Patent Publication Number: US-2004058347-A1

Title: Novel proteins and nucleic acids encoding same

Description:
RELATED APPLICATIONS  
     [0001] This application is a continuation-in-part of U.S. Ser. No. 10/051,874, filed Jan. 16, 2002, and claims priority to provisional patent applications U.S. Ser. No. 60/366,928, filed Mar. 22, 2002; U.S. Ser. No. 60/361,974, filed Mar. 6, 2002; U.S. Ser. No. 60/365,477, filed Mar. 19, 2002; and U.S. Ser. No. 60/401,661, filed Aug. 6, 2002, each of which is incorporated herein by reference in its entirety. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The present invention relates to novel polypeptides that are targets of small molecule drugs and that have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.  
       BACKGROUND  
       [0003] Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins and signal transducing components located within the cells.  
       [0004] Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for, example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect.  
       [0005] Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.  
       [0006] Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.  
       [0007] Small molecule targets have been implicated in various disease states or pathologies. These targets may be proteins, and particularly enzymatic proteins, which are acted upon by small molecule drugs for the purpose of altering target function and achieving a desired result. Cellular, animal and clinical studies can be performed to elucidate the genetic contribution to the etiology and pathogenesis of conditions in which small molecule targets are implicated in a variety of physiologic, pharmacologic or native states. These studies utilize the core technologies at CuraGen Corporation to look at differential gene expression, prqtein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions.  
       [0008] In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents. Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target. The target component may be any biological macromolecule implicated in the disease or pathology. Commonly the target is a polypeptide or protein with specific functional attributes. Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds.  
       [0009] In many cases the objective of such screening assays is to identify small molecule candidates; this is commonly approached by the use of combinatorial methodologies to develop the population of substances to be tested. The implementation of high throughput screening methodologies is advantageous when working with large, combinatorial libraries of compounds.  
       SUMMARY OF THE INVENTION  
       [0010] The invention includes nucleic acid sequences and the novel polypeptides they encode. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid, which represents the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or polypeptide sequences, which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23.  
       [0011] In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. One example is a variant of a mature form of a NOVX amino acid sequence, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. The amino acid can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also includes fragments of any of these. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.  
       [0012] Also included in the invention is a NOVX polypeptide that is a naturally occurring allelic variant of a NOVX sequence. In one embodiment, the allelic variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence. In another embodiment, the NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution. In one embodiment, the invention discloses a method for determining the presence or amount of the NOVX polypeptide in a sample. The method involves the steps of: providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample. In another embodiment, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject. This method involves the steps of: measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.  
       [0013] In a further embodiment, the invention includes a method of identifying an agent that binds to a NOVX polypeptide. This method involves the steps of: introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. In various embodiments, the agent is a cellular receptor or a downstream effector.  
       [0014] In another aspect, the invention provides a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a NOVX polypeptide. The method involves the steps of: providing a cell expressing the NOVX polypeptide and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent. In another aspect, the invention describes a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the NOVX polypeptide. This method involves the following steps: administering a test compound to a test animal at increased risk for a pathology associated with the NOVX polypeptide, wherein the test animal recombinantly expresses the NOVX polypeptide. This method involves the steps of measuring the activity of the NOVX polypeptide in the test animal after administering the compound of step; and comparing the activity of the protein in the test animal with the activity of the NOVX polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the NOVX polypeptide. In one embodiment, the test animal is a recombinant test animal that expresses a test protein transgene or expresses the transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein the promoter is not the native gene promoter of the transgene. In another aspect, the invention includes a method for modulating the activity of the NOVX polypeptide, the method comprising introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.  
       [0015] The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. In a preferred embodiment, the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence. In one embodiment, the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or a complement of the nucleotide sequence. In another aspect, the invention provides a vector or a cell expressing a NOVX nucleotide sequence.  
       [0016] In one embodiment, the invention discloses a method for modulating the activity of a NOVX polypeptide. The method includes the steps of: introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide. In another embodiment, the invention includes an isolated NOVX nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising a NOVX amino acid sequence or a variant of a mature form of the NOVX amino acid sequence, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. In another embodiment, the invention includes an amino acid sequence that is a variant of the NOVX amino acid sequence, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed.  
       [0017] In one embodiment, the invention discloses a NOVX nucleic acid fragment encoding at least a portion of a NOVX polypeptide or any variant of the polypeptide, wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed. In another embodiment, the invention includes the complement of any of the NOVX nucleic acid molecules or a naturally occurring allelic nucleic acid variant. In another embodiment, the invention discloses a NOVX nucleic acid molecule that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the invention discloses a NOVX nucleic acid, wherein the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.  
       [0018] In another aspect, the invention includes a NOVX nucleic acid, wherein one or more nucleotides in the NOVX nucleotide sequence is changed to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In one embodiment, the invention discloses a nucleic acid fragment of the NOVX nucleotide sequence and a nucleic acid fragment wherein one or more nucleotides in the NOVX nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In another embodiment, the invention includes a nucleic acid molecule wherein the nucleic acid molecule hybridizes under stringent conditions to a NOVX nucleotide sequence or a complement of the NOVX nucleotide sequence. In one embodiment, the invention includes a nucleic acid molecule, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the NOVX nucleotide sequence or a fragment thereof.  
       [0019] In a further aspect, the invention includes a method for determining the presence or amount of the NOVX nucleic acid in a sample. The method involves the steps of: providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the NOVX nucleic acid molecule, thereby determining the presence or amount of the NOVX nucleic acid molecule in the sample. In one embodiment, the presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.  
       [0020] In another aspect, the invention discloses a method for determining the presence of or predisposition to a disease associated with altered levels of the NOVX nucleic acid molecule of in a first mammalian subject. The method involves the steps of: measuring the amount of NOVX nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of NOVX nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.  
       [0021] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.  
       [0022] Other features and advantages of the invention will be apparent from the following detailed description and claims.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0023] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.  
               TABLE A                          Requences and Corresponding SEQ ID Numbers                                         SEQ   SEQ                   ID NO   ID NO       NOVX   Internal   (nuleic   (amino       Assignment   Identification   acid)   acid)   Homology               NOV1a   CG109413-01    1    2   Retinoic acid receptor                       gamma-1                       (RAR-gamma-1)—                         Homo sapiens         NOV1b   CG109413-02    3    4   Retinoic acid receptor                       gamma-1                       (RAR-gamma-1)—                         Homo sapiens         NOV2a   CG110266-01    5    6   Prostaglandin G/H                       synthase 1 precursor                       (EC 1.14.99.1)                       (Cyclooxygenase-1)                       (COX-1)                       (Prostaglandin-                       endoperoxide synthase                       1) (Prostaglandin H2                       synthase 1) (PGH                       synthase 1) (PGHS-1)                       (PHS 1)—                         Homo sapiens         NOV2b   CG110266-02    7    8   Prostaglandin G/H                       synthase 1 precursor                       (EC 1.14.99.1)                       (Cyclooxygenase-1)                       (COX-1)                       (Prostaglandin-                       endoperoxide synthase                       1) (Prostaglandin H2                       synthase 1) (PGH                       synthase 1) (PGHS-1)                       (PHS 1)—                         Homo sapiens         NOV3a   CG176765-01   19   10   follitropin receptor                       precursor       NOV4a   CG178142-01   11   12   Creatine kinase,                       sarcomeric mito-                       chondrial precursor                       (EC 2.7.3.2)                       (S-MtCK) (Mib-CK)                       (Basic-type mito-                       chondrial creatine                       kinase)—                         Homo sapiens         NOV5a   CG179317-01   13   14   Sequence 1 from                       Patent WO0190329—                         Homo sapiens         NOV6a   CG50159-02   15   16   lysosomal acid lipase       NOV6b   CG50159-03   17   18   lysosomal acid lipase       NOV6c   241065526   19   20   lysosomal acid lipase       NOV6d   241065558   21   22   lysosomal acid lipase       NOV6e   CG50159-01   23   24   lysosomal acid lipase       NOV6f   CG50159-04   25   26   lysosomal acid lipase       NOV7a   CG56099-03   27   28   Alanine--glyoxylate                       aminotransferase 2,                       mitochondrial                       precursor                       (EC 2.6.1.44) (AGT 2)                       (Beta-alanine-pyruvate                       aminotransferase)                       (Beta- ALAAT II)—                         Homo sapiens         NOV7b   CG56099-02   29   30   Alanine--glyoxylate                       aminotransferase 2,                       mitochondrial                       precursor                       (EC 2.6.1.44) (AGT 2)                       (Beta-alanine-pyruvate                       aminotransferase)                       (Beta- ALAAT II)—                         Homo sapiens         NOV7c   CG56099-01   31   32   Alanine--glyoxylate                       aminotransferase 2,                       mitochondrial                       precursor                       (EC 2.6.1.44) (AGT 2)                       (Beta-alanine-pyruvate                       aminotransferase)                       (Beta- ALAAT II)—                         Homo sapiens         NOV8a   CG59201-01   33   34   Factor VII active site                       mutant immuno-                       conjugate—                         Homo sapiens         NOV8b   CG59201-02   35   36   Factor VII active site                       mutant immuno-                       conjugate—                         Homo sapiens         NOV9a   CG94799-05   37   38   Chitotriosidase                       precursor— Homo                           sapiens         NOV9b   CG94799-03   39   40   Chitotriosidase                       precursor— Homo                           sapiens         NOV9c   CG94799-04   41   42   Chitotriosidase                       precursor— Homo                           sapiens         NOV9d   CG94799-01   43   44   Chitotriosidase—                       precursor— Homo                           sapiens         NOV9e   CG94799-02   45   46   Chitotriosidase                       precursor— Homo                           sapiens                    
 
       [0024] Table A indicates the homology of NOVX polypeptides to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table A will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table A.  
       [0025] Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to, e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn&#39;s disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation and fertility.  
       [0026] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.  
       [0027] Consistent with other known members of the family of proteins, identified in column 5 of Table A, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.  
       [0028] The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table A.  
       [0029] The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g., detection of a variety of cancers. SNP analysis for each NOVX, if applicable, is presented in Example D.  
       [0030] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.  
       [0031] NOVX Clones  
       [0032] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.  
       [0033] The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g., by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes. Specific uses are described for each of the NOVX genes, based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders.  
       [0034] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) a biological defense weapon.  
       [0035] In one specific embodiment, the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and (e) a fragment of any of (a) through (d).  
       [0036] In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 23; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 23 or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and (f) the complement of any of said nucleic acid molecules.  
       [0037] In yet another specific embodiment, the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.  
       [0038] NOVX Nucleic Acids and Polypeptides  
       [0039] One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.  
       [0040] A NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a “mature” form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product “mature” form arises, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., host cell) in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.  
       [0041] The term “probe”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single-stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.  
       [0042] The term “isolated” nucleic acid molecule, as used herein, is a nucleic acid that is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium, or of chemical precursors or other chemicals.  
       [0043] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or a complement of this nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), M OLECULAR  C LONING : A L ABORATORY  M ANUAL  2 nd  Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; and Ausubel, et al., (eds.), C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, New York, N.Y., 1993.)  
       [0044] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.  
       [0045] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.  
       [0046] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, thereby forming a stable duplex.  
       [0047] As used herein, the term “complementary” refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term “binding” means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.  
       [0048] A “fragment” provided herein is defined as a sequence of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, and is at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice.  
       [0049] A full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 5′ direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 3′ direction of the disclosed sequence.  
       [0050] A “derivative” is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An “analog” is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e.g., they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A “homolog” is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.  
       [0051] Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g., Ausubel, et al., C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, New York, N.Y., 1993, and below.  
       [0052] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.  
       [0053] A NOVX polypeptide is encoded by the open reading frame (“ORF”) of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bona fide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.  
       [0054] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g., from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23; or an anti-sense strand nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23; or of a naturally occurring mutant of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23.  
       [0055] Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe has a detectable label attached, e.g., the label can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express a NOVX protein, such as by measuring a level of a NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.  
       [0056] “A polypeptide having a biologically-active portion of a NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, that encodes a polypeptide having a NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.  
       [0057] NOVX Nucleic Acid and Polypeptide Variants  
       [0058] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 23.  
       [0059] In addition to the human NOVX nucleotide sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.  
       [0060] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from a human SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, are intended to be within the scope of the invention. Nucleic acid molecules corresponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.  
       [0061] Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least about 65% homologous to each other typically remain hybridized to each other.  
       [0062] Homologs (i.e., nucleic acids encoding NOVX proteins derived from species other than human) or other related sequences (e.g., paralogs) can be obtained by low, moderate or high stringency hybridization with all or a portion of the particular human sequence as a probe using methods well known in the art for nucleic acid hybridization and cloning.  
       [0063] As used herein, the phrase “stringent hybridization conditions” refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60° C. for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.  
       [0064] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6×SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2×SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).  
       [0065] In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5×Reinhardt&#39;s solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, N.Y., and Krieger, 1990; G ENE  T RANSFER AND  E XPRESSION , A L ABORATORY  M ANUAL , Stockton Press, N.Y.  
       [0066] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, N.Y., and Kriegler, 1990, G ENE  T RANSFER AND  E XPRESSION , A L ABORATORY  M ANUAL , Stockton Press, N.Y.; Shilo and Weinberg, 1981 . Proc Natl Acad Sci USA  78: 6789-6792.  
       [0067] Conservative Mutations  
       [0068] In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 23. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an “essential” amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are not particularly amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.  
       [0069] Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 40% homologous to the amino acid sequences of SEQ ID NO: 2n, wherein n is an integer between 1 and 23. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 23; more preferably at least about 70% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 23; still more preferably at least about 80% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 23; even more preferably at least about 90% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 23; and most preferably at least about 95% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 23.  
       [0070] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.  
       [0071] Mutations can be introduced any one of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.  
       [0072] The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved “strong” residues or fully conserved “weak” residues. The “strong” group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the “weak” group of conserved residues may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code.  
       [0073] In one embodiment, a mutant NOVX protein can be assayed for (i) the ability to form protein:protein interactions with other NOVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant NOVX protein and a NOVX ligand; or (iii) the ability of a mutant NOVX protein to bind to an intracellular target protein or biologically-active portion thereof, (e.g., avidin proteins).  
       [0074] In yet another embodiment, a mutant NOVX protein can be assayed for the ability to regulate a specific biological function (e.g., regulation of insulin release).  
       [0075] Interfering RNA  
       [0076] In one aspect of the invention, NOVX gene expression can be attenuated by RNA interference. One approach well-known in the art is short interfering RNA (siRNA) mediated gene silencing where expression products of a NOVX gene are targeted by specific double stranded NOVX derived siRNA nucleotide sequences that are complementary to at least a 19-25 nt long segment of the NOVX gene transcript, including the 5′ untranslated (UT) region, the ORF, or the 3′ UT region. See, e.g., PCT applications WO00/44895, WO99/32619, WO01/75164, WO01/92513, WO 01/29058, WO01/89304, WO02/16620, and WO02/29858, each incorporated by reference herein in their entirety. Targeted genes can be a NOVX gene, or an upstream or downstream modulator of the NOVX gene. Nonlimiting examples of upstream or downstream modulators of a NOVX gene include, e.g., a transcription factor that binds the NOVX gene promoter, a kinase or phosphatase that interacts with a NOVX polypeptide, and polypeptides involved in a NOVX regulatory pathway.  
       [0077] According to the methods of the present invention, NOVX gene expression is silenced using short interfering RNA. A NOVX polynucleotide according to the invention includes a siRNA polynucleotide. Such a NOVX siRNA can be obtained using a NOVX polynucleotide sequence, for example, by processing the NOVX ribopolynucleotide sequence in a cell-free system, such as but not limited to a Drosophila extract, or by transcription of recombinant double stranded NOVX RNA or by chemical synthesis of nucleotide sequences homologous to a NOVX sequence. See, e.g., Tuschl, Zamore, Lehmann, Bartel and Sharp (1999), Genes &amp; Dev. 13: 3191-3197, incorporated herein by reference in its entirety. When synthesized, a typical 0.2 micromolar-scale RNA synthesis provides about 1 milligram of siRNA, which is sufficient for 1000 transfection experiments using a 24-well tissue culture plate format.  
       [0078] The most efficient silencing is generally observed with siRNA duplexes composed of a 21-nt sense strand and a 21-nt antisense strand, paired in a manner to have a 2-nt 3′ overhang. The sequence of the 2-nt 3′ overhang makes an additional small contribution to the specificity of siRNA target recognition. The contribution to specificity is localized to the unpaired nucleotide adjacent to the first paired bases. In one embodiment, the nucleotides in the 3′ overhang are ribonucleotides. In an alternative embodiment, the nucleotides in the 3′ overhang are deoxyribonucleotides. Using 2′-deoxyribonucleotides in the 3′ overhangs is as efficient as using ribonucleotides, but deoxyribonucleotides are often cheaper to synthesize and are most likely more nuclease resistant.  
       [0079] A contemplated recombinant expression vector of the invention comprises a NOVX DNA molecule cloned into an expression vector comprising operatively-linked regulatory sequences flanking the NOVX sequence in a manner that allows for expression (by transcription of the DNA molecule) of both strands. An RNA molecule that is antisense to NOVX mRNA is transcribed by a first promoter (e.g., a promoter sequence 3′ of the cloned DNA) and an RNA molecule that is the sense strand for the NOVX mRNA is transcribed by a second promoter (e.g., a promoter sequence 5′ of the cloned DNA). The sense and antisense strands may hybridize in vivo to generate siRNA constructs for silencing of the NOVX gene. Alternatively, two constructs can be utilized to create the sense and anti-sense strands of a siRNA construct. Finally, cloned DNA can encode a construct having secondary structure, wherein a single transcript has both the sense and complementary antisense sequences from the target gene or genes. In an example of this embodiment, a hairpin RNAi product is homologous to all or a portion of the target gene. In another example, a hairpin RNAi product is a siRNA. The regulatory sequences flanking the NOVX sequence may be identical or may be different, such that their expression may be modulated independently, or in a temporal or spatial manner.  
       [0080] In a specific embodiment, siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA H1. One example of a vector system is the GeneSuppressor™ RNA Interference kit (commercially available from Imgenex). The U6 and H1 promoters are members of the type III class of Pol III promoters. The +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for H1 promoters is adenosine. The termination signal for these promoters is defined by five consecutive thymidines. The transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3′ UU overhang in the expressed siRNA, which is similar to the 3′ overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21-nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript.  
       [0081] A siRNA vector appears to have an advantage over synthetic siRNAs where long term knock-down of expression is desired. Cells transfected with a siRNA expression vector would experience steady, long-term mRNA inhibition. In contrast, cells transfected with exogenous synthetic siRNAs typically recover from mRNA suppression within seven days or ten rounds of cell division. The long-term gene silencing ability of siRNA expression vectors may provide for applications in gene therapy.  
       [0082] In general, siRNAs are chopped from longer dsRNA by an ATP-dependent ribonuclease called DICER. DICER is a member of the RNase III family of double-stranded RNA-specific endonucleases. The siRNAs assemble with cellular proteins into an endonuclease complex. In vitro studies in Drosophila suggest that the siRNAs/protein complex (siRNP) is then transferred to a second enzyme complex, called an RNA-induced silencing complex (RISC), which contains an endoribonuclease that is distinct from DICER. RISC uses the sequence encoded by the antisense siRNA strand to find and destroy mRNAs of complementary sequence. The siRNA thus acts as a guide, restricting the ribonuclease to cleave only mRNAs complementary to one of the two siRNA strands.  
       [0083] A NOVX mRNA region to be targeted by siRNA is generally selected from a desired NOVX sequence beginning 50 to 100 nt downstream of the start codon. Alternatively, 5′ or 3′ UTRs and regions nearby the start codon can be used but are generally avoided, 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 or RISC endonuclease complex. An initial BLAST homology search for the selected siRNA sequence is done against an available nucleotide sequence library to ensure that only one gene is targeted. Specificity of target recognition by siRNA duplexes indicate that a single point mutation located in the paired region of an siRNA duplex is sufficient to abolish target mRNA degradation. See, Elbashir et al. 2001 EMBO J. 20(23):6877-88. Hence, consideration should be taken to accommodate SNPs, polymorphisms, allelic variants or species-specific variations when targeting a desired gene.  
       [0084] In one embodiment, a complete NOVX siRNA experiment includes the proper negative control. A negative control siRNA generally has the same nucleotide composition as the NOVX siRNA but lack significant sequence homology to the genome. Typically, one would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene.  
       [0085] Two independent NOVX siRNA duplexes can be used to knock-down a target NOVX gene. This helps to control for specificity of the silencing effect. In addition, expression of two independent genes can be simultaneously knocked down by using equal concentrations of different NOVX siRNA duplexes, e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide. Availability of siRNA-associating proteins is believed to be more limiting than target mRNA accessibility.  
       [0086] A targeted NOVX region is typically a sequence of two adenines (AA) and two thymidines (TT) divided by a spacer region of nineteen (N19) residues (e.g., AA(N19)TT). A desirable spacer region has a G/C-content of approximately 30% to 70%, and more preferably of about 50%. If the sequence AA(N19)TT is not present in the target sequence, an alternative target region would be AA(N21). The sequence of the NOVX sense siRNA corresponds to (N19)TT or N21, respectively. In the latter case, conversion of the 3′ end of the sense siRNA to TT can be performed if such a sequence does not naturally occur in the NOVX polynucleotide. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3′ overhangs. Symmetric 3′ overhangs may help to ensure that the siRNPs are formed with approximately equal ratios of sense and antisense target RNA-cleaving siRNPs. See, e.g., Elbashir, Lendeckel and Tuschl (2001). Genes &amp; Dev. 15: 188-200, incorporated by reference herein in its entirely. The modification of the overhang of the sense sequence of the siRNA duplex is not expected to affect targeted mRNA recognition, as the antisense siRNA strand guides target recognition.  
       [0087] Alternatively, if the NOVX target mRNA does not contain a suitable AA(N21) sequence, one may search for the sequence NA(N21). Further, the sequence of the sense strand and antisense strand may still be synthesized as 5′ (N19)TT, as it is believed that the sequence of the 3′-most nucleotide of the antisense siRNA does not contribute to specificity. Unlike antisense or ribozyme technology, the secondary structure of the target mRNA does not appear to have a strong effect on silencing. See, Harborth, et al. (2001) J. Cell Science 114: 4557-4565, incorporated by reference in its entirety.  
       [0088] Transfection of NOVX siRNA duplexes can be achieved using standard nucleic acid transfection methods, for example, OLIGOFECTAMINE Reagent (commercially available from Invitrogen). An assay for NOVX gene silencing is generally performed approximately 2 days after transfection. No NOVX gene silencing has been observed in the absence of transfection reagent, allowing for a comparative analysis of the wild-type and silenced NOVX phenotypes. In a specific embodiment, for one well of a 24-well plate, approximately 0.84 μg of the siRNA duplex is generally sufficient. Cells are typically seeded the previous day, and are transfected at about 50% confluence. The choice of cell culture media and conditions are routine to those of skill in the art, and will vary with the choice of cell type. The efficiency of transfection may depend on the cell type, but also on the passage number and the confluency of the cells. The time and the manner of formation of siRNA-liposome complexes (e.g., inversion versus vortexing) are also critical. Low transfection efficiencies are the most frequent cause of unsuccessful NOVX silencing. The efficiency of transfection needs to be carefully examined for each new cell line to be used. Preferred cell are derived from a mammal, more preferably from a rodent such as a rat or mouse, and most preferably from a human. Where used for therapeutic treatment, the cells are preferentially autologous, although non-autologous cell sources are also contemplated as within the scope of the present invention.  
       [0089] For a control experiment, transfection of 0.84 μg single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 μg antisense siRNA has a weak silencing effect when compared to 0.84 μg of duplex siRNAs. Control experiments again allow for a comparative analysis of the wild-type and silenced NOVX phenotypes. To control for transfection efficiency, targeting of common proteins is typically performed, for example targeting of lamin A/C or transfection of a CMV-driven EGFP-expression plasmid (e.g., commercially available from Clontech). In the above example, a determination of the fraction of lamin A/C knockdown in cells is determined the next day by such techniques as immunofluorescence, Western blot, Northern blot or other similar assays for protein expression or gene expression. Lamin A/C monoclonal antibodies may be obtained from Santa Cruz Biotechnology.  
       [0090] Depending on the abundance and the half life (or turnover) of the targeted NOVX polynucleotide in a cell, a knock-down phenotype may become apparent after 1 to 3 days, or even later. In cases where no NOVX knock-down phenotype is observed, depletion of the NOVX polynucleotide may be observed by immunofluorescence or Western blotting. If the NOVX polynucleotide is still abundant after 3 days, cells need to be split and transferred to a fresh 24-well plate for re-transfection. If no knock-down of the targeted protein is observed, it may be desirable to analyze whether the target mRNA (NOVX or a NOVX upstream or downstream gene) was effectively destroyed by the transfected siRNA duplex. Two days after transfection, total RNA is prepared, reverse transcribed using a target-specific primer, and PCR-amplified with a primer pair covering at least one exon-exon junction in order to control for amplification of pre-mRNAs. RT/PCR of a non-targeted mRNA is also needed as control. Effective depletion of the mRNA yet undetectable reduction of target protein may indicate that a large reservoir of stable NOVX protein may exist in the cell. Multiple transfection in sufficiently long intervals may be necessary until the target protein is finally depleted to a point where a phenotype may become apparent. If multiple transfection steps are required, cells are split 2 to 3 days after transfection. The cells may be transfected immediately after splitting.  
       [0091] An inventive therapeutic method of the invention contemplates administering a NOVX siRNA construct as therapy to compensate for increased or aberrant NOVX expression or activity. The NOVX ribopolynucleotide is obtained and processed into siRNA fragments, or a NOVX siRNA is synthesized, as described above. The NOVX siRNA is administered to cells or tissues using known nucleic acid transfection techniques, as described above. A NOVX siRNA specific for a NOVX gene will decrease or knockdown NOVX transcription products, which will lead to reduced NOVX polypeptide production, resulting in reduced NOVX polypeptide activity in the cells or tissues.  
       [0092] The present invention also encompasses a method of treating a disease or condition associated with the presence of a NOVX protein in an individual comprising administering to the individual an RNAi construct that targets the mRNA of the protein (the mRNA that encodes the protein) for degradation. A specific RNAi construct includes a siRNA or a double stranded gene transcript that is processed into siRNAs. Upon treatment, the target protein is not produced or is not produced to the extent it would be in the absence of the treatment.  
       [0093] Where the NOVX gene function is not correlated with a known phenotype, a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like. A subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state. The NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product. These cells or tissues are treated by administering NOVX siRNA&#39;s to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described. This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX − ) phenotype in the treated subject sample. The NOVX −  phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.  
       [0094] In specific embodiments, a NOVX siRNA is used in therapy. Methods for the generation and use of a NOVX siRNA are known to those skilled in the art. Example techniques are provided below.  
       [0095] Production of RNAs  
       [0096] Sense RNA (ssRNA) and antisense RNA (asRNA) of NOVX are produced using known methods such as transcription in RNA expression vectors. In the initial experiments, the sense and antisense RNA are about 500 bases in length each. The produced ssRNA and asRNA (0.5 μM) in 10 mM Tris-HCl (pH 7.5) with 20 mM NaCl were heated to 95° C. for 1 min then cooled and annealed at room temperature for 12 to 16 h. The RNAs are precipitated and resuspended in lysis buffer (below). To monitor annealing, RNAs are electrophoresed in a 2% agarose gel in TBE buffer and stained with ethidium bromide. See, e.g., Sambrook et al., Molecular Cloning. Cold Spring Harbor Laboratory Press, Plainview, N.Y. (1989).  
       [0097] Lysate Preparation  
       [0098] Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer&#39;s directions. dsRNA is incubated in the lysate at 30° C. for 10 min prior to the addition of mRNAs. Then NOVX mRNAs are added and the incubation continued for an additional 60 min. The molar ratio of double stranded RNA and mRNA is about 200:1. The NOVX mRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis.  
       [0099] In a parallel experiment made with the same conditions, the double stranded RNA is internally radiolabeled with a  32 P-ATP. Reactions are stopped by the addition of 2×proteinase K buffer and deproteinized as described previously (Tuschl et al., Genes Dev., 13:3191-3197 (1999)). Products are analyzed by electrophoresis in 15% or 18% polyacrylamide sequencing gels using appropriate RNA standards. By monitoring the gels for radioactivity, the natural production of 10 to 25 nt RNAs from the double stranded RNA can be determined.  
       [0100] The band of double stranded RNA, about 21-23 bps, is eluded. The efficacy of these 21-23 mers for suppressing NOVX transcription is assayed in vitro using the same rabbit reticulocyte assay described above using 50 nanomolar of double stranded 21-23 mer for each assay. The sequence of these 21-23 mers is then determined using standard nucleic acid sequencing techniques.  
       [0101] RNA Preparation  
       [0102] 21 nt RNAs, based on the sequence determined above, are chemically synthesized using Expedite RNA phosphoramidites and thymidine phosphoramidite (Proligo, Germany). Synthetic oligonucleotides are deprotected and gel-purified (Elbashir, Lendeckel, &amp; Tuschl, Genes &amp; Dev. 15, 188-200 (2001)), followed by Sep-Pak C18 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)). at 90° C. followed by 1 h at 37° C.  
       [0103] Cell Culture  
       [0104] A cell culture known in the art to regularly express NOVX is propagated using standard conditions. 24 hours before transfection, at approx. 80% confluency, the cells are trypsinized and diluted 1:5 with fresh medium without antibiotics (1-3×105 cells/ml) and transferred to 24-well plates (500 ml/well). Transfection is performed using a commercially available lipofection kit and NOVX expression is monitored using standard techniques with positive and negative control. A positive control is cells that naturally express NOVX while a negative control is cells that do not express NOVX. Base-paired 21 and 22 nt siRNAs with overhanging 3′ ends mediate efficient sequence-specific mRNA degradation in lysates and in cell culture. Different concentrations of siRNAs are used. An efficient concentration for suppression in vitro in mammalian culture is between 25 nM to 100 nM final concentration. This indicates that siRNAs are effective at concentrations that are several orders of magnitude below the concentrations applied in conventional antisense or ribozyme gene targeting experiments.  
       [0105] The above method provides a way both for the deduction of NOVX siRNA sequence and the use of such siRNA for in vitro suppression. In vivo suppression may be performed using the same siRNA using well known in vivo transfection or gene therapy transfection techniques.  
       [0106] Antisense Nucleic Acids  
       [0107] Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, are additionally provided.  
       [0108] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding a NOVX protein. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding the NOVX protein. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i.e., also referred to as 5′ and 3′ untranslated regions).  
       [0109] Given the coding strand sequences encoding the NOVX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of NOVX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used).  
       [0110] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).  
       [0111] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.  
       [0112] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987 . Nucl. Acids Res . 15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (See, e.g., Inoue, et al. 1987 . Nucl. Acids Res . 15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987 . FEBS Lett . 215: 327-330.  
       [0113] Ribozymes and PNA Moieties  
       [0114] Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.  
       [0115] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988 . Nature  334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et al. and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al., (1993)  Science  261:1411-1418.  
       [0116] Alternatively, NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g., the NOVX promoter and/or enhancers) to form triple helical structures that prevent transcription of the NOVX gene in target cells. See, e.g., Helene, 1991 . Anticancer Drug Des . 6: 569-84; Helene, et al. 1992 . Ann. N.Y. Acad. Sci . 660: 27-36; Maher, 1992 . Bioassays  14: 807-15.  
       [0117] In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996 . Bioorg Med Chem  4: 5-23. As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O&#39;Keefe, et al., 1996 . Proc. Natl. Acad. Sci. USA  93: 14670-14675.  
       [0118] PNAs of NOVX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation arrest or inhibiting replication. PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., S 1  nucleases (See, Hyrup, et al., 1996. supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O&#39;Keefe, et al., 1996. supra).  
       [0119] In another embodiment, PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g., RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al., 1996 . Nucl Acids Res  24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5′ end of DNA. See, e.g., Mag, et al., 1989 . Nucl Acid Res  17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment. See, e.g., Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment. See, e.g., Petersen, et al., 1975 . Bioorg. Med. Chem. Lett . 5: 1119-11124.  
       [0120] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989 . Proc. Natl. Acad. Sci. U.S.A . 86: 6553-6556; Lemaitre, et al., 1987 . Proc. Natl. Acad. Sci . 84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988 . Bio Techniques  6:958-976) or intercalating agents (see, e.g., Zon, 1988 . Pharm. Res . 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.  
       [0121] NOVX Polypeptides  
       [0122] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO: 2n, wherein n is an integer between 1 and 23. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in any one of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof  
       [0123] In general, a NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.  
       [0124] One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.  
       [0125] An “isolated” or “purified” polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the NOVX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language “substantially free of cellular material” includes preparations of NOVX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly-produced. In one embodiment, the language “substantially free of cellular material” includes preparations of NOVX proteins having less than about 30% (by dry weight) of non-NOVX proteins (also referred to herein as a “contaminating protein”), more preferably less than about 20% of non-NOVX proteins, still more preferably less than about 10% of non-NOVX proteins, and most preferably less than about 5% of non-NOVX proteins. When the NOVX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the NOVX protein preparation.  
       [0126] The language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins in which the protein is separated fromchemical precursors or other chemicals that are involved in the synthesis of the protein. In one embodiment, the language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins having less than about 30% (by dry weight) of chemical precursors or non-NOVX chemicals, more preferably less than about 20% chemical precursors or non-NOVX chemicals, still more preferably less than about 10% chemical precursors or non-NOVX chemicals, and most preferably less than about 5% chemical precursors or non-NOVX chemicals.  
       [0127] Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 23) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a NOVX protein. Typically, biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein. A biologically-active portion of a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.  
       [0128] Moreover, other biologically-active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native NOVX protein.  
       [0129] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 23. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 23, and retains the functional activity of the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, and retains the functional activity of the NOVX proteins of SEQ ID NO: 2n, wherein n is an integer between 1 and 23.  
       [0130] Determining Homology Between Two or More Sequences  
       [0131] To determine the percent homology of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid “homology” is equivalent to amino acid or nucleic acid “identity”).  
       [0132] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970 . J Mol Biol  48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23.  
       [0133] The term “sequence identity” refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term “percentage of sequence identity” is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term “substantial identity” as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.  
       [0134] Chimeric and Fusion Proteins  
       [0135] The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX “chimeric protein” or “fusion protein” comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a NOVX protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, whereas a “non-NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within a NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of a NOVX protein. In one embodiment, a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein. In another embodiment, a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein. In yet another embodiment, a NOVX fusion protein comprises at least three biologically-active portions of a NOVX protein. Within the fusion protein, the term “operatively-linked” is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another. The non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide.  
       [0136] In one embodiment, the fusion protein is a GST-NOVX fusion protein in which the NOVX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences. Such fusion proteins can facilitate the purification of recombinant NOVX polypeptides.  
       [0137] In another embodiment, the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.  
       [0138] In yet another embodiment, the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e.g., promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand.  
       [0139] A NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fuision moiety (e.g., a GST polypeptide). A NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein.  
       [0140] NOVX Agonists and Antagonists  
       [0141] The invention also pertains to variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists. Variants of the NOVX protein can be generated by mutagenesis (e.g., discrete point mutation or truncation of the NOVX protein). An agonist of the NOVX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the NOVX protein. An antagonist of the NOVX protein can inhibit one or more of the activities of the naturally occurring form of the NOVX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the NOVX protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the NOVX proteins.  
       [0142] Variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists can be identified by screening combinatorial libraries of mutants (e.g., truncation mutants) of the NOVX proteins for NOVX protein agonist or antagonist activity. In one embodiment, a variegated library of NOVX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of NOVX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of NOVX sequences therein. There are a variety of methods which can be used to produce libraries of potential NOVX variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential NOVX sequences. Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e.g., Narang, 1983 . Tetrahedron  39: 3; Itakura, et al., 1984 . Annu. Rev. Biochem . 53: 323; Itakura, et al., 1984 . Science  198: 1056; Ike, et al., 1983 . Nucl. Acids Res . 11: 477.  
       [0143] Polypeptide Libraries  
       [0144] In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.  
       [0145] Various techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of NOVX proteins. The most widely used techniques, which are amenable to high throughput analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify NOVX variants. See, e.g., Arkin and Yourvan, 1992 . Proc. Natl. Acad. Sci. USA  89: 7811-7815; Delgrave, et al., 1993 . Protein Engineering  6:327-331.  
       [0146] Anti-NOVX Antibodies  
       [0147] Included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, F ab , F ab′ and F (ab′)2  fragments, and an F ab  expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG 1 , IgG 2 , and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.  
       [0148] An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 23, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope. Preferably, the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues. Preferred epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions.  
       [0149] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981 , Proc. Nat. Acad. Sci. USA  78: 3824-3828; Kyte and Doolittle 1982 , J. Mol. Biol . 157: 105-142, each incorporated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.  
       [0150] The term “epitope” includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (K D ) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.  
       [0151] A protein of the invention, or a derivative, fragment, analog, homolog or ortholog thereof, may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components.  
       [0152] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.  
       [0153] Polyclonal Antibodies  
       [0154] For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund&#39;s (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).  
       [0155] The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (Apr. 17, 2000), pp. 25-28).  
       [0156] Monoclonal Antibodies  
       [0157] The term “monoclonal antibody” (MAb) or “monoclonal antibody composition”, as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.  
       [0158] Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro.  
       [0159] The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, M ONOCLONAL  A NTIBODIES : P RINCIPLES AND  P RACTICE , Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (“HAT medium”), which substances prevent the growth of HGPRT-deficient cells.  
       [0160] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).  
       [0161] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.  
       [0162] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding,1986). Suitable culture media for this purpose include, for example, Dulbecco&#39;s Modified Eagle&#39;s Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.  
       [0163] The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.  
       [0164] The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or mycloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.  
       [0165] Humanized Antibodies  
       [0166] The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′) 2  or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Pat. No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fe), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)).  
       [0167] Human Antibodies  
       [0168] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: M ONOCLONAL  A NTIBODIES AND  C ANCER  T HERAPY , Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: M ONOCLONAL  A NTIBODIES AND  C ANCER  T HERAPY , Alan R. Liss, Inc., pp. 77-96).  
       [0169] In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859 (1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild et al,(Nature Biotechnology 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).  
       [0170] Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal&#39;s endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host&#39;s genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.  
       [0171] An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Pat. No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rearrangement of the locus and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.  
       [0172] A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Pat. No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.  
       [0173] In a further improvement on this procedure, a method for identifying a clinically relevant epitope on an immunogen, and a correlative method for selecting an antibody that binds immunospecifically to the relevant epitope with high affinity, are disclosed in PCT publication WO 99/53049.  
       [0174] F ab  Fragments and Single Chain Antibodies  
       [0175] According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Pat. No. 4,946,778). In addition, methods can be adapted for the construction of F ab  expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal F ab  fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F (ab′)2  fragment produced by pepsin digestion of an antibody molecule; (ii) an F ab  fragment generated by reducing the disulfide bridges of an F (ab′)2  fragment; (iii) an F ab  fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F v  fragments.  
       [0176] Bispecific Antibodies Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for an antigenic protein of the invention. The second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.  
       [0177] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).  
       [0178] Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).  
       [0179] According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g., tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g., alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.  
       [0180] Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g., F(ab′) 2  bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab′) 2  fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab′ fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives is then reconverted to the Fab′-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab′-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.  
       [0181] Additionally, Fab′ fragments can be directly recovered from  E. coli  and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab′) 2  molecule. Each Fab′ fragment was separately secreted from  E. coli  and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.  
       [0182] Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab′ portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The “diabody” technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (V H ) connected to a light-chain variable domain (V L ) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the V H  and V L  domains of one fragment are forced to pair with the complementary V L  and V H  domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).  
       [0183] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).  
       [0184] Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined; with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g., CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).  
       [0185] Heteroconjugate Antibodies  
       [0186] Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980), and for treatrnent of HIV infection (WO 91/00360; WO 92/200373; EP 03089). It is contemplated that the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Pat. No. 4,676,980.  
       [0187] Effector Function Engineering  
       [0188] It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 148: 2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fe regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989).  
       [0189] Immunoconjugates  
       [0190] The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).  
       [0191] Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include  212 Bi,  131 I,  131 In,  90 Y, and  186 Re.  
       [0192] Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al.,  Science , 238: 1098 (1987). Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.  
       [0193] In another embodiment, the antibody can be conjugated to a “receptor” (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a “ligand” (e.g., avidin) that is in turn conjugated to a cytotoxic agent.  
       [0194] Immunoliposomes  
       [0195] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.  
       [0196] Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab′ fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al., J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al., J. National Cancer Inst., 81(19): 1484 (1989).  
       [0197] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention  
       [0198] In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.  
       [0199] Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as “Therapeutics”).  
       [0200] An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidinibiotin and avidintbiotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include  125 I,  131 I,  35 S or  3 H.  
       [0201] Antibody Therapeutics  
       [0202] Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor. mediates a signal transduction pathway for which ligand is responsible.  
       [0203] Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand which may be absent or defective in the disease or pathology, binds the antibody as a surrogate effector ligand, initiating a receptor-based signal transduction event by the receptor.  
       [0204] A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.  
       [0205] Pharmaceutical Compositions of Antibodies  
       [0206] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington: The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement : Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.  
       [0207] If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.  
       [0208] The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.  
       [0209] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.  
       [0210] Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.  
       [0211] ELISA Assay  
       [0212] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., F ab  or F (ab)2 ) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Theory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.  
       [0213] NOVX Recombinant Expression Vectors and Host Cells  
       [0214] Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a NOVX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as “expression vectors”. In general, useful expression vectors in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.  
       [0215] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably-linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).  
       [0216] The term “regulatory sequence” is intended to includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).  
       [0217] The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as  Escherichia coli , insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.  
       [0218] Expression of proteins in prokaryotes is most often carried out in  Escherichia coli  with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: (i) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988 . Gene  67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.  
       [0219] Examples of suitable inducible non-fusion  E. coli  expression vectors include pTrc (Amrann et al., (1988)  Gene  69:301-315) and pET 11d (Studier et al., G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990) 60-89).  
       [0220] One strategy to maximize recombinant protein expression in  E. coli  is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g., Gottesman, G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in  E. coli  (see, e.g., Wada, et al., 1992 . Nucl. Acids Res . 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.  
       [0221] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast  Saccharomyces cerivisae  include pYepSec1 (Baldari, et al., 1987 . EMBO J . 6: 229-234), pMFa (Kurjan and Herskowitz, 1982 . Cell  30: 933-943), pJRY88 (Schultz et al., 1987 . Gene  54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).  
       [0222] Alternatively, NOVX can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, et al., 1983 . Mol. Cell. Biol . 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989 . Virology  170: 31-39).  
       [0223] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987 . Nature  329: 840) and pMT2PC (Kaufman, et al., 1987 . EMBO J . 6: 187-195). When used in mammalian cells, the expression vector&#39;s control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., M OLECULAR  C LONING : A L ABORATORY  M ANUAL . 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.  
       [0224] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987 . Genes Dev . 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988 . Adv. Immunol . 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989 . EMBO J . 8: 729-733) and immunoglobulins (Baneiji, et al., 1983 . Cell  33: 729-740; Queen and Baltimore, 1983 . Cell  33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989 . Proc. Natl. Acad. Sci. USA  86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985 . Science  230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990 . Science  249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989 . Genes Dev . 3: 537-546).  
       [0225] The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraub, et al., “Antisense RNA as a molecular tool for genetic analysis,”  Reviews - Trends in Genetics , Vol. 1(1) 1986.  
       [0226] Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.  
       [0227] A host cell can be any prokaryotic or eukaryotic cell. For example, NOVX protein can be expressed in bacterial cells such as  E. coli , insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.  
       [0228] Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (M OLECULAR  C LONING : A L ABORATORY  M ANUAL . 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.  
       [0229] For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Various selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding NOVX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).  
       [0230] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein. Accordingly, the invention further provides methods for producing NOVX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced. In another embodiment, the method further comprises isolating NOVX protein from the medium or the host cell.  
       [0231] Transgenic NOVX Animals  
       [0232] The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NOVX sequences have been altered. Such animals are useful for studying the function and/or activity of NOVX protein and for identifying and/or evaluating modulators of NOVX protein activity. As used herein, a “transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a “homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous NOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.  
       [0233] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences, i.e., any one of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: M ANIPULATING THE  M OUSE  E MBRYO , Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other transgenes.  
       [0234] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA of any one of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, can be used to construct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally disrupted (i.e., no longer encodes a functional protein; also referred to as a “knock out” vector).  
       [0235] Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous NOVX gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous NOVX protein). In the homologous recombination vector, the altered portion of the NOVX gene is flanked at its 5′- and 3′-termini by additional nucleic acid of the NOVX gene to allow for homologous recombination to occur between the exogenous NOVX gene carried by the vector and an endogenous NOVX gene in an embryonic stem cell. The additional flanking NOVX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5′- and 3′-termini) are included in the vector. See, e.g., Thomas, et al., 1987 . Cell  51: 503 for a description of homologous recombination vectors. The vector is ten introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced NOVX gene has homologously-recombined with the endogenous NOVX gene are selected. See, e.g., Li, et al., 1992 . Cell  69: 915.  
       [0236] The selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras. See, e.g., Bradley, 1987. In: T ERATOCARCFNOMAS AND  E MBRYONIC  S TEM  C ELLS : A P RACTICAL  A PPROACH , Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991 . Curr. Opin. Biotechnol . 2: 823-829; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169.  
       [0237] In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, See, e.g., Lakso, et al., 1992 . Proc. Natl. Acad. Sci. USA  89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of  Saccharomyces cerevisiae . See, O&#39;Gorman, et al., 1991 . Science  251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of “double” transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.  
       [0238] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997 . Nature  385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter G 0  phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.  
       [0239] Pharmaceutical Compositions  
       [0240] The NOVX nucleic acid molecules, NOVX proteins, and anti-NOVX antibodies (also referred to herein as “active compounds”) of the invention, and derivatives, fragments, analogs and homologs thereof, can be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier. As used herein, “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifuingal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington&#39;s Pharmaceutical Sciences, a standard reference text in the field, which is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, finger&#39;s solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.  
       [0241] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.  
       [0242] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.  
       [0243] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., a NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.  
       [0244] Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.  
       [0245] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.  
       [0246] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.  
       [0247] The compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.  
       [0248] In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.  
       [0249] It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.  
       [0250] The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Pat. No. 5,328,470) or by stereotactic injection (see, e.g., Chen, et al., 1994 . Proc. Natl. Acad. Sci. USA  91: 3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system.  
       [0251] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.  
       [0252] Screening and Detection Methods  
       [0253] The isolated nucleic acid molecules of the invention can be used to express NOVX protein (e.g., via a recombinant expression vector in a host cell in gene therapy applications), to detect NOVX mRNA (e.g., in a biological sample) or a genetic lesion in a NOVX gene, and to modulate NOVX activity, as described further, below. In addition, the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or aberrant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease (possesses anti-microbial activity) and the various dyslipidemias. In addition, the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absorption of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.  
       [0254] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.  
       [0255] Screening Assays  
       [0256] The invention provides a method (also referred to herein as a “screening assay”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity. The invention also includes compounds identified in the screening assays described herein.  
       [0257] In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the “one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g., Lam, 1997 . Anticancer Drug Design  12: 145.  
       [0258] A “small molecule” as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e.g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and/or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.  
       [0259] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al., 1993 . Proc. Natl. Acad. Sci. U.S.A . 90: 6909; Erb, et al., 1994 . Proc. Natl. Acad. Sci. U.S.A . 91: 11422; Zuckermann, et al., 1994 . J. Med. Chem . 37: 2678; Cho, et al., 1993 . Science  261: 1303; Carrell, et al., 1994 . Angew. Chem. Int. Ed. Engl . 33: 2059; Carell, et al., 1994 . Angew. Chem. Int. Ed. Engl . 33: 2061; and Gallop, et al., 1994 . J. Med. Chem . 37: 1233.  
       [0260] Libraries of compounds may be presented in solution (e.g., Houghten, 1992 . Biotechniques  13: 412-421), or on beads (Lam, 1991 . Nature  354: 82-84), on chips (Fodor, 1993 . Nature  364: 555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992 . Proc. Natl. Acad. Sci. USA  89: 1865-1869) or on phage (Scott and Smith, 1990 . Science  249: 386-390; Devlin, 1990 . Science  249: 404-406; Cwirla, et al., 1990 . Proc. Natl. Acad. Sci. U.S.A . 87: 6378-6382; Felici, 1991 . J. Mol. Biol . 222: 301-310; Ladner, U.S. Pat. No. 5,233,409.).  
       [0261] In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with  125 I,  35 S,  14 C, or  3 H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting. Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.  
       [0262] In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule. As used herein, a “target molecule” is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. A NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention. In one embodiment, a NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g., a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.  
       [0263] Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e., intracellular Ca 2+ , diacylglycerol, IP 3 , etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.  
       [0264] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the NOVX protein or biologically-acfive portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.  
       [0265] In still another embodiment, an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to a NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate a NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.  
       [0266] In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.  
       [0267] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether) n , N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).  
       [0268] In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either NOVX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-NOVX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra. Alternatively, the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.  
       [0269] Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.  
       [0270] In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.  
       [0271] In yet another aspect of the invention, the NOVX proteins can be used as “bait proteins” in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos, et al., 1993 . Cell  72: 223-232; Madura, et al., 1993 . J Biol. Chem . 268: 12046-12054; Bartel, et al., 1993 . Biotechniques  14: 920-924; Iwabuchi, et al., 1993 . Oncogene  8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) and modulate NOVX activity. Such NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.  
       [0272] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.  
       [0273] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.  
       [0274] Detection Assays  
       [0275] Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.  
       [0276] Chromosome Mapping  
       [0277] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping of the NOVX sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.  
       [0278] Briefly, NOVX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the NOVX sequences. Computer analysis of the NOVX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the NOVX sequences will yield an amplified fragment.  
       [0279] Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D&#39;Eustachio, et al., 1983 . Science  220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.  
       [0280] PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the NOVX sequences to design oligonucleotide primers, sub-localization can be achieved with panels of fragments from specific chromosomes.  
       [0281] Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually. The FISH technique can be used with a DNA sequence as short as 500 or 600 bases. However, clones larger than 1,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al., H UMAN  C HROMOSOMES : A M ANUAL OF  B ASIC  T ECHNIQUES  (Pergamon Press, New York 1988).  
       [0282] Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.  
       [0283] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, M ENDELIAN  I NHERITANCE IN  M AN , available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al., 1987 . Nature,  325: 783-787.  
       [0284] Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the NOVX gene, can be determined. If a mutation is observed in some or all of the affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent of the particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymorphisms.  
       [0285] Tissue Typing  
       [0286] The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual&#39;s genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences of the invention are useful as additional DNA markers for RFLP (“restriction fragment length polymorphisms,” described in U.S. Pat. No. 5,272,057).  
       [0287] Furthermore, the sequences of the invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual&#39;s genome. Thus, the NOVX sequences described herein can be used to prepare two PCR primers from the 5′- and 3′-termini of the sequences. These primers can then be used to amplify an individual&#39;s DNA and subsequently sequence it.  
       [0288] Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the invention can be used to obtain such identification sequences from individuals and from tissue. The NOVX sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much of the allelic variation is due to single nucleotide polymorphisms (SNPs), which include restriction fragment length polymorphisms (RFLPs).  
       [0289] Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If coding sequences, such as those of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.  
       [0290] Predictive Medicine  
       [0291] The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.  
       [0292] Another aspect of the invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as “pharmacogenomics”). Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability of the individual to respond to a particular agent.)  
       [0293] Yet another aspect of the invention pertains to monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX in clinical trials.  
       [0294] These and other agents are described in further detail in the following sections.  
       [0295] Diagnostic Assays  
       [0296] An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 23, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.  
       [0297] An agent for detecting NOVX protein is an antibody capable of binding to NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., F ab  or F(ab′) 2 ) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immutioprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.  
       [0298] In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.  
       [0299] In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting NOVX protein, mRNA, or genomic DNA, such that the presence of NOVX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of NOVX protein, mRNA or genomic DNA in the control sample with the presence of NOVX protein, mRNA or genomic DNA in the test sample.  
       [0300] The invention also encompasses kits for detecting the presence of NOVX in a biological sample. For example, the kit can comprise: a labeled compound or agent capable of detecting NOVX protein or mRNA in a biological sample; means for determining the amount of NOVX in the sample; and means for comparing the amount of NOVX in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect NOVX protein or nucleic acid.  
       [0301] Prognostic Assays  
       [0302] The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. For example, the assays described herein, such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder. Thus, the invention provides a method for identifying a disease or disorder associated with aberrant NOVX expression or activity in which a test sample is obtained from a subject and NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at riskof developing a disease or disorder associated with aberrant NOVX expression or activity. As used herein, a “test sample” refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.  
       [0303] Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant NOVX expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder. Thus, the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant NOVX expression or activity in which a test sample is obtained and NOVX protein or nucleic acid is detected (e.g., wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with aberrant NOVX expression or activity).  
       [0304] The methods of the invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of: (i) a deletion of one or more nucleotides from a NOVX gene; (ii) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) aberrant modification of a NOVX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non-wild-type splicing pattern of a messenger RNA transcript of a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in a NOVX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.  
       [0305] In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al., 1988 . Science  241: 1077-1080; and Nakazawa, et al., 1994 . Proc. Natl. Acad. Sci. USA  91: 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al., 1995 . Nucl. Acids Res . 23: 675-682). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to a NOVX gene under conditions such that hybridization and amplification of the NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.  
       [0306] Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al., 1990 . Proc. Natl. Acad. Sci. USA  87: 1874-1878), transcriptional amplification system (see, Kwoh, et al., 1989 . Proc. Natl. Acad. Sci. USA  86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988 . Bio Technology  6: 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.  
       [0307] In an alternative embodiment, mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Pat. No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.  
       [0308] In other embodiments, genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density arrays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al., 1996 . Human Mutation  7: 244-255; Kozal, et al., 1996 . Nat. Med . 2: 753-759. For example, genetic mutations in NOVX can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, et al., supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations. This is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.  
       [0309] In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence of the sample NOVX with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977 . Proc. Natl. Acad. Sci. USA  74: 560 or Sanger, 1977 . Proc. Natl. Acad. Sci. USA  74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g., Naeve, et al., 1995 . Biotechniques  19: 448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101; Cohen, et al., 1996 . Adv. Chromatography  36: 127-162; and Griffin, et al., 1993 . Appl. Biochem. Biotechnol . 38: 147-159).  
       [0310] Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al., 1985 . Science  230: 1242. In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S 1  nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al., 1988 . Proc. Natl. Acad. Sci. USA  85: 4397; Saleeba, et al., 1992 . Methods Enzymol . 217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.  
       [0311] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of  E. coli  cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al., 1994 . Carcinogenesis  15: 1657-1662. According to an exemplary embodiment, a probe based on a NOVX sequence, e.g., a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Pat. No. 5,459,039.  
       [0312] In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in NOVX genes. For example, single strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e.g., Orita, et al., 1989 . Proc. Natl. Acad. Sci. USA : 86: 2766; Cotton, 1993 . Mutat. Res . 285: 125-144; Hayashi, 1992 . Genet. Anal. Tech. Appl . 9: 73-79. Single-stranded DNA fragments of sample and control NOVX nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In one embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e.g., Keen, et al., 1991 . Trends Genet . 7: 5.  
       [0313] In yet another embodiment, the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE). See, e.g., Myers, et al., 1985 . Nature  313: 495. When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987 . Biophys. Chem . 265: 12753.  
       [0314] Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e.g., Saiki, et al., 1986 . Nature  324: 163; Saiki, et al., 1989 . Proc. Natl. Acad. Sci. USA  86: 6230. Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.  
       [0315] Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization; see, e.g., Gibbs, et al., 1989 . Nucl. Acids Res . 17: 2437-2448) or at the extreme 3′-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e.g., Prossner, 1993 . Tibtech . 11: 238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection. See, e.g., Gasparini, et al., 1992 . Mol. Cell Probes  6: 1. It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification. See, e.g., Barany, 1991 . Proc. Natl. Acad. Sci. USA  88: 189. In such cases, ligation will occur only if there is a perfect match at the 3′-terminus of the 5′ sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.  
       [0316] The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving a NOVX gene.  
       [0317] Furthermore, any cell type or tissue, preferably peripheral blood leukocytes, in which NOVX is expressed may be utilized in the prognostic assays described herein. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.  
       [0318] Pharmacogenomics  
       [0319] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.  
       [0320] In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual&#39;s genotype and that individual&#39;s response to a foreign compound or drug) of the individual may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, the pharmacogenomics of the individual permits the selection of effective agents (e.g., drugs) for prophylactic or therapeutic treatments based on a consideration of the individual&#39;s genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual.  
       [0321] Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See e.g., Eichelbaum, 1996 . Clin. Exp. Pharmacol. Physiol ., 23: 983-985; Linder, 1997 . Clin. Chem ., 43: 254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare defects or as polymorphisms. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymopathy in which the main clinical complication is hemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.  
       [0322] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.  
       [0323] Thus, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual&#39;s drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.  
       [0324] Monitoring of Effects During Clinical Trials  
       [0325] Monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX (e.g., the ability to modulate aberrant cell proliferation and/or differentiation) can be applied not only in basic drug screening, but also in clinical trials. For example, the effectiveness of an agent determined by a screening assay as described herein to increase NOVX gene expression, protein levels, or upregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting decreased NOVX gene expression, protein levels, or downregulated NOVX activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease NOVX gene expression, protein levels, or downregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting increased NOVX gene expression, protein levels, or upregulated NOVX activity. In such clinical trials, the expression or activity of NOVX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a “read out” or markers of the immune responsiveness of a particular cell.  
       [0326] By way of example, and not of limitation, genes, including NOVX, that are modulated in cells by treatment with an agent (e.g., compound, drug or small molecule) that modulates NOVX activity (e.g., identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder. The levels of gene expression (i.e., a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one of the methods as described herein, or by measuring the levels of activity of NOVX or other genes. In this manner, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment of the individual with the agent.  
       [0327] In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness of the agent.  
       [0328] Methods of Treatment  
       [0329] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.  
       [0330] These methods of treatment will be discussed more fully, below.  
       [0331] Diseases and Disorders  
       [0332] Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i.e., reduce or inhibit) activity. Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to: (i) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; (ii) antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are “dysfunctional” (i.e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to “knockout” endogenous function of an aforementioned peptide by homologous recombination (see, e.g., Capecchi, 1989 . Science  244: 1288-1292); or (v) modulators (i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide of the invention) that alter the interaction between an aforementioned peptide and its binding partner.  
       [0333] Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (i.e., are agonists to) activity. Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; or an agonist that increases bioavailability.  
       [0334] Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity of the expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (e.g., Northern assays, dot blots, in situ hybridization, and the like).  
       [0335] Prophylactic Methods  
       [0336] In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by aberrant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the NOVX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX aberrancy, for example, a NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.  
       [0337] Therapeutic Methods  
       [0338] Another aspect of the invention pertains to methods of modulating NOVX expression or activity for therapeutic purposes. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of a NOVX protein, a peptide, a NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of a NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.  
       [0339] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e.g., cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).  
       [0340] Determination of the Biological Effect of the Therapeutic  
       [0341] In various embodiments of the invention, suitable in vitro or in vivo assays are performed to determine the effect of a specific Therapeutic and whether its administration is indicated for treatment of the affected tissue.  
       [0342] In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient&#39;s disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any of the animal model system known in the art may be used prior to administration to human subjects.  
       [0343] Prophylactic and Therapeutic Uses of the Compositions of the Invention  
       [0344] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.  
       [0345] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from diseases, disorders, conditions and the like, including but not limited to those listed herein.  
       [0346] Both the novel nucleic acid encoding the NOVX protein, and the NOVX protein of the invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. A further use could be as an anti-bacterial molecule (i.e., some peptides have been found to possess anti-bacterial properties). These materials are further useful in the generation of antibodies, which immunospecifically-bind to the novel substances of the invention for use in therapeutic or diagnostic methods. 
     
