. PCR is performed in 96-well plates using the PTC-200 thermal cycler (MJ Research, Inc.). The reaction mix contains DNA template, 200 nmol of each primer, reaction buffer containing Mg 2+ , (NH 4 ) 2 SO 4 , and 2-mercaptoethanol, Taq DNA polymerase (Amersham Biosciences), ELONGASE enzyme (Invitrogen), and Pfu DNA polymerase (Stratagene), with the following 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+ are as follows: 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 times; Step 6: 68° C., 5 min; Step 7: storage at 4° C.  
      The concentration of DNA in each well is determined by dispensing 100 μl PICOGREEN quantitation reagent (0.25% (v/v) PICOGREEN; Molecular Probes, Eugene Oreg.) dissolved in 1X TE and 0.5 μl of undiluted PCR product into each well of an opaque fluorimeter plate (Corning Costar, Acton Mass.), allowing the DNA to bind to the reagent. The plate is scanned in a Fluoroskan II (Labsystems Oy, Helsinki, Finland) to measure the fluorescence of the sample and to quantify the concentration of DNA. A 5 μl to 10 μl aliquot of the reaction mixture is analyzed by electrophoresis on a 1% agarose gel to determine which reactions are successful in extending the sequence.  
      The extended nucleotides are desalted and concentrated, transferred to 384-well plates, digested with CviJI cholera virus endonuclease (Molecular Biology Research, Madison Wis., and sonicated or sheared prior to religation into pUC 18 vector (Amersham Biosciences). For shotgun sequencing, the digested nucleotides are separated on low concentration (0.6 to 0.8%) agarose gels, fragments are excised, and agar digested with Agar ACE (Promega). Extended clones were religated using T4 ligase (New England Biolabs, Beverly Mass.) into pUC 18 vector (Amersham Biosciences), treated with Pfu DNA polymerase (Stratagene) to fill-in restriction site overhangs, and transfected into competent  E. coli  cells. Transformed cells are selected on antibiotic-containing media, and individual colonies are picked and cultured overnight at 37° C. in 384-well plates in LB/2× carb liquid media.  
      The cells are lysed, and DNA is amplified by PCR using Taq DNA polymerase (Amersham Biosciences) and Pfu DNA polymerase (Stratagene) with the following 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 is quantified by PICOGREEN reagent (Molecular Probes) as described above. Samples with low DNA recoveries are reamplified using the same conditions as described above. Samples are diluted with 20% dimethysulfoxide (1:2, v/v), and sequenced using DYENAMIC energy transfer sequencing primers and the DYENAMIC DIRECT kit (Amersham Biosciences) or the ABI PRISM BIGDYE Terminator cycle sequencing ready reaction kit (Applied Biosystems).  
      In like manner, full length polynucleotides are verified using the above procedure or are used to obtain 5′ regulatory sequences using the above procedure along with oligonucleotides designed for such extension, and an appropriate genomic library.  
      IX. Identification of Single Nucleotide Polymorphisms in CADECM Encoding Polynucleotides  
      Common DNA sequence variants known as single nucleotide polymorphisms (SNPs) are identified in SEQ ID NO:32-62 using the LIFESEQ database (Incyte). Sequences from the same gene are clustered together and assembled as described in Example III, allowing the identification of all sequence variants in the gene. An algorithm consisting of a series of filters is used to distinguish SNPs from other sequence variants. Preliminary filters remove the majority of basecall errors by requiring a minimum Phred quality score of 15, and remove sequence alignment errors and errors resulting from improper trimming of vector sequences, chimeras, and splice variants. An automated procedure of advanced chromosome analysis is applied to the original chromatogram files in the vicinity of the putative SNP. Clone error filters use statistically generated algorithms to identify errors introduced during laboratory processing, such as those caused by reverse transcriptase, polymerase, or somatic mutation. Clustering error filters use statistically generated algorithms to identify errors resulting from clustering of close homologs or pseudogenes, or due to contamination by non-human sequences. A final set of filters removes duplicates and SNPs found in immunoglobulins or T-cell receptors.  
      Certain SNPs are selected for further characterization by mass spectrometry using the high throughput MASSARRAY system (Sequenom, Inc.) to analyze allele frequencies at the SNP sites in four different human populations. The Caucasian population comprises 92 individuals (46 male, 46 female), including 83 from Utah, four French, three Venezualan, and two Amish individuals. The African population comprises 194 individuals (97 male, 97 female), all African Americans. The Hispanic population comprises 324 individuals (162 male, 162 female), all Mexican Hispanic. The Asian population comprises 126 individuals (64 male, 62 female) with a reported parental breakdown of 43% Chinese, 31% Japanese, 13% Korean, 5% Vietnamese, and 8% other Asian. Allele frequencies are first analyzed in the Caucasian population; in some cases those SNPs which show no allelic variance in this population are not further tested in the other three populations.  
      X. Labeling and Use of Individual Hybridization Probes  
      Hybridization probes derived from SEQ ID NO:32-62 are employed to screen cDNAs, genomic DNAs, or mRNAs. Although the labeling of oligonucleotides, consisting of about 20 base pairs, is specifically described, essentially the same procedure is used with larger nucleotide fragments. Oligonucleotides are designed using state-of-the-art software such as OLIGO 4.06 software (National Biosciences) and labeled by combining 50 pmol of each oligomer, 250 μCi of [γ- 32 P] adenosine triphosphate (Amersham Biosciences), and T4 polynucleotide kinase (DuPont NEN, Boston Mass.). The labeled oligonucleotides are substantially purified using a SEPHADEX G-25 superfine size exclusion dextran bead column (Amersham Biosciences). An aliquot containing 10 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 following endonucleases: Ase I, Bgl II, Eco RI, Pst I, Xba I, or Pvu II (DuPont NEN).  
      The DNA from each digest is fractionated on a 0.7% agarose gel and transferred to nylon membranes (Nytran Plus, Schleicher &amp; Schuell, Durham N.H.). Hybridization is carried out for 16 hours at 40° C. To remove nonspecific signals, blots are sequentially washed at room temperature under conditions of up to, for example, 0.1× saline sodium citrate and 0.5% sodium dodecyl sulfate. Hybridization patterns are visualized using autoradiography or an alternative imaging means and compared.  
      XI. Microarrays  
      The linkage or synthesis of array elements upon a microarray can be achieved utilizing photolithography, piezoelectric printing (ink-jet printing; see, e.g., Baldeschweiler et al., supra), mechanical microspotting technologies, and derivatives thereof. The substrate in each of the aforementioned technologies should be uniform and solid with a non-porous surface (Schena, M., ed. (1999)  DNA Microarrays: A Practical Approach , Oxford University Press, London). Suggested substrates include silicon, silica, glass slides, glass chips, and silicon wafers. Alternatively, a procedure analogous to a dot or slot blot may also be used to arrange and link 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 well known to those of ordinary skill in the art and may contain any appropriate number of elements (Schena, M. et al. (1995) Science 270:467-470; Shalon, D. et al. (1996) Genome Res. 6:639-645; Marshall, A. and J. Hodgson (1998) Nat. Biotechnol. 16:27-31).  
      Full length cDNAs, Expressed Sequence Tags (ESTs), or fragments or oligomers thereof may comprise the elements of the microarray. Fragments or oligomers 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 oligo-(dT) cellulose method. Each poly(A) +  RNA sample is reverse transcribed using MMLV reverse-transcriptase, 0.05 pg/μl oligo-(dT) primer (21mer), 1× 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 Biosciences). The reverse transcription reaction is performed in a 25 ml volume containing 200 ng poly(A) +  RNA with GEMBRIGHT kits (Incyte). Specific control poly(A) +  RNAs are synthesized by in vitro 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 labeling) is treated 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, Palo Alto Calif.) 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., Holbrook N.Y.) and resuspended in 14 μl 5× SSC/0.2% SDS.  
      Microarray Preparation  
      Sequences of the present invention are used to generate array elements. Each array element is amplified from bacterial cells containing vectors with cloned cDNA inserts. PCR amplification uses primers complementary to the vector sequences flanking the cDNA insert. Array elements are amplified in thirty cycles of PCR from an initial quantity of 1-2 ng to a final quantity greater than 5 μg. Amplified array elements are then purified using SEPHACRYL400 (Amersham Biosciences).  
      Purified array elements are immobilized on polymer-coated glass slides. Glass microscope slides (Corning) are cleaned by ultrasound in 0.1% SDS and acetone, with extensive distilled water washes between and after treatments. Glass slides are etched in 4% hydrofluoric acid (VWR Scientific Products Corporation (VWR), West Chester Pa.), washed extensively in distilled water, and coated with 0.05% aminopropyl silane (Sigma-Aldrich, St. Louis Mo.) in 95% ethanol. Coated slides are cured in a 110° C. oven.  
      Array elements are applied to the coated glass substrate using a procedure described in U.S. Pat. No. 5,807,522, incorporated 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 slide.  
      Microarrays are UV-crosslinked using a STRATALINKER UV-crosslinker (Stratagene). Microarrays are washed at room temperature once in 0.2% SDS and three times in distilled water. Non-specific binding sites are blocked by incubation of microarrays in 0.2% casein in phosphate buffered saline (PBS) (Tropix, Inc., Bedford Mass.) for 30 minutes at 60° C. followed by washes in 0.2% SDS and distilled 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 5× SSC, 0.2% SDS hybridization buffer. The sample mixture is heated to 65° C. for 5 minutes and is aliquoted onto the microarray surface and covered with an 1.8 cm 2  coverslip. The arrays are transferred to a waterproof chamber having a cavity just slightly larger than a microscope slide. The chamber is kept at 100% humidity internally by the addition of 140 μl of 5× SSC in a corner 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 (1× SSC, 0.1% SDS), three times for 10 minutes each at 45° C. in a second wash buffer (0.1× 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 Calif.) capable of generating spectral lines at 488 nm for excitation of Cy3 and at 632 nm for excitation of CyS. The excitation laser light is focused on the array using a 20× microscope objective (Nikon, Inc., Melville N.Y.). The slide containing the array is placed on a computer-controlled X-Y stage on the microscope and raster-scanned past the objective. The 1.8 cm×1.8 cm array used in the present example is scanned with a resolution of 20 micrometers.  
      In two separate scans, a mixed gas multiline laser excites the two fluorophores sequentially. Emitted light is split, based on wavelength, into two photomultiplier tube detectors (PMT R1477, Hamamatsu Photonics Systems, Bridgewater N.J.) corresponding to the two fluorophores. Appropriate filters positioned between the array and the photomultiplier 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 typically 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 calibrated 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, allowing 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 cells), each labeled with a different fluorophore, are hybridized to a single array for the purpose of identifying genes that are differentially expressed, the calibration is done by labeling samples of the calibrating cDNA with the two fluorophores and adding identical amounts of each to the hybridization mixture.  
      The output of the photomultiplier tube is digitized using a 12-bit RTI-835H analog-to-digital (A/D) conversion board (Analog Devices, Inc., Norwood Mass.) installed in an IBM-compatible PC computer. The digitized data are displayed as an image where the signal intensity is mapped using a linear 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&#39;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). Array elements that exhibit at least about a two-fold change in expression, a signal-to-background ratio of at least about 2.5, and an element spot size of at least about 40%, are considered to be differentially expressed.  
      Expression  
      For example, SEQ ID NO:33 and SEQ ID NO:34 showed increased expression in ovarian cancer, as determined by microarray analysis. A normal ovary from a 79 year-old female donor was compared to an ovarian tumor from the same donor (Huntsman Cancer Institute, Salt Lake City, Utah).  
      Expression of SEQ ID NO:33 and SEQ ID NO:34 increased by at least twofold in ovarian tumor tissue versus normal ovary tissue. Therefore, SEQ ID NO:33 and SEQ ID NO:34 are useful in monitoring treatment of, and diagnostic assays for, ovarian cancer and other cell proliferative disorders.  
      As another example, SEQ ID NO:33 and SEQ ID NO:34 showed decreased expression in preadipocytes treated with differentiation medium. Primary subcutaneous preadipocytes were isolated from adipose tissue of a 40-year-old healthy female with a body mass index (BMI) of 32.47. The preadipocytes were cultured and induced to differentiate into adipocytes by culturing them in the differentiation medium containing active components PPAR-γ agonist and human insulin (Zen-Bio). Thiazolidinediones or PPAR-γ agonists can bind and activate an orphan nuclear receptor, PPAR-γ, and some of them have been proven to be able to induce human adipocyte differentiation. The preadipocytes were treated with human insulin and PPAR-γ agonist for 3 days and subsequently were switched to medium containing insulin alone for a variety of time periods ranging from one to 20 days before the cells were collected for analysis. Differentiated adipocytes were compared to untreated preadipocytes maintained in culture in the absence of inducing agents. Between 80% and 90% of the preadipocytes finally differentiated to adipocytes observed under phase contrast microscope. Expression of SEQ ID NO:33 and SEQ ID NO:34 decreased by at least twofold in differentiated adipocytes versus untreated preadipocytes. Therefore, SEQ ID NO:33 and SEQ ID NO:34 are useful for the diagnosis, prognosis, or treatment of diabetes mellitus and other disorders, such as obesity, hypertension, atherosclerosis, polycystic ovarian syndrome, and cancers including breast, prostate, and colon.  
      As another example, SEQ ID NO:36 showed decreased expression in fibroblasts associated with Tangier disease, as determined by microarray analysis. Normal and Tangier disease derived fibroblasts were compared. Human fibroblasts were obtained from skin explants from both normal subjects and two patients with homozygous Tangier disease. Cell lines were immortalized by transfection with human papillomavirus 16 genes E6 and E7 and a neomycin resistance selectable marker. In addition, both types of cells were cultured in the presence of cholesterol and compared with the same cell type cultured in the absence of cholesterol. TD derived cells are shown to be deficient in an assay of apoA-I mediated tritiated cholesterol efflux. Expression of SEQ ID NO:36 decreased by at least twofold in fibroblasts associated with Tangier disease versus normal fibroblasts. Therefore, SEQ ID NO:36 is useful in diagnostic assays for Tangier disease.  
      SEQ ID NO:40 showed differential expression in association with colon cancer from three separate donors, as determined by microarray analysis. Tissue samples were provided by the Huntsman Cancer Institute, Salt Lake City, Utah. The gene expression profile of messenger RNA isolated from grossly uninvolved colon tissue was compared to that isolated from cancerous colon tissue from three separate donors in individual matched tissue experiments. The expression of SEQ ID NO:40 was decreased by three-fold in the tumorous colon tissue as compared to the normal colon tissue from one donor, while the expression of SEQ ID NO:40 was decreased by two-fold in the tumorous colon tissue as compared to the normal colon tissue in two other donors. Thus, in an embodiment, SEQ ID NO:40 can be used in diagnostic assays for colon cancer, as well as for monitoring the progression and treatment of colon cancer, and related diseases and conditions.  
      SEQ ID NO:42 showed differential expression in association with breast cancer, as determined by microarray analysis. Gene expression profiles of nonmalignant mammary epithelial cells were compared to gene expression profiles of various breast carcinoma lines at different stages of tumor progression. The cells were grown in defined serum-free H14 medium to 70-80% confluence prior to RNA harvest. Cell lines compared included: a) MCF-10A, a breast mammary gland (luminal ductal characteristics) cell line isolated from a 36-year-old woman with fibrocystic breast disease, b) MCF7, a nonmalignant breast adenocarcinoma cell line isolated from the pleural effusion of a 69-year-old female, c) T-47D, a breast carcinoma cell line isolated from a pleural effusion obtained from a 54-year-old female with an infiltrating ductal carcinoma of the breast, d) Sk-BR-3, a breast adenocarcinoma cell line isolated from a malignant pleural effusion of a 43-year-old female, e) BT-20, a breast carcinoma cell line derived in vitro from the cells emigrating out of thin slices of the tumor mass isolated from a 74-year-old female, and f) MDA-mb-231, a breast tumor cell line isolated from the pleural effusion of a 51-year old female. The expression of SEQ ID NO:42 was decreased by at least two-fold in all five (MCF7, T-47D, Sk-BR-3, BT-20, MDA-mb-231) of the breast carcinoma cells lines assayed as compared to the nonmalignant breast epithelial cell line (MCF-10A). Therefore, in an embodiment, SEQ ID NO:42 can be used in diagnostic assays for breast cancer, as well as for monitoring the progression and treatment of breast cancer, and related diseases and conditions.  
      In addition, SEQ ID NO:39 and SEQ ID NO:42 demonstrated tissue-specific expression. RNA samples isolated from a variety of normal human tissues were compared to a common reference sample. Tissues contributing to the reference sample were selected for their ability to provide a complete distribution of RNA in the human body and include brain (4%), heart (7%), kidney (3%), lung (8%), placenta (46%), small intestine (9%), spleen (3%), stomach (6%), testis (9%), and uterus (5%). The normal tissues assayed were obtained from at least three different donors. RNA from each donor was separately isolated and individually hybridized to the microarray. Since these hybridization experiments were conducted using a common reference sample, differential expression values are directly comparable from one tissue to another. The expression of SEQ ID NO:39 was increased by at least two-fold in small intestine and blood leukocytes as compared to the reference sample. Therefore, SEQ ID NO:39 can be used as a marker for small intestine and blood leukocytes. In addition, the expression of SEQ ID NO:42 was increased by at least two-fold in aortic tissue as compared to the reference sample. Therefore, SEQ ID NO:42 can be used as a marker for aortic tissue.  
      In another example, SEQ ID NO:44 showed differential expression in breast cancer cell lines as compared to non-cancerous breast epithelial cell lines as determined by microarray analysis. Gene expression profiles of nonmalignant mammary epithelial cells were compared to gene expression profiles of various breast carcinoma lines at different stages of tumor progression. Cell lines compared included: a) HMEC, a primary breast epithelial cell line isolated from a normal donor, b) MCF-10A, a breast mammary gland cell line isolated from a 36-year-old woman with fibrocystic breast disease, c) MCF7, a nonmalignant breast adenocarcinoma cell line isolated from the pleural effusion of a 69-year-old female, d) T-47D, a breast carcinoma cell line isolated from a pleural effusion obtained from a 54-year-old female with an infiltrating ductal carcinoma of the breast, e) Sk-BR-3, a breast adenocarcinoma cell line isolated from a malignant pleural effusion of a 43-year-old female, f) BT-20, a breast carcinoma cell line derived in vitro from cells emigrating out of thin slices of the tumor mass isolated from a 74-year-old female, g) MDA-mb-231, a breast tumor cell line isolated from the pleural effusion of a 51-year-old female, and h) MDA-mb-435S, a spindle-shaped strain that evolved from the parent line (435) isolated by R. Cailieau from pleural effusion of a 31-year-old female with metastatic, ductal adenocarcinoma of the breast. Expression of SEQ ID NO:44 was decreased by at least two-fold in the MCF7 breast cancer cell lines as compared to the non-malignant HMEC and MCF-10A cells. Therefore, in an embodiment, SEQ ID NO:44 can be used in diagnostic assays for, and/or monitoring treatment of, early stages of breast cancer and related diseases and conditions.  
      In a further example, SEQ ID NO:44 and SEQ ID NO:48 showed differential expression in colon tumor tissues compared to normal colon tissue from the same donor as determined by microarray analysis. Samples of normal colon were compared to colon tumor from the same donor (Huntsman Cancer Institute, Salt Lake City, Utah). The expression of SEQ ID NO:44, was decreased at least two-fold in tumor tissue as compared to matched normal colon tissue for one donor and increased by at least twofold in another, while the expression of SEQ ID NO:48 was increased at least two-fold in tumor tissue as compared to matched normal colon tissue for one donor. Therefore, in an embodiment, SEQ ID NO:44 and SEQ ID NO:48 can be used in diagnostic assays for, and/or monitoring treatment of, colon cancer and related diseases and conditions.  
      In a further example, SEQ ID NO:44 and SEQ ID NO:47 showed differential expression in lung tumor tissues compared to normal lung tissue from the same donor as determined by microarray analysis. Samples of normal lung were compared to lung tumor from the same donor (Roy Castle International Centre for Lung Cancer Research, Liverpool, UK). The expression of SEQ ID NO:44 was increased by at least two-fold in tumor tissue as compared to the matched normal lung for one donor, while the expression of SEQ ID NO:47 was decreased by at least two-fold in tumor tissue as compared to the matched normal lung for two different donors. Therefore, in an embodiment, SEQ ID NO:44 and SEQ ID NO:47 can be used in diagnostic assays for, and/or monitoring treatment of, lung cancer and related diseases and conditions.  
      In a further example, SEQ ID NO:46 showed differential expression associated with the immune response. PBMCs from the blood of 6 healthy volunteer donors were incubated for 24 hours in the presence of graded doses of beclomethasone dissolved in DMSO. In addition, matching PBMCs were treated for the same duration with matching doses of DMSO in order to monitor the possible effects of the vehicle alone. The treated PBMC were compared to matching untreated PBMCs maintained in culture for the same duration. The expression of SEQ ID NO:46 was decreased by at least two-fold in the PBMCs treated with beclomethasone, but not in PBMCs treated with DMSO alone, as compared to untreated PBMCs. Therefore, in an embodiment, SEQ ID NO:46 can be used in diagnostic assays for, and/or monitoring treatment of autoimmune and inflammatory disorders.  
      In a further example, SEQ ID NO:46 and SEQ ID NO:47 showed tissue-specific expression. RNA samples isolated from a variety of normal human tissues were compared to a common reference sample. Tissues in the reference sample were selected for their ability to provide a complete representation of all RNA expressed in the human body and include brain (4%), heart (7%), kidney (3%), lung (8%), placenta (46%), small intestine (9%), spleen (3%), stomach (6%), testis (9%), and uterus (5%). The normal tissues assayed were obtained from at least three different donors. RNA from each donor was separately isolated and individually hybridized to the microarray. Since these hybridization experiments were conducted using a common reference sample, differential expression values are directly comparable from one tissue to another. The expression of both SEQ ID NO:46 and SEQ ID NO:47 was increased by at least two-fold in blood as compared to the reference sample. Therefore, SEQ ID NO:46 and SEQ ID NO:47 can be used as blood markers.  
      In another example, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:57 and SEQ ID NO:61 showed differential expression associated with prostate cancer, as determined by microarray analysis. Primary prostate epithelial cells were compared with prostate carcinomas representative of the different stages of tumor progression. In two experiments, cell lines compared included: a) PrEC, a primary prostate epithelial cell line isolated from a normal donor, b) DU 145, a prostate carcinoma cell line isolated from a metastatic site in the brain of 69-year old male with widespread metastatic prostate carcinoma, c) LNCaP, a prostate carcinoma cell line isolated from a lymph node biopsy of a 50-year-old male with metastatic prostate carcinoma, and d) PC-3, a prostate adenocarcinoma cell line isolated from a metastatic site in the bone of a 62-year-old male with grade IV prostate adenocarcinoma. In the first experiment, cells were grown in basal medium in the absence of growth factors and hormones. In the second experiment, cells were cultured, under optimal growth conditions, in medium supplemented with growth factors and nutrients. The expression of SEQ ID NO:61 was downregulated by at least two-fold in all three carcinoma cell lines, as compared to the primary prostate epithelial cell line, whether cells were grown in basal or supplemented medium. The expression of SEQ ID NO:56 was downregulated by at least two-fold in DU145 cells and LNCaP cells, whether cells were grown in basal or supplemented medium. The expression of SEQ ID NO:52 was decreased by at least two-fold in DU145 cells and LNCaP cells, as compared to PrEC cells, when grown in basal medium. The expression of SEQ ID NO:51 and SEQ ID NO:57 was downregulated by at least two-fold in DU145 cells grown in supplemented medium. Therefore, in various embodiments, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:56, SEQ ID NO:57 and SEQ ID NO:61 can each be used for one or more of the following: i) monitoring treatment of prostate cancer, ii) diagnostic assays for prostate cancer, and iii) developing therapeutics and/or other treatments for prostate cancer.  
      SEQ ID NO:61 showed differential expression associated with lung cancer, as determined by microarray analysis. Grossly uninvolved tissue from a donor was compared to lung tumor tissue from the same donor (Roy Castle International Centre for Lung Cancer Research, Liverpool, UK). The expression of SEQ ID NO:61 was upregulated by at least 10-fold in the lung tumor tissue as compared to uninvolved lung tissue. Therefore, in various embodiments, SEQ ID NO:61 can be used for one or more of the following: i) monitoring treatment of lung cancer, ii) diagnostic assays for lung cancer, and iii) developing therapeutics and/or other treatments for lung cancer.  
      SEQ ID NO:61 showed differential expression associated with obesity, as determined by microarray analysis. In two parallel experiments, pre-adipocytes from a healthy 28-year-old female donor, with a body mass index (BMI) of 23.59 and pre-adipocytes from an obese 40-year-old female donor with a BMI of 32.47 were induced to differentiate into adipocytes by treatment with human insulin and peroxisome proliferation-activated receptor gamma agonists for three days followed by growth in medium containing only insulin for 24 hours, 48 hours, 4 days, 1.1 weeks or 2.1 weeks. The expression of SEQ ID NO:61 was decreased by at least two-fold in differentiating pre-adipocytes from the donor with a BMI of 32.47 at the 1.1 and 2.1 weeks timepoints, as compared to the pre-adipocytes from the donor with a BMI of 23.59. Therefore, in various embodiments, SEQ ID NO:61 can be used for one or more of the following: i) monitoring treatment of, and ii) developing therapeutics and/or other treatments for obesity.  
      SEQ ID NO:56 showed differential expression associated with atherosclerosis and inflammatory immune responses, as determined by microarray analysis. Promonocyte THP-1 cells were incubated first with phorbol myristate acetate (PMA), inducing differentiation into macrophage-like cells, and then with oxidized low density lipid (oxLDL) leading to the development of a “foam” cell morphology, typically observed in macrophages that localize to vascular lesions. Macrophage and foam cells thus derived were activated by treatment with lipopolysaccharide (LPS) and examined for changes in gene expression. The expression of SEQ ID NO:56 was upregulated by at least two-fold in both activated macrophages and activated foam cells as compared to cells that were not treated with LPS, and therefore not activated. Therefore, in various embodiments, SEQ ID NO:56 can be used for one or more of the following: i) monitoring treatment of, ii) diagnostic assays for, and iii) developing therapeutics and/or other treatments for atherosclerosis.  
      SEQ ID NO:53 and SEQ ID NO:61 showed tissue-specific expression, as determined by microarray analysis. RNA samples isolated from a variety of normal human tissues were compared to a common reference sample. Tissues contributing to the reference sample were selected for their ability to provide a complete distribution of RNA in the human body and include brain (4%), heart (7%), kidney (3%), lung (8%), placenta (46%), small intestine (9%), spleen (3%), stomach (6%), testis (9%), and uterus (5%). The normal tissues assayed were obtained from at least three different donors. RNA from each donor was separately isolated and individually hybridized to the microarray. Since these hybridization experiments were conducted using a common reference sample, differential expression values are directly comparable from one tissue to another. The expression of SEQ ID NO:53 was increased by at least two-fold in brain tissue, specifically occipital and temporal cortex, as compared to the reference sample. The expression of SEQ ID NO:61 was increased by at least two-fold in esophageal tissue as compared to the reference sample. Therefore, in an embodiment, SEQ ID NO:53 can be used as a tissue marker for cortical tissue of the brain, and, in another embodiment, SEQ ID NO:61 can be used as a tissue marker for the esophagus.  
      XII. Complementary Polynucleotides  
      Sequences complementary to the CADECM-encoding sequences, or any parts thereof, are used to detect, decrease, or inhibit expression of naturally occurring CADECM. Although use of oligonucleotides comprising from about 15 to 30 base pairs is described, essentially the same procedure is used with smaller or with larger sequence fragments. Appropriate oligonucleotides are designed using OLIGO 4.06 software (National Biosciences) and the coding sequence of CADECM. To inhibit transcription, a complementary oligonucleotide is designed from the most unique 5′ sequence and used to prevent promoter binding to the coding sequence. To inhibit translation, a complementary oligonucleotide is designed to prevent ribosomal binding to the CADECM-encoding transcript.  
      XIII. Expression of CADECM  
      Expression and purification of CADECM is achieved using bacterial or virus-based expression systems. For expression of CADECM 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 limited 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 CADECM upon induction with isopropyl beta-D-thiogalactopyranoside (IPTG). Expression of CADECM in eukaryotic cells is achieved by infecting insect or mammalian cell lines with recombinant  Autographica californica  nuclear polyhedrosis virus (AcMNPV), commonly known as baculovirus. The nonessential polyhedrin gene of baculovirus is replaced with cDNA encoding CADECM 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 cells in most cases, or human hepatocytes, in some cases. Infection of the latter requires additional genetic modifications to baculovirus (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, CADECM is synthesized as a fusion protein with, e.g., glutathione S-transferase (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 japonicum , enables the purification of fusion proteins on immobilized glutathione under conditions that maintain protein activity and antigenicity (Amersham Biosciences). Following purification, the GST moiety can be proteolytically cleaved from CADECM at specifically 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 et al. (supra, ch. 10 and 16). Purified CADECM obtained by these methods can be used directly in the assays shown in Examples XVII and XVIII, where applicable.  
      XIV. Functional Assays  
      CADECM function is assessed by expressing the sequences encoding CADECM at physiologically elevated levels in mammalian cell culture systems. cDNA is subcloned into a mammalian expression vector containing a strong promoter that drives high levels of cDNA expression. Vectors of choice include PCMV SPORT plasmid (Invitrogen, Carlsbad Calif.) and PCR3.1 plasmid (Invitrogen), both of which contain the cytomegalovirus promoter. 5-10 μg of recombinant vector are transiently transfected into a human cell line, for example, an endothelial or hematopoietic cell line, using either liposome 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 cells from nontransfected cells and is a reliable 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 cells expressing GFP or CD64-GFP and to evaluate the apoptotic state of the cells and other cellular properties. FCM detects and quantifies the uptake of fluorescent molecules that diagnose events preceding or coincident with cell death. These events include changes in nuclear DNA content as measured by staining of DNA with propidium iodide; changes in cell size and granularity as measured by forward light scatter and 90 degree side light scatter; down-regulation of DNA synthesis as measured by decrease in bromodeoxyuridine uptake; alterations in expression of cell surface and intracellular 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 cell surface. Methods in flow cytometry are discussed in Ormerod, M. G. (1994 ; Flow Cytometry , Oxford, New York N.Y.).  
      The influence of CADECM on gene expression can be assessed using highly purified populations of cells transfected with sequences encoding CADECM and either CD64 or CD64-GFP. CD64 and CD64-GFP are expressed on the surface of transfected cells and bind to conserved regions of human immunoglobulin G (IgG). Transfected cells are efficiently separated from nontransfected cells using magnetic beads coated with either human IgG or antibody against CD64 (DYNAL, Lake Success N.Y.). mRNA can be purified from the cells using methods well known by those of skill in the art. Expression of mRNA encoding CADECM and other genes of interest can be analyzed by northern analysis or microarray techniques.  
      XV. Production of CADECM Specific Antibodies  
      CADECM substantially 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 animals (e.g., rabbits, mice, etc.) and to produce antibodies using standard protocols.  
      Alternatively, the CADECM amino acid sequence is analyzed using LASERGENE software (DNASTAR) to determine regions of high immunogenicity, and a corresponding oligopeptide 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 hydrophilic regions are well described in the art (Ausubel et al., supra, ch. 11).  
      Typically, oligopeptides of about 15 residues in length are synthesized using an ABI 431A peptide synthesizer (Applied 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 (Ausubel et al., supra). Rabbits are immunized with the oligopeptide-KLH complex in complete Freund&#39;s adjuvant. Resulting antisera are tested for antipeptide and anti-CADECM activity by, for example, binding the peptide or CADECM to a substrate, blocking with 1% BSA, reacting with rabbit antisera, washing, and reacting with radio-iodinated goat anti-rabbit IgG.  
      XVI. Purification of Naturally Occurring CADECM Using Specific Antibodies  
      Naturally occurring or recombinant CADECM is substantially purified by immunoaffinity chromatography using antibodies specific for CADECM. An immunoaffinity column is constructed by covalently coupling anti-CADECM antibody to an activated chromatographic resin, such as CNBr-activated SEPHAROSE (Amersham Biosciences). After the coupling, the resin is blocked and washed according to the manufacturer&#39;s instructions.  
      Media containing CADECM are passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of CADECM (e.g., high ionic strength buffers in the presence of detergent). The column is eluted under conditions that disrupt antibody/CADECM binding (e.g., a buffer of pH 2 to pH 3, or a high concentration of a chaotrope, such as urea or thiocyanate ion), and CADECM is collected.  
      XVII. Identification of Molecules Which Interact with CADECM  
      CADECM, or biologically active fragments thereof, are labeled with  125 I Bolton-Hunter reagent (Bolton, A. E. and W. M. Hunter (1973) Biochem. J. 133:529-539). Candidate molecules previously arrayed in the wells of a multi-well plate are incubated with the labeled CADECM, washed, and any wells with labeled CADECM complex are assayed. Data obtained using different concentrations of CADECM are used to calculate values for the number, affinity, and association of CADECM with the candidate molecules.  
      Alternatively, molecules interacting with CADECM 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).  
      CADECM may also be used in the PATHCALLING process (CuraGen Corp., New Haven Conn.) which employs the yeast two-hybrid system in a high-throughput manner to determine all interactions between the proteins encoded by two large libraries of genes (Nandabalan, K. et al. (2000) U.S. Pat. No. 6,057,101).  
      XVIII. Demonstration of CADECM Activity  
      An assay for CADECM activity measures the expression of CADECM on the cell surface. cDNA encoding CADECM is transfected into a non4eukocytic cell line. Cell surface proteins are labeled with biotin (de la Fuente, M. A. et al. (1997) Blood 90:2398-2405). Immunoprecipitations are performed using CADECM-specific antibodies, and immunoprecipitated samples are analyzed using SDS-PAGE and immunoblotting techniques. The ratio of labeled immunoprecipitant to unlabeled immunoprecipitant is proportional to the amount of CADECM expressed on the cell surface.  
      Alternatively, an assay for CADECM activity measures the amount of cell aggregation induced by overexpression of CADECM. In this assay, cultured cells such as NIH3T3 are transfected with cDNA encoding CADECM contained within a suitable mammalian expression vector under control of a strong promoter. Cotransfection with cDNA encoding a fluorescent marker protein, such as Green Fluorescent Protein (CLONTECH), is useful for identifying stable transfectants. The amount of cell agglutination, or clumping, associated with transfected cells is compared with that associated with untransfected cells. The amount of cell agglutination is a direct measure of CADECM activity.  
      Alternatively, an assay for CADECM activity measures the disruption of cytoskeletal filament networks upon overexpression of CADECM in cultured cell lines (Rezniczek, G. A. et al. (1998) J. Cell Biol. 141:209-225). cDNA encoding CADECM is subcloned into a mammalian expression vector that drives high levels of cDNA expression. This construct is transfected into cultured cells, such as rat kangaroo PtK2 or rat bladder carcinoma 804G cells. Actin filaments and intermediate filaments such as keratin and vimentin are visualized by immunofluorescence microscopy using antibodies and techniques well known in the art. The configuration and abundance of cyoskeletal filaments can be assessed and quantified using confocal imaging techniques. In particular, the bundling and collapse of cytoskeletal filament networks is indicative of CADECM activity.  
      Alternatively, cell adhesion activity in CADECM is measured in a 96-well plate in which wells are first coated with CADECM by adding solutions of CADECM of varying concentrations to the wells. Excess CADECM is washed off with saline, and the wells incubated with a solution of 1% bovine serum albumin to block non-specific cell binding. Aliquots of a cell suspension of a suitable cell type are then added to the wells and incubated for a period of time at 37 ° C. Non-adherent cells are washed off with saline and the cells stained with a suitable cell stain such as Coomassie blue. The intensity of staining is measured using a variable wavelength multi-well plate reader and compared to a standard curve to determine the number of cells adhering to the CADECM coated plates. The degree of cell staining is proportional to the cell adhesion activity of CADECM in the sample.  
      Various modifications and variations of the described compositions, methods, and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. It will be appreciated that the invention provides novel and useful proteins, and their encoding polynucleotides, which can be used in the drug discovery process, as well as methods for using these compositions for the detection, diagnosis, and treatment of diseases and conditions. Although the invention has been described in connection with certain embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Nor should the description of such embodiments be considered exhaustive or limit the invention to the precise forms disclosed. Furthermore, elements from one embodiment can be readily recombined with elements from one or more other embodiments. Such combinations can form a number of embodiments within the scope of the invention. It is intended that the scope of the invention be defined by the following claims and their equivalents.  
                                   TABLE 1                                       Incyte               Polypeptide   Incyte   Polynucleotide   Polynucleotide       Incyte Project ID   SEQ ID NO:   Polypeptide ID   SEQ ID NO:   ID   Incyte Full Length Clones                                                        7506690   1   7506690CD1   32   7506690CB1           7506536   2   7506536CD1   33   7506536CB1       7506537   3   7506537CD1   34   7506537CB1   7015051CA2       7506655   4   7506655CD1   35   7506655CB1       7506656   5   7506656CD1   36   7506656CB1       7510567   6   7510567CD1   37   7510567CB1       7506072   7   7506072CD1   38   7506072CB1   90022504CA2, 90022620CA2       7511354   8   7511354CD1   39   7511354CB1       7511643   9   7511643CD1   40   7511643CB1       7511400   10   7511400CD1   41   7511400CB1   90127784CA2, 90127904CA2       7511507   11   7511507CD1   42   7511507CB1       7511819   12   7511819CD1   43   7511819CB1       7511338   13   7511338CD1   44   7511338CB1   1932850CA2       7511425   14   7511425CD1   45   7511425CB1       7511534   15   7511534CD1   46   7511534CB1       7511648   16   7511648CD1   47   7511648CB1       7511600   17   7511600CD1   48   7511600CB1       7511783   18   7511783CD1   49   7511783CB1       7512383   19   7512383CD1   50   7512383CB1       7512813   20   7512813CD1   51   7512813CB1   90048154CA2, 90048278CA2       7512842   21   7512842CD1   52   7512842CB1   90205318CA2, 90205322CA2       90190613    22   90190613CD1    53   90190613CB1        7511894   23   7511894CD1   54   7511894CB1       3604804   24   3604804CD1   55   3604804CB1       7512568   25   7512568CD1   56   7512568CB1       7512812   26   7512812CD1   57   7512812CB1   90127746CA2       7512826   27   7512826CD1   58   7512826CB1       7512908   28   7512908CD1   59   7512908CB1       7512909   29   7512909CD1   60   7512909CB1       7512769   30   7512769CD1   61   7512769CB1   5578193CA2, 56050318CA2, 56050402CA2       7512871   31   7512871CD1   62   7512871CB1                  
 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                   
               
               
                 Poly- 
                   
                 GenBank 
                   
                   
               
               
                 peptide 
                 Incyte 
                 ID NO: or 
               
               
                 SEQ 
                 Polypeptide 
                 PROTEOME 
                 Probability 
               
               
                 ID NO: 
                 ID 
                 ID NO: 
                 Score 
                 Annotation 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 7506690CD1 
                 g2511666 
                 2.0e−301 
                 [ Homo sapiens ] NrCAM protein 
               
               
                   
                   
                   
                   
                 Wang, B.et al. 
               