    
    
     [0347] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.  
     EXAMPLES  
     Example A  
     Polynucleotide and Polypeptide Sequences, and Homology Data  
     Example 1  
     [0348] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.  
               TABLE 1A                       NOV1 Sequence Analysis                                                SEQ ID NO:1   1903 bp                     NOV1a,     CGTTTGGGAGAAAATGTGTCGCATATTTTGGGGCGGTCACGTGGGCGGGCGGGCTCCG         CG109413-01       DNA Sequence     AGAGGCCCCGGGACAGTCCCAGCCTAGAGCCCTGCCCCCCCAGGAGCCCCCCAGTACG                       GCGAGCCCCGGACATTGCGACGCTCCATCCAAGAGACTGCCCGACGCCGGGACCTCGG                       GGCTCCGCCGCCTCCCTTCCCCCTCCCACTCCAGCTACGGCCCAGTTCCCTCAACCTG                       ACCCAGTATGTAGAAGCCAGTCTCTGCAGGCGGCCAGCGGGACTTTTGGAGGCCCAGT                       GGGCAGGCCAGGCAGGGCGGGTACGGAGCCTCCCAGGCTGGGGCAGTGGGCATGGCCA                       GGGGCTGTGGCTGAAGACCTCGCCCGCCCACTGCAGACCCCAGGGGACTCTCACACCG                       CAGCTGCC   ATG GCCACCAATAAGGAGCGACTCTTTGCGGCTGGTGCCCTGGGGCCTGG                   ATCTGGCTACCCAGGGGCAGGTTTCCCCTTCGCCTTCCCAGGGGCACTCAGGGGGTCT                   CCGCCTTTCGAGATGCTGAGCCCTAGCTTCCGGGGCCTGCCCCAGCCTGACCTCCCCA                   AGGAGATGGCCTCTCTGTCGGTGGAGACACAGAGCACCAGCTCAGAGGAGATCGTGCC                   AAGCTCGCCCTCGCCCCCTCCCCCTCCTCGGGTCTACAAGCCATGCTTCGTGTGCAAT                   GACAAGTCCTCTGGCTACCACTATGGGGTCAGCTCTTGTGAAGGCTGCAAGGGCTTCT                   TTCGCCGAAGCATCCAGAAGAACATGGTGTACACGTGTCACCGCGACAAAAACTGTAT                   CATCAACAAGGTGACCAGGAATCGCTGCCAGTACTGCCGGCTACAGAAGTGCTTCCAA                   GTGCGCATGTCCAAGGAAGCTGTGCGAAATGACCGGAACAAGAAGAAGAAAGAGGTGA                   AGGAAGAAGGGTCACCTGACAGCTATGACCTGAGCCCTCAGTTAGAAGAGCTCATCAC                   CAAGGTCAGCAAAGCCCATCAGGAGACTTTCCCCTCGCTCTGCCAGCTGGGCAAGTAT                   ACCACGAACTCCAGTGCAGACCACCGCGTGCAGCTGGATCTGGGGCTGTGGGACAAGT                   TCAGTGAGCTGGCTACCAAGTGCATCATCAAGATCGTCCAGTTTGCCAAGCGGTTGCC                   TGGCTTTACAGGGCTCAGCATTGCTGACCAGATCACTCTGCTCAAAGCTGCCTGCCTA                   GATATCCTGATGCTGCGTATCTCCACAAGGTACACCCCAGAGCAGGACACCATGACCT                   TCTCCGACGGGCTGACCCTGAACCGGACCCAGATGCACAATGCCGGCTTCGGGCCCCT                   CACAGACCTTGTCTTTGCCTTTGCTGGGCACCTCCTGCCCCTGGAGATGGATGACACC                   GAGACAGGGCTGCTCAGCGCCATCTGCCTCATCTGCGGAGACCGCATGGACCTGGAGG                   AGCCCGAAAAAGTGGACAAGCTGCAGGAGCCACTGCTGGAAGCCCTGAGGCTGTACCC                   CCGGCGCCCGCGGCCCAGCCAGCCCTACATGTTCCCAAGGATGCTAATGAAAATCACC                   GACCTCCGGGGCATCAGCACTAAGGGAGCTGAAAGGGCCATTACTCTGAAGATGGAGA                   TTCCAGGCCCGATGCCTCCCTTAATCCGAGAGATGCTGGAGAACCCTGAAATGTTTGA                   GGATGACTCCTCCCAGCCTGGTCCCCACCCCAATGCCTCTAGCGAGGATGAGGTTCCT                   GGGGGCCAGGGCAAAGGGGGCCTGAAGTCCCCAGCC TGA   CCACGGCCCCTGACCTCCC                       CGCTGTGGGGGTTGGGGCTTCAGGCAGCAGACTGACCATCTCCCAGACCGCCAGTGAC                       TGGGGGAGGACCTGCTCTGCCCTCTCCCCAACCCCTTCCAATGAGCG                                           ORF Start:ATG at 415       ORF Stop: TGA at 1777           SEQ ID NO:2   454 aa   MW at 50341.3 kD                     NOV1a,   MATNKERLFAAGALGPGSGYPGAGFPFAFPGALRGSPPFEMLSPSFRGLGQPDLPKEM       CG109413-01       Protein   ASLSVETQSTSSEEMVPSSPSPPPPPRVYKPCFVCNDKSSGYHYGVSSCEGCKGFFRR       Sequence           SIQKNMVYTCHRDKNCIINKVTRNRCQYCRLQKCFEVGMSKEAVRNDRNKKKKEVKEE                   GSPDSYELSPQLEELITKVSKAHQETFPSLCQLGKYTTNSSADHRVQLDLGLWDKFSE                   LATKCIIKIVEFAKRLPGFTGLSIADQITLLKAACLDILMLRICTRYTPEQDTMTFSD                   GLTLNRTQMHNAGFGPLTDLVFAFAGQLLPLEMDDTETGLLSAICLICGDRMDLEEPE                   KVDKLQEPLLEALRLYARRRRPSQPYMFPRMLMKITDLRGISTKGAERAITLKMEIPG                   PMPPLIREMLENPEMFEDDSSQPGPHPNASSEDEVPGGQGKGGLKSPA                                     SEQ ID NO:3   1515 bp                     NOV1b,     CCACTGCAGACCCCAGGGGACTCTCACACCGCAGCTGCC   ATG GCCACCAATAAGGAGC       CG109413-02       DNA Sequence   GACTCTTTGCGGCTGGTGCCCTGGGCCCTGGATCTGGCTACCCAGGGGCAGGTTTCCC                   CTTCGCCTTCCCAGGGGCACTCAGGGGGTCTCCGCCTTTCGAGATGCTGAGCCCTAGC                   TTCCGGGGCCTGCGCCAGCCTGACCTCCCCAAGGAGATGGCCTCTCTGTCGGTGGAGA                   CACAGAGCACCAGCTCAGAGGAGATGGTGCCCAGCTCGCCCTCGCCCCCTCCGCCTCC                   TCGGGTCTACAAGCCATGCTTCGTGTGCAATGACAAGTCCTCTGGCTACCACTATGGG                   GTCAGCTCTTGTGAAGGCTGCAAGGGCTTCTTTCGCCGAAGCATCCAGAAGAACATGG                   TGTACACGTGTCACCGCGACAAAAACTGTATCATCAACAAGGTGACCAGGAATCGCTG                   CCACTACTGCCGGCTACAGAAGTGCTTCGAAGTGGGCATGTCCAAGGAAGCTGTGCGA                   AATGACCGGAACAAGAAGAAGAAAGAGGTGAAGGAAGAAGGGTCACCTGACAGCTATG                   AGCTGAGCCCTCAGTTAGAAGAGCTCATCACCAAGGTCAGCAAAGCCCATCAGGAGAC                   TTTCCCCTCGCTCTGCCAGCTGGGCAAGTATACCACGAACTCCAGTGCAGACCACCGC                   GTGCAGCTGGATCTGGGGCTGTGGGACAAGTTCAGTGAGCTGGCTACCAAGTGCATCA                   TCAAGATCGTGGAGTTTGCCAAGCGGTTGCCTGGCTTTACACGGCTCAGCATTGCTGA                   CCAGATCACTCTGCTCAAAGCTGCCTGCCTAGATATCCTGATGCTGCGTATCTGCACA                   AGGTACACCCCAGAGCAGGACACCATGACCTTCTCCGACGGGCTGACCCTGAACCGGA                   CCCAGATGCACAATGCCGGCTTCGGCCCCCTCACAGACCTTGTCTTTGCCTTTGCTGG                   GCAGCTCCTGCCCCTGGAGATGGATGACACCGACACAGGGCTGCTCAGCGCCATCTGC                   CTCATCTGCGGAGGTGCGGGGGCGCCCCCTGGCGTCTGCTCAGTGCTCAGTCTCCTTT                   CCCACCACTCCATGCGGAATCTGTCTGGGAGGGGGCGTGGAGGACCCAGTGGTCTCTT                   CTGC TGA   CCGCATGGACCTGGAGGAGCCCGAAAAAGTGGACAAGCTGCAGGAGCCACT                       GCTGGAAGCCCTGAGGCTGTACGCCCGGCGCCGGCGGCCCAGCCAGCCCTACATGTTC                       CCAAGGATGCTAATGAAAATCACCGACCTCCGGGGCATCAGCACTAAGGGAGCTGAAA                       GGGCCATTACTCTGAAGATGGAGATTCCAGGCCCGATGCCTCCCTTAATCCGAGAGAT                       GCTGGAGAACCCTGAAATGTTTGAGGATGACTCCTCGCAGCCTGGTCCCCACCCCAAT                       GCCTCTAGCGAGGATGAGGTTCCTGGGGGCCAGGGCAAAGGGGCCCTGAAGTCCCCAG                       CCTGACC                                           ORF Start: ATG at 40       ORF Stop: TGA at 1165           SEQ ID NO:4   375 aa   MW at 40936.6 kD                     NOV1b,   MATNKERLFAAGALGPGSGYPGAGFPFAFPGALRGSPPFEMLSPSFRGLGQPDLPKEM       CG109413-02       Protein   ASLSVETQSTSSEEMVPSSPSPPPPPRVYKPCFVCNDKSSGYHYGVSSCEGCKGFFRR       Sequence           SIQKNMVYTCHRDKMCIINKVTRNRCQYCRLQKCFEVGMSKEAVRNDRNKKKKEVKEE                   GSPDSYELSPQLEELITKVSKAHQETFPSLCQLGKYTTNSSADHRVQLDLGLWDKFSE                   LATKCIIKIVEFAKRLPGFTGLSIADQITLLKAACLDILMLRICTRYTPEQDTMTFSD                   GLTLNRTQMHNAGFGPLTDLVFAFAGQLLPLEMDDTETGLLSAICLICGGAGAPPGVC                   SVLSLLSHHSMRNLSGRGRGGPSGLFC                  
 
     [0349] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.  
               TABLE 1B                          Comparison of NOV1a against NOV1b.                                 Protein   NOV1a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV1b   1 . . . 339   339/339 (100%)               1 . . . 339   339/339 (100%)                      
 
     [0350] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C.  
               TABLE 1C                          Protein Sequence Properties NOV1a                     SignalP           analysis:   No Known Signal Sequence Predicted               PSORT II   PSG: a new signal peptide prediction method       analysis:     N-region: length 7; pos. chg 2; neg. chg 1             H-region: length 26; peak value 8.44             PSG score: 4.04           GvH: von Heijne&#39;s method for signal seq. recognition             GvH score (threshold: −2.1): −3.24             possible cleavage site: between 19 and 20           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation             Init position for calculation: 1             Tentative number of TMS(s) for the threshold 0.5: 1             Number of TMS(s) for threshold 0.5: 0             PERIPHERAL Likelihood = 3.07 (at 307)             ALOM score: −1.86 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)             Center position for calculation: 6             Charge difference: −1.0 C(1.0) − N(2.0)             N &gt;= C: N-terminal side will be inside           MITDISC: discrimination of mitochondrial targeting seq                                       R content:     2   Hyd Moment (75):   4.64             Hyd Moment (95):     4.35   G content:   8             D/E content:     2   S/T content:   3             Score:   −8.54                         Gavel: prediction of cleavage sites for mitochondrial preseq             R-2 motif at 57 FRG|LG           NUCDISC: discrimination of nuclear localization signals             pat4: KKKK (5) at 166             pat4: RRRR (5) at 366             pat4: RRRP (4) at 367             pat7: none             bipartite: none             content of basic residues: 12.6%             NLS Score: 0.40           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:             KKXX-like motif in the C-terminus: LKSP           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:             type 1: none             type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs:             Nuclear hormones receptors DNA-binding region             signature           (PS00031): ***found***             CFVCNDKSSGYHYGVSSCEGCKQFFRR at 90           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination             Prediction: nuclear             Reliability: 89           COIL: Lupas&#39;s algorithm to detect coiled-coil regions             total: 0 residues           --------------------------           Final Results (k = {fraction (9/23)})             78.3%: nuclear             13.0%: extracellular, including cell wall              4.3%: mitochondrial              4.3%: vacuolar           &gt;&gt; prediction for CG109413-01 is nuc (k = 23)                      
 
     [0351] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1D.  
               TABLE 1D                          Geneseq Results for NOV1a                                         NOV1a   Identities/               Protein/   Residues/   Similarities for       Geneseq   Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAR84723   Human retinoic   1 . . . 454   454/454 (100%)   0.0           acid receptor   1 . . . 454   454/454 (100%)           gamma— Homo               sapiens , 454 aa.           [EP683227-A1,           22 NOV. 1995]       AAR10550   Human Retinoic   1 . . . 454   454/454 (100%)   0.0           Acid Receptor-   1 . . . 454   454/454 (100%)           gamma A— Homo               sapiens , 454 aa.           [EP411323-A,           06 FEB. 1991]       AAR10182   Recombinant   1 . . . 454   454/454 (100%)   0.0           human gamma   1 . . . 454   454/454 (100%)           retinoic acid           receptor— Homo               sapiens , 454 aa.           [WO9015815-A,           27 DEC. 1990]       AAR20465   Mouse retinoic   1 . . . 449   444/449 (98%)    0.0           acid receptor   1 . . . 449   445/449 (98%)            isoform RAR-           gamma-A— Mus               musculus , 458 aa.           [CA2015766-A,           31 OCT. 1991]       AAR10549   Skin-specific   1 . . . 449   443/449 (98%)    0.0           murine Retinoic   1 . . . 449   444/449 (98%)            Acid Receptor-           gamma— Mus               musculus , 458 aa.           [EP411323-A,           06 FEB. 1991]                  
 
     [0352] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E.  
               TABLE 1E                          Public BLASTP Results for NOV1a                                         NOV1a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/   Match   the Matched   Expect       Number   Organism/Length   Residues   Portion   Value               P13631   Retinoic acid   1 . . . 454   454/454 (100%)   0.0           receptor gamma-1   1 . . . 454   454/454 (100%)           (RAR-gamma-1)—             Homo sapiens             (Human), 454 aa.       Q91VK5   Similar to retinoic   1 . . . 449   444/449 (98%)    0.0           acid receptor,   1 . . . 449   445/449 (98%)            gamma— Mus               musculus  (Mouse),           458 aa.       Q91YX2   Retinoic acid   1 . . . 449   443/449 (98%)    0.0           receptor, gamma—   1 . . . 449   444/449 (98%)              Mus musculus             (Mouse), 458 aa.       P18911   Retinoic acid   1 . . . 449   441/449 (98%)    0.0           receptor gamma-A   1 . . . 449   444/449 (98%)            (RAR-gamma-A)—             Mus musculus             (Mouse), 458 aa.       P22932   Retinoic acid   2 . . . 454   409/453 (90%)    0.0           receptor gamma-2   9 . . . 443   413/453 (90%)            (RAR-gamma-2)—             Homo sapiens             (Human), 443 aa.                  
 
     [0353] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1F.  
               TABLE 1F                          Domain Analysis of NOV1a                                     Identities/               NOV1a   Similarities for   Expect       Pfam Domain   Match Region   the Matched Region   Value               zf-C4    88 . . . 163    56/77 (73%)     1e−55                74/77 (96%)       hormone_rec   235 . . . 416    66/206 (32%)   1.1e−44               146/206 (71%)                  
 
     Example 2  
     [0354] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.  
               TABLE 2A                       NOV2 Sequence Analysis                                                SEQ ID NO:5   1807 bp                     NOV2a,     CC   ATG AGCCGGAGTCTCTTGCTCCGGTTCTTGCTGTTCCTGCTCCTGCTCCCGCCGCT       CG110266-01       DNA Sequence   CCCCGTCCTGCTCGCGGACCCAGGGGCGCCCACGCCAGTGAATCCCTGTTGTTACTAT                   CCATGCCAGCACCAGGGCATCTGTGTCCGCTTCGGCCTTGACCGCTACCAGTGTGACT                   GCACCCGCACGGGCTATTCCGGCCCCAACTGCACCATCCCTGGCCTGTGGACCTGGCT                   CCGGAATTCACTGCGGCCCAGCCCCTCTTTCACCCACTTCCTGCTCACTCACGGGCGC                   TGGTTCTGGGAGTTTGTCAATGCCACCTTCATCCGACAGATGCTCATGCGCCTGGTAC                   TCACAGTGCGCTCCAACCTTATCCCCAGTCCCCCCACCTACAACTCAGCACATGACTA                   CATCAGCTGGGAGTCTTTCTCCAACGTGAGCTATTACACTCGTATTCTCCCCTCTGTG                   CCTAAAGATTGCCCCACACCCATGGGAACCAAAGGGAAGAAGCAGTTGCCAGATGCCC                   AGCTCCTGGCCCGCCGCTTCCTGCTCAGGAGGAAGTTCATACCTGACCCCCAAGGCAC                   CAACCTCATGTTTGCCTTCTTTGCACAACACTTCACCCACCAGTTCTTCAAAACTTCT                   GGCAAGATGGGTCCTGGCTTCACCAAGGCCTTGGGCCATGGGGTAGACCTCGGCCACA                   TTTATGGAGACAATCTGGAGCGTCAGTATCAACTCCGGCTCTTTAAGGATGGGAAACT                   CAAGTACCAGGTGCTGGATGGAGAAATGTACCCGCCCTCGGTAGAAGAGGCGCCTGTG                   TTGATGCACTACCCCCGAGGCATCCCGCCCCAGAGCCAGATGGCTGTGGGCCAGGAGG                   TGTTTGGGCTGCTTCCTGGGCTCATGCTGTATGCCACGCTCTGGCTACGTGAGCACAA                   CCGTGTGTGTGACCTGCTGAAGGCTGAGCACCCCACCTGGGGCGATGAGCAGCTTTTC                   CAGACGACCCGCCTCATCCTCATAGGGGAGACCATCAAGATTGTCATCGAGGAGTACG                   TGCAGCAGCTGAGTGGCTATTTCCTCCAGCTGAAATTTGACCCAGAGCTGCTGTTCGG                   TGTCCAGTTCCAATACCGCAACCGCATTGCCATGGAGTTCAACCATCTCTACCACTGG                   CACCCCCTCATGCCTGACTCCTTCAAGGTGGGCTCCCAGGAGTACAGCTACGAGCAGT                   TCTTGTTCAACACCTCCATGTTGGTGGACTATGGGGTTGAGGCCCTGGTGGATGCCTT                   CTCTCGCCAGATTGCTGGCCGGATCGGTGGGGGCAGGAACATGGACCACCACATCCTG                   CATGTGGCTGTGCATGTCATCAGGGAGTCTCGGGAGATGCGCCTGCAGCCCTTCAATG                   AGTACCCCAAGAGGTTTGGCATGAAACCCTACACCTCCTTCCAGGAGCTCGTAGGAGA                   GAAGGAGATGGCAGCAGAGTTGGAGGAATTGTATGGAGACATTGATGCGTTGGAGTTC                   TACCCTGGACTGCTTCTTGAAAAGTGCCATCCAAACTCTATCTTTGGGGAGAGTATGA                   TAGAGATTGGGGCTCCCTTTTCCCTCAAGGGTCTCCTAGGCAATCCCATCTGTTCTCC                   GGAGTACTGGAAGCCGAGCACATTTGCCGCCGAGGTGGCCTTTAACATTGTCAAGACG                   GCCACACTGAAGAAGCTGGTCTGCCTCAACACCAAGACCTGTCCCTACGTTTCCTTCC                   GTGTGCCGGATGCCAGTCAGGATGATGGGCCTGCTGTGGAGCGACCATCCACAGAGCT                   C TGA   GGGGC                                           ORF Start: ATG at 3       ORF Stop: TGA at 1800           SEQ ID NO:6   599 aa   MW at 68655.6 kD                     NOV2a,   MSRSLLLRFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDC       CG110266-01       Protein   TRTGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVL       Sequence           TVRSNLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQ                   LLARRFLLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHI                   YGDNLERQYQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEV                   FGLLPGLMLYATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYV                   QQLSGYFLQLKFDPELLFGVQFQYRNRIANEFNHLYHWHPLMPDSFKVGSQEYSYEQF                   LFNTSMLVDYGVEALVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNE                   YRKRFGMKPYTSFQELVGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMI                   EIGAPFSLKGLLGNPICSPEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFR                   VPDASQDDGPAVERPSTEL                                     SEQ ID NO:7   1713 bp                     NOV2b,     GCGCC   ATG AGCCGGAGTCTCTTGCTCCGGTTCTTGCTGTTCCTGCTCCTGCTCCCGCC       CG110266-02       DNA Sequence   GCTCCCCGTCCTGCTCGCGGACCCAGGGGCGCCCACGCCAGTGAATCCCTGTTGTTAC                   TATCCATGCCAGCACCAGGGCATCTGTGTCCGCTTCGGCCTTGACCGCTACCAGTGTG                   ACTGCACCCGCACGGGCTATTCCGGCCCCAACTGCACCATCCCTGGCCTGTGGACCTG                   GCTCCGGAATTCACTGCGGCCCAGCCCCTCTTTCACCCACTTCCTGCTCACTCACGGG                   CGCTGGTTCTGGGAGTTTGTCAATGCCACCTTCATCCGAGAGATGCTCATGCGCCTGG                   TACTCACAGGGAAGAAGCAGTTGCCAGATGCCCAGCTCCTGGCCCGCCGCTTCCTGCT                   CGGGAGGAAGTTCATACCTGACCCCCAAGCCACCAACCTCATGTTTGCCTTCTTTGCA                   CAACACTTCACCCACCAGTTCTTCAAAACTTCTGGCAAGATGGGTCCTGGCTTCACCA                   AGGCCTTGGGCCATGGGGTAGACCTCGGCCACATTTATGGAGACAATCTGGACCGTCA                   GTATCAACTGCCGCTCTTTAAGGATGGGAAACTCAAGTACCAGGTGCTGGATGGACPA                   ATGTACCCGCCCTCGGTAGAAGAGGCGCCTGTGTTGATGCACTACCCCCGAGGCATCC                   CGCCCCAGAGCCAGATGGCTGTGGGCCAGGAGGTGTTTGGCCTGCTTCCTGGGCTCAT                   GCTGTATGCCACGCTCTGGCTACGTGAGCACAACCGTGTGTGTGACCTGCTGAAGGCT                   GAGCACCCCACCTGGGGCGATGAGCAGCTTTTCCAGACGACCCGCCTCATCCTCATAG                   GGGAGACCATCAAGATTGTCATCGAGGAGTACGTGCAGCAGCTGAGTGGCTATTTCCT                   GCAGCTGAAATTTGACCCAGAGCTGCTGTTCGGTGTCCAGTTCCAATACCGCAACCGC                   ATTGCCATGGAGTTCAACCATCTCTACCACTGGCACCCCCTCATGCCTGACTCCTTCA                   AGGTGGGCTCCCAGGAGTACAGCTACGAGCAGTTCTTGTTCAACACCTCCATGTTGGT                   GGACTATGGGGTTGAGGCCCTGGTGGATGCCTTCTCTCGCCAGATTGCTGGCCGGATC                   GGTGGGGGCAGGAACATGGACCACCACATCCTGCATGTGGCTGTGGATGTCATCAGGG                   AGTCTCGGGAGATGCGGCTGCAGCCCTTCAATGAGTACCGCAAGAGGTTTGGCATGAA                   ACCCTACACCTCCTTCCACGAGCTCGTAGGAGAGAAGGAGATGGCAGCAGAGTTGGAG                   GAATTGTATGGAGACATTGATGCGTTGGAGTTCTACCCTGGACTGCTTCTTGAAAAGT                   GCCATCCAAACTCTATCTTTGGGGAGAGTATGATAGAGATTGGGGCTCCCTTTTCCCT                   CAAGCGTCTCCTAGGGAATCCCATCTGTTCTCCGGAGTACTGGAAGCCGAGCACATTT                   GGCGGCGAGGTGGGCTTTAACATTGTCAAGACGGCCACACTGAAGAAGCTGGTCTGCC                   TCAACACCAAGACCTGTCCCTACGTTTCCTTCCGTGTGCCGGATGCCAGTCAGGATGA                   TGGGCCTGCTGTGGAGCGACCATCCACAGAGCTC TGA   GGGGCAGGAAAGCAGCATTCT                       GGAGGGGAGAGCTTTGTGCTTGTCATTCCAG                                           ORF Start: ATG at 6       ORF Stop: TGA at 1659           SEQ ID NO:8   551 aa   MW at 63156.5 kD                     NOV2b,   MSRSLLLRFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGTCVRFGLDRYQCDC       CG110266-02       Protein   TRTGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVL       Sequence           TGKKQLPDAQLLARRFLLGRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKA                   LGHGVDLGHIYGDNLERQYQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPP                   QSQMAVGQEVFGLLPGLMLYATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGE                   TIKIVIEEYVQQLSGYFLQLKFDPELLFGVQFQYRNRHVIEFNHLYHWHPLMPDSFKV                   GSQEYSYEQFLFNTSMLVDYGVEALVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRES                   REMRLQPFNEYRKRFGMKPYTSFQELVGEKEMAAELEELYGDIDALEFYPGLLLEKCH                   PNSIFGESMIEIGAPFSLKGLLGNPICSPEYWKPSTFGGEVGFNIVKTATLKKLVCLN                   TKTCPYVSFRVPDASQDDGPAVERPSTEL                  
 
     [0355] Sequence comparison of the above protein sequences yields the following sequence N relationships shown in Table 2B.  
               TABLE 2B                          Comparison of NOV2a against NOV2b.                                 Protein   NOV2a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV2b   1 . . . 599   550/599 (91%)               1 . . . 551   550/599 (91%)                      
 
     [0356] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.  
               TABLE 2C                          Protein Sequence Properties NOV2a                     SignalP           analysis:   Cleavage site between residues 25 and 26               PSORT II   PSG: a new signal peptide prediction method       analysis:     N-region: length 8; pos. chg 2; neg. chg 0             H-region: length 16; peak value 12.65             PSG score: 8.25           GvH: von Heijne&#39;s method for signal seq. recognition             GvH score (threshold: −2.1): 3.45             possible cleavage site: between 24 and 25           &gt;&gt;&gt; Seems to have a cleavable signal peptide (1 to 24)           ALOM: Klein et al&#39;s method for TM region allocation             Init position for calculation: 25             Tentative number of TMS(s) for the threshold 0.5: 0             number of TMS(s) . . . fixed             PERIPHERAL Likelihood = 1.16 (at 289)           ALOM score: 1.16 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)             Center position for calculation: 12             Charge difference: −4.0 C(−1.0) − N(3.0)             N &gt;= C: N-terminal side will be inside           MITDISC: discrimination of mitochondrial targeting seq                                       R content:     2   Hyd Moment (75):   16.14             Hyd Moment (95):     8.48   G content:    0             D/E content:     1   S/T content:    2             Score:   −0.90                         Gavel: prediction of cleavage sites for mitochondrial preseq             R-2 motif at 58 VRF|GL           NUCDISC: discrimination of nuclear localization signals             pat4: none             pat7: none             bipartite: none             content of basic residues: 9.8%             NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:             XXRR-like motif in the N-terminus: SRSL           none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: found             RIAMEFNHL at 375           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:             type 1: none             type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination             Prediction: cytoplasmic             Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions             total: 0 residues           --------------------------           Final Results (k = {fraction (9/23)})             22.2%: extracellular, including cell wall             22.2%: Golgi             22.2%: endoplasmic reticulum             11.1%: cytoplasmic             11.1%: mitochondrial             11.1%: nuclear           &gt;&gt; prediction for CG1102GG-01 is exc (k = 9)                      
 
     [0357] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.  
               TABLE 2D                          Geneseq Results for NOV2a                                         NOV2a   Identities/               Protein/   Residues/   Similarities for       Geneseq   Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABG96403   Human ovarian    1 . . . 599   599/599   0.0           cancer marker       (100%)            OV51— Homo      1 . . . 599   599/599             sapiens , 599 aa.       (100%)            [WO200271928-           A2, 19 SEP.           2002]       AAR21690   Prostaglandin    1 . . . 599   595/599   0.0           endoperoxide       (99%)           synthase— Homo      1 . . . 599   595/599             sapiens , 599 aa.       (99%)           [JP04045786-A,           14 FEB. 1992]       ABB07243   Human cyclo-    5 . . . 599   594/597   0.0           oxygenase-1       (99%)           (COX-1)   12 . . . 608   594/597           protein— Homo         (99%)             sapiens , 608 aa.           [WO200111026-           A1, 15 FEB.           2001]       ABB07241   Canine cyclo-    5 . . . 599   551/597   0.0           oxygenase-1       (92%)           (COX-1)   12 . . . 608   566/597           protein— Canis         (94%)             familiaris ,           608 aa.           [WO200111026-           A1, 15 FEB.           2001]       ABG30579   Dog   10 . . . 599   547/590   0.0           prostaglandin H       (92%)           synthase-1 or   44 . . . 633   562/590           cyclooxygenase-1       (94%)           #2— Canis               familiaris , 633 aa.           [US2002064845-           A1, 30 MAY           2002]                  
 
     [0358] In a BLAST search of public sequence databases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E.  
               TABLE 2E                          Public BLASTP Results for NOV2a                                         NOV2a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/   Match   the Matched   Expect       Number   Organism/Length   Residues   Portion   Value               P23219   Prostaglandin G/    1 . . . 599   599/599   0.0           H synthase 1       (100%)            precursor    1 . . . 599   599/599           (EC 1.14.99.1)       (100%)            (Cyclooxygenase           -1) (COX-1)           (Prostaglandin-           endoperoxide           synthase 1)           (Prostaglandin H2           synthase 1) (PGH           synthase 1)           (PGHS-1) (PHS           1)— Homo               sapiens              (Human), 599 aa.       A29947   prostaglandin-    1 . . . 599   547/599   0.0           endoperoxide       (91%)           synthase    1 . . . 599   568/599           (EC 1.14.99.1)       (94%)           precursor—sheep,           599 aa.       P05979   Prostaglandin G/    1 . . . 599   549/600   0.0           H synthase 1       (91%)           precursor    1 . . . 600   570/600           (EC 1.14.99.1)       (94%)           (Cyclooxygenase           -1) (COX-1)           (Prostaglandin-           endoperoxide           synthase 1)           (Prostaglandin           H2 synthase 1)           (PGH synthase 1)           (PGHS-1) (PHS           1)— Ovis aries             (Sheep), 600 aa.       AAN33049   Cyclo-   10 . . . 599   546/590   0.0           oxygenase—       (92%)             Canis familiaris     44 . . . 633   562/590           (Dog), 633 aa.       (94%)       S00561   prostaglandin-    1 . . . 599   548/600   0.0           endoperoxide       (91%)           synthase    1 . . . 600   568/600           (EC 1.14.99.1)       (94%)           precursor—           sheep, 600 aa.                  
 
     [0359] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.  
               TABLE 2F                          Domain Analysis of NOV2a                                     Identities/               NOV2a   Similarities for       Pfam Domain   Match Region   the Matched Region   Expect Value               EGF   36 . . . 68   12/47 (26%)   0.0097               24/47 (51%)       An_peroxidase   142 . . . 575   145/597 (24%)   3.5e−165               396/597 (66%)                  
 
     Example 3  
     [0360] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.  
               TABLE 3A                       NOV3 Sequence Analysis                                                SEQ ID NO:9   2019 bp                     NOV3a,     GATCTGTGGAGCTTTTTCTCTGCAAATGCAGGAAGAAATCAGGTGGATGGATGCATAA         CG176765-01       DNA Sequence     TT   ATG GCCCTGCTCCTGGTCTCTTTGCTCGCATTCCTGAGCTTGGGCTCAGGATGTCA                   TCATCGGATCTGTCACTCCTCTAACAGGGTTTTTCTCTGCCAAGAGAGCAAGGTGACA                   GAGATTCCTTCTGACCTCCCGACGAATGCCATTGAACTGAGGTTTGTCCTCACCAAGC                   TTCGAGTCATCCAAAAAGGTGCATTTTCAGGATTTGGGGACCTGGAGAAAATAGAGAT                   CTCTCAGAATGATGTCTTGGAGGTGATAGAGCCACATGTGTTCTCCAACCTTCCCAAA                   TTACATGAAATTAGAATTGAAAAGGCCAACAACCTGCTCTACATCAACCCTGAGGCCT                   TCCACAACCTTCCCAACCTTCAATATCTGTTAATATCCAACACAGGTATTAAGCACCT                   TCCAGATGTTCACAACATTCATTCTCTCCAAAAAGTTTTACTTGACATTCAAGATAAC                   ATAAACATCCACACAATTGAAAGAAATTCTTTCGTGGGGCTGAGCTTTGAAAGTGTGA                   TTCTATGGCTGAATAAGAATGGCATTCAAGAAATACACAACTGTGCATTCAATGGAAC                   CCAACTAGATGAGCTGAATCTAAGCGATAATAATAATTTAGAAGAATTGCCTAATGAT                   GTTTTCCACGGAGCCTCTGGACCAGTCATTCTCTCTGAGCTTCATCCAATTTGCAACA                   AATCTATTTTAAGGCAAGAAGTTGATTATATGACTCAGGCTAGGCGTCAGAGATCCTC                   TCTGGCAGAAGACAATGAGTCCAGCTACAGCAGAGGATTTGACATGACGTACACTGAG                   TTTGACTATGACTTATGCAATGAAGTGGTTGACGTGACCTGCTCCCCTAAGCCAGATG                   CATTCAACCCATGTGAAGATATCATGGGCTACAACATCCTCAGAGTCCTGATATGGTT                   TATCAGCATCCTGGCCATCACTGGGAACATCATAGTGCTAGTGATCCTAACTACCAGC                   CAATATAAACTCACAGTCCCCAGGTTCCTTATGTGCAACCTGGCCTTTGCTGATCTCT                   GCATTGGAATCTACCTGCTGCTCATTGCATCAGTTGATATCCATACCAAGAGCCAATA                   TCACAACTATGCCATTCACTGCCAAACTGGGGCAGGCTGTGATGCTGCTGCCTTTTTC                   ACTGTCTTTGCCAGTGAGCTGTCAGTCTACACTCTGACAGCTATCACCTTGGAAAGAT                   GGCATACCATCACGCATGCCATGCAGCTGGACTGCAAGGTGCAGCTCCGCCATGCTGC                   CAGTGTCATCGTGATGGGCTGGATTTTTGCTTTTGCAGCTGCCCTCTTTCCCATCTTT                   GGCATCAGCAGCTACATGAAGGTGAGCATCTGCCTGCCCATGGATATTGACAGCCCTT                   TGTCACAGCTGTATGTCATGTCCCTCCTTGTGCTCAATGTCCTGGCCTTTGTGGTCAT                   CTGTGGCTGCTATATCCACATCTACCTCACAGTGCGGAACCCCAACATCGTGTCCTCC                   TCTAGTGACACCAGGATCGCCAAGCGCATGGCCATGCTCATCTTCACTGACTTCCTCT                   GCATGGCACCCATTTCTTTCTTTGCCATTTCTGCCTCCCTCAAGGTGCCCCTCATCAC                   TGTGTCCAAAGCAAAGATTCTGCTGGTTCTGTTTCACCCCATCAACTCCTGTGCCAAC                   CCCTTCCTCTATGCCATCTTTACCAAAAACTTTCGCAGAGATTTCTTCATTCTGCTCA                   GCAAGTGTGGCTGCTATGAAATGCAAGCCCAAATTTATAGGACAGAAACTTCATCCAC                   TGTCCACAACACCCATCCAAGGAATCGCCACTGCTCTTCAGCTCCCAGAGTCACCAGT                   GGTTCCACTTACATACTTGTCCCTCTAAGTCATTTAGCCCAAAAC TAA   AACACAATGT                       GAAAATGTATCTGAGTATTGAATGATAATTCAGTCTTGCCTTTGAAG                                           ORF Start: ATG at 61       ORF Stop: TAA at 1960           SEQ ID NO:10   633 aa   MW at 71050.5 kD                     NOV3a,   MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNATELRFVLTKL       CG176765-01       Protein   RVIQKGAFSGFGDLEKIEISQNDVLEVIEADVFSNLPKLHEIRIEKANNLLYINFEAF       Sequence           QNLPNLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVI                   LWLNKNGIQETHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILSELHPICNK                   SILRQEVDYMTQARGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDA                   FNPCEDIMGYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLC                   IGIYLLLTASVDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERW                   HTITHAMQLDCKVQLRHAASVMVMCWIFAFAAALFPIFGISSYMKVSICLPMDIDSPL                   SQLYVMSLLVLNVLAFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLC                   MAPISFFAISASLKVPLITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLS                   KCGCYEMQAQIYRTETSSTVHNTHPRNGHCSSAPRVTSGSTYILVPLSHLAQN                  
 
     [0361] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.  
               TABLE 3B                       Protein Sequence Properties NOV3a                                        SignalP   Cleavage site between residues 18 and 19       analysis:                         PSORT II   PSG:   a new signal peptide prediction method                                     analysis:       N-region:   length 0;   pos. chg 0;   neg. chg 0               H-region:   length 20;   peak value   10.30                         PSG score: 5.90                             GvH:   von Heijne&#39;s method for signal seq. recognition               GvH score (threshold: −2.1): 3.92               possible cleavage site: between 15 and 16                         &gt;&gt;&gt; Seems to have a cleavable signal peptide (1 to 15)                             ALOM:   Klein et al&#39;s method for TM region allocation               Init position for calculation: 16               Tentative number of TMS(s) for the threshold 0.5: 6                                 INTEGRAL   Likelihood = −10.14   Trans-                         membrane 309-325                                 INTEGRAL   Likelihood = −5.68   Trans-                         membrane 343-359                                 INTEGRAL   Likelihood = −5.73   Trans-                         membrane 427-443                                 INTEGRAL   Likelihood = −9.82   Trans-                         membrane 467-483                                 INTEGRAL   Likelihood = −3.61   Trans-                         membrane 515-531                                 INTEGRAL   Likelihood = −0.37   Trans-                         membrane 535-551                             PERIPHERAL   Likelihood = 1.54 (at 385)           ALOM score:   −10.14 (number of TMSs: 6)                             MTOP:   Prediction of membrane topology (Hartmann et al.)               Center position for calculation: 7               Charge difference: 2.5 C (3.5) - N (1.0)               C &gt; N: C-terminal side will be inside                         &gt;&gt;&gt; Caution: Inconsistent mtop result with signal peptide           &gt;&gt;&gt; membrane topology: type 3b           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   2   Hyd Moment(75):   0.43           Hyd Moment(95):   2.06   G content:   2           D/E content:   1   S/T content:   4           Score:   −4.18                         Gavel: prediction of cleavage sites for mitochondrial preseq                         R-2 motif at 38 NRV|FL                         NUCDISC: discrimination of nuclear localization signals                         pat4: none           pat7: none           bipartite: none           content of basic residues: 7.1%           NLS Score: −0.47                         KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:                         type 1: none           type 2: none                         NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination                             Prediction:   cytoplasmic           Reliability:   94.1                             COIL:   Lupas&#39;s algorithm to detect coiled-coil regions               total: 0 residues                         Final Results (k = 9/23):                         55.6%: endoplasmic reticulum           22.2%: vacuolar           11.1%: Golgi           11.1%: mitochondrial                         &gt;&gt; prediction for CG176765-01 is end (k = 9)                      
 
     [0362] A search of the NOV3 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3C.  
               TABLE 3C                          Geneseq Results for NOV3a                                         NOV3a   Identities/               Protein/Organism/   Residues/   Similarities for       Geneseq   Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABG71117   Human follicle   1 . . . 633   603/695 (86%)   0.0           stimulating hormone   1 . . . 695   611/695 (87%)           (hFSH) -  Homo               sapiens , 695 aa.           [U.S. Pat. No.           2002128190-A1,           Sep. 12, 2002]       AAW14782   FSH receptor -   1 . . . 633   602/695 (86%)   0.0             Homo sapiens , 695   1 . . . 695   611/695 (87%)           aa. [W09711194-           A1, Mar. 27, 1997]       AAR42082   FSH receptor -   1 . . . 633   602/695 (86%)   0.0             Homo sapiens , 695   1 . . . 695   611/695 (87%)           aa. [WO9320199-A,           Oct. 14, 1993]       AAR27558   FSHR -  Homo     1 . . . 633   601/695 (86%)   0.0             sapiens , 695 aa.   1 . . . 695   611/695 (87%)           [WO9216620-A,           Oct. 1, 1992]       AAR30520   N-terminal of LH   1 . . . 633   569/634 (89%)   0.0           receptor/FSH   1 . . . 631   595/634 (93%)           receptor chimaera           #29 - Chimaeric;             homo sapiens , 634           aa. [WO9222667-A,           Dec. 23, 1992]                  
 
     [0363] In a BLAST search of public sequence databases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3D.  
               TABLE 3D                          Public BLASTP Results for NOV3a                                         NOV3a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/Organism/   Match   the Matched   Expect       Number   Length   Residues   Portion   Value               QRHUFT   follitropin receptor   1 . . . 633   603/695 (86%)   0.0           precursor - human,   1 . . . 695   611/695 (87%)           695 aa.       P23945   Follicle stimulating   1 . . . 633   602/695 (86%)   0.0           hormone receptor   1 . . . 695   611/695 (87%)           precursor (FSH-R)           (Follitropin receptor) -             Homo sapiens             (Human), 695 aa.       P32212   Follicle stimulating   1 . . . 633   587/695 (84%)   0.0           hormone receptor   1 . . . 695   602/695 (86%)           precursor (FSH-R)           (Follitropin receptor) -             Macaca fascicularis             (Crab eating macaque)           (Cynomolgus           monkey), 695 aa.       P35376   Follicle stimulating   1 . . . 633   543/695 (78%)   0.0           hormone receptor   1 . . . 695   588/695 (84%)           precursor (FSH-R)           (Follitropin receptor) -             Bos taurus  (Bovine),           695 aa.       P47799   Follicle stimulating   1 . . . 633   553/695 (79%)   0.0           hormone receptor   1 . . . 694   584/695 (83%)           precursor (FSH-R)           (Follitropin receptor) -             Equus caballus             (Horse), 694 aa.                  
 
     [0364] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3E.  
               TABLE 3E                          Domain Analysis of NOV3a                                     Identities/           Pfam       Similarities for       Domain   NOV3a Match Region   the Matched Region   Expect Value               LRRNT   17 . . . 45   13/32 (41%)   5.2e−06               24/32 (75%)       LRR   194 . . . 218   13/26 (50%)   0.016               23/26 (88%)       7tm_1   317 . . . 564    64/282 (23%)   1.8e−52               191/282 (68%)                  
 
     Example 4  
     [0365] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.  
               TABLE 4A                       NOV4 Sequence Analysis                                                SEQ ID NO:11   1609 bp                     NOV4a,     GGCTCCGGCTTCAAGATCAAAGGAAATGTTTCCCTTTGTCCCGTTTCACACTAAACGG         CG178142-01       DNA Sequence     GTTGGCGAGGAACCAGGGGAGATGTCAACCGTCTGCCGGTGACTGGGAAGTTTTCTGC                       AAGTCCTCCACAGCATAGCCAGCAGGCCACTTTTCACTAACAGAAGTCACAAGCCAAG                       TGAGACACTCATCCAAGAGGAAGG   ATG GCCAGTATCTTTTCTAAGTTGCTAACTGGCC                   GCAATGCTTCTCTGCTGTTTGCTACCATGGGCACCAGTGTCCTGACCACCGGGTACCT                   GCTGAACCGGCAGAAAGTGTGTGCCGAGGTCCGCCAGCAGCCTAGGCTATTTCCTCCA                   AGCGCAGACTACCCAGACCTGCGCAAGCACAACAACTGCATGGCCGAGTGCCTCACCC                   CCGCCATTTATTCCAAGCTTCGCAACAAGGTGACACCCAACGGCTACACGCTGGACCA                   GTGCATCCAGACTGGAGTCGACAACCCTGGCCACCCCTTCATAAAGACTGTGCCCATG                   GTGGCTGGTGACGAGGAGTCCTATGAGGTGTTTGCTGACCTTTTTGACCCCGTCATCA                   AACTAAGACACAACGGCTATGACCCCAGGGTGATGAAGCACACAACGGATCTGGATCC                   ATCAAAGTCTGCTTGGCAGATCACCCAAGGGCAGTTCGACGAGCATTACGTGCTGTCT                   TCTCGGGTGCGCACTGGCCGCAGCATCCGTGGGCTGAGCCTGCCTCCAGCCTGCACCC                   GGGCCGAGCGAAGGGAGGTAGAGAACGTGGCCATCACTGCCCTGGAGGGCCTCAAGGG                   GGACCTGGCTGGCCGCTACTACAAGCTGTCCGAGATGACGGAGCAGGACCAGCACCGG                   CTCATCGATGACCACTTTCTGTTTGATAAGCCAGTGTCCCCTTTATTAACATGTGCTG                   GGATGGCCCGTGACTGGCCAGATGCCAGGGGAATCTGGCATAATTATGATAAGACATT                   TCTCATCTGGATAAATGAGGAGGATCACACCAGGGTAATCTCAATGGAAAAAGGAGGC                   AATATGAAACGAGTATTTGAGCGATTCTGTCGTGGACTAAAAGAAGTAGAACGGTTAA                   TCCAAGAACGAGGCTGGCAGTTCATGTGGAATGAGCGCCTAGCATACATTTTGACCTG                   TCCTTCGAACCTTGGAACAGGACTACGAGCTGGTGTCCACGTTAGGATCCCAAAGCTC                   AGCAAGGACCCACGCTTTTCTAAGATCCTGGAAAACCTAAGACTCCAGAAGCGTGGCA                   CAGGTGGTGTGGACACTGCCGCGGTCGCAGATGTGTACGACATTTCCAACATAGATAG                   AATTGGTCGATCAGAGGTTGAGCTTGTTCAGATAGTCATCGATGGAGTCAATTACCTG                   GTGGATTGTGAAAAGAAGTTGGAGAGAGGCCAAGATATTAAGGTGCCACCCCCTCTGC                   CTCAGTTTGGCAAAAAG TAA   ACTTTCCCTTTCCCAATTTATAAATAATCTGTCTGCTG                       GTACAACAGACATAATCTCTACTCTGAGAGTTTTTATACACTTGGAAAAAATATAAAA                       TTGTAGATCCTGCCTATCTTTACAATAAAACTCTCCTTAATAT                                           ORF Start: ATG at 199       ORF Stop: TAA at 1468           SEQ ID NO:12   423 aa   MW at 47992.5 kD                     NOV4a,   MASIFSKLLTGRNASLLFATMGTSVLTTGYLLNRQKVCAEVREQPRLFPPSADYPDLR       CG178142-01       Protein   KHNNCMAECLTPAIYSKLRNKVTPNGYTLDQCIQTGVDNPCHPFIKTVGMVAGDEESY       Sequence           EVFADLFDPVIKLRHNGYDPRVMKHTTDLDASKSAWQITQGQFDEHYVLSSRVFTGRS                   IRGLSLPPACTRAERREVENVAITALEGLKGDLAGRYYKLSEMTEQDQQRLIDDHFLF                   DKPVSPLLTCAGMARDWPDARGIWHNYDKTFLIWINEEDHTRVISMEKGGNMKRVFER                   FCRGLKEVERLIQERGWEFMWNERLGYILTCPSNLGTGLRAGVHVRIPKLSKDPRFSK                   ILENLRLQKRGTGGVDTAAVADVYDISNIDRIGRSEVELVQIVIDGVNLVDICEKKLE                   RGQDIKVPPPLPQFGKK                  
 
     [0366] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.  
               TABLE 4B                       Protein Sequence Properties NOV4a                                        SignalP   No Known Signal Sequence Predicted       analysis:                         PSORT II   PSG:   a new signal peptide prediction method                                 analysis:   N-region:   length 7;   pos. chg 1;   neg. chg 0       H-region:   length 4;   peak value   −3.72                         PSG score: −8.12                             GvH:   von Heijne&#39;s method for signal seq. recognition               GvH score (threshold: −2.1): −5.02               possible cleavage site: between 28 and 29                         &gt;&gt;&gt; Seems to have no N-terminal signal peptide                             ALOM:   Klein et al&#39;s method for TM region allocation                         Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 0           number of TMS(s) . . . fixed           PERIPHERAL Likelihood = 1.54 (at 16)           ALOM score: 1.54 (number of TMSs: 0)                         MITDISC: discrimination of mitochondrial targeting seq                                     R content:   2   Hyd Moment(75):   6.02           Hyd Moment(95):   8.42   G content:   3           D/E content:   1   S/T content:   9           Score: −1.63                         Gavel: prediction of cleavage sites for mitochondrial preseq                         R-2 motif at 44 NRQ|KV                         NUCDISC: discrimination of nuclear localization signals                         pat4: none           pat7: none           bipartite: none           content of basic residues: 13.9%           NLS Score: −0.47                         KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:                         KKXX-like motif in the C-terminus: QFGK                         SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:                         type 1: none           type 2: none                         NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination                             Prediction:   cytoplasmic           Reliability:   76.7                             COIL:   Lupas&#39;s algorithm to detect coiled-coil regions               total: 0 residues                         Final Results (k = 9/23)                         65.2%: mitochondrial           17.4%: nuclear           13.0%: cytoplasmic            4.3%: peroxisomal                         &gt;&gt; prediction for CG178142-01 is mit (k = 23)                      
 
     [0367] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4C.  
               TABLE 4C                          Geneseq Results for NOV4a                                         NOV4a   Identities/               Protein/Organism/   Residues/   Similarities for   Ex-       Geneseq   Length   Match   the Matched   pect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU23805   Novel human    1 . . . 423   418/423 (98%)   0.0           enzyme poly-   33 . . . 451   419/423 (98%)           peptide #891 -             Homo sapiens ,           451 aa.           [WO200155301-           A2, Aug. 2,           2001]       AAO12618   Human poly-    1 . . . 423   391/430 (90%)   0.0           peptide SEQ ID   18 . . . 443   397/430 (91%)           NO 26510 -             Homo sapiens ,           443 aa.           [WO200164835-           A2, Sep. 7, 2001]       ABG96298   Human ovarian    1 . . . 417   330/417 (79%)   0.0           cancer marker    1 . . . 412   365/417 (87%)           M435 -  Homo               sapiens , 417 aa.           [WO200271928-           A2, Sep. 19,           2002]       ABP41304   Human ovarian   48 . . . 411   242/366 (66%)   e−143           antigen   11 . . . 370   289/366 (78%)           HOPJG01, SEQ           ID NO: 2436 -             Homo sapiens ,           378 aa.           [WO200200677-           A1, Jan. 3, 2002]       AAB58161   Lung cancer   48 . . . 411   236/364 (64%)   e−140           associated poly-   79 . . . 438   284/364 (77%)           peptide sequence           SEQ ID 499 -             Homo sapiens ,           446 aa.           [WO200055180-           A2, Sep. 21,           2000]                  
 
     [0368] In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4D.  
               TABLE 4D                          Public BLASTP Results for NOV4a                                         NOV4a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/Organism/   Match   the Matched   Expect       Number   Length   Residues   Portion   Value               P17540   Creatine kinase,   1 . . . 423   419/423 (99%)   0.0           sarcomeric mito-   1 . . . 419   419/423 (99%)           chondrial precursor           (EC 2.7.3.2)           (S-MtCK)           (Mib-CK)           (Basic-type mito-           chondrial creatine           kinase) -  Homo               sapiens  (Human),           419 aa.       Q8N1E1   Creatine kinase,   1 . . . 423   418/423 (98%)   0.0           mitochondrial 2   1 . . . 419   419/423 (98%)           (Sarcomeric) -             Homo sapiens             (Human), 419 aa.       O77814   Creatine kinase,   1 . . . 423   401/423 (94%)   0.0           sarcomeric mito-   1 . . . 419   409/423 (95%)           chondrial precursor           (EC 2.7.3.2)           (S-MtCK)           (Mib-CK)           (Basic-type mito-           chondrial creatine           kinase)           (RSMTCK) -             Oryctolagus               cuniculus  (Rabbit),           419 aa.       P09605   Creatine kinase,   1 . . . 423   398/423 (94%)   0.0           sarcomeric mito-   1 . . . 419   407/423 (96%)           chondrial precursor           (EC 2.7.3.2)           (S-MtCK)           (Mib-CK)           (Basic-type mito-           chondrial creatine           kinase) -  Rattus               norvegicus  (Rat),           419 aa.       P11009   Creatine kinase,   1 . . . 423   363/423 (85%)   0.0           sarcomeric mito-   1 . . . 419   393/423 (92%)           chondrial precursor           (EC 2.7.3.2)           (S-MtCK)           (Mib-CK)           (Basic-type mito-           chondrial creatine           kinase) -  Gallus               gallus  (Chicken),           419 aa.                  
 
     [0369] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4E.  
               TABLE 4E                          Domain Analysis of NOV4a                                     Identities/               NOV4a Match   Similarities for   Expect       Pfam Domain   Region   the Matched Region   Value               ATP-gua_PtransN    53 . . . 136   62/84 (74%)   4.8e−59                80/84 (95%)       ATP-gua_Ptrans   153 . . . 419   190/275 (69%)   4e−197               257/275 (93%)                  
 
     Example 5  
     [0370] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.  
               TABLE 5A                       NOV5 Sequence Analysis                                                SEQ ID NO:13   3983 bp                     NOV5a,     GGCACGAGGGGCCGCTCCAGCCGCGCGCATCTCGGCCCGCGCCCCGAGACCGCGCCCA         CG179317-01       DNA Sequence     GCTAGCCCCGGCCCCGCTCGCCGCCCCAGGCAGCTCGGCTGCGCTCGCCGCGGGACGG                       CGCGGCATGAGGCTGCGGGG   ATG CGGACCCCGGCCCGCCCTGCCTCCAGCGCAGGGGC                   CAGCGACGCTCGGCTGCTGGCGCCCCCGGGGCGGAACCCCTTCGTGCACGAGCTGCAC                   CTCACCCCCCTGCAGAAGGCCCAGGTGGCCCTCATGACACTGACGCTCTTCCCGGTCC                   GGCTCCTGGTTGCCGCTGCCATGATGCTGCTGGCCTGGCCCCTCGCACTTGTCGCATC                   CCTGGGCTCTGCGGAGAAGCAACCCGAGCAGCCCCCGGCCCTGTGGAGGAACGTTCTG                   GACTTCCTGCTGAAGGCCATCATGCGCACCATGTGGTTCGCCGGCGGCTTCCACCGGG                   TGGCCGTGAAGGGGCGGCAGGCGCTGCCCACCGAGGCGGCCATCCTCACGCTCGCGCC                   TCACTCGTCCTACTTCGACGCCATCCCTGTGACCATGACGATGTCCTCCATCGTGATG                   AAGACAGAGAGCAGACACATCCCGATCTGGGGAACTCTGATCCAGTATATACGCCCTG                   TGTTCGTGTCCCGGTCAGACCAGGATTCTCGCAGGAAAACAGTAGAAGAAATCAAGAG                   ACGGGCGCAGTCCAACGGAAAGTGGCCACAGATAATGATTTTTCCAGAAGGAACTTGT                   ACAAACAGGACCTGCCTAATTACCTTCAAACCTGGTGCATTCATCCCTGGAGCGCCCG                   TCCACCCTGGGGTTTTACGATATCCAAATAAACTCGACACCATCACATGGACGTGGCA                   AGGACCTGGAGCGCTGGAAATCCTGTGGCTCACGCTGTGTCAGTTTCACAACCAACTG                   GAAATCGAGTTCCTTCCTGTGTACAGCCCTTCTGAGGAGGAGAAGAGGAACCCCGCGC                   TGTATGCCAGCAACGTGCGGCCAGTCATGGCCGAGGCCTTGGGTGTCTCCGTGACTGA                   CTACACGTTCGAGGACTGCCAGCTGCCCCTGGCGAAAGGACAGCTCCGTCTCCCCGCT                   GACACTTGCCTTTTAGAATTTGCCAGGCTCGTGCGGGGCCTCGGGCTAAAACCAGAAA                   AGCTTGAAAAAGATCTGGACAGATACTCAGAAAGAGCCAGGATGAAGGGAGGAGAGAA                   GATAGGTATTGCGGAGTTTGCCGCCTCCCTGGAAGTCCCCGTTTCTGACTTGCTGGAA                   GACATCTTTTCACTGTTCGACGAGAGCGGCAGCGGCGAGGTGGACCTCCGACAGTGTG                   TGGTTGCCCTGTCTGTCGTCTGCTGGCCGGCCCGGACCCTCGACACCATCCAGCTGGC                   TTTCAAGATGTACGGAGCGCAAGAGGACGGCAGCGTCGGCGAAGGTGACCTGTCCTGC                   ATCCTCAAGACGGCCCTGGGGGTGGCAGAGCTCACTGTGACCGACCTATTCCGAGCCA                   TTGACCAAGAGGAGAAGGGGAAGATCACATTCGCTGACTTCCACAGGTTTGCAGAAAT                   GTACCCTGCCTTCGCAGAGGAATACCTGTACCCGGATCAGACACATTTCGAAAGCTGT                   GCAGAGACCTCACCTGCGCCAATCCCAAACGGCTTCTGTGCCGATTTCAGCCCGGAAA                   ACTCAGACGCTGGGCGGAAGCCTGTTCGCAAGAAGCTGGAT TAG   GACCCAGGGTTGCG                       GAGAGACGCGGCCCCTCCCGCGTGGACATCACCGCCATGAGCCTCTTTGCGAGTGACC                       TCTGGGCTCCGCTCCTCACTCCTGCTGTACAGGCACTGTCTTCAGCCCGAGTTCCAGG                       GGCCTCGGGGGCTGTTTGTATCTTGTTCCTTTGTGAAGTGTGTTGCAGAACCGACGCT                       TACTGTGCGAGAATCGGAGGGCGCGCACGCGGATCCCCCGCCTGGCCTGGACCCCGTG                       GGGTCAGGTTCCCTGCCGGGCGGGGGGCACCGGTGCCGCCCCGTGTTCTCCCACGGGG                       CCCTGGTTTCGAGTCTCTGTCACAGCCTCTTCCGGCGGCAGCGTGCACCGGGCGGGCC                       TCCGTGCACACTCAGCACACGCCTCCCACACAGCGTGCGCTTGCGTGTCACTCTGGCA                       CGAAACCTGTCTGCCTCTGTGGATCCACAGCCTGGCAGAGCCGAGCCGTCACCTGATT                       TTTCAGTGTTTCTACCTGTGTGCTGGAGCTCATGAGTATTTTATAAACTCCATTTAGG                       TACTTCAGGAAACATGCAGCATTTTTTAAAAAATGAAAATTGTTTTTCTACTTCATTT                       TTCCTTTTAGAGTCAAAGGATATTTATTTATAGGCCTTTTTTTTTTTAATATAGAATC                       TGAGGCTGTTTGGGCTTTGACTTAAATTTCCATCAGGCCTCTCTCCAGCAGGTAATCC                       CTCTCCTTCCGCTGGGTCCCCTGGGGAGGTGTGAACTCAAGGGCCTAGCCCCAAAACA                       CTTTTTCTGCTTTTCTTAATCCTTTTCCAGTCCCCTCTTTTTTTATAAACGTTGGCAG                       TTTGATGTTTCTGTTTCGGCATAACGTAATCCATTTCACTGTAGCCTAAACTCCAGTC                       CGAGGTTGGATATTGTTCAAATGAGCAGGGCCCGAGCTGGAAGCGCAAGGCAGCCGCC                       GCCGTGCCGCTCCTCCCTTGCCCTCAGGCCAGGTCCCTGCTGGAAGCGGCTGCATCTT                       CCTGTCAGCCCTGGTTTCCATGGTGACTGGCGTGACGCAGCCACCTGAGTATGGCTGA                       CCTTCCTGCAGAGAGAGGACCCGCAGTCTTTTGCTTGTGGAAGGAGACGCTGGGCTGT                       GCGGTGCGGAGGGTGATGAGGATGTCTGGTGACAGCCGTGCGGACACCACTCCTCTCT                       GCAGCACTGCCTCCCAGCGCCAGGGTCGCGGGCACATCCCACTGAGAGCGGGGGTCCT                       GCCCCATCTTACAGTCAAAGGCAGAGGGGCTTCCAGGCCCTGGATGGGGTATTTTGGT                       GTCACCTGAAGTCCCTCTGACATCACCTTGTTTCATCATTTTTTATGACAGAATTAGA                       AACCCATCCTTCAAGCACAATAATCATCACAGACTTGAGTTTGCTTCCTAAAGCAAAG                       GCTCCGGGTTTGTTTGGAAAATTTTTTTGATTTCTGAAATGAATTGATTTTTATATTT                       GGGGCATCTCTATAGAAAGTGACCACCAAGGCCAGTAAGTACGCGAAAAAATGTTTAC                       TAACTTCCTCAGAGATTCGTGATACGCGTTTCTCCACTGACAGACATTTAAAAACAAC                       CTTCAGCTCCGTTTCAATCAATCACCTCGACTTGTTTTTTAGCATGGACACTGCCAGC                       AGGACAGACAGGGATGGAGTAAACCGAAGTCAATTTCAGGGCTCTTGGCGTGTTGGAC                       ACAGAAGAAATCCTAGTGCAGCCTTTGGTAGCTAACAGTCACTGATTTTATAATTGGA                       GAATGCGTAAAGATTCATTTTTCAAGGAGAAGAGCCTGCAAATGGCCAATGAAGGAGG                       TAAATAAACTAAGATATTCCGAGGGAAGGGACCCAGGCCACCTCCCTTCCGCAGGTCT                       GCAGATGAAGGGTTTTTTGAATGAAATGCCACTGTGCATTTTCAGAAAAAAAAATCTC                       TGATAAACAGACTTTGAATGGATGTTTGTTCCTCCTGATTCTCTTTTCTCTTCGTGGC                       CACTTAGAGTTGGCGGATATTCCGAACTGTGAATGTACATAGCGTTGAGTTAAACCCC                       TTGTGTGTGAGACAGGACGCAGCGGGCCCCTGGTGGCCTGGGGGCCAGACCCGTGGGC                       AGGTGGGGCATGGGCCCTGGCCTGCGGGGACCTGCTGGGGTGTGAGGGCAGAGGGAGG                       GTTGCCATGAAGGAACTTGGGATTTTCAATGGAATAAATAAAACATAAAGTCTATACT                       TGGGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 137       ORF Stop: TAG at 1724           SEQ ID NO: 14   529 aa   MW at 58687.9 kD                     NOV5a,   MRTPGRPASSAGASDARLLAPPGRNPFVHELHLSALQKAQVALMTLTLFPVRLLVAAA       CG179317-01       Protein   MMLLAWPLALVASLGSAEKEPEQPPALWRKVVDFLLKAIMRTMWFAGGFHRVAVKGRQ       Sequence           ALPTEAAILTLAPHSSYFDAIPVTMTMSSIVMKTESRDIPIWGTLIQYIRPVFVSRSD                   QDSRRKTVEEIKRRAQSNGKWPQIMIFPEGTCTNRTCLITFKPGAFIPGAPVHPGVLR                   YPNKLDTITWTWQGPGALEILWLTLCQFHNQVEIEFLPVYSPSEEEKRNPALYASNVR                   RVMAEALGVSVTDYTFEDCQLALAEGQLRLPADTCLLEFARLVRGLCLKPEKLEKDLD                   RYSERARMKGGEKTGIAEFAASLEVPVSDLLEDMFSLFDESGSGEVDLRECVVALSVV                   CWPARTLDTIQLAFKMYGAQEDGSVGEGDLSCILKTALGVAELTVTDLFRAIDQEEKG                   KITFADFHRFAEMYPAFAEEYLYPDQTHFESCAETSPAPIPNGFCADFSPENSDAGRK                   PVRKKLD                  
 
     [0371] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.  
               TABLE 5B                       Protein Sequence Properties NOV5a                                        SignalP   Cleavage site between residues 17 and 18       analysis:                         PSORTII   PSG:   a new signal peptide prediction method                                 analysis:   N-region:   length 6;   pos. chg 2;   neg. chg 0           H-region:   length 8;   peak value   3.88                         PSG score: −0.53                             GvH:   von Heijne&#39;s method for signal seq. recognition               GvH score (threshold: −2.1): −3.56               possible cleavage site: between 53 and 54                         &gt;&gt;&gt; Seems to have no N-terminal signal peptide                             ALOM:   Klein et al&#39;s method for TM region allocation                         Init position for calculation: 1           Tentative number of TMS(s) for the threshold 0.5: 1           Number of TMS(s) for threshold 0.5: 1                                 INTEGRAL   Likelihood = −7.75   Trans-                         membrane 53-59                             PERIPHERAL   Likelihood = 1.80 (at 436)           ALOM score:   −7.75 (number of TMSs: 1)                             MTOP:   Prediction of membrane topology (Hartmann et al.)               Center position for calculation: 60               Charge difference: −2.0 C (0.0) - N (2.0)               N &gt;= C: N-terminal side will be inside                         &gt;&gt;&gt; membrane topology: type 2 (cytoplasmic tail 1 to 53)           MITDISC: discrimination of mitochondrial targeting seq                                     R content:   4   Hyd Moment(75):   10.59           Hyd Moment(95):   13.84   G content:   3           D/E content:   2   S/T content:   4           Score: −2.09                             Gavel:   prediction of cleavage sites for mitochondrial preseq               R-2 motif at 62 VRL|LV                         NUCDISC: discrimination of nuclear localization signals                         pat4: none           pat7: none           bipartite: none           content of basic residues: 10.8%           NLS Score: −0.47                         KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:                         XXRR-like motif in the N-terminus: RTPG           KKXX-like motif in the C-terminus: RKKL                         SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:                         type 1: none           type 2: none                         NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: too long tail           Dileucine motif in the tail: found                         LL at 18                         checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination                             Prediction:   cytoplasmic           Reliability:   94.1                             COIL:   Lupas&#39;s algorithm to detect coiled-coil regions               total: 0 residues                         Final Results (k = 9/23)                         39.1%: mitochondrial           30.4%: cytoplasmic            8.7%: Golgi            8.7%: nuclear            4.3%: vacuolar            4.3%: extracellular, including cell wall            4.3%: endoplasmic reticulum                         &gt;&gt; prediction for CG179317-01 is mit (k = 23)                      
 
     [0372] A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5C.  
               TABLE 5C                          Geneseq Results for NOV5a                                         NOV5a   Identities/               Protein/   Residues/   Similarities for       Geneseq   Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAM47927   Human acyl-    7 . . . 529   518/523   0.0           transferase family       (99%)           member 46745    12 . . . 534   518/523           SEQ ID NO 2—       (99%)             Homo sapiens ,           534 aa.           [WO200190329-           A2, 29 NOV.           2001]       AAB41989   Human ORFX    28 . . . 529   502/502   0.0           ORF1753 poly-       (100%)            peptide sequence    1 . . . 502   502/502           SEQ ID NO:       (100%)            3506— Homo               sapiens , 502 aa.           [WO200058473-           A2, 05 OCT.           2000]       ABP69752   Human poly-    98 . . . 529   427/432   0.0           peptide SEQ ID   (98%)           NO 1799— Homo      1 . . . 432   427/432             sapiens , 432 aa.   (98%)           [WO200270539-           A2, 12 SEP.           2002]       AAE10995   Human lipid    98 . . . 529   427/432   0.0           metabolism       (98%)           enzyme-4 (LME-    1 . . . 432   427/432           4) protein—       (98%)             Homo sapiens ,           432 aa.           [WO200164907-           A2, 07 SEP.           2001]       AAU07841   Novel human   293 . . . 529   236/237   e−133           serine carboxy-       (99%)           peptidase poly-    1 . . . 237   236/237           peptide #2—       (99%)             Homo sapiens ,           237 aa.           [WO200162789-           A1, 30 AUG.           2001]                  
 
     [0373] In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.  
               TABLE 5D                          Public BLASTP Results for NOV5a                                         NOV5a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/   Match   the Matched   Expect       Number   Organism/Length   Residues   Portion   Value               CAD23298   Sequence 1 from    7 . . . 529   518/523 (99%)   0.0           Patent    12 . . . 534   518/523 (99%)           WO0190329—             Homo sapiens             (Human), 534 aa.       BAC38353   16 days embryo    1 . . . 529   460/534 (86%)   0.0           head cDNA,    1 . . . 534   484/534 (90%)           RIKEN full-           length enriched           library, clone:           C130083H12           product: hypo-           thetical Phospho-           lipid and glycerol           acyltransferase           (from           ‘motifs_6.msf’)           and EF-hand           containing           protein, full insert           sequence— Mus               musculus             (Mouse), 534 aa.       Q8NF37   FLJ00365   131 . . . 529   395/399 (98%)   0.0           protein— Homo      1 . . . 399   395/399 (98%)             sapiens  (Human),           399 aa           (fragment).       Q8WUL8   Hypothetical   293 . . . 529   236/237 (99%)   e−133           protein— Homo      1 . . . 237   236/237 (99%)             sapiens  (Human),           237 aa.       Q9GZW6   Hypothetical   293 . . . 529   235/237 (99%)   e−132           protein FLJ12443    1 . . . 237   235/237 (99%)           (Hypothetical           protein           FLJ12437)—             Homo sapiens             (Human), 237 aa.                  
 