               
                   
                   
                   
                   
                 Alternative splicing of human NrCAM in neural and nonneural tissues 
               
               
                   
                   
                   
                   
                 Mol. Cell. Neurosci. 10 (5-6), 287-295 (1998) 
               
               
                   
                   
                 341732| 
                 2.3E−296 
                 [ Homo sapiens ][Adhesin/agglutinin][Plasma membrane] Neuronal cell adhesion molecule, a 
               
               
                   
                   
                 NRCAM 
                   
                 member of the immunoglobulin superfamily, predicted to have a role in neuronal cell 
               
               
                   
                   
                   
                   
                 adhesion 
               
               
                   
                   
                   
                   
                 Sehgal, A. et al. 
               
               
                   
                   
                   
                   
                 Cell adhesion molecule Nr-CAM is over-expressed in human brain tumors. 
               
               
                   
                   
                   
                   
                 Int J Cancer 76, 451-8 (1998). 
               
               
                   
                   
                 330958| 
                 1.1E−287 
                 [ Rattus norvegicus ][Adhesin/agglutinin][Plasma membrane] Neuronal cell adhesion 
               
               
                   
                   
                 Nrcam 
                   
                 molecule, a member of the immunoglobulin superfamily, predicted to be cell adhesion 
               
               
                   
                   
                   
                   
                 molecule involved in the guidance of axonal growth cones during neuronal development 
               
               
                   
                   
                   
                   
                 Lambert, S. et al. 
               
               
                   
                   
                   
                   
                 Morphogenesis of the node of Ranvier: co-clusters of ankyrin and ankyrin-binding integral 
               
               
                   
                   
                   
                   
                 proteins define early developmental intermediates. 
               
               
                   
                   
                   
                   
                 J Neurosci 17, 7025-36. (1997). 
               
               
                 2 
                 7506536CD1 
                 g16191616 
                 3.0E−218 
                 [ Homo sapiens ] putative emu1 protein 
               
               
                   
                   
                 578546| 
                 5.7E−48 
                 [ Mus musculus ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                 Collal 
                   
                 Extracellular (excluding cell wall)] Alpha 1 subunit of type I collagen, a structural protein; 
               
               
                   
                   
                   
                   
                 mutations in human COL1A1 cause Ehlers-Danlos syndrome type VII, osteoporosis, and 
               
               
                   
                   
                   
                   
                 osteogenesis imperfecta 
               
               
                   
                   
                   
                   
                 Francki, A. et al. 
               
               
                   
                   
                   
                   
                 SPARC regulates the expression of collagen type I and transforming growth factor-beta1 in 
               
               
                   
                   
                   
                   
                 mesangial cells. 
               
               
                   
                   
                   
                   
                 J Biol Chem 274, 32145-52 (1999). 
               
               
                   
                   
                 762505| 
                 7.5E−47 
                 [ Homo sapiens ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                 COL9A3 
                   
                 Extracellular (excluding cell wall)] Collagen (type IX, alpha 3), a structural component of 
               
               
                   
                   
                   
                   
                 cartilage extracellular matrix which may be involved in cartilage and muscle development; 
               
               
                   
                   
                   
                   
                 mutation of the corresponding gene causes epiphyseal dysplasia 
               
               
                   
                   
                   
                   
                 Paassilta, P. et al. 
               
               
                   
                   
                   
                   
                 COL9A3: A third locus for multiple epiphyseal dysplasia. 
               
               
                   
                   
                   
                   
                 Am J Hum Genet 64, 1036-44. (1999). 
               
               
                 3 
                 7506537CD1 
                 g16191616 
                 1.5E−58 
                 [ Homo sapiens ] putative emu1 protein 
               
               
                   
                   
                 428756| 
                 9.7E−20 
                 [ Homo sapiens ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                 EMILIN 
                   
                 Extracellular (excluding cell wall)] Elastin microfibril interface located protein, an 
               
               
                   
                   
                   
                   
                 extracellular matrix protein found between amorphous elastin and microfibrils that may play 
               
               
                   
                   
                   
                   
                 a role in elastin deposition 
               
               
                   
                   
                   
                   
                 Doliana, R. et al. 
               
               
                   
                   
                   
                   
                 EMILIN, a component of the elastic fiber and a new member of the C1q/tumor necrosis 
               
               
                   
                   
                   
                   
                 factor superfamily of proteins. 
               
               
                   
                   
                   
                   
                 J Biol Chem 274, 16773-81 (1999). 
               
               
                   
                   
                 716229| 
                 1.6E−16 
                 [ Homo sapiens ] Elastin microfibril interface located 2, a secreted glycoprotein with a 
               
               
                   
                   
                 EMILIN-2 
                   
                 globular C1q domain, a short collagenous stalk, a potential coiled-coil region, a proline-rich 
               
               
                   
                   
                   
                   
                 region and a cysteine-rich domain (EMI domain) 
               
               
                 4 
                 7506655CD1 
                 g31419 
                 6.8E−180 
                 [ Homo sapiens ] fibulin-1 C 
               
               
                   
                   
                   
                   
                 Korenberg, J. R. et al. 
               
               
                   
                   
                   
                   
                 Localization of the human gene for fibulin-1 (FBLN1) to chromosome band 22q13.3 
               
               
                   
                   
                   
                   
                 Cytogenet. Cell Genet. 68, 192-193 (1995) 
               
               
                   
                   
                 568154| 
                 5.8E−181 
                 [ Homo sapiens ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                 FBLN1 
                   
                 Extracellular (excluding cell wall)] Fibulin 1, an extracellular matrix and plasma 
               
               
                   
                   
                   
                   
                 glycoprotein that may connect elements of the extracellular matrix, may play a role in 
               
               
                   
                   
                   
                   
                 hemostasis, altered expression may play a role in tumor invasion, thrombosis, and 
               
               
                   
                   
                   
                   
                 connective tissue and blood diseases 
               
               
                   
                   
                   
                   
                 Hayashido, Y. et al. 
               
               
                   
                   
                   
                   
                 Estradiol and fibulin-1 inhibit motility of human ovarian- and breast-cancer cells induced by 
               
               
                   
                   
                   
                   
                 fibronectin. 
               
               
                   
                   
                   
                   
                 Int J Cancer 75, 654-8. (1998). 
               
               
                   
                   
                 584763|Fbln1 
                 2.8E−142 
                 [ Mus musculus ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                   
                   
                 Extracellular (excluding cell wall)] Fibulin 1, an extracellular matrix glycoprotein that may 
               
               
                   
                   
                   
                   
                 connect elements of the extracellular matrix, may play roles in heart, lung, and kidney 
               
               
                   
                   
                   
                   
                 development, epithelial mesenchymal transitions, tensile strength of cardiac valves, and 
               
               
                   
                   
                   
                   
                 tumor invasion 
               
               
                   
                   
                   
                   
                 Olin, A. I. et al. 
               
               
                   
                   
                   
                   
                 The Proteoglycans Aggrecan and Versican Form Networks with Fibulin-2 through Their 
               
               
                   
                   
                   
                   
                 Lectin Domain Binding. 
               
               
                   
                   
                   
                   
                 J Biol Chem 276, 1253-1261. (2001). 
               
               
                 5 
                 7506656CD1 
                 g31419 
                 2.7E−146 
                 [ Homo sapiens ] fibulin-1 C 
               
               
                   
                   
                   
                   
                 Korenberg, J. R. et al. (supra) 
               
               
                   
                   
                 568154| 
                 2.3E−147 
                 [ Homo sapiens ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                 FBLN1 
                   
                 Extracellular (excluding cell wall)] Fibulin 1, an extracellular matrix and plasma 
               
               
                   
                   
                   
                   
                 glycoprotein that may connect elements of the extracellular matrix, may play a role in 
               
               
                   
                   
                   
                   
                 hemostasis, altered expression may play a role in tumor invasion, thrombosis, and 
               
               
                   
                   
                   
                   
                 connective tissue and blood diseases 
               
               
                   
                   
                   
                   
                 Hayashido, Y. et al. (supra) 
               
               
                   
                   
                 584763|Fbln1 
                 4.5E−110 
                 [ Mus musculus ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                   
                   
                 Extracellular (excluding cell wall)] Fibulin 1, an extracellular matrix glycoprotein that may 
               
               
                   
                   
                   
                   
                 connect elements of the extracellular matrix, may play roles in heart, lung, and kidney 
               
               
                   
                   
                   
                   
                 development, epithelial mesenchymal transitions, tensile strength of cardiac valves, and 
               
               
                   
                   
                   
                   
                 tumor invasion 
               
               
                   
                   
                   
                   
                 Olin, A. I. et al. (supra) 
               
               
                 6 
                 7510567CD1 
                 g2842786 
                 2.9E−34 
                 [ Homo sapiens ] INTEGRIN BETA-8 SUBUNIT PRECURSOR 
               
               
                   
                   
                   
                   
                 Tin-Wollam, A. et al. 
               
               
                   
                   
                 336074| 
                 2.4E−35 
                 [ Homo sapiens ][Adhesin/agglutinin; Receptor (signalling)][Plasma membrane] Integrin beta 
               
               
                   
                   
                 ITGB8 
                   
                 8 subunit, a member of the integrin family of adhesion receptors, forms a heterodimer with 
               
               
                   
                   
                   
                   
                 alpha v integrin (ITGAV), cytoplasmic domain apparently does not promote adhesion 
               
               
                   
                   
                   
                   
                 Neufert, C. et al. 
               
               
                   
                   
                   
                   
                   Mycobacterium tuberculosis  19-kDa lipoprotein promotes neutrophil activation. 
               
               
                   
                   
                   
                   
                 J Immunol 167, 1542-9. (2001). 
               
               
                 7 
                 7506072CD1 
                 g930343 
                 1.7E−101 
                 [ Homo sapiens ] LAR-interacting protein 1b 
               
               
                   
                   
                   
                   
                 Serra-Pages, C. et al. 
               
               
                   
                   
                   
                   
                 The LAR transmembrane protein tyrosine phosphtase and a coiled-coil LAR-interacting 
               
               
                   
                   
                   
                   
                 protein co-localize at focal adhesions 
               
               
                   
                   
                   
                   
                 EMBO J. 14, 2827-2838 (1995) 
               
               
                   
                   
                 337114| 
                 1.5E−102 
                 [ Homo sapiens ][Cytoplasmic; Plasma membrane; Cell junction] Protein tyrosine 
               
               
                   
                   
                 PPFIA1 
                   
                 phosphatase receptor type f polypeptide (PTPRF) interacting protein (liprin) alpha 1, 
               
               
                   
                   
                   
                   
                 localizes the PTPRF transmembrane protein tyrosine phosphatase to focal adhesions; also 
               
               
                   
                   
                   
                   
                 interacts with PTPRS and PTPRD 
               
               
                   
                   
                   
                   
                 Pulido, R. et al. 
               
               
                   
                   
                   
                   
                 The LAR/PTP delta/PTP sigma subfamily of transmembrane protein-tyrosine- 
               
               
                   
                   
                   
                   
                 phosphatases: multiple human LAR, PTP delta, and PTP sigma isoforms are expressed in a 
               
               
                   
                   
                   
                   
                 tissue-specific manner and associate with the LAR-interacting protein LIP.1. 
               
               
                   
                   
                   
                   
                 Proc Natl Acad Sci USA 92, 11686-90 (1995). 
               
               
                   
                   
                 748465| 
                 7.6E−68 
                 [ Homo sapiens ][Cytoplasmic; Plasma membrane; Cell junction] Protein phosphatase 
               
               
                   
                   
                 PPFIA3 
                   
                 receptor f interacting protein alpha 3, member of the alpha liprin family, interacts with 
               
               
                   
                   
                   
                   
                 transmembrane protein tyrosine phosphatase PTPRF 
               
               
                   
                   
                   
                   
                 Serra-Pages, C. et al. 
               
               
                   
                   
                   
                   
                 Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. 
               
               
                   
                   
                   
                   
                 J Biol Chem 273, 15611-20 (1998). 
               
               
                 8 
                 7511354CD1 
                 g16198471 
                 0.0 
                 [ Homo sapiens ] integrin, beta 7 
               
               
                   
                   
                 336072| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin; Receptor (signalling)][Plasma membrane] Beta 7 
               
               
                   
                   
                 ITGB7 
                   
                 subunit of integrin, a member of a family of cell-surface proteins involved in cell-cell and 
               
               
                   
                   
                   
                   
                 cell-matrix interactions, involved in cell migration, cell clustering, and inflammatory 
               
               
                   
                   
                   
                   
                 responses; may play a role in Sjogren&#39;s Syndrome. 
               
               
                   
                   
                   
                   
                 Jakubowski, A., Ehrenfels, B. N., Pepinsky, 
               
               
                   
                   
                   
                   
                 R. B., and Burkly, L. C. Vascular cell adhesion 
               
               
                   
                   
                   
                   
                 molecule-Ig fusion protein selectively targets activated alpha 4-integrin receptors in vivo. 
               
               
                   
                   
                   
                   
                 Inhibition of autoimmune diabetes in an adoptive transfer model in nonobese diabetic mice. 
               
               
                   
                   
                   
                   
                 J Immunol 155, 938-46 (1995). 
               
               
                   
                   
                 587101| 
                 0.0 
                 [ Mus musculus ][Adhesin/agglutinin; Receptor (signalling)][Plasma membrane] Beta 7 
               
               
                   
                   
                 Itgb7 
                   
                 subunit of integrin, a member of a family of cell-surface proteins involved in cell-cell and 
               
               
                   
                   
                   
                   
                 cell-matrix interactions; may be involved in inflammatory responses. 
               
               
                   
                   
                   
                   
                 Wagner, N., Lohler, J., Kunkel, E. J., Ley, K., 
               
               
                   
                   
                   
                   
                 Leung, E., Krissansen, G., Rajewsky, K., and 
               
               
                   
                   
                   
                   
                 Muller, W. Critical role for beta7 integrins in formation of the gut-associated lymphoid 
               
               
                   
                   
                   
                   
                 tissue. Nature 382, 366-70 (1996). 
               
               
                   
                   
                 331094| 
                 1.0E−229 
                 [ Rattus norvegicus ][Receptor (signalling)][Plasma membrane] Beta 7 subunit of integrin, a 
               
               
                   
                   
                 Itgb7 
                   
                 member of the family of cell-surface proteins involved in cell-cell and cell-matrix 
               
               
                   
                   
                   
                   
                 interactions; may be involved in cell migration and inflammatory responses. 
               
               
                   
                   
                   
                   
                 Feng, C. G., Britton, W. J., Palendira, U., Groat, N. L., Briscoe, H., and Bean, A. G. Up- 
               
               
                   
                   
                   
                   
                 regulation of VCAM-1 and differential expansion of beta integrin-expressing T 
               
               
                   
                   
                   
                   
                 lymphocytes are associated with immunity to pulmonary  Mycobacterium tuberculosis   
               
               
                   
                   
                   
                   
                 infection. J Immunol 164, 4853-60 (2000). 
               
               
                 9 
                 7511643CD1 
                 g854175 
                 0.0 
                 [ Homo sapiens ] LI-cadherin 
               
               
                   
                   
                   
                   
                 Grotzinger C. et al. LI-cadherin: a marker of gastric metaplasia and neoplasia. Gut. 2001 
               
               
                   
                   
                   
                   
                 Jul; 49(1): 73-81. 
               
               
                   
                   
                 752595| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin; Transporter][Plasma membrane] Cadherin 17 (liver- 
               
               
                   
                   
                 CDH17 
                   
                 intestine cadherin), which mediates calcium-dependent cell to cell adhesion; is expressed in 
               
               
                   
                   
                   
                   
                 gastric intestinal metaplasia and adenocarcinomas. 
               
               
                   
                   
                   
                   
                 Meli, M. L. et al. Anti-neuroblastoma antibody chCE7 binds to an isoform of L1-CAM 
               
               
                   
                   
                   
                   
                 present in renal carcinoma cells. Int J Cancer 83, 401-8 (1999). 
               
               
                   
                   
                 608812| 
                 0.0 
                 [ Mus musculus ][Adhesin/agglutinin; Ligand; Receptor (signalling)][Plasma membrane] 
               
               
                   
                   
                 Cdh17 
                   
                 Cadherin 17 (liver-intestine cadherin), which mediates calcium-dependent cell to cell 
               
               
                   
                   
                   
                   
                 adhesion; the human protein is expressed in gastric intestinal metaplasia and 
               
               
                   
                   
                   
                   
                 adenocarcinomas. 
               
               
                   
                   
                   
                   
                 Angres, B., Kim, L., Jung, R., Gessner, R., and Tauber, R. LI-cadherin gene expression 
               
               
                   
                   
                   
                   
                 during mouse intestinal development. Dev Dyn 221, 182-93. (2001). 
               
               
                   
                   
                 757578| 
                 0.0 
                 [ Rattus norvegicus ][Adhesin/agglutinin][Basolateral plasma membrane; Plasma membrane] 
               
               
                   
                   
                 Cdh17 
                   
                 Cadherin 17 (liver-intestine cadherin), which mediates calcium-dependent cell to cell 
               
               
                   
                   
                   
                   
                 adhesion; the human protein is expressed in gastric intestinal metaplasia and 
               
               
                   
                   
                   
                   
                 adenocarcinomas. 
               
               
                   
                   
                   
                   
                 Hou, D. X. et al. Expression of cell adhesion molecule and albumin genes in 
               
               
                   
                   
                   
                   
                 primary culture of rat hepatocytes. Cell Biol Int 25, 239-44. (2001). 
               
               
                 10 
                 7511400CD1 
                 g18490857 
                 2.1E−31 
                 [ Homo sapiens ] thrombospondin 
               
               
                   
                   
                 731643| 
                 1.7E−32 
                 [ Homo sapiens ] Protein containing a type 1 thrombospondin domain, has high similarity to 
               
               
                   
                   
                 FLJ14440 
                   
                 uncharacterized mouse 2810459H04Rik. 
               
               
                   
                   
                 368602| 
                 1.6E−29 
                 [ Mus musculus ] Protein containing a type 1 thrombospondin domain, has high similarity to 
               
               
                   
                   
                 Mm.42202 
                   
                 uncharacterized human FLJ14440. 
               
               
                 11 
                 7511507CD1 
                 g4490530 
                 4.9E−165 
                 [ Homo sapiens ] fibulin-5 
               
               
                   
                   
                 567846| 
                 4.0E−166 
                 [ Homo sapiens ][Ligand][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                 FBLN5 
                   
                 Extracellular (excluding cell wall)] Fibulin 5, a member of the EGF-like family, 
               
               
                   
                   
                   
                   
                 serves as an integrin ligand during cell adhesion. 
               
               
                   
                   
                   
                   
                 Nakamura, T. et al. DANCE, a novel secreted RGD protein expressed in developing, 
               
               
                   
                   
                   
                   
                 atherosclerotic, and balloon-injured arteries. J Biol Chem 274, 22476-83 (1999). 
               
               
                   
                   
                   
                   
                 Nakamura, T. et al. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415, 
               
               
                   
                   
                   
                   
                 171-5. (2002). 
               
               
                   
                   
                 429808| 
                 4.5E−158 
                 [ Mus musculus ][Ligand][Extracellular (excluding cell wall)] Fibulin 5, a member of the 
               
               
                   
                   
                 Fbln5 
                   
                 EGF-like family, a putative ligand that functions in the response to wounding and may 
               
               
                   
                   
                   
                   
                 contribute to cell adhesion, angiogenesis, and epithelial-mesenchymal transitions during 
               
               
                   
                   
                   
                   
                 development. 
               
               
                   
                   
                   
                   
                 Yanagisawa, H. et al. Fibulin-5 is an elastin-binding protein essential for elastic fibre 
               
               
                   
                   
                   
                   
                 development in vivo. Nature 415, 168-71. (2002). 
               
               
                   
                   
                   
                   
                 Nakamura, T. et al. (1999) (supra) 
               
               
                   
                   
                   
                   
                 Nakamura, T. et al. (2002) (supra) 
               
               
                   
                   
                 609665| 
                 9.4E−158 
                 [ Rattus norvegicus ][Ligand][Extracellular (excluding cell wall)] Fibulin 5, a member of the 
               
               
                   
                   
                 Fbln5 
                   
                 EGF-like family, an integrin ligand that is secreted, functions in cell adhesion, and may be 
               
               
                   
                   
                   
                   
                 involved in vascular repair after injury. 
               
               
                   
                   
                   
                   
                 Kowal, R. C. et al. EVEC, a novel epidermal growth factor-like repeat-containing protein 
               
               
                   
                   
                   
                   
                 upregulated in embryonic and diseased adult vasculature. Circ Res 84, 1166-76 (1999). 
               
               
                   
                   
                   
                   
                 Nakamura, T. et al. (1999) (supra) 
               
               
                   
                   
                   
                   
                 Nakamura, T. et al. (2002) (supra) 
               
               
                 12 
                 7511819CD1 
                 g2695574 
                 0.0 
                 [ Homo sapiens ] leukocyte function-associated molecule-1 alpha subunit 
               
               
                   
                   
                   
                   
                 Loftus, B. J. et al., Genome duplications and other features in 12 Mb of DNA sequence 
               
               
                   
                   
                   
                   
                 from human chromosome 16p and 16q, Genomics 60, 295-308 (1999) 
               
               
                   
                   
                 336054| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin; Receptor (signaling)][Plasma membrane] Integrin 
               
               
                   
                   
                 ITGAL 
                   
                 alpha L subunit, a heterophilic cell adhesion molecule that forms a heterodimer with 
               
               
                   
                   
                   
                   
                 ITGB2, function in cell-cell adhesion via an interaction with intercellular adhesion molecule 
               
               
                   
                   
                   
                   
                 1 (ICAM-1), signals through a protein kinase C pathway 
               
               
                   
                   
                   
                   
                 Weber, K. S. et al., Specific activation of leukocyte beta2 integrins lymphocyte function- 
               
               
                   
                   
                   
                   
                 associated antigen-1 and Mac-1 by chemokines mediated by distinct pathways via the alpha 
               
               
                   
                   
                   
                   
                 subunit cytoplasmic domains., Mol Biol Cell 10, 861-73 (1999). 
               
               
                   
                   
                   
                   
                 Peled, A. et al., The chemokine SDF-1 activates the integrins LFA-1, VLA-4, and VLA-5 
               
               
                   
                   
                   
                   
                 on immature human CD34(+) cells: role in transendothelial/stromal migration and 
               
               
                   
                   
                   
                   
                 engraftment of NOD/SCID mice., Blood 95, 3289-96 (2000). 
               
               
                   
                   
                 319762|Itgal 
                 1.6E−265 
                 [ Mus musculus ][Adhesin/agglutinin; Receptor (signaling)][Plasma membrane] Integrin 
               
               
                   
                   
                   
                   
                 alpha L subunit, a heterophilic cell adhesion molecule forms a heterodimer with ITGB2, 
               
               
                   
                   
                   
                   
                 interacts with intercellular adhesion molecule 1 and 2 (Icam1)(Icam2), involved in cell 
               
               
                   
                   
                   
                   
                 migration, neutrophil rolling and in allograft rejection 
               
               
                   
                   
                   
                   
                 Stein, J. V. et al., The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, 
               
               
                   
                   
                   
                   
                 secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function- 
               
               
                   
                   
                   
                   
                 associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node 
               
               
                   
                   
                   
                   
                 high endothelial venules., J Exp Med 191, 61-76 (2000). 
               
               
                 13 
                 7511338CD1 
                 g17939541 
                 1.9E−14 
                 [ Homo sapiens ] integrin beta 4 binding protein 
               
               
                   
                   
                 336066| 
                 1.5E−15 
                 [ Homo sapiens ][Anchor Protein][Nuclear; Cytoskeletal; Plasma membrane] Integrin beta 4 
               
               
                   
                   
                 ITGB4BP 
                   
                 binding protein (translation initiation factor eIF6), prevents formation of the 80S ribosome 
               
               
                   
                   
                   
                   
                 by inhibiting the 60S ribosomal subunit, may play a role in the allergic response, 
               
               
                   
                   
                   
                   
                 upregulated during progression of colorectal cancer 
               
               
                   
                   
                   
                   
                 Sanvito, F. et al., The beta 4 integrin interactor p27(BBP/eIF6) is an essential nuclear 
               
               
                   
                   
                   
                   
                 matrix protein involved in 60S ribosomal subunit assembly., J Cell Biol 144, 823-837 
               
               
                   
                   
                   
                   
                 (1999). 
               
               
                   
                   
                   
                   
                 Sanvito, F. et al., Expression of a highly conserved protein, p27BBP, during the progression 
               
               
                   
                   
                   
                   
                 of human colorectal cancer., Cancer Res 60, 510-6 (2000). 
               
               
                   
                   
                 676861| 
                 6.6E−15 
                 [ Mus musculus ][Anchor Protein][Nuclear; Cytoplasmic; Unspecified membrane] Integrin 
               
               
                   
                   
                 Itgb4bp 
                   
                 beta 4 binding protein (translation initiation factor eIF6), may prevent formation of the 80S 
               
               
                   
                   
                   
                   
                 ribosome by inhibiting the 60S ribosomal subunit, may play a role in the allergic response, 
               
               
                   
                   
                   
                   
                 induced in inflamed asthmatic lung tissues 
               
               
                   
                   
                   
                   
                 Sanvito, F. et al. (supra) 
               
               
                   
                   
                   
                   
                 Oh, C. K. et al., Eukaryotic Translation Initiation Factor-6 Enhances Histamine and IL-2 
               
               
                   
                   
                   
                   
                 Production in Mast Cells., J Immunol 166, 3606-3611. (2001). 
               
               
                 14 
                 7511425CD1 
                 g3930583 
                 0.0 
                 [ Homo sapiens ] integrin alpha-7 
               
               
                   
                   
                   
                   
                 Vizirianakis, I. S. et al., Transfection of MCF-7 carcinoma cells with human integrin alpha7 
               
               
                   
                   
                   
                   
                 cDNA promotes adhesion to laminin, Arch. Biochem. Biophys. 385, 108-116 (2001) 
               
               
                   
                   
                 336050| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin; Receptor (signaling)][Plasma membrane] Integrin 
               
               
                   
                   
                 ITGA7 
                   
                 alpha 7, alpha subunit of an integrin laminin receptor, involved in cell adhesion and muscle 
               
               
                   
                   
                   
                   
                 development; gene mutation is associated with congenital myopathy 
               
               
                   
                   
                   
                   
                 Song, W. K. et al., Expression of alpha 7 integrin cytoplasmic domains during skeletal 
               
               
                   
                   
                   
                   
                 muscle development: alternate forms, conformational change, and homologies with 
               
               
                   
                   
                   
                   
                 serine/threonine kinases and tyrosine phosphatases., J Cell Sci, 1139-52 (1993). 
               
               
                   
                   
                   
                   
                 Hayashi, Y. K. et al., Mutations in the integrin alpha7 gene cause congenital 
               
               
                   
                   
                   
                   
                 myopathy., Nat Genet 19, 94-7 (1998). 
               
               
                   
                   
                   
                   
                 Burkin, D. J. et al., The alpha7beta1 integrin in muscle development and disease., Cell 
               
               
                   
                   
                   
                   
                 Tissue Res 296, 183-90 (1999). 
               
               
                   
                   
                 583421|Itga7 
                 0.0 
                 [ Mus musculus ][Receptor (signaling)][Plasma membrane] Integrin alpha 7, alpha subunit of 
               
               
                   
                   
                   
                   
                 an integrin laminin receptor, involved in cell adhesion, motility, and muscle development; 
               
               
                   
                   
                   
                   
                 human ITGA7 gene mutation is associated with congenital myopathy 
               
               
                   
                   
                   
                   
                 Ziober, B. L. et al., Alternative extracellular and cytoplasmic domains of the integrin alpha 
               
               
                   
                   
                   
                   
                 7 subunit are differentially expressed during development., J Biol Chem 268, 26773-83 
               
               
                   
                   
                   
                   
                 (1993). 
               
               
                   
                   
                   
                   
                 Mayer, U. et al., Absence of integrin alpha 7 causes a novel form of muscular dystrophy., 
               
               
                   
                   
                   
                   
                 Nat Genet 17, 318-23 (1997). (supra) 
               
               
                 15 
                 7511534CD1 
                 g244681 
                 0.0 
                 [ Homo sapiens ] integrin beta 7 subunit 
               
               
                   
                   
                   
                   
                 Yuan, Q. A. et al., Cloning and sequence analysis of a novel beta 2-related integrin 
               
               
                   
                   
                   
                   
                 transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of 
               
               
                   
                   
                   
                   
                 laminin B chains, Int. Immunol. 3, 1373-1374 (1991) 
               
               
                   
                   
                 336072| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin; Receptor (signaling)][Plasma membrane] Beta 7 
               
               
                   
                   
                 ITGB7 
                   
                 subunit of integrin, a member of a family of cell-surface proteins involved in cell-cell and 
               
               
                   
                   
                   
                   
                 cell-matrix interactions, involved in cell migration, cell clustering, and inflammatory 
               
               
                   
                   
                   
                   
                 responses; may play a role in Sjogren&#39;s Syndrome 
               
               
                   
                   
                   
                   
                 Higgins, J. M. et al., The role of alpha and beta chains in ligand recognition by beta 7 
               
               
                   
                   
                   
                   
                 integrins., J Biol Chem 275, 25652-64 (2000). 
               
               
                   
                   
                 587101|Itgb7 
                 6.7E−283 
                 [ Mus musculus ][Adhesin/agglutinin; Receptor (signaling)][Plasma membrane] Beta 7 
               
               
                   
                   
                   
                   
                 subunit of integrin, a member of a family of cell-surface proteins involved in cell-cell and 
               
               
                   
                   
                   
                   
                 cell-matrix interactions; may be involved in inflammatory responses 
               
               
                   
                   
                   
                   
                 Gurish, M. F. et al., Expression of murine beta 7, alpha 4, and beta 1 integrin genes by 
               
               
                   
                   
                   
                   
                 rodent mast cells., J Immunol 149, 1964-72 (1992). 
               
               
                 16 
                 7511648CD1 
                 g386753 
                 0.0 
                 [ Homo sapiens ] platelet Glycoprotein IIb (GPIIb) 
               
               
                   
                   
                   
                   
                 Heidenreich, R. et al., Organization of the gene for platelet glycoprotein IIb, Biochemistry 
               
               
                   
                   
                   
                   
                 29, 1232-1244 (1990) 
               
               
                   
                   
                 336042| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin; Isomerase; Chaperones; Receptor 
               
               
                   
                   
                 ITGA2B 
                   
                 (signaling)][Cytoskeletal; Plasma membrane] Integrin alpha 2b, subunit of the fibrinogen 
               
               
                   
                   
                   
                   
                 receptor, involved in hemostasis, blood coagulation, platelet aggregation, cell adhesion and 
               
               
                   
                   
                   
                   
                 actin reoganization, associated with immune thrombocytopenic purpura; mutation causes 
               
               
                   
                   
                   
                   
                 Glanzmann thrombasthenia 
               
               
                   
                   
                   
                   
                 Basani, R. B. et al., Glanzmann thrombasthenia due to a two amino acid deletion in the 
               
               
                   
                   
                   
                   
                 fourth calcium-binding domain of alpha IIb: demonstration of the importance of calcium- 
               
               
                   
                   
                   
                   
                 binding domains in the conformation of alpha IIb beta 3., Blood 88, 167-73 (1996). 
               
               
                   
                   
                   
                   
                 Furman, M. I. et al., The cleaved peptide of the thrombin receptor is a strong platelet 
               
               
                   
                   
                   
                   
                 agonist., Proc Natl Acad Sci USA 95, 3082-7 (1998). 
               
               
                   
                   
                 429948| 
                 0.0 
                 [ Mus musculus ][Receptor (signaling)][Plasma membrane] Integrin alpha 2b, subunit of the 
               
               
                   
                   
                 Itga2b 
                   
                 fibrinogen receptor, involved in blood coagulation, platelet aggregation, cell adhesion and 
               
               
                   
                   
                   
                   
                 actin reoganization, human ITGA2B is associated with immune thrombocytopenic purpura 
               
               
                   
                   
                   
                   
                 and Glanzmann thrombasthenia 
               
               
                   
                   
                   
                   
                 Chen, Y. Q. et al., Ectopic expression of platelet integrin alphaIIb beta3 in tumor cells from 
               
               
                   
                   
                   
                   
                 various species and histological origin., Int J Cancer 72, 642-8 (1997). 
               
               
                   
                   
                   
                   
                 Nieswandt, B. et al., Acute systemic reaction and lung alterations induced by an antiplatelet 
               
               
                   
                   
                   
                   
                 integrin gpIIb/IIIa antibody in mice., Blood 94, 684-93 (1999). 
               
               
                 17 
                 7511600CD1 
                 g6960195 
                 2.6E−147 
                 [ Mus musculus ] adhesion regulating molecule ARM-1 
               
               
                   
                   
                 711654| 
                 5.6E−148 
                 [ Rattus norvegicus ] Integral plasma membrane glycoprotein, type I transmembrane 
               
               
                   
                   
                 Gp110 
                   
                 glycoprotein that mediates Ca2+ - independent cell-cell adhesion, functions as a carrier in 
               
               
                   
                   
                   
                   
                 the transport of bile salts from hepatocytes into bile 
               
               
                   
                   
                   
                   
                 Lucka, L. et al., A short isoform of carcinoembryonic-antigen-related rat liver cell-cell 
               
               
                   
                   
                   
                   
                 adhesion molecule (C-CAM/gp110) mediates intercellular adhesion. Sequencing and 
               
               
                   
                   
                   
                   
                 recombinant functional analysis., Eur J Biochem 234, 527-35 (1995). 
               
               
                   
                   
                 428282| 
                 1.2E−116 
                 [ Homo sapiens ][Plasma membrane] Cell membrane glycoprotein 110 kDa, putative integral 
               
               
                   
                   
                 ADRM1 
                   
                 plasma membrane glycoprotein, putative tumor antigen and is expressed on human gastric 
               
               
                   
                   
                   
                   
                 carcinoma cells; upregulated in response to IFNgamma (IFNG) 
               
               
                   
                   
                   
                   
                 Shimada, S. et al., Molecular cloning and characterization of the complementary DNA of an 
               
               
                   
                   
                   
                   
                 M(r) 110,000 antigen expressed by human gastric carcinoma cells and upregulated by 
               
               
                   
                   
                   
                   
                 gamma-interferon., Cancer Res 54, 3831-6 (1994). 
               
               
                 18 
                 7511783CD1 
                 g13111859 
                 8.2E−85 
                 [ Homo sapiens ] intercellular adhesion molecule 2 
               
               
                   
                   
                 335916| 
                 6.6E−86 
                 [ Homo sapiens ][Adhesin/agglutinin; Ligand][Plasma membrane] Intercellular adhesion 
               
               
                   
                   
                 ICAM2 
                   
                 molecule 2, a surface glycoprotein and member of the immunoglobulin superfamily, binds 
               
               
                   
                   
                   
                   
                 the integrin LFA-1 (ITGB2) and promotes cell adhesion during immunological and 
               
               
                   
                   
                   
                   
                 inflammatory reactions 
               
               
                   
                   
                   
                   
                 Thomson, A. J. et al., Expression of intercellular adhesion molecules ICAM-1 and ICAM-2 
               
               
                   
                   
                   
                   
                 in human endometrium: regulation by interferon-gamma., Mol Hum Reprod 5, 64-70 
               
               
                   
                   
                   
                   
                 (1999). 
               
               
                   
                   
                   
                   
                 Shimaoka, M. et al., Reversibly locking a protein fold in an active conformation with a 
               
               
                   
                   
                   
                   
                 disulfide bond: integrin alphaL I domains with high affinity and antagonist activity in vivo., 
               
               
                   
                   
                   
                   
                 Proc Natl Acad Sci USA 98, 6009-14. (2001). 
               
               
                   
                   
                 585029| 
                 3.4E−50 
                 [ Mus musculus ][Adhesin/agglutinin; Ligand][Plasma membrane] Intercellular adhesion 
               
               
                   
                   
                 Icam2 
                   
                 molecule 2, a surface glycoprotein and member of the immunoglobulin superfamily, binds 
               
               
                   
                   
                   
                   
                 the integrin LFA-1 (Itgb2) and promotes cell adhesion during immunological and 
               
               
                   
                   
                   
                   
                 inflammatory reactions 
               
               
                   
                   
                   
                   
                 Reiss, Y. et al., T cell interaction with ICAM-1-deficient endothelium in vitro: 
               
               
                   
                   
                   
                   
                 transendothelial migration of different T cell populations is mediated by endothelial ICAM- 
               
               
                   
                   
                   
                   
                 1 and ICAM-2., Int. Immunol 11, 1527-39 (1999). 
               
               
                   
                   
                   
                   
                 Gerwin, N. et al., Prolonged eosinophil accumulation in allergic lung interstitium of ICAM- 
               
               
                   
                   
                   
                   
                 2 deficient mice results in extended hyperresponsiveness., Immunity 10, 9-19 (1999). 
               
               
                 19 
                 7512383CD1 
                 g14318638 
                 0.0 
                 [ Homo sapiens ] chondroitin sulfate proteoglycan BEHAB/brevican 
               
               
                   
                   
                 625835| 
                 0.0 
                 [ Homo sapiens ][Structural protein][Extracellular matrix (cuticle and basement membrane)] 
               
               
                   
                   
                 BCAN 
                   
                 Brevican (brain enriched hyaluronan binding protein), member of the lectican family of 
               
               
                   
                   
                   
                   
                 chondroitin sulfate proteoglycans, a brain extracellular matrix protein, may function in brain 
               
               
                   
                   
                   
                   
                 development; overexpression may enhance glioma invasiveness 
               
               
                   
                   
                   
                   
                 Zhang, H. et al., Expression of a cleaved brain-specific extracellular matrix protein 
               
               
                   
                   
                   
                   
                 mediates glioma cell invasion in vivo., J Neurosci 18, 2370-6 (1998). 
               
               
                   
                   
                   
                   
                 Gary, S. C. et al., cDNA cloning, chromosomal localization, and expression analysis of 
               
               
                   
                   
                   
                   
                 human BEHAB/brevican, a brain specific proteoglycan regulated during cortical 
               
               
                   
                   
                   
                   
                 development and in glioma, Gene 256, 139-47 (2000). 
               
               
                   
                   
                 589875|Bcan 
                 1.7E−229 
                 [ Rattus norvegicus ][Structural protein; Small molecule-binding protein][Extracellular 
               
               
                   
                   
                   
                   
                 matrix (cuticle and basement membrane); Extracellular (excluding cell wall); Plasma 
               
               
                   
                   
                   
                   
                 membrane] Brevican (brain enriched hyaluronan binding protein), member of the lectican 
               
               
                   
                   
                   
                   
                 family of chondroitin sulfate proteoglycans, a brain extracellular matrix protein, promotes 
               
               
                   
                   
                   
                   
                 neuronal cell adhesion and migration and may function in brain development 
               
               
                   
                   
                   
                   
                 Milev, P. et al., Differential regulation of expression of hyaluronan-binding proteoglycans 
               
               
                   
                   
                   
                   
                 in developing brain: aggrecan, versican, neurocan, and brevican., Biochem Biophys Res 
               
               
                   
                   
                   
                   
                 Commun 247, 207-12 (1998). 
               
               
                   
                   
                   
                   
                 Thon, N. et al., The chondroitin sulphate proteoglycan brevican is upregulated by astrocytes 
               
               
                   
                   
                   
                   
                 after entorhinal cortex lesions in adult rats., Eur J Neurosci 12, 2547-58 (2000). 
               
               
                 21 
                 7512842CD1 
                 g3169830 
                 3.4E−65 
                 [ Homo sapiens ] epithelial V-like antigen 1 
               
               
                   
                   
                   
                   
                 Guttinger, M. et al. Epithelial V-like antigen (EVA), a novel member of the 
               
               
                   
                   
                   
                   
                 immunoglobulin superfamily, expressed in embryonic epithelia with a potential role as 
               
               
                   
                   
                   
                   
                 homotypic adhesion molecule in thymus histogenesis. J Cell Biol 141: 1061-71 (1998). 
               
               
                   
                   
                 342924|EVA1 
                 2.6E−66 
                 [ Homo sapiens ][Cytoplasmic; Cytoskeletal] Epithelial V-like antigen, a member of the 
               
               
                   
                   
                   
                   
                 immunoglobulin superfamily, may mediate cell adhesion, may play a role in trophoblast 
               
               
                   
                   
                   
                   
                 invasion, placental development, and thymus organogenesis. 
               
               
                   
                   
                   
                   
                 Guttinger, M. et al. (supra) 
               
               
                   
                   
                 586553|Eva 
                 9.4E−55 
                 [ Mus musculus ][Cytoplasmic; Cytoskeletal] Epithelial V-like antigen, a member of the 
               
               
                   
                   
                   
                   
                 immunoglobulin superfamily, may mediate cell adhesion, may play a role in thymus 
               
               
                   
                   
                   
                   
                 organogenesis 
               
               
                   
                   
                   
                   
                 Teesalu, T. et al. Expression pattern of the epithelial v-like antigen (Eva) transcript suggests 
               
               
                   
                   
                   
                   
                 a possible role in placental morphogenesis. Dev Genet 23, 317-23 (1998). 
               
               
                 22 
                 90190613CD1 
                 g7407146 
                 0.0 
                 [ Homo sapiens ] protocadherin Flamingo 1 
               
               
                   
                   
                   
                   
                 Wu, Q. et al. A striking organization of a large family of human neural cadherin-like cell 
               
               
                   
                   
                   
                   
                 adhesion genes. Cell 97: 779-790 (1999) 
               
               
                   
                   
                   
                   
                 Wu, Q. et al. Large exons encoding multiple ectodomains are a characteristic feature of 
               
               
                   
                   
                   
                   
                 protocadherin genes. Proc. Natl. Acad. Sci. U.S.A. 97: 3124-3129 (2000) 
               
               
                   
                   
                 705126| 
                 0.0 
                 [ Rattus norvegicus ][Ligand; Receptor (signalling)][Plasma membrane] Protein with high 
               
               
                   
                   
                 Celsr3 
                   
                 similarity to murine Celsr1, member of the secretin family of G protein-coupled receptors 
               
               
                   
                   
                   
                   
                 (GPCR), contains nine cadherin domains, six EGF-like domains, two extracellular laminin 
               
               
                   
                   
                   
                   
                 G domains, and a Latrophilin/CL-1-like GPS domain 
               
               
                   
                   
                   
                   
                 Hill, E. et al. Cadherin Superfamily Proteins in  Caenorhabditis elegans  and  Drosophila   
               
               
                   
                   
                   
                   
                   melanogaster . J Mol Biol 305: 1011-1024 (2001). 
               
               
                   
                   
                   
                   
                 Bockaert, J. et al. Molecular tinkering of G protein-coupled receptors: an evolutionary 
               
               
                   
                   
                   
                   
                 success. Embo Journal 18: 1723-9 (1999). 
               
               
                   
                   
                 690794| 
                 0.0 
                 [ Homo sapiens ] Cadherin-EGF-LAG seven-pass G-type receptor 2, may be involved in 
               
               
                   
                   
                 CELSR2 
                   
                 transduction of extracellular signals by interacting with SH3 domain-containging proteins 
               
               
                   
                   
                   
                   
                 Vincent, J. B. et al. The human homologue of flamingo, EGFL2, encodes a brain-expressed 
               
               
                   
                   
                   
                   
                 large cadherin-like protein with epidermal growth factor-like domains, and maps to 
               
               
                   
                   
                   
                   
                 chromosome 1p13.3-p21.1. DNA Res 7: 233-5 (2000). 
               
               
                   
                   
                   
                   
                 Formstone, C. J. et al. Chromosomal localization of Celsr2 and Celsr3 in the mouse; Celsr3 
               
               
                   
                   
                   
                   
                 is a candidate for the tippy (tip) lethal mutant on chromosome 9. Mamm Genome 11: 392-4 
               
               
                   
                   
                   
                   
                 (2000). 
               
               
                 23 
                 7511894CD1 
                 g9622236 
                 4.8E−119 
                 [ Homo sapiens ] cadherin-like protein VR20 
               
               
                   
                   
                 743150| 
                 6.0E−92 
                 [ Homo sapiens ][Adhesin/agglutinin][Plasma membrane] Cadherin 2 type 1 (N-cadherin), a 
               
               
                   
                   
                 CDH2 
                   
                 calcium-dependent glycoprotein that mediates cell-cell interactions, inhibits apoptosis, has a 
               
               
                   
                   
                   
                   
                 role in development and is likely involved in tumor metastasis 
               
               
                   
                   
                   
                   
                 Williams, C. L. et al. Regulation of E-cadherin-mediated adhesion by muscarinic 
               
               
                   
                   
                   
                   
                 acetylcholine receptors in small cell lung carcinoma. J Cell Biol 121, 643-54 (1993). 
               
               
                   
                   
                   
                   
                 Husmark, J. et al. N-cadherin-mediated adhesion and aberrant catenin expression in 
               
               
                   
                   
                   
                   
                 anaplastic thyroid-carcinoma cell lines. Int J Cancer 83, 692-9 (1999). 
               
               
                   
                   
                 583765|Cdh2 
                 2.6E−91 
                 [ Mus musculus ][Adhesin/agglutinin][Plasma membrane; Cell junction] Cadherin 2 (N- 
               
               
                   
                   
                   
                   
                 cadherin), a calcium-dependent glycoprotein that mediates cell-cell interactions, inhibits 
               
               
                   
                   
                   
                   
                 apoptosis, has a role in embryogenesis and brain development, and facilitates tumor 
               
               
                   
                   
                   
                   
                 metastasis 
               
               
                   
                   
                   
                   
                 Miyatani, S. et al. Neural cadherin: role in selective cell-cell adhesion. Science 245, 631-5 
               
               
                   
                   
                   
                   
                 (1989). 
               
               
                   
                   
                   
                   
                 Hermiston, M. L. et al. Inflammatory bowel disease and adenomas in mice expressing a 
               
               
                   
                   
                   
                   
                 dominant negative N-cadherin. Science 270, 1203-7 (1995). 
               
               
                 24 
                 3604804CD1 
                 g19773543 
                 0.0 
                 [ Rattus norvegicus ] (AB076401) fat3 
               
               
                   
                   
                   
                   
                 Mitsui, K. et al. Mammalian fat3: a large protein that contains multiple cadherin and EGF- 
               
               
                   
                   
                   
                   
                 like motifs. Biochem. Biophys. Res. Commun. 290: 1260-1266 (2002) 
               
               
                   
                   
                 342032|FAT 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin][Plasma membrane] FAT tumor suppressor precursor, 
               
               
                   
                   
                   
                   
                 member of the cadherin superfamily, possibly functions in developmental processes and cell 
               
               
                   
                   
                   
                   
                 communication 
               
               
                   
                   
                   
                   
                 Dunne, J. et al. Molecular cloning and tissue expression of FAT, the human homologue of 
               
               
                   
                   
                   
                   
                 the  Drosophila  fat gene that is located on chromosome 4q34-q35 and encodes a putative 
               
               
                   
                   
                   
                   
                 adhesion molecule. Genomics 30, 207-23 (1995). 
               
               
                   
                   
                   
                   
                 Matsuyoshi, N. et al. Identification of novel cadherins expressed in human melanoma cells. 
               
               
                   
                   
                   
                   
                 J Invest Dermatol 108, 908-13 (1997). 
               
               
                   
                   
                 711832|Fat 
                 0.0 
                 [ Rattus norvegicus ] FAT tumor suppressor ( Drosophila ) homolog, member of the cadherin 
               
               
                   
                   
                   
                   
                 superfamily, has 34 cadherin repeats, five EGF-like repeats, a laminin A-G domain, a 
               
               
                   
                   
                   
                   
                 putative transmembrane domain, and a PDZ domain-binding motif, a component of 
               
               
                   
                   
                   
                   
                 intercellular junctions 
               
               
                   
                   
                   
                   
                 Ponassi, M. et al. Expression of the rat homologue of the  Drosophila  fat tumour suppressor 
               
               
                   
                   
                   
                   
                 gene. Mech Dev 80, 207-12. (1999). 
               
               
                   
                   
                   
                   
                 Inoue, T. et al. FAT is a component of glomerular slit diaphragms. Kidney Int 59, 1003-12. 
               
               
                   
                   
                   
                   
                 (2001). 
               
               
                 25 
                 7512568CD1 
                 g31191 
                 8.5E−179 
                 [ Homo sapiens ] epican 
               
               
                   
                   
                   
                   
                 Kugelman, L. C. et al. The core protein of epican, a heparan sulfate proteoglycan on 
               
               
                   
                   
                   
                   
                 keratinocytes, is an alternative form of CD44. J. Invest. Dermatol. 99: 381-385 (1992) 
               
               
                   
                   
                 309453| 
                 6.7E−180 
                 [ Homo sapiens ] Protein with high similarity to mouse Cd44, which functions as a receptor 
               
               
                   
                   
                 Hs.169322 
                   
                 for both soluble and membrane-bound hyaluronic acid, contains an extracellular link 
               
               
                   
                   
                   
                   
                 (hyaluronan-binding) domain 
               
               
                   
                   
                 575773|Cd44 
                 4.5E−144 
                 [ Mus musculus ][Adhesin/agglutinin; Receptor (signalling); Small molecule-binding 
               
               
                   
                   
                   
                   
                 protein][Plasma membrane] Cd44 antigen, type I transmembrane protein that functions as a 
               
               
                   
                   
                   
                   
                 receptor for soluble and membrane-bound hyaluronic acid, mediates cell adhesion and 
               
               
                   
                   
                   
                   
                 migration, may contribute to angiogenesis, mammary gland development, tumor metastasis 
               
               
                   
                   
                   
                   
                 and atherosclerosis 
               
               
                   
                   
                   
                   
                 Wolffe, E. J. et al. The cDNA sequence of mouse Pgp-1 and homology to human CD44 cell 
               
               
                   
                   
                   
                   
                 surface antigen and proteoglycan core/link proteins. J Biol Chem 265, 341-7 (1990). 
               
               
                   
                   
                   
                   
                 Yu, Q. et al. A new alternatively spliced exon between v9 and v10 provides a molecular 
               
               
                   
                   
                   
                   
                 basis for synthesis of soluble CD44. J Biol Chem 271, 20603-7 (1996). 
               
               
                   
                   
                   
                   
                 Screaton, G. R. et al. The identification of a new alternative exon with highly restricted 
               
               
                   
                   
                   
                   
                 tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. 
               
               
                   
                   
                   
                   
                 Comparison of all 10 variable exons between mouse, human, and rat. J Biol Chem 268, 
               
               
                   
                   
                   
                   
                 12235-8 (1993). 
               
               
                   
                   
                   
                   
                 Tolg, C. et al. Splicing choice from ten variant exons establishes CD44 variability. Nucleic 
               
               
                   
                   
                   
                   
                 Acids Res 21, 1225-9 (1993). 
               
               
                 26 
                 7512812CD1 
                 g9446402 
                 0.0 
                 [ Homo sapiens ] integrin beta-subunit 
               
               
                   
                   
                   
                   
                 Sheppard, D. et al. Complete amino acid sequence of a novel integrin beta subunit (beta 6) 
               
               
                   
                   
                   
                   
                 identified in epithelial cells using the polymerase chain reaction. J. Biol. 
               
               
                   
                   
                   
                   
                 Chem. 265: 11502-11507 (1990) 
               
               
                   
                   
                 606202| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin; Receptor (signalling)][Plasma membrane] Integrin beta 
               
               
                   
                   
                 ITGB6 
                   
                 6, member of a family of cell-surface proteins, binds fibronectin, mediates epithelial cell- 
               
               
                   
                   
                   
                   
                 matrix interactions in development, wound repair, and neoplasia, regulates lung 
               
               
                   
                   
                   
                   
                 inflammatory response, receptor for foot and mouth disease virus 
               
               
                   
                   
                   
                   
                 Jackson, T. et al. The epithelial integrin alpha v beta 6 is a receptor for foot-and-mouth 
               
               
                   
                   
                   
                   
                 disease virus. J Virol 74, 4949-56 (2000). 
               
               
                   
                   
                   
                   
                 Agrez, M. et al. The alpha v beta 6 integrin induces gelatinase B secretion in colon cancer 
               
               
                   
                   
                   
                   
                 cells. Int J Cancer 81, 90-7 (1999). 
               
               
                   
                   
                   
                   
                 Agrez, M. et al. The alpha v beta 6 integrin promotes proliferation of colon carcinoma cells 
               
               
                   
                   
                   
                   
                 through a unique region of the beta 6 cytoplasmic domain. J Cell Biol 127, 547-56 (1994). 
               
               
                   
                   
                   
                   
                 Thorne, R. F. et al. The integrins alpha 3beta 1 and alpha 6beta 1 physically and 
               
               
                   
                   
                   
                   
                 functionally associate with CD36 in human melanoma cells. REQUIREMENT FOR THE 
               
               
                   
                   
                   
                   
                 EXTRACELLULAR DOMAIN OF CD36. J Biol Chem 275: 35264-75 (2000). 
               
               
                   
                   
                 585099|Itgb5 
                 1.3E−158 
                 [ Mus musculus ][Adhesin/agglutinin; Receptor (signalling)][Plasma membrane] Integrin 
               
               
                   
                   
                   
                   
                 beta 5, forms a heterodimer with alpha V integrin (Itgav) and acts as a vitronectin receptor, 
               
               
                   
                   
                   
                   
                 involved in cell adhesion and motility. 
               
               
                   
                   
                   
                   
                 Lai, C. F. et al. Transforming Growth Factor-beta Up-regulates the beta 5 Integrin Subunit 
               
               
                   
                   
                   
                   
                 Expression via Sp1 and Smad Signaling. J Biol Chem 275, 36400-36406 (2000). 
               
               
                   
                   
                   
                   
                 Huang, X. et al. Normal development, wound healing, and adenovirus susceptibility in 
               
               
                   
                   
                   
                   
                 beta5-deficient mice. Mol Cell Biol 20, 755-9. (2000). 
               
               
                 27 
                 7512826CD1 
                 g529724 
                 0.0 
                 [ Homo sapiens ] MUC18 glycoprotein 
               
               
                   
                   
                   
                   
                 Lehmann, J. M. et al. MUC18, a marker of tumor progression in human melanoma, shows 
               
               
                   
                   
                   
                   
                 sequence similarity to the neural cell adhesion molecules of the immunoglobulin 
               
               
                   
                   
                   
                   
                 superfamily. Proc. Natl. Acad. Sci. U.S.A. 86, 9891-9895 (1989) 
               
               
                   
                   
                 432384| 
                 0.0 
                 [ Homo sapiens ][Adhesin/agglutinin][Plasma membrane] Melanoma cell adhesion molecule, 
               
               
                   
                   
                 MCAM 
                   
                 an adhesion molecule and tumor antigen that may play roles in cytoskeletal rearrangement, 
               
               
                   
                   
                   
                   
                 embryo implantation, development, angiogenesis, and inflammation, expression correlates 
               
               
                   
                   
                   
                   
                 with tumor progression and metastasis 
               
               
                   
                   
                   
                   
                 Pickl, W. F. et al. MUC18/MCAM (CD146), an activation antigen of human T 
               
               
                   
                   
                   
                   
                 lymphocytes. J Immunol 158, 2107-15 (1997). 
               
               
                   
                   
                   
                   
                 Mintz-Weber, C. S. et al. Identification of the elements regulating the expression of the cell 
               
               
                   
                   
                   
                   
                 adhesion molecule MCAM/MUC18. LOSS OF AP-2 IS NOT REQUIRED FOR MCAM 
               
               
                   
                   
                   
                   
                 EXPRESSION IN MELANOMA CELL LINES. J. Biol. Chem. 275: 34672-80 (2000). 
               
               
                   
                   
                 662705| 
                 2.8E−260 
                 [ Mus musculus ] Protein with high similarity to melanoma cell adhesion molecule (human 
               
               
                   
                   
                 Mcam 
                   
                 MCAM), which is an adhesion molecule and tumor antigen that may play roles in 
               
               
                   
                   
                   
                   
                 cytoskeletal rearrangement, development, and angiogenesis, contains five immunoglobulin 
               
               
                   
                   
                   
                   
                 (Ig) domains 
               
               
                   
                   
                   
                   
                 Vainio, O. et al. HEMCAM, an adhesion molecule expressed by c-kit+ hemopoietic 
               
               
                   
                   
                   
                   
                 progenitors. J Cell Biol 135, 1655-68 (1996). 
               
               
                   
                   
                   
                   
                 Yang, H. et al. Isolation and characterization of mouse MUC18 cDNA gene, and correlation 
               
               
                   
                   
                   
                   
                 of MUC18 expression in mouse melanoma cell lines with metastatic ability. 
               
               
                   
                   
                   
                   
                 Gene 265, 133-45. (2001). 
               
               
                 28 
                 7512908CD1 
                 g5764665 
                 1.2E−154 
                 [ Homo sapiens ] cerebral cell adhesion molecule 
               
               
                   
                   
                   
                   
                 Starzyk, R. et al. Cerebral Cell Adhesion Molecule: a novel leukocyte adhesion determinant 
               
               
                   
                   
                   
                   
                 on blood brain barrier capillary endothelium. J. Infect. Dis. 181: 181-187 (2000). 
               
               
                   
                   
                 475793| 
                 9.7E−156 
                 [ Homo sapiens ][Adhesin/agglutinin][Plasma membrane] Cerebral cell adhesion molecule, 
               
               
                   
                   
                 LOC51148 
                   
                 an adhesion molecule that is predicted to be involved in leukocyte transmigration across the 
               
               
                   
                   
                   
                   
                 blood-brain barrier 
               
               
                   
                   
                   
                   
                 Starzyk, R. M. et al. (supra) 
               
               
                   
                   
                 752557|C1orf17 
                 1.3E−105 
                 [ Homo sapiens ] mRNA KIAA0584, isolated from human brain cDNA library 
               
               
                   
                   
                   
                   
                 Sood, R. et al. Cloning and characterization of 13 novel transcripts and the human rgs8 
               
               
                   
                   
                   
                   
                 gene from the 1q25 region encompassing the hereditary prostate cancer 
               
               
                   
                   
                   
                   
                 (hpc1) locus. Genomics 73, 211-22. (2001). 
               
               
                 29 
                 7512909CD1 
                 g5764665 
                 9.7E−246 
                 [ Homo sapiens ] cerebral cell adhesion molecule 
               
               
                   
                   
                   
                   
                 Starzyk, R. et al. (supra) 
               
               
                   
                   
                 475793| 
                 7.6E−247 
                 [ Homo sapiens ][Adhesin/agglutinin][Plasma membrane] Cerebral cell adhesion molecule, 
               
               
                   
                   
                 LOC51148 
                   
                 an adhesion molecule that is predicted to be involved in leukocyte transmigration across the 
               
               
                   
                   
                   
                   
                 blood-brain barrier 
               
               
                   
                   
                   
                   
                 Starzyk, R. M. et al. (supra) 
               
               
                   
                   
                 752557|C1orf17 
                 1.7E−148 
                 [ Homo sapiens ] mRNA KIAA0584, isolated from human brain cDNA library 
               
               
                   
                   
                   
                   
                 Sood, R. et al. (supra) 
               
               
                 30 
                 7512769CD1 
                 g2654433 
                 2.6E−35 
                 [ Homo sapiens ] extracellular matrix protein 1 
               
               
                   
                   
                   
                   
                 Smits, P. et al. The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA 
               
               
                   
                   
                   
                   
                 cloning, expression pattern, and chromosomal localization. Genomics 45: 487-495 (1997) 
               
               
                   
                   
                 662414| 
                 2.0E−36 
                 [ Homo sapiens ][Extracellular matrix (cuticle and basement membrane); Extracellular 
               
               
                   
                   
                 ECM1 
                   
                 (excluding cell wall)] Extracellular matrix protein 1, may possess angiogenic properties that 
               
               
                   
                   
                   
                   
                 promote tumor progression 
               
               
                   
                   
                   
                   
                 Deckers, M. M. et al. Recombinant human extracellular matrix protein 1 inhibits alkaline 
               
               
                   
                   
                   
                   
                 phosphatase activity and mineralization of mouse embryonic metatarsals in vitro. Bone 28, 
               
               
                   
                   
                   
                   
                 14-20. (2001). 
               
               
                   
                   
                   
                   
                 Han, Z. et al. Extracellular matrix protein 1 (ECM1) has angiogenic properties and is 
               
               
                   
                   
                   
                   
                 expressed by breast tumor cells. FASEB J 15: 988-94. (2001). 
               
               
                   
                   
                 584057|Ecm1 
                 1.6E−16 
                 [ Mus musculus ][Structural protein][Extracellular matrix (cuticle and basement membrane); 
               
               
                   
                   
                   
                   
                 Extracellular (excluding cell wall)] Extracellular matrix protein 1, functions as a negative 
               
               
                   
                   
                   
                   
                 regulator of bone formation and may contribute to angiogenesis; human ECM1 may 
               
               
                   
                   
                   
                   
                 promote tumor progression 
               
               
                   
                   
                   
                   
                 Bhalerao, J. et al. Molecular cloning, characterization, and genetic mapping of the cDNA 
               
               
                   
                   
                   
                   
                 coding for a novel secretory protein of mouse. Demonstration of alternative splicing in skin 
               
               
                   
                   
                   
                   
                 and cartilage. J Biol Chem 270, 16385-94 (1995). 
               
               
                 31 
                 7512871CD1 
                 g1911530 
                 2.6E−168 
                 [ Homo sapiens ] ficolin 
               
               
                   
                   
                   
                   
                 Lu, J. et al. Human ficolin: cDNA cloning, demonstration of peripheral blood leucocytes as 
               
               
                   
                   
                   
                   
                 the major site of synthesis and assignment of the gene to chromosome 9. Biochem. J. 
               
               
                   
                   
                   
                   
                 313: 473-478 (1996) 
               
               
                   
                   
                 571024|FCN1 
                 1.8E−170 
                 [ Homo sapiens ][Structural protein; Small molecule-binding protein] Ficolin-1, a peripheral 
               
               
                   
                   
                   
                   
                 leukocyte GlcNAc-binding lectin containing collagen- and fibrinogen-like domains, forms a 
               
               
                   
                   
                   
                   
                 complex with mannose-binding lectin-associated serine proteases (MASPs) that activates 
               
               
                   
                   
                   
                   
                 complement, may play a role in innate immunity 
               
               
                   
                   
                   
                   
                 Matsushita, M. et al. A novel human serum lectin with collagen- and fibrinogen-like 
               
               
                   
                   
                   
                   
                 domains that functions as an opsonin. J Biol Chem 271, 2448-54 (1996). 
               
               
                   
                   
                   
                   
                 Matsushita, M. et al. Cutting edge: complement-activating complex of ficolin and mannose- 
               
               
                   
                   
                   
                   
                 binding lectin-associated serine protease. J Immunol 164, 2281-4. (2000). 
               