     [0374] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.  
               TABLE 5E                          Domain Analysis of NOV5a                                     Identities/               NOV5a   Similarities for   Expect       Pfam Domain   Match Region   the Matched Region   Value               Acyltransferase   110 . . . 229   34/170 (20%)   0.00071               81/170 (48%)       efhand   378 . . . 406    9/29 (31%)   0.06                  22/29 (76%)       efhand   450 . . . 478    7/29 (24%)   0.94                  19/29 (66%)                  
 
     Example 6  
     [0375] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.  
               TABLE 6A                       NOV6 Sequence Analysis                                                SEQ ID NO:15   1267 bp                     NOV6a,     G   TCC AAAATGTGGCTGCTTTTAACAACAACTTGTTTGATCTGTGGAACTTTAAATGCT       CG50159-02       DNA Sequence   GGTGGATTCCTTGATTTGGAAAATGAAGTGAATCCTGAGGTGTGGATGAATACTAGTG                   AATCATCATCTACAATGGCTACCCCAGTGAAAGAGTATGAAGTCACCACTCAAGATGG                   GTATATACTCCTTGTCGACAGAATTCCTTATGGGCGAACACATGCTGGGAGCACAGGT                   CCCCGGCCAGTTGTGTATATGCAGCATGCCCTGTTTGCAGACAATGCCTACTGGCTTG                   AGAATTATCCTAATGGAAGCCTTGGATTCCTTCTAGCAGATGCAGGTTATGATGTATG                   GATGGGAAACAGTCGGGGAAACACTTGGTCAAGAAGACACAAAACACTCTCAGAGACA                   GATGAGAAATTCTGGGCCTTTAGTTTTGATGAAATGGCCAAATATGATCTCCCAGGAG                   TAATAGACTTCATTGTAAATAAAACTGGTCAGGAGAAATTGTATTTCATTCGACATTC                   ACTTGGCACTACAATAGGGTTTGTAGCCTTTTCCACCATGCCTGAACTGGCACAAAGA                   ATCAAAATGAATTTTGCCTTGGGTCCTACGATCTCATTCAAATATCCCACGGGCATTT                   TTACCAGGTTTTTTCTACTTCCAAATTCCATAATCAAGGCTGTTTTTGGTACCAAAGG                   TTTCTTTTTAGAAGATAAGAAAACGAAGATAGCTTCTAACAAAATCTGCAACAATAAG                   ATACTCTGGTTGATATGTAGCGAATTTATGTCCTTATGGGCTGGATCCAACAAGAAAA                   ATATGAATCAGCTTTACCACTCTGATGAATTCAGAGCTTATGACTGGGGAAATGGCGC                   TGATAATATGAAACATTACAATCAGAGTCATCCCCCTATATATGACCTGACTGCCATG                   AAAGTGCCTACTGCTATTTGGGCTGGTGGACATGATGTCCTCGTAACACCCCAGGATG                   TGGCCAGGATACTCCCTCATCAAAGAAGTCTTCATTACTTTAAGCTATTGCCAGATTG                   GAACCACTTTGATTTTGTCTCGGGCCTCGATGCCCCTCAACGGATGTACAGTGAAATC                   ATAGCTTTAATGAAGGCATATTCC TAA   ATGCAATGCATTTACTTTTCAATTAAAAGTT                       GCTTCCAAGCCCATAAGGGACTTTAGAAAAAATAGTAACCAACAATGAGGTTGTCCCC                       CAGCACCCTGGGGGAGATGCACAGTGGAGTCTGTTTTCCAAGTCAATTG                                           ORF Start: at 2       ORF Stop: TAA at 1127           SEQ ID NO:16   375 aa   MW at 42809.6 kD                     NOV6a,   SKMWLLLTTTCLICGTLNAGGFLDLENEVNPEVWMNTSEIIIYNGYPSEEYEVTTEDG       CG50159-02       Protein   YILLVDRIPYGRTHAGSTGPRPVVYMQHALFADNAYWLENYPNGSLGFLLADAGYDVW       Sequence           MGNSRGNTWSRRHKTLSETDEKFWAFSFDEMAKYDLPGVIDFIVNKTGQEKLYFIGHS                   LGTTIGFVAFSTMPELAQRIKMNFALGPTISFKYPTGIFTRFFLLPNSIIKAVFGTKG                   FFLEDKKTKIASNKICNNKILWLICSEFMSLWAGSNKKNMNQLYHSDEFRAYDWGNGA                   DNMKHYNQSHPPIYDLTAMKVPTAIWAGGHDVLVTPQDVARILPQIKSLHYFKLLPDW                   NHFDFVWGLDAPQRMYSEIIALMKAYS                                     SEQ ID NO:17   1138 bp                     NOV6b,     GTCCAAA   ATG TGGCTGCTTTTAACAACAACTTGTTTGATCTGTGGAACTTTAAATGCT       CG50159-03       DNA Sequence   GGTGGATTCCTTGATTTGGAAAATGAAGTGAATCCTGACGTGTGGATGAATACTAGTG                   AAATCATCATCTACAATGGCTACCCCAGTGAAGAGTATGAAGTCACCACTGAAGATGG                   GTATATACTCCTTGTCAACAGAATTCCTTATGGGCGAACACATCCTAGGAGCACAGGT                   CCCCGGCCAGTTGTGTATATGCAGCATGCCCTGTTTGCAGACAATGCCTACTGGCTTG                   AGAATTATGCTAATGGAAGCCTTGGATTCCTTCTAGCAGATGCAGGTTATGATGTATG                   GATGGGAAACAGTCGGGGAAACACTTGGTCAAGAAGACACAAAACACTCTCAGAGACA                   GATGAGAAATTCTGGGCCTTTGGTTTTGATGAATGGCCAAAATATGATCTCCCAGGAG                   TAATAGACTTCATTGTAAATAAAACTGGTCAGGAGAAATTGTATTTCATTCGACATTC                   ACTTGGCACTACAATAGGGTTTGTAGCCTTTTCCACCATGCCTGAACTGGCACAAAGA                   ATCAAAATGAATTTTGCCTTGGGTCCTACGATCTCATTCAAATATCCCACGGGCATTT                   TTACCAGGTTTTTTCTACTTCCAAATTCCATAATCAAGGCTGTTTTTGGTACCAAAGG                   TTTCTTTTTAGAAGATAAGAAAACGAAGATAGCTTCTACCAAAATCTGCAACAATAAG                   ATACTCTGGTTGATATGTAGCGAATTTATGTCCTTATGGGCTGGATCCAACAAGAAAA                   ATATGAATCAGCTTTACCACTCTGATGAAAATTCACAGCTTATGACTGGGGATGACGC                   TGATAATATGAAACATTACAATCAGAGTCATCCCCCTATATATGACCTGACTGCCATG                   AAAGTGCCTACTGCTATTTGGGCTGGTGGACATGATGTCCTCGTAACACCCCAGGATG                   TGCCCAGGATACTCCCTCAAATCAAGAGTCTTCATTACTTTAAGCTATTGCCAGATTG                   CAACCACTTTGATTTTGTCTGGGGCCTCGATGCCCCTCAACGGATGTACAGTGAAATC                   ATAGCTTTAATGAAGGCATATTCC TAA   ATGCAATGC                                           ORF Start: ATG at 8       ORF Stop: TAA at 1127           SEQ ID NO:18   373 aa   MW at 42681.4 kD                     NOV6b,   MWLLLTTTCLICGTLNAGGFLDLENEVNPEVWMNTSEIIIYNGYPSEEYEVTTEDGYI       CG50159-03       Protein   LLVNRIPYGRTHARSTGPRPVVYMQHALFADNAYWLENYANGSLGFLLADAGYDVWMG       Sequence           NSRGNTWSRRHKTLSETDEKFWAFGFDEMAKYDLPGVIDFIVNKTGQEKLYFIGHSLG                   TTIGFVAFSTMPELAQRIKMNFALGPTISFKYPTGIFTRFFLLPNSILKAVFGTKGFF                   LEDKKTKIASTKICNNKILWLICSEFMSLWAGSNKKNMNQLYHSDEFRAYDWGNDADN                   MKHYNQSHPPIYDLTAMKVPTAIWAGGHDVLVTPQDVARILPQIKSLHYFKLLPDWNH                   FDFVWGLDAPQRMYSEIIALMKAYS                                     SEQ ID NO:19   1080 bp                     NOV6C,     AGA TCTGGTGGATTCCTTGATTTGGAAAATGAAGTGAATCCTGAGGTGTGGATGAATA       241065526       DNA Sequence   CTAGTGAAATCATCATCTACAATGGCTACCCCAGTGAAGAGTATGAAGTCACCACTGA                   AGATGGGTATATACTCCTTGTCAACACAATTCCTTATGGGCGAACACATGCTAGGAGC                   ACAGGTCCCCGGCCAGTTGTGTATATGCAGCATGCCCTGTTTGCAGACAATGCCTACT                   GGCTTGAGAATTATGCCAATGGAAGCCTTGGATTCCTTCTAGCAGATGCAGGTTATGA                   TGTATGGATGGGAAACAGTCGGGGAAACACTTGGTCAAGAAGACACAAAACACTCTCA                   GACACAGATGAGAAATTCTGGGCCTTTAGTTTTGATGAAATGGCCAAATATGATCTCC                   CAGGAGTAATAGACTTCATTGTAAATAAAACTGGTCAGGAGAAATTGTATTTCATTGG                   ACATTCACTTGGCACTACAATAGGGTTTGTAGCCTTTTCCACCATGCCTGAACTGGCA                   CAAAGAATCAAAATGAATTTTGCCTTGGGTCCTACGATCTCATTCAAATATCCCACGG                   GCATTTTTACCAGGTTTTTTCTACTTCCAAATTCCATAATCAAGGCTGTTTTTGGTAC                   CAAAGGTTTCTTTTTAGAAGATAAGAAAACGAAGATAGCTTCTACCAAAATCTGCAAC                   AATAAGATACTCTGGTTGATATGTAGCGAATTTATGTCCTTATGGGCTGGATCCAACA                   AGAAAAATATGAATCAGCTTTACCACTCTGATGAATTCAGAGCTTATGACTGGGGAAA                   TGACGCTGATAATATGAAACATTACAATCAGAGTCATCCCCCTATATATGACCTGACT                   GCCATGAAAGTGCCTACTGCTATTTGGGCTGGTGGACATGATGTCCTCGTAACACCCC                   ACGATGTGGCCAGGATACTCCCTCAAATCAAGAGTCTTCATTACTTTAAGCTATTGCC                   AGATTGGAACCACTTTGATTTTGTCTGGGGCCTCGATGCCCCTCAACGGATGTACAGT                   GAAATCATAGCTTTAATGAAGGCATATTCCCTCGAG                                         ORF Start: at 1       ORF Stop: end of sequence           SEQ ID NO:20   360 aa   MW at 41347.7 kD                     NOV6C,   RSGGFLDLENEVNPEVWMNTSEIIIYNGYPSEEYEVTTEDGYILLVNRIPYGRTHARS       241065526       Protein   TGPRPVVYMQHALFADNAYWLENYANGSLGFLLADAGYDVWMGNSRGNTWSRRHKTLS       Sequence           ETDEKFWAFSFDEMAKYDLPGVIDFIVNKTGQEKLYFIGHSLGTTIGFVAFSTMPELA                   QRIKMNFALGPTISFKYPTGIFTRFFLLPNSIIKAVFGTKGFFLEDKKTKIASTKICN                   NKILWLICSEFMSLWAGSNKKNNNQLYNSDEFRAYDWGNDADNMKHYNQSHPPIYDLT                   AMKVPTAIWAGGHDVLVTPQDVARILPQIKSLHYFKLLPDWNHFDFVWGLDAPQRMYS                   EIIALMKAYSLE                                     SEQ ID NO:21   801 bp                     NOV6d,     AGA TCTTATGATGTATGGATGGGAAACAGTCGGGGAAACACTTGGTCAAGAAGACACA       241065558       DNA   AAACACTCTCAGAGACAGATGAGAAATTCTGGGCCTTTAGTTTTGATGAAATGGCCAA       Sequence           ATATGATCTCCCAGGAGTAATAGACTTCATTGTAAATAAAACTGGTCAGGAGAAATTG                   TATTTCATTGGACATTCACTTGGCACTACAATAGGGTTTGTAGCCTTTTCCACCATGC                   CTGAACTGGCACAAAGAATCAAAATGAATTTTGCCTTGGGTCCTACGATCTCATTCAA                   ATATCCCACGGGCATTTTTACCAGGTTTTTTCTACTTCCAAATTCCATAATCAAGGCT                   GTTTTTGGTACCAAAGGTTTCTTTTTAGAAGATAAGAAAACGAAGATAGCTTCTACCA                   AAATCTGCAACAATAACATACTCTGGTTGATATGTAGCGAATTTATGTCCTTATGGGC                   TGGATCCAACAAGAAAAATATGAATCAGCTTTACCACTCTGATGAATTCAGAGCTTAT                   GACTGGGGAAATGACGCTGATAATATGAAACATTACAATCAGAGTCATCCCCCTATAT                   ATGACCTGACTGCCATGAAAGTGCCTACTGCTATTTGGGCTGGTGGACATGATGTCCT                   CGTAACACCCCAGGATGTGGCCAGGATACTCCCTCAAATCAAGAGTCTTCATTACTTT                   AAGCTATTGCCACATTGGAACCACTTTGATTTTGTCTGGGGCCTCGATGCCCCTCAAC                   GGATGTACAGTGAAATCATAGCTTTAATGAAGGCATATTCCCTCGAG                                         ORF Start: at 1       ORF Stop: end of sequence           SEQ ID NO:22   267 aa   MW at 30874.2 kD                     NOV6d,   RSYDVWMGNSRGNTWSRRHKTLSETDEKFWAFSFDEMAKYDLPGVIDFIVNKTGQEKL       241065558       Protein   YFIGHSLGTTIGFVAFSTMPELAQRIKMNFALGPTISFKYPTGIFTRFFLLPNSIIKA       Sequence           VFGTKGFFLEDKKTKIASTKICNNKILWLICSEFMSLWAGSNKKNMNQLYHSDEFRAY                   DWGNDADNMKHYNQSHPPIYDLTAMKVPTAIWAGGHDVLVTPQDVARILPQIKSLHYF                   LPDWNHFDFVWGLDAPQRMYSEIIALMKAYSLE                                     SEQ ID NO:23   1267 bp                     NOV6e,     GTCCAAA   ATG TGGCTGCTTTTAACAACAACTTGTTTGATCTGTGGAACTTTAAATGCT       CG50159-01       DNA Sequence   GGTGGATTCCTTGATTTGGAAAATGAAGTGAATCCTGAGGTGTGGATGAATACTAGTG                   AAATCATCATCTACAATGGCTACCCCAGTGAAGAGTATGAAGTCACCACTGAAGATGG                   GTATATACTCCTTGTCAACAGAATTCCTTATGGGCGAACACATGCTAGGAGCACAGGT                   CCCCGGCCAGTTCTGTATATGCAGCATGCCCTGTTTGCAGACAATGCCTACTGGCTTC                   AGAATTATGCTAATGGAAGCCTTGGATTCCTTCTAGCAGATGCAGGTTATGATGTATG                   GATGGGAAACAGTCGGGGAAACACTTGGTCAAGAAGACACAAAACACTCTCAGAGACA                   GATGAGAAATTCTGGGCCTTTGGTTTTGATGAAATGGCCAAATATGATCTCCCAGGAG                   TAATAGACTTCATTGTAAATAAAACTGGTCAGGAGAAATTGTATTTCATTGGACATTC                   ACTTGGCACTACAATACGGTTTGTAGCCTTTTCCACCATGCCTGAACTGGCACAAAGA                   ATCAAAATGAATTTTGCCTTGGGTCCTACGATCTCATTCAAATATCCCACGGGCATTT                   TTACCAGGTTTTTTCTACTTCCAAATTCCATAATCAAGGCTGTTTTTGGTACCAAAGG                   TTTCTTTTTAGAAGATAAGAAAACGAAGATAGCTTCTACCAAAATCTGCAACAATAAG                   ATACTCTGGTTGATATGTAGCGAATTTATGTCCTTATGGGCTGGATCCAACAAGAAAA                   ATATGAATCAGCTTTACCACTCTGATGAATTCAGAGCTTATGACTGGGGAAATGACGC                   TGATAATATGAAACATTACAATCAGAGTCATCCCCCTATATATGACCTGACTGCCATG                   AAAGTGCCTACTGCTATTTGGGCTGGTGGACATGATGTCCTCGTAACACCCCAGGATG                   TGGCCAGGATACTCCCTCAAATCAAGAGTCTTCATTACTTTAAGCTATTGCCAGATTG                   GAACCACTTTGATTTTGTCTGGGGCCTCGATGCCCCTCAACGGATGTACAGTGAAATC                   ATAGCTTTAATGAAGGCATATTCC TAA   ATGCAATGCATTTACTTTTCAATTAAAAGTT                       GCTTCCAAGCCCATAAGGGACTTTAGAAAAAATAGTAACCAACAATGAGGTTGTCCCC                       CAGCACCCTGGGGGAGATGCACAGTGGAGTCTGTTTTCCAAGTCAATTG                                           ORF Start: ATG at 8       ORF Stop: TAA at 1127           SEQ ID NO:24   373 aa   MW at 42681.4 kD                     NOV6e,   MWLLLTTTCLICGTLNAGGFLDLENEVNPEVWMNTSEIIIYNGYPSEEYEVTTEDGYI       CG50159-01       Protein   LLVNRIPYGRTHARSTGPRPVVYMQHALFADNAYWLENYANGSLGFLLADAGYDVWNG       Sequence           USRGNTWSRRHKTLSETDEKFWAFGFDEMAKYDLPGVIDFIVNKTGQEKLYFIGHSLG                   TTIGFVAFSTMPELAQRIKMNFALGPTISFKYPTGIFTRFFLLPNSIIKAVFGTKGFF                   LEDKKTKIASTKICNNKILWLICSEFMSLWAGSNKKNMNQLYHSDEFRAYDWGMDADN                   MKHYNQSHPPIYDLTANKVPTAIWAGGHDVLVTPQDVARILPQIKSLHYFKLLPDWNH                   FDFVWGLDAPQRMYSEIIALMKAYS                                     SEQ ID NO:25   1195 bp                     NOV6f,     GTCCAAA   ATG TGGCTGCTTTTAACAACAACTTGTTTGATCTGTGGAACTTTAAATGCT       CG50159-04       DNA Sequence   GGTCGATTCCTTGATTTGGAAAATGAAGTGAATCCTGAGGTGTGGATGAATACTAGTG                   AAATCATCATCTACAATGGCTACCCCAGTGAAGAGTATGAAGTCACCACTGAAGATGG                   GTATATACTCCTTGTCAACAGAATTCCTTATGGGCGAACACATGCTAGGAGCACAGGT                   CCCCGGCCAGTTGTGTATATGCAGCATGCCCTGTTTGCAGACAATGCCTACTGGCTTG                   AGAATTATGCTAATGGAAGCCTTGGATTCCTTCTAGCAGATGCAGGTTATGATGTATG                   GATGGGAAACAGTCGGGGAAACACTTGGTCAAGAAGACACAAAACACTCTCAGAGACA                   GATGAGAAATTCTGGGCCTTTGGTTTTGATGAAATGGCCAAATATGATCTCCCAGGAC                   TAATAGACTTCATTGTAAATAAAACTGGTCAGGAGAAATTGTATTTCATTGGACATTC                   ACTTGGCACTACAATAGGGTTTGTAGCCTTTTCCACCATGCCTGAACTGGCACAAAGA                   ATCAAAATGAATTTTGCCTTGGGTCCTACGATCTCATTCAAATATCCCACGGGCATTT                   TTACCAGGTTTTTTCTACTTCCAAATTCCATAATCAAGGCTGTTTTTGGTACCAAAGG                   TTTCTTTTTAGAAGATAAGAAAACGAAGATAGCTTCTACCAAAATCTGCAACAATAAG                   ATACTCTGGTTGATATGTAGCGATTTATCTCCTTATGGGCTGGATCCAACAAGAAAAA                   ATATGAATCAGAGTCATCCCCCTATATATGACCTGACTGCCATGAAAGTGCCTACTGC                   TATTTGGCCTGGTGGACATGATGTCCTCGTAACACCCCAGGATGTCGCCAGGATACTC                   CCTCAAATCAAGAGTCTTCATTACTTTAAGCTATTGCCAGATTGGAACCACTTTGATT                   TTGTCTGGGGCCTCGATGCCCCTCAACGGATGTACAGTGAAATCATAGCTTTAATGAA                   GGCATATTCC TAA   ATGCAATGCATTTACTTTTCGATTAAAAGTTGCTTCCAAGCCCAT                       AAGGGACTTTAGAAAAAATAGTAACCAACAATGAGGTTGTCCCCCAGCAACCTGGGGG                       AGATGCACAGTGCAGTCTGTTTTCCAAGTCAATTG                                           ORF Start: ATG at 8       ORF Stop: TAA at 1055           SEQ ID NO:26   349 aa   MW at 39709.3 kD                     NOV6f,   MWLLLTTTCLICGTLNAGGFLDLENEVNPEVWMNTSEIIIYNGYPSEEYEVTTEDGYI       CG50159-04       Protein   LLVNRIPYGRTHARSTGPRPVVYMQHAWFADNAYWLENYAAGSLGFLLAAAGYDTAAG       Sequence           NSRGNTWSRRHKTLSETDEKFWAFGFDEAAKYDLPGVIDFIAAKTGQEKLYFIGHSLG                   TTIGFVAFSTMPELAQRIKMNFALGPTISFKYPTGIFTRFFLLPNSIIKAVFGTKGFF                   LEDKKTKIASTKICNNKILWLICSEFMSLAWAGSNKKNMNQSHPPIYDLTAMKVPTIW                   AGGHDVLVTPQDVARILPQIKSLHYFKLLPDWNHFDFVWGLDAPQRMYSEIIALMKAYS                  
 
     [0376] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 6B.  
               TABLE 6B                          Comparison of NOV6a against NOV6b through NOV6f.                                 Protein   NOV6a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV6b   3 . . . 375   367/373 (98%)               1 . . . 373   368/373 (98%)           NOV6c   19 . . . 375    351/357 (98%)               2 . . . 358   353/357 (98%)           NOV6d   113 . . . 375    261/263 (99%)               3 . . . 265   261/263 (99%)           NOV6e   3 . . . 375   367/373 (98%)               1 . . . 373   368/373 (98%)           NOV6f   3 . . . 375   344/373 (92%)               1 . . . 349   345/373 (92%)                      
 
     [0377] Further analysis of the NOV6a protein yielded the following properties shown in Table 6C.  
               TABLE 6C                          Protein Sequence Properties NOV6a                     SignalP           analysis:   Cleavage site between residues 20 and 21               PSORT II   PSG: a new signal peptide prediction method       analysis:     N-region: length 2; pos. chg 1; neg. chg 0             H-region: length 21; peak value 9.03             PSG score: 4.62           GvH: von Heijne&#39;s method for signal seq. recognition             GvH score (threshold: −2.1): −3.30             possible cleavage site: between 15 and 16           &gt;&gt;&gt; Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation             Init position for calculation: 1             Tentative number of TMS(s) for the threshold 0.5: 0             number of TMS(s) . . . fixed             PERIPHERAL Likelihood = 1.22 (at 3)             ALOM score: 1.22 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)             Center position for calculation: 6             Charge difference: −6.0 C(−4.0) − N(2.0)             N &gt;= C: N-terminal side will be inside           MITDISC: discrimination of mitochondrial targeting seq                                       R content:     0   Hyd Moment (75):   3.85             Hyd Moment (95):     5.34   G content:   3             D/E content:     1   S/T content:   5             Score:   −5.32                         Gavel: prediction of cleavage sites for mitochondrial preseq             cleavage site motif not found           NUCDISC: discrimination of nuclear localization signals             pat4: RRHK (3) at 127             pat7: none             bipartite: none             content of basic residues: 8.8%             NLS Score: −0.29           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:             KRXX-like motif in the C-terminus: MKAY           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:             type 1: none             type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination             Prediction: cytoplasmic             Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions             total: 0 residues           --------------------------           Final Results (k = {fraction (9/23)})             33.3%: extracellular, including cell wall             22.2%: nuclear             11.1%: cytoplasnic             11.1%: mitochondrial             11.1%: vacuollar             11.1%: endoplasmic reticulum           &gt;&gt; prediction for CG50159-02 is exc (k = 9)                      
 
     [0378] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6D.  
               TABLE 6D                          Geneseq Results for NOV6a                                         NOV6a   Identities/               Protein/   Residues/   Similarities for       Geneseq   Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABP53569   Human NOV1   3 . . . 375   367/373 (98%)   0.0           protein SEQ ID   1 . . . 373   368/373 (98%)           NO: 2— Homo               sapiens , 373 aa.           [WO200262999-           A2, 15 AUG.           2002]       ABP53569   Human NOV1   3 . . . 375   367/373 (98%)   0.0           protein SEQ ID   1 . . . 373   368/373 (98%)           NO: 2— Homo               sapiens , 373 aa.           [WO200262999-           A2, 15 AUG.           2002]       AAU98539   Human lysosomal   1 . . . 375   369/399 (92%)   0.0           acid lipase protein   29 . . . 427    370/399 (92%)           #2— Homo               sapiens , 427 aa.           [WO200236754-           A2, 10 MAY           2002]       AAU77493   Human lipid   1 . . . 375   367/399 (91%)   0.0           metabolism   5 . . . 403   368/399 (91%)           enzyme,           LMM-1— Homo               sapiens , 403 aa.           [WO200216597-           A2, 28 FEB.           2002]       AAO18226   Human lysosomal   3 . . . 365   349/389 (89%)   0.0           acid lipase—   2 . . . 390   352/389 (89%)             Homo sapiens ,           395 aa.           [US6387680-B1,           14 MAY 2002]                  
 
     [0379] In a BLAST search of public sequence databases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6E.  
               TABLE 6E                          Public BLASTP Results for NOV6a                                         NOV6a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/   Match   the Matched   Expect       Number   Organism/Length   Residues   Portion   Value               G01416   lysosomal acid   2 . . . 374   198/397 (49%)   e−112           lipase—human,   2 . . . 398   261/397 (64%)           399 aa.       S41408   lysosomal acid lipase   2 . . . 374   198/397 (49%)   e−112           (EC 3.1.1.-)/sterol   2 . . . 398   261/397 (64%)           esterase (EC 3.1.1.13)           precursor—human,           399 aa.       P38571   Lysosomal acid lipase/   2 . . . 374   197/397 (49%)   e−111           cholesteryl ester   2 . . . 398   260/397 (64%)           hydrolase precursor           (EC 3.1.1.13) (LAL)           (Acid cholesteryl           ester hydrolase) (Sterol           esterase) (Lipase A)           (Cholesteryl           esterase)— Homo               sapiens  (Human),           399 aa.       Q9D6T5   Adult male tongue   3 . . . 371   193/393 (49%)   e−110           cDNA, RIKEN full-   1 . . . 392   254/393 (64%)           length enriched           library, clone:           2310061A13, full           insert sequence— Mus               musculus  (Mouse),           395 aa.       Q9CPP7   2310051B21 Rik   3 . . . 371   193/393 (49%)   e−110           protein— Mus     1 . . . 392   254/393 (64%)           musculus (Mouse),           395 aa.                  
 
     [0380] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6F.  
               TABLE 6F                          Domain Analysis of NOV6a                                     Identities/               NOV6a   Similarities for   Expect       Pfam Domain   Match Region   the Matched Region   Value               abhydro_lipase   29 . . . 99    36/71 (51%)   4.5e−29                56/71 (79%)       abhydrolase   113 . . . 368    43/261 (16%)   2.2e−16               178/261 (68%)                  
 
     Example 7  
     [0381] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.  
               TABLE 7A                       NOV7 Sequence Analysis                                                SEQ ID NO:27   1606 bp                     NOV7a,     ATG ACTCTAATCTGGAGACATTTGCTGAGACCCTTGTGCCTGGTCACTTCCGCTCCCA       CG56099-03       DNA Sequence   GGATCCTTGAGATGCATCCTTTCCTGAGCCTAGGTACTTCCCGGACATCAGTAACCAA                   GCTCAGTCTTCATACAAAGCCCAGAATGCCTCCATGTGACTTCATGCCTGAAAGATAC                   CAGTCCCTTCGCTACAACCGTGTCCTGGAAATCCACAAGGAACATCTTTCTCCTGTGG                   TGACGGCATATTTCCAGAAACCCCTGCTGCTCCACCAGGGGCACATGGAGTGGCTCTT                   TGATGCTGAAGGAAACAGATACCTGGATTTCTTTTCCGGGATTGTTACTGTCAGTGTT                   GGCCACTGCCACCCGGTGTGTGCAGGAGGGACGTGGCACGCAGTGCAGGTAACTCTGC                   TGTACTGCTTATCCAGAAAGGTGAATGCAGTGGCACAAAAGCAGCTCGGCCGCCTGTG                   GCATACAAGCACCGTCTTCTTCCACCCTCCAATGCATGAATATGCAGAGAAGCTTGCC                   GCACTTCTTCCTGAGCCTCTTAAGGTCATTTTCTTGGTGAACAGTGGCTCAGAAGCCA                   ATGAGCTCGCCATGCTGATGGCCAGGGCGCACTCAAACAACATAGACATCATTTCTTT                   CAGAGGAGCCTACCATGGATGCAGTCCTTACACACTTGGCTTGACAAACGTAGGGATC                   TACAAGATGGAACTCCCTGGTGGGACAGGTTGCCAACCAACAATGTGTCCAGATGTTT                   TTCGTGGCCCTTGGGGAGGAAGCCACTGTCGAGATTCTCCAGTGCAAACAATCAGGAA                   GTGCAGCTGTGCACCAGACTGCTGCCAAGCTAAAGATCAGTATATTGAGCAATTCAAA                   GATACGCTGAGCACATCTGTGCCCAAGTCAATTGCTGGATTTTTCGCAGAACCTATTC                   AAGGTGTGAATGGAGTTGTCCAGTACCCAAAGGGGTTTCTAAAGGAAGCCTTTGAGCT                   GGTGCGAACAAGGGGAGGCGTGTGCATTGCAGATGAAGTGCAGACAGGATTTGGAAGG                   TTGGGCTCTCACTTCTGGGGCTTCCAAACCCACGATGTCCTGCCTGACATTGTCACCA                   TGGCTAAAGGGATTGGGAATGGCCTTCCCATGGCAGCAGTCATAACCACTCCAGAGAT                   TGCCAAATCTTTGGCGAAATGCCTGCAGCACTTCAACACCTTTGGAGGGAACCCCATG                   GCCTGTGCCATTGGATCTGCTGTGCTTGAGGTGATTAAAGAAGAAAATCTACAGGAAA                   ACAGTCAAGAAGTTGCGACCTACATGTTACTAAAGTTTGCTAAGCTGCGGGATGAATT                   TGAAATTGTTGGAGACGTCCGAGGCAAAGGCCTCATGATAGGCATAGAAATGGTGCAG                   GATAAGATAAGCTGTCGGCCTCTTCCCCGTGAAGAAGTAAATCAGATCCATGAGGACT                   GCAAGCACATGGGACTCCTCGTTGGCAGAGGCAGCATTTTTTCTCAGACATTTCGCAT                   TGCGCCCTCAATGTGCATCACTAAACCAGAAGTTGATTTTGCAGTAGAAGTATTTCGT                   TCTGCCTTAACCCAACACATGGAAAGAGAGCTAAG TAA   C                                           ORF Start: ATG at 1       ORF Stop: TAA at 1603           SEQ ID NO:28   534 aa   MW at 59350.4 kD                     NOV7a,   MTLIWRHLLRPLCLVTSAPRILEMHPFLSLGTSRTSVTKLSLHTKPRMPPCDFMPERY       CG56099-03       Protein   QSLGYNRVLEIHKEHLSPVVTAYFQKPLLLHQGHMEWLFDAEGNRYLDFFSGIAAVSV       Sequence           GHCHPVCAGGTWHAVQVTLLYCLSRKVNAVAQKQLGRLWHTSTVFFHPPMHEYAEAAA                   ALLPEPLKVIFLVNSGSEANELAMLMARAHSNNIDIISFRGAYHGCSPYTLGLTNVGI                   YKMELPGGTGCQPTMCPDVFRGPWGGSHCRDSPVQTIRKCSCAPDCCQAAAQYIEQFK                   DTLSTSVAKSIAGFFAEPIQGVNGVVQYPKGFLKEAFELVRTRGGVCIAAEVQTGFGR                   LGSHFWGFQTHDVLPDIVTMAKGIGNGLPMAAVITTPEIAKSLAKCLQHFNTFGGNPM                   ACAIGSAVLEVIKEENLQENSQEVGTYMLLKFAKLRDEFEIVGDAAGKGLMIGIEAAQ                   DKISCRPLPREEVNQIHEDCKHMGLLVGRGSIFSQTFRIAPSMCITKPEVDFAVEVFR                   SALTQHMERRAK                                     SEQ ID NO:29   1335 bp                     NOV7b,     AA   ATG ACTCTAATCTGGAGACATTTGCTGAGACCCTTGTGCCTGGTCACTTCCGCTCC       CG56099-02       DNA Sequence   CAGGATCCTTGAGATGCATCCTTTCCTGAGCCTAGGTACTTCCCGGACATCAGTAACC                   AAGCTCAGTCTTCATACAAAGCCCAGAATGCCTCCATGTGACTTCATGCCTGAAAGAT                   ACCAGTCCCTTGGCTACAACCGTGTCCTGGAAATCCACAAGGAACATCTTTCTCCTGT                   GGTGACGGCATATTTCCAGAAACCCCTGCTGCTCCACCAGGGGCACATGGAGTGGCTC                   TTTGATGCTGAAGGAAGCAGATACCTGGATTTCTTTTCCGGGATTGTTACTGTCAGTG                   TTGGCCATTGCCACCCAAAGGTGAATGCAGTGGCACAAAAGCAGCTCGGCCGCCTGTG                   GCATACAAGCACCGTCTTCTTCCACCCTCCAATCCATGAATATGCAGAGAAGCTTGCC                   GCACTTCTTCCTGAGCCTCTTAAGGTCATTTTCTTGGTGAACAGTGGCTCAGAACCCA                   ATCAGCTGGCCATGCTGATGCCCAGGGCGCACTCAAACAACATAGACATCATTTCTTT                   CAGAGGAGCCTACCATGGATGCAGTCCTTACACACTTGGCTTGACAAACGTAGGGACC                   TACAAGATGGAACTCCCTGGTGGGACAGGTTGCCAACCAACAATGTGTCCAGATGTTT                   TTCGTGGCCCTTGGGGAGGAAGCCACTGTCGAGATTCTCCAGTGCAAACAATCAGGAA                   GTGCAGCTGTGCACCAGACTGCTGCCAAGCTAAAGATCAGTATATTGAGCAATTCAAA                   GATACGCTGAGCACATCTGTGGCCAAGTCAATTGCTGGATTTTTCGCAGAACCTATTC                   AAGGTGTGAATGGAGTTGTCCAGTACCCAAAGGGGTTTCTAAAGGAAGCCTTTGAGCT                   GGTGCGAGCAAGGGGAGGCGTGTGCATTGCAGATGAAGTGATTAAAGAAGAAAATCTA                   CAGGAAACAGTCAAGAAGTTGGGACCTACATGTTACTAAAAGTTTGCTAAGCTGCGGG                   ATGAATTTGAAATTGTTGGAGACGTCCGAGGCAAAGGCCTCATGATAGGCATAGAAAT                   GGTGCAGGATAAGATAAGCTGTCGGCCTCTTCCCCGTGAAGAAGTAAATCAGATCCAT                   GAGGACCGCAAGCACATGGGACTCCTCGTTGGCAGAGGCAGCATTTTTTCTCAGACAT                   TTCGCATTGCGCCCTCAATGTGCATCACTAAACCAGAAGTTGATTTTGCAGTAGAAGT                   ATTTCGTTCTGCCTTAACCCAACACATGGAAAGAAGAGCTAAG TAA   CATTGTCAGAAA                       T                                           ORF Start: ATG at 3       ORF Stop: TAA at 1320           SEQ ID NO:30   439 aa   MW at 49349.8 kD                     NOV7b,   MTLIWRHLLRPLCLVTSAPRILEMHPFLSLGTSRTSVTKLSHTIKPRMPPCDFMPERY       CG56099-02       Protein   QSLGYNRVLEIHKEHLSPVVTAYFQKPLLLHQGHMEWLFDAEGSRYLDFFSGIAAVSV       Sequence           GHCHPKVNAVAQKQLGRLWHTSTVFFHPPMHEYAEKLAALLPEPLKVIFLVNSGSEAN                   ELAMLMARAHSNNTDIISFRGAYHGCSPYTLGLTNVGTYKMELPGGTGCQPTMCPDVF                   RGPWGGSHCRDSPVQTIRKCSCAPDCCQAAAQYIEQFAATLSTSVAKSIAGFFAEPIQ                   GVNGVVQYPKGFLKEAFELVRARGGVCIAAEVIKEENLQENSQEVGTYMLLKFAKLRD                   EFEIVGDVRGKGLMIGIEMVQDKISCRPLPREEVNQIHEDRKHMGLLVGRGSIFSQTF                   RIAPSMCTTKPEVDFAVEVFRSALTQHMERAAK                                     SEQ ID NO:31   1554 bp                     NOV7C,     AA   ATG ACTCTAATCTGGAGACATTTGCTGAGACCCTTGTGCCTGGTCACTTCCTCTCC       CG56099-01       DNA Sequence   CAGGATCCTTGAGATGCATCCTTTCCTGAGCCTAGGTACTTCCCGGACATCAGTAACC                   AAGCTCAGTCTTCATATAAAGCCCAGAATGCCTCCATGTGACTTCATGCCTCAAAGAT                   ACCAGTCCCTTGGCTACAACCGTGTCCTGGAAATCCACAAGGAACATCTTTCTCCTGT                   GGTGACGCCATATTTCCAGAAACCCCTGCTGCTCCACCAGGGGCACATGGAGTGGCTC                   TTTGATGCTGAAGCAAACAGATACCTGGATTTTTTTTCCGGGATTGTTACTGTCAGTG                   TTGGCCATTGCCACCCGAAGGTGAATGCAGTGGCACAAAAGCAGCTCGGCCGCCTGTG                   GCATACAAGCACCATCTTCTTCCACCCTCCAATGCATGAATATGCAGAGAAGCTTGCC                   GCACTTCTTCCTGAGCCTCTTAAGGTAATTTTCTTGGTGAACAGTGGCTCAGAAGCCA                   ATGAGCTGCCCATGCTGATGGCCAGGGCGCACTCAAACAACATAGACATCATTTCTTT                   CAGAGGAGCCTACCATGGATGCAGTCCTTACACACTTGGCTTGACAAACGTAGGGACC                   TACAAGATGGAACTCCCTGGTGGGACAGGTTGCCAACCAGTGACAATGTGTCCAGATG                   TTTTTCGTGGCCCTTGGGGAGGAAGCCACTGTCGAGATTCTCCAGTGCAAACAATCAG                   GAAGTGCAGCTGTGCACCAGACTGCTGCCAAGCTAAAGATCAGTATATTGAGCAATTC                   AAAGATACGCTGAGCACATCTGTGGCCAAGTCAATTGCTGGATTTTTCGCAGAACCTA                   TTCAAGGTGTGAATGGAGTTGTCCAGTACCCAAAGGGGTTTCTAAAGGAAGCCTTTGA                   GCTGGTGCGAGCAAGGGGAGGCGTGTGCATTGCAGATGAAGTGCAGACAGGATTTGGA                   AGGTTGGGCTCTCACTTCTGCGGCTTCCAAACCCACGATGTCCTGCCTGACATTGTCA                   CCATGGCTAAAGGGATTGGGAATGGCTTTCCCATGGCAGCAGTCATAACCACTCCAGA                   GATTGCCAAATCTTTGGCGAAATGCCTGCAGCACTTCAACACCTTTGGAGGGAACCCC                   ATGGCCTGTGCCATTGGATCTGCTGTGCTTGAGGTGATTAAAGAAGAAAATCTACAGG                   AAAACAGTCAAGAAGTTGGGACCTACATGTTACTAAAGTTTGCTAAGCTGCGGGATGA                   ATTTGAAATTGTTGGAGACGTCCGAGGCAAAGGTCTCATGATAGGCATAGAAATGGTG                   CAGGATAAGATAAGCTGTCGGCCTCTTCCCCGTGAAGAAGTAAATCAGATCCATGAGG                   ACTGCAAGCACATGGGACTCCTCGTTGGCAGAGGCAGCATTTTTTCTCAGACATTTCG                   CATTGCGCCCTCAATGTGCATCACTAAACCAGAAGTTGATTTTGCAGTAGAAGTATTT                   CGTTCTGCCTTAACCCAACACATGGAAAGAAGAGC TAA   GTAACATT                                           ORF Start: ATG at 3       ORF Stop: TAA at 1548           SEQ ID NO:32   1515 aa   MW at 57324.0 kD                     NOV7C,   MTLIWRHLLRPLCLVTSSPRILEMHPFLSLGTSRTSVTKLSLHIKPRMPPCDFMPERY       CG56099-01       Protein   QSLGYNRVLEIHKEHLSPVVTAYFQKPLLLHQGHMEWLFDAEGNRYLDFFSGIAAVSV       Sequence           GHCHPKVNAVAQKQLGRLWHTSTIFFHPPMHEYAEKLAALLPEPLKVIFLVNSGSEAA                   ELAMLMARAHSMNIDIISFRGAYHGCSPYTLGLTNVGTYKMELPGGTGCQPVTMCPDV                   FRGPWGGSHCRDSPVQTIRKCSCAPDCCQAAAQYIEQFAATLSTSVAKSIAGFFAEPI                   QGVNGVVQYPKGFLKEAFELVRARGGVCIADEVQTGFGRLGSHFWGFQTHDVLPDIVT                   MAKGIGNGFPMAAVITTPEIAKSLAKCLQHFNTFGGNPAACAIGSAAAEVIKEENLQE                   NSQEVGTYMLLKFAKLRDEFEIVGDAAGKGLMIGIEMVQDKISCRPLPREEVNQIHED                   CKHMGLLVGRGSIFSQTFRIAPSMCITKPEAAFAVEVFRSAATQHMERAAK                  
 
     [0382] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 7B.  
               TABLE 7B                          Comparison of NOV7a against NOV7b and NOV7c.                                 Protein   NOV7a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV7b   1 . . . 342   319/342 (93%)               1 . . . 322   320/342 (93%)           NOV7c   1 . . . 534   508/535 (94%)               1 . . . 515   510/535 (94%)                      
 
     [0383] Further analysis of the NOV7a protein yielded the following properties shown in Table 7C.  
               TABLE 7C                          Protein Sequence Properties NOV7a                     SignalP           analysis:   Cleavage site between residues 18 and 19               PSORT II   PSG: a new signal peptide prediction method       analysis:     N-region: length 10; pos. chg 2; neg. chg 0             H-region: length 9; peak value 7.01             PSG score: 2.61           GvH: von Heijne&#39;s method for signal seq. recognition             GvH score (threshold: −2.1): −4.80             possible cleavage site: between 33 and 34           &gt;&gt;&gt;Seems to have no N-terminal signal peptide           ALOM: Klein et al&#39;s method for TM region allocation             Init position for calculation: 1             Tentative number of TMS(s) for the threshold 0.5: 0             number of TMS(s) . . . fixed             PERIPHERAL Likelihood = 1.85 (at 173)             ALOM score: 1.85 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)             Center position for calculation: 6             Charge difference: 0.0 C(2.5) − N(2.5)             N &gt;= C: N-terminal side will be inside           MITDISC: discrimination of mitochondrial targeting seq                                       R content:     3   Hyd Monent (75):   8.40             Hyd Moment (95):     9.67   G content:   0             D/E content:     1   S/T content:   3             Score:   −0.62                         Gavel: prediction of cleavage sites for mitochondrial preseq             R-2 motif at 57 PRM|PP           NUCDISC: discrimination of nuclear localization signals             pat4: none             pat7: none             bipartite: none             content of basic residues: 9.9%             NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:             type 1: none             type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRt: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination             Prediction: cytoplasmic             Reliability: 94.1           COIL: Lupas&#39;s algorithm to detect coiled-coil regions             total: 0 residues           --------------------------           Final Results (k = {fraction (9/23)})             60.9%: mitochondrial             17.4%: cytoplasmic              8.7%: nuclear              4.3%: extracellular, including cell wall              4.3%: vacuolar              4.3%: endoplasmic reticulum           &gt;&gt; prediction for CG56099-03 is mit (k = 23)                      
 
     [0384] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7D.  
               TABLE 7D                          Geneseq Results for NOV7a                                         NOV7a   Identities/               Protein/   Residues/   Similarities for       Geneseq   Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAE21055   Human drug    1 . . . 534   512/534 (95%)   0.0           metabolising    1 . . . 514   512/534 (95%)           enzyme (DME-           13) protein—             Homo sapiens ,           514 aa.           [WO200212467-           A2, 14 FEB.           2002]       AAM40159   Human poly-    1 . . . 534   508/534 (95%)   0.0           peptide SEQ ID    1 . . . 514   510/534 (95%)           NO 3304— Homo               sapiens , 514 aa.           [WO200153312-           A1, 26 JUL.           2001]       AAE22521   Human amino-    1 . . . 534   508/534 (95%)   0.0           transferase-like    1 . . . 513   509/534 (95%)           enzyme protein—             Homo sapiens ,           513 aa.           [WO200226945-           A2, 04 APR.           2002]       AAM52652   Human amino-    1 . . . 534   507/534 (94%)   0.0           transferase    1 . . . 513   508/534 (94%)           23686— Homo               sapiens , 513 aa.           [WO200183720-           A2, 08 NOV.           2001]       AAM41945   Human poly-   177 . . . 534   351/358 (98%)   0.0           peptide SEQ ID    57 . . . 414   354/358 (98%)           NO 6876— Homo               sapiens , 414 aa.           [WO200153312-           A1, 26 JUL.           2001]                  
 
     [0385] In a BLAST search of public sequence databases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7E.  
               TABLE 7E                          Public BLASTP Results for NOV7a                                         NOV7a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/   Match   the Matched   Expect       Number   Organism/Length   Residues   Portion   Value               Q9BYV1   Alanine--    1 . . . 534   510/534 (95%)   0.0           glyoxylate amino-    1 . . . 514   511/534 (95%)           transferase 2,           mitochondrial           precursor           (EC 2.6.1.44)           (AGT 2) (Beta-           alanine-pyruvate           aminotransferase)           (Beta- ALAAT           II)— Homo               sapiens  (Human),           514 aa.       CAD19365   Sequence 1 from    1 . . . 534   509/534 (95%)   0.0           Patent    1 . . . 513   510/534 (95%)           WO0183720—             Homo sapiens             (Human), 513 aa.       Q64565   Alanine--    1 . . . 534   422/534 (79%)   0.0           glyoxylate amino-    1 . . . 512   456/534 (85%)           transferase 2,           mitochondrial           precursor           (EC 2.6.1.44)           (AGT 2) (Beta-           alanine-pyruvate           aminotransferase)           (Beta- ALAAT           II)— Rattus               norvegicus  (Rat),           512 aa.       Q9VNR7   CG11241   48 . . . 527   260/482 (53%)   e−149           protein—    9 . . . 468   328/482 (67%)             Drosophila               melanogaster             (Fruit fly),           474 aa.       Q95TT3   LD24726p—   48 . . . 527   259/482 (53%)   e−149             Drosophila     43 . . . 502   327/482 (67%)             melanogaster             (Fruit fly),           508 aa.                  
 
     [0386] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7F.  
               TABLE 7F                          Domain Analysis of NOV7a                                     Identities/               NOV7a   Similarities for   Expect       Pfam Domain   Match Region   the Matched Region   Value               aminotran_3   76 . . . 529   167/513 (33%)   5.6e−87               334/513 (65%)                  
 
     Example 8  
     [0387] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.  
               TABLE 8A                       NOV8 Sequence Analysis                                                SEQ ID NO:33   2422 bp                     NOV8a,     CCTCCCGACAATACAGGGGCAGCACTGCAGAGATTTC   ATC ATGGTCTCCCAGGCCCTC       CG59201-01       DNA Sequence   AGGCTCCTCTGCCTTCTGCTTGGGCTTCAGGGCTGCCTGGCTGCAGTCTTCGTAACCC                   AGGAGGAAGCCCACGGCGTCCTGCACCGGCGCCGGCGCGCCAACGCGTTCCTGGAGGA                   GCTGCGGCCGGGCTCCCTGGAGAGGGAGTGCAAGGAGGAGCAGTGCTCCTTCGAGGAG                   GCCCGGGAGATCTTCAAGGACGCGGAGAGGACGAAGCTGTTCTGGATTTCTTACAGTG                   ATGGGGACCAGTGTGCCTCAAGTCCATGCCAGAATGGCGGCTCCTGCAAGGACCAGCT                   CCAGTCCTATATCTGCTTCTGCCTCCCTGCCTTCGACGGCCGGAACTGTGAGACGCAC                   AAGGATGACCAGCTGATCTGTGTGAACGAGAACGGCGGCTGTGAGCAGTACTGCAGTG                   ACCACACGGGCACCAAGCGCTCCTGTCGGTGCCACGAGGGGTACTCTCTGCTGGCAGA                   CGGGGTGTCCTGCACACCCACAGTTGAATATCCATGTGGAAAAATACCTATTCTAGAA                   AAAAGAAATCCCAGCAAACCCCAAGGCCCAATTGTGGGGGGCAAGGTGTGCCCCAAAG                   GGGAGTGTCCATCGCAGGTCCTGTTGTTGGTGAATGGAGCTCAGTTGTGTGGGGGGAC                   CCTGATCAACACCATCTGGGTGGTCTCCGCGGCCCACTGTTTCGACAAAATCAAGAAC                   TGGAGGAACCTGATCGCGGTGCTGGGCGAGCACGACCTCAGCGAGCACGACGGGGATG                   AGCAGAGCCGGCGGGTGGCGCAGGTCATCATCCCCAGCACGTACGTCCCGGGCACCAC                   CAACCACGACATCGCGCTGCTCCGCCTGCACCAGCCCGTGGTCCTCACTGACCATGTG                   GTGCCCCTCTGCCTGCCCGAACGGACGTTCTCTGAGAGGACGCTGGCCTTCGTGCGCT                   TCTCATTGGTCAGCGGCTGGGGCCACCTGCTGGACCGTGGCGCCACGGCCCTGGAGCT                   CATGGTCCTCAACGTGCCCCGGCTGATGACCCAGGACTGCCTGCAGCAGTCACGGAAG                   GTGGGAGACTCCCCAAATATCACGGAGTACATGTTCTGTGCCGGCTACTCCGATGGCA                   CCAAGGACTCCTGCAAGGGGGACAGTGGAGCCCCACATGCCACCCACTACCGGGGCAC                   GTGGTACCTGACGGGCATCGTCAGCTGGGGCCAGGGCTGCGCAACCGTGGGCCACTTT                   GGGGTGTACACCAGGGTCTCCCAGTACATCGAGTGGCTGCAAAAGCTCATGCGCTCAG                   AGCCACGCCCAGGAGTCCTCCTGCGAGCCCCATTTCCC TAG   CCCAGCAGCCCTGGCCT                       GTGGAGAGAAAGCCAAGGCTCCGTCGAACTGTCCTCGCACCAAATCCCATATATTCTT                       CTGCAGTTAATGGCGTAGAGGAGGGCATGGGAGGGAGGGAGAGGTGGGGAGGGAGACA                       GAGACAGAAACACAGAGAGACAGAGACAGAGAGAGACTGAGGGAGAGACTCTGAGGAC                       ATGGAGAGAGACTCAAAGAGACTCCAAGATTCAAAGAGACTAATAGAGACACAGAGAT                       GGAATAGAAAAGATGAGAGGCAGAGGCAGACAGGCGCTGGACAGAGGGGCAGGGGAGT                       GCCAAGGTTGTCCTGGAGGCAGACAGCCCAGCTGAGCCTCCTTACCTCCCTTCAGCCA                       AGCCCCACCTGCACGTGATCTGCTGGCCCTCAGGCTGCTGCTCTGCCTTCATTGCTGG                       AGACAGTAGAGGCATGAACACACATGGATGCACACACACACACGCCAATGCACACACA                       CAGAGATATGCACACACACGGATGCACACACAGATGGTCACACAGAGATACGCAAACA                       CACCCATGCACACGCACATAGAGATATGCACACACAGATGCACACACAGATATACACA                       TGGATGCACGCACATGCCAATGCACGCACACATCAGTGCACACGGATGCACAGAGATA                       TGCACACACCGATGTGCGCACACACAGATATGCACACACATGGATGAGCACACACACA                       CCAAGTGCGCACACACACCGATGTACACACACAGATGCACACACAGATGCACACACAC                       CGATGCTGACTCCATGTGTGCTGTCCTCTGAAGGCGGTTGTTTAGCTCTCACTTTTCT                       GGTTCTTATCCATTATCATCTTCACTTCAGACAATTCAGAAGCATCACCATGCATGGT                       GGCGAATGCCCCCAAACTCTCCCCCAAATGTATTTCTCCCTTCGCTGGGTGCCGGGCT                       GCACAGACTATTCCCCACCTGCTTCCCAGCTTCACAATAAACGGCTGCGTCTCCTCCG                       CACACCTGTGGTGCCTGCCACCCAAAAAAAAAAAAAAAAAAAAAAA                                           ORF Start: ATG at 41       ORF Stop: TAG at 1373           SEQ ID NO:34   444 aa   MW at 49319.8 kD                     NOV8a,   MVSQALRLLCLLLGLQGCLAAVFVTQEEAHGVLHRRRRANAFLEELRPGSLERECKEE       CG59201-01       Protein   QCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQNGGSCAAQLQSYICFCLPAFEG       Sequence           RNCETHKDDQLICVNENGGCEQYCSDHTGTKRSCRCHEGYSLLADGVSCTPTVEYPCG                   KIPILEKRNASKPQGRIVGGKVCPKGECPWQVLLLVNGAQLCGGTLINTIWVVSAAHC                   FDKIKNWRNLIAVLGEHDLSEHDGDEQSRRVAQVIIPSTYVPGTTNHDIALLRLNQPV                   VLTDHVVPLCLPERTFSERTLAFVRFSLVSGWGQLLDRGATALELMVLAAPRLMTQDC                   LQQSRKVGDSPNITEYMFCAGYSDGSKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGC                   ATVGHFGVYTRVSQYIEWLQKLMRSEPRPGVLLRAPFP                                     SEQ ID NO:35   1361 bp                     NOV8b,     TGGGGAATGTCAACAGGCAGGGGCAGCACTGCAGAGATTTCATC   ATG GTCTCCCAGGC       CG59201-02       DNA Sequence   CCTCAGGCTCCTCTGCCTTCTGCTTGGGCTTCAGGGCTGCCTGGCTGCAGCCGGGGTC                   GCTAAGGCCTCAGGAGGAGAAACACGGGACATCCCGTGGAAGCCGGGGCCTCACAGAG                   TCTTCGTAACCCAGGAGGAAGCCCACGGCGTCCTGCACCGGCGCCCGCGCGCCAACGC                   GTTCCTGGAGGAGCTGCGGCCGGGCTCCCTGGAGAGGGAGTGCAAGGAGGAGCAGTGC                   TCCTTCGAGGAGGCCCGGGAGATCTTCAAGGACGCGGAGAGGACGAAGCTGTTCTGGA                   TTTCTTACAGTGATGGGGACCAGTGTGCCTCAAGTCCATGCCAGAATGGGGGCTCCTG                   CAAGGACCAGCTCCAGTCCTATATCTGCTTCTGCCTCCCTGCCTTCGAGGGCCGGAAC                   TGTGAGACGCTTGAATATCCATGTGGAAAAATACCTATTCTAGAAAAAAGAAATGCCA                   GCAAACCCCAAGGCCGAATTGTGGGGGGCAAGGTGTGCCCCAAAGGGGAGTGTCCATG                   GCAGGTCCTGTTGTTGGTGAATGGAGCTCAGTTGTGTGGGGGGACCCTGATCAACACC                   ATCTGGGTGGTCTCCGCGGCCCACTGTTTCGACAAAATCAAGAACTGGAGGAACCTGA                   TCGCGGTGCTGGGCGAGCACGACCTCAGCGAGCACGACGGGGATGAGCAGAGCCGGCG                   GGTGGCGCAGGTCATCATCCCCAGCACGTACGTCCCGGGCACCACCAACCACGACATC                   GCGCTGCTCCGCCTGCACCAGCCCGTGGTCCTCACTGACCATGTGGTGCCCCTCTGCC                   TGCCCGAACGGACGTTCTCTGAGAGGACGCTGGCCTTCGTCCGCTTCTCATTGGTCAG                   CGGCTGGGGCCAGCTGCTGGACCGTGGCGCCACGGCCCTGGAGCTCATGGTCCTCAAC                   GTGCCCCGGCTGATCACCCAGGACTGCCTGCAGCAGTCACGGAAGGTGGGAGACTCCC                   CAAATATCACGGAGTACATGTTCTGTGCCGGCTACTCGGATGGCAGCAAGGACTCCTG                   CAAGGGGGACAGTGGAGGCCCACATGCCACCCACTACCGGGGCACGTGCTACCTGACG                   GGCATCGTCAGCTGGGGCCAGGGCTGCGCAACCGTGGGCCACTTTGGGGTGTACACCA                   GGGTCTCCCAGTACATCGAGTGGCTGCAAAAGCTCATGCGCTCAGAGCCACGCCCAGG                   AGTCCTCCTGCGAGCCCCATTTCCC TAG   CCCAGCAGCCCTGGCCTGTCCAGAGAAAGC                       CAAGGCTGCGTCGAACTGTCCTGGCAC                                           ORF Start: ATG at 45       ORF Stop: TAG at 1302           SEQ ID NO:36   419 aa   MW at 46492.8 kD                     NOV8b,   MVSQALRLLCLLLGLQGCLAAGGVAKASGGETRDMPWKPGPHRVFVTQEEAHGVLHRR       CG59201-02       Protein   RRANAFLEELRPGSLERECKEEQCSFEEAREIFKDAERTKLFWISYSDGDQCASSPCQ       Sequence           NGGSCKDQLQSYICFCLPAFEGRNCETLEYPCGKIPILEKRNASKPQGRIVGGKVCPK                   GECPWQVLLLVNGAQLCGGTLINTIWVVSAAHCFDKIKNWRNLIAVLGEHDLSEHDGD                   EQSRRVAQVIIPSTYVPGTTNHDIALLRLHQPVVLTDHVVPLCLPERTFSERTLAFVR                   FSLVSGWGQLLDRGATALELMVLNVPRLMTQDCLQQSRKVGDSPNITEYMFCAGYSDG                   SKDSCKGDSGGPHATHYRGTWYLTGIVSWGQGCATVGHFGVYTRVSQYIEWLQKLMRS                   EPRPGVLLRAPFP                  
 
     [0388] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 8B.  
               TABLE 8B                          Comparison of NOV8a against NOV8b.                                 Protein   NOV8a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV8b   1 . . . 444   396/466 (84%)               1 . . . 419   397/466 (84%)                      
 
     [0389] Further analysis of the NOV8a protein yielded the following properties shown in Table 8C.  
               TABLE 8C                          Protein Sequence Properties NOV8a                     SignalP           analysis:   Cleavage site between residues 21 and 22               PSORT II   PSO: a new signal peptide prediction method       analysis:     N-region: length 7; pos. chg 1; neg. chg 0             H-region: length 19; peak value 10.35           PSG score: 5.95           GvH: von Heijne&#39;s method for signal seq. recognition             GvH score (threshold: −2.1): 7.54             possible cleavage site: between 20 and 21           &gt;&gt;&gt; Seems to have a cleavable signal peptide (1 to 20)           ALOM: Klein et al&#39;s method for TM region allocation             Init position for calculation: 21             Tentative number of TMS(s) for the threshold 0.5: 0             number of TMS(s) . . . fixed             PERIPHERAL Likelihood = 1.64 (at 205)             ALOM score: 1.64 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)             Center position for calculation: 10             Charge difference: 1.0 C(3.0) − N(2.0)             C &gt; N: C-terminal side will be inside           &gt;&gt;&gt;Caution: Inconsistent mtop result with signal peptide           MITDISC: discrimination of mitochondrial targeting seq                                       R content:   1   Hyd Moment (75):   5.10             Hyd Moment (95):   10.18   G content:   2             D/E content:   1   S/T content:   2             Score:   −4.10                         Gavel: prediction of cleavage sites for mitochondrial preseq             R-2 motif at 17 LRL|LC           NUCDISC: discrimination of nuclear localization signals             pat4: HRRR (3) at 34             pat4: RRRR (5) at 35             pat7: none             bipartite: none             content of basic residues: 10.4%             NLS Score: 0.03           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals: none           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:             type 1: none             type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination             Prediction: cytoplasmic             Reliability: 76.7           COIL: Lupas&#39;s algorithm to detect coiled-coil regions            48 G 0.96            49 S 0.97            50 L 0.97            51 E 0.97            52 R 0.97            53 E 0.97            54 C 0.97            55 K 0.97            56 E 0.97            57 E 0.97            58 Q 0.97            59 C 0.97            60 S 0.97            61 F 0.97            62 E 0.97            63 E 0.97            64 A 0.97            65 R 0.97            66 E 0.97            67 I 0.97            68 F 0.97            69 K 0.97            70 D 0.97            71 A 0.97            72 E 0.97            73 R 0.97            74 T 0.97            75 K 0.97            76 L 0.97            77 F 0.91            78 W 0.54             total: 31 residues           --------------------------           Final Results (k = {fraction (9/23)}):             33.3%: extracellular, including cell wall             22.2%: vacuolar             22.2%: mitochondrial             22.2%: endoplasmic reticulum           &gt;&gt; prediction for CG59201-01 is exc (k = 9)                      
 
     [0390] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8D.  
               TABLE 8D                          Geneseq Results for NOV8a                                         NOV8a   Identities/               Protein/   Residues/   Similarities for       Geneseq   Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB61992   Human Factor   1 . . . 444   444/444 (100%)   0.0           VII polypeptide—   1 . . . 444   444/444 (100%)             Homo sapiens ,           444 aa.           [US6183743-B1,           06 FEB. 2001]       AAR64205   Factor VII—   1 . . . 444   444/444 (100%)   0.0           modified forms of   1 . . . 444   444/444 (100%)           this act as an           anticoagulant—             Homo sapiens ,           444 aa.           [WO9427631-A,           08 DEC. 1994]       AAW31687     Homo sapiens     1 . . . 444   443/444 (99%)    0.0           Ser344Ala   1 . . . 444   444/444 (99%)            modified factor           VII— Homo               sapiens , 444 aa.           [WO9747651-A1,           18 DEC. 1997]       AAY67967   Factor VII SEQ   1 . . . 444   443/444 (99%)    0.0           ID NO: 2—   1 . . . 444   443/444 (99%)            Unidentified,           444 aa.           [US5997864-A,           07 DEC. 1999]       AAW69606   Human Factor   1 . . . 444   444/466 (95%)    0.0           VIIa— Homo     1 . . . 466   444/466 (95%)              sapiens , 466 aa.           [WO9831394-A2,           23 JUL. 1998]                  
 
     [0391] In a BLAST search of public sequence databases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8E.  
               TABLE 8E                          Public BLASTP Results for NOV8a                                             Identities/                   NOV8a   Similarities       Protein       Residues/   for the       Accession   Protein/   Match   Matched   Expect       Number   Organism/Length   Residues   Portion   Value               AAK58686   Factor VII active    1 . . . 444   443/444   0.0           site mutant immuno-       (99%)           conjugate— Homo      1 . . . 444   443/444             sapiens  (Human),       (99%)           679 aa.       P08709   Coagulation factor    1 . . . 444   444/466   0.0           VII precursor       (95%)           (EC 3.4.21.21)    1 . . . 466   444/466           (Serum prothrombin       (95%)           conversion           accelerator)           (Eptacog alfa)—             Homo sapiens             (Human), 466 aa.       Q96PQ8   Factor VII active    1 . . . 444   443/466   0.0           site mutant immuno-       (95%)           conjugate— Homo      1 . . . 466   443/466             sapiens  (Human),       (95%)           701 aa.       CAC69301   Sequence 2 from   39 . . . 444   406/406   0.0           Patent       (100%)            WO0158935—    1 . . . 406   406/406             Homo sapiens         (100%)            (Human), 406 aa           (fragment).       E964740   SYNTHETIC   39 . . . 444   405/406   0.0           AMINO ACID       (99%)           SEQUENCE FOR    1 . . . 406   405/406           MODIFIED       (99%)           FACTOR VII/           VIIA—vectors,           406 aa.                  
 
     [0392] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8F.  
               TABLE 8F                          Domain Analysis of NOV8a                                     Identities/               NOV8a   Similarities for   Expect       Pfam Domain   Match Region   the Matched Region   Value               gla   41 . . . 84   25/42 (60%)   4.3e−18               38/42 (90%)       EGF    88 . . . 119   14/47 (30%)   8.4e−06               23/47 (49%)       EGF   129 . . . 165   12/47 (26%)   0.79               25/47 (53%)       trypsin   191 . . . 425   99/265 (37%)    3.4e−69               182/265 (69%)                   
 
     Example 9  
     [0393] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.  
               TABLE 9A                       NOV9 Sequence Analysis                                                SEQ ID NO:37   1399 bp                     NOV9a,     CACCGGATCCACC   ATG GTGCGGTCTGTGGCCTGGGCAGGTTTCATGGTCCTGCTGATG       CG94799-05       DNA Sequence   ATCCCATGGGGCTCTGCTGCAAAACTGGTCTGCTACTTCACCAACTGGGCCCAGTACA                   GACAGGGGGAGGCTCGCTTCCTGCCCAAGGACTTGGACCCCAGCCTTTGCACCCACCT                   CATCTACCCCTTCGCTGGCATGACCAACCACCAGCTGAGCACCACTGAGTGGAATGAC                   GAGACTCTCTACCAGGAGTTCAATGGCCTGAAGAAGATGAATCCCAAGCTGAAGACCC                   TGTTACCCATCGGAGGCTGGAATTTCGGCACTCAGAAGTTCACAGATATGGTAGCCAC                   GGCCAACAACCGTCAGACCTTTGTCAACTCGGCCATCAGGTTTCTGCGCAAATACAGC                   TTTGACGGCCTTGACCTTGACTGGGAGTACCCAGGAAGCCAGGGCAGCCCTGCCGTAG                   ACAAGGAGCGCTTCACAACCCTGGTACAGGACTTGGCCAATGCCTTCCAGCAGGAAGC                   CCAGACCTCAGGGAAGGAACGCCTTCTTCTGAGTGCAGCGGTTCCAGCTCGGCAGACC                   TATGTGGATOCTCGATACGAGGTGGACAAAATCGCCCAGAACCTGGATTTTGTCAACC                   TTATGGCCTACGACTTCCATGGCTCTTGGGAGAAGGTCACGGGACATAACAGCCCCCT                   CTACAAGAGGCAAGAAGAGAGTGGTGCAGCAGCCAGCCTCAACGTGGATGCTGCTGTG                   CAACAGTGGCTGCAGAAGGGGACCCCTGCCAGCAAGCTGATCCTTGGCATGCCTACCT                   ACGGACGCTCCTTCACACTGGCCTCCTCATCAGACACCAGAGTGGGGGCCCCAGCCAC                   AGGGTCTGGCACTCCAGGCCCCTTCACCAAGGAAGGAGGGATGCTGGCCTACTATGAA                   GTCTCCTCCTGGAAGGGGGCCACCAAACAGAGAATCCAGGATCAGAAGGTGCCCTACA                   TCTTCCGGGACAACCAGTGGGTGGGCTTTGATGATGTGGAGAGCTTCPAAACCAAGGT                   CAGCTATCTGAAGCAGAAGGGACTGGGCGGGGCCATGGTCTGGGCACTGGACTTAGAT                   GACTTTGCCGGCTTCTCCTGCAACCAGGGCCGATACCCCCTCATCCAGACGCTACGGC                   AGGAACTGAGCACCCCAGAGCTTCAAGTTCCAAAACCACGTCAGCCCTCTGAACCTGA                   GCATGGCCCCAGCCCTGGACAAGACACGTTCTGCCAGGGCAAAGCTGATGGGCTCTAT                   CCCAATCCTCGGGAACGGTCCAGCTTCTACAGCTGTGCAGCGGGGCGGCTGTTCCAGC                   AAAGCTCCCCGACACGCCTGGTGTTCAGCAACTCCTGCAAATGCTGCACCTGGAATGT                   C GACGGC                                           ORF Start: ATG at 14       ORF Stop: at 1391           SEQ ID NO:38   459 aa   MW at 50953.0 kD                     NOV9a,   MVRSVAWAGFMVLLMIPWGSAAKLVCYFTNWAQYRQGEARFLPKDLDPSLCTHLIYAF       CG94799-05       Protein   AGMTNHQLSTTEWNDETLYQEFNGLKKMNPKLKTLLAIGGWNFGTQKFTDMVATANNR       Sequence           QTFVNSAIRFLRKYSFDGLDLDWEYPCSQGSPAVDKERFTTLVQDLANAFQQEAQTSG                   KERLLLSAAVPAGQTYVDAGYEVDKIAQNLDFVNLMAYDFHGSWEKVTGHNSPLYKRQ                   EESGAAASLNVDAAVQQWLQKGTPASKLILGMPTYGRSFTLASSSDTRVGAPATGSGT                   PGPFTKEGGMLAYYEVCSWKGATKQRIQDQKVPYIFRDNQWVGFDDVESFKTKVSYLK                   QKGLGGAMVWALDLDDFAGFSCNQGRYPLIQTLRQELSTPELEVPKPGQPSEPEHGPS                   PGQDTFCQGKADGLYPNPRERSSFYSCAAGRLFQQSCPTGLVFSNSCKCCTWN                                     SEQ ID NO:39   1043 bp                     NOV9b,     TGGGCTGCAGCCTGCCGCTGAGCTGCATC   ATG GTGCGGTCTGTGGCCTGGGCAGGTTT       CG94799-03       DNA Sequence   CATGGTCCTGCTGATGATCCCATGGGGCTCTGCTGCAAAACTGGTCTGCTACTTCACC                   AACTGGGCCCAGTACAGACAGGGGGAGGCTCGCTTCCTGCCCAAGGACTTGGACCCCA                   GCCTTTGCACCCACCTCATCTACGCCTTCGCTGGCATGACCAACCACCAGCTGAGCAC                   CACTGAGTGGAATGACGAGACTCTCTACCAGGAGTTCAATGGCCTGAAGAAGATGTTC                   ACAGATATGGTAGCCACGGCCAACAACCGTCAGACCTTTGTCAACTCGGCCATCAGGT                   TTCTGCGCAAATACAGCTTTGACGGCCTTGACCTTUACTGGGAGTACCCAGGAAGCCA                   GGGGAGCCCTGCCGTAGACAAGGAGCGCTTCACAACCCTCGTACAGGACTTGGCCAAT                   GCCTTCCAGCAGGAAGCCCAGACCTCAGGGAAGGAACGCCTTCTTCTGAGTGCAGCGG                   TTCCAGCTGGGCAGACCTATGTGGATGCTGGATACGAGGTGGACAAAATCGCCCAGAA                   CCTGGATTTTGTCAACCTTATGGCCTACGACTTCCATGGCTCTTGGGAGAAGGTCACG                   GGACATAACAGCCCCCTCTACAAGAGGCAAGAAGAGACTGGTGCAGCAGCCAGCCTCA                   ACGTGGGCCGATACCCCCTCATCCAGACGCTACGGCAGGAACTGAGTCTTCCATACTT                   GCCTTCAGGCACCCCAGAGCTTGAAGTTCCAAAACCAGGTCAGCCCTCTGAACCTGAG                   CATGGCCCCAGCCCTGGACAAGACACGTTCTGCCAGGGCAAAGCTGATGGGCTCTATC                   CCAATCCTCGGGAACGGTCCAGCTTCTACAGCTGTGCAGCGGGGCGGCTGTTCCAGCA                   AAGCTGCCCGACAGGCCTGGTGTTCAGCAACTCCTGCATGCTGCAAACCTGGAAT TGA                       GTCGCTAAAGCCCCTCCAGTCCCAGCTTTGAGGCTGGGCCCAGGATCACTCTACAGC                                           ORF Start: ATG at 30       ORF Stop: TGA at 984           SEQ ID NO:40   1318 aa   MW at 35558.6 kD                     NOV9b,   MVRSVAWAGFMVLLMIPWGSAAKLVCYFTNWAQYRQGEARFLPKDLDPSLCTHLIYAP       CG94799-03       Protein   AGMTNHQLSTTEWNDETLYQEFNGLKAAFTDAAATAANRQTFAASAIRFLRKYSFDGL       Sequence           DLDWEYPGSQGSPAVDKERFTTLVQDLAAAFQQEAQTSGKERLLLSAAVPAGQTYAAA                   GYEVDKIAQNLDFAALMAYDFHGSWEKAAGHNSPLYAAQEESGAAASLNVGRYPLIQT                   LRQELSLPYLPSGTPELEVPKKPGQPSEPEHGPSPGQDTCQGKADGLYPNPRERSSFY                   SCAAGRLFQQSCPTGLVFSNSCKCCTWN                                     SEQ ID NO:41   1546 bp                     NOV9C,     CTGAGCTGCATC   ATG GTGCGGTCTGTGGCCTGGGCAGGTTTCATGGTCCTGCTGATGA       CG94799-04       DNA Sequence   TCCCATGGGGCTCTGCTGCAAAACTGGTCTGCTACTTCACCAACTGGGCCCAGTACAG                   ACAGGGGGAGGCTCGCTTCCTGCCCAAGGACTTGGACCCCAGCCTTTGCACCCACCTC                   ATCTACGCCTTCGCTCGCATGACCAACCACCAGCTGAGCACCACTGAGTGGAATGACG                   AGACTCTCTACCAGGAGTTCAATGGCCTGAAGAAGATGAATCCCAAGCTGAAGACCCT                   GTTAGCCATCGGAGGCTGGAATTTCGGCACTCAGAAGTTCACAGATATGGTAGCCACG                   GCCAACAACCGTCAGACCTTTGTCAACTCGGCCATCAGGTTTCTGCGCAAATACAGCT                   TTGACGGCCTTGACCTTGACTGGGAGTACCCAGGAAGCCAGGGGAGCCCTGCCGTAGA                   CAAGGAGCGCTTCACAACCCTGGTACAGGACTTGGCCAATGCCTTCCAGCAGGAAGCC                   CAGACCTCAGGGAAGGAACGCCTTCTTCTGAGTGCAGCGGTTCCAGCTGGGCAGACCT                   ATGTGGATGCTGGATACGAGGTGGACAAAATCGCCCAGAACCTGGATTTTGTCAACCT                   TATGGCCTACGACTTCCATGGCTCTTGGGAGAAGGTCACGGGACATAACAGCCCCCTC                   TACAAGAGGCAAGAAGAGAGTGGTGCAGCAGCCAGCCTCAACGTGGATGCTGCTGTGC                   AACAGTGCCTGCAGAAGGGGACCCCTGCCAGCAAGCTGATCCTTGGCATCCCTACCTA                   CGGACGCTCCTTCACACTGGCCTCCTCATCAGACACCAGAGTGGGGGCCCCAGCCACA                   GGGTCTGGCACTCCAGGCCCCTTCACCAAGGAAGGAGGGATGCTGGCCTACTATGAAG                   TCTGCTCCTGGAAGGGGGCCACCAAACAGAGAATCCAGGATCAGAAGGTGCCCTACAT                   CTTCCGGGACAACCAGTGGGTGGGCTTTGATGATGTGGAGAGCTTCAAAACCAAGGGC                   CGATACCCCCTCATCCAGACGCTACGGCAGGAACTGAGTCTTCCATACTTGCCTTCAG                   GCACCCCAGAGCTTGAAGTTCCAAAACCAGGTCAGCCCTCTGAACCTGAGCATGGCCC                   CAGCCCTGGACAAGACACGTTCTGCCAGGGCAAAGCTGATGGGCTCTATCCCAATCCT                   CGGGAACGGTCCAGCTTCTACAGCTGTGCAGCGGGGCGGCTGTTCCAGCAAAGCTGCC                   CGACAGGCCTGGTGTTCAGCAACTCCTGCAAATGCTGCACCTGGAAT TGA   GTCGTAAA                       GCCCCTCCAGTCCAGCTTTGAGGCTGGGCCCAGGATCACTCTACAGCCTGCCTCCTGG                       GTTTTCCTGGGGGCCGCAATCTGGCTCCTGCAGGCCTTTCTGTGGTCTTCCTTTATCC                       AGGCTTTCTGCTCTCAGCCTTGCCTTCCTTTTTTCTGGGTCTCCTGGGCTGCCCCTTT                       CACTTGCAAAATAAATCTTTGGTTTGTGCCCCTCTTCA                                           Start: ATG at 13       ORF Stop: TGA at 1324           SEQ ID NO:42   437 aa   MW at 48564.3 kD                     NOV9C,   MVRSVAWAGFMVLLMIPWGSAAKLVCYFTNWAQYRQGEIAAFLPAALDPSLCTHIYAF       CG94799-04       Protein   AGMTNHQLSTTEWNDETLYQEFNGLKAANPKLKTLLAIGGAAFGTQKFTDAAATANNR       Sequence           QTFVNSAIRFLRKYSFDGLDLDWEYPGSQGSPAVDKERFTTLVQTDLANAFQQEQTSG                   KERLLLSAAVPAGQTYVDAGYEVDKIAQNLDFVNLMAYDFHGSWEKVTGHNSPLYKRQ                   EESGAAASLNVDAAVQQWLQKGTPASKLILGMPTYGRSFTLASSSDTRVGAPATGSGT                   PGPFTKEGGMLAYYEVCSWKGATKQRIQDQAAPYIFRDNQWVGFDDVESFKTKGRYPL                   IQTLRQELSLPYLPSGTPELEVPKPGQPSEPEHGPSPGQDTFCQGKADGLYPNPRERS                   SFYSCAAGRLFQQSCPTGLVFSNSCKCCTWN                                     SEQ ID NO:43   1380 bp                     NOV9d,     GC   TCT GCATACAAACTGGTCTGCTACTTCACCAACTGGGCCCAGTACAGACAGGGGGA       CG94799-01       DNA Sequence   GGCTCGCTTCCTGCCCAAGGACTTGGACCCCAGCCTTTGCACCCACCTCATCTACGCC                   TTCGCTGGCATGACCAACCACCAGCTGAGCACCACTGAGTGGAATGACGAGACTCTCT                   ACCAGGAGTTCAATGGCCTGAAGAAGATGAATCCCAAGCTGAAGACCCTGTTAGCCAT                   CGGAGGCTGGAATTTCAGCACTCAGAAGTTCACAGATATGGTAGCCACGGCCAACAAC                   CGTCAGACCTTTGTCAACTCGGCCATCAGGTTTCTGCGCAAATACAGCTTTGACCGCC                   TTGACCTTGACTGGGAGTACCCAGGAAGCCAGGGGAGCCCTGCCGTAGACAAGGAGCG                   CTTCACAACCCTGGTACAGGACTTGGCCAATCCCTTCCAGCAGGAAGCCCAGACCTCA                   GGGAAGGAACGCCTTCTTCTGAGTGCAGCGGTTCCAGCTGGGCAGACCTATGTGGATG                   CTGGATACGAGGTGGACAAAATCGCCCAGAACCTGGATTTTGTCAACCTTATGGCCTA                   CGACTTCCATGGCTCTTGGGAGAAGGTCACGGGACATAACAGCCCCCTCTACAAGAGG                   CAAGAAGAGAGTGGTGCAGCAGCCAGCCTCAACGTGGATGCTGCTGTGCAACAGTGGC                   TGCAGAAGGGGACCCCTGCCAGCAAGCTGATCCTTGGCATGCCTACCTACGGACGCTC                   CTTCACACTGGCCTCCTCATCAGACACCAGAGTGGCGGCCCCAGCCACAGGGTCTGGC                   ACTCCAGGCCCCTTCACCAAGGAAGGAGGGATGCTGGCCTACTATGAAGTCTGCTCCT                   GGAAGGGGGCCACCAACAGAGAAATCCAGGATCAGAAGGTGCCCTACATCTTCCGGGA                   CAACCAGTGGGTCGGCTTTGATGATGTGGAGAGCTTCAAAACCAAGGTCAGCTATCTG                   AAGCAGAAGGGACTGGGCGGCGCCATGGTCTGGGCACTGGACTTAGATGACTTTGCCG                   GCTTCTCCTGCAACCAGGGCCGATACCCCCTCATCCAGACGCTACGGCAGGAACTCAG                   TCTTCCATACTTGCCTTCAGGCAAACCCAGAGCTTGAAGTTCCAAACCAGGTCAGCCC                   TCTGACCTGAGCATGGCCCCAAGCCCTGGACAAGACACGTTCTGCCAGGGCAAAGCTG                   ATGGGCTCTATCCCAATCCTCGGGAACGGTCCAGCTTCTACAGCTGTGCAGCGGGGCG                   GCTGTTCCAGCAAAGCTGCCCGACAGGCCTGGTGTTCAGCAACTCCTGCAAATGCTGC                   ACCTGGAAT TGA   GTCGCTAAAGCCCCTCCAGTCCCAGCTTTGAGGC                                           ORF Start: at 3       ORF Stop: TGA at 1344           SEQ ID NO:44   447 aa   MW at 49656.3 kD                     NOV9d,   SAYAAVCYFTNWAQYRQGEAAFLPAALDPSLCTHLIYAFAGMTNHQLSTTEAADETLY       CG94799-01       Protein   QEFNGLKAANPKLKTLLAIGGWNFSTQKFTDMVATAANRQTFAASAIRFLRKYSFDGL       Sequence           DLDWEYPGSQGSPAVDKERFTTLVQDLAAAFQQEAQTSGKERLLLSAAVPAGQTYAAA                   GYEVDKIAQNLDFVNLMAYDFHGSWEKVTGHNSPLYKRQEESGAAASLNVDAAVQQWL                   QKGTPASKLILGMPTYGRSFTLASSSDTRVGAPATGSGTPGPFTKEGGMLAYYEVCSW                   KGATKQRIQDQKVPYIFRDNQWVGFDDVESFKTKVSYLKQKGLGGAMVWALDLDDFAG                   FSCNQGRYPLIQTLRQELSLPYLPSGTPELEVPKPGQPSEPEHGPSPGQDTFCQGKAA                   GLYPNPRERSSFYSCAAGRLFQQSCPTGLVFSNSCKCCTWN                                     SEQ ID NO:45   1599 bp                     NOV9e,     TTTTGTATGGGCTGCAGCCTGCCGCTGAGCTGCATC   ATG GTGCGGTCTGTGGCCTGGG       CG94799-02       DNA Sequence   CAGGTTTCATGGTCCTGCTGATGATCCCATGGGGCTCTGCTGCAAAACTGGTCTGCTA                   CTTCACCAACTGGGCCCAGTACAGACAGGGGGAGGCTCGCTTCCTGCCCAAGGACTTG                   GACCCCAGCCTTTGCACCCACCTCATCTACGCCTTCGCTGGCATGACCAACCACCAGC                   TGAGCACCACTGAGTGGAATGACGAGACTCTCTACCAGGAGTTCAATGGCCTGAAGAA                   GATGTTCACAGATATGGTAGCCACGGCCAACAACCGTCACACCTTTGTCAACTCGCCC                   ATCAGGTTTCTGCGCAAATACAGCTTTGACGGCCTTGACCTTGACTGGGAGTACCCAG                   GAAGCCAGGGGAGCCCTGCCGTAGACAAGGAGCGCTTCACAACCCTGGTACAGGACTT                   GGCCAATGCCTTCCAGCAGGAAGCCCAGACCTCAGGGAAGGAACGCCTTCTTCTGAGT                   GCAGCGGTTCCAGCTGGGCAGACCTATGTGGATGCTGGATACGAGGTGGACAAAATCG                   CCCAGAACCTGGATTTTGTCAACCTTATGGCCTACGACTTCCATGGCTCTTGGGAGAA                   GGTCACGGGACATAACAGCCCCCTCTACAAGAGGCAAGAAGAGAGTGGTGCAGCAGCC                   AGCCTCAACGTGGATGCTGCTGTGCAACAGTGGCTGCAGAAGGGGACCCCTGCCAGCA                   AGCTGATCCTTGGCATGCCTACCTACGGACGCTCCTTCACACTGGCCTCCTCATCAGA                   CACCAGAGTGGGGGCCCCAGCCACAGGGTCTGGCACTCCAGGCCCCTTCACCAAGGAA                   GGAGGGATGCTGGCCTACTATGAAGTCTGCTCCTGGAAGGGGGCCACCAAACAGAGAA                   TCCAGGATCAGAAGCTGCCCTACATCTTCCGGGACAACCAGTGGGTGGGCTTTGATGA                   TGTGGAGAGCTTCAAAACCAAGGTCAGCTATCTGAAGCAGAAGGGACTGGGCGGGGCC                   ATCGTCTGGGCACTGGACTTAGATGACTTTGCCGGCTTCTCCTGCAACCAGGGCCGAT                   ACCCCCTCATCCAGACGCTACGGCAGGAACTGAGTCTTCCATACTTGCCTTCAGGCAC                   CCCAGAGCTTGAAGTTCCAAAACCAGGTCAGCCCTCTGAACCTGAGCATGGCCCCAGC                   CCTGGACAAGACACGTTCTGCCAGGGCAAAGCTGATGGGCTCTATCCCAATCCTCGGG                   AACGGTCCAGCTTCTACAGCTGTGCAGGGGGGCGGCTGTTCCAGCAAAGCTGCCCGAC                   AGGCCTGGTGTTCAGCAACTCCTGCAAATGCTGCACACTGGAATTGAGTCGCTAAGCC                     CCTCCAGTCCCAGCTTTGAGGCTGGGCCCAGGATCACTCTACAGCCTGCCTCCTGGGT                       TTTCCCTGGGGGCCGCAATCTGGCTCCTGCAGGCCTTTCTGTGGTCTTCCTTTATCCA                       AACTTTCTGCTCTCAGCCTTGCCTTCCTTTTTTCTGGGTCTCCTGGGCTGCCCCTTTC                       TTGCAAAATAAATCTTTGGTTTGTGCCCCTC                                           ORF Start: ATG at 37       ORF Stop: TGA at 1378           SEQ ID NO:46   447 aa   MW at 49598.4 kD                     NOV9e,   MVRSVAWAGFMVLLMIPWGSAAKLVCYFTNWAQYRQGEARFLPAALDPSLCTHLIYAF       CG94799-02       Protein   AGMTNHQLSTTEWNDETLYQEFNGLKKMFTDMVATANNRQTFAASAIRFLRKYSFDGL       Sequence           DLDWEYPGSQGSPAAAKERFTTLVQDLAAAFQQEAQTSGKERLLLSAAVPAGQTYAAA                   GYEVDKIAQNLDFVNLMAYDFHGSWEKVTGHNSPLYKRQEESGAAASLNVDAAVQQWL                   QKGTPASKLILGMPTYGRSFTLASSSDTRVGAPATGSGTPGPFTKEGGMLAYYEVCSW                   KGATKQRIQDQKVPYIFRDMQWVGFDDVESFKTKVSYLKQKGLGGAMVWALDLDDFAG                   FSCNQGRYPLIQTLRQELSLPYLPSGTPELEVPKPGQPSEPEHGPSPCQDTFCQGKAA                   GLYPNPRERSSFYSCACGRLFQQSCPTGLVFSNSCKCCTWN                  
 
     [0394] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 9B.  
               TABLE 9B                          Comparison of NOV9a against NOV9b through NOV9e.                                 Protein   NOV9a Residues/   Identities/Similarities           Sequence   Match Residues   for the Matched Region                       NOV9b   1 . . . 243   224/243 (92%)               1 . . . 224   224/243 (92%)           NOV9c   1 . . . 459   430/466 (92%)               1 . . . 437   430/466 (92%)           NOV9d   20 . . . 459    438/447 (97%)               1 . . . 447   438/447 (97%)           NOV9e   1 . . . 459   439/466 (94%)               1 . . . 447   439/466 (94%)                      
 
     [0395] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C.  
               TABLE 9C                          Protein Sequence Properties NOV9a                     SignalP           analysis:   Cleavage site between residues 23 and 24               PSORT II   PSG: a new signal peptide prediction method       analysis:     N-region: length 3; pos. chg 1; neg. chg 0             H-region: length 19; peak value 11.93             PSG score: 7.53           GvH: von Heijne&#39;s method for signal seq. recognition             GvH score (threshold: −2.1): −1.04             possible cleavage site: between 21 and 22           &gt;&gt;&gt; Seems to have a cleavable signal peptide (1 to 21)           ALOM: Klein et al&#39;s method for TM region allocation             Init position for calculation: 22             Tentative number of TMS(s) for the threshold 0.5: 0             number of TMS(s) . . . fixed             PERIPHERAL Likelihood = 5.83 (at 352)             ALOM score: 5.83 (number of TMSs: 0)           MTOP: Prediction of membrane topology (Hartmann et al.)             Center position for calculation: 10             Charge difference: 0.0 C(2.0) − N(2.0)             N &gt;= C: N-terminal side will be inside           MITDISC: discrimination of mitochondrial targeting seq                                       R content:   2   Hyd Moment (75):   8.38             Hyd Moment (95):   8.91   G content:   3             D/E content:   1   S/T content:   3             Score:   −3.05                         Gavel: prediction of cleavage sites for mitochondrial preseg             R-2 motif at 45 YRQ|GE           NUCDISC: discrimination of nuclear localization signals             pat4: none             pat7: none             bipartite: none             content of basic residues: 9.6%             NLS Score: −0.47           KDEL: ER retention motif in the C-terminus: none           ER Membrane Retention Signals:             XXRR-like motif in the N-terminus: VRSV           SKL: peroxisomal targeting signal in the C-terminus: none           PTS2: 2nd peroxisomal targeting signal: none           VAC: possible vacuolar targeting motif: none           RNA-binding motif: none           Actinin-type actin-binding motif:             type 1: none             type 2: none           NMYR: N-myristoylation pattern: none           Prenylation motif: none           memYQRL: transport motif from cell surface to Golgi: none           Tyrosines in the tail: none           Dileucine motif in the tail: none           checking 63 PROSITE DNA binding motifs: none           checking 71 PROSITE ribosomal protein motifs: none           checking 33 PROSITE prokaryotic DNA binding motifs: none           NNCN: Reinhardt&#39;s method for Cytoplasmic/Nuclear           discrimination             Prediction: cytoplasmic             Reliability: 76.7           COIL: Lupas&#39;s algorithm to detect coiled-coil regions             total: 0 residues           --------------------------           Final Results (k = {fraction (9/23)})             44.4%: endoplasmic reticulum             22.2%: vacuolar             22.2%: extracellular, including cell wall             11.1%: Golgi           &gt;&gt; prediction for CG94799-05 is end (k = 9)                      
 
     [0396] A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9D.  
               TABLE 9D                          Geneseq Results for NOV9a                                         NOV9a   Identities/               Protein/   Residues/   Similarities for       Geneseq   Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABB76291   Human chitinase -   1 . . . 459   459/466 (98%)   0.0             Homo sapiens , 466   1 . . . 466   459/466 (98%)           aa. [U.S. Pat. No.           6372212-B1,           Apr. 16, 2002]       AAE25903   Human chitinase   1 . . . 459   459/466 (98%)   0.0           allelic variant   1 . . . 466   459/466 (98%)           clone, MO-218           protein -  Homo               sapiens , 466 aa.           [U.S. Pat. No.           6399571-B1,           Jun. 4, 2002]       AAE00432   Human chitinase   1 . . . 459   459/466 (98%)   0.0           protein from clone   1 . . . 466   459/466 (98%)           pMO-218 -  Homo               sapiens , 466 aa.           [WO200123430-A2,           Apr. 5, 2001]       AAY42425   MO-218 clone of   1 . . . 459   459/466 (98%)   0.0           human Chitinase,   1 . . . 466   459/466 (98%)           amino acid           sequence -  Homo               sapiens , 466 aa.           [WO9946390-A1,           Sep. 16, 1999]       AAW40259   Human chitinase   1 . . . 459   459/466 (98%)   0.0           protein from clone   1 . . . 466   459/466 (98%)           MO-218 -  Homo               sapiens , 466 aa.           [WO9747752-A1,           Dec. 18, 1997]                  
 
     [0397] In a BLAST search of public sequence databases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9E.  
               TABLE 9E                          Public BLASTP Results for NOV9a                                         NOV9a   Identities/           Protein       Residues/   Similarities for       Accession   Protein/   Match   the Matched   Expect       Number   Organism/Length   Residues   Portion   Value               Q13231   Chitotriosidase   1 . . . 459   459/466 (98%)   0.0           precursor -  Homo     1 . . . 466   459/466 (98%)             sapiens  (Human),           466 aa.       CAC37768   Sequence 3 from   1 . . . 459   458/466 (98%)   0.0           Patent   1 . . . 466   458/466 (98%)           WO0123430 -             Homo sapiens             (Human), 466 aa.       Q9H3V8   Chitotriosidase   1 . . . 386   385/386 (99%)   0.0           precursor -  Homo     1 . . . 386   386/386 (99%)             sapiens  (Human),           387 aa.       Q9D7Q1   2300002L19Rik   1 . . . 347   264/347 (76%)   e−157           protein -  Mus     1 . . . 345   293/347 (84%)             musculus  (Mouse),           396 aa.       Q9BZP6   Acidic mammalian   1 . . . 458   245/475 (51%)   e−149           chitinase precursor   1 . . . 475   321/475 (67%)           (EC 3.2.1.14) -             Homo sapiens             (Human), 476 aa.                  
 
     [0398] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9F.  
               TABLE 9F                          Domain Analysis of NOV9a                                 NOV9a Match   Identities/Similarities   Expect       Pfam Domain   Region   for the Matched Region   Value               Glyco_hydro_18    22 . . . 363   164/400 (41%)   3.8e−157               314/400 (78%)       CBM_14   413 . . . 459   17/59 (29%)   3.4e−05                37/59 (63%)                  
 
     Example B  
     Sequencing Methodology and Identification of NOVX Clones  
     [0399] 1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each of the restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing of the gene fragment.  
     [0400] 2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen&#39;s proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation&#39;s database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.  
     [0401] 3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation&#39;s proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.  
     [0402] The laboratory screening was performed using the methods summarized below:  
     [0403] cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Ga14-activation domain (Ga14-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from  E.coli  into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).  
     [0404] Ga14-binding domain (Ga14-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Ga14-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Ga14-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation&#39;s database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.  
     [0405] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).  
     [0406] 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.  
     [0407] 5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain-amygdala, brain-cerebellum, brain-hippocampus, brain-substantia nigra, brain-thalamus, brain-whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma-Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation&#39;s database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.  
     [0408] 6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.  
     [0409] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.  
     Example C  
     Quantitative Expression Analysis of Clones in Various Cells and Tissues  
     [0410] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer&#39;s diseased brains).  
     [0411] RNA integrity from all samples is controlled for quality by visual assessment of agarose gel electropherograms using 28S and 18S ribosomal RNA staining intensity ratio as a guide (2:1 to 2.5:1 28s:18s) and the absence of low molecular weight RNAs that would be indicative of degradation products. Samples are controlled against genomic DNA contamination by RTQ PCR reactions run in the absence of reverse transcriptase using probe and primer sets designed to amplify across the span of a single exon.  
     [0412] First, the RNA samples were normalized to reference nucleic acids such as constitutively expressed genes (for example, β-actin and GAPDH). Normalized RNA (5 ul) was converted to cDNA and analyzed by RTQ-PCR using One Step RT-PCR Master Mix Reagents (Applied Biosystems; Catalog No. 4309169) and gene-specific primers according to the manufacturer&#39;s instructions.  
     [0413] In other cases, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Corporation; Catalog No. 18064-147) and random hexamers according to the manufacturer&#39;s instructions. Reactions containing up to 10 μg of total RNA were performed in a volume of 20 μl and incubated for 60 minutes at 42° C. This reaction can be scaled up to 50 μg of total RNA in a final volume of 100 μl. sscDNA samples are then normalized to reference nucleic acids as described previously, using 1X TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer&#39;s instructions.  
     [0414] Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version I for Apple Computer&#39;s Macintosh Power PC) or a similar algorithm using the target sequence as input. Default settings were used for reaction conditions and the following parameters were set before selecting primers: primer concentration=250 nM, primer melting temperature (Tm) range=58°-60° C., primer optimal Tm=59° C., maximum primer difference=2° C., probe does not have 5′G, probe Tm must be 10° C. greater than primer Tm, amplicon size 75 bp to 100 bp. The probes and primers selected (see below) were synthesized by Synthegen (Houston, Tex., USA). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5′ and 3′ ends of the probe, respectively. Their final concentrations were: forward and reverse primers, 900 nM each, and probe, 200 nM.  
     [0415] PCR conditions: When working with RNA samples, normalized RNA from each tissue and each cell line was spotted in each well of either a 96 well or a 384-well PCR plate (Applied Biosystems). PCR cocktails included either a single gene specific probe and primers set, or two multiplexed probe and primers sets (a set specific for the target clone and another gene-specific set multiplexed with the target probe). PCR reactions were set up using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803) following manufacturer&#39;s instructions. Reverse transcription was performed at 48° C. for 30 minutes followed by amplification/PCR cycles as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression is then obtained by taking the reciprocal of this RNA difference and multiplying by 100.  
     [0416] When working with sscDNA samples, normalized sscDNA was used as described previously for RNA samples. PCR reactions containing one or two sets of probe and primers were set up as described previously, using 1X TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer&#39;s instructions. PCR amplification was performed as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were analyzed and processed as described previously.  
     [0417] Panels 1, 1.1, 1.2, and 1.3D  
     [0418] The plates for Panels 1, 1.1, 1.2 and 1.3D include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in these panels are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in these panels are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on these panels are comprised of samples derived from all major organ systems from single adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose.  
     [0419] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:  
     [0420] ca.=carcinoma,  
     [0421] *=established from metastasis,  
     [0422] met=metastasis,  
     [0423] s cell var=small cell variant,  
     [0424] non-s=non-sm=non-small,  
     [0425] squam=squamous,  
     [0426] pl. eff=pl effusion=pleural effusion,  
     [0427] glio=glioma,  
     [0428] astro=astrocytoma, and  
     [0429] neuro=neuroblastoma.  
     [0430] General_screening_panel_v1.4, v1.5, v1.6 and 1.7  
     [0431] The plates for Panels 1.4, 1.5, 1.6 and 1.7 include 2 control wells (genomic DNA control and chemistry control) and 88 to 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, 1.6 and 1.7 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panels 1.4, 1.5, 1.6 and 1.7 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panels 1.4, 1.5, 1.6 and 1.7 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.3D.  
     [0432] Panels 2D, 2.2, 2.3 and 2.4  
     [0433] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute&#39;s Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e., immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.  
     [0434] HASS Panel v 1.0  
     [0435] The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls. Specifically, 81 of these samples are derived from cultured human cancer cell lines that had been subjected to serum starvation, acidosis and anoxia for different time periods as well as controls for these treatments, 3 samples of human primary cells, 9 samples of malignant brain cancer (4 medulloblastomas and 5 glioblastomas) and 2 controls. The human cancer cell lines are obtained from ATCC (American Type Culture Collection) and fall into the following tissue groups: breast cancer, prostate cancer, bladder carcinomas, pancreatic cancers and CNS cancer cell lines. These cancer cells are all cultured under standard recommended conditions. The treatments used (serum starvation, acidosis and anoxia) have been previously published in the scientific literature. The primary human cells were obtained from Clonetics (Walkersville, Md.) and were grown in the media and conditions recommended by Clonetics. The malignant brain cancer samples are obtained as part of a collaboration (Henry Ford Cancer Center) and are evaluated by a pathologist prior to CuraGen receiving the samples. RNA was prepared from these samples using the standard procedures. The genomic and chemistry control wells have been described previously.  
     [0436] ARDAIS Panel v 1.0  
     [0437] The plates for ARDAIS panel v 1.0 generally include 2 control wells and 22 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Corporation. The tissues are derived from human lung malignancies (lung adenocarcinoma or lung squamous cell carcinoma) and in cases where indicated many malignant samples have “matched margins” obtained from noncancerous lung tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e., immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue) in the results below. The tumor tissue and the “matched margins” are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). Unmatched malignant and non-malignant RNA samples from lungs were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state of the patient.  
     [0438] ARDAIS Prostate v 1.0  
     [0439] The plates for ARDAIS prostate 1.0 generally include 2 control wells and 68 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Corporation. The tissues are derived from human prostate malignancies and in cases where indicated malignant samples have “matched margins” obtained from noncancerous prostate tissue just adjacent to the tumor. These matched margins are taken from the tissue surrounding (i.e., immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue) in the results below. The tumor tissue and the “matched margins” are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). RNA from unmatched malignant and non-malignant prostate samples were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state of the patient.  
     [0440] Panel 3D, 3.1 and 3.2  
     [0441] The plates of Panel 3D, 3.1, and 3.2 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D, 3.1, 3.2, 1, 1.1., 1.2, 1.3D, 1.4, 1.5, and 1.6 are of the most common cell lines used in the scientific literature.  
     [0442] Panels 4D, 4R, and 4.1D  
     [0443] Panel 4 includes samples on a 96 well plate (2 control wells, 94 test samples) composed of RNA (Panel 4R) or cDNA (Panels 4D/4.1D) isolated from various human cell lines or tissues related to inflammatory conditions. Total RNA from control normal tissues such as colon and lung (Stratagene, La Jolla, Calif.) and thymus and kidney (Clontech) was employed. Total RNA from liver tissue from cirrhosis patients and kidney from lupus patients was obtained from BioChain (Biochain Institute, Inc., Hayward, Calif.). Intestinal tissue for RNA preparation from patients diagnosed as having Crohn&#39;s disease and ulcerative colitis was obtained from the National Disease Research Interchange (NDRI) (Philadelphia, Pa.).  
     [0444] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, Md.) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.  
     [0445] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×10 6  cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10 −5 M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.  
     [0446] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer&#39;s instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco), 50 μg/ml GMCSF and 5 μg/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.  
     [0447] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet according to the manufacturer&#39;s instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beads were then used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and plated at 10 6  cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CD8 cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.  
     [0448] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 10 6  cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24,48 and 72 hours.  
     [0449] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 10 5 -10 6  cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated T1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (1 μg/ml) to prevent apoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.  
     [0450] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×10 5  cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×10 5  cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10 −5 M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCl-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.  
     [0451] For these cell lines and blood cells, RNA was prepared by lysing approximately 10 7  cells/ml using Trizol (Gibco BRL). Briefly, {fraction (1/10)} volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with {fraction (1/10)} volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.  
     [0452] AI_comprehensive panel_v1.0  
     [0453] The plates for AI_comprehensive panel_v1.0 include two control wells and 89 test samples comprised of cDNA isolated from surgical and postmortem human tissues obtained from the Backus Hospital and Clinomics (Frederick, Md.). Total RNA was extracted from tissue samples from the Backus Hospital in the Facility at CuraGen. Total RNA from other tissues was obtained from Clinomics.  
     [0454] Joint tissues including synovial fluid, synovium, bone and cartilage were obtained from patients undergoing total knee or hip replacement surgery at the Backus Hospital. Tissue samples were immediately snap frozen in liquid nitrogen to ensure that isolated RNA was of optimal quality and not degraded. Additional samples of osteoarthritis and rheumatoid arthritis joint tissues were obtained from Clinomics. Normal control tissues were supplied by Clinomics and were obtained during autopsy of trauma victims.  
     [0455] Surgical specimens of psoriatic tissues and adjacent matched tissues were provided as total RNA by Clinomics. Two male and two female patients were selected between the ages of 25 and 47. None of the patients were taking prescription drugs at the time samples were isolated.  
     [0456] Surgical specimens of diseased colon from patients with ulcerative colitis and Crohns disease and adjacent matched tissues were obtained from Clinomics. Bowel tissue from three female and three male Crohn&#39;s patients between the ages of 41-69 were used. Two patients were not on prescription medication while the others were taking dexamethasone, phenobarbital, or tylenol. Ulcerative colitis tissue was from three male and four female patients. Four of the patients were taking lebvid and two were on phenobarbital.  
     [0457] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-lanti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.  
     [0458] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:  
     [0459] AI=Autoimmunity  
     [0460] Syn=Synovial  
     [0461] Normal=No apparent disease  
     [0462] Rep22/Rep20=individual patients  
     [0463] RA=Rheumatoid arthritis  
     [0464] Backus=From Backus Hospital  
     [0465] OA=Osteoarthritis  
     [0466] (SS)(BA)(MF)=Individual patients  
     [0467] Adj=Adjacent tissue  
     [0468] Match control=adjacent tissues  
     [0469] −M=Male  
     [0470] −F=Female  
     [0471] COPD=Chronic obstructive pulmonary disease  
     [0472] AI.05 Chondrosarcoma  
     [0473] The AI.05 chondrosarcoma plates are comprised of SW1353 cells that had been subjected to serum starvation and treatment with cytokines that are known to induce MMP (1, 3 and 13) synthesis (eg. IL1beta). These treatments include: IL-1beta (10 ng/ml), IL-1beta+TNF-alpha (50 ng/ml), IL-1beta+Oncostatin (50 ng/ml) and PMA (100 ng/ml). The SW1353 cells were obtained from the ATCC (American Type Culture Collection) and were all cultured under standard recommended conditions. The SW1353 cells were plated at 3×10 5  cells/ml (in DMEM medium-10% FBS) in 6-well plates. The treatment was done in triplicate, for 6 and 18 h. The supernatants were collected for analysis of MMP 1, 3 and 13 production and for RNA extraction. RNA was prepared from these samples using the standard procedures.  
     [0474] Panels 5D and 51  
     [0475] The plates for Panel 5D and 5I include two control wells and a variety of cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. Metabolic tissues were obtained from patients enrolled in the Gestational Diabetes study. Cells were obtained during different stages in the differentiation of adipocytes from human mesenchymal stem cells. Human pancreatic islets were also obtained.  
     [0476] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (less than 1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted and fast frozen within 5 minutes from the time of removal. The tissue was then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus) and subcutaneous adipose. Patient descriptions are as follows:  
     [0477] Patient 2: Diabetic Hispanic, overweight, not on insulin  
     [0478] Patient 7-9: Nondiabetic Caucasian and obese (BMI&gt;30)  
     [0479] Patient 10: Diabetic Hispanic, overweight, on insulin  
     [0480] Patient 11: Nondiabetic African American and overweight  
     [0481] Patient 12: Diabetic Hispanic on insulin  
     [0482] Adiocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:  
     [0483] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose  
     [0484] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated  
     [0485] Donor 2 and 3 AD: Adipose, Adipose Differentiated  
     [0486] Human cell lines were generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: kidney proximal convoluted tubule, uterine smooth muscle cells, small intestine, liver HepG2 cancer cells, heart primary stromal cells, and adrenal cortical adenoma cells. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. All samples were processed at CuraGen to produce single stranded cDNA.  
     [0487] Panel 5I contains all samples previously described with the addition of pancreatic islets from a 58 year old female patient obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at an outside source and delivered to CuraGen for addition to panel 5I.  
     [0488] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:  
     [0489] GO Adipose=Greater Omentum Adipose  
     [0490] SK=Skeletal Muscle  
     [0491] UT=Uterus  
     [0492] PL=Placenta  
     [0493] AD=Adipose Differentiated  
     [0494] AM=Adipose Midway Differentiated  
     [0495] U=Undifferentiated Stem Cells  
     [0496] Human Metabolic RTQ-PCR Panel  
     [0497] The plates for the Human Metabolic RTQ-PCR Panel include two control wells (genomic DNA control and chemistry control) and 211 cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. This panel is useful for establishing the tissue and cellular expression profiles for genes believed to play a role in the etiology and pathogenesis of obesity and/or diabetes and to confirm differential expression of such genes derived from other methods. Metabolic tissues were obtained from patients enrolled in the CuraGen Gestational Diabetes study and from autopsy tissues from Type II diabetics and age, sex and race-matched control patients. One or more of the following were used to characterize the patients: body mass index [BMI=wt (kg)/ht(m 2 )], serum glucose, HgbA1c. Cell lines used in this panel are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines. RNA from human Pancreatic Islets was also obtained.  
     [0498] In the Gestational Diabetes study, subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarian section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (less than 1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted, and then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus), and subcutaneous adipose. Patient descriptions are as follows:  
     [0499] Patient 7—Non-diabetic Caucasian and obese  
     [0500] Patient 8—Non-diabetic Caucasian and obese  
     [0501] Patient 12—Diabetic Caucasian with unknown BMI and on insulin  
     [0502] Patient 13—Diabetic Caucasian, overweight, not on insulin  
     [0503] Patient 15—Diabetic Caucasian, obese, not on insulin  
     [0504] Patient 17—Diabetic Caucasian, normal weight, not on insulin  
     [0505] Patient 18—Diabetic Hispanic, obese, not on insulin  
     [0506] Patient 19—Non-diabetic Caucasian and normal weight  
     [0507] Patient 20—Diabetic Caucasian, overweight, and on insulin  
     [0508] Patient 21—Non-diabetic Caucasian and overweight  
     [0509] Patient 22—Diabetic Caucasian, normal weight, on insulin  
     [0510] Patient 23—Non-diabetic Caucasian and overweight  
     [0511] Patient 25—Diabetic Caucasian, normal weight, not on insulin  
     [0512] Patient 26—Diabetic Caucasian, obese, on insulin  
     [0513] Patient 27—Diabetic Caucasian, obese, on insulin  
     [0514] Total RNA was isolated from metabolic tissues of 12 Type II diabetic patients and 12 matched control patients included hypothalamus, liver, pancreas, small intestine, psoas muscle, diaphragm muscle, visceral adipose, and subcutaneous adipose. The diabetics and non-diabetics were matched for age, sex, ethnicity, and BMI where possible.  
     [0515] The panel also contains pancreatic islets from a 22 year old male patient (with a BMI of 35) obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at CuraGen.  
     [0516] Cell lines used in this panel are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured at an outside facility. The RNA was extracted at CuraGen according to CuraGen protocols. All samples were then processed at CuraGen to produce single stranded cDNA.  
     [0517] In the labels used to identify tissues in the Human Metabolic panel, the following abbreviations are used:  
     [0518] Pl=placenta  
     [0519] Go=greater omentum  
     [0520] Sk=skeletal muscle  
     [0521] Ut=uterus  
     [0522] CC=Caucasian  
     [0523] HI=Hispanic  
     [0524] AA=African American  
     [0525] AS=Asian  
     [0526] Diab=Type II diabetic  
     [0527] Norm=Non-diabetic  
     [0528] Overwt=Overweight; med BMI  
     [0529] Obese=Hi BMI  
     [0530] Low BM=20-25  
     [0531] Med BM=26-30  
     [0532] Hi BMI=Greater than 30  
     [0533] M=Male  
     [0534] #=Patient identifier  
     [0535] Vis.=Visceral  
     [0536] SubQ=Subcutaneous  
     [0537] Panel CNSD.01  
     [0538] The plates for Panel CNSD.01 include two control wells and 94 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center. Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.  
     [0539] Disease diagnoses are taken from patient records. The panel contains two brains from each of the following diagnoses: Alzheimer&#39;s disease, Parkinson&#39;s disease, Huntington&#39;s disease, Progressive Supernuclear Palsy, Depression, and “Normal controls”. Within each of these brains, the following regions are represented: cingulate gyrus, temporal pole, globus palladus, substantia nigra, Brodman Area 4 (primary motor strip), Brodman Area 7 (parietal cortex), Brodman Area 9 (prefrontal cortex), and Brodman area 17 (occipital cortex). Not all brain regions are represented in all cases; e.g., Huntington&#39;s disease is characterized in part by neurodegeneration in the globus palladus, thus this region is impossible to obtain from confirmed Huntington&#39;s cases. Likewise Parkinson&#39;s disease is characterized by degeneration of the substantia nigra making this region more difficult to obtain. Normal control brains were examined for neuropathology and found to be free of any pathology consistent with neurodegeneration.  
     [0540] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:  
     [0541] PSP=Progressive supranuclear palsy  
     [0542] Sub Nigra=Substantia nigra  
     [0543] Glob Palladus=Globus palladus  
     [0544] Temp Pole=Temporal pole  
     [0545] Cing Gyr=Cingulate gyrus  
     [0546] BA 4=Brodman Area 4  
     [0547] Panel CNS_Neurodegeneration_V1.0  
     [0548] The plates for Panel CNS_Neurodegeneration_V1.0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.  
     [0549] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer&#39;s disease (AD) patients, and eight brains from “Normal controls” who showed no evidence of dementia prior to death. The eight normal control brains are divided into two categories: Controls with no dementia and no Alzheimer&#39;s like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer&#39;s like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senile plaque load). Within each of these brains, the following regions are represented: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), and occipital cortex (Brodman area 17). These regions were chosen to encompass all levels of neurodegeneration in AD. The hippocampus is a region of early and severe neuronal loss in AD; the temporal cortex is known to show neurodegeneration in AD after the hippocampus; the parietal cortex shows moderate neuronal death in the late stages of the disease; the occipital cortex is spared in AD and therefore acts as a “control” region within AD patients. Not all brain regions are represented in all cases.  
     [0550] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:  
     [0551] AD=Alzheimer&#39;s disease brain; patient was demented and showed AD-like pathology upon autopsy  
     [0552] Control=Control brains; patient not demented, showing no neuropathology  
     [0553] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology  
     [0554] SupTemporal Ctx=Superior Temporal Cortex  
     [0555] Inf Temporal Ctx=Inferior Temporal Cortex  
     [0556] Panel CNS_Neurodegeneration_V2.0  
     [0557] The plates for Panel CNS_Neurodegeneration_V2.0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.  
     [0558] Disease diagnoses are taken from patient records. The panel contains sixteen brains from Alzheimer&#39;s disease (AD) patients, and twenty-nine brains from “Normal controls” who showed no evidence of dementia prior to death. The twenty-nine normal control brains are divided into two categories: Fourteen controls with no dementia and no Alzheimer&#39;s like pathology (Controls) and fifteen controls with no dementia but evidence of severe Alzheimer&#39;s like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senile plaque load). Tissue from the temporal cotex (Broddmann Area 21) was selected for all samples from the Harvard Brain Tissue Resource Center; from the two sample from the Human Brain and Spinal Fluid Resource Center (samples 1 and 2) tissue from the inferior and superior temporal cortex was used; each sample on the panel represents a pool of inferior and superior temporal cortex from an individual patient. The temporal cortex was chosen as it shows a loss of neurons in the intermediate stages of the disease. Selection of a region which is affected in the early stages of Alzheimer&#39;s disease (e.g., hippocampus or entorhinal cortex) could potentially result in the examination of gene expression after vulnerable neurons are lost, and missing genes involved in the actual neurodegeneration process.  
     [0559] In the labels employed to identify tissues in the CNS_Neurodegeneration_V2.0 panel, the following abbreviations are used:  
     [0560] AD=Alzheimer&#39;s disease brain; patient was demented and showed AD-like pathology upon autopsy  
     [0561] Control=Control braids; patient not demented, showing no neuropathology  
     [0562] AH3=Control brains; pateint not demented but showing sever AD-like pathology  
     [0563] Inf &amp; Sup Temp Ctx Pool=Pool of inferior and superior temporal cortex for a given individual  
     [0564] A. CG109413-02: Retinoic Acid Receptor Gamma-1.  
     [0565] Expression of gene CG109413-02 was assessed using the primer-probe set Ag6444, described in Table AA. Results of the RTQ-PCR runs are shown in Table AB.  
               TABLE AA                          Probe Name Ag6444                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tgctcagtgctcagtctcct-3′   20   1081   47               Probe   TET-5′-caccactccatgcggaatctgtctg-3′-TAMRA   25   1105   48               Reverse   5′-agtggctcctgcagcttg-3′   18   1201   49                  
 
     [0566]               TABLE AB                          General_screening_panel_v1.6       Column A - Rel. Exp. (%) Ag6444, Run 277249377                             Tissue Name   A                                         Adipose   11.2           Melanoma* Hs688(A).T   4.8           Melanoma* Hs688(B).T   10.2           Melanoma* M14   6.9           Melanoma* LOXIMVI   19.3           Melanoma* SK-MEL-5   2.5           Squamous cell carcinoma SCC-4   2.5           Testis Pool   2.6           Prostate ca.* (bone met) PC-3   36.6           Prostate Pool   20.3           Placenta   1.3           Uterus Pool   3.6           Ovarian ca. OVCAR-3   19.2           Ovarian ca. SK-OV-3   16.3           Ovarian ca. OVCAR-4   0.9           Ovarian ca. OVCAR-5   20.0           Ovarian ca. IGROV-1   1.0           Ovarian Ca. OVCAR-8   1.9           Ovary   7.2           Breast Ca. MCF-7   17.2           Breast Ca. MDA-MB-231   3.1           Breast ca. BT 549   40.3           Breast Ca. T47D   9.0           Breast Ca. MDA-N   2.7           Breast Pool   31.6           Trachea   27.2           Lung   0.0           Fetal Lung   40.9           Lung ca. NCI-N417   8.1           Lung ca. LX-1   8.6           Lung ca. NCI-H146   0.0           Lung ca. SHP-77   1.3           Lung ca. A549   21.9           Lung ca. NCI-H526   0.0           Lung ca. NCI-H23   31.4           Lung ca. NCI-H460   0.8           Lung ca. HOP-62   0.0           Lung ca. NCI-H522   9.9           Liver   0.0           Fetal Liver   3.0           Liver ca. HepG2   0.0           Kidney Pool   49.7           Fetal Kidney   35.1           Renal ca. 786-0   10.1           Renal ca. A498   4.5           Renal ca. ACHN   5.5           Renal ca. UO-31   15.1           Renal ca. TK-10   16.8           Bladder   26.2           Gastric ca. (liver met.) NCI-N87   100.0           Gastric ca. KATO III   21.2           Colon ca. SW-948   4.9           Colon ca. SW480   11.1           Colon ca.* (SW480 met) SW620   4.2           Colon ca. HT29   6.1           Colon ca. HCT-116   20.2           Colon ca. CaCo-2   8.1           Colon cancer tissue   10.9           Colon ca. SW1116   3.7           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon Pool   12.3           Small Intestine Pool   19.9           Stomach Pool   21.0           Bone Marrow Pool   10.3           Fetal Heart   6.0           Heart Pool   9.5           Lymph Node Pool   9.9           Fetal Skeletal Muscle   4.2           Skeletal Muscle Pool   9.2           Spleen Pool   4.1           Thymus Pool   18.8           CNS cancer (glio/astro) U87-MG   11.2           CNS cancer (glio/astro) U-118-MG   69.3           CNS cancer (neuro;met) SK-N-AS   9.7           CNS cancer (astro) SF-539   10.4           CNS cancer (astro) SNB-75   6.3           CNS cancer (glio) SNB-19   0.0           CNS cancer (glio) SF-295   0.0           Brain (Amygdala) Pool   2.4           Brain (cerebellum)   22.4           Brain (fetal)   12.7           Brain (Hippocampus) Pool   43.5           Cerebral Cortex Pool   0.0           Brain ( Substantia nigra ) Pool   1.3           Brain (Thalamus) Pool   0.0           Brain (whole)   4.4           Spinal Cord Pool   9.0           Adrenal Gland   15.6           Pituitary gland Pool   8.1           Salivary Gland   10.0           Thyroid (female)   5.3           Pancreatic ca. CAPAN2   64.6           Pancreas Pool   0.0                        
     [0567] General_screening_anel_v1.6 Summary: Ag6444 This gene is has the highest expression in a gastric cancer cell line (CT=33). Thus, expression of this gene could be used as a marker to detect the presence of gastric cancer, and in the treatment of gastric cancer to identify effective therapeutic modalities.  
     [0568] B. CG110266-02: Prostaglandin G/H Synthase 1.  
     [0569] Expression of gene CG110266-02 was assessed using the primer-probe set Ag6450, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC and BD.  
               TABLE BA                          Probe Name Ag6450                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tggttctgggagtttgtcaat-3′   21   294   50               Probe   TET-5′-ctgcttcttccctgtgagtaccaggc-3′-TAMRA   26   343   51               Reverse   5′-caggagctgggcatctg-3′   17   373   52                  
 
     [0570]               TABLE BB                          CNS_neurodegeneration_v1.0       Column A - Rel. Exp. (%) Ag6450, Run 269225321       Column B - Rel. Exp. (%) Ag6450, Run 276596792                                 Tissue Name   A   B                                             AD 1 Hippo   17.4   32.1           AD 2 Hippo   0.0   12.0           AD 3 Hippo   3.2   23.8           AD 4 Hippo   7.1   5.1           AD 5 Hippo   100.0   100.0           AD 6 Hippo   59.9   60.7           Control 2 Hippo   57.4   41.2           Control 4 Hippo   13.0   5.8           Control (Path) 3 Hippo   0.0   0.0           AD 1 Temporal Ctx   17.0   0.0           AD 2 Temporal Ctx   4.1   12.2           AD 3 Temporal Ctx   0.0   0.0           AD 4 Temporal Ctx   4.5   0.0           AD 5 Inf Temporal Ctx   18.2   27.9           AD 5 Sup Temporal Ctx   16.5   29.7           AD 6 Inf Temporal Ctx   3.8   47.6           AD 6 Sup Temporal Ctx   0.0   1.9           Control 1 Temporal Ctx   0.0   7.4           Control 2 Temporal Ctx   3.8   6.0           Control 3 Temporal Ctx   4.0   10.7           Control 3 Temporal Ctx   0.0   0.0           Control (Path) 1 Temporal Ctx   5.0   4.7           Control (Path) 2 Temporal Ctx   14.5   0.0           Control (Path) 3 Temporal Ctx   0.0   0.0           Control (Path) 4 Temporal Ctx   2.1   0.0           AD 1 Occipital Ctx   20.2   15.6           AD 2 Occipital Ctx (Missing)   0.0   0.0           AD 3 Occipital Ctx   4.3   15.8           AD 4 Occipital Ctx   2.5   0.0           AD 5 Occipital Ctx   12.1   0.0           AD 6 Occipital Ctx   29.1   8.5           Control 1 Occipital Ctx   0.0   0.0           Control 2 Occipital Ctx   50.3   77.9           Control 3 Occipital Ctx   9.7   23.2           Control 4 Occipital Ctx   0.0   4.3           Control (Path) 1 Occipital Ctx   48.0   81.8           Control (Path) 2 Occipital Ctx   0.0   5.8           Control (Path) 3 Occipital Ctx   4.4   4.9           Control (Path) 4 Occipital Ctx   4.6   24.7           Control 1 Parietal Ctx   0.0   0.0           Control 2 Parietal Ctx   4.3   6.7           Control 3 Parietal Ctx   13.5   11.1           Control (Path) 1 Parietal Ctx   30.1   12.0           Control (Path) 2 Parietal Ctx   4.4   0.0           Control (Path) 3 Parietal Ctx   8.5   4.1           Control (Path) 4 Parietal Ctx   2.9   13.0                        
     [0571]               TABLE BC                          General_screening_panel_v1.6       Column A - Rel. Exp. (%) Ag6450, Run 277221124                             Tissue Name   A                                         Adipose   6.0           Melanoma* Hs688(A).T   3.3           Melanoma* Hs688(B).T   6.9           Melanoma* M14   0.0           Melanoma* LOXIMVI   0.0           Melanoma* SK-MEL-5   0.0           Squamous cell carcinoma SCC-4   1.4           Testis Pool   2.5           Prostate ca.* (bone met) PC-3   0.0           Prostate Pool   11.0           Placenta   0.6           Uterus Pool   0.0           Ovarian ca. OVCAR-3   10.5           Ovarian ca. SK-OV-3   1.0           Ovarian ca. OVCAR-4   21.2           Ovarian ca. OVCAR-5   2.5           Ovarian ca. IGRO V-1   0.0           Ovarian ca. OVCAR-8   0.0           Ovary   0.4           Breast ca. MCF-7   0.0           Breast ca. MDA-MB-231   0.0           Breast ca. BT 549   0.0           Breast ca. T47D   0.0           Breast ca. MDA-N   0.0           Breast Pool   1.4           Trachea   3.7           Lung   0.5           Fetal Lung   0.0           Lung ca. NCI-N417   0.8           Lung ca. LX-1   0.6           Lung ca. NCI-H146   0.0           Lung ca. SHP-77   3.0           Lung ca. A549   0.0           Lung ca. NCI-H526   6.5           Lung ca. NCI-H23   0.0           Lung ca. NCI-H460   0.0           Lung ca. HOP-62   0.6           Lung ca. NCI-H522   0.0           Liver   0.0           Fetal Liver   1.3           Liver ca. HepG2   0.0           Kidney Pool   1.1           Fetal Kidney   1.5           Renal ca. 786-0   0.0           Renal ca. A498   0.0           Renal ca. ACHN   0.0           Renal ca. UO-31   0.0           Renal ca. TK-10   1.0           Bladder   6.7           Gastric ca. (liver met.) NCI-N87   2.5           Gastric ca. KATO III   0.0           Colon ca. SW-948   0.0           Colon ca. SW480   0.6           Colon ca.* (SW480 met) SW620   0.0           Colon ca. HT29   2.7           Colon ca. HCT-116   3.6           Colon ca. CaCo-2   0.6           Colon cancer tissue   6.7           Colon ca. SW 1116   0.8           Colon ca. Colo-205   0.0           Colon ca. SW-48   0.0           Colon Pool   0.5           Small Intestine Pool   0.4           Stomach Pool   4.0           Bone Marrow Pool   0.7           Fetal Heart   0.7           Heart Pool   3.7           Lymph Node Pool   0.0           Fetal Skeletal Muscle   0.0           Skeletal Muscle Pool   0.0           Spleen Pool   0.0           Thymus Pool   2.9           CNS cancer (glio/astro) U87-MG   0.0           CNS cancer (glio/astro) U-118-MG   100.0           CNS cancer (neuro;met) SK-N-AS   1.4           CNS cancer (astro) SF-539   0.0           CNS cancer (astro) SNB-75   1.4           CNS cancer (glio) SNB-19   0.0           CNS cancer (glio) SF-295   0.0           Brain (Amygdala) Pool   0.7           Brain (cerebellum)   0.0           Brain (fetal)   0.9           Brain (Hippocampus) Pool   1.4           Cerebral Cortex Pool   3.3           Brain ( Substantia nigra ) Pool   0.0           Brain (Thalamus) Pool   1.5           Brain (whole)   3.1           Spinal Cord Pool   1.9           Adrenal Gland   0.8           Pituitary gland Pool   1.6           Salivary Gland   0.0           Thyroid (female)   2.0           Pancreatic ca. CAPAN2   0.0           Pancreas Pool   0.8                        
     [0572]               TABLE BD                          Panel 4.1D       Column A - Rel. Exp. (%) Ag6450, Run 269239957       Column B - Rel. Exp. (%) Ag6450, Run 276596866       Column C - Rel. Exp. (%) Ag6450, Run 276686882                             Tissue Name   A   B   C                                     Secondary Th1 act   0.0   0.0   0.0       Secondary Th2 act   0.0   0.0   0.0       Secondary Tr1 act   0.0   0.0   0.0       Secondary Th1 rest   0.0   0.0   0.0       Secondary Th2 rest   0.0   0.0   0.0       Secondary Tr1 rest   0.0   0.0   0.0       Primary Th1 act   0.0   0.0   0.0       Primary Th2 act   0.0   0.0   0.0       Primary Tr1 act   0.0   0.0   0.0       Primary Th1 rest   0.0   0.0   0.0       Primary Th2 rest   0.0   0.0   0.0       Primary Tr1 rest   0.0   0.0   0.0       CD45RA CD4 lymphocyte act   12.5   35.1   35.4       CD45RO CD4 lymphocyte act   0.0   5.1   0.0       CD8 lymphocyte act   0.0   0.0   0.0       Secondary CD8 lymphocyte rest   0.0   0.0   0.0       Secondary CD8 lymphocyte act   0.0   0.0   0.0       CD4 lymphocyte none   0.0   0.0   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0   0.0   0.0       LAK cells rest   13.2   15.1   4.5       LAK cells IL-2   0.0   0.0   0.0       LAK cells IL-2 + IL-12   0.0   0.0   0.0       LAK cells IL-2 + IFN gamma   0.0   0.0   0.0       LAK cells IL-2 + IL-18   0.0   0.0   0.0       LAK cells PMA/ionomycin   15.5   0.0   7.6       NK Cells IL-2 rest   2.7   0.0   6.4       Two Way MLR 3 day   0.0   0.0   11.5       Two Way MLR 5 day   0.0   0.0   0.0       Two Way MLR 7 day   0.0   0.0   0.0       PBMC rest   0.0   4.9   0.0       PBMC PWM   0.0   0.0   0.0       PBMC PHA-L   0.0   7.3   0.0       Ramos (B cell) none   0.0   0.0   0.0       Ramos (B cell) ionomycin   0.0   0.0   0.0       B lymphocytes PWM   0.0   0.0   6.9       B lymphocytes CD40L and IL-4   0.0   0.0   0.0       EOL-1 dbcAMP   3.0   13.0   5.6       EOL-1 dbcAMP PMA/ionomycin   35.6   45.4   40.3       Dendritic cells none   7.4   42.3   40.3       Dendritic cells LPS   0.0   0.0   3.4       Dendritic cells anti-CD40   22.7   27.9   7.9       Monocytes rest   0.0   15.7   0.0       Monocytes LPS   2.7   0.0   0.0       Macrophages rest   0.0   0.0   19.5       Macrophages LPS   0.0   6.0   1.6       HUVEC none   1.2   0.0   5.1       HUVEC starved   11.3   23.3   4.7       HUVEC IL-1 beta   5.3   42.9   3.2       HUVEC IFN gamma   7.9   37.1   22.1       HUVEC TNF alpha + IFN gamma   2.7   0.0   0.0       HUVEC TNF alpha + IL4   8.7   5.4   7.6       HUVEC IL-11   18.3   6.1   22.1       Lung Microvascular EC none   0.0   0.0   0.0       Lung Microvascular EC TNFalpha + IL-1 beta   0.0   0.0   0.0       Microvascular Dermal EC none   0.0   0.0   0.0       Microvascular Dermal EC TNFalpha + IL-1 beta   0.0   0.0   0.0       Bronchial epithelium TNFalpha + IL1 beta   0.0   0.0   0.0       Small airway epithelium none   0.0   0.0   0.0       Small airway epithelium TNFalpha + IL-1 beta   6.3   5.8   0.0       Coronery artery SMC rest   12.7   21.2   27.9       Coronery artery SMC TNFalpha + IL-1 beta   4.5   0.0   2.1       Astrocytes rest   0.0   0.0   0.0       Astrocytes TNFalpha + IL-1 beta   0.0   0.0   0.0       KU-812 (Basophil) rest   0.0   6.7   17.7       KU-812 (Basophil) PMA/ionomycin   8.0   10.1   4.5       CCD1106 (Keratinocytes) none   16.4   19.1   40.3       CCD1106 (Keratinocytes) TNFalpha + IL-1 beta   10.4   10.7   4.8       Liver cirrhosis   3.7   0.0   1.6       NCI-H292 none   3.5   0.0   9.7       NCI-H292 IL-4   2.6   0.0   21.5       NCI-H292 IL-9   3.2   14.7   1.5       NCI-H292 IL-13   5.7   7.9   6.0       NCI-H292 IFN gamma   3.2   0.0   0.0       HPAEC none   0.0   0.0   35.1       HPAEC TNF alpha + IL-1 beta   1.4   1.8   5.1       Lung fibroblast none   20.0   27.0   56.3       Lung fibroblast TNF alpha + IL-1 beta   10.0   10.2   26.2       Lung fibroblast IL-4   1.4   17.7   3.3       Lung fibroblast IL-9   20.4   24.8   0.0       Lung fibroblast IL-13   5.9   2.1   18.8       Lung fibroblast IFN gamma   32.1   64.2   40.1       Dermal fibroblast CCD1070 rest   100.0   100.0   100.0       Dermal fibroblast CCD1070 TNF alpha   81.2   22.4   81.8       Dermal fibroblast CCD1070 IL-1 beta   32.8   90.8   77.4       Dermal fibroblast IFN gamma   15.8   11.0   12.4       Dermal fibroblast IL-4   4.3   0.0   8.6       Dermal Fibroblasts rest   18.4   22.2   22.8       Neutrophils TNFa + LPS   2.6   5.9   21.5       Neutrophils rest   9.0   0.0   0.0       Colon   0.0   0.0   0.0       Lung   5.5   0.0   6.8       Thymus   0.0   0.0   0.0       Kidney   1.3   0.0   0.0                    
     [0573] CNS_neurodegeneration_v1.0 Summary: Ag6450 Two experiments with the same probe and primer set produce results that are in excellent agreement. This profile confirms the expression of this gene at low but significant levels in brain derived samples. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Parkinson&#39;s disease, schizophrenia, multiple sclerosis, stroke and epilepsy.  
     [0574] General_screening_panel_v1.6 Summary: Ag6450 Highest expression of this gene is seen in a brain cancer cell line (CT=30.9). Thus, expression of this gene could be used to detect the presence of brain cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of brain cancer.  
     [0575] Panel 4.1D Summary: Ag6450 Three experiments with the same probe and primer produce results that are in excellent agreement. Highest expression is seen in resting dermal fibroblasts (CTs=33), with low but significant expression also detected in treated dermal fibroblasts, activated eosinophils, some HUVEC derived samples, and resting dendritic cells. Thus, this gene may be involved in the pathogenesis and/or diagnosis of immune diseases, including psoriasis.  
     [0576] C. CG179317-01: Novel Calcium Binding Protein.  
     [0577] Expression of gene CG179317-01 was assessed using the primer-probe set Ag6661, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB, CC and CD.  
               TABLE CA                          Probe Name Ag6661                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tgcagcctttggtagctaac-3′   20   3439   53               Probe   TET-5′-cgcattctccaattataaaatcagtga-3′-TAMRA   27   3461   54               Reverse   5′-gcaggctcttctccttgaa-3′   19   3501   55                  
 