               
                   
                   
                 418853|Fcnb 
                 9.0E−121 
                 [ Mus musculus ][Extracellular (excluding cell wall)] Ficolin B, a member of the ficolin 
               
               
                   
                   
                   
                   
                 family of proteins that bind carbohydrates, elastin, and corticosteroids, expressed in liver 
               
               
                   
                   
                   
                   
                 and forms 12-mers in plasma 
               
               
                   
                   
                   
                   
                 Ohashi, T. et al. Oligomeric structure and tissue distribution of ficolins from mouse, pig and 
               
               
                   
                   
                   
                   
                 human. Arch Biochem Biophys 360, 223-32 (1998). 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                   
               
               
                 SEQ 
                 Incyte 
                   
                 Potential 
                   
                   
                   
               
               
                 ID 
                 Polypeptide 
                 Amino Acid 
                 Phosphorylation 
                 Potential 
                   
                 Analytical Methods 
               
               
                 NO: 
                 ID 
                 Residues 
                 Sites 
                 Glycosylation Sites 
                 Signature Sequences, Domains and Motifs 
                 and Databases 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 1 
                 7506690CD1 
                 1252 
                 S47 S91 S96 S129 
                 N240 N322 N426 
                 Signal_cleavage: M1-A24 
                 SPSCAN 
               
               
                   
                   
                   
                 S178 S190 S243 
                 N463 N500 N769 
               
               
                   
                   
                   
                 S252 S306 S324 
                 N795 N883 N898 
               
               
                   
                   
                   
                 S336 S341 S347 
                 N1027 N1038 
               
               
                   
                   
                   
                 S418 S441 S451 
                 N1059 N1236 
               
               
                   
                   
                   
                 S488 S567 S660 
               
               
                   
                   
                   
                 S734 S837 S918 
               
               
                   
                   
                   
                 S956 S1018 S1176 
               
               
                   
                   
                   
                 S1202 T230 T427 
               
               
                   
                   
                   
                 T465 T478 T554 
               
               
                   
                   
                   
                 T613 T634 T756 
               
               
                   
                   
                   
                 T789 T876 T1001 
               
               
                   
                   
                   
                 T1040 T1061 
               
               
                   
                   
                   
                 T1086 T1188 
               
               
                   
                   
                   
                 T1193 T1225 Y516 
               
               
                   
                   
                   
                 Y582 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P6-A24 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-G22 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A24 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-I27 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Fibronectin type III domain: P645-S731, P842-V929, E1022-S1098, P744-P830 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin domain: G278-A335, G553-A611, Y462-A520, G368-T427, G155-A215, R56-A120 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Fibronectin type 3 domain: P645-S728, P842-G926, E745-G827, E1022-S1098 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin: A270-K351, P545-L627, L147-L234, N454-K536, P360-L443, A48-S137 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin C-2 Type: L276-G340, I460-G525, A366-G432, R551-D616, D54-G125, Q153-T220 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 I type Ig domains from SCOP: K536-P633, T260-L357, V445-V535 
                 HMMER_INCY 
               
               
                   
                   
                   
                   
                   
                 Ig superfamily from SCOP: W356-R448, L450-T539, P266-P354, I541-Q630, T44-P140, P143-H218 
                 HMMER_INCY 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: K1144-A1252; 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: G1121-I1143; 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-Q1120 
               
               
                   
                   
                   
                   
                   
                 CELL ADHESION PRECURSOR SIGNAL MOLECULE 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN GLYCOPROTEIN 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE REPEAT FOLD PD003273: I1139-S1243 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR SIGNAL ADHESION CELL 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN IMMUNOGLOBULIN FOLD REPEAT MOLECULE 
               
               
                   
                   
                   
                   
                   
                 NEURAL PD003129: N122-L231 
               
               
                   
                   
                   
                   
                   
                 NEUROFASCIN PRECURSOR SIGNAL PD065767: 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 E1017-T1108 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR SIGNAL CONTACTIN CELL ADHESION 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 NEUROFASCIN GLYCOPROTEIN GP135 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN FOLD PD001890: L732-A844 
               
               
                   
                   
                   
                   
                   
                 NEURAL CELL ADHESION MOLECULE L1 DM02463| 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 S26180|1027-1247: G1012-K1228 
               
               
                   
                   
                   
                   
                   
                 P35331|1009-1259: V923-A969, I1025-K1228 
               
               
                   
                   
                   
                   
                   
                 S26180|1027-1247: Q922-S1011 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN DM00001 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 |S26180|352-436: K351-A436 
               
               
                   
                   
                   
                   
                   
                 |S26180|45-129: T44-S129 
               
               
                 2 
                 7506536CD1 
                 421 
                 S31 S72 S103 S188 
                 N51 N138 N374 
                 Signal_cleavage: M1-A21 
                 SPSCAN 
               
               
                   
                   
                   
                 T80 T89 T122 
               
               
                   
                   
                   
                 T146 T160 T172 
               
               
                   
                   
                   
                 T242 T282 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P4-A22 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A21 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A22 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-S24 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A28 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Collagen triple helix repeat (20 copies): G299-R358, G208-P267 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: M1-A6; Transmembrane 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 domain: W7-P29; Non-cytosolic 
               
               
                   
                   
                   
                   
                   
                 domain: F30-P421 
               
               
                   
                   
                   
                   
                   
                 COLLAGEN ALPHA PRECURSOR CHAIN REPEAT 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 SIGNAL CONNECTIVE TISSUE EXTRACELLULAR 
               
               
                   
                   
                   
                   
                   
                 MATRIX PD000007: G223-G332, P291-E369, G293-E369, 
               
               
                   
                   
                   
                   
                   
                 G199-P277, P165-G256, G293-G368, Q164-G238 
               
               
                   
                   
                   
                   
                   
                 SIMILAR TO CUTICULAR COLLAGEN PD067228: 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 G217-G314, D191-G305, P224-G317, E163-R270, P291-K370, 
               
               
                   
                   
                   
                   
                   
                 P291-G368, P306-G409, P297-D398, P257-Q357, 
               
               
                   
                   
                   
                   
                   
                 G235-G332, P165-G259 
               
               
                   
                   
                   
                   
                   
                 PRECOLLAGEN P PRECURSOR SIGNAL PD072959: 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 G293-H372, G223-G329, G293-H372, G181-P277 G247-P349, 
               
               
                   
                   
                   
                   
                   
                 G229-G341G256-P367, G299-P401 
               
               
                   
                   
                   
                   
                   
                 ZK265.2 PROTEIN PD068401: G226-P337, P294-P367, 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 P173-G259, G190-P310 
               
               
                   
                   
                   
                   
                   
                 FIBRILLAR COLLAGEN CARBOXYL-TERMINAL 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00019 
               
               
                   
                   
                   
                   
                   
                 |S18803|1304-1528: P176-K370 
               
               
                   
                   
                   
                   
                   
                 |P20908|1300-1524: P176-K370 
               
               
                   
                   
                   
                   
                   
                 |P20908|1300-1524: P167-G368 
               
               
                   
                   
                   
                   
                   
                 |P02457|915-1139: G181-G396 
               
               
                   
                   
                   
                   
                   
                 |P20908|1300-1524: G202-G368 
               
               
                   
                   
                   
                   
                   
                 S18803|1304-1528: G181-G368 
               
               
                   
                   
                   
                   
                   
                 |P05997|957-1181: G181-G409 
               
               
                   
                   
                   
                   
                   
                 FIBRILLAR COLLAGEN CARBOXYL-TERMINAL 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00019 
               
               
                   
                   
                   
                   
                   
                 |P20908|1300-1524: P168-G368 
               
               
                   
                   
                   
                   
                   
                 |S18803|1304-1528: P168-G368 
               
               
                   
                   
                   
                   
                   
                 |S18803|1304-1528: G205-G368 
               
               
                   
                   
                   
                   
                   
                 |P02457|915-1139: G202-G420 
               
               
                   
                   
                   
                   
                   
                 |P05997|957-1181: P167-G368 
               
               
                   
                   
                   
                   
                   
                 |P05997|957-1181: P167-G368 
               
               
                   
                   
                   
                   
                   
                 FIBRILLAR COLLAGEN CARBOXYL-TERMINAL 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00019 
               
               
                   
                   
                   
                   
                   
                 |P02457|915-1139: P168-G338 
               
               
                   
                   
                   
                   
                   
                 |P05997|957-1181: V166-G332 
               
               
                   
                   
                   
                   
                   
                 |P20908|1300-1524: G293-P421 
               
               
                   
                   
                   
                   
                   
                 S18803|1304-1528: G293-P421 
               
               
                   
                   
                   
                   
                   
                 |P02457|915-1139: G296-P421 
               
               
                   
                   
                   
                   
                   
                 |S18803|1304-1528: P165-G314 
               
               
                   
                   
                   
                   
                   
                 FIBRILLAR COLLAGEN CARBOXYL-TERMINAL 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00019 
               
               
                   
                   
                   
                   
                   
                 |P20908|1300-1524: P167-G308 
               
               
                   
                   
                   
                   
                   
                 |P20908|1300-1524: G296-G420 
               
               
                   
                   
                   
                   
                   
                 |S18803|1304-1528: G296-G420 
               
               
                   
                   
                   
                   
                   
                 |P02457|915-1139: P167-G265 
               
               
                   
                   
                   
                   
                   
                 |P02457|915-1139: P167-G238 
               
               
                 3 
                 7506537CD1 
                 124 
                 S31 S72 S103 T80 
                 N51 N120 
                 Signal_cleavage: M1-A21 
                 SPSCAN 
               
               
                   
                   
                   
                 T89 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P4-A22 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A21 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A22 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-S24 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A28 
                 HMMER 
               
               
                 4 
                 7506655CD1 
                 398 
                 S7 S71 S213 S226 
                 N98 
                 Signal_cleavage: M1-A29 
                 SPSCAN 
               
               
                   
                   
                   
                 S239 S259 S285 
               
               
                   
                   
                   
                 T161 T193 T250 
               
               
                   
                   
                   
                 T333 T369 T391 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P11-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: R9-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: R8-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A25 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: L12-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P6-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: V10-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Anaphylotoxin-like domain: C36-C69, C112-C144, H77-C110 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Epidermal growth factor-like domain.: R179-E215, E265-I307, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 E219-K261 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain: D262-I307, D216-K261 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Anaphylatoxin domain proteins BL01177: G18-A29, S200-E215, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 F277-L303 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN EGFLIKE DOMAIN PRECURSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 FIBULIN1 ISOFORM SIGNAL EXTRACELLULAR 
               
               
                   
                   
                   
                   
                   
                 MATRIX PLASMA PD006208: V27-N177 
               
               
                   
                   
                   
                   
                   
                 FIBULIN2 PRECURSOR SIGNAL GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX PLASMA EGFLIKE 
               
               
                   
                   
                   
                   
                   
                 DOMAIN CALCIUMBINDING ALTERNATIVE 
               
               
                   
                   
                   
                   
                   
                 SPLICING REPEAT PD166194: C186-C227 
               
               
                   
                   
                   
                   
                   
                 EGF DM00003|P98095|720-782: V217-N281 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 EGF-LIKE DOMAIN DM00864|I55476|159-241: R181-E267 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 Anaphylatoxin domain signature: C36-C69, H77-C110, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 C112-C144 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 2: C199-C214 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain pattern signature: D216-C242, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 D262-C288 
               
               
                 5 
                 7506656CD1 
                 288 
                 S7 S71 S213 S226 
                 N98 
                 Signal_cleavage: M1-A29 
                 SPSCAN 
               
               
                   
                   
                   
                 S239 S259 T161 
               
               
                   
                   
                   
                 T193 T250 T274 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P11-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: R9-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: R8-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A25 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: L12-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P6-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: V10-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Anaphylotoxin-like domain: C36-C69, C112-C144, H77-C110 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain: C180-C214 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Anaphylatoxin homologous domain: C36-C69, C112-C144, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 H77-C110 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain: D216-K261 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Anaphylatoxin domain proteins BL01177: G18-A29, S200-E215, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 G184-F202, S209-S226 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN EGFLIKE DOMAIN PRECURSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 FIBULIN1 ISOFORM SIGNAL EXTRACELLULAR 
               
               
                   
                   
                   
                   
                   
                 MATRIX PLASMA PD006208: V27-N177 
               
               
                   
                   
                   
                   
                   
                 FIBULIN2 PRECURSOR SIGNAL GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX PLASMA EGFLIKE 
               
               
                   
                   
                   
                   
                   
                 DOMAIN CALCIUMBINDING ALTERNATIVE 
               
               
                   
                   
                   
                   
                   
                 SPLICING REPEAT PD166194: C186-C227 
               
               
                   
                   
                   
                   
                   
                 Anaphylatoxin domain signature: C36-C69, H77-C110, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 C112-C144 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 2: C199-C214 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain pattern signature: D216-C242 
                 MOTIFS 
               
               
                 6 
                 7510567CD1 
                 78 
                   
                   
                 Signal_cleavage: M1-G42 
                 SPSCAN 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: R21-G42 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: P23-G42 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: R20-G42 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN BETA8 SUBUNIT PRECURSOR CELL 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 ADHESION TRANSMEMBRANE GLYCOPROTEIN 
               
               
                   
                   
                   
                   
                   
                 REPEAT EXTRACELLULAR PD136783: M1-A52 
               
               
                   
                   
                   
                   
                   
                 INTEGRINS BETA CHAIN CYSTEINE-RICH DOMAIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00846|P26012|24-457: A24-E72 
               
               
                 7 
                 7506072CD1 
                 203 
                 S10 S28 S34 S42 
                 N119 N186 
                 PROTEIN LAR-INTERACTING LIPRINALPHA2 1A 1B 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                 S133 S138 S156 
                   
                 F59F5.6 PD023244: Q29-T94, P87-K180, E89-Q147, Q88-Q147 
               
               
                   
                   
                   
                 S166 T8 T53 T190 
               
               
                   
                   
                   
                 T197 
               
               
                 8 
                 7511354CD1 
                 650 
                 S15 S19 S27 S163 
                 N68 N279 N434 
                 signal_cleavage: M1-S19 
                 SPSCAN 
               
               
                   
                   
                   
                 S188 S195 S410 
                 N477 N517 N526 
                 Signal Peptide: M1-G17, M1-S19, M1-A23 
                 HMMER 
               
               
                   
                   
                   
                 S611 T131 T218 
                   
                 Cytosolic domain: R599-L650 
                 TMHMMER 
               
               
                   
                   
                   
                 T287 T294 T323 
                   
                 Transmembrane domain: T576-Y598 
               
               
                   
                   
                   
                 T472 Y327 
                   
                 Non-cytosolic domain: M1-H575 
               
               
                   
                   
                   
                   
                   
                 Integrins, beta chain: S50-C476 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Integrin beta subunits (N-terminal): S50-C476 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Domain found in Plexins, Semaphorins and Integrins: S44-P92 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Integrin beta, C-terminus IPB001169: R79-L96, L140-V180, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 R181-C216, V232-L283, L284-L313, F325-V368, G369-S410, 
               
               
                   
                   
                   
                   
                   
                 C478-C497 
               
               
                   
                   
                   
                   
                   
                 Integrin beta subunit signature PR01186: A48-C64, C80-P99, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 Q122-G135, Y150-L168, R190-P209, C223-F242, 
               
               
                   
                   
                   
                   
                   
                 D256-R278, R282-D297, D326-T349, L362-Y386, S489-D502, 
               
               
                   
                   
                   
                   
                   
                 D574-G591, G591-E609, S626-T636 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN GLYCOPROTEIN CELL ADHESION 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE REPEAT PRECURSOR 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR SUBUNIT SIGNAL 
               
               
                   
                   
                   
                   
                   
                 PD001811: S50-C476 
               
               
                   
                   
                   
                   
                   
                 PD001794: C497-A645 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN BETA-7 SUBUNIT PRECURSOR CELL 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 ADHESION TRANSMEMBRANE GLYCOPROTEIN 
               
               
                   
                   
                   
                   
                   
                 REPEAT EXTRACELLULAR PD041877: M1-P49 
               
               
                   
                   
                   
                   
                   
                 INTEGRINS BETA CHAIN CYSTEINE-RICH DOMAIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00846: 
               
               
                   
                   
                   
                   
                   
                 |P26010|17-465: G17-L466 
               
               
                   
                   
                   
                   
                   
                 |S32659|2-437: S50-E464 
               
               
                   
                   
                   
                   
                   
                 |P32592|3-435: S50-E464 
               
               
                   
                   
                   
                   
                   
                 |P12607|2-453: A48-L466 
               
               
                 9 
                 7511643CD1 
                 752 
                 S37 S129 S134 
                 N149 N184 N250 
                 signal_cleavage: M1-G22 
                 SPSCAN 
               
               
                   
                   
                   
                 S212 S223 S272 
                 N419 N456 N546 
                 Signal Peptide: M1-G22 
                 HMMER 
               
               
                   
                   
                   
                 S409 S425 S484 
                 N587 
                 Cadherin domain: F571-C685, T345-I440, Y131-T235, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                 S601 S649 S686 
                   
                 G455-T558, K243-K331, M34-K117 
               
               
                   
                   
                   
                 T113 T151 T228 
                   
                 Cadherin repeats.: I259-P338, L362-P447, V148-P242, Y39-P124, 
                 HMMER_SMART 
               
               
                   
                   
                   
                 T345 T363 T385 
                   
                 I472-Q565, V588-P672 
               
               
                   
                   
                   
                 T458 T475 T589 
                   
                 Cytosolic domain: R729-S752 
                 TMHMMER 
               
               
                   
                   
                   
                 T653 Y418 
                   
                 Transmembrane domain: G706-I728 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-V705 
               
               
                   
                   
                   
                   
                   
                 Cadherin domain IPB002126: D605-E628, E657-V705 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: L94-F145 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 Cadherin signature PR00205: D67-R86, F126-D155, S206-G218, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 P319-P338, P564-E577, Q288-D314 
               
               
                   
                   
                   
                   
                   
                 CELL ADHESION GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE CALCIUM BINDING REPEAT LI 
               
               
                   
                   
                   
                   
                   
                 CADHERIN LIVER INTESTINE CADHERIN 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR CADHERIN 17 
               
               
                   
                   
                   
                   
                   
                 PD024554: I2-G64 
               
               
                   
                   
                   
                   
                   
                 PD024555: H698-S752 
               
               
                   
                   
                   
                   
                   
                 PD151760: E236-G268 
               
               
                   
                   
                   
                   
                   
                 CADHERIN REPEAT DM00030 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 |S55396|481-593: F481-E594 
               
               
                   
                   
                   
                   
                   
                 |S55396|265-369: N265-E370 
               
               
                   
                   
                   
                   
                   
                 |S55396|371-479: N371-P480 
               
               
                   
                   
                   
                   
                   
                 |S55396|54-154: N54-D155 
               
               
                   
                   
                   
                   
                   
                 Cell attachment sequence: R603-D605 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: I114-P124, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 V328-P338 
               
               
                 10 
                 7511400CD1 
                 180 
                 S29 S130 T126 
                 N17 N97 
                 signal_cleavage: M1-C21 
                 SPSCAN 
               
               
                   
                   
                   
                 T136 T146 T175 
                   
                 Signal Peptide: M1-G23 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-C21 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Furin-like repeats: Y18-P71 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Thrombospondin type 1 repeats: V84-P141 
                 HMMER_SMART 
               
               
                 11 
                 7511507CD1 
                 407 
                 S163 S205 S211 
                 N242 N255 
                 signal_cleavage: M1-A23 
                 SPSCAN 
               
               
                   
                   
                   
                 S244 S316 S344 
                   
                 Signal Peptide: M1-A23, M1-A25, I4-A23 
                 HMMER 
               
               
                   
                   
                   
                 T48 T156 T330 
                   
                 EGF-like domain: C170-C204, C131-C164, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 C210-C245, C251-C291 
               
               
                   
                   
                   
                   
                   
                 Epidermal growth factor-like domain.: E209-Q246, E169-S205, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 E130-Q165, E250-M292 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain: D206-Q246, D166-S205 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 D127-Q165, D247-M292, D42-T86 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain IPB000561: C149-L157 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain IPB001881: C149-E159, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 C180-C191 
               
               
                   
                   
                   
                   
                   
                 Laminin-type EGF-like (LE) domain IPB002049: R290-C300 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 Type II EGF-like signature PR00010: D127-Q138, G201-D208, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 G226-Y236 
               
               
                   
                   
                   
                   
                   
                 LAMININ CHAIN EGF-LIKE DOMAIN PD00320: G226-L239 
                 BLIMPS_PRODOM 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN EGF-LIKE DOMAIN T16 H411 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR SIGNAL UPH1 UP50 PD030337: Q26-E130 
               
               
                   
                   
                   
                   
                   
                 EGF-LIKE DOMAIN GLYCOPROTEIN PRECURSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 SIGNAL EXTRACELLULAR MATRIX PLASMA 
               
               
                   
                   
                   
                   
                   
                 CALCIUMBINDING REPEAT PD008104: R290-V402 
               
               
                   
                   
                   
                   
                   
                 EGF-LIKE DOMAIN DM00864|I55476|159-241: G134-C210, 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 C176-E252 
               
               
                   
                   
                   
                   
                   
                 EGF DM00003|P35556|2219-2292: N174-D247 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 EGF DM00003|P35556|2219-2292: C140-D206 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 EGF DM00003|A57278|2213-2286: C140-D206 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 EGF DM00003|A57278|2213-2286: N174-D247 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 EGF DM00003|P98163|1373-1460: C136-M207 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 Cell attachment sequence: R54-D56 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Aspartic acid and asparagine hydroxylation site: C140-C151, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 C180-C191, C221-C232 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 2: C149-C164, C189-C204, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 C230-C245 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain pattern signature: D42-C68, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 E121-C149, D127-C149, D166-C189, D206-C230, 
               
               
                   
                   
                   
                   
                   
                 D247-C273 
               
               
                 12 
                 7511819CD1 
                 681 
                 S187 S201 S338 
                 N65 N89 N188 
                 signal_cleavage: M1-S25 
                 SPSCAN 
               
               
                   
                   
                   
                 S566 S611 S625 
                 N649 
               
               
                   
                   
                   
                 S641 T84 T91 
               
               
                   
                   
                   
                 T204 T263 T337 
               
               
                   
                   
                   
                 T681 Y124 Y211 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A23, M1-S25, M9-S25 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Integrin alpha (beta-propellor repeats: P517-E570, I456-Q511, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 R400-H452, A41-G87, G577-E628 
               
               
                   
                   
                   
                   
                   
                 von Willebrand factor (vWF) type A domain: N154-K329 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 FG-GAP repeat: L518-L575, G457-Y516, A401-Q455, I578-P630, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 G42-T91 
               
               
                   
                   
                   
                   
                   
                 von Willebrand factor type A domain: D156-L327 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: M1-S4 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: C5-N27 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: L28-T681 
               
               
                   
                   
                   
                   
                   
                 Integrins alpha chain IPB000413: S66-T77, G366-G375, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 G453-A482, R520-P544 
               
               
                   
                   
                   
                   
                   
                 Von Willebrand factor type A domain signature PR00453: 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 V155-F172, Q192-F206, V258-E266 
               
               
                   
                   
                   
                   
                   
                 Integrin alpha subunit signature PR01185: A401-S413, L419-M430, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 G453-G473, R520-P544, F581-G602, Q606-S625 
               
               
                   
                   
                   
                   
                   
                 von Willebrand factor type A domain proteins. PF00092: 
                 BLIMPS_PFAM 
               
               
                   
                   
                   
                   
                   
                 G481-G491 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN PRECURSOR SIGNAL GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 ALPHA CELL ADHESION TRANSMEMBRANE 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX PD001221: K381-G503, 
               
               
                   
                   
                   
                   
                   
                 L484-S658, S35-Y71, V56-G106 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN PRECURSOR CELL LEUKOCYTE 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 ADHESION LFA1 ALPHA CHAIN FUNCTION 
               
               
                   
                   
                   
                   
                   
                 ASSOCIATED PD152352: G114-V155 
               
               
                   
                   
                   
                   
                   
                 VON WILLEBRAND FACTOR TYPE A REPEAT 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00219|P20701|148-316: Q148-F317 
               
               
                   
                   
                   
                   
                   
                 DM00219|P24063|145-314: Q148-F317 
               
               
                   
                   
                   
                   
                   
                 INTEGRINS ALPHA CHAIN DM00458|P20701|35-147: 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 S35-F147 
               
               
                   
                   
                   
                   
                   
                 CELL SURFACE GLYCOPROTEIN CD11B 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM02945|P20701|560-1036: G560-Q664 
               
               
                 13 
                 7511338CD1 
                 59 
                 S51 
                   
                 signal_cleavage: M1-S31 
                 SPSCAN 
               
               
                 14 
                 7511425CD1 
                 1113 
                 S97 S127 S234 
                 N86 N742 N921 
                 signal_cleavage: M1-A33 
                 SPSCAN 
               
               
                   
                   
                   
                 S269 S301 S461 
                 N957 N977 
               
               
                   
                   
                   
                 S659 S744 S788 
               
               
                   
                   
                   
                 S796 S832 S852 
               
               
                   
                   
                   
                 S914 S983 S1082 
               
               
                   
                   
                   
                 T229 T532 T599 
               
               
                   
                   
                   
                 T625 T776 T786 
               
               
                   
                   
                   
                 T959 T979 
               
               
                   
                   
                   
                   
                   
                 Integrin alpha (beta-propellor repeats: P377-E430, L316-R372, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 P48-Q110, L259-S312, G435-E491 
               
               
                   
                   
                   
                   
                   
                 FG-GAP repeat: D378-G435, S318-P377, G49-M114, I436-D489, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 N260-T317 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domains: M1-G11, K1037-A1113 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domains: A12-F34, W1014-W1036 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: N35-P1013 
               
               
                   
                   
                   
                   
                   
                 Integrins alpha chain IPB000413: R87-L98, G215-G224, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 G313-P342, M380-P404, W1015-R1043 
               
               
                   
                   
                   
                   
                   
                 Integrins alpha chain signature: V1016-T1074 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 Integrin alpha subunit signature PR01185: N260-G272, S280-K291, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 G313-G333, M380-P404, F439-G460, T465-A484, 
               
               
                   
                   
                   
                   
                   
                 D584-L597, G1024-R1043 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN PRECURSOR SIGNAL GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 ALPHA CELL ADHESION TRANSMEMBRANE 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX PD001221: G46-G132, 
               
               
                   
                   
                   
                   
                   
                 Q193-Q361, V339-Q880, V882-R1043 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN ALPHA PRECURSOR SIGNAL ALPHA7 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PD146538: W1036-A1113 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN PRECURSOR CELL GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 SIGNAL ADHESION TRANSMEMBRANE 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX CYTOSKELETON 
               
               
                   
                   
                   
                   
                   
                 PD001587: A33-R147 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN PRECURSOR SIGNAL ALPHA ALPHA6 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 VLA6 CELL ADHESION GLYCOPROTEIN 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE PD001486: E155-E192 
               
               
                   
                   
                   
                   
                   
                 INTEGRINS ALPHA CHAIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM01028|I61186|420-951: G179-Q238, P307-A341, F381-D406, 
               
               
                   
                   
                   
                   
                   
                 G420-Q880, D881-R928 
               
               
                   
                   
                   
                   
                   
                 DM01028|P23229|416-932: P307-A341, F381-D406, G420-Q897 
               
               
                   
                   
                   
                   
                   
                 DM01028|P26007|410-931: P307-A341, S379-D406, G420-Q897 
               
               
                   
                   
                   
                   
                   
                 DM00458|I61186|42-233: L42-S233 
               
               
                   
                   
                   
                   
                   
                 Integrins alpha chain signature: W1036-R1043 
                 MOTIFS 
               
               
                 15 
                 7511534CD1 
                 601 
                 S15 S19 S27 S163 
                 N68 N279 N434 
                 signal_cleavage: M1-S19 
                 SPSCAN 
               
               
                   
                   
                   
                 S188 S195 S410 
                 N477 N531 
               
               
                   
                   
                   
                 S514 S519 S538 
               
               
                   
                   
                   
                 T131 T218 T287 
               
               
                   
                   
                   
                 T294 T323 T472 
               
               
                   
                   
                   
                 Y327 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-G17, M1-S19, M1-A23 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Integrin beta subunits (N-terminal portion of extracellular 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 region): S50-C476 
               
               
                   
                   
                   
                   
                   
                 Domain found in plexins, semaphorins and integrins: S44-P92 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Integrins, beta chain: S50-C476 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Integrin beta, C-terminus IPB001169: R79-L96, L140-V180, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 R181-C216, V232-L283, L284-L313, F325-V368, G369-S410, 
               
               
                   
                   
                   
                   
                   
                 G491-C513, A529-C550 
               
               
                   
                   
                   
                   
                   
                 Integrins beta chain cysteine-rich domain signature: R506-G571 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 Integrin beta subunit signature PR01186: A48-C64, C80-P99, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 Q122-G135, Y150-L168, R190-P209, C223-F242, 
               
               
                   
                   
                   
                   
                   
                 D256-R278, R282-D297, D326-T349, L362-Y386, C537-C550 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN GLYCOPROTEIN CELL ADHESION 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE REPEAT PRECURSOR 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR SUBUNIT SIGNAL PD001811: S50-C476 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN GLYCOPROTEIN CELL ADHESION 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE REPEAT SUBUNIT PRECURSOR 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX PD149771: P483-L558 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN BETA7 SUBUNIT PRECURSOR CELL 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 ADHESION TRANSMEMBRANE GLYCOPROTEIN 
               
               
                   
                   
                   
                   
                   
                 REPEAT EXTRACELLULAR PD041877: M1-P49 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN CELL ADHESION TRANSMEMBRANE 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN REPEAT PRECURSOR SIGNAL BETA 
               
               
                   
                   
                   
                   
                   
                 GPD154651: A485-S551 
               
               
                   
                   
                   
                   
                   
                 INTEGRINS BETA CHAIN CYSTEINE-RICH DOMAIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00846|P26010|17-465: G17-L466 
               
               
                   
                   
                   
                   
                   
                 DM00846|P32592|3-435: S50-E464 
               
               
                   
                   
                   
                   
                   
                 DM00846|S32659|2-437: S50-E464 
               
               
                   
                   
                   
                   
                   
                 DM00846|P12607|2-453: A48-L466 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 1: C500-C511, C548-C559 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Integrins beta chain cysteine-rich domain signature: C537-C550 
                 MOTIFS 
               
               
                 16 
                 7511648CD1 
                 1005 
                 S77 S130 S168 
                 N46 N280 N601 
                 signal_cleavage: M1-A31 
                 SPSCAN 
               
               
                   
                   
                   
                 S237 S257 S347 
                 N711 
               
               
                   
                   
                   
                 S415 S451 S695 
               
               
                   
                   
                   
                 T117 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A26, M1-A31, Q9-A26, L11-A26 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Integrin alpha (beta-propellor repeats): L383-D439, M316-L377, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 N46-L103, T444-D495, F262-R312 
               
               
                   
                   
                   
                   
                   
                 FG-GAP repeat: A317-Y384, G47-T107, G445-L497, G385-T444, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 D263-M316 
               
               
                   
                   
                   
                   
                   
                 Integrin alpha cytoplasmic region: K986-D1000 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: K986-E1005 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: I963-W985 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-P962 
               
               
                   
                   
                   
                   
                   
                 Integrins alpha chain IPB000413: E80-A91, G215-G224, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 G313-P342, R386-P410, W964-R992 
               
               
                   
                   
                   
                   
                   
                 Integrins alpha chain signature: V966-E1005 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 Integrin alpha subunit signature PR01185: D263-F275, E283-T294, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 G313-G333, R386-P410, F448-G469, Q475-Q494, 
               
               
                   
                   
                   
                   
                   
                 D591-L604, G973-R992 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN PRECURSOR SIGNAL GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 ALPHA CELL ADHESION TRANSMEMBRANE 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX PD001221: S192-V420, 
               
               
                   
                   
                   
                   
                   
                 E355-E608, Q707-L952, E957-R992 
               
               
                   
                   
                   
                   
                   
                 PLATELET MEMBRANE GLYCOPROTEIN IIB 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR GPIIB INTEGRIN ALPHA CD41 CELL 
               
               
                   
                   
                   
                   
                   
                 ADHESION TRANSMEMBRANE EXTRACELLULAR 
               
               
                   
                   
                   
                   
                   
                 MATRIX CYTOSKELETON SIGNAL POLYMORPHISM 
               
               
                   
                   
                   
                   
                   
                 DISEASE MUTATION PD175312: N145-F191 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN PRECURSOR CELL GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 SIGNAL ADHESION TRANSMEMBRANE 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX CYTOSKELETON 
               
               
                   
                   
                   
                   
                   
                 PD001587: A31-E148 
               
               
                   
                   
                   
                   
                   
                 INTEGRINS ALPHA CHAIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM01028|P08514|429-913: P36-A70, S318-A341, G429-A914 
               
               
                   
                   
                   
                   
                   
                 DM01028|A60163|428-911: P36-A70, 318-A341, G429-A914 
               
               
                   
                   
                   
                   
                   
                 DM00458|P08514|40-239: T40-P240 
               
               
                   
                   
                   
                   
                   
                 DM01028|P53708|390-888: G429-P877 
               
               
                   
                   
                   
                   
                   
                 Integrins alpha chain signature: W985-R992 
                 MOTIFS 
               
               
                 17 
                 7511600CD1 
                 330 
                 S19 S32 S104 S169 
                 N123 
                 signal_cleavage: M1-G17 
                 SPSCAN 
               
               
                   
                   
                   
                 S185 S315 T75 
               
               
                   
                   
                   
                 T284 T320 T323 
               
               
                   
                   
                   
                 T326 T330 
               
               
                   
                   
                   
                   
                   
                 Dopamine D4 receptor signature PR00569: G140-G157, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 T182-A196, L304-R325 
               
               
                   
                   
                   
                   
                   
                 PROTEIN CELL MEMBRANE GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 C56G2.7 CHROMOSOME III T9J22.26 PD022277: S15-V85, 
               
               
                   
                   
                   
                   
                   
                 E72-I133 
               
               
                   
                   
                   
                   
                   
                 PROTEIN CELL MEMBRANE GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 C56G2.7 CHROMOSOME III T9J22.26 PD021964: S214-Q299 
               
               
                 18 
                 7511783CD1 
                 186 
                 S88 Y69 
                 N64 N87 N98 
                 C2 type Ig domains from SCOP: M1-Y127 
                 HMMER_INCY 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: F159-P186 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: V136-I158 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-M135 
               
               
                   
                   
                   
                   
                   
                 Intercellular adhesion molecule/vascular cell adhesion 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 molecule PR01472: P20-T33, V37-P52, P52-E70 
               
               
                   
                   
                   
                   
                   
                 Intercellular adhesion molecule (ICAM) family sign 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 PR01473: P32-C45, G111-Y127 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR SIGNAL ADHESION TRANSMEMBRANE 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 INTERCELLULAR IMMUNOGLOBULIN FOLD CELL 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN REPEAT PD005863: E21-C156 
               
               
                   
                   
                   
                   
                   
                 INTERCELLULAR ADHESION ICAM2 MOLECULE2 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR CD102 IMMUNOGLOBULIN FOLD CELL 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN PD024043: F157-P186 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00001|P13598|115-200: V26-G112 
               
               
                   
                   
                   
                   
                   
                 DM00001|P35330|115-199: V26-G112 
               
               
                 19 
                 7512383CD1 
                 806 
                 S29 S67 S74 S116 
                 N130 N337 
                 signal_cleavage: M1-A22 
                 SPSCAN 
               
               
                   
                   
                   
                 S165 S310 S319 
               
               
                   
                   
                   
                 S419 S446 S615 
               
               
                   
                   
                   
                 S704 S708 S727 
               
               
                   
                   
                   
                 T212 T219 T269 
               
               
                   
                   
                   
                 T382 T386 T397 
               
               
                   
                   
                   
                 T420 T430 T545 
               
               
                   
                   
                   
                 T558 T660 T705 
               
               
                   
                   
                   
                 T728 Y135 Y459 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A17, M1-A19, M1-A20, M1-A22, M1-V24 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 C-type lectin (CTL) or carbohydrate-recognition domain: 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 C688-R806 
               
               
                   
                   
                   
                   
                   