     [0578]               TABLE CB                          CNS_neurodegeneration_v1.0       Column A - Rel. Exp. (%) Ag6661, Run 275777963                             Tissue Name   A                                         AD 1 Hippo   16.3           AD 2 Hippo   28.3           AD 3 Hippo   18.7           AD 4 Hippo   8.1           AD 5 Hippo   22.4           AD 6 Hippo   63.3           Control 2 Hippo   3.8           Control 4 Hippo   12.8           Control (Path) 3 Hippo   7.4           AD 1 Temporal Ctx   13.4           AD 2 Temporal Ctx   15.2           AD 3 Temporal Ctx   10.4           AD 4 Temporal Ctx   14.2           AD 5 Inf Temporal Ctx   50.7           AD 5 Sup Temporal Ctx   15.8           AD 6 Inf Temporal Ctx   28.9           AD 6 Sup Temporal Ctx   100.0           Control 1 Temporal Ctx   17.7           Control 2 Temporal Ctx   23.2           Control 3 Temporal Ctx   31.2           Control 3 Temporal Ctx   20.4           Control (Path) 1 Temporal Ctx   22.7           Control (Path) 2 Temporal Ctx   50.0           Control (Path) 3 Temporal Ctx   15.8           Control (Path) 4 Temporal Ctx   7.9           AD 1 Occipital Ctx   15.4           AD 2 Occipital Ctx (Missing)   0.0           AD 3 Occipital Ctx   10.4           AD 4 Occipital Ctx   8.4           AD 5 Occipital Ctx   41.5           AD 6 Occipital Ctx   11.5           Control 1 Occipital Ctx   6.0           Control 2 Occipital Ctx   18.7           Control 3 Occipital Ctx   18.4           Control 4 Occipital Ctx   6.5           Control (Path) 1 Occipital Ctx   40.9           Control (Path) 2 Occipital Ctx   7.3           Control (Path) 3 Occipital Ctx   10.1           Control (Path) 4 Occipital Ctx   16.4           Control 1 Parietal Ctx   9.3           Control 2 Parietal Ctx   60.7           Control 3 Parietal Ctx   11.7           Control (Path) 1 Parietal Ctx   62.9           Control (Path) 2 Parietal Ctx   32.5           Control (Path) 3 Parietal Ctx   14.7           Control (Path) 4 Parietal Ctx   21.0                        
     [0579]               TABLE CC                          General_screening_panel_v1.6       Column A - Rel. Exp. (%) Ag6661, Run 277258097                             Tissue Name   A                                         Adipose   3.7           Melanoma* Hs688(A).T   8.3           Melanoma* Hs688(B).T   7.0           Melanoma* M14   21.2           Melanoma* LOXIMVI   23.8           Melanoma* SK-MEL-5   20.0           Squamous cell carcinoma SCC-4   13.0           Testis Pool   1.7           Prostate ca.* (bone met) PC-3   5.1           Prostate Pool   1.9           Placenta   6.4           Uterus Pool   1.0           Ovarian ca. OVCAR-3   15.4           Ovarian ca. SK-OV-3   41.5           Ovarian ca. OVCAR-4   4.5           Ovarian ca. OVCAR-5   34.2           Ovarian ca. IGROV-1   20.7           Ovarian ca. OVCAR-8   4.0           Ovary   2.5           Breast ca. MCF-7   17.0           Breast ca. MDA-MB-231   36.6           Breast ca. BT 549   49.0           Breast ca. T47D   8.6           Breast ca. MDA-N   14.6           Breast Pool   5.5           Trachea   1.1           Lung   1.4           Fetal Lung   18.0           Lung ca. NCI-N417   12.2           Lung ca. LX-1   6.3           Lung ca. NCI-H146   5.7           Lung ca. SHP-77   26.1           Lung ca. A549   17.4           Lung ca. NCI-H526   6.8           Lung ca. NCI-H23   17.8           Lung ca. NCI-H460   9.8           Lung ca. HOP-62   10.7           Lung ca. NCI-H522   4.8           Liver   0.1           Fetal Liver   2.3           Liver ca. HepG2   13.0           Kidney Pool   5.3           Fetal Kidney   3.0           Renal ca. 786-0   58.6           Renal ca. A498   100.0           Renal ca. ACHN   13.0           Renal ca. UO-31   23.5           Renal ca. TK-10   16.8           Bladder   6.5           Gastric ca. (liver met.) NCI-N87   10.0           Gastric ca. KATO III   45.4           Colon ca. SW-948   13.4           Colon ca. SW480   18.7           Colon ca.* (SW480 met) SW620   14.0           Colon ca. HT29   12.2           Colon ca. HCT-116   23.0           Colon ca. CaCo-2   6.9           Colon cancer tissue   8.5           Colon ca. SW1116   7.2           Colon ca. Colo-205   33.4           Colon ca. SW-48   4.1           Colon Pool   5.1           Small Intestine Pool   2.5           Stomach Pool   2.2           Bone Marrow Pool   2.0           Fetal Heart   0.6           Heart Pool   1.5           Lymph Node Pool   4.2           Fetal Skeletal Muscle   0.7           Skeletal Muscle Pool   0.2           Spleen Pool   13.4           Thymus Pool   7.3           CNS cancer (glio/astro) U87-MG   9.9           CNS cancer (glio/astro) U-118-MG   8.7           CNS cancer (neuro;met) SK-N-AS   7.3           CNS cancer (astro) SF-539   7.5           CNS cancer (astro) SNB-75   68.3           CNS cancer (glio) SNB-19   37.4           CNS cancer (glio) SF-295   12.7           Brain (Amygdala) Pool   2.4           Brain (cerebellum)   10.0           Brain (fetal)   13.8           Brain (Hippocampus) Pool   4.4           Cerebral Cortex Pool   4.2           Brain ( Substantia nigra ) Pool   3.0           Brain (Thalamus) Pool   5.7           Brain (whole)   3.1           Spinal Cord Pool   2.2           Adrenal Gland   3.0           Pituitary gland Pool   2.5           Salivary Gland   0.3           Thyroid (female)   1.1           Pancreatic ca. CAPAN2   2.9           Pancreas Pool   2.1                        
     [0580]               TABLE CD                          Panel 4.1D       Column A - Rel. Exp. (%) Ag6661, Run 276043885                             Tissue Name   A                                         Secondary Th1 act   8.4           Secondary Th2 act   11.1           Secondary Tr1 act   1.8           Secondary Th1 rest   0.8           Secondary Th2 rest   0.5           Secondary Tr1 rest   1.3           Primary Th1 act   1.8           Primary Th2 act   5.6           Primary Tr1 act   6.4           Primary Th1 rest   1.0           Primary Th2 rest   1.4           Primary Tr1 rest   0.2           CD45RA CD4 lymphocyte act   3.1           CD45RO CD4 lymphocyte act   3.6           CD8 lymphocyte act   3.9           Secondary CD8 lymphocyte rest   1.1           Secondary CD8 lymphocyte act   2.1           CD4 lymphocyte none   1.7           2ry Th1/Th2/Tr1_anti-CD95 CH11   0.4           LAK cells rest   1.5           LAK cells IL-2   7.1           LAK cells IL-2 + IL-12   0.3           LAK cells IL-2 + IFN gamma   1.4           LAK cells IL-2 + IL-18   1.4           LAK cells PMA/ionomycin   5.3           NK Cells IL-2 rest   16.0           Two Way MLR 3 day   2.8           Two Way MLR 5 day   1.1           Two Way MLR 7 day   1.3           PBMC rest   0.7           PBMC PWM   3.6           PBMC PHA-L   2.2           Ramos (B cell) none   1.1           Ramos (B cell) ionomycin   3.3           B lymphocytes PWM   1.7           B lymphocytes CD40L and IL-4   8.8           EOL-1 dbcAMP   6.2           EOL-1 dbcAMP PMA/ionomycin   3.3           Dendritic cells none   3.0           Dendritic cells LPS   0.6           Dendritic cells anti-CD40   0.7           Monocytes rest   2.1           Monocytes LPS   3.1           Macrophages rest   1.0           Macrophages LPS   0.8           HUVEC none   5.1           HUVEC starved   5.6           HUVEC IL-1 beta   11.2           HUVEC INF gamma   5.3           HUVEC TNF alpha + IFN gamma   2.7           HUVEC TNF alpha + IL4   2.2           HUVEC IL-11   3.4           Lung Microvascular EC none   7.5           Lung Microvascular EC TNFalpha + IL-1 beta   2.6           Microvascular Dermal EC none   0.9           Microvascular Dermal EC TNFalpha + IL-1 beta   1.6           Bronchial epithelium TNFalpha + IL1 beta   2.8           Small airway epithelium none   3.3           Small airway epithelium TNFalpha + IL-1 beta   2.8           Coronery artery SMC rest   3.5           Coronery artery SMC TNFalpha + IL-1 beta   3.9           Astrocytes rest   1.5           Astrocytes TNFalpha + IL-1 beta   1.9           KU-812 (Basophil) rest   0.1           KU-812 (Basophil) PMA/ionomycin   0.3           CCD1106 (Keratinocytes) none   6.4           CCD1106 (Keratinocytes) TNFalpha + IL-1 beta   0.9           Liver cirrhosis   1.7           NCI-H292 none   8.9           NCI-H292 IL-4   11.3           NCI-H292 IL-9   9.1           NCI-H292 IL-13   11.3           NCI-H292 IFN gamma   4.8           HPAEC none   2.5           HPAEC TNFalpha + IL-1 beta   11.7           Lung fibroblast none   5.6           Lung fibroblast TNF alpha + IL-1 beta   6.2           Lung fibroblast IL-4   6.3           Lung fibroblast IL-9   8.7           Lung fibroblast IL-13   3.1           Lung fibroblast IFN gamma   9.1           Dermal fibroblast CCD1070 rest   9.7           Dermal fibroblast CCD1070 TNF alpha   10.8           Dermal fibroblast CCD1070 IL-1 beta   6.9           Dermal fibroblast IFN gamma   7.1           Dermal fibroblast IL-4   5.4           Dermal Fibroblasts rest   6.4           Neutrophils TNFa + LPS   100.0           Neutrophils rest   8.0           Colon   0.4           Lung   5.9           Thymus   1.0           Kidney   3.6                        
     [0581] CNS_neurodegeneration_v1.0 Summary: Ag6661 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals.  
     [0582] General_screening_anel_v1.6 Summary: Ag6661 Highest expression of this gene is detected in a renal cancer A498 cell line (CT=28.4). Moderate levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.  
     [0583] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.  
     [0584] In addition, this gene is expressed at moderate to low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia and depression.  
     [0585] Interestingly, this gene is expressed at much higher levels in fetal (CTs=31-34) when compared to adult lung and liver (CTs=34-38). This observation suggests that expression of this gene can be used to determine the effects of treatment or disease between fetal lung and liver and adult lung and liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance lung and liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung and liver related diseases.  
     [0586] Panel 4.1D Summary: Ag6661 Highest expression of this gene is detected in TNFa+LPS activated neutrophils. Expression of this gene is reduced in resting neutrophils. In addition, low expression of this gene is also seen in activated polarized T cells, activated naive and memory T cells, activated LAK cells, resting IL-2 treated NK cells, activated HUVEC and HPAEC cells, small airway epithelial cells, lund and dermal fibroblasts, activated B lymphocytes and Ramos B cells, resting keratinocytes, mucoepidermoid cells, normal lung and kidney. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.  
     [0587] D. CG50159-03: Gastric Lipase.  
     [0588] Expression of gene CG50159-03 was assessed using the primer-probe sets Ag1456, Ag1899, Ag2059, Ag2132, Ag2444 and Ag2446, described in Tables DA, DB, DC, DD, DE and DF. Results of the RTQ-PCR runs are shown in Tables DG, DH, DI, DJ and DK. Please note that CG50159-03 represents a full length physical clone.  
               TABLE DA                          Probe Name Ag1456                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                     Forward   5′-tcctgaggtgtggatgaatact-3′22   91   56               Probe   TET-5′-catcatctacaatggctaccccagtga-3′-TAMRA   27   121   57   27   j 121   57               Reverse   5′-ccatcttcagtggtgacttcat-3′   22   153   58                  
 
     [0589]               TABLE DB                          Probe Name Ag1899                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-tcctgaggtgtggatgaatact-3′   22   91   59               Probe   TET-5′-catcatctacaatggctaccccagtga-3′-TAMRA   27   121   60               Reverse   5′-ccatcttcagtggtgacttcat-3′   22   153   61                    
     [0590]               TABLE DC                          Probe Name Ag2059                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ggggaaatgacgctgataatat-3′   22   858   62               Probe   TET-5′-cccctatatatgacctgactgccatg-3′-TAMRA   26   903   63               Reverse   5′-cccaaatagcagtaggcacttt-3′   22   929   64                    
     [0591]               TABLE DD                          Probe Name Ag2132                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ggggaaatgacgctgataatat-3′   22   858   65               Probe   TET-5′-cccctatatatgacctgactgccatg-3′-TAMRA   26   903   66               Reverse   5′-cccaaatagcagtaggcacttt-3′   22   929   67                    
     [0592]               TABLE DE                          Probe Name Ag2444                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gaaacagtcggggaaacact-3′   20   354   68               Probe   TET-5′-tggtcaagaagacacaaaacactctca-3′-TAMRA   27   374   69               Reverse   5′-aaaccaaaggcccagaattt-3′   20   413   70                    
     [0593]               TABLE DF                          Probe Name Ag2446                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gaaacagtcggggaaacact-3′   20   354   71               Probe   TET-5′-tggtcaagaagacacaaaacactctca-3′-TAMRA   27   374   72               Reverse   5 -aaaccaaaggcccagaattt-3′   20   413   73                    
     [0594]               TABLE DG                          AI_comprehensive panel_v1.0       Column A - Rel. Exp. (%) Ag1456, Run 224501612                             Tissue Name   A                                         110967 COPD-F   0.0           110980 COPD-F   2.1           110968 COPD-M   0.0           110977 COPD-M   0.0           110989 Emphysema-F   2.6           110992 Emphysema-F   0.0           110993 Emphysema-F   0.0           110994 Emphysema-F   0.0           110995 Emphysema-F   0.0           110996 Emphysema-F   0.0           110997 Asthma-M   5.0           111001 Asthma-F   1.6           111002 Asthma-F   2.5           111003 Atopic Asthma-F   0.0           111004 Atopic Asthma-F   0.0           111005 Atopic Asthma-F   0.0           111006 Atopic Asthma-F   0.0           111417 Allergy-M   0.0           112347 Allergy-M   0.8           112349 Normal Lung-F   10.0           112357 Normal Lung-F   0.0           112354 Normal Lung-M   0.0           112374 Crohns-F   2.4           112389 Match Control Crohns-F   100.0           112375 Crohns-F   0.0           112732 Match Control Crohns-F   5.0           112725 Crohns-M   1.5           112387 Match Control Crohns-M   0.0           112378 Crohns-M   0.0           112390 Match Control Crohns-M   2.3           112726 Crohns-M   0.0           112731 Match Control Crohns-M   0.0           112380 Ulcer Col-F   0.0           112734 Match Control Ulcer Col-F   52.5           112384 Ulcer Col-F   0.0           112737 Match Control Ulcer Col-F 2.5           112386 Ulcer Col-F   2.4           112738 Match Control Ulcer Col-F   3.3           112381 Ulcer Col-M   0.0           112735 Match Control Ulcer Col-M   1.4           112382 Ulcer Col-M   28.5           112383 Ulcer Col-M   0.0           112736 Match Control Ulcer Col-M   74.2           112423 Psoriasis-F   4.4           112427 Match Control Psoriasis-F   0.0           112418 Psoriasis-M   0.0           112723 Match Control Psoriasis-M   0.0           112419 Psoriasis-M   4.4           112424 Match Control Psoriasis-M   0.0           112420 Psoriasis-M   4.4           112425 Match Control Psoriasis-M   0.0           104689 (MF) OA Bone-Backus   0.0           104690 (MF) Adj “Normal” Bone-Backus   3.0           104691 (MF) OA Synovium-Backus   35.1           104692 (BA) OA Cartilage-Backus   0.0           104694 (BA) OA Bone-Backus   3.2           104695 (BA) Ad “Normal” Bone-Backus   3.1           104696 (BA) OA Synovium-Backus   20.9           104700 (SS) OA Bone-Backus   39.0           104701 (SS) Ad “Normal” Bone-Backus   3.3           104702 (SS) OA Synovium-Backus   5.0           117093 OA Cartilage Rep7   0.0           112672 OA Bone5   0.0           112673 OA Synovium5   0.0           112674 OA Synovial Fluid cells5   0.0           117100 OA Cartilage Rep 14   0.0           112756 OA Bone9   0.0           112757 OA Synovium9   0.0           112758 OA Synovial Fluid Cells9   1.3           117125 RA Cartilage Rep2   0.0           113492 Bone2 RA   62.0           113493 Synovium2 RA   8.7           113494 Syn Fluid Cells RA   21.0           113499 Cartilage4 RA   20.6           113500 Bone4 RA   25.5           113501 Synovium4 RA   15.3           113502 Syn Fluid Cells4 RA   8.5           113495 Cartilage3 RA   33.7           113496 Bone3 RA   33.7           113497 Synovium3 RA   19.9           113498 Syn Fluid Cells3 RA   37.6           117106 Normal Cartilage Rep20   0.0           113663 Bone3 Normal   0.0           113664 Synovium3 Normal   0.9           113665 Syn Fluid Cells3 Normal   0.0           117107 Normal Cartilage Rep22   2.4           113667 Bone4 Normal   0.0           113668 Synovium4 Normal   0.0           113669 Syn Fluid Cells4 Normal   0.0                        
     [0595]               TABLE DH                          Panel 1.2       Column A - Rel. Exp. (%) Ag1456, Run 138374123                             Tissue Name   A                                         Endothelial cells   0.0           Heart (Fetal)   0.6           Pancreas   0.0           Pancreatic ca. CAPAN 2   0.0           Adrenal Gland   10.7           Thyroid   1.3           Salivary gland   3.2           Pituitary gland   0.3           Brain (fetal)   0.6           Brain (whole)   0.0           Brain (amygdala)   0.5           Brain (cerebellum)   0.0           Brain (hippocampus)   0.7           Brain (thalamus)   0.7           Cerebral Cortex   0.0           Spinal cord   2.1           glio/astro U87-MG   0.0           glio/astro U-118-MG   1.8           astrocytoma SW1783   0.0           neuro*; met SK-N-AS   0.0           astrocytoma SF-539   0.0           astrocytoma SNB-75   0.0           glioma SNB-19   0.0           glioma U251   0.0           glioma SF-295   0.0           Heart   9.9           Skeletal Muscle   8.2           Bone marrow   0.0           Thymus   0.6           Spleen   12.3           Lymph node   0.9           Colorectal Tissue   1.9           Stomach   2.0           Small intestine   1.2           Colon ca. SW480   0.5           Colon ca.* SW620 (SW480 met)   3.1           Colon ca. HT29   0.0           Colon ca. HCT-116   0.0           Colon ca. CaCo-2   0.5           Colon ca. Tissue (ODO3866)   8.2           Colon ca. HCC-2998   0.0           Gastric ca.* (liver met) NCI-N87   2.4           Bladder   29.1           Trachea   0.6           Kidney   3.1           Kidney (fetal)   2.5           Renal ca. 786-0   0.0           Renal ca. A498   0.0           Renal ca. RXF 393   0.0           Renal ca. ACHN   0.0           Renal ca. UO-31   0.0           Renal ca. TK-10   0.0           Liver   4.1           Liver (fetal)   4.5           Liver ca. (hepatoblast) HepG2   0.0           Lung   5.6           Lung (fetal)   1.2           Lung ca. (small cell) LX-1   5.9           Lung ca. (small cell) NCI-H69   1.7           Lung ca. (s. cell var.) SHP-77   0.0           Lung ca. (large cell) NCI-H460   0.0           Lung ca. (non-sm. cell) A549   0.0           Lung ca. (non-s. cell) NCI-H23   60.3           Lung ca. (non-s. cell) HOP-62   0.0           Lung ca. (non-s. cl) NCI-H522   2.8           Lung ca. (squam.) SW 900   0.0           Lung ca. (squam.) NCI-H596   0.0           Mammary gland   0.0           Breast ca.* (pl. ef) MCF-7   0.9           Breast ca.* (pl. ef) MDA-MB-231   0.0           Breast ca.* (pl. ef) T47D   0.0           Breast ca. BT-549   0.0           Breast ca. MDA-N   0.0           Ovary   0.0           Ovarian ca. OVCAR-3   0.0           Ovarian ca. OVCAR-4   0.0           Ovarian ca. OVCAR-5   1.4           Ovarian ca. OVCAR-8   0.0           Ovarian ca. IGROV-1   0.0           Ovarian ca. (ascites) SK-OV-3   0.0           Uterus   0.4           Placenta   2.2           Prostate   1.4           Prostate ca.* (bone met) PC-3   0.0           Testis   0.0           Melanoma Hs688(A).T   0.0           Melanoma* (met) Hs688(B).T   0.0           Melanoma UACC-62   0.0           Melanoma M14   0.0           Melanoma LOX IMVI   0.0           Melanoma* (met) SK-MEL-5   1.2                        
     [0596]               TABLE DI                          Panel 1.3D       Column A—Rel. Exp. (%) Ag1456, Run 147644869       Column B—Rel. Exp. (%) Ag1456, Run 165529464       Column C—Rel. Exp. (%) Ag2132, Run 160164823       Column D—Rel. Exp. (%) Ag2444, Run 165629988                                 Tissue Name   A   B   C   D                                         Liver adenocarcinoma   0.0   0.0   0.0   0.0       Pancreas   0.0   0.0   0.0   1.9       Pancreatic ca. CAPAN 2   0.0   0.0   0.0   0.0       Adrenal gland   9.2   7.6   5.2   1.9       Thyroid   0.0   0.0   0.0   1.6       Salivary gland   0.0   0.0   0.0   0.4       Pituitary gland   0.0   0.0   0.0   0.6       Brain (fetal)   0.0   0.0   0.0   1.4       Brain (whole)   0.0   0.0   0.0   0.3       Brain (amygdala)   0.0   0.0   0.0   0.0       Brain (cerebellum)   0.0   0.0   0.0   0.0       Brain (hippocampus)   0.0   0.0   0.0   0.4       Brain (substantia nigra)   4.6   0.0   0.0   0.4       Brain (thalamus)   0.0   0.0   0.0   0.0       Cerebral Cortex   0.0   0.0   0.0   0.5       Spinal cord   0.0   10.4   3.5   1.2       glio/astro U87-MG   0.0   0.0   0.0   0.0       glio/astro U-118-MG   12.4   0.0   10.7   8.5       astrocytoma SW1783   0.0   0.0   0.0   0.0       neuro*; met SK-N-AS   0.0   0.0   0.0   0.0       astrocytoma SF-539   0.0   0.0   0.0   0.0       astrocytoma SNB-75   0.0   0.0   0.0   2.5       glioma SNB-19   0.0   0.0   0.0   0.0       glioma U251   0.0   0.0   0.0   0.6       glioma SF-295   0.0   0.0   0.0   0.0       Heart (fetal)   5.8   0.0   0.0   0.0       Heart   0.0   0.0   0.0   0.5       Skeletal muscle (fetal)   0.0   0.0   0.0   0.3       Skeletal muscle   0.0   6.2   5.0   0.6       Bone marrow   100.0   100.0   66.4   0.0       Thymus   0.0   0.0   7.2   0.0       Lymph node   5.0   7.4   0.0   1.3       Spleen   11.4   8.8   21.2   0.0       Colorectal   0.0   0.0   0.0   0.3       Stomach   0.0   0.0   0.0   0.9       Small intestine   0.0   0.0   0.0   0.4       Colon ca. *SW480   0.0   0.0   0.0   0.0       Colon ca. HT29   0.0   0.0   0.0   1.1       Colon ca. HCT-116   0.0   0.0   0.0   0.0       Colon ca. CaCo-2   0.0   0.0   0.0   0.8       Colon ca. tissue (OD03866)   10.8   17.3   23.2   0.6       Colon ca. HCC-2998   0.0   0.0   0.0   1.4       Gastric ca.* (liver met) NCI-N87   0.0   0.0   1.8   100.0       Bladder   0.0   6.7   0.0   1.5       Trachea   0.0   0.0   31.6   1.2       Kidney   0.0   0.0   0.0   0.6       Kidney (fetal)   5.1   0.0   0.0   0.0       Renal ca. 786-0   0.0   0.0   0.0   0.0       Renal ca. A498   0.0   0.0   3.9   0.1       Renal ca. RXF 393   0.0   0.0   0.0   1.4       Renal ca. ACHN   0.0   0.0   0.0   24.7       Renal ca. UO-3 1   0.0   0.0   0.0   0.0       Renal ca. TK-l0   0.0   0.0   0.0   0.0       Liver   0.0   0.0   0.0   0.0       Liver (fetal)   3.7   0.0   0.0   0.9       Liver ca. (hepatoblast) HepG2   0.0   0.0   0.0   0.0       Lung   38.4   25.0   100.0   1.3       Lung (fetal)   18.9   5.7   15.1   0.0       Lung ca. (small cell) LX-1   11.7   0.0   0.0   0.3       Lung ca. (small cell) NCI-H69   0.0   0.0   0.0   2.3       Lung ca. (s.cell var.) SHP-77   0.0   0.0   0.0   0.0       Lung ca. (large cell) NCI-H460   0.0   0.0   0.0   0.5       Lung ca. (non-sm. cell) A549   0.0   0.0   0.0   3.3       Lung ca. (non-s.cell) NCI-H23   38.2   17.9   10.2   21.5       Lung ca. (non-s.cell) HOP-62   0.0   0.0   0.0   0.0       Lung ca. (non-s.d) NCI-H522   0.0   0.0   0.0   0.3       Lung ca. (squam.) SW 900   0.0   0.0   0.0   2.2       Lung ca. (squam.) NCI-H596   0.0   0.0   0.0   0.5       Mammary gland   0.0   0.0   0.0   0.6       Breast ca.* (pl. ef) MCF-7   0.0   0.0   0.0   35.4       Breast ca.* (pl. ef) MDA-MB-231   0.0   0.0   0.0   0.0       Breast ca.* (pl. ef) T47D   0.0   0.0   0.0   5.6       Breast ca. BT-549   0.0   0.0   0.0   1.7       Breast ca. MDA-N   0.0   0.0   0.0   0.0       Ovary   0.0   0.0   0.0   2.3       Ovarian ca. OVCAR-3   0.0   0.0   0.0   17.7       Ovarian ca. OVCAR-4   0.0   0.0   0.0   17.1       Ovarian ca. OVCAR-5   0.0   0.0   0.0   0.9       Ovarian ca. OVCAR-8   0.0   0.0   0.0   4.4       Ovarian ca. IGROV-1   0.0   0.0   0.0   0.0       Ovarian ca.* (ascites) SK-OV-3   0.0   0.0   0.0   8.0       Uterus   0.0   0.0   0.0   3.0       Placenta   5.3   0.0   16.5   0.0       Prostate   0.0   0.0   0.0   0.0       Prostate ca.* (bone met) PC-3   0.0   0.0   0.0   32.8       Testis   5.3   0.0   0.0   1.3       Melanoma Hs688(A).T   0.0   0.0   0.0   0.0       Melanoma* (met) Hs688(B).T   0.0   0.0   0.0   0.0       Melanoma UACC-62   0.0   0.0   0.0   0.5       Melanoma M14   0.0   0.0   0.0   0.6       Melanoma LOX IMVI   0.0   0.0   0.0   0.0       Melanoma* (met) SK-MEL-5   0.0   0.0   0.0   0.0       Adipose   27.0   14.3   10.7   4.0                    
     [0597]               TABLE DJ                          Panel 2D       Column A - Rel. Exp. (%) Ag1456, Run 147644930       Column B - Rel. Exp. (%) Ag1456, Run 148059395       Column C - Rel. Exp. (%) Ag1456, Run 162599938                             Tissue Name   A   B   C                                     Normal Colon   13.2   2.1   6.3       CC Well to Mod Diff (ODO3866)   5.5   2.4   2.6       CC Margin (ODO3866)   2.1   3.2   2.3       CC Gr.2 rectosigmoid (ODO3868)   0.6   0.0   1.7       CC Margin (ODO3868)   0.0   0.0   0.8       CC Mod Diff (ODO3920)   1.8   2.9   3.5       CC Margin (ODO3920)   0.5   1.2   2.6       CC Gr. 2 ascend colon (ODO3921)   1.3   9.2   6.5       CC Margin (ODO3921)   0.0   0.5   1.7       CC from Partial Hepatectomy (ODO4309)   2.3   6.7   7.1       Mets       Liver Margin (ODO4309)   3.2   7.3   2.3       Colon mets to lung (OD04451-01)   1.3   0.6   0.0       Lung Margin (OD04451-02)   2.0   4.5   1.9       Normal Prostate 6546-1   0.0   0.0   0.0       Prostate Cancer (OD04410)   0.7   0.0   2.9       Prostate Margin (OD04410)   0.6   0.0   0.0       Prostate Cancer (OD04720-01)   0.6   0.0   0.0       Prostate Margin (OD04720-02)   2.8   0.2   2.9       Normal Lung 061010   7.4   8.2   0.0       Lung Met to Muscle (ODO4286)   6.1   2.0   5.8       Muscle Margin (ODO4286)   1.5   0.6   1.1       Lung Malignant Cancer (OD03126)   9.9   7.3   4.1       Lung Margin (OD03126)   33.9   28.1   27.0       Lung Cancer (OD04404)   13.3   11.2   13.0       Lung Margin (OD04404)   32.8   22.2   28.3       Lung Cancer (OD04565)   4.5   1.3   5.7       Lung Margin (OD04565)   0.0   7.2   4.9       Lung Cancer (OD04237-01)   2.1   1.6   3.5       Lung Margin (OD04237-02)   100.0   100.0   100.0       Ocular Mel Met to Liver (ODO4310)   0.3   0.0   0.0       Liver Margin (ODO4310)   1.9   0.6   0.7       Melanoma Mets to Lung (OD04321)   0.5   0.0   0.0       Lung Margin (OD04321)   22.8   27.5   24.5       Normal Kidney   0.0   0.6   1.6       Kidney Ca, Nuclear grade 2 (OD04338)   8.7   11.5   16.5       Kidney Margin (OD04338)   2.0   6.1   3.2       Kidney Ca Nuclear grade 1/2 (OD04339)   1.4   0.6   0.8       Kidney Margin (OD04339)   0.0   0.5   2.6       Kidney Ca, Clear cell type (OD04340)   20.0   26.8   25.9       Kidney Margin (OD04340)   7.2   3.4   9.7       Kidney Ca, Nuclear grade 3 (OD04348)   0.7   0.0   0.5       Kidney Margin (OD04348)   1.2   1.4   1.8       Kidney Cancer (OD04622-01)   11.2   11.2   20.9       Kidney Margin (OD04622-03)   1.6   1.0   1.4       Kidney Cancer (OD04450-01)   0.7   0.0   0.0       Kidney Margin (OD04450-03)   0.0   1.4   3.2       Kidney Cancer 8120607   0.0   0.0   0.0       Kidney Margin 8120608   0.0   0.6   1.0       Kidney Cancer 8120613   1.0   0.8   0.8       Kidney Margin 8120614   0.0   0.0   0.0       Kidney Cancer 9010320   17.9   13.8   15.0       Kidney Margin 9010321   0.7   1.4   1.4       Normal Uterus   0.0   0.0   0.0       Uterus Cancer 064011   1.2   0.5   2.1       Normal Thyroid   0.0   0.6   0.7       Thyroid Cancer 064010   0.0   1.3   2.8       Thyroid Cancer A302152   1.9   0.6   3.0       Thyroid Margin A302153   0.0   0.0   1.9       Normal Breast   0.8   1.9   0.0       Breast Cancer (OD04566)   0.0   0.0   0.0       Breast Cancer (OD04590-01)   0.0   1.9   0.0       Breast Cancer Mets (OD04590-03)   0.9   0.5   1.4       Breast Cancer Metastasis (OD04655-05)   1.1   0.6   1.7       Breast Cancer 064006   0.0   0.7   0.0       Breast Cancer 1024   0.7   0.0   0.9       Breast Cancer 9100266   0.0   0.0   0.0       Breast Margin 9100265   0.7   0.0   0.0       Breast Cancer A209073   0.8   0.0   0.0       Breast Cancer A209073   0.0   0.0   0.0       Normal Liver   0.0   0.0   1.1       Liver Cancer 064003   1.4   0.0   0.0       Liver Cancer 1025   0.0   0.0   0.8       Liver Cancer 1026   2.2   1.8   0.9       Liver Cancer 6004-T   1.2   1.0   0.0       Liver Cancer 6004-N   1.1   0.7   2.7       Liver Cancer 6005-T   0.0   0.0   0.8       Liver Tissue 6005-N   0.0   0.0   0.6       Normal Bladder   3.9   1.8   8.4       Bladder Cancer 1023   0.0   0.0   0.0       Bladder Cancer A302173   3.3   5.2   1.7       Bladder Cancer (OD04718-01)   13.0   11.0   11.8       Bladder Normal Adjacent (OD04718-03)   14.6   12.7   15.9       Normal Ovary   0.0   0.0   0.0       Ovarian Cancer 064008   0.0   0.8   0.0       Ovarian Cancer (OD04768-07)   2.9   2.3   6.0       Ovary Margin (OD04768-08)   16.7   20.9   12.9       Normal Stomach   1.1   3.3   3.2       Gastric Cancer 9060358   0.0   0.0   0.0       Stomach Margin 9060359   3.1   5.9   3.3       Gastric Cancer 9060395   13.2   3.7   11.0       Stomach Margin 9060394   1.6   2.7   4.3       Gastric Cancer 9060397   19.1   7.4   9.8       Stomach Margin 9060396   0.0   1.2   0.8       Gastric Cancer 064005   4.3   5.6   3.9                    
     [0598]               TABLE DK                          Panel 4D       Column A - Rel. Exp. (%) Ag1456, Run 139309823       Column B - Rel. Exp. (%) Ag1456, Run 144691235       Column C - Rel. Exp. (%) Ag1899, Run 165870453       Column D - Rel. Exp. (%) Ag2059, Run 161426290       Column E - Rel. Exp. (%) Ag2132, Run 159366502                                     Tissue Name   A   B   C   D   E                                             Secondary Th1 act   0.0   0.0   0.0   0.0   0.0       Secondary Th2 act   0.4   0.4   0.0   0.0   0.0       Secondary Tr1 act   0.0   0.0   0.0   0.0   0.0       Secondary Th1 rest   0.0   0.0   0.3   0.0   0.0       Secondary Th2 rest   6.1   4.8   2.4   0.8   2.7       Secondary Tr1 rest   0.4   0.0   0.3   0.0   1.4       Primary Th1 act   0.0   0.7   0.0   0.0   0.0       Primary Th2 act   1.5   0.3   0.6   0.0   0.0       Primary Tr1 act   0.0   0.6   0.1   0.0   0.0       Primary Th1 rest   4.5   4.1   7.9   3.0   5.3       Primary Th2 rest   6.5   2.9   3.7   6.3   1.1       Primary Tr1 rest   2.7   3.5   1.6   2.5   1.0       CD45RA CD4 lymphocyte act   0.0   0.0   0.0   0.0   0.0       CD45RO CD4 lymphocyte act   0.0   0.4   0.3   0.0   0.0       CD8 lymphocyte act   0.0   0.0   0.0   0.0   0.0       Secondary CD8 lymphocyte rest   0.5   0.0   0.2   0.0   0.0       Secondary CD8 lymphocyte act   0.6   0.0   0.0   0.0   0.0       CD4 lymphocyte none   3.1   1.1   1.4   5.1   0.0       2ry Th1/Th2/Tr1_anti-CD95 CH11   4.3   5.9   4.7   2.1   3.5       LAK cells rest   0.5   1.1   0.5   0.0   0.0       LAK cells IL-2   1.0   1.4   0.8   0.0   1.6       LAK cells IL-2 + IL-12   1.0   0.9   0.2   0.0   0.0       LAK cells IL-2 + IFN gamma   0.5   2.1   0.6   0.0   0.0       LAK cells IL-2 + IL-18   1.0   0.4   0.4   0.0   0.0       LAK cells PMA/ionomycin   17.1   17.8   8.0   8.5   10.0       NK Cells IL-2 rest   0.0   0.0   0.2   1.2   0.0       Two Way MLR 3 day   0.0   0.0   0.0   1.5   0.0       Two Way MLR 5 day   0.0   0.3   0.0   0.0   0.0       Two Way MLR 7 day   0.0   0.5   0.0   0.0   0.0       PBMC rest   20.3   22.2   18.4   6.7   14.0       PBMC PWM   0.5   0.0   0.0   0.0   1.3       PBMC PHA-L   0.0   1.0   0.2   0.0   0.0       Ramos (B cell) none   36.1   48.6   21.0   0.0   7.2       Ramos (B cell) ionomycin   100.0   87.1   16.6   44.1   27.9       B lymphocytes PWM   0.5   0.0   0.0   1.6   0.0       B lymphocytes CD40L and IL-4   0.5   0.0   0.0   0.0   0.0       EOL-1 dbcAMP   0.0   0.0   0.2   0.0   0.0       EOL-1 dbcAMP PMA/ionomycin   0.4   0.0   0.6   1.1   1.2       Dendritic cells none   5.6   4.7   4.3   3.7   8.4       Dendritic cells LPS   3.0   1.8   2.3   3.7   1.8       Dendritic cells anti-CD40   2.6   3.2   2.0   4.7   0.0       Monocytes rest   97.3   100.0   100.0   100.0   100.0       Monocytes LPS   34.2   34.4   20.3   15.8   19.3       Macrophages rest   5.1   5.5   3.0   4.0   1.3       Macrophages LPS   7.5   9.7   4.8   3.0   0.0       HUVEC none   0.0   0.0   0.0   0.0   0.0       HUVEC starved   0.0   0.0   0.0   0.0   0.0       HUVEC IL-1 beta   0.0   0.0   0.0   0.0   0.0       HUVEC IFN gamma   0.0   0.0   0.0   0.0   0.0       HUVEC TNF alpha + IFN gamma   0.0   0.0   0.0   0.0   0.0       HUVEC TNF alpha + IL4   0.0   0.0   0.0   0.0   0.0       HUVEC IL-11   0.0   0.0   0.0   0.0   0.0       Lung Microvascular EC none   0.0   0.0   0.0   0.0   0.0       Lung Microvascular EC TNFalpha +   0.0   0.0   0.0   0.0   0.0       IL-1 beta       Microvascular Dermal EC none   0.0   0.0   0.0   0.0   0.0       Microvascular Dermal EC   0.0   0.0   0.0   0.0   0.0       TNFalpha + IL-1 beta       Bronchial epithelium TNFalpha +   0.0   0.0   0.0   0.0   0.0       IL1 beta       Small airway epithelium none   0.5   0.5   0.5   0.0   0.0       Small airway epithelium TNFalpha +   4.0   3.8   2.1   6.2   6.3       IL-1 beta       Coronery artery SMC rest   0.0   0.0   0.0   0.0   0.0       Coronery artery SMC TNFalpha +   0.0   0.0   0.0   0.0   0.0       IL-1 beta       Astrocytes rest   0.0   0.0   0.0   0.0   0.0       Astrocytes TNFalpha + IL-1 beta   0.0   0.0   0.0   0.0   0.0       KU-812 (Basophil) rest   0.0   0.0   0.0   0.0   0.0       KU-812 (Basophil) PMA/ionomycin   0.0   0.0   0.0   0.0   0.0       CCD1106 (Keratinocytes) none   0.0   0.0   0.0   0.0   0.0       CCD1106 (Keratinocytes)   0.0   0.4   0.2   0.0   0.0       TNFalpha + IL-1 beta       Liver cirrhosis   5.4   5.4   6.9   3.0   1.4       Lupus kidney   0.4   0.4   0.9   0.0   0.0       NCI-H292 none   0.0   0.4   0.0   0.0   1.5       NCI-H292 IL-4   0.0   0.0   0.0   0.0   0.0       NCI-H292 IL-9   0.0   0.0   0.3   0.0   0.0       NCI-H292 IL-13   0.0   0.0   0.0   0.0   0.0       NCI-H292 IFN gamma   0.0   0.0   0.0   0.0   0.0       HPAEC none   0.0   0.0   0.0   0.0   0.0       HPAEC TNF alpha + IL-1 beta   0.0   0.0   0.0   0.0   0.0       Lung fibroblast none   0.0   0.0   0.0   0.0   0.0       Lung fibroblast TNF alpha + IL-1   0.0   0.0   0.0   0.0   0.0       beta       Lung fibroblast IL-4   0.0   0.0   0.0   0.0   0.0       Lung fibroblast IL-9   0.0   0.0   0.0   0.0   0.0       Lung fibroblast IL-13   0.0   0.0   0.0   0.0   0.0       Lung fibroblast IFN gamma   0.0   0.0   0.0   0.0   0.0       Dermal fibroblast CCD1070 rest   0.0   0.0   0.0   0.0   0.0       Dermal fibroblast CCD1070 TNF   1.6   0.0   0.2   0.0   0.0       alpha       Dermal fibroblast CCD 1070 IL-1   0.0   0.0   0.0   0.0   0.0       beta       Dermal fibroblast IFN gamma   0.0   0.0   0.1   0.0   0.0       Dermal fibroblast IL-4   0.5   0.0   0.0   0.0   0.0       IBD Colitis 2   0.6   0.0   1.4   0.0   0.0       IBD Crohn&#39;s   1.4   1.5   2.0   0.0   0.0       Colon   0.6   0.0   0.6   0.0   3.1       Lung   3.7   5.2   1.5   2.1   4.9       Thymus   0.5   0.0   0.2   0.0   0.0       Kidney   2.6   4.4   0.6   1.6   0.0                    
     [0599] AI_comprehensive panel_v1.0 Summary: Ag 1456 Highest expression of this transcript is found in normal colon tissue adjacent to tissue affected by Crohn&#39;s or ulcerative colitis (CTs=33). This transcript is also found in normal colon on panels 1.2 and 2D. Since this transcript appears to be down regulated in diseased colon, therapeutic modulation of the expression or function of the this gene or its protein product, through the use protein therapeutics, could regulate normal homeostasis of this tissue and be beneficial for the treatment of inflammatory bowel diseases.  
     [0600] Panel 1.2 Summary: Ag1456 Highest expression of this gene is detected in bone marrow (CT=28.9). Furthermore, the difference in expression between heart (CT=31.2) and fetal heart tissue (CT=36.2) is significant in this panel. Thus, the expression of this gene could be used to distinguish bone marrow from the other samples in the panel. In addition, the expression of this gene could be used to distinguish effects of therapy or disease between adult heart tissue and fetal heart tissue.  
     [0601] This gene is also expressed in many tissues with metabolic function, including the heart, fetal and adult liver, skeletal muscle and adrenal gland. The protein encoded by this gene is a lipase homolog and may be involved in the dynamic mobilization of fat in these tissues. Therefore, administration of this gene product or an agonist designed to it could enhance lipolysis and may act as an effective therapy against obesity and lipodystrophy. Conversely, an antagonist of this gene product may be useful in the treatment of conditions involving excessive depletion of fat reserves, such as cachexia.  
     [0602] Panel 1.3D Summary: Ag1456/Ag2132/Ag2444 Three out of four experiments using different probe and primer sets show expression of the this gene in bone marrow (CTs=33-34) and the lung (CT=32.4). The high expression in bone marrow is consistent with its expression seen in Panel 1.2. Thus, the expression of this gene could be used to distinguish samples derived from bone marrow and lung from other tissues on this panel. Furthermore, expression of this gene could be used to distinguish gene expression between adult and fetal lung tissue.  
     [0603] Ag2059/Ag2446 Expression of the gene is low/undetectable (Ct values&gt;35) in all samples in Panel 1.3D.  
     [0604] Panel 2D Summary: Ag1456 Three experiments with the same probe and primer produce results that are in excellent agreement, with highest expression of this gene in normal lung tissue adjacent to a tumor (CTs=30-31). In addition, this gene appears to be overexpressed in three pairs of normal lung tissue when compared to corresponding cancerous tissue. In addition, four of nine kidney cancers show overexpression of this gene when compared to their respective normal adjacent tissue. Thus, the expression of this gene could be used to distinguish normal lung tissue from malignant lung tissue as well as malignant kidney from normal kidney. Moreover, therapeutic modulation of the expression of this gene or its gene product, through the use of small molecule drugs, antibodies or protein therapeutics may be effective in the treatment of kidney cancer or lung cancer.  
     [0605] Panel 4D Summary: Ag1456/Ag1899/Ag2059/Ag2132 Multiple experiments with different probe and primer sets show highest expression of this gene in resting monocytes (CTs=29-32). The gene appears to be downregulated in these cells following LPS treatment (CTs=32-34) and is not expressed at detectable levels in macrophages. The protein encoded by the gene is homologous to acidic lipases and may play a role in lipid metabolism, differentiation, and activities such as phagocytosis, of these cells. Therefore, therapeutic modulation of the expression or function of this gene or its protein product, through the use of protein therapeutics, could regulate monocyte function and/or differentiation.  
     [0606] Conversely, modulation of the expression or activity of the putative protein encoded by this transcript by antibodies or small molecules can reduce or prevent the inflammatory symptoms associated with accumulation of monocytes observed in diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis.  
     [0607] E. CG59201-02: Coagulation Factor VII Precursor.  
     [0608] Expression of gene CG59201-02 was assessed using the primer-probe set Ag6390, described in Table EA. Results of the RTQ-PCR runs are shown in Table EB.  
               TABLE EA                          Probe Name Ag6390                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-gaccagctccagtcctatatctg-3′   23   411   74               Probe   TET-5′-ctgtgagacgcttgaatatccatgtggaaaaatac-3′-TAMRA   35   464   75               Reverse   5′-tggggtttgctggcat-3′   16   517   76                  
 
     [0609]               TABLE EB                          General_screening_panel_v1.6       Column A—Rel. Exp. (%) Ag6390, Run 277247696                             Tissue Name   A   Tissue Name   A                                     Adipose   0.0   Renal ca. TK-10   14.5       Melanoma* Hs688(A).T   0.0   Bladder   3.0       Melanoma* Hs688(B).T   0.0   Gastric ca. (liver met.) NCI-N87   0.0       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   0.0   Colon ca. SW-948   0.0       Melanoma* SK-MEL-5   0.0   Colon ca. SW480   0.0       Squamous Cell   0.0   Colon ca.* (SW480 met) SW620   0.0       Carcinoma SCC-4       Testis Pool   0.0   Colon ca. HT29   0.0       Prostate ca.* (bone met)   0.0   Colon ca. HCT-116   0.0       PC-3       Prostate Pool   2.1   Colon ca. CaCo-2   0.0       Placenta   0.0   Colon cancer tissue   0.0       Uterus Pool   0.0   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   0.0   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   3.4   Colon ca. SW-48   2.1       Ovarian ca. OVCAR-4   5.8   Colon Pool   4.6       Ovarian ca. OVCAR-5   4.0   Small Intestine Pool   3.2       Ovarian ca. IGROV-1   0.0   Stomach Pool   4.0       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   1.9       Ovary   9.6   Fetal Heart   0.0       Breast ca. MCF-7   4.9   Heart Pool   0.0       Breast ca. MDA-MB-231   0.0   Lymph Node Pool   3.9       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   8.4       Breast ca. T47D   7.3   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   0.0   Spleen Pool   0.0       Breast Pool   2.3   Thymus Pool   10.3       Trachea   0.0   CNS cancer (glio/astro)   0.0               U87-MG       Lung   3.0   CNS cancer (glio/astro)   0.0               U-118-MG       Fetal Lung   0.0   CNS cancer (neuro; met)   0.0               SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.0       Lung ca. LX-1   0.0   CNS cancer (astro) SNB-75   0.0       Lung ca. NCI-H146   26.1   CNS cancer (glio) SNB-19   0.0       Lung ca. SHP-77   5.9   CNS cancer (glio) SF-295   0.0       Lung ca. A549   11.1   Brain (Amygdala) Pool   10.6       Lung ca. NCI-H526   0.0   Brain (cerebellum)   17.2       Lung ca. NCI-H23   0.0   Brain (fetal)   8.2       Lung ca. NCI-H460   0.0   Brain (Hippocampus) Pool   6.3       Lung ca. HOP-62   0.0   Cerebral Cortex Pool   15.4       Lung ca. NCI-11522   0.0   Brain (Substantia nigra) Pool   16.2       Liver   5.5   Brain (Thalamus)   6.3       Fetal Liver   12.2   Brain (whole)   9.9       Liver ca. HepG2   20.3   Spinal Cord Pool   6.8       Kidney Pool   0.0   Adrenal Gland   0.0       Fetal Kidney   0.0   Pituitary gland Pool   3.2       Renal ca. 786-0   0.0   Salivary Gland   8.2       Renal ca. A498   0.0   Thyroid (female)   0.0       Renal ca. ACHN   0.0   Pancreatic ca. CAPAN2   0.0       Renal ca. UO-31   0.0   Pancreas Pool   0.0                    
     [0610] General_screening_panel_v1.6 Summary: Ag6390 Expression of this gene is significant in colon cancer cell line (CT=34.2). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of colon cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon cancer.  
     [0611] F. CG94799-03: Chitotriosidase Precursor.  
     [0612] Expression of gene CG94799-03 was assessed using the primer-probe set Ag6512, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB and FC.  
               TABLE FA                          Probe Name Ag6512                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-ctcaacgtgggccgatac-3′   18   693   77               Probe   TET-5′-caggaactgagtcttccatacttgccttcag3′-TAMRA   31   732   78               Reverse   5′-ctcaggttcagagggctga-3′   19   794   79                  
 
     [0613]               TABLE FB                          AI_comprehensive panel_v1.0       Column A—Rel. Exp. (%) Ag6512, Run 296559277                             Tissue Name   A   Tissue Name   A                                     110967 COPD-F   0.0   112427 Match Control   6.5               Psoriasis-F       110980 COPD-F   0.0   112418 Psoriasis-M   0.0       110968 COPD-M   0.0   112723 Match Control   0.0               Psoriasis-M       110977 COPD-M   2.3   112419 Psoriasis-M   0.0       110989 Emphysema-F   0.8   112424 Match Control   0.0               Psoriasis-M       110992 Emphysema-F   0.0   112420 Psoriasis-M   0.5       110993 Emphysema-F   0.0   112425 Match Control   2.2               Psoriasis-M       110994 Emphysema-F   0.0   104689 (MF) GA Bone-Backus   25.0       110995 Emphysema-F   2.8   104690 (MF) Adj “Normal”   0.8               Bone-Backus       110996 Emphysema-F   0.0   104691 (MF) OA Synovium-   0.7               Backus       110997 Asthma-M   0.0   104692 (BA) OA Cartilage-   0.0               Backus       111001 Asthma-F   0.0   104694 (BA) OA Bone-Backus   2.4       111002 Asthma-F   0.0   104695 (BA) Adj “Normal”   2.7               Bone-Backus       111003 Atopic Asthma-F   0.0   104696 (BA) OA Synovium-   8.4               Backus       111004 Atopic Asthma-F   2.0   104700 (SS) OA Bone-Backus   31.2       111005 Atopic Asthma-F   0.0   104701 (SS) Adj “Normal”   14.0               Bone-Backus       111006 Atopic Asthma-F   0.0   104702 (SS) GA Synovium-   71.7               Backus       111417 Allergy-M   0.0   117093 OA Cartilage Rep7   0.0       112347 Allergy-M   0.0   112672 OA Bone5   0.0       112349 Normal Lung-F   0.0   112673 OA Synovium5   0.0       112357 Normal Lung-F   20.6   112674 OA Synovial Fluid   0.0               cells5       112354 Normal Lung-M   3.3   117100 OA Cartilage Rep14   0.0       112374 Crohns-F   0.5   112756 OA Bone9   3.7       112389 Match Control   0.0   112757 OA Synovium9   3.5       Crohns-F       112375 Crohns-F   0.0   112758 OA Synovial Fluid   0.0               Cells9       112732 Match Control   8.2   117125 RA Cartilage Rep2   0.0       Crohns-F       112725 Crohns-M   0.0   113492 Bone2 RA   100.0       112387 Match Control   0.0   113493 Synovium2 RA   28.3       Crohns-M       112378 Crohns-M   0.0   113494 Syn Fluid Cells RA   46.0       112390 Match Control   8.2   113499 Cartilage4 RA   52.1       Crohns-M       112726 Crohns-M   1.8   113500 Bone4 RA   60.3       112731 Match Control   32.8   113501 Synovium4 RA   29.5       Crohns-M       112380 Ulcer Col-F   0.5   113502 Syn Fluid Cells4 RA   46.0       112734 Match Control   14.7   113495 Cartilage3 RA   28.5       Ulcer Col-F       112384 Ulcer Col-F   0.0   113496 Bone3 RA   33.0       112737 Match Control   2.7   113497 Synovium3 RA   24.7       Ulcer Col-F       112386 Ulcer Col-F   0.0   113498 Syn Fluid Cells3 RA   45.7       112738 Match Control   4.0   117106 Normal Cartilage Rep20   0.0       Ulcer Col-F       112381 Ulcer Col-M   0.0   113663 Bone3 Normal   0.0       112735 Match Control   0.0   113664 Synovium3 Normal   0.0       Ulcer Col-M       112382 Ulcer Col-M   0.0   113665 Syn Fluid Cells3 Normal   0.0       112394 Match Control   0.0   117107 Normal Cartilage Rep22   0.0       Ulcer Col-M       112383 Ulcer Col-M   0.9   113667 Bone4 Normal   0.0       112736 Match Control   0.0   113668 Synovium4 Normal   0.6       Ulcer Col-M       112423 Psoriasis-F   0.0   113669 Syn Fluid Cells4 Normal   0.0                    
     [0614]               TABLE FC                          Panel 4.1D       Column A—Rel. Exp. (%) Ag6512, Run 271409604                             Tissue Name   A   Tissue Name   A                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.0       Secondary Th2 act   0.0   HUVEC IFN gamma   0.0       Secondary Tn act   0.0   HUVEC TNF alpha +   0.0               IFN gamma       Secondary Th1 rest   0.0   HUVEC TNF alpha + 1L4   0.0       Secondary Th2 rest   0.0   HUVEC IL-11   0.0       Secondary Tr1 rest   0.0   Lung Microvascular EC none   0.0       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNFalpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC none   0.0       Primary Tr1 act   0.0   Microvascular Dermal EC   0.0               TNFalpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNFalpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium none   0.0       Primary Tr1 rest   0.0   Small airway epithelium   0.0               TNFalpha + IL-1beta       CD45RA CD4   0.0   Coronery artery SMC rest   0.0       lymphocyte act       CD45RO CD4   0.0   Coronery artery SMC   0.0       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.0       Secondary CD8   0.0   Astrocytes TNFalpha + IL-1beta   0.0       lymphocyte rest       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte rest       CD4 lymphocyte none   0.0   KU-812 (Basophil) PMA/   0.0               ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106 (Keratinocytes) none   0.0       CD95 CH11       LAK cells rest   1.5   CCD1106 (Keratinocytes)   0.0               TNFalpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.3   NCI-H292 none   0.0       LAK cells IL-2 + IFN   0.0   NCI-H292 IL-4   0.0       gamma       LAK cells IL-2 + IL-18   0.7   NCI-H292 IL-9   0.0       LAK cells PMA/   4.5   NCI-H292 IL-13   0.0       ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   0.1   HPAEC none   0.0       Two Way MLR 5 day   0.2   HPAEC TNF alpha + IL-1 beta   0.0       Two Way MLR 7 day   0.0   Lung fibroblast none   0.0       PBMC rest   0.0   Lung fibroblast TNF alpha +   0.0               IL-1 beta       PBMC PWM   0.0   Lung fibroblast IL-4   0.0       PBMC PHA-L   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   0.0       Ramos (B cell)   0.0   Lung fibroblast IFN gamma   0.0       ionomycin       B lymphocytes PWM   0.0   Dermal fibroblast CCD1070 rest   0.0       B lymphocytes CD40L   0.0   Dermal fibroblast CCD1070   0.0       and IL-4       TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast CCD1070   0.0               IL-1 beta       EOL-1 dbcAMP PMA/   0.0   Dermal fibroblast IFN gamma   0.0       ionomycin       Dendritic cells none   0.0   Dermal fibroblast IL-4   0.0       Dendritic cells LPS   0.3   Dermal Fibroblasts rest   0.0       Dendritic cells anti-CD40   0.0   Neutrophils TNFa + LPS   0.0       Monocytes rest   0.0   Neutrophils rest   0.3       Monocytes LPS   0.0   Colon   0.0       Macrophages rest   44.8   Lung   0.0       Macrophages LPS   100.0   Thymus   0.0       HUVEC none   0.0   Kidney   0.0       HUVEC starved   0.0                    
     [0615] AI_comprehensive panel_v1.0 Summary: Ag6512 Highest expression of this gene is detected in rheumotoid arthritis bone (CT=32.2). Moderate to low expression of this gene is also detected in samples derived from rheumatoid arthritis bone, cartilage, synovium and synovial fluid samples, from osteoarthritis Synovium and bone, from normal lung, normal matched Crohn&#39;s disease and ulcerative colitis. Expression of this gene is low/undetectable in normal bone. Therefore, therapeutic modulation of this gene product through the use of small molecule drug may be useful in the treatment of rheumatoid arthritis and osteoarthritis. In addition, the expression profile of this gene suggests that it could be used as diagnostic marker for rhuemotoid and osteoarthritis.  
     [0616] Panel 4.1D Summary: Ag6512 This gene is exclusively expressed in resting and activated macrophage (CTs=30-31). Therefore, antibody or small molecule therapeutics designed against the protein encoded by this gene may reduce or inhibit inflammation in diseases such as asthma, IBD, psoriasis, arthritis and allergy and improve the efficacy of vaccines and antiviral or antibacterial treatments.  
     [0617] G. CG94799-04 and CG94799-05: Chitotriosidase.  
     [0618] Expression of gene CG94799-04 and CG94799-05 was assessed using the 10 primer-probe set Ag6513, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB, GC, GD and GE. Please note that CG94799-05 represents a full-length physical clone.  
               TABLE GA                          Probe Name Ag6513                                             Start   SEQ ID       Primers   Sequences   Length   Position   No                                         Forward   5′-agtggctgcagaagggg-3′   17   758   80               Probe   TET-5′-tggcatgcctacctacggacgc-3′-TAMRA   22   798   81               Reverse   5′-cccccactctggtgtctg-3′   18   842   82                  
 
     [0619]               TABLE GB                          AI_comprehensive panel_v1.0       Column A—Rel. Exp. (%) Ag6513, Run 297445439                             Tissue Name   A   Tissue Name   A                                     110967 COPD-F   0.1   112427 Match Control   0.8               Psorasis-F       110980 COPD-F   0.0   112418 Psoriasis-M   0.0       110968 COPD-M   0.2   112723 Match Control   0.0               Psoriasis-M       110989 Emphysema-F   0.2   112424 Match Control   0.0               Psoriasis-M       110993 Emphysema-F   0.2   112425 Match Control   1.2               Psoriasis-M       110994 Emphysema-F   0.1   104689 (MF) OA Bone-Backus   62.9       110995 Emphysema-F   0.2   104690 (MF) Adj “Normal”   0.8               Bone-Backus       110996 Emphysema-F   0.1   104691 (MF) OA Synovium-   1.7               Backus       110997 Asthma-M   0.0   104692 (BA) OA Cartilage-   0.0               Backus       111001 Asthma-F   0.0   104694 (BA) OA Bone-Backus   2.7       111002 Asthma-F   0.1   104695 (BA) Adj “Normal”   1.4               Bone-Backus       111003 Atopic Asthma-F   0.3   104696 (BA) OA Synovium-   5.6               Backus       111004 Atopic Asthma-F   0.4   104700 (SS) OA Bone-Backus   25.7       111005 Atopic Asthma-F   0.4   104701 (SS) Adj “Normal”   4.7               Bone-Backus       111006 Atopic Asthma-F   0.0   104702 (SS) OA Synovium-   27.2               Backus       111417 Allergy-M   0.0   117093 OA Cartilage Rep7   0.1       112347 Allergy-M   0.0   112672 OA Bone5   0.1       112349 Normal Lung-F   0.0   112673 OA Synovium5   0.0       112357 Normal Lung-F   5.0   112674 OA Synovial Fluid   0.2               cells5       112354 Normal Lung-M   1.4   117100 OA Cartilage Rep14   0.0       112374 Crohns-F   0.2   112756 OA Bone9   0.9       112389 Match Control   0.0   112757 OA Synovium9   1.8       Crohns-F       112375 Crohns-F   0.2   112758 OA Synovial Fluid   0.1               Cells9       112732 Match Control   5.1   117125 RA Cartilage Rep2   0.1       Crohns-F       112725 Crohns-M   0.0   113492 Bone2 RA   100.0       112387 Match Control   0.1   113493 Synovium2 RA   32.5       Crohns-M       112378 Crohns-M   0.0   113494 Syn Fluid Cells RA   61.1       112390 Match Control   0.5   113499 Cartilage4 RA   42.6       Crohns-M       112726 Crohns-M   1.2   113500 Bone4 RA   39.8       112731 Match Control   9.9   113501 Synovium4 RA   25.2       Crohns-M       112380 Ulcer Col-F   0.2   113502 Fluid Cells4 RA   17.2       112734 Match Control   6.8   113495 Cartilage3 RA   38.2       Ulcer Col-F       112384 Ulcer Col-F   0.3   113496 Bone3 RA   38.2       112737 Match Control   1.7   113497 Synovium3 RA   21.5       Ulcer Col-F       112386 Ulcer Col-F   0.1   113498 Syn Fluid Cells3 RA   46.3       112738 Match Control   1.2   117106 Normal Cartilage Rep20   0.0       Ulcer Col-F       112381 Ulcer Col-M   0.0   113663 Bone3 Normal   0.0       112735 Match Control   0.0   113664 Synovium3 Normal   0.0       Ulcer Col-M       112382 Ulcer Col-M   0.1   113665 Syn Fluid Cells3 Normal   0.0       112394 Match Control   0.1   117107 Normal Cartilage Rep22   0.0       Ulcer Col-M       112383 Ulcer Col-M   0.4   113667 Bone4 Normal   0.0       112736 Match Control   0.1   113668 Synovium4 Normal   0.2       Ulcer Col-M       112423 Psoriasis-F   0.1   113669 Syn Fluid Cells4   0.2               Normal                    
     [0620]               TABLE GC                          CNS_neurodegeneration_v1.0       Column A—Rel. Exp. (%) Ag6513, Run 271673345                             Tissue Name   A   Tissue Name   A                                     AD 1 Hippo   6.9   Control (Path) 3 Temporal Ctx   0.0       AD 2 Hippo   63.7   Control (Path) 4 Temporal Ctx   16.6       AD 3 Hippo   36.9   AD 1 Occipital Ctx   3.0       AD 4 Hippo   16.6   AD 2 Occipital Ctx (Missing)   0.0       AD 5 hippo   35.6   AD 3 Occipital Ctx   8.2       AD 6 Hippo   40.1   AD 4 Occipital Ctx   23.7       Control 2 Hippo   27.0   AD 5 Occipital Ctx   62.9       Control 4 Hippo   48.3   AD 6 Occipital Ctx   20.4       Control (Path) 3 Hippo   0.0   Control Occipital Ctx   15.2       AD 1 Temporal Ctx   16.0   Control 2 Occipital Ctx   10.4       AD 2 Temporal Ctx   29.5   Control 3 Occipital Ctx   6.7       AD 3 Temporal Ctx   14.1   Control 4 Occipital Ctx   31.4       AD 4 Temporal Ctx   15.4   Control (Path) 1 Occipital Ctx   17.6       AD 5 Inf Temporal Ctx   17.2   Control (Path) 2 Occipital Ctx   8.2       AD 5 SupTemporal Ctx   47.3   Control (Path) 3 Occipital Ctx   0.0       AD 6 Inf Temporal Ctx   55.1   Control (Path) 4 Occipital Ctx   31.4       AD 6 Sup Temporal Ctx   100.0   Control 1 Parietal Ctx   17.6       Control 1 Temporal Ctx   18.8   Control 2 Parietal Ctx   8.2       Control 2 Temporal Ctx   25.0   Control 3 Parietal Ctx   20.4       Control 3 Temporal Ctx   16.5   Control (Path) 1 Parietal Ctx   51.8       Control 4 Temporal Ctx   22.7   Control (Path) 2 Parietal Ctx   20.2       Control (Path) 1   51.4   Control (Path) 3 Parietal Ctx   2.9       Temporal Ctx       Control (Path) 2   63.7   Control (Path) 4 Parietal Ctx   18.7       Temporal Ctx                    
     [0621]               TABLE GD                          General_screening_panel_v1.6       Column A—Rel. Exp. (%) Ag6513, Run 277253285                             Tissue Name   A   Tissue Name   A                                     Adipose   9.6   Renal ca. TK-10   0.0       Melanoma* Hs688(A).T   0.0   Bladder   22.7       Melanoma* Hs688(B).T   0.0   Gastric ca. (liver met.) NCI-N87   1.8       Melanoma* M14   0.0   Gastric ca. KATO III   0.0       Melanoma* LOXIMVI   0.0   Colon ca. SW-948   0.0       Melanoma* SK-MEL-5   0.0   Colon ca. SW480   0.0       Squamous Cell   0.0   Colon ca.* (SW480 met) SW620   2.8       Carcinoma SCC-4       Testis Pool   0.0   Colon ca. HT29   0.0       Prostate ca.* (bone met)   0.0   Colon ca. HCT-116   0.0       PC-3       Prostate Pool   0.0   Colon ca. CaCo-2   1.6       Placenta   5.5   Colon cancer tissue   100.0       Uterus Pool   0.0   Colon ca. SW1116   0.0       Ovarian ca. OVCAR-3   3.5   Colon ca. Colo-205   0.0       Ovarian ca. SK-OV-3   3.1   Colon ca. SW-48   0.0       Ovarian ca. OVCAR-4   0.0   Colon Pool   1.7       Ovarian ca. OVCAR-5   1.1   Small Intestine Pool   5.6       Ovarian ca. IGROV-1   16.7   Stomach Pool   0.0       Ovarian ca. OVCAR-8   0.0   Bone Marrow Pool   1.8       Ovary   23.0   Fetal Heart   1.9       Breast ca. MCF-7   2.0   Heart Pool   1.9       Breast ca. MDA-MB-231   0.0   Lymph Node Pool   2.5       Breast ca. BT 549   0.0   Fetal Skeletal Muscle   2.8       Breast ca. T47D   0.0   Skeletal Muscle Pool   0.0       Breast ca. MDA-N   0.0   Spleen Pool   15.1       Breast Pool   0.0   Thymus Pool   48.3       Trachea   14.6   CNS cancer (glio/astro)   0.0               U87-MG       Lung   3.7   CNS cancer (glio/astro)   0.0               U-118-MG       Fetal Lung   5.4   CNS cancer (neuro; met)   0.0               SK-N-AS       Lung ca. NCI-N417   0.0   CNS cancer (astro) SF-539   0.0       Lung ca. LX-1   0.0   CNS cancer (astro) SNB-75   3.6       Lung ca. NCI-H146   0.0   CNS cancer (glio) SNB-19   13.7       Lung ca. SHP-77   39.0   CNS cancer (glio) SF-295   0.0       Lung ca. A549   0.0   Brain (Amygdala) Pool   7.7       Lung ca. NCI-H526   0.0   Brain (cerebellum)   5.1       Lung ca. NCI-H23   3.7   Brain (fetal)   18.0       Lung ca. NCI-H460   0.0   Brain (Hippocampus) Pool   5.3       Lung ca. HOP-62   1.7   Cerebral Cortex Pool   15.3       Lung ca. NCI-11522   3.7   Brain (Substantia nigra) Pool   12.2       Liver   0.0   Brain (Thalamus)   7.7       Fetal Liver   4.4   Brain (whole)   9.0       Liver ca. HepG2   0.0   Spinal Cord Pool   53.2       Kidney Pool   0.0   Adrenal Gland   3.5       Fetal Kidney   0.0   Pituitary gland Pool   0.0       Renal ca. 786-0   0.0   Salivary Gland   5.2       Renal ca. A498   0.0   Thyroid (female)   5.4       Renal ca. ACHN   1.7   Pancreatic ca. CAPAN2   0.0       Renal ca. UO-31   4.1   Pancreas Pool   4.6                    
     [0622]               TABLE GE                          Panel 4.1D       Column A—Rel. Exp. (%) Ag6513, Run 271401001                             Tissue Name   A   Tissue Name   A                                     Secondary Th1 act   0.0   HUVEC IL-1beta   0.0       Secondary Th2 act   0.0   HUVEC IFN gamma   0.0       Secondary Tn act   0.0   HUVEC TNF alpha +   0.0               IFN gamma       Secondary Th1 rest   0.1   HUVEC TNF alpha + 1L4   0.0       Secondary Th2 rest   0.0   HUVEC IL-11   0.1       Secondary Tr1 rest   0.0   Lung Microvascular EC none   0.0       Primary Th1 act   0.0   Lung Microvascular EC   0.0               TNFalpha + IL-1beta       Primary Th2 act   0.0   Microvascular Dermal EC none   0.0       Primary Tr1 act   0.0   Microvascular Dermal EC   0.0               TNFalpha + IL-1beta       Primary Th1 rest   0.0   Bronchial epithelium   0.0               TNFalpha + IL1beta       Primary Th2 rest   0.0   Small airway epithelium none   0.0       Primary Tr1 rest   0.0   Small airway epithelium   0.0               TNFalpha + IL-1beta       CD45RA CD4   0.0   Coronery artery SMC rest   0.0       lymphocyte act       CD45RO CD4   0.1   Coronery artery SMC   0.0       lymphocyte act       TNFalpha + IL-1beta       CD8 lymphocyte act   0.0   Astrocytes rest   0.1       Secondary CD8   0.0   Astrocytes TNFalpha + IL-1beta   0.0       lymphocyte rest       Secondary CD8   0.0   KU-812 (Basophil) rest   0.0       lymphocyte rest       CD4 lymphocyte none   0.0   KU-812 (Basophil) PMA/   0.0               ionomycin       2ry Th1/Th2/Tr1_anti-   0.0   CCD1106 (Keratinocytes) none   0.0       CD95 CH11       LAK cells rest   2.2   CCD1106 (Keratinocytes)   0.0               TNFalpha + IL-1beta       LAK cells IL-2   0.0   Liver cirrhosis   0.0       LAK cells IL-2 + IL-12   0.0   NCI-H292 none   0.0       LAK cells IL-2 + IFN   0.8   NCI-H292 IL-4   0.0       gamma       LAK cells IL-2 + IL-18   0.7   NCI-H292 IL-9   0.0       LAK cells PMA/   5.3   NCI-H292 IL-13   0.0       ionomycin       NK Cells IL-2 rest   0.0   NCI-H292 IFN gamma   0.0       Two Way MLR 3 day   0.6   HPAEC none   0.0       Two Way MLR 5 day   0.4   HPAEC TNF alpha + IL-1 beta   0.0       Two Way MLR 7 day   0.8   Lung fibroblast none   0.0       PBMC rest   0.0   Lung fibroblast TNF alpha +   0.0               IL-1 beta       PBMC PWM   0.0   Lung fibroblast IL-4   0.0       PBMC PHA-L   0.0   Lung fibroblast IL-9   0.0       Ramos (B cell) none   0.0   Lung fibroblast IL-13   0.0       Ramos (B cell)   0.0   Lung fibroblast IFN gamma   0.0       ionomycin       B lymphocytes PWM   0.3   Dermal fibroblast CCD1070 rest   0.0       B lymphocytes CD40L   0.5   Dermal fibroblast CCD1070   0.2       and IL-4       TNF alpha       EOL-1 dbcAMP   0.0   Dermal fibroblast CCD1070   0.0               IL-1 beta       EOL-1 dbcAMP PMA/   0.0   Dermal fibroblast IFN gamma   0.0       ionomycin       Dendritic cells none   0.2   Dermal fibroblast IL-4   0.0       Dendritic cells LPS   2.5   Dermal Fibroblasts rest   0.0       Dendritic cells anti-CD40   0.4   Neutrophils TNFa + LPS   0.3       Monocytes rest   0.1   Neutrophils rest   0.8       Monocytes LPS   0.3   Colon   0.0       Macrophages rest   100.0   Lung   0.0       Macrophages LPS   65.1   Thymus   0.0       HUVEC none   0.0   Kidney   0.0       HUVEC starved   0.0                    
     [0623] AI_comprehensive panel_v1.0 Summary: Ag6513 Highest expression of this gene is detected in rheumotoid arthritis bone (CT=27). Moderate to low expression of this gene is also detected in samples derived from rheumatoid arthritis bone, cartilage, synovium and synovial fluid samples, from osteoarthritis bone and the normal adjacent bone, from normal lung, normal matched Crohn&#39;s disease and ulcerative colitis. Expression of this gene is low/undetectable in normal bone. Therefore, therapeutic modulation of this gene product through the use of small molecule drug may be useful in the treatment of rheumatoid arthritis and osteoarthritis. In addition, the expression profile of this gene suggests that it could be used as diagnostic marker for rhuemotoid and osteoarthritis.  
     [0624] General_screening_panel_v1.6 Summary: Ag6513 Highest expression of this gene is seen in colon cancer tissue sample (CT=30.9). Low expression of this gene is also seen in a number of cancer cell line derived from brain, lung and ovarian cancers. Therefore, therapeutic modulation of this gene through the use of small molecule drug may be useful in the treatment of colon, lung, brain and ovarian cancers.  
     [0625] In addition, this gene is expressed at moderate to low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer&#39;s disease, Parkinson&#39;s disease, epilepsy, multiple sclerosis, schizophrenia and depression.  
     [0626] Panel 4.1D Summary: Ag6513 This gene is mainly expressed in resting and activated macrophage (CTs=27-27.8). In addition, moderate to low expression of this gene is also seen in activated monocytes, LAK cells, resting neutrophils, and thymus. Therefore, antibody or small molecule therapeutics designed against the protein encoded by this gene may reduce or inhibit inflammation in diseases such as asthma, IBD, psoriasis, arthritis and allergy and improve the efficacy of vaccines and antiviral or antibacterial treatments.  
     Example D  
     Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences  
     [0627] Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution can be either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.  
     [0628] SeqCalling assemblies produced by the exon linking process were selected and extended using the following criteria. Genomic clones having regions with 98% identity to all or part of the initial or extended sequence were identified by BLASTN searches using the relevant sequence to query human genomic databases. The genomic clones that resulted were selected for further analysis because this identity indicates that these clones contain the genomic locus for these SeqCalling assemblies. These sequences were analyzed for putative coding regions as well as for similarity to the known DNA and protein sequences. Programs used for these analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and other relevant programs.  
     [0629] Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified was manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation&#39;s human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.  
     [0630] The regions defined by the procedures described above were then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones was reiterated to derive the full length sequence (Alderbom et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).  
     [0631] Variants are reported individually but any combination of all or a select subset of variants are also included as contemplated NOVX embodiments of the invention.  
     [0632] NOV1b SNP Data (CG109413-01)  
     [0633] One polymorphic variants of NOV1b has been identified and is shown here in table SNP 1.  
               TABLE SNP1                          Variant of NOV1b                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13378521   264   C   A   75   Pro   Pro       13377957   337   T   C   100   Tyr   His       13378522   1428    C   T   0                  
 
     [0634] NOV3a SNP Data (CG176765-01)  
               TABLE SNP2                          Variants of NOV3a                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13382198   32   G   A   0               13382199   221   T   C   54   Val   Ala       13382201   410   A   G   117   Gln   Arg       13382202   498   A   G   146   Lys   Lys       13382203   1478    T   A   473   Leu   His       13382205   1913    G   A   618   Ser   Asn                  
 
     [0635] NOV4a SNP Data (CG178142-01)  
               TABLE SNP3                          Variant of NOV4a                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                             13382181   1513   A   G   0                      
 
     [0636] NOV5a SNP Data (CG179317-01)  
               TABLE SNP4                          Variants of NOV5a                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                             13382190   2772   T   C   0           13382191   3394   T   C   0       13382196   3794   G   A   0       13382192   3924   A   G   0                  
 
     [0637] NOV6a SNP Data (CG51059-03)  
               TABLE SNP5                          Variants of NOV6b                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13375592   221   A   G   72   Arg   Gly       13373919   299   G   C   98   Ala   Pro       13373884   301   T   C   98   Ala   Ala       13373921   399   C   T   131   Ser   Leu       13375593   428   G   A   141   Gly   Ser       13375594   735   C   A   243   Thr   Asn       13375595   867   A   G   287   Asp   Gly                  
 
     [0638] NOV7a SNP Data (CG56099-02)  
               TABLE SNP6                          Variants of NOV7b                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified               13375819   838   A   G   279   Lys   Arg       13375818   884   A   G   294   Gly   Gly       13382184   1082    C   T   360   Gly   Gly       13375817   1252    C   G   417   Pro   Arg                  
 
     [0639] NOV8b SNP Data (CG59201-02)  
               TABLE SNP7                          Variant of NOV8b                             Nucleotides   Amino Acids                                         Variant   Position   Initial   Modified   Position   Initial   Modified                                                 13382188   473   G   A   143   Thr   Thr       13382187   1089   A   G   349   Ser   Gly       13382186   1141   G   A   366   Arg   Gln                  
 
     OTHER EMBODIMENTS  
     [0640] Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.  
    
     
       
         1 
         
           
             82  
           
           
             1  
             1903  
             DNA  
             Homo sapiens  
             
               CDS  
               (415)..(1776)  
             
           
            1 

cgtttgggag aaaatgtgtc ggatattttg gggcggtcac gtgggcgggc gggctccgag     60 

aggccccggg acagtcccag cctagagccg tgccccccca ggagcccccc agtacggcga    120 

gccccggaca ttgcgacgct ccatccaaga gactgcccga cgccgggacc tcggggctcc    180 

gccgcctccc ttccccctcc cactccagct acggcccagt tccctcaacc tgacccagta    240 

tgtagaagcc agtctctgca ggcggccagc gggacttttg gaggcccagt gggcaggcca    300 

ggcagggcgg gtacggagcc tcccaggctg gggcagtggg catgggcagg ggctgtggct    360 

gaagacctcg cccgcccact gcagacccca ggggactctc acaccgcagc tgcc atg      417 
                                                            Met 
                                                            1 
gcc acc aat aag gag cga ctc ttt gcg gct ggt gcc ctg ggg cct gga      465 
Ala Thr Asn Lys Glu Arg Leu Phe Ala Ala Gly Ala Leu Gly Pro Gly 
            5                   10                  15 

tct ggc tac cca ggg gca ggt ttc ccc ttc gcc ttc cca ggg gca ctc      513 
Ser Gly Tyr Pro Gly Ala Gly Phe Pro Phe Ala Phe Pro Gly Ala Leu 
        20                  25                  30 

agg ggg tct ccg cct ttc gag atg ctg agc cct agc ttc cgg ggc ctg      561 
Arg Gly Ser Pro Pro Phe Glu Met Leu Ser Pro Ser Phe Arg Gly Leu 
    35                  40                  45 

ggc cag cct gac ctc ccc aag gag atg gcc tct ctg tcg gtg gag aca      609 
Gly Gln Pro Asp Leu Pro Lys Glu Met Ala Ser Leu Ser Val Glu Thr 
50                  55                  60                  65 

cag agc acc agc tca gag gag atg gtg cca agc tcg ccc tcg ccc cct      657 
Gln Ser Thr Ser Ser Glu Glu Met Val Pro Ser Ser Pro Ser Pro Pro 
                70                  75                  80 

ccg cct cct cgg gtc tac aag cca tgc ttc gtg tgc aat gac aag tcc      705 
Pro Pro Pro Arg Val Tyr Lys Pro Cys Phe Val Cys Asn Asp Lys Ser 
            85                  90                  95 

tct ggc tac cac tat ggg gtc agc tct tgt gaa ggc tgc aag ggc ttc      753 
Ser Gly Tyr His Tyr Gly Val Ser Ser Cys Glu Gly Cys Lys Gly Phe 
        100                 105                 110 

ttt cgc cga agc atc cag aag aac atg gtg tac acg tgt cac cgc gac      801 
Phe Arg Arg Ser Ile Gln Lys Asn Met Val Tyr Thr Cys His Arg Asp 
    115                 120                 125 

aaa aac tgt atc atc aac aag gtg acc agg aat cgc tgc cag tac tgc      849 
Lys Asn Cys Ile Ile Asn Lys Val Thr Arg Asn Arg Cys Gln Tyr Cys 
130                 135                 140                 145 

cgg cta cag aag tgc ttc gaa gtg ggc atg tcc aag gaa gct gtg cga      897 
Arg Leu Gln Lys Cys Phe Glu Val Gly Met Ser Lys Glu Ala Val Arg 
                150                 155                 160 

aat gac cgg aac aag aag aag aaa gag gtg aag gaa gaa ggg tca cct      945 
Asn Asp Arg Asn Lys Lys Lys Lys Glu Val Lys Glu Glu Gly Ser Pro 
            165                 170                 175 

gac agc tat gag ctg agc cct cag tta gaa gag ctc atc acc aag gtc      993 
Asp Ser Tyr Glu Leu Ser Pro Gln Leu Glu Glu Leu Ile Thr Lys Val 
        180                 185                 190 

agc aaa gcc cat cag gag act ttc ccc tcg ctc tgc cag ctg ggc aag     1041 
Ser Lys Ala His Gln Glu Thr Phe Pro Ser Leu Cys Gln Leu Gly Lys 
    195                 200                 205 

tat acc acg aac tcc agt gca gac cac cgc gtg cag ctg gat ctg ggg     1089 
Tyr Thr Thr Asn Ser Ser Ala Asp His Arg Val Gln Leu Asp Leu Gly 
210                 215                 220                 225 

ctg tgg gac aag ttc agt gag ctg gct acc aag tgc atc atc aag atc     1137 
Leu Trp Asp Lys Phe Ser Glu Leu Ala Thr Lys Cys Ile Ile Lys Ile 
                230                 235                 240 

gtg gag ttt gcc aag cgg ttg cct ggc ttt aca ggg ctc agc att gct     1185 
Val Glu Phe Ala Lys Arg Leu Pro Gly Phe Thr Gly Leu Ser Ile Ala 
            245                 250                 255 

gac cag atc act ctg ctc aaa gct gcc tgc cta gat atc ctg atg ctg     1233 
Asp Gln Ile Thr Leu Leu Lys Ala Ala Cys Leu Asp Ile Leu Met Leu 
        260                 265                 270 

cgt atc tgc aca agg tac acc cca gag cag gac acc atg acc ttc tcc     1281 
Arg Ile Cys Thr Arg Tyr Thr Pro Glu Gln Asp Thr Met Thr Phe Ser 
    275                 280                 285 

gac ggg ctg acc ctg aac cgg acc cag atg cac aat gcc ggc ttc ggg     1329 
Asp Gly Leu Thr Leu Asn Arg Thr Gln Met His Asn Ala Gly Phe Gly 
290                 295                 300                 305 

ccc ctc aca gac ctt gtc ttt gcc ttt gct ggg cag ctc ctg ccc ctg     1377 
Pro Leu Thr Asp Leu Val Phe Ala Phe Ala Gly Gln Leu Leu Pro Leu 
                310                 315                 320 

gag atg gat gac acc gag aca ggg ctg ctc agc gcc atc tgc ctc atc     1425 
Glu Met Asp Asp Thr Glu Thr Gly Leu Leu Ser Ala Ile Cys Leu Ile 
            325                 330                 335 

tgc gga gac cgc atg gac ctg gag gag ccc gaa aaa gtg gac aag ctg     1473 
Cys Gly Asp Arg Met Asp Leu Glu Glu Pro Glu Lys Val Asp Lys Leu 
        340                 345                 350 

cag gag cca ctg ctg gaa gcc ctg agg ctg tac gcc cgg cgc cgg cgg     1521 
Gln Glu Pro Leu Leu Glu Ala Leu Arg Leu Tyr Ala Arg Arg Arg Arg 
    355                 360                 365 

ccc agc cag ccc tac atg ttc cca agg atg cta atg aaa atc acc gac     1569 
Pro Ser Gln Pro Tyr Met Phe Pro Arg Met Leu Met Lys Ile Thr Asp 
370                 375                 380                 385 

ctc cgg ggc atc agc act aag gga gct gaa agg gcc att act ctg aag     1617 
Leu Arg Gly Ile Ser Thr Lys Gly Ala Glu Arg Ala Ile Thr Leu Lys 
                390                 395                 400 

atg gag att cca ggc ccg atg cct ccc tta atc cga gag atg ctg gag     1665 
Met Glu Ile Pro Gly Pro Met Pro Pro Leu Ile Arg Glu Met Leu Glu 
            405                 410                 415 

aac cct gaa atg ttt gag gat gac tcc tcg cag cct ggt ccc cac ccc     1713 
Asn Pro Glu Met Phe Glu Asp Asp Ser Ser Gln Pro Gly Pro His Pro 
        420                 425                 430 

aat gcc tct agc gag gat gag gtt cct ggg ggc cag ggc aaa ggg ggc     1761 
Asn Ala Ser Ser Glu Asp Glu Val Pro Gly Gly Gln Gly Lys Gly Gly 
    435                 440                 445 

ctg aag tcc cca gcc tgaccagggc ccctgacctc cccgctgtgg gggttggggc     1816 
Leu Lys Ser Pro Ala 
450 

ttcaggcagc agactgacca tctcccagac cgccagtgac tgggggagga cctgctctgc   1876 

cctctcccca accccttcca atgagcg                                       1903 

 
           
             2  
             454  
             PRT  
             Homo sapiens  
           
            2 

Met Ala Thr Asn Lys Glu Arg Leu Phe Ala Ala Gly Ala Leu Gly Pro 
1               5                   10                  15 

Gly Ser Gly Tyr Pro Gly Ala Gly Phe Pro Phe Ala Phe Pro Gly Ala 
            20                  25                  30 

Leu Arg Gly Ser Pro Pro Phe Glu Met Leu Ser Pro Ser Phe Arg Gly 
        35                  40                  45 

Leu Gly Gln Pro Asp Leu Pro Lys Glu Met Ala Ser Leu Ser Val Glu 
    50                  55                  60 

Thr Gln Ser Thr Ser Ser Glu Glu Met Val Pro Ser Ser Pro Ser Pro 
65                  70                  75                  80 

Pro Pro Pro Pro Arg Val Tyr Lys Pro Cys Phe Val Cys Asn Asp Lys 
                85                  90                  95 

Ser Ser Gly Tyr His Tyr Gly Val Ser Ser Cys Glu Gly Cys Lys Gly 
            100                 105                 110 

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

Asp Lys Asn Cys Ile Ile Asn Lys Val Thr Arg Asn Arg Cys Gln Tyr 
    130                 135                 140 

Cys Arg Leu Gln Lys Cys Phe Glu Val Gly Met Ser Lys Glu Ala Val 
145                 150                 155                 160 

Arg Asn Asp Arg Asn Lys Lys Lys Lys Glu Val Lys Glu Glu Gly Ser 
                165                 170                 175 

Pro Asp Ser Tyr Glu Leu Ser Pro Gln Leu Glu Glu Leu Ile Thr Lys 
            180                 185                 190 

Val Ser Lys Ala His Gln Glu Thr Phe Pro Ser Leu Cys Gln Leu Gly 
        195                 200                 205 

Lys Tyr Thr Thr Asn Ser Ser Ala Asp His Arg Val Gln Leu Asp Leu 
    210                 215                 220 

Gly Leu Trp Asp Lys Phe Ser Glu Leu Ala Thr Lys Cys Ile Ile Lys 
225                 230                 235                 240 

Ile Val Glu Phe Ala Lys Arg Leu Pro Gly Phe Thr Gly Leu Ser Ile 
                245                 250                 255 

Ala Asp Gln Ile Thr Leu Leu Lys Ala Ala Cys Leu Asp Ile Leu Met 
            260                 265                 270 

Leu Arg Ile Cys Thr Arg Tyr Thr Pro Glu Gln Asp Thr Met Thr Phe 
        275                 280                 285 

Ser Asp Gly Leu Thr Leu Asn Arg Thr Gln Met His Asn Ala Gly Phe 
    290                 295                 300 

Gly Pro Leu Thr Asp Leu Val Phe Ala Phe Ala Gly Gln Leu Leu Pro 
305                 310                 315                 320 

Leu Glu Met Asp Asp Thr Glu Thr Gly Leu Leu Ser Ala Ile Cys Leu 
                325                 330                 335 

Ile Cys Gly Asp Arg Met Asp Leu Glu Glu Pro Glu Lys Val Asp Lys 
            340                 345                 350 

Leu Gln Glu Pro Leu Leu Glu Ala Leu Arg Leu Tyr Ala Arg Arg Arg 
        355                 360                 365 

Arg Pro Ser Gln Pro Tyr Met Phe Pro Arg Met Leu Met Lys Ile Thr 
    370                 375                 380 

Asp Leu Arg Gly Ile Ser Thr Lys Gly Ala Glu Arg Ala Ile Thr Leu 
385                 390                 395                 400 

Lys Met Glu Ile Pro Gly Pro Met Pro Pro Leu Ile Arg Glu Met Leu 
                405                 410                 415 

Glu Asn Pro Glu Met Phe Glu Asp Asp Ser Ser Gln Pro Gly Pro His 
            420                 425                 430 

Pro Asn Ala Ser Ser Glu Asp Glu Val Pro Gly Gly Gln Gly Lys Gly 
        435                 440                 445 

Gly Leu Lys Ser Pro Ala 
    450 

 
           
             3  
             1515  
             DNA  
             Homo sapiens  
             
               CDS  
               (40)..(1164)  
             
           
            3 

ccactgcaga ccccagggga ctctcacacc gcagctgcc atg gcc acc aat aag        54 
                                           Met Ala Thr Asn Lys 
                                           1               5 

gag cga ctc ttt gcg gct ggt gcc ctg ggg cct gga tct ggc tac cca      102 
Glu Arg Leu Phe Ala Ala Gly Ala Leu Gly Pro Gly Ser Gly Tyr Pro 
                10                  15                  20 

ggg gca ggt ttc ccc ttc gcc ttc cca ggg gca ctc agg ggg tct ccg      150 
Gly Ala Gly Phe Pro Phe Ala Phe Pro Gly Ala Leu Arg Gly Ser Pro 
            25                  30                  35 

cct ttc gag atg ctg agc cct agc ttc cgg ggc ctg ggc cag cct gac      198 
Pro Phe Glu Met Leu Ser Pro Ser Phe Arg Gly Leu Gly Gln Pro Asp 
        40                  45                  50 

ctc ccc aag gag atg gcc tct ctg tcg gtg gag aca cag agc acc agc      246 
Leu Pro Lys Glu Met Ala Ser Leu Ser Val Glu Thr Gln Ser Thr Ser 
    55                  60                  65 

tca gag gag atg gtg ccc agc tcg ccc tcg ccc cct ccg cct cct cgg      294 
Ser Glu Glu Met Val Pro Ser Ser Pro Ser Pro Pro Pro Pro Pro Arg 
70                  75                  80                  85 

gtc tac aag cca tgc ttc gtg tgc aat gac aag tcc tct ggc tac cac      342 
Val Tyr Lys Pro Cys Phe Val Cys Asn Asp Lys Ser Ser Gly Tyr His 
                90                  95                  100 

tat ggg gtc agc tct tgt gaa ggc tgc aag ggc ttc ttt cgc cga agc      390 
Tyr Gly Val Ser Ser Cys Glu Gly Cys Lys Gly Phe Phe Arg Arg Ser 
            105                 110                 115 

atc cag aag aac atg gtg tac acg tgt cac cgc gac aaa aac tgt atc      438 
Ile Gln Lys Asn Met Val Tyr Thr Cys His Arg Asp Lys Asn Cys Ile 
        120                 125                 130 

atc aac aag gtg acc agg aat cgc tgc cag tac tgc cgg cta cag aag      486 
Ile Asn Lys Val Thr Arg Asn Arg Cys Gln Tyr Cys Arg Leu Gln Lys 
    135                 140                 145 

tgc ttc gaa gtg ggc atg tcc aag gaa gct gtg cga aat gac cgg aac      534 
Cys Phe Glu Val Gly Met Ser Lys Glu Ala Val Arg Asn Asp Arg Asn 
150                 155                 160                 165 

aag aag aag aaa gag gtg aag gaa gaa ggg tca cct gac agc tat gag      582 
Lys Lys Lys Lys Glu Val Lys Glu Glu Gly Ser Pro Asp Ser Tyr Glu 
                170                 175                 180 

ctg agc cct cag tta gaa gag ctc atc acc aag gtc agc aaa gcc cat      630 
Leu Ser Pro Gln Leu Glu Glu Leu Ile Thr Lys Val Ser Lys Ala His 
            185                 190                 195 

cag gag act ttc ccc tcg ctc tgc cag ctg ggc aag tat acc acg aac      678 
Gln Glu Thr Phe Pro Ser Leu Cys Gln Leu Gly Lys Tyr Thr Thr Asn 
        200                 205                 210 

tcc agt gca gac cac cgc gtg cag ctg gat ctg ggg ctg tgg gac aag      726 
Ser Ser Ala Asp His Arg Val Gln Leu Asp Leu Gly Leu Trp Asp Lys 
    215                 220                 225 

ttc agt gag ctg gct acc aag tgc atc atc aag atc gtg gag ttt gcc      774 
Phe Ser Glu Leu Ala Thr Lys Cys Ile Ile Lys Ile Val Glu Phe Ala 
230                 235                 240                 245 

aag cgg ttg cct ggc ttt aca ggg ctc agc att gct gac cag atc act      822 
Lys Arg Leu Pro Gly Phe Thr Gly Leu Ser Ile Ala Asp Gln Ile Thr 
                250                 255                 260 

ctg ctc aaa gct gcc tgc cta gat atc ctg atg ctg cgt atc tgc aca      870 
Leu Leu Lys Ala Ala Cys Leu Asp Ile Leu Met Leu Arg Ile Cys Thr 
            265                 270                 275 

agg tac acc cca gag cag gac acc atg acc ttc tcc gac ggg ctg acc      918 
Arg Tyr Thr Pro Glu Gln Asp Thr Met Thr Phe Ser Asp Gly Leu Thr 
        280                 285                 290 

ctg aac cgg acc cag atg cac aat gcc ggc ttc ggg ccc ctc aca gac      966 
Leu Asn Arg Thr Gln Met His Asn Ala Gly Phe Gly Pro Leu Thr Asp 
    295                 300                 305 

ctt gtc ttt gcc ttt gct ggg cag ctc ctg ccc ctg gag atg gat gac     1014 
Leu Val Phe Ala Phe Ala Gly Gln Leu Leu Pro Leu Glu Met Asp Asp 
310                 315                 320                 325 

acc gag aca ggg ctg ctc agc gcc atc tgc ctc atc tgc gga ggt gcg     1062 
Thr Glu Thr Gly Leu Leu Ser Ala Ile Cys Leu Ile Cys Gly Gly Ala 
                330                 335                 340 

ggg gcg ccc cct ggc gtc tgc tca gtg ctc agt ctc ctt tcc cac cac     1110 
Gly Ala Pro Pro Gly Val Cys Ser Val Leu Ser Leu Leu Ser His His 
            345                 350                 355 

tcc atg cgg aat ctg tct ggg agg ggg cgt gga gga ccc agt ggt ctc     1158 
Ser Met Arg Asn Leu Ser Gly Arg Gly Arg Gly Gly Pro Ser Gly Leu 
        360                 365                 370 

ttc tgc tgaccgcatg gacctggagg agcccgaaaa agtggacaag ctgcaggagc      1214 
Phe Cys 
    375 

cactgctgga agccctgagg ctgtacgccc ggcgccggcg gcccagccag ccctacatgt   1274 

tcccaaggat gctaatgaaa atcaccgacc tccggggcat cagcactaag ggagctgaaa   1334 

gggccattac tctgaagatg gagattccag gcccgatgcc tcccttaatc cgagagatgc   1394 

tggagaaccc tgaaatgttt gaggatgact cctcgcagcc tggtccccac cccaatgcct   1454 

ctagcgagga tgaggttcct gggggccagg gcaaaggggg cctgaagtcc ccagcctgac   1514 

c                                                                   1515 

 
           
             4  
             375  
             PRT  
             Homo sapiens  
           
            4 

Met Ala Thr Asn Lys Glu Arg Leu Phe Ala Ala Gly Ala Leu Gly Pro 
1               5                   10                  15 

Gly Ser Gly Tyr Pro Gly Ala Gly Phe Pro Phe Ala Phe Pro Gly Ala 
            20                  25                  30 

Leu Arg Gly Ser Pro Pro Phe Glu Met Leu Ser Pro Ser Phe Arg Gly 
        35                  40                  45 

Leu Gly Gln Pro Asp Leu Pro Lys Glu Met Ala Ser Leu Ser Val Glu 
    50                  55                  60 

Thr Gln Ser Thr Ser Ser Glu Glu Met Val Pro Ser Ser Pro Ser Pro 
65                  70                  75                  80 

Pro Pro Pro Pro Arg Val Tyr Lys Pro Cys Phe Val Cys Asn Asp Lys 
                85                  90                  95 

Ser Ser Gly Tyr His Tyr Gly Val Ser Ser Cys Glu Gly Cys Lys Gly 
            100                 105                 110 

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

Asp Lys Asn Cys Ile Ile Asn Lys Val Thr Arg Asn Arg Cys Gln Tyr 
    130                 135                 140 

Cys Arg Leu Gln Lys Cys Phe Glu Val Gly Met Ser Lys Glu Ala Val 
145                 150                 155                 160 

Arg Asn Asp Arg Asn Lys Lys Lys Lys Glu Val Lys Glu Glu Gly Ser 
                165                 170                 175 

Pro Asp Ser Tyr Glu Leu Ser Pro Gln Leu Glu Glu Leu Ile Thr Lys 
            180                 185                 190 

Val Ser Lys Ala His Gln Glu Thr Phe Pro Ser Leu Cys Gln Leu Gly 
        195                 200                 205 

Lys Tyr Thr Thr Asn Ser Ser Ala Asp His Arg Val Gln Leu Asp Leu 
    210                 215                 220 

Gly Leu Trp Asp Lys Phe Ser Glu Leu Ala Thr Lys Cys Ile Ile Lys 
225                 230                 235                 240 

Ile Val Glu Phe Ala Lys Arg Leu Pro Gly Phe Thr Gly Leu Ser Ile 
                245                 250                 255 

Ala Asp Gln Ile Thr Leu Leu Lys Ala Ala Cys Leu Asp Ile Leu Met 
            260                 265                 270 

Leu Arg Ile Cys Thr Arg Tyr Thr Pro Glu Gln Asp Thr Met Thr Phe 
        275                 280                 285 

Ser Asp Gly Leu Thr Leu Asn Arg Thr Gln Met His Asn Ala Gly Phe 
    290                 295                 300 

Gly Pro Leu Thr Asp Leu Val Phe Ala Phe Ala Gly Gln Leu Leu Pro 
305                 310                 315                 320 

Leu Glu Met Asp Asp Thr Glu Thr Gly Leu Leu Ser Ala Ile Cys Leu 
                325                 330                 335 

Ile Cys Gly Gly Ala Gly Ala Pro Pro Gly Val Cys Ser Val Leu Ser 
            340                 345                 350 

Leu Leu Ser His His Ser Met Arg Asn Leu Ser Gly Arg Gly Arg Gly 
        355                 360                 365 

Gly Pro Ser Gly Leu Phe Cys 
    370                 375 

 
           
             5  
             1807  
             DNA  
             Homo sapiens  
             
               CDS  
               (3)..(1799)  
             
           
            5 

cc atg agc cgg agt ctc ttg ctc cgg ttc ttg ctg ttc ctg ctc ctg        47 
   Met Ser Arg Ser Leu Leu Leu Arg Phe Leu Leu Phe Leu Leu Leu 
   1               5                   10                  15 

ctc ccg ccg ctc ccc gtc ctg ctc gcg gac cca ggg gcg ccc acg cca       95 
Leu Pro Pro Leu Pro Val Leu Leu Ala Asp Pro Gly Ala Pro Thr Pro 
                20                  25                  30 

gtg aat ccc tgt tgt tac tat cca tgc cag cac cag ggc atc tgt gtc      143 
Val Asn Pro Cys Cys Tyr Tyr Pro Cys Gln His Gln Gly Ile Cys Val 
            35                  40                  45 

cgc ttc ggc ctt gac cgc tac cag tgt gac tgc acc cgc acg ggc tat      191 
Arg Phe Gly Leu Asp Arg Tyr Gln Cys Asp Cys Thr Arg Thr Gly Tyr 
        50                  55                  60 

tcc ggc ccc aac tgc acc atc cct ggc ctg tgg acc tgg ctc cgg aat      239 
Ser Gly Pro Asn Cys Thr Ile Pro Gly Leu Trp Thr Trp Leu Arg Asn 
    65                  70                  75 

tca ctg cgg ccc agc ccc tct ttc acc cac ttc ctg ctc act cac ggg      287 
Ser Leu Arg Pro Ser Pro Ser Phe Thr His Phe Leu Leu Thr His Gly 
80                  85                  90                  95 

cgc tgg ttc tgg gag ttt gtc aat gcc acc ttc atc cga gag atg ctc      335 
Arg Trp Phe Trp Glu Phe Val Asn Ala Thr Phe Ile Arg Glu Met Leu 
                100                 105                 110 

atg cgc ctg gta ctc aca gtg cgc tcc aac ctt atc ccc agt ccc ccc      383 
Met Arg Leu Val Leu Thr Val Arg Ser Asn Leu Ile Pro Ser Pro Pro 
            115                 120                 125 

acc tac aac tca gca cat gac tac atc agc tgg gag tct ttc tcc aac      431 
Thr Tyr Asn Ser Ala His Asp Tyr Ile Ser Trp Glu Ser Phe Ser Asn 
        130                 135                 140 

gtg agc tat tac act cgt att ctg ccc tct gtg cct aaa gat tgc ccc      479 
Val Ser Tyr Tyr Thr Arg Ile Leu Pro Ser Val Pro Lys Asp Cys Pro 
    145                 150                 155 

aca ccc atg gga acc aaa ggg aag aag cag ttg cca gat gcc cag ctc      527 
Thr Pro Met Gly Thr Lys Gly Lys Lys Gln Leu Pro Asp Ala Gln Leu 
160                 165                 170                 175 

ctg gcc cgc cgc ttc ctg ctc agg agg aag ttc ata cct gac ccc caa      575 
Leu Ala Arg Arg Phe Leu Leu Arg Arg Lys Phe Ile Pro Asp Pro Gln 
                180                 185                 190 

ggc acc aac ctc atg ttt gcc ttc ttt gca caa cac ttc acc cac cag      623 
Gly Thr Asn Leu Met Phe Ala Phe Phe Ala Gln His Phe Thr His Gln 
            195                 200                 205 

ttc ttc aaa act tct ggc aag atg ggt cct ggc ttc acc aag gcc ttg      671 
Phe Phe Lys Thr Ser Gly Lys Met Gly Pro Gly Phe Thr Lys Ala Leu 
        210                 215                 220 

ggc cat ggg gta gac ctc ggc cac att tat gga gac aat ctg gag cgt      719 
Gly His Gly Val Asp Leu Gly His Ile Tyr Gly Asp Asn Leu Glu Arg 
    225                 230                 235 

cag tat caa ctg cgg ctc ttt aag gat ggg aaa ctc aag tac cag gtg      767 
Gln Tyr Gln Leu Arg Leu Phe Lys Asp Gly Lys Leu Lys Tyr Gln Val 
240                 245                 250                 255 

ctg gat gga gaa atg tac ccg ccc tcg gta gaa gag gcg cct gtg ttg      815 
Leu Asp Gly Glu Met Tyr Pro Pro Ser Val Glu Glu Ala Pro Val Leu 
                260                 265                 270 

atg cac tac ccc cga ggc atc ccg ccc cag agc cag atg gct gtg ggc      863 
Met His Tyr Pro Arg Gly Ile Pro Pro Gln Ser Gln Met Ala Val Gly 
            275                 280                 285 

cag gag gtg ttt ggg ctg ctt cct ggg ctc atg ctg tat gcc acg ctc      911 
Gln Glu Val Phe Gly Leu Leu Pro Gly Leu Met Leu Tyr Ala Thr Leu 
        290                 295                 300 

tgg cta cgt gag cac aac cgt gtg tgt gac ctg ctg aag gct gag cac      959 
Trp Leu Arg Glu His Asn Arg Val Cys Asp Leu Leu Lys Ala Glu His 
    305                 310                 315 

ccc acc tgg ggc gat gag cag ctt ttc cag acg acc cgc ctc atc ctc     1007 
Pro Thr Trp Gly Asp Glu Gln Leu Phe Gln Thr Thr Arg Leu Ile Leu 
320                 325                 330                 335 

ata ggg gag acc atc aag att gtc atc gag gag tac gtg cag cag ctg     1055 
Ile Gly Glu Thr Ile Lys Ile Val Ile Glu Glu Tyr Val Gln Gln Leu 
                340                 345                 350 

agt ggc tat ttc ctg cag ctg aaa ttt gac cca gag ctg ctg ttc ggt     1103 
Ser Gly Tyr Phe Leu Gln Leu Lys Phe Asp Pro Glu Leu Leu Phe Gly 
            355                 360                 365 

gtc cag ttc caa tac cgc aac cgc att gcc atg gag ttc aac cat ctc     1151 
Val Gln Phe Gln Tyr Arg Asn Arg Ile Ala Met Glu Phe Asn His Leu 
        370                 375                 380 

tac cac tgg cac ccc ctc atg cct gac tcc ttc aag gtg ggc tcc cag     1199 
Tyr His Trp His Pro Leu Met Pro Asp Ser Phe Lys Val Gly Ser Gln 
    385                 390                 395 

gag tac agc tac gag cag ttc ttg ttc aac acc tcc atg ttg gtg gac     1247 
Glu Tyr Ser Tyr Glu Gln Phe Leu Phe Asn Thr Ser Met Leu Val Asp 
400                 405                 410                 415 

tat ggg gtt gag gcc ctg gtg gat gcc ttc tct cgc cag att gct ggc     1295 
Tyr Gly Val Glu Ala Leu Val Asp Ala Phe Ser Arg Gln Ile Ala Gly 
                420                 425                 430 

cgg atc ggt ggg ggc agg aac atg gac cac cac atc ctg cat gtg gct     1343 
Arg Ile Gly Gly Gly Arg Asn Met Asp His His Ile Leu His Val Ala 
            435                 440                 445 

gtg gat gtc atc agg gag tct cgg gag atg cgg ctg cag ccc ttc aat     1391 
Val Asp Val Ile Arg Glu Ser Arg Glu Met Arg Leu Gln Pro Phe Asn 
        450                 455                 460 

gag tac cgc aag agg ttt ggc atg aaa ccc tac acc tcc ttc cag gag     1439 
Glu Tyr Arg Lys Arg Phe Gly Met Lys Pro Tyr Thr Ser Phe Gln Glu 
    465                 470                 475 

ctc gta gga gag aag gag atg gca gca gag ttg gag gaa ttg tat gga     1487 
Leu Val Gly Glu Lys Glu Met Ala Ala Glu Leu Glu Glu Leu Tyr Gly 
480                 485                 490                 495 

gac att gat gcg ttg gag ttc tac cct gga ctg ctt ctt gaa aag tgc     1535 
Asp Ile Asp Ala Leu Glu Phe Tyr Pro Gly Leu Leu Leu Glu Lys Cys 
                500                 505                 510 

cat cca aac tct atc ttt ggg gag agt atg ata gag att ggg gct ccc     1583 
His Pro Asn Ser Ile Phe Gly Glu Ser Met Ile Glu Ile Gly Ala Pro 
            515                 520                 525 

ttt tcc ctc aag ggt ctc cta ggg aat ccc atc tgt tct ccg gag tac     1631 
Phe Ser Leu Lys Gly Leu Leu Gly Asn Pro Ile Cys Ser Pro Glu Tyr 
        530                 535                 540 

tgg aag ccg agc aca ttt ggc ggc gag gtg ggc ttt aac att gtc aag     1679 
Trp Lys Pro Ser Thr Phe Gly Gly Glu Val Gly Phe Asn Ile Val Lys 
    545                 550                 555 

acg gcc aca ctg aag aag ctg gtc tgc ctc aac acc aag acc tgt ccc     1727 
Thr Ala Thr Leu Lys Lys Leu Val Cys Leu Asn Thr Lys Thr Cys Pro 
560                 565                 570                 575 

tac gtt tcc ttc cgt gtg ccg gat gcc agt cag gat gat ggg cct gct     1775 
Tyr Val Ser Phe Arg Val Pro Asp Ala Ser Gln Asp Asp Gly Pro Ala 
                580                 585                 590 

gtg gag cga cca tcc aca gag ctc tgaggggc                            1807 
Val Glu Arg Pro Ser Thr Glu Leu 
            595 

 
           
             6  
             599  
             PRT  
             Homo sapiens  
           
            6 

Met Ser Arg Ser Leu Leu Leu Arg Phe Leu Leu Phe Leu Leu Leu Leu 
1               5                   10                  15 

Pro Pro Leu Pro Val Leu Leu Ala Asp Pro Gly Ala Pro Thr Pro Val 
            20                  25                  30 

Asn Pro Cys Cys Tyr Tyr Pro Cys Gln His Gln Gly Ile Cys Val Arg 
        35                  40                  45 

Phe Gly Leu Asp Arg Tyr Gln Cys Asp Cys Thr Arg Thr Gly Tyr Ser 
    50                  55                  60 

Gly Pro Asn Cys Thr Ile Pro Gly Leu Trp Thr Trp Leu Arg Asn Ser 
65                  70                  75                  80 

Leu Arg Pro Ser Pro Ser Phe Thr His Phe Leu Leu Thr His Gly Arg 
                85                  90                  95 

Trp Phe Trp Glu Phe Val Asn Ala Thr Phe Ile Arg Glu Met Leu Met 
            100                 105                 110 

Arg Leu Val Leu Thr Val Arg Ser Asn Leu Ile Pro Ser Pro Pro Thr 
        115                 120                 125 

Tyr Asn Ser Ala His Asp Tyr Ile Ser Trp Glu Ser Phe Ser Asn Val 
    130                 135                 140 

Ser Tyr Tyr Thr Arg Ile Leu Pro Ser Val Pro Lys Asp Cys Pro Thr 
145                 150                 155                 160 

Pro Met Gly Thr Lys Gly Lys Lys Gln Leu Pro Asp Ala Gln Leu Leu 
                165                 170                 175 

Ala Arg Arg Phe Leu Leu Arg Arg Lys Phe Ile Pro Asp Pro Gln Gly 
            180                 185                 190 

Thr Asn Leu Met Phe Ala Phe Phe Ala Gln His Phe Thr His Gln Phe 
        195                 200                 205 

Phe Lys Thr Ser Gly Lys Met Gly Pro Gly Phe Thr Lys Ala Leu Gly 
    210                 215                 220 

His Gly Val Asp Leu Gly His Ile Tyr Gly Asp Asn Leu Glu Arg Gln 
225                 230                 235                 240 

Tyr Gln Leu Arg Leu Phe Lys Asp Gly Lys Leu Lys Tyr Gln Val Leu 
                245                 250                 255 

Asp Gly Glu Met Tyr Pro Pro Ser Val Glu Glu Ala Pro Val Leu Met 
            260                 265                 270 

His Tyr Pro Arg Gly Ile Pro Pro Gln Ser Gln Met Ala Val Gly Gln 
        275                 280                 285 

Glu Val Phe Gly Leu Leu Pro Gly Leu Met Leu Tyr Ala Thr Leu Trp 
    290                 295                 300 

Leu Arg Glu His Asn Arg Val Cys Asp Leu Leu Lys Ala Glu His Pro 
305                 310                 315                 320 

Thr Trp Gly Asp Glu Gln Leu Phe Gln Thr Thr Arg Leu Ile Leu Ile 
                325                 330                 335 

Gly Glu Thr Ile Lys Ile Val Ile Glu Glu Tyr Val Gln Gln Leu Ser 
            340                 345                 350 

Gly Tyr Phe Leu Gln Leu Lys Phe Asp Pro Glu Leu Leu Phe Gly Val 
        355                 360                 365 

Gln Phe Gln Tyr Arg Asn Arg Ile Ala Met Glu Phe Asn His Leu Tyr 
    370                 375                 380 

His Trp His Pro Leu Met Pro Asp Ser Phe Lys Val Gly Ser Gln Glu 
385                 390                 395                 400 

Tyr Ser Tyr Glu Gln Phe Leu Phe Asn Thr Ser Met Leu Val Asp Tyr 
                405                 410                 415 

Gly Val Glu Ala Leu Val Asp Ala Phe Ser Arg Gln Ile Ala Gly Arg 
            420                 425                 430 

Ile Gly Gly Gly Arg Asn Met Asp His His Ile Leu His Val Ala Val 
        435                 440                 445 

Asp Val Ile Arg Glu Ser Arg Glu Met Arg Leu Gln Pro Phe Asn Glu 
    450                 455                 460 

Tyr Arg Lys Arg Phe Gly Met Lys Pro Tyr Thr Ser Phe Gln Glu Leu 
465                 470                 475                 480 

Val Gly Glu Lys Glu Met Ala Ala Glu Leu Glu Glu Leu Tyr Gly Asp 
                485                 490                 495 

Ile Asp Ala Leu Glu Phe Tyr Pro Gly Leu Leu Leu Glu Lys Cys His 
            500                 505                 510 

Pro Asn Ser Ile Phe Gly Glu Ser Met Ile Glu Ile Gly Ala Pro Phe 
        515                 520                 525 

Ser Leu Lys Gly Leu Leu Gly Asn Pro Ile Cys Ser Pro Glu Tyr Trp 
    530                 535                 540 

Lys Pro Ser Thr Phe Gly Gly Glu Val Gly Phe Asn Ile Val Lys Thr 
545                 550                 555                 560 

Ala Thr Leu Lys Lys Leu Val Cys Leu Asn Thr Lys Thr Cys Pro Tyr 
                565                 570                 575 

Val Ser Phe Arg Val Pro Asp Ala Ser Gln Asp Asp Gly Pro Ala Val 
            580                 585                 590 

Glu Arg Pro Ser Thr Glu Leu 
        595 

 
           
             7  
             1713  
             DNA  
             Homo sapiens  
             
               CDS  
               (6)..(1658)  
             
           
            7 

gcgcc atg agc cgg agt ctc ttg ctc cgg ttc ttg ctg ttc ctg ctc ctg     50 
      Met Ser Arg Ser Leu Leu Leu Arg Phe Leu Leu Phe Leu Leu Leu 
      1               5                   10                  15 

ctc ccg ccg ctc ccc gtc ctg ctc gcg gac cca ggg gcg ccc acg cca       98 
Leu Pro Pro Leu Pro Val Leu Leu Ala Asp Pro Gly Ala Pro Thr Pro 
                20                  25                  30 

gtg aat ccc tgt tgt tac tat cca tgc cag cac cag ggc atc tgt gtc      146 
Val Asn Pro Cys Cys Tyr Tyr Pro Cys Gln His Gln Gly Ile Cys Val 
            35                  40                  45 

cgc ttc ggc ctt gac cgc tac cag tgt gac tgc acc cgc acg ggc tat      194 
Arg Phe Gly Leu Asp Arg Tyr Gln Cys Asp Cys Thr Arg Thr Gly Tyr 
        50                  55                  60 

tcc ggc ccc aac tgc acc atc cct ggc ctg tgg acc tgg ctc cgg aat      242 
Ser Gly Pro Asn Cys Thr Ile Pro Gly Leu Trp Thr Trp Leu Arg Asn 
    65                  70                  75 

tca ctg cgg ccc agc ccc tct ttc acc cac ttc ctg ctc act cac ggg      290 
Ser Leu Arg Pro Ser Pro Ser Phe Thr His Phe Leu Leu Thr His Gly 
80                  85                  90                  95 

cgc tgg ttc tgg gag ttt gtc aat gcc acc ttc atc cga gag atg ctc      338 
Arg Trp Phe Trp Glu Phe Val Asn Ala Thr Phe Ile Arg Glu Met Leu 
                100                 105                 110 

atg cgc ctg gta ctc aca ggg aag aag cag ttg cca gat gcc cag ctc      386 
Met Arg Leu Val Leu Thr Gly Lys Lys Gln Leu Pro Asp Ala Gln Leu 
            115                 120                 125 

ctg gcc cgc cgc ttc ctg ctc ggg agg aag ttc ata cct gac ccc caa      434 
Leu Ala Arg Arg Phe Leu Leu Gly Arg Lys Phe Ile Pro Asp Pro Gln 
        130                 135                 140 

ggc acc aac ctc atg ttt gcc ttc ttt gca caa cac ttc acc cac cag      482 
Gly Thr Asn Leu Met Phe Ala Phe Phe Ala Gln His Phe Thr His Gln 
    145                 150                 155 

ttc ttc aaa act tct ggc aag atg ggt cct ggc ttc acc aag gcc ttg      530 
Phe Phe Lys Thr Ser Gly Lys Met Gly Pro Gly Phe Thr Lys Ala Leu 
160                 165                 170                 175 

ggc cat ggg gta gac ctc ggc cac att tat gga gac aat ctg gag cgt      578 
Gly His Gly Val Asp Leu Gly His Ile Tyr Gly Asp Asn Leu Glu Arg 
                180                 185                 190 

cag tat caa ctg cgg ctc ttt aag gat ggg aaa ctc aag tac cag gtg      626 
Gln Tyr Gln Leu Arg Leu Phe Lys Asp Gly Lys Leu Lys Tyr Gln Val 
            195                 200                 205 

ctg gat gga gaa atg tac ccg ccc tcg gta gaa gag gcg cct gtg ttg      674 
Leu Asp Gly Glu Met Tyr Pro Pro Ser Val Glu Glu Ala Pro Val Leu 
        210                 215                 220 

atg cac tac ccc cga ggc atc ccg ccc cag agc cag atg gct gtg ggc      722 
Met His Tyr Pro Arg Gly Ile Pro Pro Gln Ser Gln Met Ala Val Gly 
    225                 230                 235 

cag gag gtg ttt ggg ctg ctt cct ggg ctc atg ctg tat gcc acg ctc      770 
Gln Glu Val Phe Gly Leu Leu Pro Gly Leu Met Leu Tyr Ala Thr Leu 
240                 245                 250                 255 

tgg cta cgt gag cac aac cgt gtg tgt gac ctg ctg aag gct gag cac      818 
Trp Leu Arg Glu His Asn Arg Val Cys Asp Leu Leu Lys Ala Glu His 
                260                 265                 270 

ccc acc tgg ggc gat gag cag ctt ttc cag acg acc cgc ctc atc ctc      866 
Pro Thr Trp Gly Asp Glu Gln Leu Phe Gln Thr Thr Arg Leu Ile Leu 
            275                 280                 285 

ata ggg gag acc atc aag att gtc atc gag gag tac gtg cag cag ctg      914 
Ile Gly Glu Thr Ile Lys Ile Val Ile Glu Glu Tyr Val Gln Gln Leu 
        290                 295                 300 

agt ggc tat ttc ctg cag ctg aaa ttt gac cca gag ctg ctg ttc ggt      962 
Ser Gly Tyr Phe Leu Gln Leu Lys Phe Asp Pro Glu Leu Leu Phe Gly 
    305                 310                 315 

gtc cag ttc caa tac cgc aac cgc att gcc atg gag ttc aac cat ctc     1010 
Val Gln Phe Gln Tyr Arg Asn Arg Ile Ala Met Glu Phe Asn His Leu 
320                 325                 330                 335 

tac cac tgg cac ccc ctc atg cct gac tcc ttc aag gtg ggc tcc cag     1058 
Tyr His Trp His Pro Leu Met Pro Asp Ser Phe Lys Val Gly Ser Gln 
                340                 345                 350 

gag tac agc tac gag cag ttc ttg ttc aac acc tcc atg ttg gtg gac     1106 
Glu Tyr Ser Tyr Glu Gln Phe Leu Phe Asn Thr Ser Met Leu Val Asp 
            355                 360                 365 

tat ggg gtt gag gcc ctg gtg gat gcc ttc tct cgc cag att gct ggc     1154 
Tyr Gly Val Glu Ala Leu Val Asp Ala Phe Ser Arg Gln Ile Ala Gly 
        370                 375                 380 

cgg atc ggt ggg ggc agg aac atg gac cac cac atc ctg cat gtg gct     1202 
Arg Ile Gly Gly Gly Arg Asn Met Asp His His Ile Leu His Val Ala 
    385                 390                 395 

gtg gat gtc atc agg gag tct cgg gag atg cgg ctg cag ccc ttc aat     1250 
Val Asp Val Ile Arg Glu Ser Arg Glu Met Arg Leu Gln Pro Phe Asn 
400                 405                 410                 415 

gag tac cgc aag agg ttt ggc atg aaa ccc tac acc tcc ttc cag gag     1298 
Glu Tyr Arg Lys Arg Phe Gly Met Lys Pro Tyr Thr Ser Phe Gln Glu 
                420                 425                 430 

ctc gta gga gag aag gag atg gca gca gag ttg gag gaa ttg tat gga     1346 
Leu Val Gly Glu Lys Glu Met Ala Ala Glu Leu Glu Glu Leu Tyr Gly 
            435                 440                 445 

gac att gat gcg ttg gag ttc tac cct gga ctg ctt ctt gaa aag tgc     1394 
Asp Ile Asp Ala Leu Glu Phe Tyr Pro Gly Leu Leu Leu Glu Lys Cys 
        450                 455                 460 

cat cca aac tct atc ttt ggg gag agt atg ata gag att ggg gct ccc     1442 
His Pro Asn Ser Ile Phe Gly Glu Ser Met Ile Glu Ile Gly Ala Pro 
    465                 470                 475 

ttt tcc ctc aag ggt ctc cta ggg aat ccc atc tgt tct ccg gag tac     1490 
Phe Ser Leu Lys Gly Leu Leu Gly Asn Pro Ile Cys Ser Pro Glu Tyr 
480                 485                 490                 495 

tgg aag ccg agc aca ttt ggc ggc gag gtg ggc ttt aac att gtc aag     1538 
Trp Lys Pro Ser Thr Phe Gly Gly Glu Val Gly Phe Asn Ile Val Lys 
                500                 505                 510 

acg gcc aca ctg aag aag ctg gtc tgc ctc aac acc aag acc tgt ccc     1586 
Thr Ala Thr Leu Lys Lys Leu Val Cys Leu Asn Thr Lys Thr Cys Pro 
            515                 520                 525 

tac gtt tcc ttc cgt gtg ccg gat gcc agt cag gat gat ggg cct gct     1634 
Tyr Val Ser Phe Arg Val Pro Asp Ala Ser Gln Asp Asp Gly Pro Ala 
        530                 535                 540 

gtg gag cga cca tcc aca gag ctc tgaggggcag gaaagcagca ttctggaggg    1688 
Val Glu Arg Pro Ser Thr Glu Leu 
    545                 550 

gagagctttg tgcttgtcat tccag                                         1713 

 
           
             8  
             551  
             PRT  
             Homo sapiens  
           
            8 

Met Ser Arg Ser Leu Leu Leu Arg Phe Leu Leu Phe Leu Leu Leu Leu 
1               5                   10                  15 

Pro Pro Leu Pro Val Leu Leu Ala Asp Pro Gly Ala Pro Thr Pro Val 
            20                  25                  30 

Asn Pro Cys Cys Tyr Tyr Pro Cys Gln His Gln Gly Ile Cys Val Arg 
        35                  40                  45 

Phe Gly Leu Asp Arg Tyr Gln Cys Asp Cys Thr Arg Thr Gly Tyr Ser 
    50                  55                  60 

Gly Pro Asn Cys Thr Ile Pro Gly Leu Trp Thr Trp Leu Arg Asn Ser 
65                  70                  75                  80 

Leu Arg Pro Ser Pro Ser Phe Thr His Phe Leu Leu Thr His Gly Arg 
                85                  90                  95 

Trp Phe Trp Glu Phe Val Asn Ala Thr Phe Ile Arg Glu Met Leu Met 
            100                 105                 110 

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

Ala Arg Arg Phe Leu Leu Gly Arg Lys Phe Ile Pro Asp Pro Gln Gly 
    130                 135                 140 

Thr Asn Leu Met Phe Ala Phe Phe Ala Gln His Phe Thr His Gln Phe 
145                 150                 155                 160 

Phe Lys Thr Ser Gly Lys Met Gly Pro Gly Phe Thr Lys Ala Leu Gly 
                165                 170                 175 

His Gly Val Asp Leu Gly His Ile Tyr Gly Asp Asn Leu Glu Arg Gln 
            180                 185                 190 

Tyr Gln Leu Arg Leu Phe Lys Asp Gly Lys Leu Lys Tyr Gln Val Leu 
        195                 200                 205 

Asp Gly Glu Met Tyr Pro Pro Ser Val Glu Glu Ala Pro Val Leu Met 
    210                 215                 220 

His Tyr Pro Arg Gly Ile Pro Pro Gln Ser Gln Met Ala Val Gly Gln 
235                 230                 235                 240 

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

Leu Arg Glu His Asn Arg Val Cys Asp Leu Leu Lys Ala Glu His Pro 
            260                 265                 270 

Thr Trp Gly Asp Glu Gln Leu Phe Gln Thr Thr Arg Leu Ile Leu Ile 
        275                 280                 285 

Gly Glu Thr Ile Lys Ile Val Ile Glu Glu Tyr Val Gln Gln Leu Ser 
    290                 295                 300 

Gly Tyr Phe Leu Gln Leu Lys Phe Asp Pro Glu Leu Leu Phe Gly Val 
305                 310                 315                 320 

Gln Phe Gln Tyr Arg Asn Arg Ile Ala Met Glu Phe Asn His Leu Tyr 
                325                 330                 335 

His Trp His Pro Leu Met Pro Asp Ser Phe Lys Val Gly Ser Gln Glu 
            340                  345                 350 

Tyr Ser Tyr Glu Gln Phe Leu Phe Asn Thr Ser Met Leu Val Asp Tyr 
        355                 360                 365 

Gly Val Glu Ala Leu Val Asp Ala Phe Ser Arg Gln Ile Ala Gly Arg 
    370                 375                 380 

Ile Gly Gly Gly Arg Asn Met Asp His His Ile Leu His Val Ala Val 
385                 390                 395                 400 

Asp Val Ile Arg Glu Ser Arg Glu Met Arg Leu Gln Pro Phe Asn Glu 
                405                 410                 415 

Tyr Arg Lys Arg Phe Gly Met Lys Pro Tyr Thr Ser Phe Gln Glu Leu 
            420                 425                 430 

Val Gly Glu Lys Glu Met Ala Ala Glu Leu Glu Glu Leu Tyr Gly Asp 
        435                 440                 445 

Ile Asp Ala Leu Glu Phe Tyr Pro Gly Leu Leu Leu Glu Lys Cys His 
    450                 455                 460 

Pro Asn Ser Ile Phe Gly Glu Ser Met Ile Glu Ile Gly Ala Pro Phe 
465                 470                 475                 480 

Ser Leu Lys Gly Leu Leu Gly Asn Pro Ile Cys Ser Pro Glu Tyr Trp 
                485                 490                 495 

Lys Pro Ser Thr Phe Gly Gly Glu Val Gly Phe Asn Ile Val Lys Thr 
            500                 505                 510 

Ala Thr Leu Lys Lys Leu Val Cys Leu Asn Thr Lys Thr Cys Pro Tyr 
        515                 520                 525 

Val Ser Phe Arg Val Pro Asp Ala Ser Gln Asp Asp Gly Pro Ala Val 
    530                 535                 540 

Glu Arg Pro Ser Thr Glu Leu 
545                 550 

 
           
             9  
             2019  
             DNA  
             Homo sapiens  
             
               CDS  
               (61)..(1959)  
             