                 Epidermal growth factor-like domain.: D649-D682 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin: D42-K155 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin V-Type: A52-V139 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Link (Hyaluronan-binding): N256-R354, K155-A252 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain: C650-C681 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Extracellular link domain: G257-F353, G156-Y251 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin domain: G50-V139 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Lectin C-type domain: T705-L764, E266-T286, Y168-E190 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Link domain IPB000538: G174-G226 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 C-type lectin domain IPB001304: W692-C716, W744-F756 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 Link module signature PR01265: R167-C179, A195-L208, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 V213-C224, Y246-L255 
               
               
                   
                   
                   
                   
                   
                 BREVICAN CORE PROTEIN PRECURSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN HYALURONIC ACID 
               
               
                   
                   
                   
                   
                   
                 PROTEOGLYCAN LECTIN SIGNAL PD022317: L479-V651 
               
               
                   
                   
                   
                   
                   
                 BREVICAN CORE PROTEIN PRECURSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN HYALURONIC ACID 
               
               
                   
                   
                   
                   
                   
                 PROTEOGLYCAN LECTIN SIGNAL PD021260: R354-E455 
               
               
                   
                   
                   
                   
                   
                 CORE PROTEIN PRECURSOR GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 HYALURONIC ACID PROTEOGLYCAN EGFLIKE 
               
               
                   
                   
                   
                   
                   
                 DOMAIN REPEAT PD150847: D28-V154 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN PRECURSOR PROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PROTEOGLYCAN SIGNAL REPEAT CORE EGFLIKE 
               
               
                   
                   
                   
                   
                   
                 DOMAIN IMMUNOGLOBULIN PD000918: G156-Y251, 
               
               
                   
                   
                   
                   
                   
                 K267-F353 
               
               
                   
                   
                   
                   
                   
                 COMPLEMENT FACTOR H REPEAT 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00260|A54423|142-252: G142-E253, G238-D355 
               
               
                   
                   
                   
                   
                   
                 DM00260|P41725|142-252: G142-E253, G238-D355 
               
               
                   
                   
                   
                   
                   
                 DM00260|A53908|141-251: G142-E253, G238-D355 
               
               
                   
                   
                   
                   
                   
                 DM00260|A54423|254-355: K153-E253, D254-S356 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 1: C670-C681 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 2: C670-C681 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulins and major histocompatibility complex 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 proteins signature: Y135-H141 
               
               
                   
                   
                   
                   
                   
                 Link domain signature: C179-C224, C277-C322 
                 MOTIFS 
               
               
                 20 
                 7512813CD1 
                 32 
                 S28 
                   
                 signal_cleavage: M1-H18 
                 SPSCAN 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: E4-S28 
                 PROFILESCAN 
               
               
                 21 
                 7512842CD1 
                 142 
                 S6 S88 S127 T31 
                 N39 N118 
                 signal_cleavage: M1-L21 
                 SPSCAN 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A20, M1-W22, M1-A26 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin: S32-L137 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin V-Type: D42-Y125 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin domain: G40-Y125 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 V type Ig domains: V27-H142 
                 HMMER_INCY 
               
               
                   
                   
                   
                   
                   
                 Ig superfamily: E28-L128 
                 HMMER_INCY 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: M1-R8 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: A9-T31 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: S32-H142 
               
               
                   
                   
                   
                   
                   
                 EPITHELIAL V-LIKE ANTIGEN PRECURSOR SIGNAL 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PD178398: M1-A26 (P = 1.1E−08) 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR GLYCOPROTEIN SIGNAL CHANNEL 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE IMMUNOGLOBULIN FOLD 
               
               
                   
                   
                   
                   
                   
                 PROTEIN MYELIN SODIUM PD013099: I29-C123 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00001|P10522|3-108: I29-C123 
               
               
                   
                   
                   
                   
                   
                 DM00001|P37301|32-137: I29-C123 
               
               
                   
                   
                   
                   
                   
                 DM00001|P20938|30-135: I29-C123 
               
               
                   
                   
                   
                   
                   
                 DM00001|A57843|32-137: L35-C123 
               
               
                 22 
                 90190613CD1  
                 3317 
                 S30 S94 S187 S195 
                 N632 N847 N1182 
                 signal_cleavage: M1-Q31 
                 SPSCAN 
               
               
                   
                   
                   
                 S223 S241 S410 
                 N1222 N1317 
               
               
                   
                   
                   
                 S498 S546 S659 
                 N1327 N1649 
               
               
                   
                   
                   
                 S834 S866 S881 
                 N1713 N1770 
               
               
                   
                   
                   
                 S883 S984 S1031 
                 N2053 N2182 
               
               
                   
                   
                   
                 S1181 S1231 S1348 
                 N2201 N2391 
               
               
                   
                   
                   
                 S1367 S1579 S1631 
                 N2479 N2511 
               
               
                   
                   
                   
                 S1660 S1661 S1686 
                 N2702 N2751 
               
               
                   
                   
                   
                 S1738 S1830 S1904 
                 N2813 N3259 
               
               
                   
                   
                   
                 S1935 S1995 S2132 
               
               
                   
                   
                   
                 S2341 S2374 S2378 
               
               
                   
                   
                   
                 S2387 S2532 S2568 
               
               
                   
                   
                   
                 S2571 S2682 S2725 
               
               
                   
                   
                   
                 S2838 S2841 S2849 
               
               
                   
                   
                   
                 S2866 S2897 S2899 
               
               
                   
                   
                   
                 S2904 S2916 S2938 
               
               
                   
                   
                   
                 S2975 S2999 S3072 
               
               
                   
                   
                   
                 S3300 
               
               
                   
                   
                   
                 T201 T251 T267 
                   
                 Signal Peptide: M2-E32 
                 HMMER 
               
               
                   
                   
                   
                 T308 T404 T422 
               
               
                   
                   
                   
                 T441 T458 T528 
               
               
                   
                   
                   
                 T534 T568 T570 
               
               
                   
                   
                   
                 T745 T757 T779 
               
               
                   
                   
                   
                 T832 T853 T932 
               
               
                   
                   
                   
                 T945 T986 T1021 
               
               
                   
                   
                   
                 T1090 T1224 
               
               
                   
                   
                   
                 T1247 T1276 
               
               
                   
                   
                   
                 T1305 T1434 
               
               
                   
                   
                   
                 T1466 T1489 
               
               
                   
                   
                   
                 T1842 T2085 
               
               
                   
                   
                   
                 T2203 T2235 
               
               
                   
                   
                   
                 T2501 T2728 
               
               
                   
                   
                   
                 T2882 T2983 
               
               
                   
                   
                   
                 T2998 T3292 Y400 
               
               
                   
                   
                   
                 Y450 Y843 Y2318 
               
               
                   
                   
                   
                   
                   
                 Cadherin repeats: I673-P754, L455-P543, I983-P1065, I880-P959, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 V347-P431, V567-P649, I1089-P1167, V778-P856, 
               
               
                   
                   
                   
                   
                   
                 I1195-L1271 
               
               
                   
                   
                   
                   
                   
                 Epidermal growth factor-like domain: L1438-E1471, F1725-Q1758, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 A1949-V1982, A1984-E2020, V1378-E1433, 
               
               
                   
                   
                   
                   
                   
                 R1478-E1514, P2039-N2108 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain: E1435-E1471, C1479-E1514, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 N1948-V1982, C1726-Q1758, D1983-E2020 
               
               
                   
                   
                   
                   
                   
                 G-protein-coupled receptor proteolytic site: S2481-R2534 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Domain present in hormone receptors: L2125-S2192 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Laminin G domain: F1535-R1702, V1785-T1924 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 7 transmembrane receptor (Secretin family): L2541-A2783 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain: C1726-C1757, C1479-C1513, C1985-C2019, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 C1439-C1470, C1950-C1981, R1420-C1432, C1379-V1393 
               
               
                   
                   
                   
                   
                   
                 Latrophilin/CL-1-like GPS domain: S2481-R2534 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Hormone receptor domain: Y2126-F2188 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cadherin domain: Y550-V642, F656-L747, Y966-Q1058, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Y438-L536, Y330-A424, F1072-V1160, Y863-N952, Y761-T849, 
               
               
                   
                   
                   
                   
                   
                 P1188-I1266 
               
               
                   
                   
                   
                   
                   
                 Laminin G domain: F1543-D1705, F1793-G1927 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domains: S2568-G2578, R2634-G2645, R2711-R2730 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domains: A2545-L2567, I2579-T2601, 
               
               
                   
                   
                   
                   
                   
                 A2611-Y2633, A2646-L2668, I2688-A2710, S2731-V2750 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domains: M1-L2544, H2602-V2610, D2669-L2687, 
               
               
                   
                   
                   
                   
                   
                 N2751-S3317 
               
               
                   
                   
                   
                   
                   
                 G-protein coupled receptors family 2 (secretin-like) 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 IPB000832: C2129-A2156, V2551-L2596, C2607-L2632, 
               
               
                   
                   
                   
                   
                   
                 G2654-F2678, W2689-Q2718, S2725-G2746, G2766-R2794 
               
               
                   
                   
                   
                   
                   
                 Laminin-type EGF-like (LE) domain IPB002049: R1420-D1430, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 S2034-V2044, S2086-C2096, C2098-F2114 
               
               
                   
                   
                   
                   
                   
                 Cadherin domain IPB002126: D1005-E1028 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: V403-I452, 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 V512-V564, L618-V670, G725-V775, A930-V980, 
               
               
                   
                   
                   
                   
                   
                 V1032-V1086 
               
               
                   
                   
                   
                   
                   
                 Type II EGF-like signature PR00010: E1435-N1446, G1487-P1494, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 G1742-F1752 
               
               
                   
                   
                   
                   
                   
                 Cadherin signature PR00205: E374-R393, F545-K574, E615-R627, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 P735-P754, P856-E869, D909-D935, S1151-V1168 
               
               
                   
                   
                   
                   
                   
                 MEGF2 CELL ADHESION GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE CALCIUM-BINDING REPEAT 
               
               
                   
                   
                   
                   
                   
                 PD185010: S260-F282, W2787-S3317 
               
               
                   
                   
                   
                   
                   
                 PD182204: Q31-L333 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE SEVEN PASS RECEPTOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR SIGNAL MEGF2 CELL ADHESION 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN CALCIUM-BINDING 
               
               
                   
                   
                   
                   
                   
                 PD155621: M1761-V1946 
               
               
                   
                   
                   
                   
                   
                 PD155993: E2246-E2407 
               
               
                   
                   
                   
                   
                   
                 HORMONE; EMR1; LEUCOCYTE; ANTIGEN; 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM05221|A57172|465-886: M2444-R2784 
               
               
                   
                   
                   
                   
                   
                 DM05221|I37225|347-738: R2480-L2792 
               
               
                   
                   
                   
                   
                   
                 DM05221|P48960|347-738: R2480-L2792 
               
               
                   
                   
                   
                   
                   
                 G-PROTEIN COUPLED RECEPTORS FAMILY 2 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00378|P47866|1-405: Y2126-W2175 V2554-A2786 
               
               
                   
                   
                   
                   
                   
                 Aspartic acid and asparagine hydroxylation site: C1961-C1972 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: V421-P431, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 I533-P543, I639-P649, V744-P754, V949-P959, 
               
               
                   
                   
                   
                   
                   
                 V1055-P1065, V1157-P1167 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 1: C1421-C1432, C1459-C1470, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 C1746-C1757, C1970-C1981, C2008-C2019, C2096-C2107 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 2: C1421-C1432, C1746-C1757, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 C1970-C1981, C2008-C2019 
               
               
                   
                   
                   
                   
                   
                 Laminin-type EGF-like (LE) domain signature: C2096-C2122 
                 MOTIFS 
               
               
                 23 
                 7511894CD1 
                 638 
                 S3 S23 S56 S111 
                 N85 N89 N175 
                 signal_cleavage: M1-I24 
                 SPSCAN 
               
               
                   
                   
                   
                 S589 T63 T145 
                 N181 N466 
               
               
                   
                   
                   
                 T177 T332 T503 
               
               
                   
                   
                   
                 T552 T567 T606 
               
               
                   
                   
                   
                 Y50 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-Q21, M1-V22, M1-I24, M1-S27, M1-I25, 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 M1-Q30 
               
               
                   
                   
                   
                   
                   
                 Cadherin repeats: M191-P277, F422-P502, L300-A399, P76-P167 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Cadherin domain: F174-Q270, F405-S495, Y284-Q390, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 R509-C599, E116-S160 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: M1-H6 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: P7-I25 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: D26-C638 
               
               
                   
                   
                   
                   
                   
                 Cadherin domain IPB002126: L53-N85, D438-E461, T485-L494 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: T246-L298, 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 F469-L522 
               
               
                   
                   
                   
                   
                   
                 Cadherin signature PR00205: L109-R128, F169-E198, Q244-E256, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 S258-P277, P277-E290, N337-N363, A486-T503 
               
               
                   
                   
                   
                   
                   
                 CADHERIN REPEAT 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00030|P33150|392-505: T310-S429 
               
               
                   
                   
                   
                   
                   
                 DM00030|P55290|392-505: T310-S429 
               
               
                   
                   
                   
                   
                   
                 DM00030|P33147|413-526: T310-D428 
               
               
                   
                   
                   
                   
                   
                 DM00030|P55291|290-403: W313-S429 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: I157-P167, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 L492-P502 
               
               
                 24 
                 3604804CD1 
                 4560 
                 S85 S132 S189 
                 N49 N342 N482 
                 Signal Peptide: M5-S30, M5-G32, V9-G32 
                 HMMER 
               
               
                   
                   
                   
                 S216 S384 S412 
                 N563 N668 N800 
               
               
                   
                   
                   
                 S461 S495 S497 
                 N880 N899 N1007 
               
               
                   
                   
                   
                 S529 S538 S601 
                 N1368 N1430 
               
               
                   
                   
                   
                 S617 S677 S682 
                 N1755 N1948 
               
               
                   
                   
                   
                 S813 S862 S901 
                 N1997 N2000 
               
               
                   
                   
                   
                 S942 S1025 S1051 
                 N2212 N2296 
               
               
                   
                   
                   
                 S1072 S1081 S1092 
                 N2335 N2471 
               
               
                   
                   
                   
                 S1130 S1161 S1178 
                 N3004 N3205 
               
               
                   
                   
                   
                 S1209 S1232 S1294 
                 N3333 N3453 
               
               
                   
                   
                   
                 S1314 S1315 S1374 
                 N3622 N3745 
               
               
                   
                   
                   
                 S1404 S1499 S1505 
                 N3930 N4186 
               
               
                   
                   
                   
                 S1574 S1643 S1780 
                 N4191 N4205 
               
               
                   
                   
                   
                 S1808 S1868 S1909 
                 N4472 
               
               
                   
                   
                   
                 S1924 S1993 S2153 
               
               
                   
                   
                   
                 S2197 S2247 S2422 
               
               
                   
                   
                   
                 S2427 S2438 S2473 
               
               
                   
                   
                   
                 S2611 S2649 S2728 
               
               
                   
                   
                   
                 S2820 S2860 S2914 
               
               
                   
                   
                   
                 S2950 S3021 S3047 
               
               
                   
                   
                   
                 S3055 S3172 S3207 
               
               
                   
                   
                   
                 S3280 S3297 S3491 
               
               
                   
                   
                   
                 S3529 S3616 S3624 
               
               
                   
                   
                   
                 S3660 S3687 S3747 
               
               
                   
                   
                   
                 S3819 S3857 S3911 
               
               
                   
                   
                   
                 S3935 S3939 S3972 
               
               
                   
                   
                   
                 S4007 S4250 S4273 
               
               
                   
                   
                   
                 S4300 S4304 S4331 
               
               
                   
                   
                   
                 S4335 S4349 S4369 
               
               
                   
                   
                   
                 S4389 S4516 S4534 
               
               
                   
                   
                   
                 S4538 
               
               
                   
                   
                   
                 T51 T71 T166 
                   
                 Cadherin repeats: V3156-P3237, V1065-P1146, V3261-P3342, 
                 HMMER_SMART 
               
               
                   
                   
                   
                 T181 T183 T249 
                   
                 V2839-P2925, I1170-P1252, V494-P576, L3366-P3447, 
               
               
                   
                   
                   
                 T286 T431 T437 
                   
                 V853-P934, L958-H1039, I1801-P1884, V2312-P2395, 
               
               
                   
                   
                   
                 T448 T530 T565 
                   
                 V3054-P3132, I748-P829, I1696-P1770, I1482-P1564, 
               
               
                   
                   
                   
                 T654 T656 T764 
                   
                 L2949-P3030, V180-P264, V2521-P2601, I2211-P2288, 
               
               
                   
                   
                   
                 T802 T921 T1009 
                   
                 V2007-P2085, V1588-P1672, V394-P470, V2419-P2497, 
               
               
                   
                   
                   
                 T1066 T1101 
                   
                 I1380-P1458, L3471-P3552, V1908-L1983, A1278-P1354, 
               
               
                   
                   
                   
                 T1121 T1184 
                   
                 I70-P156, G2727-P2815, V600-H673, V2109-P2187, 
               
               
                   
                   
                   
                 T1208 T1225 
                   
                 V2625-P2709 
               
               
                   
                   
                   
                 T1328 T1342 
               
               
                   
                   
                   
                 T1361 T1370 
               
               
                   
                   
                   
                 T1468 T1485 
               
               
                   
                   
                   
                 T1589 T1665 
               
               
                   
                   
                   
                 T1728 T1804 
               
               
                   
                   
                   
                 T1822 T1911 
               
               
                   
                   
                   
                 T1943 T2110 
                   
                 Cadherin domain: Y3244-T3335, Y3349-S3440, Y3139-L3230, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                 T2173 T2214 
                   
                 V1048-E1139, Y1153-L1245, Y941-V1032, Y836-D927, 
               
               
                   
                   
                   
                 T2260 T2298 
                   
                 Y477-G569, Y2504-V2594, Y1465-E1557, Y2822-T2918, 
               
               
                   
                   
                   
                 T2351 T2364 
                   
                 Y1679-V1763, Y1777-E1875, Y163-E257, Y3037-E3125, 
               
               
                   
                   
                   
                 T2524 T2558 
                   
                 Y1571-T1665, Y2194-N2281, Y2295-S2388, S731-E822, 
               
               
                   
                   
                   
                 T2588 T2719 
                   
                 Y1259-I1350, Y2092-V2182, Y1990-E2078, Y2932-S3023, 
               
               
                   
                   
                   
                 T2732 T2767 
                   
                 Y2402-L2490, Y2608-L2702, Y3454-I3545, C583-L672, 
               
               
                   
                   
                   
                 T2880 T3006 
                   
                 Y1367-L1451, F1886-K1976, Y2716-L2808, F3560-E3641, 
               
               
                   
                   
                   
                 T3228 T3247 
                   
                 Y381-E463, Y48-L149 
               
               
                   
                   
                   
                 T3264 T3270 
               
               
                   
                   
                   
                 T3474 T3549 
               
               
                   
                   
                   
                 T3563 T3579 
               
               
                   
                   
                   
                 T3653 T3675 
               
               
                   
                   
                   
                 T3682 T3772 
               
               
                   
                   
                   
                 T4056 T4097 
               
               
                   
                   
                   
                 T4278 Y506 Y1000 
               
               
                   
                   
                   
                 Y1080 Y1276 
               
               
                   
                   
                   
                 Y1545 Y1966 
               
               
                   
                   
                   
                 Y2020 Y2468 
               
               
                   
                   
                   
                 Y2822 Y4397 
               
               
                   
                   
                   
                   
                   
                 Epidermal growth factor-like domain: A4027-E4061, E4104-G4137, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 A4066-E4099, P3801-S3836 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain: D4101-G4137, D4026-E4061, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 E4063-E4099 
               
               
                   
                   
                   
                   
                   
                 Laminin G domain: E3860-N3997 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain: C4105-C4136, C4067-C4098, C4028-C4060, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 C3802-C3835 
               
               
                   
                   
                   
                   
                   
                 Laminin G domain: L3868-P4000 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: R4179-V4560 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: I4159-F4178 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-L4158 
               
               
                   
                   
                   
                   
                   
                 Cadherin domain IPB002126: S3176-E3199, S3430-I3439, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 E4315-M4363 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: T1117-V1167, 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 V1224-G1272, L1742-V1791, L2259-V2309, 
               
               
                   
                   
                   
                   
                   
                 V2367-V2416, F2784-L2836, F2892-V2946, I3206-V3258, 
               
               
                   
                   
                   
                   
                   
                 V3313-V3363, L3418-I3468 
               
               
                   
                   
                   
                   
                   
                 Cadherin signature PR00205: V418-T437, F472-K501, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 E1219-P1231, S3218-P3237, P3342-E3355, V3397-D3423, 
               
               
                   
                   
                   
                   
                   
                 S3431-V3448 
               
               
                   
                   
                   
                   
                   
                 CADHERIN-RELATED TUMOR SUPPRESSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 HOMOLOG PRECURSOR FAT PROTEIN HOMOLOG 
               
               
                   
                   
                   
                   
                   
                 CELL ADHESION SIGNAL GLYCOPROTEIN 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE CALCIUM-BINDING REPEAT 
               
               
                   
                   
                   
                   
                   
                 EGF-LIKE DOMAIN 
               
               
                   
                   
                   
                   
                   
                 PD140312: V4153-V4560 
               
               
                   
                   
                   
                   
                   
                 PD131818: V2088-A2196 
               
               
                   
                   
                   
                   
                   
                 CELL ADHESION GLYCOPROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE CALCIUM-BINDING REPEAT 
               
               
                   
                   
                   
                   
                   
                 HOMOLOG PROTEIN MEGF1 CADHERIN-RELATED 
               
               
                   
                   
                   
                   
                   
                 PD152384: F41-T166 
               
               
                   
                   
                   
                   
                   
                 CADHERIN REPEAT 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00030|P33450|3576-3680: P3375-S3478, G3269-S3373, 
               
               
                   
                   
                   
                   
                   
                 G756-D859, N2322-S2426, R1074-D1176, G966-S1072, 
               
               
                   
                   
                   
                   
                   
                 N758-L860, G3164-D3267, N3271-D3372 
               
               
                   
                   
                   
                   
                   
                 DM00030|P08641|300-409: N3376-S3478, N2849-D2955 
               
               
                   
                   
                   
                   
                   
                 Aspartic acid and asparagine hydroxylation site: C4116-C4127 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Cadherins extracellular repeated domain signature: I460-P470, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 I819-P829, I1136-P1146, V1242-P1252, I1448-P1458, 
               
               
                   
                   
                   
                   
                   
                 V1554-P1564, I1760-P1770, I1874-P1884, V2075-P2085, 
               
               
                   
                   
                   
                   
                   
                 L2278-P2288, I2385-P2395, V2591-P2601, I2805-P2815, 
               
               
                   
                   
                   
                   
                   
                 V2915-P2925, V3020-P3030, L3122-P3132, I3227-P3237, 
               
               
                   
                   
                   
                   
                   
                 I3332-P3342, I3437-P3447 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 1: C4049-C4060, C4087-C4098, 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 C4125-C4136 
               
               
                   
                   
                   
                   
                   
                 EGF-like domain signature 2: C4125-C4136 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Calcium-binding EGF-like domain pattern signature: D4101-C4125 
                 MOTIFS 
               
               
                 25 
                 7512568CD1 
                 330 
                 S45 S112 S131 
                 N25 N57 N100 
                 signal_cleavage: M1-A20 
                 SPSCAN 
               
               
                   
                   
                   
                 S182 S184 S190 
                 N110 N120 N224 
               
               
                   
                   
                   
                 S209 S260 S285 
               
               
                   
                   
                   
                 T27 T76 T163 
               
               
                   
                   
                   
                 T174 T314 Y169 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A20 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Link (Hyaluronan-binding): F30-N120 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Extracellular link domain: A31-F119 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: R261-V330 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: W238-S260 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-E237 
               
               
                   
                   
                   
                   
                   
                 Link domain IPB000538: T226-A278 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 CD44 antigen precursor signature PR00658: D23-Y42, G73-P93, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 Y114-D134, N149-I168, E220-L239, I240-R262, C264-K283, 
               
               
                   
                   
                   
                   
                   
                 D310-G329 
               
               
                   
                   
                   
                   
                   
                 Link module signature PR01265: R41-C53, A69-I82, V86-C97, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 Y114-A123 
               
               
                   
                   
                   
                   
                   
                 CD44 GLYCOPROTEIN ANTIGEN PRECURSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PHAGOCYTIC I PGP1 HUTCHI EXTRACELLULAR 
               
               
                   
                   
                   
                   
                   
                 MATRIX 
               
               
                   
                   
                   
                   
                   
                 PD006761: V254-V330 
               
               
                   
                   
                   
                   
                   
                 PD004309: N120-S227, Y161-W238 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN PRECURSOR PROTEIN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PROTEOGLYCAN SIGNAL REPEAT CORE EGFLIKE 
               
               
                   
                   
                   
                   
                   
                 DOMAIN IMMUNOGLOBULIN PD000918: V33-F119 
               
               
                   
                   
                   
                   
                   
                 CD44; LONG; SURFACE; ADHESION; 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM03720|S24631|462-698: V178-V330 
               
               
                   
                   
                   
                   
                   
                 DM03720|A53286|153-365: Y161-V330 
               
               
                   
                   
                   
                   
                   
                 DM03720|B38745|157-502: T163-V330 
               
               
                   
                   
                   
                   
                   
                 DM03720|P20944|155-361: R90-P124, S187-V330 
               
               
                   
                   
                   
                   
                   
                 Link domain signature: C53-C97 
                 MOTIFS 
               
               
                 26 
                 7512812CD1 
                 681 
                 S80 S144 S176 
                 N48 N97 N260 
                 Signal Peptide: M1-G21 
                 HMMER 
               
               
                   
                   
                   
                 S270 S297 S366 
                 N387 N396 N463 
               
               
                   
                   
                   
                 S373 S407 S464 
                 N471 N541 N664 
               
               
                   
                   
                   
                 S501 S512 S589 
               
               
                   
                   
                   
                 S628 T30 T151 
               
               
                   
                   
                   
                 T188 T189 T305 
               
               
                   
                   
                   
                 T579 T661 T666 
               
               
                   
                   
                   
                   
                   
                 Integrin beta subunits (N-terminal portion): T30-C454 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Domain found in Plexins, Semaphorins and Integrins: G22-Q71 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Integrins, beta chain: T30-C454 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: K624-C681 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: I601-W623 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-N600 
               
               
                   
                   
                   
                   
                   
                 Integrin beta, C-terminus IPB001169: R58-I75, L121-K161, 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 E162-C197, I213-H264, L266-L295, L307-V350, G351-A392, 
               
               
                   
                   
                   
                   
                   
                 G470-C492, K503-C524 
               
               
                   
                   
                   
                   
                   
                 Integrins beta chain cysteine-rich domain signature: G487-G549 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 Type III EGF-like signature PR00011: G472-C490 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 Integrin beta subunit signature PR01186: A28-C44, C59-P78, 
                 BLIMPS_PRINTS 
               
               
                   
                   
                   
                   
                   
                 Q103-G116, Y131-L149, R171-P190, C204-F223, 
               
               
                   
                   
                   
                   
                   
                 D237-R259, H264-D279, E308-T331, L344-Y368, C511-C524, 
               
               
                   
                   
                   
                   
                   
                 P599-G616, G616-E634, T651-T661 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN GLYCOPROTEIN CELL ADHESION 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE REPEAT PRECURSOR 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR SUBUNIT SIGNAL 
               
               
                   
                   
                   
                   
                   
                 PD001811: T30-C454 
               
               
                   
                   
                   
                   
                   
                 PD001794: S556-Y667 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN GLYCOPROTEIN CELL ADHESION 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 TRANSMEMBRANE REPEAT SUBUNIT PRECURSOR 
               
               
                   
                   
                   
                   
                   
                 EXTRACELLULAR MATRIX PD149771: D455-Y536 
               
               
                   
                   
                   
                   
                   
                 INTEGRIN CELL ADHESION TRANSMEMBRANE 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN REPEAT PRECURSOR SIGNAL BETA 
               
               
                   
                   
                   
                   
                   
                 G PD154651: N463-Y536 
               
               
                   
                   
                   
                   
                   
                 INTEGRINS BETA CHAIN CYSTEINE-RICH DOMAIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00846|P18564|1-442: M1-A443 
               
               
                   
                   
                   
                   
                   
                 DM00846|P18084|7-451: C23-A443 
               
               
                   
                   
                   
                   
                   
                 DM00846|P05106|9-449: C23-A443 
               
               
                   
                   
                   
                   
                   
                 DM00846|P12607|2-453: Q20-D442 
               
               
                   
                   
                   
                   
                   
                 Cell attachment sequence: R514-D516 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 Integrins beta chain cysteine-rich domain signature: C511-C524 
                 MOTIFS 
               
               
                 27 
                 7512826CD1 
                 614 
                 S58 S93 S290 S315 
                 N56 N418 N449 
                 signal_cleavage: M1-G23 
                 SPSCAN 
               
               
                   
                   
                   
                 S369 S471 S561 
                 N467 N508 
               
               
                   
                   
                   
                 S571 S582 S595 
               
               
                   
                   
                   
                 T107 T249 T298 
               
               
                   
                   
                   
                 T469 T495 Y222 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-C17, M1-C18, M1-R20, M1-G23, M1-V24, 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 M1-A28, 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin: P33-Y133, P350-F428, E257-N341, E437-E517, 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 I148-P244 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin C-2 Type: K263-T327, Q356-I414, K153-K209 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Immunoglobulin domain: G358-A409, G265-G322, N445-A501, 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 G41-G118, E156-L225 
               
               
                   
                   
                   
                   
                   
                 Ig superfamily from SCOP: V346-G416, W253-L325, E29-E138, 
                 HMMER_INCY 
               
               
                   
                   
                   
                   
                   
                 M433-E517, I141-P248 
               
               
                   
                   
                   
                   
                   
                 b7/CD80/CD86 multiple Ig domain: E29-E255 
                 HMMER_INCY 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: Y551-H614 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: V528-L550 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: M1-G527 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN ANTIGEN PRECURSOR 
                 BLIMPS_PRODOM 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN. PD02327: L130-I141, T160-L181 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR SIGNAL IMMUNOGLOBULIN FOLD 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN TRANSMEMBRANE CELL ANTIGEN 
               
               
                   
                   
                   
                   
                   
                 ADHESION RECEPTOR PD004088: F10-L229 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR SIGNAL HEMCAM CELL ADHESION 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 SURFACE GLYCOPROTEIN MUC18 MELANOMA- 
               
               
                   
                   
                   
                   
                   
                 ASSOCIATED ANTIGEN 
               
               
                   
                   
                   
                   
                   
                 PD012722: L323-T469 
               
               
                   
                   
                   
                   
                   
                 PD012723: Q478-T567 
               
               
                   
                   
                   
                   
                   
                 CELL SURFACE GLYCOPROTEIN MUC18 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR MELANOMA-ASSOCIATED ANTIGEN 
               
               
                   
                   
                   
                   
                   
                 A32 SENDO 1 ENDOTHELIAL ASSOCIATED CD146 
               
               
                   
                   
                   
                   
                   
                 MELANOMA ADHESION MOLECULE 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN FOLD TRANSMEMBRANE 
               
               
                   
                   
                   
                   
                   
                 SIGNAL PD074165: A470-L516 
               
               
                   
                   
                   
                   
                   
                 IMMUNOGLOBULIN 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00001|P43121|142-233: Q142-H234 
               
               
                   
                   
                   
                   
                   
                 DM00001|P43121|434-509: A434-S510 
               
               
                   
                   
                   
                   
                   
                 DM00001|P43121|254-330: L254-L331 
               
               
                   
                   
                   
                   
                   
                 DM00001|P43121|347-417: R347-N418 
               
               
                 28 
                 7512908CD1 
                 385 
                 S220 S311 S315 
                 N75 N153 N237 
                 signal_cleavage: M1-A22 
                 SPSCAN 
               
               
                   
                   
                   
                 S340 S347 T155 
               
               
                   
                   
                   
                 Y105 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A22, M1-V25, M1-S28, M1-A26, M1-E27 
                 HMMER 
               
               
                 29 
                 7512909CD1 
                 527 
                 S220 S311 S315 
                 N75 N153 N237 
                 signal_cleavage: M1-A22 
                 SPSCAN 
               
               
                   
                   
                   
                 S340 S347 S380 
                 N360 
               
               
                   
                   
                   
                 S397 S479 S485 
               
               
                   
                   
                   
                 S491 S500 S506 
               
               
                   
                   
                   
                 T155 T385 T503 
               
               
                   
                   
                   
                 Y105 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A22, M1-V25, M1-S28, M1-A26, M1-E27 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Glycosyltransferase family 25 (LPS biosynthesis protein): 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 F319-L478 
               
               
                 30 
                 7512769CD1 
                 84 
                 T4 
                   
                 signal_cleavage: M1-A19 
                 SPSCAN 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M1-A19, M1-S21, M1-G23, M1-F25, M1-G29, 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 M1-A20 
               
               
                   
                   
                   
                   
                   
                 Cytosolic domain: M1-R6 
                 TMHMMER 
               
               
                   
                   
                   
                   
                   
                 Transmembrane domain: A7-G29 
               
               
                   
                   
                   
                   
                   
                 Non-cytosolic domain: Q30-C84 
               
               
                   
                   
                   
                   
                   
                 MATRIX PROTEIN EXTRACELLULAR PRECURSOR 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 SECRETORY COMPONENT P85 SIGNAL 
               
               
                   
                   
                   
                   
                   
                 GLYCOPROTEIN REPEAT PD014357: M1-P81 
               
               
                 31 
                 7512871CD1 
                 311 
                 S44 S222 S300 T32 
                 N290 
                 signal_cleavage: M1-A27 
                 SPSCAN 
               
               
                   
                   
                   
                 Y126 Y232 
               
               
                   
                   
                   
                   
                   
                 Signal Peptide: M8-A27, M8-A29, M8-T32, M1-A29 
                 HMMER 
               
               
                   
                   
                   
                   
                   
                 Fibrinogen-related domains (FReDs): T113-A311 
                 HMMER_SMART 
               
               
                   
                   
                   
                   
                   
                 Collagen triple helix repeat (20 copies): L50-S108 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Fibrinogen beta and gamma chains, C-terminal: G114-A311 
                 HMMER_PFAM 
               
               
                   
                   
                   
                   
                   
                 Fibrinogen beta and gamma chains C-terminal globular 
                 BLIMPS_BLOCKS 
               
               
                   
                   
                   
                   
                   
                 IPB002181: A59-I69, L122-L136, V144-G180, E185-T197, 
               
               
                   
                   
                   
                   
                   
                 L204-Y220, Y232-Q246, N254-E283, A286-P310 
               
               
                   
                   
                   
                   
                   
                 Fibrinogen beta and gamma chains C-terminal domain 
                 PROFILESCAN 
               
               
                   
                   
                   
                   
                   
                 signature: D245-G296 
               
               
                   
                   
                   
                   
                   
                 PRECURSOR GLYCOPROTEIN SIGNAL FIBRINOGEN 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 BLOOD COAGULATION CHAIN PLASMA PROTEIN 
               
               
                   
                   
                   
                   
                   
                 PLATELET PD001241: T113-A244, D245-P310 
               
               
                   
                   
                   
                   
                   
                 FICOLIN PD168236: G52-C111 
                 BLAST_PRODOM 
               
               
                   
                   
                   
                   
                   
                 FIBRINOGEN BETA/GAMMA 
                 BLAST_DOMO 
               
               
                   
                   
                   
                   
                   
                 DM00531|S61517|64-326: G64-A311 
               
               
                   
                   
                   
                   
                   
                 DM00531|B47172|64-326: G64-R309 
               
               
                   
                   
                   
                   
                   
                 DM00531|JN0596|27-305: E95-W264, D245-P310 
               
               
                   
                   
                   
                   
                   
                 DM00531|A45445|1099-1341: P115-P310 
               
               
                   
                   
                   
                   
                   
                 Fibrinogen beta and gamma chains C-terminal domain 
                 MOTIFS 
               
               
                   
                   
                   
                   
                   
                 signature: W263-G275 
               
               
                   
                   
                   
                   
                   
                 Lipocalin signature: N254-A266 
                 MOTIFS 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                   
               
               
                 Polynucleotide 
                   
               
               
                 SEQ ID NO:/ 
               
               
                 Incyte ID/Sequence 
               
               
                 Length 
                 Sequence Fragments 
               
               
                   
               
             
            
               
                 32/7506690CB1/ 
                 1-652, 1-724, 1-779, 1-812, 1-3988, 9-571, 10-735, 26-733, 26-778, 
               
               
                 4000 
                 226-641, 226-781, 282-907, 308-554, 340-907, 341-820, 371-907, 391-731, 
               
               
                   
                 411-731, 421-934, 421-1091, 455-728, 783-1408, 787-1510, 965-1580, 
               
               
                   
                 965-1669, 965-1679, 965-1724, 985-1646, 994-1444, 999-1907, 
               
               
                   
                 1008-1664, 1032-1685, 1090-1701, 1115-1886, 1160-1907, 1184-1536, 
               
               
                   
                 1210-1907, 1257-1907, 1259-1906, 1278-1847, 1283-2114, 
               
               
                   
                 1284-2114, 1285-2114, 1326-1905, 1327-1584, 1327-1768, 
               
               
                   
                 1329-2114, 1337-1907, 1341-1907, 1344-2114, 1372-1907, 
               
               
                   
                 1379-2114, 1401-1926, 
               
               
                   
                 1450-2106, 1462-2054, 1493-2106, 1535-2060, 1589-2247, 
               
               
                   
                 1768-2171, 1926-2277, 1997-2454, 1997-2467, 1997-2505, 1997-2515, 
               
               
                   
                 1997-2541, 2052-2651, 2105-2386, 2162-2836, 2167-2836, 2238-2752, 
               
               
                   
                 2257-2524, 2257-2676, 2257-2758, 2257-2799, 2257-2919, 2267-2391, 
               
               
                   
                 2267-2517, 2267-2535, 2267-2795, 2267-2844, 2269-2795, 2286-2962, 
               
               
                   
                 2350-2516, 2373-2457, 2460-2659, 2465-3044, 2502-2876, 
               
               
                   
                 2505-2597, 2609-2917, 2614-3012, 2791-3004, 2893-3049, 3046-3239, 
               
               
                   
                 3065-3231, 3086-3239, 3191-3280, 3232-3670, 3468-3991, 
               
               
                   
                 3469-4000, 3549-3699, 3670-4000, 3768-4000 
               
               
                 33/7506536CB1/ 
                 1-505, 1-711, 10-483, 10-1448, 18-651, 101-651, 217-372, 270-472, 
               
               
                 1448 
                 327-641, 327-893, 335-581, 417-1023, 492-697, 539-856, 552-863, 
               
               
                   
                 593-834, 650-1091, 763-1050, 763-1213, 774-1005, 774-1045, 774-1200, 
               
               
                   
                 774-1217, 778-1041, 787-1083, 914-1403, 914-1407, 967-1202, 
               
               
                   
                 968-1433, 1144-1382, 1243-1433 
               
               
                 34/7506537CB1/ 
                 1-590, 1-699, 1-792, 1-1331, 60-759, 176-331, 229-376, 
               
               
                 1430 
                 374-669, 374-676, 375-677, 406-647, 463-904, 576-863, 576-1065, 587-818, 587-858, 
               
               
                   
                 587-1013, 587-1047, 587-1065, 587-1127, 587-1133, 587-1187, 587-1218, 
               
               
                   
                 587-1219, 587-1236, 587-1237, 587-1245, 587-1247, 587-1249, 
               
               
                   
                 587-1290, 587-1305, 587-1315, 587-1317, 591-854, 600-896, 682-1269, 
               
               
                   
                 682-1318, 690-1346, 715-1057, 769-1208, 780-1015, 794-1089, 
               
               
                   
                 795-1092, 824-1108, 830-1430, 970-1216, 974-1114, 1141-1369 
               
               
                 35/7506655CB1/ 
                 1-616, 5-2437, 17-500, 17-608, 17-631, 23-471, 31-250, 32-324, 67-253, 
               
               
                 2529 
                 73-645, 76-299, 76-314, 96-209, 118-484, 126-845, 131-382, 132-720, 
               
               
                   
                 133-794, 138-249, 143-401, 145-434, 147-582, 153-835, 160-620, 163-408, 
               
               
                   
                 177-474, 180-386, 180-435, 180-439, 189-424, 191-447, 
               
               
                   
                 192-370, 192-509, 193-458, 199-744, 203-770, 211-506, 211-616, 221-378, 
               
               
                   
                 223-883, 225-331, 229-596, 247-694, 259-482, 261-918, 262-535, 
               
               
                   
                 262-715, 262-723, 262-745, 262-818, 262-846, 262-851, 262-878, 262-933, 
               
               
                   
                 262-947, 262-950, 262-967, 264-934, 267-961, 273-590, 
               
               
                   
                 295-884, 308-524, 308-582, 310-557, 312-451, 312-582, 317-563, 332-966, 
               
               
                   
                 335-966, 338-458, 346-595, 346-907, 346-1164, 349-1140, 354-588, 
               
               
                   
                 360-447, 364-653, 364-665, 366-628, 367-606, 376-672, 380-967, 386-581, 
               
               
                   
                 388-966, 391-914, 395-633, 398-619, 398-656, 407-636, 
               
               
                   
                 416-709, 429-687, 431-651, 431-706, 435-815, 435-839, 442-710, 448-967, 
               
               
                   
                 454-756, 456-706, 458-712, 475-753, 479-725, 479-740, 479-757, 
               
               
                   
                 480-943, 493-691, 497-781, 503-835, 503-883, 503-920, 503-957, 503-961, 
               
               
                   
                 503-967, 504-733, 506-742, 
               
               
                   
                 506-746, 509-902, 518-775, 519-743, 521-760, 522-863, 523-804, 527-754, 
               
               
                   
                 529-662, 530-967, 534-835, 538-835, 539-720, 544-967, 551-637, 
               
               
                   
                 555-831, 561-821, 562-861, 571-850, 581-967, 586-902, 590-789, 611-904, 
               
               
                   
                 616-896, 616-906, 622-907, 625-885, 636-908, 638-785, 
               
               
                   
                 645-963, 645-967, 648-941, 650-907, 655-848, 655-884, 663-757, 663-875, 
               
               
                   
                 663-907, 663-964, 666-934, 668-955, 672-823, 675-916, 677-936, 
               
               
                   
                 681-916, 687-954, 687-960, 689-967, 691-945, 698-967, 702-967, 707-963, 
               
               
                   
                 710-967, 716-967, 730-943, 735-939, 739-967, 743-962, 
               
               
                   
                 794-893, 796-967, 849-967, 862-967, 873-967, 963-1374, 963-1457, 963-1500, 963-1520, 
               
               
                   
                 963-1529, 963-1559, 965-1081, 967-1224, 972-1686, 
               
               
                   
                 973-1233, 974-1815, 986-1255, 989-1235, 1006-1175, 1018-1173, 1018-1250, 
               
               
                   
                 1022-1252, 1029-1303, 1035-1703, 1046-1520, 1056-1348, 
               
               
                   
                 1064-1285, 1066-1370, 1072-1336, 1074-1325, 1078-1539, 1086-1333, 1098-1669, 
               
               
                   
                 1099-1627, 1101-1259, 1101-1336, 1104-1391, 
               
               
                   
                 1106-1668, 1110-1333, 1114-1664, 1117-1416, 1117-1422, 1120-1755, 1121-1241, 
               
               
                   
                 1121-1409, 1134-1382, 1135-1712, 
               
               
                   
                 1139-1422, 1141-1341, 1145-1735, 1154-1398, 1164-1460, 1165-1412, 1171-1429, 
               
               
                   
                 1171-1740, 1175-1448, 1181-1621, 1184-1476, 1187-1429, 
               
               
                   
                 1187-1487, 1192-1449, 1192-1746, 1192-1760, 1193-1897, 1206-1385, 1206-1439, 
               
               
                   
                 1208-1475, 1208-1485, 1208-1532, 1208-1726, 
               
               
                   
                 1212-1486, 1212-1492, 1212-1550, 1213-1785, 1224-1809, 1229-1543, 1232-1818, 
               
               
                   
                 1233-1555, 1235-1529, 1237-1691, 1238-1540, 1242-1440, 
               
               
                   
                 1245-1518, 1246-1744, 1247-1557, 1248-1885, 1250-1498, 1253-1700, 1256-1880, 
               
               
                   
                 1257-1897, 1260-1529, 1260-1540, 1262-1555, 
               
               
                   
                 1262-1560, 1262-1726, 1263-1528, 1263-1831, 1266-1630, 1277-1402, 1277-1500, 
               
               
                   
                 1277-1791, 1283-1562, 1290-1575, 1300-1557, 1300-1595, 
               
               
                   
                 1308-1565, 1313-1606, 1314-1558, 1319-1571, 1323-1515, 1323-1587, 1324-1598, 
               
               
                   
                 1329-1601, 1329-1758, 1331-1915, 1333-1556, 
               
               
                   
                 1335-1433, 1335-1574, 1335-1649, 1335-1795, 1336-1938, 1337-2009, 1338-1564, 
               
               
                   
                 1338-1595, 1341-1536, 1341-1582, 1341-1585, 1341-1627, 
               
               
                   
                 1341-1979, 1342-1978, 1343-1559, 1343-1606, 1348-1945, 1354-1599, 1354-1625, 
               
               
                   
                 1355-1605, 1356-1820, 1356-2137, 1362-1563, 
               
               
                   
                 1363-1898, 
               
               
                   
                 1369-1628, 1370-1649, 1371-1733, 1373-1644, 1375-1713, 1375-1837, 1383-1663, 
               
               
                   
                 1383-1692, 1383-1868, 1387-1573, 1390-1662, 1392-1636, 
               
               
                   
                 1395-1985, 1406-1677, 1406-1994, 1408-1864, 1409-1921, 1414-2040, 1414-2069, 
               
               
                   
                 1415-1921, 1416-1656, 1418-1834, 1419-1884, 
               
               
                   
                 1423-1694, 1423-1712, 1425-1876, 1431-1697, 1432-2029, 1434-1684, 1435-2015, 
               
               
                   
                 1438-1722, 1439-2037, 1442-1902, 1443-1964, 1447-1759, 
               
               
                   
                 1449-1726, 1450-1833, 1452-2089, 1460-1776, 1467-2074, 1468-1729, 1468-1947, 
               
               
                   
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                 1475-1749, 1476-1590, 1483-1734, 1485-1775, 1485-2127, 1494-1755, 1495-1752, 
               
               
                   
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                 1530-1769, 1530-1771, 1530-1772, 1530-1980, 1531-1816, 1531-2130, 1532-1813, 
               
               
                   
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                 1546-2120, 
               
               
                   
                 1546-2126, 1548-1825, 1548-1975, 1550-2049, 1551-1841, 1551-2101, 1555-1823, 
               
               
                   
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                 1578-1841, 1579-1847, 1579-1905, 1579-2099, 
               
               
                   
                 1581-1863, 1581-2174, 1582-1800, 1582-1833, 1584-1829, 1585-1837, 1587-1829, 
               
               
                   
                 1597-1842, 1598-1866, 1599-1748, 1599-2418, 1600-2132, 
               
               
                   
                 1616-1914, 1619-1791, 1622-2118, 1624-1945, 1624-2118, 1626-1866, 1632-2102, 
               
               
                   
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                 1646-1904, 1652-2194, 1653-1934, 1656-1931, 1664-1779, 1669-1938, 1670-2250, 
               
               
                   
                 1671-1907, 1671-1957, 1671-2256, 1673-2179, 1673-2256, 
               
               
                   
                 1675-1940, 1675-2179, 1679-1939, 1683-2182, 1684-1929, 1686-1932, 1686-2018, 
               
               
                   
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                 1706-1971, 1709-1959, 1709-1975, 1711-1972, 1713-1994, 1723-1881, 1723-1954, 
               
               
                   
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                 1734-1993, 1734-2015, 1739-2030, 1741-2125, 1745-2238, 1748-2076, 1751-2032, 
               
               
                   
                 1753-2057, 1753-2074, 1770-2304, 1778-1984, 
               
               
                   
                 1781-2050, 
               
               
                   
                 1781-2052, 1784-2093, 1794-2035, 1794-2077, 1794-2092, 1803-2081, 1804-2011, 
               
               
                   
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                 1824-2366, 1825-2123, 1826-1945, 1832-2089, 
               
               
                   
                 1843-2371, 1844-2147, 1844-2294, 1847-2090, 1848-2113, 1848-2150, 1852-2102, 
               
               
                   
                 1853-2071, 1853-2094, 1853-2108, 1853-2117, 1858-2128, 
               
               
                   
                 1859-2333, 1861-2339, 1862-2071, 1862-2074, 1862-2160, 1863-2027, 1863-2173, 
               
               
                   
                 1865-2448, 1867-2102, 1867-2118, 1867-2225, 
               
               
                   
                 1868-2169, 1875-2135, 1876-2119, 1877-2134, 1877-2146, 1877-2396, 1880-2057, 
               
               
                   
                 1880-2130, 1880-2185, 1881-2143, 1886-2126, 1886-2133, 
               
               
                   
                 1890-2422, 1897-2131, 1903-2208, 1904-2451, 1910-2437, 1913-2362, 1914-2067, 
               
               
                   
                 1915-2409, 1921-2109, 1922-2170, 1922-2182, 
               
               
                   
                 1925-2226, 1933-2425, 1942-2423, 1943-2441, 1944-2122, 1944-2129, 1944-2441, 
               
               
                   
                 1948-2094, 1950-2119, 1950-2196, 1950-2423, 1961-2437, 
               
               
                   
                 1961-2444, 1962-2425, 1965-2440, 1969-2133, 1969-2194, 1973-2440, 1974-2271, 
               
               
                   
                 1975-2425, 1976-2423, 1978-2431, 1981-2402, 
               
               
                   
                 1982-2420, 
               
               
                   
                 1982-2427, 1984-2239, 1985-2421, 1986-2455, 1999-2370, 2000-2161, 2000-2443, 
               
               
                   
                 2001-2133, 2002-2449, 2003-2420, 2004-2236, 2004-2440, 
               
               
                   
                 2005-2421, 2005-2422, 2005-2447, 2006-2364, 2006-2422, 2007-2420, 2007-2443, 
               
               
                   
                 2011-2427, 2011-2449, 2012-2237, 2012-2263, 
               
               
                   
                 2012-2269, 2012-2424, 2012-2426, 2014-2423, 2015-2422, 2018-2440, 2022-2117, 
               
               
                   
                 2024-2421, 2027-2376, 2028-2422, 2029-2315, 2030-2324, 
               
               
                   
                 2030-2420, 2031-2422, 2032-2423, 2033-2443, 2034-2422, 2035-2442, 2036-2171, 
               
               
                   
                 2036-2419, 2040-2420, 2044-2422, 2047-2419, 
               
               
                   
                 2048-2422, 2048-2429, 2055-2423, 2056-2333, 2056-2419, 2057-2422, 2065-2419, 
               
               
                   
                 2068-2437, 2070-2321, 2070-2422, 2080-2439, 2085-2422, 
               
               
                   
                 2086-2417, 2087-2422, 2090-2424, 2091-2420, 2091-2424, 2093-2370, 2094-2420, 
               
               
                   
                 2098-2347, 2098-2422, 2099-2422, 2100-2419, 
               
               
                   
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                 2136-2419, 2136-2422, 2137-2418, 2143-2404, 2145-2388, 
               
               
                   
                 2151-2419, 2154-2443, 2162-2392, 2168-2431, 2169-2434, 2172-2448, 2175-2434, 
               
               
                   
                 2183-2274, 2191-2422, 2191-2432, 2191-2442, 
               
               
                   
                 2193-2431, 
               
               
                   
                 2198-2395, 2198-2436, 2200-2373, 2200-2435, 2202-2422, 2205-2422, 2210-2402, 
               
               
                   
                 2216-2419, 2224-2432, 2230-2420, 2233-2419, 2235-2455, 
               
               
                   
                 2239-2419, 2247-2415, 2247-2432, 2250-2457, 2251-2420, 2253-2422, 2253-2426, 
               
               
                   
                 2257-2423, 2277-2529, 2308-2498, 2310-2419, 
               
               
                   
                 2325-2417, 2338-2514, 2348-2461, 2348-2477, 2359-2467 
               
               
                 36/7506656CB1/ 
                 1-616, 5-2763, 17-500, 17-608, 17-631, 23-471, 31-250, 32-324, 67-253, 
               
               
                 2763 
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                 521-760, 522-799, 523-799, 527-754, 529-662, 539-720, 551-637, 568-1028, 
               
               
                   
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                 797-1053, 797-1059, 
               
               
                   
                 797-1070, 797-1082, 797-1092, 797-1137, 797-1157, 797-1164, 797-1298, 797-1452, 
               
               
                   
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                 806-924, 809-1521, 812-1090, 813-1051, 813-1060, 813-1241, 813-1487, 814-1053, 
               
               
                   
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                 881-1129, 882-1134, 882-1339, 882-1377, 882-1508, 
               
               
                   
                 883-1135, 883-1144, 883-1145, 883-1149, 884-1541, 886-1510, 889-1178, 889-1652, 
               
               
                   
                 892-1164, 892-1448, 893-1015, 893-1119, 893-1147, 
               
               
                   
                 893-1175, 894-1297, 896-1150, 896-1175, 897-1143, 897-1158, 897-1184, 899-1105, 
               
               
                   
                 899-1132, 899-1192, 899-1410, 
               
               
                   
                 900-1067, 901-1145, 901-1167, 901-1359, 903-1055, 903-1158, 905-1136, 905-1173, 
               
               
                   
                 905-1176, 910-1161, 910-1486, 911-1176, 911-1472, 
               
               
                   
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                 923-1369, 933-1048, 937-1390, 939-1184, 941-1163, 
               
               
                   
                 941-1165, 941-1173, 941-1174, 943-1198, 944-1366, 946-1476, 948-1224, 952-1484, 
               
               
                   
                 954-1618, 955-1101, 955-1221, 955-1443, 955-1498, 
               
               
                   
                 956-1262, 959-1273, 959-1547, 960-1579, 961-1136, 961-1270, 962-1146, 962-1212, 
               
               
                   
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                 999-1233, 1002-1139, 1002-1214, 1003-1305, 1003-1401, 1005-1511, 1006-1244, 1006-1254, 
               
               
                   
                 1008-1482, 1008-1780, 1009-1204, 1009-1267, 
               
               
                   
                 1009-1294, 1009-1606, 1010-1274, 1010-1315, 1011-1303, 1012-1275, 1013-1267, 1013-1278, 
               
               
                   
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                 1015-1542, 1017-1672, 1021-1313, 1023-1522, 1025-1607, 1027-1235, 1027-1294, 1027-1301, 
               
               
                   
                 1027-1308, 1030-1279, 1030-1284, 
               
               
                   
                 1031-1621, 1039-1324, 1039-1584, 1040-1475, 1041-1546, 1043-1353, 1044-1636, 1047-1329, 
               
               
                   
                 1048-1295, 1055-1347, 1057-1456, 1059-1311, 
               
               
                   
                 1060-1305, 1065-1270, 1065-1371, 1065-1653, 1068-1655, 1072-1264, 1072-1360, 1072-1518, 
               
               
                   
                 1072-1549, 1073-1389, 1077-1229, 
               
               
                   
                 1077-1232, 1079-1522, 1079-1644, 1083-1623, 1085-1200, 1085-1355, 1088-1342, 1088-1365, 
               
               
                   
                 1088-1655, 1090-1300, 1094-1339, 1096-1395, 
               
               
                   
                 1096-1588, 1099-1388, 1103-1384, 1103-1627, 1109-1502, 1109-1561, 1110-1592, 1115-1640, 
               
               
                   
                 1117-1374, 1117-1699, 1122-1584, 
               
               
                   
                 1122-1595, 1124-1383, 1125-1582, 1126-1401, 1126-1644, 1129-1357, 1129-1512, 1132-1388, 
               
               
                   
                 1132-1680, 1133-1632, 1138-1404, 1139-1373, 
               
               
                   
                 1139-1414, 1140-1385, 1141-1477, 1141-1487, 1143-1630, 1144-1318, 1144-1602, 1144-1607, 
               
               
                   
                 1145-1652, 1147-1385, 1147-1573, 
               
               
                   
                 1149-1655, 1150-1416, 1150-1421, 1150-1432, 1150-1637, 1151-1831, 1152-1398, 1152-1434, 
               
               
                   
                 1152-1640, 1156-1405, 1156-1442, 1157-1808, 
               
               
                   
                 1158-1648, 1159-1405, 1161-1391, 1161-1494, 1162-1449, 1162-1463, 1162-1472, 1163-1420, 
               
               
                   
                 1164-1739, 1168-1697, 1169-1641, 
               
               
                   
                 1171-1390, 
               
               
                   
                 1171-1414, 1171-1434, 1178-1449, 1178-1466, 1179-1963, 1181-1442, 1183-1400, 1186-1336, 
               
               
                   
                 1186-1598, 1188-1448, 1190-1476, 1190-1485, 
               
               
                   
                 1190-1666, 1192-1430, 1192-1472, 1192-1651, 1195-1433, 1198-1479, 1205-1588, 1207-1436, 
               
               
                   
                 1210-1456, 1211-1442, 1211-1481, 
               
               
                   
                 1211-1490, 1211-1508, 1211-1551, 1211-1598, 1213-1396, 1213-1509, 1213-1818, 1225-1476, 
               
               
                   
                 1225-1518, 1229-1520, 1229-1655, 1233-1629, 
               
               
                   
                 1235-1335, 1235-1655, 1240-1499, 1242-1458, 1242-1896, 1248-1433, 1248-1440, 1248-1536, 
               
               
                   
                 1249-1540, 1251-1449, 1253-1509, 
               
               
                   
                 1253-1562, 1253-1636, 1253-1654, 1255-1461, 1256-1529, 1258-1549, 1258-1589, 1258-1653, 
               
               
                   
                 1258-1655, 1260-1502, 1262-1552, 1264-1543, 
               
               
                   
                 1269-1538, 1274-1604, 1275-1628, 1276-1545, 1276-1871, 1278-1604, 1278-1632, 1281-1536, 
               
               
                   
                 1282-1492, 1282-1511, 1285-1574, 
               
               
                   
                 1285-1788, 1290-1496, 1290-1709, 1290-1729, 1290-1795, 1290-1838, 1290-1858, 1290-1867, 
               
               
                   
                 1291-1501, 1292-1712, 1294-1558, 1294-1566, 
               
               
                   
                 1295-1582, 1295-1583, 1295-1593, 1296-1578, 1297-1530, 1297-1546, 1297-1747, 1297-1786, 
               
               
                   
                 1298-1559, 1298-1593, 1299-1540, 
               
               
                   
                 1299-1897, 
               
               
                   
                 1303-1419, 1305-1559, 1305-1562, 1310-2024, 1311-1571, 1312-1494, 1312-2153, 1321-1636, 
               
               
                   
                 1324-1593, 1327-1573, 1335-1589, 1338-1553, 
               
               
                   
                 1341-1636, 1344-1513, 1345-1595, 1352-1655, 1354-1616, 1355-1562, 1355-1620, 1355-1655, 
               
               
                   
                 1356-1511, 1356-1588, 1357-1596, 
               
               
                   
                 1358-1486, 1360-1524, 1360-1590, 1360-1596, 1360-1604, 1360-1606, 1360-1617, 1360-1618, 
               
               
                   
                 1360-1627, 1360-1655, 1360-1659, 1361-1664, 
               
               
                   
                 1362-1661, 1363-1624, 1367-1625, 1367-1641, 1368-1573, 1371-1520, 1371-1655, 1371-1659, 
               
               
                   
                 1373-1623, 1373-2041, 1377-1635, 
               
               
                   
                 1381-1628, 1383-1655, 1384-1606, 1384-1655, 1384-1858, 1387-1588, 1387-1606, 1387-1613, 
               
               
                   
                 1387-1632, 1387-1636, 1387-1646, 1387-1655, 
               
               
                   
                 1389-1607, 1389-1655, 1394-1686, 1398-1651, 1402-1615, 1402-1623, 1404-1625, 1404-1708, 
               
               
                   
                 1407-1640, 1410-1674, 1412-1655, 
               
               
                   
                 1412-1663, 1416-1877, 1423-1709, 1424-1671, 1429-1621, 1432-1655, 1436-1655, 1436-2007, 
               
               
                   
                 1437-1965, 1438-1607, 1439-1597, 1439-1674, 
               
               
                   
                 1442-1729, 1444-2006, 1448-1604, 1448-1671, 1452-2002, 1455-1754, 1455-1760, 1458-2093, 
               
               
                   
                 1459-1579, 1459-1747, 1461-1655, 
               
               
                   
                 1462-1529, 
               
               
                   
                 1462-1809, 1463-1728, 1465-1655, 1472-1720, 1473-2050, 1477-1760, 1479-1679, 1483-2073, 
               
               
                   
                 1491-1797, 1492-1736, 1493-1781, 1502-1772, 
               
               
                   
                 1502-1798, 1503-1750, 1504-1626, 1509-1758, 1509-1767, 1509-2078, 1513-1786, 1519-1959, 
               
               
                   
                 1522-1814, 1525-1767, 1525-1825, 
               
               
                   
                 1530-1787, 1530-1814, 1530-2084, 1530-2098, 1531-2235, 1533-1798, 1544-1723, 1544-1777, 
               
               
                   
                 1546-1812, 1546-1813, 1546-1823, 1546-1870, 
               
               
                   
                 1546-2064, 1550-1824, 1550-1830, 1550-1888, 1551-2123, 1552-1804, 1562-2147, 1567-1881, 
               
               
                   
                 1570-2156, 1571-1893, 1573-1867, 
               
               
                   
                 1574-1820, 1575-2029, 1576-1878, 1580-1778, 1583-1856, 1584-2082, 1585-1895, 1586-2223, 
               
               
                   
                 1588-1836, 1591-2038, 1594-2218, 1595-2235, 
               
               
                   
                 1598-1867, 1598-1878, 1600-1893, 1600-1898, 1600-2064, 1601-1866, 1601-2169, 1604-1968, 
               
               
                   
                 1615-1740, 1615-1838, 1615-2129, 
               
               
                   
                 1621-1900, 1628-1913, 1638-1895, 1638-1933, 1646-1903, 1651-1944, 1652-1896, 1657-1909, 
               
               
                   
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                 1667-2096, 1669-2253, 1671-1894, 1673-1771, 1673-1912, 1673-1987, 1673-2133, 1674-2276, 
               
               
                   
                 1675-2347, 1676-1902, 1676-1933, 
               
               
                   
                 1679-1874, 
               
               
                   
                 1679-1920, 1679-1923, 1679-1965, 1679-2317, 1680-2316, 1681-1897, 1681-1944, 1686-2283, 
               
               
                   
                 1692-1937, 1692-1963, 1693-1943, 1694-2158, 
               
               
                   
                 1694-2475, 1700-1901, 1701-2236, 1707-1966, 1708-1987, 1709-2071, 1711-1982, 1713-2051, 
               
               
                   
                 1713-2175, 1721-2001, 1721-2030, 
               
               
                   
                 1721-2206, 1725-1911, 1728-2000, 1730-1974, 1733-2323, 1744-2015, 1744-2332, 1746-2202, 
               
               
                   
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                 1754-1994, 1756-2172, 1757-2222, 1761-2032, 1761-2050, 1763-2214, 1769-2035, 1770-2367, 
               
               
                   
                 1772-2022, 1773-2353, 1776-2060, 
               
               
                   
                 1777-2375, 1780-2240, 1781-2302, 1785-2097, 1787-2064, 1788-2171, 1790-2427, 1798-2114, 
               
               
                   
                 1805-2412, 1806-2067, 1806-2285, 1808-2274, 
               
               
                   
                 1810-2279, 1812-2064, 1812-2073, 1813-2087, 1814-1928, 1821-2072, 1823-2113, 1823-2465, 
               
               
                   
                 1832-2093, 1833-2090, 1837-2084, 
               
               
                   
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                 1871-2115, 
               
               
                   
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                 1889-2439, 1893-2161, 1893-2309, 
               
               
                   
                 1894-2183, 1894-2432, 1900-2156, 1901-2270, 1903-2377, 1904-2191, 1905-2177, 1914-2160, 
               
               
                   
                 1914-2168, 1916-2160, 1916-2177, 1916-2179, 
               
               
                   
                 1917-2185, 1917-2243, 1917-2437, 1919-2201, 1919-2512, 1920-2138, 1920-2171, 1922-2167, 
               
               
                   
                 1923-2175, 1925-2167, 1935-2180, 
               
               
                   
                 1936-2204, 1937-2086, 1937-2756, 1938-2470, 1954-2252, 1957-2129, 1960-2456, 1962-2283, 
               
               
                   
                 1962-2456, 1964-2204, 1970-2440, 1972-2248, 
               
               
                   
                 1973-2225, 1979-2434, 1982-2647, 1990-2532, 1991-2272, 1994-2269, 2002-2117, 2002-2252, 
               
               
                   
                 2007-2276, 2008-2588, 2009-2245, 
               
               
                   
                 2009-2295, 2009-2594, 2011-2517, 2011-2594, 2013-2278, 2013-2517, 2017-2277, 2021-2520, 
               
               
                   
                 2022-2267, 2024-2270, 2024-2356, 2026-2325, 
               
               
                   
                 2032-2296, 2033-2275, 2044-2309, 2047-2274, 2047-2297, 2047-2313, 2049-2310, 2051-2332, 
               
               
                   
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                 2062-2327, 
               
               
                   
                 2062-2552, 2068-2412, 2072-2308, 2072-2331, 2072-2353, 2077-2368, 2079-2463, 2083-2576, 
               
               
                   
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                 37/7510567CB1/ 
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                 2454 
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                 1-431, 1-624, 1-2250, 124-515, 124-842, 255-1214, 305-1214, 386-495, 
               
               
                 2255 
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                 1823-2218, 
               
               
                   
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                 1934-2095, 1934-2227, 1947-2227, 1949-2227, 
               
               
                   
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                 39/7511354CB1/ 
                 1-251, 1-609, 12-305, 12-544, 13-511, 13-666, 14-613, 14-657, 14-674, 
               
               
                 2285 
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                 54/7511894CB1/ 
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                 57/7512812CB1/ 
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                 2292 
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                 1877-2161, 1878-2544, 1885-2119, 1893-2111, 1893-2490, 1899-2167, 
               
               
                   
                 1900-2400, 1903-2563, 1903-2571, 1910-2177, 1911-2460, 1911-2580, 
               
               
                   
                 1912-2171, 1912-2183, 1916-2403, 1917-2197, 1918-2216, 
               
               
                   
                 1918-2505, 1920-2567, 1921-2168, 1925-2478, 1925-2511, 1926-2174, 
               
               
                   
                 1927-2160, 1928-2167, 1928-2460, 1930-2217, 1931-2479, 1932-2187, 
               
               
                   
                 1936-2205, 1936-2210, 1936-2460, 1937-2460, 1939-2240, 1940-2507, 
               
               
                   
                 1941-2182, 1941-2460, 1943-2579, 1946-2456, 1946-2739, 
               
               
                   
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                 1971-2527, 1972-2152, 1972-2754, 1974-2402, 1974-2489, 1978-2459, 
               
               
                   
                 1979-2252, 1979-2256, 1984-2211, 1984-2754, 1988-2592, 
               
               
                   
                 1990-2466, 
               
               
                   
                 1996-2420, 1996-2477, 1997-2544, 2002-2275, 2003-2592, 2008-2285, 
               
               
                   
                 2009-2271, 2015-2273, 2015-2290, 2017-2270, 2017-2271, 2020-2755, 
               
               
                   
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                 2073-2364, 2073-2476, 2074-2738, 2076-2588, 2083-2362, 2084-2476, 
               
               
                   
                 2084-2694, 2088-2340, 2088-2352, 2088-2556, 2089-2442, 
               
               
                   
                 2094-2460, 2096-2385, 2096-2389, 2098-2324, 2100-2460, 2102-2398, 
               
               
                   
                 2102-2710, 2102-2753, 2103-2342, 2104-2390, 2107-2460, 2109-2346, 
               
               
                   
                 2114-2423, 2117-2300, 2117-2368, 2117-2386, 2121-2337, 2124-2375, 
               
               
                   
                 2131-2369, 2131-2386, 2135-2754, 2137-2680, 2137-2747, 
               
               
                   
                 2140-2617, 2141-2163, 2141-2320, 2141-2460, 2141-2476, 2142-2460, 
               
               
                   
                 2144-2695, 2144-2755, 2146-2460, 2147-2363, 2147-2460, 2152-2402, 
               
               
                   
                 2154-2439, 2154-2445, 2156-2257, 2156-2460, 2158-2755, 2159-2402, 
               
               
                   
                 2159-2413, 2159-2426, 2159-2460, 2159-2592, 2161-2460, 
               
               
                   
                 2162-2453, 
               
               
                   
                 2163-2439, 2171-2455, 2176-2439, 2176-2442, 2176-2463, 2184-2432, 
               
               
                   