           
            9 

gatctgtgga ggtttttctc tgcaaatgca ggaagaaatc aggtggatgg atgcataatt     60 

atg gcc ctg ctc ctg gtc tct ttg ctg gca ttc ctg agc ttg ggc tca      108 
Met Ala Leu Leu Leu Val Ser Leu Leu Ala Phe Leu Ser Leu Gly Ser 
1               5                   10                  15 

gga tgt cat cat cgg atc tgt cac tgc tct aac agg gtt ttt ctc tgc      156 
Gly Cys His His Arg Ile Cys His Cys Ser Asn Arg Val Phe Leu Cys 
            20                  25                  30 

caa gag agc aag gtg aca gag att cct tct gac ctc ccg agg aat gcc      204 
Gln Glu Ser Lys Val Thr Glu Ile Pro Ser Asp Leu Pro Arg Asn Ala 
        35                  40                  45 

att gaa ctg agg ttt gtc ctc acc aag ctt cga gtc atc caa aaa ggt      252 
Ile Glu Leu Arg Phe Val Leu Thr Lys Leu Arg Val Ile Gln Lys Gly 
    50                  55                  60 

gca ttt tca gga ttt ggg gac ctg gag aaa ata gag atc tct cag aat      300 
Ala Phe Ser Gly Phe Gly Asp Leu Glu Lys Ile Glu Ile Ser Gln Asn 
65                  70                  75                  80 

gat gtc ttg gag gtg ata gag gca gat gtg ttc tcc aac ctt ccc aaa      348 
Asp Val Leu Glu Val Ile Glu Ala Asp Val Phe Ser Asn Leu Pro Lys 
                85                  90                  95 

tta cat gaa att aga att gaa aag gcc aac aac ctg ctc tac atc aac      396 
Leu His Glu Ile Arg Ile Glu Lys Ala Asn Asn Leu Leu Tyr Ile Asn 
            100                 105                 110 

cct gag gcc ttc cag aac ctt ccc aac ctt caa tat ctg tta ata tcc      444 
Pro Glu Ala Phe Gln Asn Leu Pro Asn Leu Gln Tyr Leu Leu Ile Ser 
        115                 120                 125 

aac aca ggt att aag cac ctt cca gat gtt cac aag att cat tct ctc      492 
Asn Thr Gly Ile Lys His Leu Pro Asp Val His Lys Ile His Ser Leu 
    130                 135                 140 

caa aaa gtt tta ctt gac att caa gat aac ata aac atc cac aca att      540 
Gln Lys Val Leu Leu Asp Ile Gln Asp Asn Ile Asn Ile His Thr Ile 
145                 150                 155                 160 

gaa aga aat tct ttc gtg ggg ctg agc ttt gaa agt gtg att cta tgg      588 
Glu Arg Asn Ser Phe Val Gly Leu Ser Phe Glu Ser Val Ile Leu Trp 
                165                 170                 175 

ctg aat aag aat ggg att caa gaa ata cac aac tgt gca ttc aat gga      636 
Leu Asn Lys Asn Gly Ile Gln Glu Ile His Asn Cys Ala Phe Asn Gly 
            180                 185                 190 

acc caa cta gat gag ctg aat cta agc gat aat aat aat tta gaa gaa      684 
Thr Gln Leu Asp Glu Leu Asn Leu Ser Asp Asn Asn Asn Leu Glu Glu 
        195                 200                 205 

ttg cct aat gat gtt ttc cac gga gcc tct gga cca gtc att ctc tct      732 
Leu Pro Asn Asp Val Phe His Gly Ala Ser Gly Pro Val Ile Leu Ser 
    210                 215                 220 

gag ctt cat cca att tgc aac aaa tct att tta agg caa gaa gtt gat      780 
Glu Leu His Pro Ile Cys Asn Lys Ser Ile Leu Arg Gln Glu Val Asp 
225                 230                 235                 240 

tat atg act cag gct agg ggt cag aga tcc tct ctg gca gaa gac aat      828 
Tyr Met Thr Gln Ala Arg Gly Gln Arg Ser Ser Leu Ala Glu Asp Asn 
                245                 250                 255 

gag tcc agc tac agc aga gga ttt gac atg acg tac act gag ttt gac      876 
Glu Ser Ser Tyr Ser Arg Gly Phe Asp Met Thr Tyr Thr Glu Phe Asp 
            260                 265                 270 

tat gac tta tgc aat gaa gtg gtt gac gtg acc tgc tcc cct aag cca      924 
Tyr Asp Leu Cys Asn Glu Val Val Asp Val Thr Cys Ser Pro Lys Pro 
        275                 280                 285 

gat gca ttc aac cca tgt gaa gat atc atg ggg tac aac atc ctc aga      972 
Asp Ala Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Asn Ile Leu Arg 
    290                 295                 300 

gtc ctg ata tgg ttt atc agc atc ctg gcc atc act ggg aac atc ata     1020 
Val Leu Ile Trp Phe Ile Ser Ile Leu Ala Ile Thr Gly Asn Ile Ile 
305                 310                 315                 320 

gtg cta gtg atc cta act acc agc caa tat aaa ctc aca gtc ccc agg     1068 
Val Leu Val Ile Leu Thr Thr Ser Gln Tyr Lys Leu Thr Val Pro Arg 
                325                 330                 335 

ttc ctt atg tgc aac ctg gcc ttt gct gat ctc tgc att gga atc tac     1116 
Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Leu Cys Ile Gly Ile Tyr 
            340                 345                 350 

ctg ctg ctc att gca tca gtt gat atc cat acc aag agc caa tat cac     1164 
Leu Leu Leu Ile Ala Ser Val Asp Ile His Thr Lys Ser Gln Tyr His 
        355                 360                 365 

aac tat gcc att gac tgg caa act ggg gca ggc tgt gat gct gct ggc     1212 
Asn Tyr Ala Ile Asp Trp Gln Thr Gly Ala Gly Cys Asp Ala Ala Gly 
    370                 375                 380 

ttt ttc act gtc ttt gcc agt gag ctg tca gtc tac act ctg aca gct     1260 
Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu Thr Ala 
385                 390                 395                 400 

atc acc ttg gaa aga tgg cat acc atc acg cat gcc atg cag ctg gac     1308 
Ile Thr Leu Glu Arg Trp His Thr Ile Thr His Ala Met Gln Leu Asp 
                405                 410                 415 

tgc aag gtg cag ctc cgc cat gct gcc agt gtc atg gtg atg ggc tgg     1356 
Cys Lys Val Gln Leu Arg His Ala Ala Ser Val Met Val Met Gly Trp 
            420                 425                 430 

att ttt gct ttt gca gct gcc ctc ttt ccc atc ttt ggc atc agc agc     1404 
Ile Phe Ala Phe Ala Ala Ala Leu Phe Pro Ile Phe Gly Ile Ser Ser 
        435                 440                 445 

tac atg aag gtg agc atc tgc ctg ccc atg gat att gac agc cct ttg     1452 
Tyr Met Lys Val Ser Ile Cys Leu Pro Met Asp Ile Asp Ser Pro Leu 
    450                 455                 460 

tca cag ctg tat gtc atg tcc ctc ctt gtg ctc aat gtc ctg gcc ttt     1500 
Ser Gln Leu Tyr Val Met Ser Leu Leu Val Leu Asn Val Leu Ala Phe 
465                 470                 475                 480 

gtg gtc atc tgt ggc tgc tat atc cac atc tac ctc aca gtg cgg aac     1548 
Val Val Ile Cys Gly Cys Tyr Ile His Ile Tyr Leu Thr Val Arg Asn 
                485                 490                 495 

ccc aac atc gtg tcc tcc tct agt gac acc agg atc gcc aag cgc atg     1596 
Pro Asn Ile Val Ser Ser Ser Ser Asp Thr Arg Ile Ala Lys Arg Met 
            500                 505                 510 

gcc atg ctc atc ttc act gac ttc ctc tgc atg gca ccc att tct ttc     1644 
Ala Met Leu Ile Phe Thr Asp Phe Leu Cys Met Ala Pro Ile Ser Phe 
        515                 520                 525 

ttt gcc att tct gcc tcc ctc aag gtg ccc ctc atc act gtg tcc aaa     1692 
Phe Ala Ile Ser Ala Ser Leu Lys Val Pro Leu Ile Thr Val Ser Lys 
    530                 535                 540 

gca aag att ctg ctg gtt ctg ttt cac ccc atc aac tcc tgt gcc aac     1740 
Ala Lys Ile Leu Leu Val Leu Phe His Pro Ile Asn Ser Cys Ala Asn 
545                 550                 555                 560 

ccc ttc ctc tat gcc atc ttt acc aaa aac ttt cgc aga gat ttc ttc     1788 
Pro Phe Leu Tyr Ala Ile Phe Thr Lys Asn Phe Arg Arg Asp Phe Phe 
                565                 570                 575 

att ctg ctg agc aag tgt ggc tgc tat gaa atg caa gcc caa att tat     1836 
Ile Leu Leu Ser Lys Cys Gly Cys Tyr Glu Met Gln Ala Gln Ile Tyr 
            580                 585                 590 

agg aca gaa act tca tcc act gtc cac aac acc cat cca agg aat ggc     1884 
Arg Thr Glu Thr Ser Ser Thr Val His Asn Thr His Pro Arg Asn Gly 
        595                 600                 605 

cac tgc tct tca gct ccc aga gtc acc agt ggt tcc act tac ata ctt     1932 
His Cys Ser Ser Ala Pro Arg Val Thr Ser Gly Ser Thr Tyr Ile Leu 
    610                 615                 620 

gtc cct cta agt cat tta gcc caa aac taaaacacaa tgtgaaaatg           1979 
Val Pro Leu Ser His Leu Ala Gln Asn 
625                 630 

tatctgagta ttgaatgata attcagtctt gcctttgaag                         2019 

 
           
             10  
             633  
             PRT  
             Homo sapiens  
           
            10 

Met Ala Leu Leu Leu Val Ser Leu Leu Ala Phe Leu Ser Leu Gly Ser 
1               5                   10                  15 

Gly Cys His His Arg Ile Cys His Cys Ser Asn Arg Val Phe Leu Cys 
            20                  25                  30 

Gln Glu Ser Lys Val Thr Glu Ile Pro Ser Asp Leu Pro Arg Asn Ala 
        35                  40                  45 

Ile Glu Leu Arg Phe Val Leu Thr Lys Leu Arg Val Ile Gln Lys Gly 
    50                  55                  60 

Ala Phe Ser Gly Phe Gly Asp Leu Glu Lys Ile Glu Ile Ser Gln Asn 
65                  70                  75                  80 

Asp Val Leu Glu Val Ile Glu Ala Asp Val Phe Ser Asn Leu Pro Lys 
                85                  90                  95 

Leu His Glu Ile Arg Ile Glu Lys Ala Asn Asn Leu Leu Tyr Ile Asn 
            100                 105                 110 

Pro Glu Ala Phe Gln Asn Leu Pro Asn Leu Gln Tyr Leu Leu Ile Ser 
        115                 120                 125 

Asn Thr Gly Ile Lys His Leu Pro Asp Val His Lys Ile His Ser Leu 
    130                 135                 140 

Gln Lys Val Leu Leu Asp Ile Gln Asp Asn Ile Asn Ile His Thr Ile 
145                 150                 155                 160 

Glu Arg Asn Ser Phe Val Gly Leu Ser Phe Glu Ser Val Ile Leu Trp 
                165                 170                 175 

Leu Asn Lys Asn Gly Ile Gln Glu Ile His Asn Cys Ala Phe Asn Gly 
            180                 185                 190 

Thr Gln Leu Asp Glu Leu Asn Leu Ser Asp Asn Asn Asn Leu Glu Glu 
        195                 200                 205 

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

Glu Leu His Pro Ile Cys Asn Lys Ser Ile Leu Arg Gln Glu Val Asp 
225                 230                 235                 240 

Tyr Met Thr Gln Ala Arg Gly Gln Arg Ser Ser Leu Ala Glu Asp Asn 
                245                 250                 255 

Glu Ser Ser Tyr Ser Arg Gly Phe Asp Met Thr Tyr Thr Glu Phe Asp 
            260                 265                 270 

Tyr Asp Leu Cys Asn Glu Val Val Asp Val Thr Cys Ser Pro Lys Pro 
        275                 280                 285 

Asp Ala Phe Asn Pro Cys Glu Asp Ile Met Gly Tyr Asn Ile Leu Arg 
    290                 295                 300 

Val Leu Ile Trp Phe Ile Ser Ile Leu Ala Ile Thr Gly Asn Ile Ile 
305                 310                 315                 320 

Val Leu Val Ile Leu Thr Thr Ser Gln Tyr Lys Leu Thr Val Pro Arg 
                325                 330                 335 

Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Leu Cys Ile Gly Ile Tyr 
            340                 345                 350 

Leu Leu Leu Ile Ala Ser Val Asp Ile His Thr Lys Ser Gln Tyr His 
        355                 360                 365 

Asn Tyr Ala Ile Asp Trp Gln Thr Gly Ala Gly Cys Asp Ala Ala Gly 
    370                 375                 380 

Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr Thr Leu Thr Ala 
385                 390                 395                 400 

Ile Thr Leu Glu Arg Trp His Thr Ile Thr His Ala Met Gln Leu Asp 
                405                 410                 415 

Cys Lys Val Gln Leu Arg His Ala Ala Ser Val Met Val Met Gly Trp 
            420                 425                 430 

Ile Phe Ala Phe Ala Ala Ala Leu Phe Pro Ile Phe Gly Ile Ser Ser 
        435                 440                 445 

Tyr Met Lys Val Ser Ile Cys Leu Pro Met Asp Ile Asp Ser Pro Leu 
    450                 455                 460 

Ser Gln Leu Tyr Val Met Ser Leu Leu Val Leu Asn Val Leu Ala Phe 
465                 470                 475                 480 

Val Val Ile Cys Gly Cys Tyr Ile His Ile Tyr Leu Thr Val Arg Asn 
                485                 490                 495 

Pro Asn Ile Val Ser Ser Ser Ser Asp Thr Arg Ile Ala Lys Arg Met 
            500                 505                 510 

Ala Met Leu Ile Phe Thr Asp Phe Leu Cys Met Ala Pro Ile Ser Phe 
        515                 520                 525 

Phe Ala Ile Ser Ala Ser Leu Lys Val Pro Leu Ile Thr Val Ser Lys 
    530                 535                 540 

Ala Lys Ile Leu Leu Val Leu Phe His Pro Ile Asn Ser Cys Ala Asn 
545                 550                 555                 560 

Pro Phe Leu Tyr Ala Ile Phe Thr Lys Asn Phe Arg Arg Asp Phe Phe 
                565                 570                 575 

Ile Leu Leu Ser Lys Cys Gly Cys Tyr Glu Met Gln Ala Gln Ile Tyr 
            580                 585                 590 

Arg Thr Glu Thr Ser Ser Thr Val His Asn Thr His Pro Arg Asn Gly 
        595                 600                 605 

His Cys Ser Ser Ala Pro Arg Val Thr Ser Gly Ser Thr Tyr Ile Leu 
    610                 615                 620 

Val Pro Leu Ser His Leu Ala Gln Asn 
625                 630 

 
           
             11  
             1609  
             DNA  
             Homo sapiens  
             
               CDS  
               (199)..(1467)  
             
           
            11 

ggctccggct tcaagatcaa aggaaatgtt tccctttgtc ccgtttcaca ctaaacgggt     60 

tggggaggaa ccaggggaga tgtcaaccgt ctgccggtga ctgggaagtt ttctgcaagt    120 

cctccacagc atagccagca ggccactttt cactaacaga agtcacaagc caagtgagac    180 

actcatccaa gaggaagg atg gcc agt atc ttt tct aag ttg cta act ggc      231 
                    Met Ala Ser Ile Phe Ser Lys Leu Leu Thr Gly 
                    1               5                   10 
cgc aat gct tct ctg ctg ttt gct acc atg ggc acc agt gtc ctg acc      279 
Arg Asn Ala Ser Leu Leu Phe Ala Thr Met Gly Thr Ser Val Leu Thr 
            15                  20                  25 

acc ggg tac ctg ctg aac cgg cag aaa gtg tgt gcc gag gtc cgg gag      327 
Thr Gly Tyr Leu Leu Asn Arg Gln Lys Val Cys Ala Glu Val Arg Glu 
        30                  35                  40 

cag cct agg cta ttt cct cca agc gca gac tac cca gac ctg cgc aag      375 
Gln Pro Arg Leu Phe Pro Pro Ser Ala Asp Tyr Pro Asp Leu Arg Lys 
    45                  50                  55 

cac aac aac tgc atg gcc gag tgc ctc acc ccc gcc att tat tcc aag      423 
His Asn Asn Cys Met Ala Glu Cys Leu Thr Pro Ala Ile Tyr Ser Lys 
60                  65                  70                  75 

ctt cgc aac aag gtg aca ccc aac ggc tac acg ctg gac cag tgc atc      471 
Leu Arg Asn Lys Val Thr Pro Asn Gly Tyr Thr Leu Asp Gln Cys Ile 
                80                  85                  90 

cag act gga gtg gac aac cct ggc cac ccc ttc ata aag act gtg ggc      519 
Gln Thr Gly Val Asp Asn Pro Gly His Pro Phe Ile Lys Thr Val Gly 
            95                  100                 105 

atg gtg gct ggt gac gag gag tcc tat gag gtg ttt gct gac ctt ttt      567 
Met Val Ala Gly Asp Glu Glu Ser Tyr Glu Val Phe Ala Asp Leu Phe 
        110                 115                 120 

gac ccc gtc atc aaa cta aga cac aac ggc tat gac ccc agg gtg atg      615 
Asp Pro Val Ile Lys Leu Arg His Asn Gly Tyr Asp Pro Arg Val Met 
    125                 130                 135 

aag cac aca acg gat ctg gat gca tca aag tct gct tgg cag atc acc      663 
Lys His Thr Thr Asp Leu Asp Ala Ser Lys Ser Ala Trp Gln Ile Thr 
140                 145                 150                 155 

caa ggg cag ttc gac gag cat tac gtg ctg tct tct cgg gtg cgc act      711 
Gln Gly Gln Phe Asp Glu His Tyr Val Leu Ser Ser Arg Val Arg Thr 
                160                 165                 170 

ggc cgc agc atc cgt ggg ctg agc ctg cct cca gcc tgc acc cgg gcc      759 
Gly Arg Ser Ile Arg Gly Leu Ser Leu Pro Pro Ala Cys Thr Arg Ala 
            175                 180                 185 

gag cga agg gag gta gag aac gtg gcc atc act gcc ctg gag ggc ctc      807 
Glu Arg Arg Glu Val Glu Asn Val Ala Ile Thr Ala Leu Glu Gly Leu 
        190                 195                 200 

aag ggg gac ctg gct ggc cgc tac tac aag ctg tcc gag atg acg gag      855 
Lys Gly Asp Leu Ala Gly Arg Tyr Tyr Lys Leu Ser Glu Met Thr Glu 
    205                 210                 215 

cag gac cag cag cgg ctc atc gat gac cac ttt ctg ttt gat aag cca      903 
Gln Asp Gln Gln Arg Leu Ile Asp Asp His Phe Leu Phe Asp Lys Pro 
220                 225                 230                 235 

gtg tcc cct tta tta aca tgt gct ggg atg gcc cgt gac tgg cca gat      951 
Val Ser Pro Leu Leu Thr Cys Ala Gly Met Ala Arg Asp Trp Pro Asp 
                240                 245                 250 

gcc agg gga atc tgg cat aat tat gat aag aca ttt ctc atc tgg ata      999 
Ala Arg Gly Ile Trp His Asn Tyr Asp Lys Thr Phe Leu Ile Trp Ile 
            255                 260                 265 

aat gag gag gat cac acc agg gta atc tca atg gaa aaa gga ggc aat     1047 
Asn Glu Glu Asp His Thr Arg Val Ile Ser Met Glu Lys Gly Gly Asn 
        270                 275                 280 

atg aaa cga gta ttt gag cga ttc tgt cgt gga cta aaa gaa gta gaa     1095 
Met Lys Arg Val Phe Glu Arg Phe Cys Arg Gly Leu Lys Glu Val Glu 
    285                 290                 295 

cgg tta atc caa gaa cga ggc tgg gag ttc atg tgg aat gag cgc cta     1143 
Arg Leu Ile Gln Glu Arg Gly Trp Glu Phe Met Trp Asn Glu Arg Leu 
300                 305                 310                 315 

gga tac att ttg acc tgt cct tcg aac ctt gga aca gga cta cga gct     1191 
Gly Tyr Ile Leu Thr Cys Pro Ser Asn Leu Gly Thr Gly Leu Arg Ala 
                320                 325                 330 

ggt gtc cac gtt agg atc cca aag ctc agc aag gac cca cgc ttt tct     1239 
Gly Val His Val Arg Ile Pro Lys Leu Ser Lys Asp Pro Arg Phe Ser 
            335                 340                 345 

aag atc ctg gaa aac cta aga ctc cag aag cgt ggc aca ggt ggt gtg     1287 
Lys Ile Leu Glu Asn Leu Arg Leu Gln Lys Arg Gly Thr Gly Gly Val 
        350                 355                 360 

gac act gcc gcg gtc gca gat gtg tac gac att tcc aac ata gat aga     1335 
Asp Thr Ala Ala Val Ala Asp Val Tyr Asp Ile Ser Asn Ile Asp Arg 
    365                 370                 375 

att ggt cga tca gag gtt gag ctt gtt cag ata gtc atc gat gga gtc     1383 
Ile Gly Arg Ser Glu Val Glu Leu Val Gln Ile Val Ile Asp Gly Val 
380                 385                 390                 395 

aat tac ctg gtg gat tgt gaa aag aag ttg gag aga ggc caa gat att     1431 
Asn Tyr Leu Val Asp Cys Glu Lys Lys Leu Glu Arg Gly Gln Asp Ile 
                400                 405                 410 

aag gtg cca ccc cct ctg cct cag ttt ggc aaa aag taaactttcc          1477 
Lys Val Pro Pro Pro Leu Pro Gln Phe Gly Lys Lys 
            415                 420 

ctttcccaat ttataaataa tctgtctgct ggtacaacag acataaatct ctactctgag   1537 

agtttttata cacttggaaa aatataaaat tgtagatcct gcctatcttt acaataaaac   1597 

tctccttaat at                                                       1609 

 
           
             12  
             423  
             PRT  
             Homo sapiens  
           
            12 

Met Ala Ser Ile Phe Ser Lys Leu Leu Thr Gly Arg Asn Ala Ser Leu 
1               5                   10                  15 

Leu Phe Ala Thr Met Gly Thr Ser Val Leu Thr Thr Gly Tyr Leu Leu 
            20                  25                  30 

Asn Arg Gln Lys Val Cys Ala Glu Val Arg Glu Gln Pro Arg Leu Phe 
        35                  40                  45 

Pro Pro Ser Ala Asp Tyr Pro Asp Leu Arg Lys His Asn Asn Cys Met 
    50                  55                  60 

Ala Glu Cys Leu Thr Pro Ala Ile Tyr Ser Lys Leu Arg Asn Lys Val 
65                  70                  75                  80 

Thr Pro Asn Gly Tyr Thr Leu Asp Gln Cys Ile Gln Thr Gly Val Asp 
                85                  90                  95 

Asn Pro Gly His Pro Phe Ile Lys Thr Val Gly Met Val Ala Gly Asp 
            100                 105                 110 

Glu Glu Ser Tyr Glu Val Phe Ala Asp Leu Phe Asp Pro Val Ile Lys 
        115                 120                 125 

Leu Arg His Asn Gly Tyr Asp Pro Arg Val Met Lys His Thr Thr Asp 
    130                 135                 140 

Leu Asp Ala Ser Lys Ser Ala Trp Gln Ile Thr Gln Gly Gln Phe Asp 
145                 150                 155                 160 

Glu His Tyr Val Leu Ser Ser Arg Val Arg Thr Gly Arg Ser Ile Arg 
                165                 170                 175 

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

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

Gly Arg Tyr Tyr Lys Leu Ser Glu Met Thr Glu Gln Asp Gln Gln Arg 
    210                 215                 220 

Leu Ile Asp Asp His Phe Leu Phe Asp Lys Pro Val Ser Pro Leu Leu 
225                 230                 235                 240 

Thr Cys Ala Gly Met Ala Arg Asp Trp Pro Asp Ala Arg Gly Ile Trp 
                245                 250                 255 

His Asn Tyr Asp Lys Thr Phe Leu Ile Trp Ile Asn Glu Glu Asp His 
            260                 265                 270 

Thr Arg Val Ile Ser Met Glu Lys Gly Gly Asn Met Lys Arg Val Phe 
        275                 280                 285 

Glu Arg Phe Cys Arg Gly Leu Lys Glu Val Glu Arg Leu Ile Gln Glu 
    290                 295                 300 

Arg Gly Trp Glu Phe Met Trp Asn Glu Arg Leu Gly Tyr Ile Leu Thr 
305                 310                 315                 320 

Cys Pro Ser Asn Leu Gly Thr Gly Leu Arg Ala Gly Val His Val Arg 
                325                 330                 335 

Ile Pro Lys Leu Ser Lys Asp Pro Arg Phe Ser Lys Ile Leu Glu Asn 
            340                 345                 350 

Leu Arg Leu Gln Lys Arg Gly Thr Gly Gly Val Asp Thr Ala Ala Val 
        355                 360                 365 

Ala Asp Val Tyr Asp Ile Ser Asn Ile Asp Arg Ile Gly Arg Ser Glu 
    370                 375                 380 

Val Glu Leu Val Gln Ile Val Ile Asp Gly Val Asn Tyr Leu Val Asp 
385                 390                 395                 400 

Cys Glu Lys Lys Leu Glu Arg Gly Gln Asp Ile Lys Val Pro Pro Pro 
                405                 410                 415 

Leu Pro Gln Phe Gly Lys Lys 
            420 

 
           
             13  
             3983  
             DNA  
             Homo sapiens  
             
               CDS  
               (137)..(1723)  
             
           
            13 

ggcacgaggg gccgctccag ccgcgcgcat ctcggcccgc gccccgagac cgcgcccagc     60 

tagccccggc cccgctcggc gccccaggca gctcggctgc gctcgccgcg ggacggcgcg    120 

gcatgaggct gcgggg atg cgg acc ccg ggc cgc cct gcc tcc agc gca ggg    172 
                  Met Arg Thr Pro Gly Arg Pro Ala Ser Ser Ala Gly 
                  1               5                   10 

gcc agc gac gct cgg ctg ctg gcg ccc ccg ggg cgg aac ccc ttc gtg      220 
Ala Ser Asp Ala Arg Leu Leu Ala Pro Pro Gly Arg Asn Pro Phe Val 
        15                  20                  25 

cac gag ctg cac ctc agc gcc ctg cag aag gcc cag gtg gcc ctc atg      268 
His Glu Leu His Leu Ser Ala Leu Gln Lys Ala Gln Val Ala Leu Met 
    30                  35                  40 

aca ctg acg ctc ttc ccg gtc cgg ctc ctg gtt gcc gct gcc atg atg      316 
Thr Leu Thr Leu Phe Pro Val Arg Leu Leu Val Ala Ala Ala Met Met 
45                  50                  55                  60 

ctg ctg gcc tgg ccc ctc gca ctt gtc gca tcc ctg ggc tct gcg gag      364 
Leu Leu Ala Trp Pro Leu Ala Leu Val Ala Ser Leu Gly Ser Ala Glu 
                65                  70                  75 

aag gaa ccc gag cag ccc ccg gcc ctg tgg agg aag gtt gtg gac ttc      412 
Lys Glu Pro Glu Gln Pro Pro Ala Leu Trp Arg Lys Val Val Asp Phe 
            80                  85                  90 

ctg ctg aag gcc atc atg cgc acc atg tgg ttc gcc ggc ggc ttc cac      460 
Leu Leu Lys Ala Ile Met Arg Thr Met Trp Phe Ala Gly Gly Phe His 
        95                  100                 105 

cgg gtg gcc gtg aag ggg cgg cag gcg ctg ccc acc gag gcg gcc atc      508 
Arg Val Ala Val Lys Gly Arg Gln Ala Leu Pro Thr Glu Ala Ala Ile 
    110                 115                 120 

ctc acg ctc gcg cct cac tcg tcc tac ttc gac gcc atc cct gtg acc      556 
Leu Thr Leu Ala Pro His Ser Ser Tyr Phe Asp Ala Ile Pro Val Thr 
125                 130                 135                 140 

atg acg atg tcc tcc atc gtg atg aag aca gag agc aga gac atc ccg      604 
Met Thr Met Ser Ser Ile Val Met Lys Thr Glu Ser Arg Asp Ile Pro 
                145                 150                 155 

atc tgg gga act ctg atc cag tat ata cgg cct gtg ttc gtg tcc cgg      652 
Ile Trp Gly Thr Leu Ile Gln Tyr Ile Arg Pro Val Phe Val Ser Arg 
            160                 165                 170 

tca gac cag gat tct cgc agg aaa aca gta gaa gaa atc aag aga cgg      700 
Ser Asp Gln Asp Ser Arg Arg Lys Thr Val Glu Glu Ile Lys Arg Arg 
        175                 180                 185 

gcg cag tcc aac gga aag tgg cca cag ata atg att ttt cca gaa gga      748 
Ala Gln Ser Asn Gly Lys Trp Pro Gln Ile Met Ile Phe Pro Glu Gly 
    190                 195                 200 

act tgt aca aac agg acc tgc cta att acc ttc aaa cct ggt gca ttc      796 
Thr Cys Thr Asn Arg Thr Cys Leu Ile Thr Phe Lys Pro Gly Ala Phe 
205                 210                 215                 220 

atc cct gga gcg ccc gtc cac cct ggg gtt tta cga tat cca aat aaa      844 
Ile Pro Gly Ala Pro Val His Pro Gly Val Leu Arg Tyr Pro Asn Lys 
                225                 230                 235 

ctg gac acc atc aca tgg acg tgg caa gga cct gga gcg ctg gaa atc      892 
Leu Asp Thr Ile Thr Trp Thr Trp Gln Gly Pro Gly Ala Leu Glu Ile 
            240                 245                 250 

ctg tgg ctc acg ctg tgt cag ttt cac aac caa gtg gaa atc gag ttc      940 
Leu Trp Leu Thr Leu Cys Gln Phe His Asn Gln Val Glu Ile Glu Phe 
        255                 260                 265 

ctt cct gtg tac agc cct tct gag gag gag aag agg aac ccc gcg ctg      988 
Leu Pro Val Tyr Ser Pro Ser Glu Glu Glu Lys Arg Asn Pro Ala Leu 
    270                 275                 280 

tat gcc agc aac gtg cgg cga gtc atg gcc gag gcc ttg ggt gtc tcc     1036 
Tyr Ala Ser Asn Val Arg Arg Val Met Ala Glu Ala Leu Gly Val Ser 
285                 290                 295                 300 

gtg act gac tac acg ttc gag gac tgc cag ctg gcc ctg gcg gaa gga     1084 
Val Thr Asp Tyr Thr Phe Glu Asp Cys Gln Leu Ala Leu Ala Glu Gly 
                305                 310                 315 

cag ctc cgt ctc ccc gct gac act tgc ctt tta gaa ttt gcc agg ctc     1132 
Gln Leu Arg Leu Pro Ala Asp Thr Cys Leu Leu Glu Phe Ala Arg Leu 
            320                 325                 330 

gtg cgg ggc ctc ggg cta aaa cca gaa aag ctt gaa aaa gat ctg gac     1180 
Val Arg Gly Leu Gly Leu Lys Pro Glu Lys Leu Glu Lys Asp Leu Asp 
        335                 340                 345 

aga tac tca gaa aga gcc agg atg aag gga gga gag aag ata ggt att     1228 
Arg Tyr Ser Glu Arg Ala Arg Met Lys Gly Gly Glu Lys Ile Gly Ile 
    350                 355                 360 

gcg gag ttt gcc gcc tcc ctg gaa gtc ccc gtt tct gac ttg ctg gaa     1276 
Ala Glu Phe Ala Ala Ser Leu Glu Val Pro Val Ser Asp Leu Leu Glu 
365                 370                 375                 380 

gac atg ttt tca ctg ttc gac gag agc ggc agc ggc gag gtg gac ctg     1324 
Asp Met Phe Ser Leu Phe Asp Glu Ser Gly Ser Gly Glu Val Asp Leu 
                385                 390                 395 

cga gag tgt gtg gtt gcc ctg tct gtc gtc tgc tgg ccg gcc cgg acc     1372 
Arg Glu Cys Val Val Ala Leu Ser Val Val Cys Trp Pro Ala Arg Thr 
            400                 405                 410 

ctg gac acc atc cag ctg gct ttc aag atg tac gga gcg caa gag gac     1420 
Leu Asp Thr Ile Gln Leu Ala Phe Lys Met Tyr Gly Ala Gln Glu Asp 
        415                 420                 425 

ggc agc gtc ggc gaa ggt gac ctg tcc tgc atc ctc aag acg gcc ctg     1468 
Gly Ser Val Gly Glu Gly Asp Leu Ser Cys Ile Leu Lys Thr Ala Leu 
    430                 435                 440 

ggg gtg gca gag ctc act gtg acc gac cta ttc cga gcc att gac caa     1516 
Gly Val Ala Glu Leu Thr Val Thr Asp Leu Phe Arg Ala Ile Asp Gln 
445                 450                 455                 460 

gag gag aag ggg aag atc aca ttc gct gac ttc cac agg ttt gca gaa     1564 
Glu Glu Lys Gly Lys Ile Thr Phe Ala Asp Phe His Arg Phe Ala Glu 
                465                 470                 475 

atg tac cct gcc ttc gca gag gaa tac ctg tac ccg gat cag aca cat     1612 
Met Tyr Pro Ala Phe Ala Glu Glu Tyr Leu Tyr Pro Asp Gln Thr His 
            480                 485                 490 

ttc gaa agc tgt gca gag acc tca cct gcg cca atc cca aac ggc ttc     1660 
Phe Glu Ser Cys Ala Glu Thr Ser Pro Ala Pro Ile Pro Asn Gly Phe 
        495                 500                 505 

tgt gcc gat ttc agc ccg gaa aac tca gac gct ggg cgg aag cct gtt     1708 
Cys Ala Asp Phe Ser Pro Glu Asn Ser Asp Ala Gly Arg Lys Pro Val 
    510                 515                 520 

cgc aag aag ctg gat taggacccag ggttgcggag agacgcggcc cctcccgcgt     1763 
Arg Lys Lys Leu Asp 
525 

ggacatcacc gccatgagcc tctttgcgag tgacctctgg gctccgctcc tcactcctgc   1823 

tgtacaggca ctgtcttcag cccgagttcc aggggcctcg ggggctgttt gtatcttgtt   1883 

cctttgtgaa gtgtgttgca gaaccgacgc ttactgtgcg agaatcggag ggcgcgcacg   1943 

cggatccccc gcctggcctg gaccccgtgg ggtcaggttc cctgccgggc ggggggcacc   2003 

ggtgccgccc cgtgttctcc cacggggccc tggtttcgag tctctgtcac agcctcttcc   2063 

ggcggcagcg tgcaccgggc gggcctccgt gcacactcag cacacgcctg ccacacagcg   2123 

tgcgcttgcg tgtcactctg gcacgaaacc tgtctgcctc tgtggatcca cagcctggca   2183 

gagccgagcc gtcacctgat ttttcagtgt ttctacctgt gtgctggagc tcatgagtat   2243 

tttataaact ccatttaggt acttcaggaa acatgcagca ttttttaaaa aatgaaaatt   2303 

gtttttctac ttcatttttc cttttagagt caaaggatat ttatttatag gccttttttt   2363 

ttttaatata gaatctgagg ctgtttgggc tttgacttaa atttccatca ggcctctctc   2423 

cagcaggtaa tccctctcct tccgctgggt cccctgggga ggtgtgaact caagggccta   2483 

gccccaaaac actttttctg cttttcttaa tccttttcca gtcccctctt tttttataaa   2543 

cgttggcagt ttgatgtttc tgtttcggca taacgtaatc catttcactg tagcctaaac   2603 

tccagtccga ggttggatat tgttcaaatg agcagggccc gagctggaag cgcaaggcag   2663 

ccgccgccgt gccgctcctc ccttgccctc aggccaggtc cctgctggaa gcggctgcat   2723 

cttcctgtca gccctggttt ccatggtgac tggcgtgacg cagccacctg agtatggctg   2783 

accttcctgc agagagagga gccgcagtct tttgcttgtg gaaggagacg ctgggctgtg   2843 

cggtgcggag ggtgatgagg atgtctggtg acagccgtgc ggacaccact cctctctgca   2903 

gcactgcctc ccagcgccag ggtcgcgggc acatcccact gagagcgggg gtcctgcccc   2963 

atcttagagt caaaggcaga ggggcttcca ggccctggat ggggtatttt ggtgtcacct   3023 

gaagtccctc tgacatcacc ttgtttcatc attttttatg acagaattag aaacccatcc   3083 

ttcaagcaca ataatcatca cagacttgag tttgcttcct aaagcaaagg ctccgggttt   3143 

gtttggaaaa tttttttgat ttctgaaatg aattgatttt tatatttggg gcatctctat   3203 

agaaagtgac caccaaggcc agtaagtacg ggaaaaaatg tttactaact tcctcagaga   3263 

ttcgtgatac gcgtttctcc actgacagac atttaaaaac aaccttcagc tccgtttcaa   3323 

tcaatcacct cgacttgttt tttagcatgg acactgccag caggacagac agggatggag   3383 

taaaccgaag tcaatttcag ggctcttggc gtgttggaca cagaagaaat cctagtgcag   3443 

cctttggtag ctaacagtca ctgattttat aattggagaa tgcgtaaaga ttcatttttc   3503 

aaggagaaga gcctgcaaat ggccaatgaa ggaggtaaat aaactaagat attccgaggg   3563 

aagggaccca ggccacctcc cttccgcagg tctgcagatg aagggttttt tgaatgaaat   3623 

gccactgtgc attttcagaa aaaaaaatct ctgataaaca gactttgaat ggatgtttgt   3683 

tcctcctgat tctcttttct cttcgtggcg acttagagtt ggcggatatt cggaactgtg   3743 

aatgtacata gcgttgagtt aaaccccttg tgtgtgagac aggacgcagc gggcccctgg   3803 

tggcctgggg gccagacccg tgggcaggtg gggcatgggc cctggcctgc ggggacctgc   3863 

tggggtgtga gggcagaggg agggttgcca tgaaggaact tgggattttc aatggaataa   3923 

ataaaacata aagtctatac ttgggaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa   3983 

 
           
             14  
             529  
             PRT  
             Homo sapiens  
           
            14 

Met Arg Thr Pro Gly Arg Pro Ala Ser Ser Ala Gly Ala Ser Asp Ala 
1               5                   10                  15 

Arg Leu Leu Ala Pro Pro Gly Arg Asn Pro Phe Val His Glu Leu His 
            20                  25                  30 

Leu Ser Ala Leu Gln Lys Ala Gln Val Ala Leu Met Thr Leu Thr Leu 
        35                  40                  45 

Phe Pro Val Arg Leu Leu Val Ala Ala Ala Met Met Leu Leu Ala Trp 
    50                  55                  60 

Pro Leu Ala Leu Val Ala Ser Leu Gly Ser Ala Glu Lys Glu Pro Glu 
65                  70                  75                  80 

Gln Pro Pro Ala Leu Trp Arg Lys Val Val Asp Phe Leu Leu Lys Ala 
                85                  90                  95 

Ile Met Arg Thr Met Trp Phe Ala Gly Gly Phe His Arg Val Ala Val 
            100                 105                 110 

Lys Gly Arg Gln Ala Leu Pro Thr Glu Ala Ala Ile Leu Thr Leu Ala 
        115                 120                 125 

Pro His Ser Ser Tyr Phe Asp Ala Ile Pro Val Thr Met Thr Met Ser 
    130                 135                 140 

Ser Ile Val Met Lys Thr Glu Ser Arg Asp Ile Pro Ile Trp Gly Thr 
145                 150                 155                 160 

Leu Ile Gln Tyr Ile Arg Pro Val Phe Val Ser Arg Ser Asp Gln Asp 
                165                 170                 175 

Ser Arg Arg Lys Thr Val Glu Glu Ile Lys Arg Arg Ala Gln Ser Asn 
            180                 185                 190 

Gly Lys Trp Pro Gln Ile Met Ile Phe Pro Glu Gly Thr Cys Thr Asn 
        195                 200                 205 

Arg Thr Cys Leu Ile Thr Phe Lys Pro Gly Ala Phe Ile Pro Gly Ala 
    210                 215                 220 

Pro Val His Pro Gly Val Leu Arg Tyr Pro Asn Lys Leu Asp Thr Ile 
225                 230                 235                 240 

Thr Trp Thr Trp Gln Gly Pro Gly Ala Leu Glu Ile Leu Trp Leu Thr 
                245                 250                 255 

Leu Cys Gln Phe His Asn Gln Val Glu Ile Glu Phe Leu Pro Val Tyr 
            260                 265                 270 

Ser Pro Ser Glu Glu Glu Lys Arg Asn Pro Ala Leu Tyr Ala Ser Asn 
        275                 280                 285 

Val Arg Arg Val Met Ala Glu Ala Leu Gly Val Ser Val Thr Asp Tyr 
    290                 295                 300 

Thr Phe Glu Asp Cys Gln Leu Ala Leu Ala Glu Gly Gln Leu Arg Leu 
305                 310                 315                 320 

Pro Ala Asp Thr Cys Leu Leu Glu Phe Ala Arg Leu Val Arg Gly Leu 
                325                 330                 335 

Gly Leu Lys Pro Glu Lys Leu Glu Lys Asp Leu Asp Arg Tyr Ser Glu 
            340                 345                 350 

Arg Ala Arg Met Lys Gly Gly Glu Lys Ile Gly Ile Ala Glu Phe Ala 
        355                 360                 365 

Ala Ser Leu Glu Val Pro Val Ser Asp Leu Leu Glu Asp Met Phe Ser 
    370                 375                 380 

Leu Phe Asp Glu Ser Gly Ser Gly Glu Val Asp Leu Arg Glu Cys Val 
385                 390                 395                 400 

Val Ala Leu Ser Val Val Cys Trp Pro Ala Arg Thr Leu Asp Thr Ile 
                405                 410                 415 

Gln Leu Ala Phe Lys Met Tyr Gly Ala Gln Glu Asp Gly Ser Val Gly 
            420                 425                 430 

Glu Gly Asp Leu Ser Cys Ile Leu Lys Thr Ala Leu Gly Val Ala Glu 
        435                 440                 445 

Leu Thr Val Thr Asp Leu Phe Arg Ala Ile Asp Gln Glu Glu Lys Gly 
    450                 455                 460 

Lys Ile Thr Phe Ala Asp Phe His Arg Phe Ala Glu Met Tyr Pro Ala 
465                 470                 475                 480 

Phe Ala Glu Glu Tyr Leu Tyr Pro Asp Gln Thr His Phe Glu Ser Cys 
                485                 490                 495 

Ala Glu Thr Ser Pro Ala Pro Ile Pro Asn Gly Phe Cys Ala Asp Phe 
            500                 505                 510 

Ser Pro Glu Asn Ser Asp Ala Gly Arg Lys Pro Val Arg Lys Lys Leu 
        515                 520                 525 

Asp 

 
           
             15  
             1267  
             DNA  
             Homo sapiens  
             
               CDS  
               (2)..(1126)  
             
           
            15 

g tcc aaa atg tgg ctg ctt tta aca aca act tgt ttg atc tgt gga act     49 
  Ser Lys Met Trp Leu Leu Leu Thr Thr Thr Cys Leu Ile Cys Gly Thr 
  1               5                   10                  15 

tta aat gct ggt gga ttc ctt gat ttg gaa aat gaa gtg aat cct gag       97 
Leu Asn Ala Gly Gly Phe Leu Asp Leu Glu Asn Glu Val Asn Pro Glu 
            20                  25                  30 

gtg tgg atg aat act agt gaa atc atc atc tac aat ggc tac ccc agt      145 
Val Trp Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser 
        35                  40                  45 

gaa gag tat gaa gtc acc act gaa gat ggg tat ata ctc ctt gtc gac      193 
Glu Glu Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asp 
    50                  55                  60 

aga att cct tat ggg cga aca cat gct ggg agc aca ggt ccc cgg cca      241 
Arg Ile Pro Tyr Gly Arg Thr His Ala Gly Ser Thr Gly Pro Arg Pro 
65                  70                  75                  80 

gtt gtg tat atg cag cat gcc ctg ttt gca gac aat gcc tac tgg ctt      289 
Val Val Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu 
                85                  90                  95 

gag aat tat cct aat gga agc ctt gga ttc ctt cta gca gat gca ggt      337 
Glu Asn Tyr Pro Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly 
            100                 105                 110 

tat gat gta tgg atg gga aac agt cgg gga aac act tgg tca aga aga      385 
Tyr Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg 
        115                 120                 125 

cac aaa aca ctc tca gag aca gat gag aaa ttc tgg gcc ttt agt ttt      433 
His Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Ser Phe 
    130                 135                 140 

gat gaa atg gcc aaa tat gat ctc cca gga gta ata gac ttc att gta      481 
Asp Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val 
145                 150                 155                 160 

aat aaa act ggt cag gag aaa ttg tat ttc att gga cat tca ctt ggc      529 
Asn Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly 
                165                 170                 175 

act aca ata ggg ttt gta gcc ttt tcc acc atg cct gaa ctg gca caa      577 
Thr Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln 
            180                 185                 190 

aga atc aaa atg aat ttt gcc ttg ggt cct acg atc tca ttc aaa tat      625 
Arg Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr 
        195                 200                 205 

ccc acg ggc att ttt acc agg ttt ttt cta ctt cca aat tcc ata atc      673 
Pro Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile 
    210                 215                 220 

aag gct gtt ttt ggt acc aaa ggt ttc ttt tta gaa gat aag aaa acg      721 
Lys Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr 
225                 230                 235                 240 

aag ata gct tct aac aaa atc tgc aac aat aag ata ctc tgg ttg ata      769 
Lys Ile Ala Ser Asn Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile 
                245                 250                 255 

tgt agc gaa ttt atg tcc tta tgg gct gga tcc aac aag aaa aat atg      817 
Cys Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met 
            260                 265                 270 

aat cag ctt tac cac tct gat gaa ttc aga gct tat gac tgg gga aat      865 
Asn Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn 
        275                 280                 285 

ggc gct gat aat atg aaa cat tac aat cag agt cat ccc cct ata tat      913 
Gly Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr 
    290                 295                 300 

gac ctg act gcc atg aaa gtg cct act gct att tgg gct ggt gga cat      961 
Asp Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His 
305                 310                 315                 320 

gat gtc ctc gta aca ccc cag gat gtg gcc agg ata ctc cct caa atc     1009 
Asp Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile 
                325                 330                 335 

aag agt ctt cat tac ttt aag cta ttg cca gat tgg aac cac ttt gat     1057 
Lys Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp 
            340                 345                 350 

ttt gtc tgg ggc ctc gat gcc cct caa cgg atg tac agt gaa atc ata     1105 
Phe Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile 
        355                 360                 365 

gct tta atg aag gca tat tcc taaatgcaat gcatttactt ttcaattaaa        1156 
Ala Leu Met Lys Ala Tyr Ser 
    370                 375 

agttgcttcc aagcccataa gggactttag aaaaaatagt aaccaacaat gaggttgtcc   1216 

cccagcaccc tgggggagat gcacagtgga gtctgttttc caagtcaatt g            1267 

 
           
             16  
             375  
             PRT  
             Homo sapiens  
           
            16 

Ser Lys Met Trp Leu Leu Leu Thr Thr Thr Cys Leu Ile Cys Gly Thr 
1               5                   10                  15 

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

Val Trp Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser 
        35                  40                  45 

Glu Glu Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asp 
    50                  55                  60 

Arg Ile Pro Tyr Gly Arg Thr His Ala Gly Ser Thr Gly Pro Arg Pro 
65                  70                  75                  80 

Val Val Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu 
                85                  90                  95 

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

Tyr Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg 
        115                 120                 125 

His Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Ser Phe 
    130                 135                 140 

Asp Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val 
145                 150                 155                 160 

Asn Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly 
                165                 170                 175 

Thr Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln 
            180                 185                 190 

Arg Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr 
        195                 200                 205 

Pro Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile 
    210                 215                 220 

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

Lys Ile Ala Ser Asn Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile 
                245                 250                 255 

Cys Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met 
            260                 265                 270 

Asn Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn 
        275                 280                 285 

Gly Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr 
    290                 295                 300 

Asp Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His 
305                 310                 315                 320 

Asp Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile 
                325                 330                 335 

Lys Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp 
            340                 345                 350 

Phe Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile 
        355                 360                 365 

Ala Leu Met Lys Ala Tyr Ser 
    370                 375 

 
           
             17  
             1138  
             DNA  
             Homo sapiens  
             
               CDS  
               (8)..(1126)  
             
           
            17 

gtccaaa atg tgg ctg ctt tta aca aca act tgt ttg atc tgt gga act       49 
        Met Trp Leu Leu Leu Thr Thr Thr Cys Leu Ile Cys Gly Thr 
        1               5                   10 

tta aat gct ggt gga ttc ctt gat ttg gaa aat gaa gtg aat cct gag       97 
Leu Asn Ala Gly Gly Phe Leu Asp Leu Glu Asn Glu Val Asn Pro Glu 
15                  20                  25                  30 

gtg tgg atg aat act agt gaa atc atc atc tac aat ggc tac ccc agt      145 
Val Trp Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser 
                35                  40                  45 

gaa gag tat gaa gtc acc act gaa gat ggg tat ata ctc ctt gtc aac      193 
Glu Glu Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn 
            50                  55                  60 

aga att cct tat ggg cga aca cat gct agg agc aca ggt ccc cgg cca      241 
Arg Ile Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro 
        65                  70                  75 

gtt gtg tat atg cag cat gcc ctg ttt gca gac aat gcc tac tgg ctt      289 
Val Val Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu 
    80                  85                  90 

gag aat tat gct aat gga agc ctt gga ttc ctt cta gca gat gca ggt      337 
Glu Asn Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly 
95                  100                 105                 110 

tat gat gta tgg atg gga aac agt cgg gga aac act tgg tca aga aga      385 
Tyr Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg 
                115                 120                 125 

cac aaa aca ctc tca gag aca gat gag aaa ttc tgg gcc ttt ggt ttt      433 
His Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Gly Phe 
            130                 135                 140 

gat gaa atg gcc aaa tat gat ctc cca gga gta ata gac ttc att gta      481 
Asp Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val 
        145                 150                 155 

aat aaa act ggt cag gag aaa ttg tat ttc att gga cat tca ctt ggc      529 
Asn Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly 
    160                 165                 170 

act aca ata ggg ttt gta gcc ttt tcc acc atg cct gaa ctg gca caa      577 
Thr Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln 
175                 180                 185                 190 

aga atc aaa atg aat ttt gcc ttg ggt cct acg atc tca ttc aaa tat      625 
Arg Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr 
                195                 200                 205 

ccc acg ggc att ttt acc agg ttt ttt cta ctt cca aat tcc ata atc      673 
Pro Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile 
            210                 215                 220 

aag gct gtt ttt ggt acc aaa ggt ttc ttt tta gaa gat aag aaa acg      721 
Lys Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr 
        225                 230                 235 

aag ata gct tct acc aaa atc tgc aac aat aag ata ctc tgg ttg ata      769 
Lys Ile Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile 
    240                 245                 250 

tgt agc gaa ttt atg tcc tta tgg gct gga tcc aac aag aaa aat atg      817 
Cys Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met 
255                 260                 265                 270 

aat cag ctt tac cac tct gat gaa ttc aga gct tat gac tgg gga aat      865 
Asn Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn 
                275                 280                 285 

gac gct gat aat atg aaa cat tac aat cag agt cat ccc cct ata tat      913 
Asp Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr 
            290                 295                 300 

gac ctg act gcc atg aaa gtg cct act gct att tgg gct ggt gga cat      961 
Asp Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His 
        305                 310                 315 

gat gtc ctc gta aca ccc cag gat gtg gcc agg ata ctc cct caa atc     1009 
Asp Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile 
    320                 325                 330 

aag agt ctt cat tac ttt aag cta ttg cca gat tgg aac cac ttt gat     1057 
Lys Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp 
335                 340                 345                 350 

ttt gtc tgg ggc ctc gat gcc cct caa cgg atg tac agt gaa atc ata     1105 
Phe Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile 
                355                 360                 365 

gct tta atg aag gca tat tcc taaatgcaat gc                           1138 
Ala Leu Met Lys Ala Tyr Ser 
            370 

 
           
             18  
             373  
             PRT  
             Homo sapiens  
           
            18 

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

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

Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser Glu Glu 
        35                  40                  45 

Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn Arg Ile 
    50                  55                  60 

Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro Val Val 
65                  70                  75                  80 

Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu Glu Asn 
                85                  90                  95 

Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly Tyr Asp 
            100                 105                 110 

Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg His Lys 
        115                 120                 125 

Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Gly Phe Asp Glu 
    130                 135                 140 

Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val Asn Lys 
145                 150                 155                 160 

Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr Thr 
                165                 170                 175 

Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg Ile 
            180                 185                 190 

Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro Thr 
        195                 200                 205 

Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys Ala 
    210                 215                 220 

Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys Ile 
225                 230                 235                 240 

Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile Cys Ser 
                245                 250                 255 

Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met Asn Gln 
            260                 265                 270 

Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn Asp Ala 
        275                 280                 285 

Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr Asp Leu 
    290                 295                 300 

Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His Asp Val 
305                 310                 315                 320 

Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile Lys Ser 
                325                 330                 335 

Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp Phe Val 
            340                 345                 350 

Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile Ala Leu 
        355                 360                 365 

Met Lys Ala Tyr Ser 
    370 

 
           
             19  
             1080  
             DNA  
             Homo sapiens  
             
               CDS  
               (1)..(1080)  
             
           
            19 

aga tct ggt gga ttc ctt gat ttg gaa aat gaa gtg aat cct gag gtg       48 
Arg Ser Gly Gly Phe Leu Asp Leu Glu Asn Glu Val Asn Pro Glu Val 
1               5                   10                  15 

tgg atg aat act agt gaa atc atc atc tac aat ggc tac ccc agt gaa       96 
Trp Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser Glu 
            20                  25                  30 

gag tat gaa gtc acc act gaa gat ggg tat ata ctc ctt gtc aac aga      144 
Glu Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn Arg 
        35                  40                  45 

att cct tat ggg cga aca cat gct agg agc aca ggt ccc cgg cca gtt      192 
Ile Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro Val 
    50                  55                  60 

gtg tat atg cag cat gcc ctg ttt gca gac aat gcc tac tgg ctt gag      240 
Val Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu Glu 
65                  70                  75                  80 

aat tat gcc aat gga agc ctt gga ttc ctt cta gca gat gca ggt tat      288 
Asn Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly Tyr 
                85                  90                  95 

gat gta tgg atg gga aac agt cgg gga aac act tgg tca aga aga cac      336 
Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg His 
            100                 105                 110 

aaa aca ctc tca gag aca gat gag aaa ttc tgg gcc ttt agt ttt gat      384 
Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Ser Phe Asp 
        115                 120                 125 

gaa atg gcc aaa tat gat ctc cca gga gta ata gac ttc att gta aat      432 
Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val Asn 
    130                 135                 140 

aaa act ggt cag gag aaa ttg tat ttc att gga cat tca ctt ggc act      480 
Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr 
145                 150                 155                 160 

aca ata ggg ttt gta gcc ttt tcc acc atg cct gaa ctg gca caa aga      528 
Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg 
                165                 170                 175 

atc aaa atg aat ttt gcc ttg ggt cct acg atc tca ttc aaa tat ccc      576 
Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro 
            180                 185                 190 

acg ggc att ttt acc agg ttt ttt cta ctt cca aat tcc ata atc aag      624 
Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys 
        195                 200                 205 

gct gtt ttt ggt acc aaa ggt ttc ttt tta gaa gat aag aaa acg aag      672 
Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys 
    210                 215                 220 

ata gct tct acc aaa atc tgc aac aat aag ata ctc tgg ttg ata tgt      720 
Ile Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile Cys 
225                 230                 235                 240 

agc gaa ttt atg tcc tta tgg gct gga tcc aac aag aaa aat atg aat      768 
Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met Asn 
                245                 250                 255 

cag ctt tac cac tct gat gaa ttc aga gct tat gac tgg gga aat gac      816 
Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn Asp 
            260                 265                 270 

gct gat aat atg aaa cat tac aat cag agt cat ccc cct ata tat gac      864 
Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr Asp 
        275                 280                 285 

ctg act gcc atg aaa gtg cct act gct att tgg gct ggt gga cat gat      912 
Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His Asp 
    290                 295                 300 

gtc ctc gta aca ccc cag gat gtg gcc agg ata ctc cct caa atc aag      960 
Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile Lys 
305                 310                 315                 320 

agt ctt cat tac ttt aag cta ttg cca gat tgg aac cac ttt gat ttt     1008 
Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp Phe 
                325                 330                 335 

gtc tgg ggc ctc gat gcc cct caa cgg atg tac agt gaa atc ata gct     1056 
Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile Ala 
            340                 345                 350 

tta atg aag gca tat tcc ctc gag                                     1080 
Leu Met Lys Ala Tyr Ser Leu Glu 
        355                 360 

 
           
             20  
             360  
             PRT  
             Homo sapiens  
           
            20 

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

Trp Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser Glu 
            20                  25                  30 

Glu Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn Arg 
        35                  40                  45 

Ile Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro Val 
    50                  55                  60 

Val Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu Glu 
65                  70                  75                  80 

Asn Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly Tyr 
                85                  90                  95 

Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg His 
            100                 105                 110 

Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Ser Phe Asp 
        115                 120                 125 

Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val Asn 
    130                 135                 140 

Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr 
145                 150                 155                 160 

Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg 
                165                 170                 175 

Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro 
            180                 185                 190 

Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys 
        195                 200                 205 

Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys 
    210                 215                 220 

Ile Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile Cys 
225                 230                 235                 240 

Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met Asn 
                245                 250                 255 

Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn Asp 
            260                 265                 270 

Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr Asp 
        275                 280                 285 

Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His Asp 
    290                 295                 300 

Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile Lys 
305                 310                 315                 320 

Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp Phe 
                325                 330                 335 

Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile Ala 
            340                 345                 350 

Leu Met Lys Ala Tyr Ser Leu Glu 
        355                 360 

 
           
             21  
             801  
             DNA  
             Homo sapiens  
             
               CDS  
               (1)..(801)  
             
           
            21 

aga tct tat gat gta tgg atg gga aac agt cgg gga aac act tgg tca       48 
Arg Ser Tyr Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser 
  1               5                  10                  15 

aga aga cac aaa aca ctc tca gag aca gat gag aaa ttc tgg gcc ttt       96 
Arg Arg His Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe 
             20                  25                  30 

agt ttt gat gaa atg gcc aaa tat gat ctc cca gga gta ata gac ttc      144 
Ser Phe Asp Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe 
         35                  40                  45 

att gta aat aaa act ggt cag gag aaa ttg tat ttc att gga cat tca      192 
Ile Val Asn Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser 
     50                  55                  60 

ctt ggc act aca ata ggg ttt gta gcc ttt tcc acc atg cct gaa ctg      240 
Leu Gly Thr Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu 
 65                  70                  75                  80 

gca caa aga atc aaa atg aat ttt gcc ttg ggt cct acg atc tca ttc      288 
Ala Gln Arg Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe 
                 85                  90                  95 

aaa tat ccc acg ggc att ttt acc agg ttt ttt cta ctt cca aat tcc      336 
Lys Tyr Pro Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser 
            100                 105                 110 

ata atc aag gct gtt ttt ggt acc aaa ggt ttc ttt tta gaa gat aag      384 
Ile Ile Lys Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys 
        115                 120                 125 

aaa acg aag ata gct tct acc aaa atc tgc aac aat aag ata ctc tgg      432 
Lys Thr Lys Ile Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp 
    130                 135                 140 

ttg ata tgt agc gaa ttt atg tcc tta tgg gct gga tcc aac aag aaa      480 
Leu Ile Cys Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys 
145                 150                 155                 160 

aat atg aat cag ctt tac cac tct gat gaa ttc aga gct tat gac tgg      528 
Asn Met Asn Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp 
                165                 170                 175 

gga aat gac gct gat aat atg aaa cat tac aat cag agt cat ccc cct      576 
Gly Asn Asp Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro 
            180                 185                 190 

ata tat gac ctg act gcc atg aaa gtg cct act gct att tgg gct ggt      624 
Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly 
        195                 200                 205 

gga cat gat gtc ctc gta aca ccc cag gat gtg gcc agg ata ctc cct      672 
Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro 
    210                 215                 220 

caa atc aag agt ctt cat tac ttt aag cta ttg cca gat tgg aac cac      720 
Gln Ile Lys Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His 
225                 230                 235                 240 

ttt gat ttt gtc tgg ggc ctc gat gcc cct caa cgg atg tac agt gaa      768 
Phe Asp Phe Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu 
                245                 250                 255 

atc ata gct tta atg aag gca tat tcc ctc gag                          801 
Ile Ile Ala Leu Met Lys Ala Tyr Ser Leu Glu 
            260                 265 

 
           
             22  
             267  
             PRT  
             Homo sapiens  
           
            22 

Arg Ser Tyr Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser 
1               5                   10                  15 

Arg Arg His Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe 
            20                  25                  30 

Ser Phe Asp Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe 
        35                  40                  45 

Ile Val Asn Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser 
    50                  55                  60 

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

Ala Gln Arg Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe 
                85                  90                  95 

Lys Tyr Pro Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser 
            100                 105                 110 

Ile Ile Lys Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys 
        115                 120                 125 

Lys Thr Lys Ile Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp 
    130                 135                 140 

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

Asn Met Asn Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp 
                165                 170                 175 

Gly Asn Asp Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro 
            180                 185                 190 

Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly 
        195                 200                 205 

Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro 
    210                 215                 220 

Gln Ile Lys Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His 
225                 230                 235                 240 

Phe Asp Phe Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu 
                245                 250                 255 

Ile Ile Ala Leu Met Lys Ala Tyr Ser Leu Glu 
            260                 265 

 
           
             23  
             1267  
             DNA  
             Homo sapiens  
             
               CDS  
               (8)..(1126)  
             
           
            23 

gtccaaa atg tgg ctg ctt tta aca aca act tgt ttg atc tgt gga act       49 
        Met Trp Leu Leu Leu Thr Thr Thr Cys Leu Ile Cys Gly Thr 
        1               5                   10 

tta aat gct ggt gga ttc ctt gat ttg gaa aat gaa gtg aat cct gag       97 
Leu Asn Ala Gly Gly Phe Leu Asp Leu Glu Asn Glu Val Asn Pro Glu 
15                  20                  25                  30 

gtg tgg atg aat act agt gaa atc atc atc tac aat ggc tac ccc agt      145 
Val Trp Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser 
                35                  40                  45 

gaa gag tat gaa gtc acc act gaa gat ggg tat ata ctc ctt gtc aac      193 
Glu Glu Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn 
            50                  55                  60 

aga att cct tat ggg cga aca cat gct agg agc aca ggt ccc cgg cca      241 
Arg Ile Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro 
        65                  70                  75 

gtt gtg tat atg cag cat gcc ctg ttt gca gac aat gcc tac tgg ctt      289 
Val Val Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu 
    80                  85                  90 

gag aat tat gct aat gga agc ctt gga ttc ctt cta gca gat gca ggt      337 
Glu Asn Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly 
95                  100                 105                 110 

tat gat gta tgg atg gga aac agt cgg gga aac act tgg tca aga aga      385 
Tyr Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg 
                115                 120                 125 

cac aaa aca ctc tca gag aca gat gag aaa ttc tgg gcc ttt ggt ttt      433 
His Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Gly Phe 
            130                 135                 140 

gat gaa atg gcc aaa tat gat ctc cca gga gta ata gac ttc att gta      481 
Asp Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val 
        145                 150                 155 

aat aaa act ggt cag gag aaa ttg tat ttc att gga cat tca ctt ggc      529 
Asn Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly 
    160                 165                 170 

act aca ata ggg ttt gta gcc ttt tcc acc atg cct gaa ctg gca caa      577 
Thr Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln 
175                 180                 185                 190 

aga atc aaa atg aat ttt gcc ttg ggt cct acg atc tca ttc aaa tat      625 
Arg Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr 
                195                 200                 205 

ccc acg ggc att ttt acc agg ttt ttt cta ctt cca aat tcc ata atc      673 
Pro Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile 
            210                 215                 220 

aag gct gtt ttt ggt acc aaa ggt ttc ttt tta gaa gat aag aaa acg      721 
Lys Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr 
        225                 230                 235 

aag ata gct tct acc aaa atc tgc aac aat aag ata ctc tgg ttg ata      769 
Lys Ile Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile 
    240                 245                 250 

tgt agc gaa ttt atg tcc tta tgg gct gga tcc aac aag aaa aat atg      817 
Cys Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met 
255                 260                 265                 270 

aat cag ctt tac cac tct gat gaa ttc aga gct tat gac tgg gga aat      865 
Asn Gln Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn 
                275                 280                 285 

gac gct gat aat atg aaa cat tac aat cag agt cat ccc cct ata tat      913 
Asp Ala Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr 
            290                 295                 300 

gac ctg act gcc atg aaa gtg cct act gct att tgg gct ggt gga cat      961 
Asp Leu Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His 
        305                 310                 315 

gat gtc ctc gta aca ccc cag gat gtg gcc agg ata ctc cct caa atc     1009 
Asp Val Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile 
    320                 325                 330 

aag agt ctt cat tac ttt aag cta ttg cca gat tgg aac cac ttt gat     1057 
Lys Ser Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp 
335                 340                 345                 350 

ttt gtc tgg ggc ctc gat gcc cct caa cgg atg tac agt gaa atc ata     1105 
Phe Val Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile 
                355                 360                 365 

gct tta atg aag gca tat tcc taaatgcaat gcatttactt ttcaattaaa        1156 
Ala Leu Met Lys Ala Tyr Ser 
            370 

agttgcttcc aagcccataa gggactttag aaaaaatagt aaccaacaat gaggttgtcc   1216 

cccagcaccc tgggggagat gcacagtgga gtctgttttc caagtcaatt g            1267 

 
           
             24  
             373  
             PRT  
             Homo sapiens  
           
            24 

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

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

Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser Glu Glu 
        35                  40                  45 

Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn Arg Ile 
    50                  55                  60 

Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro Val Val 
65                  70                  75                  80 

Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu Glu Asn 
                85                  90                  95 

Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly Tyr Asp 
            100                 105                 110 

Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg His Lys 
        115                 120                 125 

Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Gly Phe Asp Glu 
    130                 135                 140 

Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val Asn Lys 
145                 150                 155                 160 

Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr Thr 
                165                 170                 175 

Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg Ile 
            180                 185                 190 

Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro Thr 
        195                 200                 205 

Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys Ala 
    210                 215                 220 

Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys Ile 
225                 230                 235                 240 

Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile Cys Ser 
                245                 250                 255 

Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met Asn Gln 
            260                 265                 270 

Leu Tyr His Ser Asp Glu Phe Arg Ala Tyr Asp Trp Gly Asn Asp Ala 
        275                 280                 285 

Asp Asn Met Lys His Tyr Asn Gln Ser His Pro Pro Ile Tyr Asp Leu 
    290                 295                 300 

Thr Ala Met Lys Val Pro Thr Ala Ile Trp Ala Gly Gly His Asp Val 
305                 310                 315                 320 

Leu Val Thr Pro Gln Asp Val Ala Arg Ile Leu Pro Gln Ile Lys Ser 
                325                 330                 335 