                 2187-2755, 2192-2458, 2192-2481, 2195-2753, 2198-2473, 2200-2420, 
               
               
                   
                 2200-2460, 2203-2480, 2204-2470, 2205-2460, 2207-2389, 2208-2460, 
               
               
                   
                 2214-2438, 2215-2360, 2215-2497, 2216-2460, 2219-2501, 
               
               
                   
                 2221-2385, 2221-2460, 2221-2479, 2221-2500, 2228-2460, 2229-2739, 
               
               
                   
                 2231-2514, 2234-2445, 2234-2501, 2234-2504, 2234-2512, 2236-2725, 
               
               
                   
                 2237-2460, 2240-2532, 2244-2486, 2249-2473, 2251-2449, 2252-2533, 
               
               
                   
                 2252-2541, 2253-2410, 2254-2460, 2265-2468, 2266-2460, 
               
               
                   
                 2269-2474, 2278-2460, 2278-2532, 2297-2517, 2299-2722, 2303-2458, 
               
               
                   
                 2304-2570, 2305-2753, 2310-2588, 2311-2473, 2317-2460, 2317-2486, 
               
               
                   
                 2318-2644, 2322-2460, 2323-2755, 2324-2474, 2332-2460, 2340-2603, 
               
               
                   
                 2341-2555, 2343-2460, 2345-2736, 2346-2460, 2347-2460, 
               
               
                   
                 2348-2754, 2349-2628, 2351-2615, 2356-2605, 2359-2530, 2361-2597, 
               
               
                   
                 2367-2460, 2371-2462, 2373-2460, 2378-2463, 2384-2460, 2388-2460, 
               
               
                   
                 2391-2583, 2397-2737, 2398-2755, 2402-2473, 2406-2639, 2409-2460, 
               
               
                   
                 2563-2644 
               
               
                 59/7512908CB1/ 
                 1-554, 9-1708, 11-729, 19-828, 28-642, 30-260, 32-304, 
               
               
                 1708 
                 35-266, 36-272, 37-754, 38-799, 44-736, 45-245, 47-640, 51-187, 
               
               
                   
                 56-355, 72-312, 
               
               
                   
                 111-395, 165-839, 221-432, 221-458, 250-533, 250-610, 250-673, 
               
               
                   
                 255-516, 256-757, 259-533, 260-1123, 262-995, 263-576, 265-521, 273-895, 
               
               
                   
                 311-929, 316-973, 317-919, 332-606, 336-929, 340-603, 340-774, 
               
               
                   
                 340-869, 340-1007, 340-1095, 340-1103, 348-608, 348-614, 350-781, 
               
               
                   
                 350-962, 359-1059, 368-742, 368-863, 382-667, 389-670, 392-638, 
               
               
                   
                 392-639, 393-984, 400-946, 400-987, 401-680, 413-781, 420-682, 
               
               
                   
                 425-1120, 434-687, 437-1055, 448-1100, 460-884, 464-1017, 479-742, 
               
               
                   
                 480-741, 486-729, 486-768, 491-1068, 498-738, 501-752, 507-802, 
               
               
                   
                 509-719, 511-764, 533-846, 536-1124, 540-765, 544-774, 552-1115, 
               
               
                   
                 562-824, 601-878, 601-910, 604-1019, 606-844, 608-1124, 613-1116, 
               
               
                   
                 613-1121, 618-910, 627-882, 627-890, 629-850, 649-926, 649-934, 
               
               
                   
                 650-898, 650-913, 680-992, 685-847, 695-952, 705-834, 727-964, 
               
               
                   
                 727-1040, 
               
               
                   
                 727-1116, 728-989, 729-995, 753-1059, 759-908, 759-1017, 775-982, 
               
               
                   
                 775-1124, 776-1032, 789-1060, 
               
               
                   
                 799-1044, 804-1087, 819-1051, 824-1060, 825-1124, 828-1124, 856-961, 
               
               
                   
                 868-1124, 873-1079, 873-1124, 877-1124, 885-1075, 885-1119, 
               
               
                   
                 888-1124, 900-1109, 901-1124, 905-1068, 905-1124, 906-1114, 916-1124, 
               
               
                   
                 933-1036, 939-1108, 972-1122, 1071-1597, 1115-1597, 1122-1461, 
               
               
                   
                 1123-1343, 1123-1421, 1123-1496, 1123-1533, 1123-1557, 1123-1574, 
               
               
                   
                 1123-1582, 1123-1593, 1123-1594, 1123-1603, 1124-1594, 
               
               
                   
                 1124-1595, 1124-1599, 1125-1597, 1126-1327, 1126-1594, 1127-1590, 
               
               
                   
                 1127-1594, 1128-1603, 1131-1594, 1131-1599, 1131-1603, 1132-1594, 
               
               
                   
                 1133-1594, 1133-1603, 1134-1392, 1134-1603, 1138-1594, 1139-1594, 
               
               
                   
                 1140-1594, 1142-1594, 1152-1594, 1154-1563, 1154-1578, 
               
               
                   
                 1154-1596, 1154-1603, 1157-1594, 1157-1603, 1159-1578, 1161-1345, 
               
               
                   
                 1162-1585, 1162-1597, 1162-1603, 1163-1578, 1163-1601, 1164-1594, 
               
               
                   
                 1165-1578, 1173-1602, 1174-1585, 1175-1594, 1175-1597, 1177-1578, 
               
               
                   
                 1177-1594, 1182-1594, 1183-1416, 1183-1601, 1185-1578, 
               
               
                   
                 1186-1389, 1186-1423, 1186-1603, 1187-1594, 1189-1603, 1199-1442, 
               
               
                   
                 1199-1592, 1199-1593, 1200-1634, 1203-1526, 1204-1593, 1204-1594, 
               
               
                   
                 1209-1456, 1214-1326, 1220-1603, 1225-1486, 1227-1603, 1232-1598, 
               
               
                   
                 1235-1507, 1238-1544, 1240-1585, 1241-1594, 1242-1516, 1244-1594, 
               
               
                   
                 1253-1585, 1255-1528, 1259-1575, 1259-1594, 1262-1585, 1263-1602, 
               
               
                   
                 1263-1603, 1268-1594, 1268-1603, 1272-1594, 1274-1576, 
               
               
                   
                 1284-1585, 1284-1603, 1285-1549, 1296-1603, 1316-1584, 1345-1594, 
               
               
                   
                 1354-1602, 1371-1603, 1387-1594, 1392-1597, 1396-1603, 1401-1594, 
               
               
                   
                 1409-1594, 1427-1534, 1430-1603, 1436-1578, 1442-1602, 1448-1597, 
               
               
                   
                 1453-1594, 1470-1704 
               
               
                 60/7512909CB1/ 
                 1-554, 9-1637, 11-729, 19-828, 28-642, 30-260, 32-304, 35-266, 
               
               
                 1637 
                 36-272, 37-754, 38-799, 44-736, 45-245, 47-640, 51-187, 56-355, 72-312, 
               
               
                   
                 111-395, 165-839, 221-432, 221-458, 250-533, 250-610, 250-673, 255-516, 
               
               
                   
                 256-757, 259-533, 260-1132, 262-995, 263-576, 265-521, 273-895, 
               
               
                   
                 311-929, 316-973, 317-919, 332-606, 336-929, 340-603, 340-774, 340-869, 
               
               
                   
                 340-1007, 340-1095, 340-1103, 348-608, 348-614, 350-781, 
               
               
                   
                 350-962, 359-1059, 368-742, 368-863, 382-667, 388-1260, 389-670, 
               
               
                   
                 392-638, 392-639, 393-984, 400-946, 400-987, 401-680, 413-781, 
               
               
                   
                 420-682, 425-1120, 434-687, 437-1055, 448-1100, 460-884, 464-1017, 
               
               
                   
                 479-742, 480-741, 486-729, 486-768, 491-1068, 498-738, 501-752, 
               
               
                   
                 507-802, 509-719, 511-764, 533-846, 536-1160, 540-765, 544-774, 551-1196, 
               
               
                   
                 552-1201, 562-824, 601-878, 601-910, 604-1019, 606-844, 
               
               
                   
                 608-1249, 613-1116, 613-1121, 613-1177, 613-1221, 613-1240, 613-1247, 
               
               
                   
                 613-1288, 618-910, 627-882, 627-890, 629-850, 636-1157, 649-926, 
               
               
                   
                 649-934, 650-898, 650-913, 662-1313, 664-1258, 680-992, 685-847, 
               
               
                   
                 695-952, 698-1332, 705-834, 
               
               
                   
                 717-1174, 721-1301, 727-964, 727-1040, 727-1116, 728-989, 729-995, 
               
               
                   
                 729-1270, 729-1344, 750-1272, 753-1059, 759-908, 759-1017, 769-1326, 
               
               
                   
                 769-1377, 775-982, 775-1253, 776-1032, 776-1348, 779-1348, 782-1332, 
               
               
                   
                 788-1377, 789-1060, 792-1234, 795-1367, 797-1221, 799-1044, 
               
               
                   
                 804-1087, 812-1346, 819-1051, 824-1060, 825-1280, 828-1262, 849-1523, 
               
               
                   
                 856-961, 862-1162, 868-1143, 873-1079, 873-1136, 875-1369, 
               
               
                   
                 877-1130, 880-1153, 881-1202, 885-1075, 885-1133, 888-1132, 893-1369, 
               
               
                   
                 900-1109, 900-1150, 901-1214, 905-1068, 905-1132, 905-1140, 
               
               
                   
                 905-1385, 906-1167, 916-1158, 916-1172, 918-1286, 929-1158, 929-1297, 
               
               
                   
                 929-1355, 929-1385, 933-1036, 933-1354, 939-1108, 941-1385, 
               
               
                   
                 943-1228, 944-1178, 972-1301, 972-1367, 972-4384, 978-1192, 982-1346, 
               
               
                   
                 995-1245, 1013-1298, 1016-1260, 1017-1272, 1017-1282, 
               
               
                   
                 1029-1205, 1030-1252, 1031-1306, 1039-1289, 1039-1301, 1049-1254, 
               
               
                   
                 1054-1322, 1055-1333, 1059-1301, 1064-1354, 1069-1281, 1076-1327, 
               
               
                   
                 1086-1384, 1100-1354, 1103-1361, 1106-1343, 1110-1385, 1145-1243, 
               
               
                   
                 1176-1385, 1179-1385, 1193-1385, 1383-1526, 
               
               
                   
                 1385-1507, 1385-1523, 1385-1531, 1385-1532, 1386-1526, 1399-1633 
               
               
                 61/7512769CB1/ 
                 1-654, 7-264, 10-302, 11-1866, 12-292, 13-347, 15-241, 16-238, 
               
               
                 1866 
                 17-146, 17-310, 25-214, 25-326, 33-331, 34-193, 34-276, 34-285, 34-287, 
               
               
                   
                 34-288, 34-291, 34-296, 34-305, 35-213, 35-279, 35-316, 36-145, 36-221, 
               
               
                   
                 36-258, 36-273, 36-284, 36-287, 36-306, 36-311, 36-314, 36-316, 
               
               
                   
                 36-317, 36-491, 36-581, 36-617, 36-657, 37-289, 37-309, 37-326, 
               
               
                   
                 37-347, 39-309, 40-272, 40-347, 41-257, 41-267, 41-272, 41-296, 41-331, 
               
               
                   
                 41-347, 42-274, 42-313, 42-340, 44-276, 44-281, 44-286, 44-288, 
               
               
                   
                 44-328, 46-296, 46-347, 61-261, 85-247, 154-318, 168-257, 179-837, 
               
               
                   
                 190-305, 
               
               
                   
                 193-472, 230-292, 346-511, 346-566, 346-580, 346-592, 346-809, 
               
               
                   
                 346-821, 352-569, 354-604, 359-630, 361-597, 369-621, 373-922, 
               
               
                   
                 379-656, 383-616, 390-580, 391-655, 410-915, 411-647, 420-1012, 
               
               
                   
                 420-1074, 432-525, 432-808, 437-730, 439-1072, 441-751, 450-1011, 
               
               
                   
                 461-705, 463-1186, 463-1235, 464-695, 467-710, 468-889, 469-984, 
               
               
                   
                 470-722, 484-1123, 490-784, 497-1053, 501-782, 514-1362, 521-750, 
               
               
                   
                 521-1010, 546-1015, 546-1223, 546-1294, 552-753, 552-911, 552-1291, 
               
               
                   
                 552-1331, 557-1084, 
               
               
                   
                 557-1362, 560-679, 563-1362, 571-781, 571-1029, 604-1220, 608-876, 
               
               
                   
                 610-698, 618-889, 626-1188, 636-846, 637-920, 641-901, 646-1362, 
               
               
                   
                 659-1178, 659-1218, 659-1343, 664-799, 669-955, 669-1057, 692-1176, 
               
               
                   
                 694-1113, 697-1005, 701-1099, 701-1224, 720-1244, 721-978, 728-1157, 
               
               
                   
                 729-977, 732-1329, 740-1335, 742-1349, 742-1426, 747-1424, 752-1385, 
               
               
                   
                 771-1049, 781-1508, 788-1286, 791-1154, 791-1298, 792-1154, 
               
               
                   
                 793-1298, 797-1063, 798-1507, 799-1065, 799-1101, 799-1591, 815-1507, 
               
               
                   
                 817-1019, 841-1222, 842-1794, 856-1170, 869-1506, 877-1539, 
               
               
                   
                 878-1508, 879-1017, 879-1172, 879-1508, 882-1539, 884-1464, 888-1103, 
               
               
                   
                 903-1352, 905-1513, 906-1526, 929-1060, 931-1249, 937-1546, 
               
               
                   
                 938-1196, 941-1455, 959-1175, 960-1237, 972-1281, 977-1402, 980-1291, 
               
               
                   
                 984-1247, 986-1722, 987-1211, 987-1258, 992-1226, 993-1278, 
               
               
                   
                 995-1599, 999-1269, 1012-1251, 1019-1284, 1019-1728, 1026-1279, 1026-1618, 
               
               
                   
                 1027-1312, 1030-1604, 1032-1265, 1032-1508, 
               
               
                   
                 1034-1284, 1035-1322, 1037-1325, 1037-1639, 1049-1282, 1049-1312, 
               
               
                   
                 1049-1636, 1056-1313, 1063-1747, 1065-1325, 
               
               
                   
                 1066-1654, 1069-1312, 1077-1323, 1081-1218, 1082-1365, 1083-1341, 
               
               
                   
                 1086-1654, 1095-1353, 1111-1424, 1112-1792, 1118-1569, 1118-1609, 
               
               
                   
                 1121-1463, 1121-1576, 1121-1619, 1121-1621, 1130-1639, 1153-1445, 
               
               
                   
                 1153-1743, 1159-1445, 1163-1616, 1164-1419, 1165-1455, 
               
               
                   
                 1167-1457, 1169-1476, 1171-1448, 1172-1442, 1176-1351, 1178-1399, 
               
               
                   
                 1178-1403, 1182-1759, 1188-1799, 1197-1351, 1198-1428, 1199-1458, 
               
               
                   
                 1202-1569, 1214-1725, 1219-1701, 1221-1481, 1222-1492, 1222-1515, 
               
               
                   
                 1222-1516, 1236-1446, 1239-1507, 1244-1720, 1245-1473, 
               
               
                   
                 1246-1542, 1247-1496, 1251-1598, 1252-1502, 1253-1734, 1255-1520, 
               
               
                   
                 1256-1760, 1270-1540, 1272-1764, 1276-1515, 1277-1494, 1279-1799, 
               
               
                   
                 1284-1794, 1292-1727, 1298-1750, 1301-1477, 1303-1766, 1304-1733, 
               
               
                   
                 1305-1748, 1310-1594, 1314-1786, 1323-1614, 1328-1725, 
               
               
                   
                 1331-1794, 1332-1579, 1332-1781, 1337-1595, 1337-1742, 1337-1792, 
               
               
                   
                 1343-1794, 1348-1795, 1349-1620, 1354-1741, 1358-1536, 1362-1799, 
               
               
                   
                 1372-1792, 1372-1794, 1373-1799, 1374-1604, 1374-1791, 1374-1794, 
               
               
                   
                 1378-1627, 1381-1792, 1382-1780, 1385-1640, 1388-1799, 
               
               
                   
                 1406-1641, 
               
               
                   
                 1406-1688, 1409-1799, 1409-1866, 1411-1718, 1413-1794, 1415-1707, 
               
               
                   
                 1415-1793, 1432-1676, 1432-1791, 1437-1691, 1441-1617, 1441-1799, 
               
               
                   
                 1442-1646, 1443-1793, 1443-1794, 1446-1663, 1449-1799, 1455-1713, 
               
               
                   
                 1456-1801, 1467-1794, 1472-1793, 1478-1793, 1480-1793, 
               
               
                   
                 1487-1799, 1499-1767, 1507-1769, 1508-1771, 1508-1799, 1508-1801, 
               
               
                   
                 1522-1852, 1557-1799, 1601-1794, 1601-1866, 1602-1735, 1602-1793, 
               
               
                   
                 1602-1794, 1605-1794, 1606-1678, 1607-1801, 1610-1854, 1621-1799, 
               
               
                   
                 1635-1793, 1635-1794, 1650-1793, 1685-1801, 1747-1783 
               
               
                 62/7512871CB1/ 
                 1-234, 1-235, 1-240, 1-241, 1-265, 1-300, 1-422, 1-444, 
               
               
                 1191 
                 1-447, 1-452, 1-494, 1-497, 1-509, 1-511, 1-516, 1-559, 4-535, 
               
               
                   
                 5-383, 5-663, 6-234, 
               
               
                   
                 6-254, 6-361, 6-412, 6-486, 6-528, 6-585, 6-622, 6-1191, 7-703, 
               
               
                   
                 8-251, 9-182, 9-423, 9-591, 12-220, 12-232, 12-273, 14-259, 14-278, 
               
               
                   
                 14-701, 
               
               
                   
                 15-243, 15-250, 15-546, 16-245, 16-624, 22-662, 27-227, 27-235, 
               
               
                   
                 27-252, 28-247, 28-263, 33-245, 33-275, 33-296, 34-184, 34-452, 
               
               
                   
                 35-287, 
               
               
                   
                 38-606, 39-274, 39-295, 43-246, 43-628, 47-263, 47-301, 47-498, 
               
               
                   
                 50-279, 50-476, 54-426, 55-528, 55-684, 63-300, 63-406, 63-498, 
               
               
                   
                 63-526, 
               
               
                   
                 65-304, 68-611, 75-357, 99-770, 103-259, 103-345, 121-287, 
               
               
                   
                 121-406, 123-457, 123-597, 152-770, 157-663, 165-770, 176-554, 
               
               
                   
                 196-770, 
               
               
                   
                 203-554, 221-464, 221-554, 221-604, 254-469, 256-754, 257-770, 
               
               
                   
                 339-494, 343-579, 385-586, 413-622, 414-766, 418-694, 442-672, 
               
               
                   
                 442-746, 484-770, 535-746, 723-909, 723-1136, 723-1142, 770-1000, 
               
               
                   
                 770-1022, 770-1104, 770-1185, 770-1189, 770-1191, 772-1185, 773-1188, 
               
               
                   
                 774-1044, 776-1185, 778-955, 778-1130, 778-1183, 782-1179, 
               
               
                   
                 789-1185, 794-1181, 
               
               
                   
                 796-1170, 796-1185, 800-1183, 801-1103, 804-1191, 807-1177, 
               
               
                   
                 808-1041, 808-1164, 808-1185, 810-1191, 811-1021, 811-1028, 813-1045, 
               
               
                   
                 815-1069, 818-1053, 818-1190, 820-1181, 822-1191, 840-1191, 
               
               
                   
                 847-1182, 853-1147, 884-1181, 889-1181, 890-1191, 892-1083, 902-1150, 
               
               
                   
                 908-1181, 919-1179, 923-1142, 959-1145, 959-1191, 961-1142, 
               
               
                   
                 962-1164, 964-1191, 972-1185, 993-1089, 996-1116, 1050-1184, 1056-1181, 
               
               
                   
                 1077-1176 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                   
               
               
                 Polynucleotide 
                   
                 Representative 
                   
               
               
                 SEQ ID NO: 
                 Incyte Project ID: 
                 Library 
               
               
                   
               
             
            
               
                 32 
                 7506690CB1 
                 LIVRTUE01 
                   
               
               
                   
               
               
                 33 
                 7506536CB1 
                 BRAINOT09 
               
               
                   
               
               
                 34 
                 7506537CB1 
                 BRAINOT09 
               
               
                   
               
               
                 35 
                 7506655CB1 
                 ARTANOT06 
               
               
                   
               
               
                 36 
                 7506656CB1 
                 PROSTUT09 
               
               
                   
               
               
                 37 
                 7510567CB1 
                 KIDNTUT13 
               
               
                   
               
               
                 38 
                 7506072CB1 
                 PROSTMY01 
               
               
                   
               
               
                 39 
                 7511354CB1 
                 EOSIHET02 
               
               
                   
               
               
                 40 
                 7511643CB1 
                 COLTDIT04 
               
               
                   
               
               
                 42 
                 7511507CB1 
                 NEURDNV05 
               
               
                   
               
               
                 43 
                 7511819CB1 
                 THYMNOR02 
               
               
                   
               
               
                 44 
                 7511338CB1 
                 MYEPTXT01 
               
               
                   
               
               
                 45 
                 7511425CB1 
                 CONNNOT01 
               
               
                   
               
               
                 46 
                 7511534CB1 
                 EOSIHET02 
               
               
                   
               
               
                 47 
                 7511648CB1 
                 BMARNOT03 
               
               
                   
               
               
                 48 
                 7511600CB1 
                 TESTTUT02 
               
               
                   
               
               
                 49 
                 7511783CB1 
                 LUNGFET05 
               
               
                   
               
               
                 50 
                 7512383CB1 
                 BRAITUT12 
               
               
                   
               
               
                 51 
                 7512813CB1 
                 PLACFER01 
               
               
                   
               
               
                 52 
                 7512842CB1 
                 UTRSTDT01 
               
               
                   
               
               
                 53 
                 90190613CB1 
                 BRAXNOT01 
               
               
                   
               
               
                 54 
                 7511894CB1 
                 PROSTMT01 
               
               
                   
               
               
                 55 
                 3604804CB1 
                 BRAIFER05 
               
               
                   
               
               
                 56 
                 7512568CB1 
                 BEPINOT01 
               
               
                   
               
               
                 57 
                 7512812CB1 
                 LUNGDIS03 
               
               
                   
               
               
                 58 
                 7512826CB1 
                 ENDCNOT04 
               
               
                   
               
               
                 59 
                 7512908CB1 
                 BRAUNOR01 
               
               
                   
               
               
                 60 
                 7512909CB1 
                 BRAUNOR01 
               
               
                   
               
               
                 61 
                 7512769CB1 
                 EPIGNOT01 
               
               
                   
               
               
                 62 
                 7512871CB1 
                 LEUKNOT03 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 6 
               
               
                   
               
               
                   
               
               
                 Library 
                 Vector 
                 Library Description 
               
               
                   
               
             
            
               
                 ARTANOT06 
                 pINCY 
                 Library was constructed using RNA isolated from aortic adventitia tissue 
               
               
                   
                   
                 removed from a 48-year-old Caucasian male. 
               
               
                 BEPINOT01 
                 PSPORT1 
                 Library was constructed using RNA isolated from a bronchial epithelium 
               
               
                   
                   
                 primary cell line derived from a 54-year-old Caucasian male. 
               
               
                 BMARNOT03 
                 pINCY 
                 Library was constructed using RNA isolated from the left tibial bone marrow 
               
               
                   
                   
                 tissue of a 16-year-old Caucasian male during a partial left tibial ostectomy with free skin graft. 
               
               
                   
                   
                 Patient history included an abnormality of the red blood cells. Previous surgeries included bone 
               
               
                   
                   
                 and bone marrow biopsy, and soft tissue excision. Family history included osteoarthritis. 
               
               
                 BRAIFER05 
                 pINCY 
                 Library was constructed using RNA isolated from brain tissue removed from a 
               
               
                   
                   
                 Caucasian male fetus who was stillborn with a hypoplastic left heart at 23 weeks&#39; gestation. 
               
               
                 BRAINOT09 
                 pINCY 
                 Library was constructed using RNA isolated from brain tissue removed from a 
               
               
                   
                   
                 Caucasian male fetus, who died at 23 weeks&#39;gestation. 
               
               
                 BRAITUT12 
                 pINCY 
                 Library was constructed using RNA isolated from brain tumor tissue removed 
               
               
                   
                   
                 from the left frontal lobe of a 40-year-old Caucasian female during excision of a cerebral 
               
               
                   
                   
                 meningeal lesion. Pathology indicated grade 4 gemistocytic astrocytoma. 
               
               
                 BRAUNOR01 
                 pINCY 
                 This random primed library was constructed using RNA isolated from striatum, 
               
               
                   
                   
                 globus pallidus and posterior putamen tissue removed from an 81-year-old Caucasian female 
               
               
                   
                   
                 who died from a hemorrhage and ruptured thoracic aorta due to atherosclerosis. Pathology 
               
               
                   
                   
                 indicated moderate atherosclerosis involving the internal carotids, bilaterally; microscopic infarcts 
               
               
                   
                   
                 of the frontal cortex and hippocampus, and scattered diffuse amyloid plaques and neurofibrillary 
               
               
                   
                   
                 tangles, consistent with age. Grossly, the leptomeninges showed only mild thickening and 
               
               
                   
                   
                 hyalinization along the superior sagittal sinus. The remainder of the leptomeninges was thin 
               
               
                   
                   
                 and contained some congested blood vessels. Mild atrophy was found mostly in the frontal poles 
               
               
                   
                   
                 and lobes, and temporal lobes, bilaterally. Microscopically, there were pairs of Alzheimer type II 
               
               
                   
                   
                 astrocytes within the deep layers of the neocortex. There was increased satellitosis around 
               
               
                   
                   
                 neurons in the deep gray matter in the middle frontal cortex. 
               
               
                   
                   
                 The amygdala contained rare diffuse 
               
               
                   
                   
                 plaques and neurofibrillary tangles. The posterior hippocampus contained a 
               
               
                   
                   
                 microscopic area of cystic cavitation with hemosiderin-laden macrophages surrounded 
               
               
                   
                   
                 by reactive gliosis. Patient history included sepsis, cholangitis, post-operative 
               
               
                   
                   
                 atelectasis, pneumonia CAD, cardiomegaly due to left ventricular hypertrophy, splenomegaly, 
               
               
                   
                   
                 arteriolonephrosclerosis, nodular colloidal goiter, emphysema, CHF, hypothyroidism, and 
               
               
                   
                   
                 peripheral vascular disease. 
               
               
                 BRAXNOT01 
                 pINCY 
                 Library was constructed using RNA isolated from cerebellar tissue 
               
               
                   
                   
                 removed from a 70-year-old male. Patient history included 
               
               
                   
                   
                 chronic obstructive airways disease and left ventricular failure. 
               
               
                 COLTDIT04 
                 pINCY 
                 Library was constructed using RNA isolated from diseased transverse 
               
               
                   
                   
                 colon tissue removed from a 16-year-old Caucasian male 
               
               
                   
                   
                 during partial colectomy, temporary ileostomy, and colonoscopy. 
               
               
                   
                   
                 Pathology indicated innumerable (greater than 100) 
               
               
                   
                   
                 adenomatous polyps with low-grade dysplasia involving the entire colonic 
               
               
                   
                   
                 mucosa in the setting of familial polyposis coli. 
               
               
                   
                   
                 Family history included benign col on neoplasm, benign hypertension, 
               
               
                   
                   
                 cerebrovascular disease, breast cancer, uterine cancer, 
               
               
                   
                   
                 and type II diabetes. 
               
               
                 CONNNOT01 
                 pINCY 
                 Library was constructed using RNA isolated from mesentery fat 
               
               
                   
                   
                 tissue obtained from a 71-year-old Caucasian male during a 
               
               
                   
                   
                 partial colectomy and permanent colostomy. Family history included atherosclerotic 
               
               
                   
                   
                 coronary artery disease, myocardial infarction, and extrinsic asthma. 
               
               
                 ENDCNOT04 
                 pINCY 
                 Library was constructed using RNA isolated from coronary 
               
               
                   
                   
                 artery endothelial cell tissue removed from a 3-year-old Caucasian male. 
               
               
                 EOSIHET02 
                 PBLUESCRIPT 
                 Library was constructed using RNA isolated from peripheral 
               
               
                   
                   
                 blood cells apheresed from a 48-year-old Caucasian male. Patient 
               
               
                   
                   
                 history included hypereosinophilia. The cell population was determined to be 
               
               
                   
                   
                 greater than 77% eosinophils by Wright&#39;s staining. 
               
               
                 EPIGNOT01 
                 pINCY 
                 Library was constructed using RNA isolated from epiglottic tissue 
               
               
                   
                   
                 removed from a 71-year-old male during laryngectomy with 
               
               
                   
                   
                 right parathyroid biopsy. Pathology for the associated tumor tissue indicated 
               
               
                   
                   
                 recurrent grade 1 papillary thyroid carcinoma. 
               
               
                 KIDNTUT13 
                 pINCY 
                 Library was constructed using RNA isolated from kidney tumor tissue removed from 
               
               
                   
                   
                 a 51-year-old Caucasian female during a nephroureterectomy. Pathology indicated a grade 3 
               
               
                   
                   
                 renal cell carcinoma. Patient history included depressive disorder, hypoglycemia, and uterine 
               
               
                   
                   
                 endometriosis. Family history included calculus of the kidney, colon cancer, and type II diabetes. 
               
               
                 LEUKNOT03 
                 pINCY 
                 Library was constructed using RNA isolated from white blood cells of a 27-year-old female 
               
               
                   
                   
                 with blood type A+. The donor tested negative for cytomegalovirus (CMV). 
               
               
                 LIVRTUE01 
                 PCDNA2.1 
                 This 5′ biased random primed library was constructed using RNA isolated from 
               
               
                   
                   
                 liver tumor tissue removed from a 72-year-old Caucasian male during partial hepatectomy. Pathology 
               
               
                   
                   
                 indicated metastatic grade 2 (of 4) neuroendocrine carcinoma forming a mass. The patient 
               
               
                   
                   
                 presented with metastatic liver cancer. Patient history included benign hypertension, type I diabetes, 
               
               
                   
                   
                 prostatic hyperplasia, prostate cancer, alcohol abuse in remission, and tobacco abuse 
               
               
                   
                   
                 in remission. Previous surgeries included destruction of a pancreatic lesion, closed prostatic 
               
               
                   
                   
                 biopsy, transurethral prostatectomy, removal of bilateral testes and total splenectomy. Patient 
               
               
                   
                   
                 medications included Eulexin, Hytrin, Proscar, Ecotrin, and insulin. Family history included 
               
               
                   
                   
                 atherosclerotic coronary artery disease and acute myocardial infarction in the mother; atherosclerotic 
               
               
                   
                   
                 coronary artery disease and type II diabetes in the father. 
               
               
                 LUNGDIS03 
                 pINCY 
                 Library was constructed using diseased lung tissue. 0.76 million clones from a 
               
               
                   
                   
                 diseased lung tissue library were subjected to two rounds of subtraction hybridization with 
               
               
                   
                   
                 5.1 million clones from a normal lung tissue library. The starting library for 
               
               
                   
                   
                 subtraction was constructed using polyA RNA isolated from diseased lung tissue. Patient history 
               
               
                   
                   
                 included idiopathic pulmonary disease. Subtractive hybridization conditions were based on the methodologies 
               
               
                   
                   
                 of Swaroop et al. (1991) Nucleic Acids Res. 19: 1954; and Bonaldo et al. Genome Res. (1996) 6: 791. 
               
               
                 LUNGFET05 
                 PSPORT1 
                 Library was constructed using RNA isolated from lung tissue removed from a Caucasian 
               
               
                   
                   
                 female fetus, who died at 20 weeks&#39; gestation from anencephalus. 
               
               
                 MYEPTXT01 
                 pINCY 
                 Library was constructed using RNA isolated from a treated K-562 cell line, derived from 
               
               
                   
                   
                 chronic myelogenous leukemia precursor cells obtained from a 53-year-old female. The cells were treated 
               
               
                   
                   
                 with 5-aza-2′deoxycytidine. 
               
               
                 NEURDNV05 
                 PCR2-TOPOTA 
                 Library was constructed using pooled cDNA from different donors. cDNA was generated 
               
               
                   
                   
                 using mRNA isolated from pooled skeletal muscle tissue removed from ten 21 to 57-year-old Caucasian male and 
               
               
                   
                   
                 female donors who died from sudden death; from pooled thymus tissue removed from nine 18 to 
               
               
                   
                   
                 32-year-old Caucasian male and female donors who died from sudden death; from pooled liver tissue removed 
               
               
                   
                   
                 from 32 Caucasian male and female fetuses who died at 18-24 weeks gestation due to spontaneous abortion; 
               
               
                   
                   
                 from kidney tissue removed from 59 Caucasian male and female fetuses who died at 20-33 weeks 
               
               
                   
                   
                 gestation due to spontaneous abortion; and from brain tissue removed from a Caucasian male fetus 
               
               
                   
                   
                 who died at 23 weeks gestation due to fetal demise. 
               
               
                 PLACFER01 
                 pINCY 
                 The library was constructed using RNA isolated from placental tissue removed from a Caucasian 
               
               
                   
                   
                 fetus, who died after 16 weeks&#39; gestation from fetal demise and hydrocephalus. Patient history included umbilical 
               
               
                   
                   
                 cord wrapped around the head (3 times) and the shoulders (1 time). Serology was positive for anti-CMV. Family 
               
               
                   
                   
                 history included multiple pregnancies and live births, and an abortion. 
               
               
                 PROSTMT01 
                 pINCY 
                 Library was constructed using RNA isolated from diseased prostate tissue removed from a 
               
               
                   
                   
                 67-year-old Caucasian male during radical prostatectomy with regional lymph node excision. Pathology indicated 
               
               
                   
                   
                 adenofibromatous hyperplasia. Pathology for the associated tumor tissue indicated grade 3, Gleason 
               
               
                   
                   
                 grade 3 + 3 adenocarcinoma. The patient presented elevated prostate specific 
               
               
                   
                   
                 antigen (PSA) and induration. Patient history included hyperlipidemia cerebrovascular disease, and a 
               
               
                   
                   
                 depressive disorder. Family history included atherosclerotic coronary artery disease and hyperlipidemia. 
               
               
                 PROSTMY01 
                 pINCY 
                 This large size-fractionated cDNA and normalized library was constructed using RNA 
               
               
                   
                   
                 isolated from diseased prostate tissue removed from a 55-year-old Caucasian male during closed prostatic 
               
               
                   
                   
                 biopsy, radical prostatectomy, and regional lymph node excision. Pathology indicated adenofibromatous hyperplasia. 
               
               
                   
                   
                 Pathology for the matched tumor tissue indicated adenocarcinoma Gleason grade 4 forming a predominant 
               
               
                   
                   
                 mass involving the left side peripherally with extension into the right posterior superior region. The tumor 
               
               
                   
                   
                 invaded the capsule and perforated the capsule to involve periprostatic tissue in the left posterior 
               
               
                   
                   
                 superior region. The left inferior posterior and left superior posterior surgical margins are positive. 
               
               
                   
                   
                 One left pelvic lymph node is metastatically involved. Patient history included calculus of the kidney. 
               
               
                   
                   
                 Family history included lung cancer and breast cancer. The size-selected library was normalized in 1 round 
               
               
                   
                   
                 using conditions adapted from Soares et al., PNAS (1994) 91: 9228-9232 and Bonaldo et al., 
               
               
                   
                   
                 Genome Research (1996) 6: 791. 
               
               
                 PROSTUT09 
                 pINCY 
                 Library was constructed using RNA isolated from prostate tumor tissue removed from 
               
               
                   
                   
                 a 66-year-old Caucasian male during a radical prostatectomy, radical cystectomy, and urinary diversion. 
               
               
                   
                   
                 Pathology indicated grade 3 transitional cell carcinoma. The patient presented with prostatic inflammatory 
               
               
                   
                   
                 disease. Patient history included lung neoplasm, and benign hypertension. Family history included a malignant 
               
               
                   
                   
                 breast neoplasm, tuberculosis, cerebrovascular disease, atherosclerotic coronary artery disease and 
               
               
                   
                   
                 lung cancer. 
               
               
                 TESTTUT02 
                 pINCY 
                 Library was constructed using RNA isolated from testicular tumor removed from a 
               
               
                   
                   
                 31-year-old Caucasian male during unilateral orchiectomy. Pathology indicated embryonal carcinoma. 
               
               
                 THYMNOR02 
                 pINCY 
                 The library was constructed using RNA isolated from thymus tissue removed from 
               
               
                   
                   
                 a 2-year-old Caucasian female during a thymectomy and patch closure of left atrioventricular fistula. 
               
               
                   
                   
                 Pathology indicated there was no gross abnormality of the thymus. The patient presented with congenital 
               
               
                   
                   
                 heart abnormalities. Patient history included double inlet left ventricle and a rudimentary right ventricle, pulmonary 
               
               
                   
                   
                 hypertension, cyanosis, subaortic stenosis, seizures, and a fracture of the skull base. 
               
               
                   
                   
                 Family history included reflux neuropathy. 
               
               
                 UTRSTDT01 
                 pINCY 
                 Library was constructed using RNA isolated from uterus tissue removed from a 46-year-old 
               
               
                   
                   
                 Caucasian female who died from cardiopulmonary arrest. Patient history included liver and breast cancer. 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
             
               
                 TABLE 7 
               
               
                   
               
               
                   
               
               
                 Program 
                 Description 
                 Reference 
                 Parameter Threshold 
               
               
                   
               
             
            
               
                 ABI 
                 A program that removes vector sequences and masks 
                 Applied Biosystems, Foster City, CA. 
                   
               
               
                 FACTURA 
                 ambiguous bases in nucleic acid sequences. 
               
               
                 ABI/ 
                 A Fast Data Finder useful in comparing and 
                 Applied Biosystems, Foster City, CA; 
                 Mismatch &lt;50% 
               
               
                 PARACEL 
                 annotating amino acid or nucleic acid sequences. 
                 Paracel Inc., Pasadena, CA. 
               
               
                 FDF 
               
               
                 ABI 
                 A program that assembles nucleic acid sequences. 
                 Applied Biosystems, Foster City, CA. 
               
               
                 AutoAssembler 
               
               
                 BLAST 
                 A Basic Local Alignment Search Tool useful in 
                 Altschul, S. F. et al. (1990) J. Mol. Biol. 
                 ESTs: Probability value = 
               
               
                   
                 sequence similarity search for amino acid and nucleic 
                 215: 403-410; Altschul, S. F. et al. (1997) 
                 1.0E−8 or less; Full 
               
               
                   
                 acid sequences. BLAST includes five functions: 
                 Nucleic Acids Res. 25: 3389-3402. 
                 Length sequences: Probability 
               
               
                   
                 blastp, blastn, blastx, tblastn, and tblastx. 
                   
                 value = 1.0E−10 
               
               
                   
                   
                   
                 or less 
               
               
                 FASTA 
                 A Pearson and Lipman algorithm that searches for 
                 Pearson, W. R. and D. J. Lipman (1988) Proc. 
                 ESTs: fasta E value = 
               
               
                   
                 similarity between a query sequence and a group of 
                 Natl. Acad Sci. USA 85: 2444-2448; Pearson, 
                 1.06E−6; Assembled ESTs: 
               
               
                   
                 sequences of the same type. FASTA comprises as 
                 W. R. (1990) Methods Enzymol. 183: 63-98; 
                 fasta Identity = 95% 
               
               
                   
                 least five functions: fasta, tfasta, fastx, tfastx, and 
                 and Smith, T. F. and M. S. Waterman (1981) 
                 or greater and Match 
               
               
                   
                 ssearch. 
                 Adv. Appl. Math. 2: 482-489. 
                 length = 200 bases or greater; 
               
               
                   
                   
                   
                 fastx E value = 
               
               
                   
                   
                   
                 1.0E−8 or less; 
               
               
                   
                   
                   
                 Full Length sequences: 
               
               
                   
                   
                   
                 fastx score = 
               
               
                   
                   
                   
                 100 or greater 
               
               
                 BLIMPS 
                 A BLocks IMProved Searcher that matches a 
                 Henikoff, S. and J. G. Henikoff (1991) 
                 Probability value = 
               
               
                   
                 sequence against those in BLOCKS, PRINTS, 
                 Nucleic Acids Res. 19: 6565-6572; 
                 1.0E−3 or less 
               
               
                   
                 DOMO, PRODOM, and PFAM databases to search 
                 Henikoff, J. G. and S. Henikoff (1996) 
               
               
                   
                 for gene families, sequence homology, and structural 
                 Methods Enzymol. 266: 88-105; 
               
               
                   
                 fingerprint regions. 
                 and Attwood, T. K. et al. (1997) J. Chem. Inf. 
               
               
                   
                   
                 Comput. Sci. 37: 
               
               
                 HMMER 
                 An algorithm for searching a query sequence against 
                 417-424. Krogh, A. et al. (1994) J. Mol. Biol. 
                 PFAM, INCY, SMART or 
               
               
                   
                 hidden Markov model (HMM)-based databases of 
                 235: 1501-1531; Sonnhammer, E. L. L. et al. 
                 TIGRFAM hits: 
               
               
                   
                 protein family consensus sequences, such as PFAM, 
                 (1988) Nucleic Acids Res. 26: 320-322; 
                 Probability value = 
               
               
                   
                 INCY, SMART and TIGRFAM. 
                 Durbin, R. et al. (1998) Our World View, in 
                 1.0E−3 or less; 
               
               
                   
                   
                 a Nutshell, Cambridge Univ. Press, pp. 1-350. 
                 Signal peptide hits: 
               
               
                   
                   
                   
                 Score = 0 or greater 
               
               
                 ProfileScan 
                 An algorithm that searches for structural and 
                 Gribskov, M. et al. (1988) CABIOS 4: 61-66; 
                 Normalized quality 
               
               
                   
                 sequence motifs in protein sequences that match 
                 Gribskov, M. et al. (1989) Methods 
                 specified “HIGH” value for 
               
               
                   
                 sequence patterns defined in Prosite. 
                 Enzymol. 183: 146-159; Bairoch, A. et al. 
                 that score ≧ GCG 
               
               
                   
                   
                 (1997) Nucleic Acids Res. 25: 217-221. 
                 particular 
               
               
                   
                   
                   
                 Prosite motif. 
               
               
                   
                   
                   
                 Generally, score = 
               
               
                   
                   
                   
                 1.4-2.1. 
               
               
                 Phred 
                 A base-calling algorithm that examines automated 
                 Ewing, B. et al. (1998) Genome Res. 8: 
               
               
                   
                 sequencer traces with high sensitivity and probability. 
                 175-185; Ewing, B. and 
               
               
                   
                   
                 P. Green (1998) Genome 
               
               
                   
                   
                 Res. 8: 186-194. 
               
               
                 Phrap 
                 A Phils Revised Assembly Program including 
                 Smith, T. F. and M. S. Waterman (1981) Adv. 
                 Score = 120 or greater; 
               
               
                   
                 SWAT and CrossMatch, programs based on efficient 
                 Appl. Math. 2: 482-489; Smith, T. F. and 
                 Match length = 56 
               
               
                   
                 implementation of the Smith-Waterman algorithm, 
                 M. S. Waterman (1981) J. Mol. Biol. 147: 
                 or greater 
               
               
                   
                 useful in searching sequence homology and 
                 195-197; and Green, P., University of 
               
               
                   
                 assembling DNA sequences. 
                 Washington, Seattle, WA. 
               
               
                 Consed 
                 A graphical tool for viewing and editing Phrap 
                 Gordon, D. et al. (1998) Genome Res. 8: 
               
               
                   
                 assemblies. 
                 195-202. 
               
               
                 SPScan 
                 A weight matrix analysis program that scans protein 
                 Nielson, H. et al. (1997) Protein Engineering 
                 Score = 3.5 or greater 
               
               
                   
                 sequences for the presence of secretory signal 
                 10: 1-6; Claverie, J. M. and S. Audic (1997) 
               
               
                   
                 peptides. 
                 CABIOS 12: 431-439. 
               
               
                 TMAP 
                 A program that uses weight matrices to delineate 
                 Persson, B. and P. Argos (1994) J. Mol. Biol. 
               
               
                   
                 transmembrane segments on protein sequences and 
                 237: 182-192; Persson, B. and P. Argos 
               
               
                   
                 determine orientation. 
                 (1996) Protein Sci. 5: 363-371. 
               
               
                 TMHMMER 
                 A program that uses a hidden Markov model (HMM) 
                 Sonnhammer, E. L. et al. (1998) Proc. Sixth 
               
               
                   
                 to delineate transmembrane segments on protein 
                 Intl. Conf. On Intelligent Systems for Mol. 
               
               
                   
                 sequences and determine orientation. 
                 Biol., Glasgow et al., eds., The Am. Assoc. 
               
               
                   
                   
                 for Artificial Intelligence (AAAI) Press, 
               
               
                   
                   
                 Menlo Park, CA, and MIT Press, Cambridge, 
               
               
                   
                   
                 MA, pp. 175-182. 
               
               
                 Motifs 
                 A program that searches amino acid sequences for 
                 Bairoch, A. et al. (1997) Nucleic Acids Res. 
               
               
                   
                 patterns that matched those defined in Prosite. 
                 25: 217-221; Wisconsin Package Program 
               
               
                   
                   
                 Manual, version 9, page M51-59, Genetics 
               
               
                   
                   
                 Computer Group, Madison, WI. 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
               
                 TABLE 8 
               
               
                   
               
               
                   
               
               
                 SEQ 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 Caucasian 
                 African 
                 Asian 
                 Hispanic 
               
               
                 ID 
                   
                   
                   
                 EST 
                 CB1 
                 EST 
                   
                 Al- 
                 Amino 
                 Allele 1 
                 Allele 1 
                 Allele 1 
                 Allele 1 
               
               
                 NO: 
                 PID 
                 EST ID 
                 SNP ID 
                 SNP 
                 SNP 
                 Allele 
                 Allele 1 
                 lele 2 
                 Acid 
                 frequency 
                 frequency 
                 frequency 
                 frequency 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 32 
                 7506690 
                 2700047H1 
                 SNP00049844 
                 45 
                 2311 
                 C 
                 C 
                 T 
                 S696 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 32 
                 7506690 
                 8014939J2 
                 SNP00049844 
                 341 
                 2312 
                 C 
                 C 
                 T 
                 S696 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 33 
                 7506536 
                 1456901H1 
                 SNP00027692 
                 199 
                 790 
                 C 
                 C 
                 G 
                 P231 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 33 
                 7506536 
                 1794980H1 
                 SNP00052100 
                 268 
                 1030 
                 G 
                 G 
                 C 
                 G311 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 33 
                 7506536 
                 3403559H1 
                 SNP00052099 
                 208 
                 542 
                 G 
                 G 
                 A 
                 R148 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 33 
                 7506536 
                 3403559H1 
                 SNP00098207 
                 90 
                 424 
                 C 
                 G 
                 C 
                 A109 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 33 
                 7506536 
                 3506466H1 
                 SNP00052100 
                 244 
                 1029 
                 G 
                 G 
                 C 
                 G311 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 33 
                 7506536 
                 3743207H1 
                 SNP00052100 
                 33 
                 1026 
                 C 
                 G 
                 C 
                 P310 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 34 
                 7506537 
                 1456901H1 
                 SNP00027692 
                 199 
                 603 
                 C 
                 C 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 34 
                 7506537 
                 1794980H1 
                 SNP00052100 
                 268 
                 843 
                 G 
                 G 
                 C 
                 noncoding 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 34 
                 7506537 
                 3506466H1 
                 SNP00052100 
                 244 
                 842 
                 G 
                 G 
                 C 
                 noncoding 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 34 
                 7506537 
                 3743207H1 
                 SNP00052100 
                 33 
                 839 
                 C 
                 G 
                 C 
                 noncoding 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 34 
                 7506537 
                 3752762H1 
                 SNP00098207 
                 98 
                 382 
                 C 
                 G 
                 C 
                 H109 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 34 
                 7506537 
                 6334553H1 
                 SNP00052099 
                 126 
                 353 
                 A 
                 G 
                 A 
                 H99 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 1311380H1 
                 SNP00097606 
                 7 
                 485 
                 C 
                 C 
                 T 
                 G157 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 1378619H1 
                 SNP00062747 
                 123 
                 1704 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 1649327H1 
                 SNP00097606 
                 85 
                 492 
                 C 
                 C 
                 T 
                 Q160 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 1678558H1 
                 SNP00062747 
                 185 
                 1682 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 1782173H1 
                 SNP00008154 
                 23 
                 2190 
                 T 
                 T 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 2638672H1 
                 SNP00062747 
                 126 
                 1701 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 2904178H1 
                 SNP00062747 
                 186 
                 1703 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 3069052H1 
                 SNP00062747 
                 169 
                 1700 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 3168038H1 
                 SNP00062747 
                 165 
                 1699 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 3326702H1 
                 SNP00097606 
                 110 
                 484 
                 C 
                 C 
                 T 
                 A157 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 3353963H1 
                 SNP00097606 
                 124 
                 475 
                 C 
                 C 
                 T 
                 A154 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 3602992H1 
                 SNP00097606 
                 41 
                 482 
                 C 
                 C 
                 T 
                 G156 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 3720990H1 
                 SNP00062747 
                 82 
                 1698 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 3902692H1 
                 SNP00106135 
                 237 
                 1310 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 4564431H1 
                 SNP00097606 
                 97 
                 483 
                 C 
                 C 
                 T 
                 R157 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 4648883H1 
                 SNP00062747 
                 184 
                 1702 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 5199479H1 
                 SNP00062747 
                 231 
                 1705 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 6413315H1 
                 SNP00062747 
                 341 
                 1697 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 6479857H1 
                 SNP00008153 
                 403 
                 973 
                 C 
                 T 
                 C 
                 A320 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 684419H1 
                 SNP00098150 
                 15 
                 917 
                 A 
                 A 
                 G 
                 E301 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 35 
                 7506655 
                 7039242H1 
                 SNP00008153 
                 192 
                 980 
                 T 
                 T 
                 C 
                 S322 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 7081283H1 
                 SNP00130169 
                 64 
                 7 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 35 
                 7506655 
                 7127858H1 
                 SNP00062747 
                 28 
                 1655 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1006142H1 
                 SNP00098150 
                 106 
                 918 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 36 
                 7506656 
                 1311380H1 
                 SNP00097606 
                 7 
                 485 
                 C 
                 C 
                 T 
                 G157 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1378619H1 
                 SNP00062747 
                 123 
                 2042 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1649327H1 
                 SNP00097606 
                 85 
                 492 
                 C 
                 C 
                 T 
                 Q160 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1672772H1 
                 SNP00098150 
                 168 
                 930 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 36 
                 7506656 
                 1678558H1 
                 SNP00062747 
                 185 
                 2020 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1679821H1 
                 SNP00153045 
                 117 
                 1143 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1698338H1 
                 SNP00008153 
                 174 
                 921 
                 T 
                 T 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1782173H1 
                 SNP00008154 
                 23 
                 2528 
                 T 
                 T 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 1800953H1 
                 SNP00092571 
                 204 
                 1413 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 193898H1 
                 SNP00098150 
                 31 
                 931 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 36 
                 7506656 
                 2187682H1 
                 SNP00098150 
                 16 
                 929 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 36 
                 7506656 
                 2638672H1 
                 SNP00062747 
                 126 
                 2039 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 2904178H1 
                 SNP00062747 
                 186 
                 2041 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3069052H1 
                 SNP00062747 
                 169 
                 2038 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3168038H1 
                 SNP00062747 
                 165 
                 2037 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3212643H1 
                 SNP00098150 
                 111 
                 927 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 36 
                 7506656 
                 3285931H1 
                 SNP00098150 
                 32 
                 928 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 36 
                 7506656 
                 3321710H1 
                 SNP00092571 
                 149 
                 1412 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3326702H1 
                 SNP00097606 
                 110 
                 484 
                 C 
                 C 
                 T 
                 A157 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3353963H1 
                 SNP00097606 
                 124 
                 475 
                 C 
                 C 
                 T 
                 A154 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3602992H1 
                 SNP00097606 
                 41 
                 482 
                 C 
                 C 
                 T 
                 G156 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3642390H1 
                 SNP00153045 
                 2 
                 1140 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3690567H1 
                 SNP00008153 
                 203 
                 918 
                 T 
                 T 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3720990H1 
                 SNP00062747 
                 82 
                 2036 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 3885387H2 
                 SNP00098150 
                 14 
                 917 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 36 
                 7506656 
                 3902692H1 
                 SNP00106135 
                 237 
                 1648 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 4564431H1 
                 SNP00097606 
                 97 
                 483 
                 C 
                 C 
                 T 
                 R157 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 4648883H1 
                 SNP00062747 
                 184 
                 2040 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 5199479H1 
                 SNP00062747 
                 231 
                 2043 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 5289285H1 
                 SNP00153045 
                 55 
                 1142 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 6413315H1 
                 SNP00062747 
                 341 
                 2035 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 7081283H1 
                 SNP00130169 
                 64 
                 7 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 36 
                 7506656 
                 7127858H1 
                 SNP00062747 
                 28 
                 1993 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 37 
                 7510567 
                 4218337F6 
                 SNP00148602 
                 37 
                 896 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 37 
                 7510567 
                 7137262H1 
                 SNP00071130 
                 184 
                 257 
                 G 
                 A 
                 G 
                 G43 
                 0.92 
                 0.92 
                 0.89 
                 0.89 
               
               
                 38 
                 7506072 
                 1535170H1 
                 SNP00009199 
                 149 
                 1756 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 1535170H1 
                 SNP00037178 
                 68 
                 1675 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 1535170H1 
                 SNP00144912 
                 35 
                 1642 
                 T 
                 T 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 2681553H1 
                 SNP00125000 
                 231 
                 1755 
                 G 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 2790256H2 
                 SNP00037177 
                 57 
                 894 
                 G 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 2924591H1 
                 SNP00037177 
                 185 
                 898 
                 G 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 3817244H1 
                 SNP00144911 
                 198 
                 1458 
                 A 
                 C 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 3880004H1 
                 SNP00144911 
                 226 
                 1460 
                 A 
                 C 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 4069389H1 
                 SNP00009199 
                 251 
                 1754 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 4069389H1 
                 SNP00144912 
                 137 
                 1640 
                 T 
                 T 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 4163749H1 
                 SNP00009199 
                 32 
                 1755 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 4183639H1 
                 SNP00037178 
                 174 
                 1673 
                 T 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 4709207H1 
                 SNP00144911 
                 224 
                 1459 
                 A 
                 C 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 7027968H1 
                 SNP00125000 
                 402 
                 1757 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 38 
                 7506072 
                 7374370H1 
                 SNP00053945 
                 541 
                 540 
                 A 
                 A 
                 G 
                 E110 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 39 
                 7511354 
                 1658373T6 
                 SNP00015452 
                 2 
                 2260 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 39 
                 7511354 
                 1872966T6 
                 SNP00015452 
                 37 
                 2275 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 39 
                 7511354 
                 7168495H1 
                 SNP00132303 
                 109 
                 285 
                 A 
                 A 
                 G 
                 T32 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 39 
                 7511354 
                 7168495H1 
                 SNP00132304 
                 126 
                 302 
                 A 
                 A 
                 G 
                 H38 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 39 
                 7511354 
                 7422001T1 
                 SNP00015452 
                 42 
                 2237 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 40 
                 7511643 
                 1335233H1 
                 SNP00070206 
                 135 
                 2035 
                 A 
                 A 
                 C 
                 E659 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 40 
                 7511643 
                 1736837F6 
                 SNP00040689 
                 328 
                 2382 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 40 
                 7511643 
                 1808096F6 
                 SNP00040688 
                 213 
                 2069 
                 T 
                 T 
                 C 
                 G670 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 40 
                 7511643 
                 5654454H1 
                 SNP00040689 
                 268 
                 2386 
                 A 
                 A 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 40 
                 7511643 
                 6454710H1 
                 SNP00067649 
                 402 
                 402 
                 G 
                 A 
                 G 
                 E115 
                 0.17 
                 0.13 
                 0.33 
                 0.29 
               
               
                 40 
                 7511643 
                 6801870J1 
                 SNP00070206 
                 130 
                 2014 
                 C 
                 A 
                 C 
                 P652 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 40 
                 7511643 
                 7007828H1 
                 SNP00010482 
                 335 
                 1999 
                 G 
                 G 
                 A 
                 R647 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 41 
                 7511400 
                 4767844H1 
                 SNP00134633 
                 31 
                 569 
                 T 
                 T 
                 C 
                 W87 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 41 
                 7511400 
                 4767844H1 
                 SNP00134634 
                 140 
                 678 
                 C 
                 C 
                 T 
                 P123 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 42 
                 7511507 
                 1254303F1 
                 SNP00009660 
                 349 
                 1232 
                 C 
                 C 
                 T 
                 I274 
                 0.73 
                 0.73 
                 0.8  
                 0.79 
               
               
                 42 
                 7511507 
                 1254303F1 
                 SNP00009661 
                 526 
                 1409 
                 C 
                 C 
                 T 
                 Y333 
                 0.92 
                 0.95 
                 0.97 
                 0.91 
               
               
                 42 
                 7511507 
                 1254303F1 
                 SNP00116740 
                 96 
                 979 
                 G 
                 G 
                 A 
                 R190 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 42 
                 7511507 
                 1298133H1 
                 SNP00037904 
                 77 
                 2409 
                 A 
                 A 
                 C 
                 noncoding 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 42 
                 7511507 
                 1322651T6 
                 SNP00009662 
                 222 
                 2148 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 1414920T6 
                 SNP00009662 
                 241 
                 2160 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 1436024T6 
                 SNP00009662 
                 225 
                 2178 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 1557825F6 
                 SNP00009660 
                 139 
                 1233 
                 C 
                 C 
                 T 
                 H275 
                 0.73 
                 0.73 
                 0.8  
                 0.79 
               
               
                 42 
                 7511507 
                 1557825T6 
                 SNP00009662 
                 219 
                 2162 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 1600521T6 
                 SNP00009662 
                 205 
                 2181 
                 G 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 1682522F6 
                 SNP00116740 
                 222 
                 981 
                 G 
                 G 
                 A 
                 G191 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 42 
                 7511507 
                 1955727H1 
                 SNP00058560 
                 144 
                 1775 
                 C 
                 C 
                 T 
                 noncoding 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 42 
                 7511507 
                 2060177T6 
                 SNP00009662 
                 239 
                 2169 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 2543695T6 
                 SNP00009662 
                 216 
                 2168 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 2734727H1 
                 SNP00116739 
                 191 
                 667 
                 C 
                 C 
                 A 
                 T86 
                 n/d 
                 n/a 
                 n/d 
                 n/d 
               
               
                 42 
                 7511507 
                 2890616T6 
                 SNP00009662 
                 191 
                 2198 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 3113405H1 
                 SNP00116738 
                 11 
                 2 
                 C 
                 C 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 42 
                 7511507 
                 3905760H1 
                 SNP00054891 
                 112 
                 1467 
                 T 
                 C 
                 T 
                 L353 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 42 
                 7511507 
                 424333R6 
                 SNP00116740 
                 228 
                 980 
                 G 
                 G 
                 A 
                 R190 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 42 
                 7511507 
                 4805531H1 
                 SNP00009660 
                 18 
                 1234 
                 C 
                 C 
                 T 
                 A275 
                 0.73 
                 0.73 
                 0.8  
                 0.79 
               
               
                 42 
                 7511507 
                 4805531H1 
                 SNP00009661 
                 195 
                 1411 
                 C 
                 C 
                 T 
                 P334 
                 0.92 
                 0.95 
                 0.97 
                 0.91 
               
               
                 42 
                 7511507 
                 7644762J1 
                 SNP00009662 
                 111 
                 2149 
                 A 
                 A 
                 G 
                 noncoding 
                 0.97 
                 n/d 
                 n/d 
                 0.99 
               
               
                 42 
                 7511507 
                 7708989J1 
                 SNP00009661 
                 241 
                 1410 
                 C 
                 C 
                 T 
                 P334 
                 0.92 
                 0.95 
                 0.97 
                 0.91 
               
               
                 42 
                 7511507 
                 7752348J1 
                 SNP00009660 
                 299 
                 1203 
                 C 
                 C 
                 T 
                 H265 
                 0.73 
                 0.73 
                 0.8  
                 0.79 
               
               
                 42 
                 7511507 
                 7752348J1 
                 SNP00009661 
                 476 
                 1380 
                 C 
                 C 
                 T 
                 L324 
                 0.92 
                 0.95 
                 0.97 
                 0.91 
               
               
                 42 
                 7511507 
                 7752348J1 
                 SNP00116740 
                 46 
                 950 
                 A 
                 G 
                 A 
                 stop180 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 42 
                 7511507 
                 7762216J1 
                 SNP00009660 
                 353 
                 1207 
                 C 
                 C 
                 T 
                 T266 
                 0.73 
                 0.73 
                 0.8  
                 0.79 
               
               
                 42 
                 7511507 
                 7762216J1 
                 SNP00116740 
                 100 
                 954 
                 G 
                 G 
                 A 
                 D182 
                 n/d 
                 n/d 
                 n/d 
                 n/d 
               
               
                 43 
                 7511819 
                 1556245F6 
                 SNP00114741 
                 11 
                 3747 
                 A 
                 A 
                 G 
                 noncoding 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 43 
                 7511819 
                 1556245F6 
                 SNP00114742 
                 26 
                 3762 
                 A 
                 A 
                 G 
                 noncoding 
                 0.98 
                 n/a 
                 n/a 
                 n/a 
               
               
                 43 
                 7511819 
                 2304978H1 
                 SNP00036174 
                 57 
                 2430 
                 G 
                 G 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 43 
                 7511819 
                 3000013H1 
                 SNP00042735 
                 170 
                 1746 
                 G 
                 A 
                 G 
                 V551 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 43 
                 7511819 
                 5043136H1 
                 SNP00114740 
                 126 
                 3305 
                 G 
                 G 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 43 
                 7511819 
                 7761779J1 
                 SNP00036174 
                 419 
                 2399 
                 G 
                 G 
                 C 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 028327H1 
                 SNP00139433 
                 23 
                 684 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 1700475T6 
                 SNP00139433 
                 152 
                 685 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 1843678H1 
                 SNP00008138 
                 183 
                 138 
                 C 
                 C 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 1906256H1 
                 SNP00034004 
                 223 
                 881 
                 C 
                 C 
                 G 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 1976291T6 
                 SNP00139433 
                 13 
                 837 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 2061585T6 
                 SNP00116497 
                 29 
                 820 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 2061585T6 
                 SNP00139433 
                 163 
                 686 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 2367548H1 
                 SNP00116497 
                 195 
                 818 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 2502746H1 
                 SNP00125461 
                 103 
                 188 
                 C 
                 C 
                 T 
                 N10 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 6016362H1 
                 SNP00050967 
                 37 
                 245 
                 T 
                 T 
                 G 
                 G29 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 44 
                 7511338 
                 6828414H1 
                 SNP00050967 
                 505 
                 246 
                 T 
                 T 
                 G 
                 C30 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 1007336H1 
                 SNP00027190 
                 48 
                 3075 
                 C 
                 C 
                 G 
                 S982 
                 0.95 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 1299176T6 
                 SNP00150051 
                 94 
                 3764 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 1868109H1 
                 SNP00025347 
                 245 
                 2466 
                 G 
                 G 
                 A 
                 E779 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 1957925H1 
                 SNP00076280 
                 205 
                 2994 
                 C 
                 C 
                 T 
                 L955 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 2692870H1 
                 SNP00076279 
                 70 
                 2081 
                 G 
                 A 
                 G 
                 R651 
                 0.47 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 2692870H1 
                 SNP00100766 
                 83 
                 2094 
                 T 
                 T 
                 C 
                 C655 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 3170918H1 
                 SNP00103142 
                 27 
                 2147 
                 C 
                 C 
                 T 
                 T673 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 6710722H1 
                 SNP00141033 
                 33 
                 3510 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 724339T6 
                 SNP00141033 
                 309 
                 3602 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 842889T6 
                 SNP00141033 
                 314 
                 3595 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 8617639H1 
                 SNP00150051 
                 107 
                 3439 
                 G 
                 G 
                 A 
                 A1104 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 8617639J1 
                 SNP00150051 
                 473 
                 3464 
                 G 
                 G 
                 A 
                 S1112 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 45 
                 7511425 
                 873395T6 
                 SNP00141033 
                 404 
                 3515 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 46 
                 7511534 
                 1658373T6 
                 SNP00015452 
                 2 
                 2484 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 46 
                 7511534 
                 1830479T6 
                 SNP00015452 
                 68 
                 2485 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 46 
                 7511534 
                 1872966T6 
                 SNP00015452 
                 37 
                 2499 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 46 
                 7511534 
                 7168495H1 
                 SNP00132303 
                 109 
                 285 
                 A 
                 A 
                 G 
                 T32 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 46 
                 7511534 
                 7168495H1 
                 SNP00132304 
                 126 
                 302 
                 A 
                 A 
                 G 
                 H38 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 46 
                 7511534 
                 7422001T1 
                 SNP00015452 
                 42 
                 2461 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 47 
                 7511648 
                 4056310T6 
                 SNP00105090 
                 164 
                 2987 
                 C 
                 C 
                 T 
                 V987 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 47 
                 7511648 
                 7057433F6 
                 SNP00141841 
                 216 
                 2884 
                 T 
                 T 
                 C 
                 L953 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 48 
                 7511600 
                 1275278H1 
                 SNP00020695 
                 89 
                 776 
                 C 
                 C 
                 T 
                 A233 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 48 
                 7511600 
                 1480416H1 
                 SNP00020694 
                 79 
                 369 
                 A 
                 A 
                 G 
                 A97 
                 0.95 
                 n/a 
                 n/a 
                 n/a 
               
               
                 48 
                 7511600 
                 3016303H1 
                 SNP00136636 
                 173 
                 680 
                 C 
                 C 
                 A 
                 T201 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 48 
                 7511600 
                 3088849H1 
                 SNP00020446 
                 65 
                 137 
                 G 
                 A 
                 G 
                 S20 
                 n/d 
                 n/d 
                 n/d 
                 n/a 
               
               
                 48 
                 7511600 
                 8020007J1 
                 SNP00020694 
                 480 
                 397 
                 A 
                 A 
                 G 
                 K107 
                 0.95 
                 n/a 
                 n/a 
                 n/a 
               
               
                 48 
                 7511600 
                 8020007J1 
                 SNP00136636 
                 169 
                 708 
                 C 
                 C 
                 A 
                 G210 
                 n/d 
                 n/a 
                 n/a 
                 n/a 
               
               
                 49 
                 7511783 
                 1456284H1 
                 SNP00140641 
                 213 
                 427 
                 C 
                 C 
                 A 
                 A90 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 49 
                 7511783 
                 2110750H1 
                 SNP00053655 
                 125 
                 713 
                 G 
                 G 
                 A 
                 R185 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 49 
                 7511783 
                 2138747H1 
                 SNP00050861 
                 186 
                 156 
                 G 
                 G 
                 T 
                 noncoding 
                 0.99 
                 n/a 
                 n/a 
                 n/a 
               
               
                 49 
                 7511783 
                 2138747T6 
                 SNP00053655 
                 62 
                 752 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 49 
                 7511783 
                 2359491T6 
                 SNP00140641 
                 393 
                 433 
                 C 
                 C 
                 A 
                 T92 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1230087T6 
                 SNP00011822 
                 245 
                 2873 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1230947H1 
                 SNP00011822 
                 178 
                 2892 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1290019H1 
                 SNP00011822 
                 38 
                 3256 
                 C 
                 C 
                 T 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1372412T6 
                 SNP00011822 
                 243 
                 2889 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1396849H1 
                 SNP00069830 
                 89 
                 1700 
                 G 
                 G 
                 A 
                 E504 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1482967T6 
                 SNP00011822 
                 241 
                 2886 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1614437F6 
                 SNP00011822 
                 133 
                 2894 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1618583T6 
                 SNP00011822 
                 243 
                 2872 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1619082T6 
                 SNP00011822 
                 239 
                 2868 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1939843R6 
                 SNP00011822 
                 259 
                 2853 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 1993601T6 
                 SNP00011822 
                 245 
                 2867 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 2105564H1 
                 SNP00020343 
                 93 
                 1257 
                 C 
                 C 
                 T 
                 S356 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 2105564T6 
                 SNP00011822 
                 242 
                 2882 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 2114872T6 
                 SNP00011822 
                 244 
                 2883 
                 G 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 4259235T1 
                 SNP00011822 
                 221 
                 2893 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 613960R7 
                 SNP00069403 
                 212 
                 474 
                 G 
                 G 
                 A 
                 G95 
                 0.99 
                 n/a 
                 n/a 
                 n/a 
               
               
                 50 
                 7512383 
                 7418612T1 
                 SNP00011822 
                 174 
                 2891 
                 A 
                 G 
                 A 
                 noncoding 
                 n/a 
                 n/a 
                 n/a 
                 n/a