Leu His Tyr Phe Lys Leu Leu Pro Asp Trp Asn His Phe Asp Phe Val 
            340                 345                 350 

Trp Gly Leu Asp Ala Pro Gln Arg Met Tyr Ser Glu Ile Ile Ala Leu 
        355                 360                 365 

Met Lys Ala Tyr Ser 
    370 

 
           
             25  
             1195  
             DNA  
             Homo sapiens  
             
               CDS  
               (8)..(1054)  
             
           
            25 

gtccaaa atg tgg ctg ctt tta aca aca act tgt ttg atc tgt gga act       49 
        Met Trp Leu Leu Leu Thr Thr Thr Cys Leu Ile Cys Gly Thr 
        1               5                   10 

tta aat gct ggt gga ttc ctt gat ttg gaa aat gaa gtg aat cct gag       97 
Leu Asn Ala Gly Gly Phe Leu Asp Leu Glu Asn Glu Val Asn Pro Glu 
15                  20                  25                  30 

gtg tgg atg aat act agt gaa atc atc atc tac aat ggc tac ccc agt      145 
Val Trp Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser 
                35                  40                  45 

gaa gag tat gaa gtc acc act gaa gat ggg tat ata ctc ctt gtc aac      193 
Glu Glu Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn 
            50                  55                  60 

aga att cct tat ggg cga aca cat gct agg agc aca ggt ccc cgg cca      241 
Arg Ile Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro 
        65                  70                  75 

gtt gtg tat atg cag cat gcc ctg ttt gca gac aat gcc tac tgg ctt      289 
Val Val Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu 
    80                  85                  90 

gag aat tat gct aat gga agc ctt gga ttc ctt cta gca gat gca ggt      337 
Glu Asn Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly 
95                  100                 105                 110 

tat gat gta tgg atg gga aac agt cgg gga aac act tgg tca aga aga      385 
Tyr Asp Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg 
                115                 120                 125 

cac aaa aca ctc tca gag aca gat gag aaa ttc tgg gcc ttt ggt ttt      433 
His Lys Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Gly Phe 
            130                 135                 140 

gat gaa atg gcc aaa tat gat ctc cca gga gta ata gac ttc att gta      481 
Asp Glu Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val 
        145                 150                 155 

aat aaa act ggt cag gag aaa ttg tat ttc att gga cat tca ctt ggc      529 
Asn Lys Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly 
    160                 165                 170 

act aca ata ggg ttt gta gcc ttt tcc acc atg cct gaa ctg gca caa      577 
Thr Thr Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln 
175                 180                 185                 190 

aga atc aaa atg aat ttt gcc ttg ggt cct acg atc tca ttc aaa tat      625 
Arg Ile Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr 
                195                 200                 205 

ccc acg ggc att ttt acc agg ttt ttt cta ctt cca aat tcc ata atc      673 
Pro Thr Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile 
            210                 215                 220 

aag gct gtt ttt ggt acc aaa ggt ttc ttt tta gaa gat aag aaa acg      721 
Lys Ala Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr 
        225                 230                 235 

aag ata gct tct acc aaa atc tgc aac aat aag ata ctc tgg ttg ata      769 
Lys Ile Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile 
    240                 245                 250 

tgt agc gaa ttt atg tcc tta tgg gct gga tcc aac aag aaa aat atg      817 
Cys Ser Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met 
255                 260                 265                 270 

aat cag agt cat ccc cct ata tat gac ctg act gcc atg aaa gtg cct      865 
Asn Gln Ser His Pro Pro Ile Tyr Asp Leu Thr Ala Met Lys Val Pro 
                275                 280                 285 

act gct att tgg gct ggt gga cat gat gtc ctc gta aca ccc cag gat      913 
Thr Ala Ile Trp Ala Gly Gly His Asp Val Leu Val Thr Pro Gln Asp 
            290                 295                 300 

gtg gcc agg ata ctc cct caa atc aag agt ctt cat tac ttt aag cta      961 
Val Ala Arg Ile Leu Pro Gln Ile Lys Ser Leu His Tyr Phe Lys Leu 
        305                 310                 315 

ttg cca gat tgg aac cac ttt gat ttt gtc tgg ggc ctc gat gcc cct     1009 
Leu Pro Asp Trp Asn His Phe Asp Phe Val Trp Gly Leu Asp Ala Pro 
    320                 325                 330 

caa cgg atg tac agt gaa atc ata gct tta atg aag gca tat tcc         1054 
Gln Arg Met Tyr Ser Glu Ile Ile Ala Leu Met Lys Ala Tyr Ser 
335                 340                 345 

taaatgcaat gcatttactt ttcgattaaa agttgcttcc aagcccataa gggactttag   1114 

aaaaaatagt aaccaacaat gaggttgtcc cccagcaacc tgggggagat gcacagtgga   1174 

gtctgttttc caagtcaatt g                                             1195 

 
           
             26  
             349  
             PRT  
             Homo sapiens  
           
            26 

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

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

Met Asn Thr Ser Glu Ile Ile Ile Tyr Asn Gly Tyr Pro Ser Glu Glu 
        35                  40                  45 

Tyr Glu Val Thr Thr Glu Asp Gly Tyr Ile Leu Leu Val Asn Arg Ile 
    50                  55                  60 

Pro Tyr Gly Arg Thr His Ala Arg Ser Thr Gly Pro Arg Pro Val Val 
65                  70                  75                  80 

Tyr Met Gln His Ala Leu Phe Ala Asp Asn Ala Tyr Trp Leu Glu Asn 
                85                  90                  95 

Tyr Ala Asn Gly Ser Leu Gly Phe Leu Leu Ala Asp Ala Gly Tyr Asp 
            100                 105                 110 

Val Trp Met Gly Asn Ser Arg Gly Asn Thr Trp Ser Arg Arg His Lys 
        115                 120                 125 

Thr Leu Ser Glu Thr Asp Glu Lys Phe Trp Ala Phe Gly Phe Asp Glu 
    130                 135                 140 

Met Ala Lys Tyr Asp Leu Pro Gly Val Ile Asp Phe Ile Val Asn Lys 
145                 150                 155                 160 

Thr Gly Gln Glu Lys Leu Tyr Phe Ile Gly His Ser Leu Gly Thr Thr 
                165                 170                 175 

Ile Gly Phe Val Ala Phe Ser Thr Met Pro Glu Leu Ala Gln Arg Ile 
            180                 185                 190 

Lys Met Asn Phe Ala Leu Gly Pro Thr Ile Ser Phe Lys Tyr Pro Thr 
        195                 200                 205 

Gly Ile Phe Thr Arg Phe Phe Leu Leu Pro Asn Ser Ile Ile Lys Ala 
    210                 215                 220 

Val Phe Gly Thr Lys Gly Phe Phe Leu Glu Asp Lys Lys Thr Lys Ile 
225                 230                 235                 240 

Ala Ser Thr Lys Ile Cys Asn Asn Lys Ile Leu Trp Leu Ile Cys Ser 
                245                 250                 255 

Glu Phe Met Ser Leu Trp Ala Gly Ser Asn Lys Lys Asn Met Asn Gln 
            260                 265                 270 

Ser His Pro Pro Ile Tyr Asp Leu Thr Ala Met Lys Val Pro Thr Ala 
        275                 280                 285 

Ile Trp Ala Gly Gly His Asp Val Leu Val Thr Pro Gln Asp Val Ala 
    290                 295                 300 

Arg Ile Leu Pro Gln Ile Lys Ser Leu His Tyr Phe Lys Leu Leu Pro 
305                 310                 315                 320 

Asp Trp Asn His Phe Asp Phe Val Trp Gly Leu Asp Ala Pro Gln Arg 
                325                 330                 335 

Met Tyr Ser Glu Ile Ile Ala Leu Met Lys Ala Tyr Ser 
            340                 345 

 
           
             27  
             1606  
             DNA  
             Homo sapiens  
             
               CDS  
               (1)..(1602)  
             
           
            27 

atg act cta atc tgg aga cat ttg ctg aga ccc ttg tgc ctg gtc act       48 
Met Thr Leu Ile Trp Arg His Leu Leu Arg Pro Leu Cys Leu Val Thr 
1               5                   10                  15 

tcc gct ccc agg atc ctt gag atg cat cct ttc ctg agc cta ggt act       96 
Ser Ala Pro Arg Ile Leu Glu Met His Pro Phe Leu Ser Leu Gly Thr 
            20                  25                  30 

tcc cgg aca tca gta acc aag ctc agt ctt cat aca aag ccc aga atg      144 
Ser Arg Thr Ser Val Thr Lys Leu Ser Leu His Thr Lys Pro Arg Met 
        35                  40                  45 

cct cca tgt gac ttc atg cct gaa aga tac cag tcc ctt ggc tac aac      192 
Pro Pro Cys Asp Phe Met Pro Glu Arg Tyr Gln Ser Leu Gly Tyr Asn 
    50                  55                  60 

cgt gtc ctg gaa atc cac aag gaa cat ctt tct cct gtg gtg acg gca      240 
Arg Val Leu Glu Ile His Lys Glu His Leu Ser Pro Val Val Thr Ala 
65                  70                  75                  80 

tat ttc cag aaa ccc ctg ctg ctc cac cag ggg cac atg gag tgg ctc      288 
Tyr Phe Gln Lys Pro Leu Leu Leu His Gln Gly His Met Glu Trp Leu 
                85                  90                  95 

ttt gat gct gaa gga aac aga tac ctg gat ttc ttt tcc ggg att gtt      336 
Phe Asp Ala Glu Gly Asn Arg Tyr Leu Asp Phe Phe Ser Gly Ile Val 
            100                 105                 110 

act gtc agt gtt ggc cac tgc cac ccg gtg tgt gca gga ggg acg tgg      384 
Thr Val Ser Val Gly His Cys His Pro Val Cys Ala Gly Gly Thr Trp 
        115                 120                 125 

cac gca gtg cag gta act ctg ctg tac tgc tta tcc aga aag gtg aat      432 
His Ala Val Gln Val Thr Leu Leu Tyr Cys Leu Ser Arg Lys Val Asn 
    130                 135                 140 

gca gtg gca caa aag cag ctc ggc cgc ctg tgg cat aca agc acc gtc      480 
Ala Val Ala Gln Lys Gln Leu Gly Arg Leu Trp His Thr Ser Thr Val 
145                 150                 155                 160 

ttc ttc cac cct cca atg cat gaa tat gca gag aag ctt gcc gca ctt      528 
Phe Phe His Pro Pro Met His Glu Tyr Ala Glu Lys Leu Ala Ala Leu 
                165                 170                 175 

ctt cct gag cct ctt aag gtc att ttc ttg gtg aac agt ggc tca gaa      576 
Leu Pro Glu Pro Leu Lys Val Ile Phe Leu Val Asn Ser Gly Ser Glu 
            180                 185                 190 

gcc aat gag ctg gcc atg ctg atg gcc agg gcg cac tca aac aac ata      624 
Ala Asn Glu Leu Ala Met Leu Met Ala Arg Ala His Ser Asn Asn Ile 
        195                 200                 205 

gac atc att tct ttc aga gga gcc tac cat gga tgc agt cct tac aca      672 
Asp Ile Ile Ser Phe Arg Gly Ala Tyr His Gly Cys Ser Pro Tyr Thr 
    210                 215                 220 

ctt ggc ttg aca aac gta ggg atc tac aag atg gaa ctc cct ggt ggg      720 
Leu Gly Leu Thr Asn Val Gly Ile Tyr Lys Met Glu Leu Pro Gly Gly 
225                 230                 235                 240 

aca ggt tgc caa cca aca atg tgt cca gat gtt ttt cgt ggc cct tgg      768 
Thr Gly Cys Gln Pro Thr Met Cys Pro Asp Val Phe Arg Gly Pro Trp 
                245                 250                 255 

gga gga agc cac tgt cga gat tct cca gtg caa aca atc agg aag tgc      816 
Gly Gly Ser His Cys Arg Asp Ser Pro Val Gln Thr Ile Arg Lys Cys 
            260                 265                 270 

agc tgt gca cca gac tgc tgc caa gct aaa gat cag tat att gag caa      864 
Ser Cys Ala Pro Asp Cys Cys Gln Ala Lys Asp Gln Tyr Ile Glu Gln 
        275                 280                 285 

ttc aaa gat acg ctg agc aca tct gtg gcc aag tca att gct gga ttt      912 
Phe Lys Asp Thr Leu Ser Thr Ser Val Ala Lys Ser Ile Ala Gly Phe 
    290                 295                 300 

ttc gca gaa cct att caa ggt gtg aat gga gtt gtc cag tac cca aag      960 
Phe Ala Glu Pro Ile Gln Gly Val Asn Gly Val Val Gln Tyr Pro Lys 
305                 310                 315                 320 

ggg ttt cta aag gaa gcc ttt gag ctg gtg cga aca agg gga ggc gtg     1008 
Gly Phe Leu Lys Glu Ala Phe Glu Leu Val Arg Thr Arg Gly Gly Val 
                325                 330                 335 

tgc att gca gat gaa gtg cag aca gga ttt gga agg ttg ggc tct cac     1056 
Cys Ile Ala Asp Glu Val Gln Thr Gly Phe Gly Arg Leu Gly Ser His 
            340                 345                 350 

ttc tgg ggc ttc caa acc cac gat gtc ctg cct gac att gtc acc atg     1104 
Phe Trp Gly Phe Gln Thr His Asp Val Leu Pro Asp Ile Val Thr Met 
        355                 360                 365 

gct aaa ggg att ggg aat ggc ctt ccc atg gca gca gtc ata acc act     1152 
Ala Lys Gly Ile Gly Asn Gly Leu Pro Met Ala Ala Val Ile Thr Thr 
    370                 375                 380 

cca gag att gcc aaa tct ttg gcg aaa tgc ctg cag cac ttc aac acc     1200 
Pro Glu Ile Ala Lys Ser Leu Ala Lys Cys Leu Gln His Phe Asn Thr 
385                 390                 395                 400 

ttt gga ggg aac ccc atg gcc tgt gcc att gga tct gct gtg ctt gag     1248 
Phe Gly Gly Asn Pro Met Ala Cys Ala Ile Gly Ser Ala Val Leu Glu 
                405                 410                 415 

gtg att aaa gaa gaa aat cta cag gaa aac agt caa gaa gtt ggg acc     1296 
Val Ile Lys Glu Glu Asn Leu Gln Glu Asn Ser Gln Glu Val Gly Thr 
            420                 425                 430 

tac atg tta cta aag ttt gct aag ctg cgg gat gaa ttt gaa att gtt     1344 
Tyr Met Leu Leu Lys Phe Ala Lys Leu Arg Asp Glu Phe Glu Ile Val 
        435                 440                 445 

gga gac gtc cga ggc aaa ggc ctc atg ata ggc ata gaa atg gtg cag     1392 
Gly Asp Val Arg Gly Lys Gly Leu Met Ile Gly Ile Glu Met Val Gln 
    450                 455                 460 

gat aag ata agc tgt cgg cct ctt ccc cgt gaa gaa gta aat cag atc     1440 
Asp Lys Ile Ser Cys Arg Pro Leu Pro Arg Glu Glu Val Asn Gln Ile 
465                 470                 475                 480 

cat gag gac tgc aag cac atg gga ctc ctc gtt ggc aga ggc agc att     1488 
His Glu Asp Cys Lys His Met Gly Leu Leu Val Gly Arg Gly Ser Ile 
                485                 490                 495 

ttt tct cag aca ttt cgc att gcg ccc tca atg tgc atc act aaa cca     1536 
Phe Ser Gln Thr Phe Arg Ile Ala Pro Ser Met Cys Ile Thr Lys Pro 
            500                 505                 510 

gaa gtt gat ttt gca gta gaa gta ttt cgt tct gcc tta acc caa cac     1584 
Glu Val Asp Phe Ala Val Glu Val Phe Arg Ser Ala Leu Thr Gln His 
        515                 520                 525 

atg gaa aga aga gct aag taac                                        1606 
Met Glu Arg Arg Ala Lys 
    530 

 
           
             28  
             534  
             PRT  
             Homo sapiens  
           
            28 

Met Thr Leu Ile Trp Arg His Leu Leu Arg Pro Leu Cys Leu Val Thr 
1               5                   10                  15 

Ser Ala Pro Arg Ile Leu Glu Met His Pro Phe Leu Ser Leu Gly Thr 
            20                  25                  30 

Ser Arg Thr Ser Val Thr Lys Leu Ser Leu His Thr Lys Pro Arg Met 
        35                  40                  45 

Pro Pro Cys Asp Phe Met Pro Glu Arg Tyr Gln Ser Leu Gly Tyr Asn 
    50                  55                  60 

Arg Val Leu Glu Ile His Lys Glu His Leu Ser Pro Val Val Thr Ala 
65                  70                  75                  80 

Tyr Phe Gln Lys Pro Leu Leu Leu His Gln Gly His Met Glu Trp Leu 
                85                  90                  95 

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

Thr Val Ser Val Gly His Cys His Pro Val Cys Ala Gly Gly Thr Trp 
        115                 120                 125 

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

Ala Val Ala Gln Lys Gln Leu Gly Arg Leu Trp His Thr Ser Thr Val 
145                 150                 155                 160 

Phe Phe His Pro Pro Met His Glu Tyr Ala Glu Lys Leu Ala Ala Leu 
                165                 170                 175 

Leu Pro Glu Pro Leu Lys Val Ile Phe Leu Val Asn Ser Gly Ser Glu 
            180                 185                 190 

Ala Asn Glu Leu Ala Met Leu Met Ala Arg Ala His Ser Asn Asn Ile 
        195                 200                 205 

Asp Ile Ile Ser Phe Arg Gly Ala Tyr His Gly Cys Ser Pro Tyr Thr 
    210                 215                 220 

Leu Gly Leu Thr Asn Val Gly Ile Tyr Lys Met Glu Leu Pro Gly Gly 
225                 230                 235                 240 

Thr Gly Cys Gln Pro Thr Met Cys Pro Asp Val Phe Arg Gly Pro Trp 
                245                 250                 255 

Gly Gly Ser His Cys Arg Asp Ser Pro Val Gln Thr Ile Arg Lys Cys 
            260                 265                 270 

Ser Cys Ala Pro Asp Cys Cys Gln Ala Lys Asp Gln Tyr Ile Glu Gln 
        275                 280                 285 

Phe Lys Asp Thr Leu Ser Thr Ser Val Ala Lys Ser Ile Ala Gly Phe 
    290                 295                 300 

Phe Ala Glu Pro Ile Gln Gly Val Asn Gly Val Val Gln Tyr Pro Lys 
305                 310                 315                 320 

Gly Phe Leu Lys Glu Ala Phe Glu Leu Val Arg Thr Arg Gly Gly Val 
                325                 330                 335 

Cys Ile Ala Asp Glu Val Gln Thr Gly Phe Gly Arg Leu Gly Ser His 
            340                 345                 350 

Phe Trp Gly Phe Gln Thr His Asp Val Leu Pro Asp Ile Val Thr Met 
        355                 360                 365 

Ala Lys Gly Ile Gly Asn Gly Leu Pro Met Ala Ala Val Ile Thr Thr 
    370                 375                 380 

Pro Glu Ile Ala Lys Ser Leu Ala Lys Cys Leu Gln His Phe Asn Thr 
385                 390                 395                 400 

Phe Gly Gly Asn Pro Met Ala Cys Ala Ile Gly Ser Ala Val Leu Glu 
                405                 410                 415 

Val Ile Lys Glu Glu Asn Leu Gln Glu Asn Ser Gln Glu Val Gly Thr 
            420                 425                 430 

Tyr Met Leu Leu Lys Phe Ala Lys Leu Arg Asp Glu Phe Glu Ile Val 
        435                 440                 445 

Gly Asp Val Arg Gly Lys Gly Leu Met Ile Gly Ile Glu Met Val Gln 
    450                 455                 460 

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

His Glu Asp Cys Lys His Met Gly Leu Leu Val Gly Arg Gly Ser Ile 
                485                 490                 495 

Phe Ser Gln Thr Phe Arg Ile Ala Pro Ser Met Cys Ile Thr Lys Pro 
            500                 505                 510 

Glu Val Asp Phe Ala Val Glu Val Phe Arg Ser Ala Leu Thr Gln His 
        515                 520                 525 

Met Glu Arg Arg Ala Lys 
    530 

 
           
             29  
             1335  
             DNA  
             Homo sapiens  
             
               CDS  
               (3)..(1319)  
             
           
            29 

aa atg act cta atc tgg aga cat ttg ctg aga ccc ttg tgc ctg gtc        47 
   Met Thr Leu Ile Trp Arg His Leu Leu Arg Pro Leu Cys Leu Val 
   1               5                   10                  15 

act tcc gct ccc agg atc ctt gag atg cat cct ttc ctg agc cta ggt       95 
Thr Ser Ala Pro Arg Ile Leu Glu Met His Pro Phe Leu Ser Leu Gly 
                20                  25                  30 

act tcc cgg aca tca gta acc aag ctc agt ctt cat aca aag ccc aga      143 
Thr Ser Arg Thr Ser Val Thr Lys Leu Ser Leu His Thr Lys Pro Arg 
            35                  40                  45 

atg cct cca tgt gac ttc atg cct gaa aga tac cag tcc ctt ggc tac      191 
Met Pro Pro Cys Asp Phe Met Pro Glu Arg Tyr Gln Ser Leu Gly Tyr 
        50                  55                  60 

aac cgt gtc ctg gaa atc cac aag gaa cat ctt tct cct gtg gtg acg      239 
Asn Arg Val Leu Glu Ile His Lys Glu His Leu Ser Pro Val Val Thr 
    65                  70                  75 

gca tat ttc cag aaa ccc ctg ctg ctc cac cag ggg cac atg gag tgg      287 
Ala Tyr Phe Gln Lys Pro Leu Leu Leu His Gln Gly His Met Glu Trp 
80                  85                  90                  95 

ctc ttt gat gct gaa gga agc aga tac ctg gat ttc ttt tcc ggg att      335 
Leu Phe Asp Ala Glu Gly Ser Arg Tyr Leu Asp Phe Phe Ser Gly Ile 
                100                 105                 110 

gtt act gtc agt gtt ggc cat tgc cac cca aag gtg aat gca gtg gca      383 
Val Thr Val Ser Val Gly His Cys His Pro Lys Val Asn Ala Val Ala 
            115                 120                 125 

caa aag cag ctc ggc cgc ctg tgg cat aca agc acc gtc ttc ttc cac      431 
Gln Lys Gln Leu Gly Arg Leu Trp His Thr Ser Thr Val Phe Phe His 
        130                 135                 140 

cct cca atg cat gaa tat gca gag aag ctt gcc gca ctt ctt cct gag      479 
Pro Pro Met His Glu Tyr Ala Glu Lys Leu Ala Ala Leu Leu Pro Glu 
    145                 150                 155 

cct ctt aag gtc att ttc ttg gtg aac agt ggc tca gaa gcc aat gag      527 
Pro Leu Lys Val Ile Phe Leu Val Asn Ser Gly Ser Glu Ala Asn Glu 
160                 165                 170                 175 

ctg gcc atg ctg atg gcc agg gcg cac tca aac aac ata gac atc att      575 
Leu Ala Met Leu Met Ala Arg Ala His Ser Asn Asn Ile Asp Ile Ile 
                180                 185                 190 

tct ttc aga gga gcc tac cat gga tgc agt cct tac aca ctt ggc ttg      623 
Ser Phe Arg Gly Ala Tyr His Gly Cys Ser Pro Tyr Thr Leu Gly Leu 
            195                 200                 205 

aca aac gta ggg acc tac aag atg gaa ctc cct ggt ggg aca ggt tgc      671 
Thr Asn Val Gly Thr Tyr Lys Met Glu Leu Pro Gly Gly Thr Gly Cys 
        210                 215                 220 

caa cca aca atg tgt cca gat gtt ttt cgt ggc cct tgg gga gga agc      719 
Gln Pro Thr Met Cys Pro Asp Val Phe Arg Gly Pro Trp Gly Gly Ser 
    225                 230                 235 

cac tgt cga gat tct cca gtg caa aca atc agg aag tgc agc tgt gca      767 
His Cys Arg Asp Ser Pro Val Gln Thr Ile Arg Lys Cys Ser Cys Ala 
240                 245                 250                 255 

cca gac tgc tgc caa gct aaa gat cag tat att gag caa ttc aaa gat      815 
Pro Asp Cys Cys Gln Ala Lys Asp Gln Tyr Ile Glu Gln Phe Lys Asp 
                260                 265                 270 

acg ctg agc aca tct gtg gcc aag tca att gct gga ttt ttc gca gaa      863 
Thr Leu Ser Thr Ser Val Ala Lys Ser Ile Ala Gly Phe Phe Ala Glu 
            275                 280                 285 

cct att caa ggt gtg aat gga gtt gtc cag tac cca aag ggg ttt cta      911 
Pro Ile Gln Gly Val Asn Gly Val Val Gln Tyr Pro Lys Gly Phe Leu 
        290                 295                 300 

aag gaa gcc ttt gag ctg gtg cga gca agg gga ggc gtg tgc att gca      959 
Lys Glu Ala Phe Glu Leu Val Arg Ala Arg Gly Gly Val Cys Ile Ala 
    305                 310                 315 

gat gaa gtg att aaa gaa gaa aat cta cag gaa aac agt caa gaa gtt     1007 
Asp Glu Val Ile Lys Glu Glu Asn Leu Gln Glu Asn Ser Gln Glu Val 
320                 325                 330                 335 

ggg acc tac atg tta cta aag ttt gct aag ctg cgg gat gaa ttt gaa     1055 
Gly Thr Tyr Met Leu Leu Lys Phe Ala Lys Leu Arg Asp Glu Phe Glu 
                340                 345                 350 

att gtt gga gac gtc cga ggc aaa ggc ctc atg ata ggc ata gaa atg     1103 
Ile Val Gly Asp Val Arg Gly Lys Gly Leu Met Ile Gly Ile Glu Met 
            355                 360                 365 

gtg cag gat aag ata agc tgt cgg cct ctt ccc cgt gaa gaa gta aat     1151 
Val Gln Asp Lys Ile Ser Cys Arg Pro Leu Pro Arg Glu Glu Val Asn 
        370                 375                 380 

cag atc cat gag gac cgc aag cac atg gga ctc ctc gtt ggc aga ggc     1199 
Gln Ile His Glu Asp Arg Lys His Met Gly Leu Leu Val Gly Arg Gly 
    385                 390                 395 

agc att ttt tct cag aca ttt cgc att gcg ccc tca atg tgc atc act     1247 
Ser Ile Phe Ser Gln Thr Phe Arg Ile Ala Pro Ser Met Cys Ile Thr 
400                 405                 410                 415 

aaa cca gaa gtt gat ttt gca gta gaa gta ttt cgt tct gcc tta acc     1295 
Lys Pro Glu Val Asp Phe Ala Val Glu Val Phe Arg Ser Ala Leu Thr 
                420                 425                 430 

caa cac atg gaa aga aga gct aag taacattgtc agaaat                   1335 
Gln His Met Glu Arg Arg Ala Lys 
            435 

 
           
             30  
             439  
             PRT  
             Homo sapiens  
           
            30 

Met Thr Leu Ile Trp Arg His Leu Leu Arg Pro Leu Cys Leu Val Thr 
1               5                   10                  15 

Ser Ala Pro Arg Ile Leu Glu Met His Pro Phe Leu Ser Leu Gly Thr 
            20                  25                  30 

Ser Arg Thr Ser Val Thr Lys Leu Ser Leu His Thr Lys Pro Arg Met 
        35                  40                  45 

Pro Pro Cys Asp Phe Met Pro Glu Arg Tyr Gln Ser Leu Gly Tyr Asn 
    50                  55                  60 

Arg Val Leu Glu Ile His Lys Glu His Leu Ser Pro Val Val Thr Ala 
65                  70                  75                  80 

Tyr Phe Gln Lys Pro Leu Leu Leu His Gln Gly His Met Glu Trp Leu 
                85                  90                  95 

Phe Asp Ala Glu Gly Ser Arg Tyr Leu Asp Phe Phe Ser Gly Ile Val 
            100                 105                 110 

Thr Val Ser Val Gly His Cys His Pro Lys Val Asn Ala Val Ala Gln 
        115                 120                 125 

Lys Gln Leu Gly Arg Leu Trp His Thr Ser Thr Val Phe Phe His Pro 
    130                 135                 140 

Pro Met His Glu Tyr Ala Glu Lys Leu Ala Ala Leu Leu Pro Glu Pro 
145                 150                 155                 160 

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

Ala Met Leu Met Ala Arg Ala His Ser Asn Asn Ile Asp Ile Ile Ser 
            180                 185                 190 

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

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

Pro Thr Met Cys Pro Asp Val Phe Arg Gly Pro Trp Gly Gly Ser His 
225                 230                 235                 240 

Cys Arg Asp Ser Pro Val Gln Thr Ile Arg Lys Cys Ser Cys Ala Pro 
                245                 250                 255 

Asp Cys Cys Gln Ala Lys Asp Gln Tyr Ile Glu Gln Phe Lys Asp Thr 
            260                 265                 270 

Leu Ser Thr Ser Val Ala Lys Ser Ile Ala Gly Phe Phe Ala Glu Pro 
        275                 280                 285 

Ile Gln Gly Val Asn Gly Val Val Gln Tyr Pro Lys Gly Phe Leu Lys 
    290                 295                 300 

Glu Ala Phe Glu Leu Val Arg Ala Arg Gly Gly Val Cys Ile Ala Asp 
305                 310                 315                 320 

Glu Val Ile Lys Glu Glu Asn Leu Gln Glu Asn Ser Gln Glu Val Gly 
                325                 330                 335 

Thr Tyr Met Leu Leu Lys Phe Ala Lys Leu Arg Asp Glu Phe Glu Ile 
            340                 345                 350 

Val Gly Asp Val Arg Gly Lys Gly Leu Met Ile Gly Ile Glu Met Val 
        355                 360                 365 

Gln Asp Lys Ile Ser Cys Arg Pro Leu Pro Arg Glu Glu Val Asn Gln 
    370                 375                 380 

Ile His Glu Asp Arg Lys His Met Gly Leu Leu Val Gly Arg Gly Ser 
385                 390                 395                 400 

Ile Phe Ser Gln Thr Phe Arg Ile Ala Pro Ser Met Cys Ile Thr Lys 
                405                 410                 415 

Pro Glu Val Asp Phe Ala Val Glu Val Phe Arg Ser Ala Leu Thr Gln 
            420                 425                 430 

His Met Glu Arg Arg Ala Lys 
        435 

 
           
             31  
             1554  
             DNA  
             Homo sapiens  
             
               CDS  
               (3)..(1547)  
             
           
            31 

aa atg act cta atc tgg aga cat ttg ctg aga ccc ttg tgc ctg gtc        47 
   Met Thr Leu Ile Trp Arg His Leu Leu Arg Pro Leu Cys Leu Val 
   1               5                   10                  15 

act tcc tct ccc agg atc ctt gag atg cat cct ttc ctg agc cta ggt       95 
Thr Ser Ser Pro Arg Ile Leu Glu Met His Pro Phe Leu Ser Leu Gly 
                 20                  25                  30 

act tcc cgg aca tca gta acc aag ctc agt ctt cat ata aag ccc aga      143 
Thr Ser Arg Thr Ser Val Thr Lys Leu Ser Leu His Ile Lys Pro Arg 
             35                  40                  45 

atg cct cca tgt gac ttc atg cct gaa aga tac cag tcc ctt ggc tac      191 
Met Pro Pro Cys Asp Phe Met Pro Glu Arg Tyr Gln Ser Leu Gly Tyr 
         50                  55                  60 

aac cgt gtc ctg gaa atc cac aag gaa cat ctt tct cct gtg gtg acg      239 
Asn Arg Val Leu Glu Ile His Lys Glu His Leu Ser Pro Val Val Thr 
     65                  70                  75 

gca tat ttc cag aaa ccc ctg ctg ctc cac cag ggg cac atg gag tgg      287 
Ala Tyr Phe Gln Lys Pro Leu Leu Leu His Gln Gly His Met Glu Trp 
 80                  85                  90                  95 

ctc ttt gat gct gaa gga aac aga tac ctg gat ttt ttt tcc ggg att      335 
Leu Phe Asp Ala Glu Gly Asn Arg Tyr Leu Asp Phe Phe Ser Gly Ile 
                100                 105                 110 

gtt act gtc agt gtt ggc cat tgc cac ccg aag gtg aat gca gtg gca      383 
Val Thr Val Ser Val Gly His Cys His Pro Lys Val Asn Ala Val Ala 
            115                 120                 125 

caa aag cag ctc ggc cgc ctg tgg cat aca agc acc atc ttc ttc cac      431 
Gln Lys Gln Leu Gly Arg Leu Trp His Thr Ser Thr Ile Phe Phe His 
        130                 135                 140 

cct cca atg cat gaa tat gca gag aag ctt gcc gca ctt ctt cct gag      479 
Pro Pro Met His Glu Tyr Ala Glu Lys Leu Ala Ala Leu Leu Pro Glu 
    145                 150                 155 

cct ctt aag gta att ttc ttg gtg aac agt ggc tca gaa gcc aat gag      527 
Pro Leu Lys Val Ile Phe Leu Val Asn Ser Gly Ser Glu Ala Asn Glu 
160                 165                 170                 175 

ctg gcc atg ctg atg gcc agg gcg cac tca aac aac ata gac atc att      575 
Leu Ala Met Leu Met Ala Arg Ala His Ser Asn Asn Ile Asp Ile Ile 
                180                 185                 190 

tct ttc aga gga gcc tac cat gga tgc agt cct tac aca ctt ggc ttg      623 
Ser Phe Arg Gly Ala Tyr His Gly Cys Ser Pro Tyr Thr Leu Gly Leu 
            195                 200                 205 

aca aac gta ggg acc tac aag atg gaa ctc cct ggt ggg aca ggt tgc      671 
Thr Asn Val Gly Thr Tyr Lys Met Glu Leu Pro Gly Gly Thr Gly Cys 
        210                 215                 220 

caa cca gtg aca atg tgt cca gat gtt ttt cgt ggc cct tgg gga gga      719 
Gln Pro Val Thr Met Cys Pro Asp Val Phe Arg Gly Pro Trp Gly Gly 
    225                 230                 235 

agc cac tgt cga gat tct cca gtg caa aca atc agg aag tgc agc tgt      767 
Ser His Cys Arg Asp Ser Pro Val Gln Thr Ile Arg Lys Cys Ser Cys 
240                 245                 250                 255 

gca cca gac tgc tgc caa gct aaa gat cag tat att gag caa ttc aaa      815 
Ala Pro Asp Cys Cys Gln Ala Lys Asp Gln Tyr Ile Glu Gln Phe Lys 
                260                 265                 270 

gat acg ctg agc aca tct gtg gcc aag tca att gct gga ttt ttc gca      863 
Asp Thr Leu Ser Thr Ser Val Ala Lys Ser Ile Ala Gly Phe Phe Ala 
            275                 280                 285 

gaa cct att caa ggt gtg aat gga gtt gtc cag tac cca aag ggg ttt      911 
Glu Pro Ile Gln Gly Val Asn Gly Val Val Gln Tyr Pro Lys Gly Phe 
        290                 295                 300 

cta aag gaa gcc ttt gag ctg gtg cga gca agg gga ggc gtg tgc att      959 
Leu Lys Glu Ala Phe Glu Leu Val Arg Ala Arg Gly Gly Val Cys Ile 
    305                 310                 315 

gca gat gaa gtg cag aca gga ttt gga agg ttg ggc tct cac ttc tgg     1007 
Ala Asp Glu Val Gln Thr Gly Phe Gly Arg Leu Gly Ser His Phe Trp 
320                 325                 330                 335 

ggc ttc caa acc cac gat gtc ctg cct gac att gtc acc atg gct aaa     1055 
Gly Phe Gln Thr His Asp Val Leu Pro Asp Ile Val Thr Met Ala Lys 
                340                 345                 350 

ggg att ggg aat ggc ttt ccc atg gca gca gtc ata acc act cca gag     1103 
Gly Ile Gly Asn Gly Phe Pro Met Ala Ala Val Ile Thr Thr Pro Glu 
            355                 360                 365 

att gcc aaa tct ttg gcg aaa tgc ctg cag cac ttc aac acc ttt gga     1151 
Ile Ala Lys Ser Leu Ala Lys Cys Leu Gln His Phe Asn Thr Phe Gly 
        370                 375                 380 

ggg aac ccc atg gcc tgt gcc att gga tct gct gtg ctt gag gtg att     1199 
Gly Asn Pro Met Ala Cys Ala Ile Gly Ser Ala Val Leu Glu Val Ile 
    385                 390                 395 

aaa gaa gaa aat cta cag gaa aac agt caa gaa gtt ggg acc tac atg     1247 
Lys Glu Glu Asn Leu Gln Glu Asn Ser Gln Glu Val Gly Thr Tyr Met 
400                 405                 410                 415 

tta cta aag ttt gct aag ctg cgg gat gaa ttt gaa att gtt gga gac     1295 
Leu Leu Lys Phe Ala Lys Leu Arg Asp Glu Phe Glu Ile Val Gly Asp 
                420                 425                 430 

gtc cga ggc aaa ggt ctc atg ata ggc ata gaa atg gtg cag gat aag     1343 
Val Arg Gly Lys Gly Leu Met Ile Gly Ile Glu Met Val Gln Asp Lys 
            435                 440                 445 

ata agc tgt cgg cct ctt ccc cgt gaa gaa gta aat cag atc cat gag     1391 
Ile Ser Cys Arg Pro Leu Pro Arg Glu Glu Val Asn Gln Ile His Glu 
        450                 455                 460 

gac tgc aag cac atg gga ctc ctc gtt ggc aga ggc agc att ttt tct     1439 
Asp Cys Lys His Met Gly Leu Leu Val Gly Arg Gly Ser Ile Phe Ser 
    465                 470                 475 

cag aca ttt cgc att gcg ccc tca atg tgc atc act aaa cca gaa gtt     1487 
Gln Thr Phe Arg Ile Ala Pro Ser Met Cys Ile Thr Lys Pro Glu Val 
480                 485                 490                 495 

gat ttt gca gta gaa gta ttt cgt tct gcc tta acc caa cac atg gaa     1535 
Asp Phe Ala Val Glu Val Phe Arg Ser Ala Leu Thr Gln His Met Glu 
                500                 505                 510 

aga aga gct aag taacatt                                             1554 
Arg Arg Ala Lys 
            515 

 
           
             32  
             515  
             PRT  
             Homo sapiens  
           
            32 

Met Thr Leu Ile Trp Arg His Leu Leu Arg Pro Leu Cys Leu Val Thr 
1               5                   10                  15 

Ser Ser Pro Arg Ile Leu Glu Met His Pro Phe Leu Ser Leu Gly Thr 
            20                  25                  30 

Ser Arg Thr Ser Val Thr Lys Leu Ser Leu His Ile Lys Pro Arg Met 
        35                  40                  45 

Pro Pro Cys Asp Phe Met Pro Glu Arg Tyr Gln Ser Leu Gly Tyr Asn 
    50                  55                  60 

Arg Val Leu Glu Ile His Lys Glu His Leu Ser Pro Val Val Thr Ala 
65                  70                  75                  80 

Tyr Phe Gln Lys Pro Leu Leu Leu His Gln Gly His Met Glu Trp Leu 
                85                  90                  95 

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

Thr Val Ser Val Gly His Cys His Pro Lys Val Asn Ala Val Ala Gln 
        115                 120                 125 

Lys Gln Leu Gly Arg Leu Trp His Thr Ser Thr Ile Phe Phe His Pro 
    130                 135                 140 

Pro Met His Glu Tyr Ala Glu Lys Leu Ala Ala Leu Leu Pro Glu Pro 
145                 150                 155                 160 

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

Ala Met Leu Met Ala Arg Ala His Ser Asn Asn Ile Asp Ile Ile Ser 
            180                 185                 190 

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

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

Pro Val Thr Met Cys Pro Asp Val Phe Arg Gly Pro Trp Gly Gly Ser 
225                 230                 235                 240 

His Cys Arg Asp Ser Pro Val Gln Thr Ile Arg Lys Cys Ser Cys Ala 
                245                 250                 255 

Pro Asp Cys Cys Gln Ala Lys Asp Gln Tyr Ile Glu Gln Phe Lys Asp 
            260                 265                 270 

Thr Leu Ser Thr Ser Val Ala Lys Ser Ile Ala Gly Phe Phe Ala Glu 
        275                 280                 285 

Pro Ile Gln Gly Val Asn Gly Val Val Gln Tyr Pro Lys Gly Phe Leu 
    290                 295                 300 

Lys Glu Ala Phe Glu Leu Val Arg Ala Arg Gly Gly Val Cys Ile Ala 
305                 310                 315                 320 

Asp Glu Val Gln Thr Gly Phe Gly Arg Leu Gly Ser His Phe Trp Gly 
                325                 330                 335 

Phe Gln Thr His Asp Val Leu Pro Asp Ile Val Thr Met Ala Lys Gly 
            340                 345                 350 

Ile Gly Asn Gly Phe Pro Met Ala Ala Val Ile Thr Thr Pro Glu Ile 
        355                 360                 365 

Ala Lys Ser Leu Ala Lys Cys Leu Gln His Phe Asn Thr Phe Gly Gly 
    370                 375                 380 

Asn Pro Met Ala Cys Ala Ile Gly Ser Ala Val Leu Glu Val Ile Lys 
385                 390                 395                 400 

Glu Glu Asn Leu Gln Glu Asn Ser Gln Glu Val Gly Thr Tyr Met Leu 
                405                 410                 415 

Leu Lys Phe Ala Lys Leu Arg Asp Glu Phe Glu Ile Val Gly Asp Val 
            420                 425                 430 

Arg Gly Lys Gly Leu Met Ile Gly Ile Glu Met Val Gln Asp Lys Ile 
        435                 440                 445 

Ser Cys Arg Pro Leu Pro Arg Glu Glu Val Asn Gln Ile His Glu Asp 
    450                 455                 460 

Cys Lys His Met Gly Leu Leu Val Gly Arg Gly Ser Ile Phe Ser Gln 
465                 470                 475                 480 

Thr Phe Arg Ile Ala Pro Ser Met Cys Ile Thr Lys Pro Glu Val Asp 
                485                 490                 495 

Phe Ala Val Glu Val Phe Arg Ser Ala Leu Thr Gln His Met Glu Arg 
            500                 505                 510 

Arg Ala Lys 
        515 

 
           
             33  
             2422  
             DNA  
             Homo sapiens  
             
               CDS  
               (41)..(1372)  
             
           
            33 

cctcccgaca atacaggggc agcactgcag agatttcatc atg gtc tcc cag gcc       55 
                                            Met Val Ser Gln Ala 
                                            1               5 

ctc agg ctc ctc tgc ctt ctg ctt ggg ctt cag ggc tgc ctg gct gca      103 
Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln Gly Cys Leu Ala Ala 
                10                  15                  20 

gtc ttc gta acc cag gag gaa gcc cac ggc gtc ctg cac cgg cgc cgg      151 
Val Phe Val Thr Gln Glu Glu Ala His Gly Val Leu His Arg Arg Arg 
            25                  30                  35 

cgc gcc aac gcg ttc ctg gag gag ctg cgg ccg ggc tcc ctg gag agg      199 
Arg Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro Gly Ser Leu Glu Arg 
        40                  45                  50 

gag tgc aag gag gag cag tgc tcc ttc gag gag gcc cgg gag atc ttc      247 
Glu Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu Ala Arg Glu Ile Phe 
    55                  60                  65 

aag gac gcg gag agg acg aag ctg ttc tgg att tct tac agt gat ggg      295 
Lys Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile Ser Tyr Ser Asp Gly 
70                  75                  80                  85 

gac cag tgt gcc tca agt cca tgc cag aat ggg ggc tcc tgc aag gac      343 
Asp Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly Gly Ser Cys Lys Asp 
                90                  95                  100 

cag ctc cag tcc tat atc tgc ttc tgc ctc cct gcc ttc gag ggc cgg      391 
Gln Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro Ala Phe Glu Gly Arg 
            105                 110                 115 

aac tgt gag acg cac aag gat gac cag ctg atc tgt gtg aac gag aac      439 
Asn Cys Glu Thr His Lys Asp Asp Gln Leu Ile Cys Val Asn Glu Asn 
        120                 125                 130 

ggc ggc tgt gag cag tac tgc agt gac cac acg ggc acc aag cgc tcc      487 
Gly Gly Cys Glu Gln Tyr Cys Ser Asp His Thr Gly Thr Lys Arg Ser 
    135                 140                 145 

tgt cgg tgc cac gag ggg tac tct ctg ctg gca gac ggg gtg tcc tgc      535 
Cys Arg Cys His Glu Gly Tyr Ser Leu Leu Ala Asp Gly Val Ser Cys 
150                 155                 160                 165 

aca ccc aca gtt gaa tat cca tgt gga aaa ata cct att cta gaa aaa      583 
Thr Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile Pro Ile Leu Glu Lys 
                170                 175                 180 

aga aat gcc agc aaa ccc caa ggc cga att gtg ggg ggc aag gtg tgc      631 
Arg Asn Ala Ser Lys Pro Gln Gly Arg Ile Val Gly Gly Lys Val Cys 
            185                 190                 195 

ccc aaa ggg gag tgt cca tgg cag gtc ctg ttg ttg gtg aat gga gct      679 
Pro Lys Gly Glu Cys Pro Trp Gln Val Leu Leu Leu Val Asn Gly Ala 
        200                 205                 210 

cag ttg tgt ggg ggg acc ctg atc aac acc atc tgg gtg gtc tcc gcg      727 
Gln Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile Trp Val Val Ser Ala 
    215                 220                 225 

gcc cac tgt ttc gac aaa atc aag aac tgg agg aac ctg atc gcg gtg      775 
Ala His Cys Phe Asp Lys Ile Lys Asn Trp Arg Asn Leu Ile Ala Val 
230                 235                 240                 245 

ctg ggc gag cac gac ctc agc gag cac gac ggg gat gag cag agc cgg      823 
Leu Gly Glu His Asp Leu Ser Glu His Asp Gly Asp Glu Gln Ser Arg 
                250                 255                 260 

cgg gtg gcg cag gtc atc atc ccc agc acg tac gtc ccg ggc acc acc      871 
Arg Val Ala Gln Val Ile Ile Pro Ser Thr Tyr Val Pro Gly Thr Thr 
            265                 270                 275 

aac cac gac atc gcg ctg ctc cgc ctg cac cag ccc gtg gtc ctc act      919 
Asn His Asp Ile Ala Leu Leu Arg Leu His Gln Pro Val Val Leu Thr 
        280                 285                 290 

gac cat gtg gtg ccc ctc tgc ctg ccc gaa cgg acg ttc tct gag agg      967 
Asp His Val Val Pro Leu Cys Leu Pro Glu Arg Thr Phe Ser Glu Arg 
    295                 300                 305 

acg ctg gcc ttc gtg cgc ttc tca ttg gtc agc ggc tgg ggc cag ctg     1015 
Thr Leu Ala Phe Val Arg Phe Ser Leu Val Ser Gly Trp Gly Gln Leu 
310                 315                 320                 325 

ctg gac cgt ggc gcc acg gcc ctg gag ctc atg gtc ctc aac gtg ccc     1063 
Leu Asp Arg Gly Ala Thr Ala Leu Glu Leu Met Val Leu Asn Val Pro 
                330                 335                 340 

cgg ctg atg acc cag gac tgc ctg cag cag tca cgg aag gtg gga gac     1111 
Arg Leu Met Thr Gln Asp Cys Leu Gln Gln Ser Arg Lys Val Gly Asp 
            345                 350                 355 

tcc cca aat atc acg gag tac atg ttc tgt gcc ggc tac tcg gat ggc     1159 
Ser Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala Gly Tyr Ser Asp Gly 
        360                 365                 370 

agc aag gac tcc tgc aag ggg gac agt gga ggc cca cat gcc acc cac     1207 
Ser Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly Pro His Ala Thr His 
    375                 380                 385 

tac cgg ggc acg tgg tac ctg acg ggc atc gtc agc tgg ggc cag ggc     1255 
Tyr Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val Ser Trp Gly Gln Gly 
390                 395                 400                 405 

tgc gca acc gtg ggc cac ttt ggg gtg tac acc agg gtc tcc cag tac     1303 
Cys Ala Thr Val Gly His Phe Gly Val Tyr Thr Arg Val Ser Gln Tyr 
                410                 415                 420 

atc gag tgg ctg caa aag ctc atg cgc tca gag cca cgc cca gga gtc     1351 
Ile Glu Trp Leu Gln Lys Leu Met Arg Ser Glu Pro Arg Pro Gly Val 
            425                 430                 435 

ctc ctg cga gcc cca ttt ccc tagcccagca gccctggcct gtggagagaa        1402 
Leu Leu Arg Ala Pro Phe Pro 
        440 

agccaaggct gcgtcgaact gtcctggcac caaatcccat atattcttct gcagttaatg   1462 

gggtagagga gggcatggga gggagggaga ggtggggagg gagacagaga cagaaacaga   1522 

gagagacaga gacagagaga gactgaggga gagactctga ggacatggag agagactcaa   1582 

agagactcca agattcaaag agactaatag agacacagag atggaataga aaagatgaga   1642 

ggcagaggca gacaggcgct ggacagaggg gcaggggagt gccaaggttg tcctggaggc   1702 

agacagccca gctgagcctc cttacctccc ttcagccaag ccccacctgc acgtgatctg   1762 

ctggccctca ggctgctgct ctgccttcat tgctggagac agtagaggca tgaacacaca   1822 

tggatgcaca cacacacacg ccaatgcaca cacacagaga tatgcacaca cacggatgca   1882 

cacacagatg gtcacacaga gatacgcaaa cacaccgatg cacacgcaca tagagatatg   1942 

cacacacaga tgcacacaca gatatacaca tggatgcacg cacatgccaa tgcacgcaca   2002 

catcagtgca cacggatgca cagagatatg cacacaccga tgtgcgcaca cacagatatg   2062 

cacacacatg gatgagcaca cacacaccaa gtgcgcacac acaccgatgt acacacacag   2122 

atgcacacac agatgcacac acaccgatgc tgactccatg tgtgctgtcc tctgaaggcg   2182 

gttgtttagc tctcactttt ctggttctta tccattatca tcttcacttc agacaattca   2242 

gaagcatcac catgcatggt ggcgaatgcc cccaaactct cccccaaatg tatttctccc   2302 

ttcgctgggt gccgggctgc acagactatt ccccacctgc ttcccagctt cacaataaac   2362 

ggctgcgtct cctccgcaca cctgtggtgc ctgccaccca aaaaaaaaaa aaaaaaaaaa   2422 

 
           
             34  
             444  
             PRT  
             Homo sapiens  
           
            34 

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

Gly Cys Leu Ala Ala Val Phe Val Thr Gln Glu Glu Ala His Gly Val 
            20                  25                  30 

Leu His Arg Arg Arg Arg Ala Asn Ala Phe Leu Glu Glu Leu Arg Pro 
        35                  40                  45 

Gly Ser Leu Glu Arg Glu Cys Lys Glu Glu Gln Cys Ser Phe Glu Glu 
    50                  55                  60 

Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg Thr Lys Leu Phe Trp Ile 
65                  70                  75                  80 

Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser Ser Pro Cys Gln Asn Gly 
                85                  90                  95 

Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr Ile Cys Phe Cys Leu Pro 
            100                 105                 110 

Ala Phe Glu Gly Arg Asn Cys Glu Thr His Lys Asp Asp Gln Leu Ile 
        115                 120                 125 

Cys Val Asn Glu Asn Gly Gly Cys Glu Gln Tyr Cys Ser Asp His Thr 
    130                 135                 140 

Gly Thr Lys Arg Ser Cys Arg Cys His Glu Gly Tyr Ser Leu Leu Ala 
145                 150                 155                 160 

Asp Gly Val Ser Cys Thr Pro Thr Val Glu Tyr Pro Cys Gly Lys Ile 
                165                 170                 175 

Pro Ile Leu Glu Lys Arg Asn Ala Ser Lys Pro Gln Gly Arg Ile Val 
            180                 185                 190 

Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln Val Leu Leu 
        195                 200                 205 

Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile Asn Thr Ile 
    210                 215                 220 

Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys Asn Trp Arg 
225                 230                 235                 240 

Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu His Asp Gly 
                245                 250                 255 

Asp Glu Gln Ser Arg Arg Val Ala Gln Val Ile Ile Pro Ser Thr Tyr 
            260                 265                 270 

Val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg Leu His Gln 
        275                 280                 285 

Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu Pro Glu Arg 
    290                 295                 300 

Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser Leu Val Ser 
305                 310                 315                 320 

Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu Glu Leu Met 
                325                 330                 335 

Val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu Gln Gln Ser 
            340                 345                 350 

Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met Phe Cys Ala 
        355                 360                 365 

Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp Ser Gly Gly 
    370                 375                 380 

Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr Gly Ile Val 
385                 390                 395                 400 

Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly Val Tyr Thr 
                405                 410                 415 

Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met Arg Ser Glu 
            420                 425                 430 

Pro Arg Pro Gly Val Leu Leu Arg Ala Pro Phe Pro 
        435                 440 

 
           
             35  
             1361  
             DNA  
             Homo sapiens  
             
               CDS  
               (45)..(1301)  
             
           
            35 

tggggaatgt caacaggcag gggcagcact gcagagattt catc atg gtc tcc cag      56 
                                                 Met Val Ser Gln 
                                                 1 

gcc ctc agg ctc ctc tgc ctt ctg ctt ggg ctt cag ggc tgc ctg gct      104 
Ala Leu Arg Leu Leu Cys Leu Leu Leu Gly Leu Gln Gly Cys Leu Ala 
5                   10                  15                  20 

gca ggc ggg gtc gct aag gcc tca gga gga gaa aca cgg gac atg ccg      152 
Ala Gly Gly Val Ala Lys Ala Ser Gly Gly Glu Thr Arg Asp Met Pro 
                25                  30                  35 

tgg aag ccg ggg cct cac aga gtc ttc gta acc cag gag gaa gcc cac      200 
Trp Lys Pro Gly Pro His Arg Val Phe Val Thr Gln Glu Glu Ala His 
            40                  45                  50 

ggc gtc ctg cac cgg cgc cgg cgc gcc aac gcg ttc ctg gag gag ctg      248 
Gly Val Leu His Arg Arg Arg Arg Ala Asn Ala Phe Leu Glu Glu Leu 
        55                  60                  65 

cgg ccg ggc tcc ctg gag agg gag tgc aag gag gag cag tgc tcc ttc      296 
Arg Pro Gly Ser Leu Glu Arg Glu Cys Lys Glu Glu Gln Cys Ser Phe 
    70                  75                  80 

gag gag gcc cgg gag atc ttc aag gac gcg gag agg acg aag ctg ttc      344 
Glu Glu Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg Thr Lys Leu Phe 
85                  90                  95                  100 

tgg att tct tac agt gat ggg gac cag tgt gcc tca agt cca tgc cag      392 
Trp Ile Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser Ser Pro Cys Gln 
                105                 110                 115 

aat ggg ggc tcc tgc aag gac cag ctc cag tcc tat atc tgc ttc tgc      440 
Asn Gly Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr Ile Cys Phe Cys 
            120                 125                 130 

ctc cct gcc ttc gag ggc cgg aac tgt gag acg ctt gaa tat cca tgt      488 
Leu Pro Ala Phe Glu Gly Arg Asn Cys Glu Thr Leu Glu Tyr Pro Cys 
        135                 140                 145 

gga aaa ata cct att cta gaa aaa aga aat gcc agc aaa ccc caa ggc      536 
Gly Lys Ile Pro Ile Leu Glu Lys Arg Asn Ala Ser Lys Pro Gln Gly 
    150                 155                 160 

cga att gtg ggg ggc aag gtg tgc ccc aaa ggg gag tgt cca tgg cag      584 
Arg Ile Val Gly Gly Lys Val Cys Pro Lys Gly Glu Cys Pro Trp Gln 
165                 170                 175                 180 

gtc ctg ttg ttg gtg aat gga gct cag ttg tgt ggg ggg acc ctg atc      632 
Val Leu Leu Leu Val Asn Gly Ala Gln Leu Cys Gly Gly Thr Leu Ile 
                185                 190                 195 

aac acc atc tgg gtg gtc tcc gcg gcc cac tgt ttc gac aaa atc aag      680 
Asn Thr Ile Trp Val Val Ser Ala Ala His Cys Phe Asp Lys Ile Lys 
            200                 205                 210 

aac tgg agg aac ctg atc gcg gtg ctg ggc gag cac gac ctc agc gag      728 
Asn Trp Arg Asn Leu Ile Ala Val Leu Gly Glu His Asp Leu Ser Glu 
        215                 220                 225 

cac gac ggg gat gag cag agc cgg cgg gtg gcg cag gtc atc atc ccc      776 
His Asp Gly Asp Glu Gln Ser Arg Arg Val Ala Gln Val Ile Ile Pro 
    230                 235                 240 

agc acg tac gtc ccg ggc acc acc aac cac gac atc gcg ctg ctc cgc      824 
Ser Thr Tyr Val Pro Gly Thr Thr Asn His Asp Ile Ala Leu Leu Arg 
245                 250                 255                 260 

ctg cac cag ccc gtg gtc ctc act gac cat gtg gtg ccc ctc tgc ctg      872 
Leu His Gln Pro Val Val Leu Thr Asp His Val Val Pro Leu Cys Leu 
                265                 270                 275 

ccc gaa cgg acg ttc tct gag agg acg ctg gcc ttc gtg cgc ttc tca      920 
Pro Glu Arg Thr Phe Ser Glu Arg Thr Leu Ala Phe Val Arg Phe Ser 
            280                 285                 290 

ttg gtc agc ggc tgg ggc cag ctg ctg gac cgt ggc gcc acg gcc ctg      968 
Leu Val Ser Gly Trp Gly Gln Leu Leu Asp Arg Gly Ala Thr Ala Leu 
        295                 300                 305 

gag ctc atg gtc ctc aac gtg ccc cgg ctg atg acc cag gac tgc ctg     1016 
Glu Leu Met Val Leu Asn Val Pro Arg Leu Met Thr Gln Asp Cys Leu 
    310                 315                 320 

cag cag tca cgg aag gtg gga gac tcc cca aat atc acg gag tac atg     1064 
Gln Gln Ser Arg Lys Val Gly Asp Ser Pro Asn Ile Thr Glu Tyr Met 
325                 330                 335                 340 

ttc tgt gcc ggc tac tcg gat ggc agc aag gac tcc tgc aag ggg gac     1112 
Phe Cys Ala Gly Tyr Ser Asp Gly Ser Lys Asp Ser Cys Lys Gly Asp 
                345                 350                 355 

agt gga ggc cca cat gcc acc cac tac cgg ggc acg tgg tac ctg acg     1160 
Ser Gly Gly Pro His Ala Thr His Tyr Arg Gly Thr Trp Tyr Leu Thr 
            360                 365                 370 

ggc atc gtc agc tgg ggc cag ggc tgc gca acc gtg ggc cac ttt ggg     1208 
Gly Ile Val Ser Trp Gly Gln Gly Cys Ala Thr Val Gly His Phe Gly 
        375                 380                 385 

gtg tac acc agg gtc tcc cag tac atc gag tgg ctg caa aag ctc atg     1256 
Val Tyr Thr Arg Val Ser Gln Tyr Ile Glu Trp Leu Gln Lys Leu Met 
    390                 395                 400 

cgc tca gag cca cgc cca gga gtc ctc ctg cga gcc cca ttt ccc         1301 
Arg Ser Glu Pro Arg Pro Gly Val Leu Leu Arg Ala Pro Phe Pro 
405                 410                 415 

tagcccagca gccctggcct gtggagagaa agccaaggct gcgtcgaact gtcctggcac   1361 

 
           
             36  
             419  
             PRT  
             Homo sapiens  
           
            36 

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

Gly Cys Leu Ala Ala Gly Gly Val Ala Lys Ala Ser Gly Gly Glu Thr 
            20                  25                  30 

Arg Asp Met Pro Trp Lys Pro Gly Pro His Arg Val Phe Val Thr Gln 
        35                  40                  45 

Glu Glu Ala His Gly Val Leu His Arg Arg Arg Arg Ala Asn Ala Phe 
    50                  55                  60 

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

Gln Cys Ser Phe Glu Glu Ala Arg Glu Ile Phe Lys Asp Ala Glu Arg 
                85                  90                  95 

Thr Lys Leu Phe Trp Ile Ser Tyr Ser Asp Gly Asp Gln Cys Ala Ser 
            100                 105                 110 

Ser Pro Cys Gln Asn Gly Gly Ser Cys Lys Asp Gln Leu Gln Ser Tyr 
        115                 120                 125 

Ile Cys Phe Cys Leu Pro Ala Phe Glu Gly Arg Asn Cys Glu Thr Leu 
    130                 135                 140 

Glu Tyr Pro Cys Gly Lys Ile Pro Ile Leu Glu Lys Arg Asn Ala Ser 
145                 150                 155                 160 

Lys Pro Gln Gly Arg Ile Val Gly Gly Lys Val Cys Pro Lys Gly Glu 
                165                 170                 175 

Cys Pro Trp Gln Val Leu Leu Leu Val Asn Gly Ala Gln Leu Cys Gly 
            180                 185                 190 

Gly Thr Leu Ile Asn Thr Ile Trp Val Val Ser Ala Ala His Cys Phe 
        195                 200                 205 

Asp Lys Ile Lys Asn Trp Arg Asn Leu Ile Ala Val Leu Gly Glu His 
    210                 215                 220 

Asp Leu Ser Glu His Asp Gly Asp Glu Gln Ser Arg Arg Val Ala Gln 
225                 230                 235                 240 

Val Ile Ile Pro Ser Thr Tyr Val Pro Gly Thr Thr Asn His Asp Ile 
                245                 250                 255 

Ala Leu Leu Arg Leu His Gln Pro Val Val Leu Thr Asp His Val Val 
            260                 265                 270 

Pro Leu Cys Leu Pro Glu Arg Thr Phe Ser Glu Arg Thr Leu Ala Phe 
        275                 280                 285 

Val Arg Phe Ser Leu Val Ser Gly Trp Gly Gln Leu Leu Asp Arg Gly 
    290                 295                 300 

Ala Thr Ala Leu Glu Leu Met Val Leu Asn Val Pro Arg Leu Met Thr 
305                 310                 315                 320 

Gln Asp Cys Leu Gln Gln Ser Arg Lys Val Gly Asp Ser Pro Asn Ile 
                325                 330                 335 

Thr Glu Tyr Met Phe Cys Ala Gly Tyr Ser Asp Gly Ser Lys Asp Ser 
            340                 345                 350 

Cys Lys Gly Asp Ser Gly Gly Pro His Ala Thr His Tyr Arg Gly Thr 
        355                 360                 365 

Trp Tyr Leu Thr Gly Ile Val Ser Trp Gly Gln Gly Cys Ala Thr Val 
    370                 375                 380 

Gly His Phe Gly Val Tyr Thr Arg Val Ser Gln Tyr Ile Glu Trp Leu 
385                 390                 395                 400 

Gln Lys Leu Met Arg Ser Glu Pro Arg Pro Gly Val Leu Leu Arg Ala 
                405                 410                 415 

Pro Phe Pro 

 
           
             37  
             1399  
             DNA  
             Homo sapiens  
             
               CDS  
               (14)..(1390)  
             
           
            37 

caccggatcc acc atg gtg cgg tct gtg gcc tgg gca ggt ttc atg gtc        49 
               Met Val Arg Ser Val Ala Trp Ala Gly Phe Met Val 
               1               5                   10 

ctg ctg atg atc cca tgg ggc tct gct gca aaa ctg gtc tgc tac ttc       97 
Leu Leu Met Ile Pro Trp Gly Ser Ala Ala Lys Leu Val Cys Tyr Phe 
        15                  20                  25 

acc aac tgg gcc cag tac aga cag ggg gag gct cgc ttc ctg ccc aag      145 
Thr Asn Trp Ala Gln Tyr Arg Gln Gly Glu Ala Arg Phe Leu Pro Lys 
    30                  35                  40 

gac ttg gac ccc agc ctt tgc acc cac ctc atc tac gcc ttc gct ggc      193 
Asp Leu Asp Pro Ser Leu Cys Thr His Leu Ile Tyr Ala Phe Ala Gly 
45                  50                  55                  60 

atg acc aac cac cag ctg agc acc act gag tgg aat gac gag act ctc      241 
Met Thr Asn His Gln Leu Ser Thr Thr Glu Trp Asn Asp Glu Thr Leu 
                65                  70                  75 

tac cag gag ttc aat ggc ctg aag aag atg aat ccc aag ctg aag acc      289 
Tyr Gln Glu Phe Asn Gly Leu Lys Lys Met Asn Pro Lys Leu Lys Thr 
            80                  85                  90 

ctg tta gcc atc gga ggc tgg aat ttc ggc act cag aag ttc aca gat      337 
Leu Leu Ala Ile Gly Gly Trp Asn Phe Gly Thr Gln Lys Phe Thr Asp 
        95                  100                 105 

atg gta gcc acg gcc aac aac cgt cag acc ttt gtc aac tcg gcc atc      385 
Met Val Ala Thr Ala Asn Asn Arg Gln Thr Phe Val Asn Ser Ala Ile 
    110                 115                 120 

agg ttt ctg cgc aaa tac agc ttt gac ggc ctt gac ctt gac tgg gag      433 
Arg Phe Leu Arg Lys Tyr Ser Phe Asp Gly Leu Asp Leu Asp Trp Glu 
125                 130                 135                 140 

tac cca gga agc cag ggg agc cct gcc gta gac aag gag cgc ttc aca      481 
Tyr Pro Gly Ser Gln Gly Ser Pro Ala Val Asp Lys Glu Arg Phe Thr 
                145                 150                 155 

acc ctg gta cag gac ttg gcc aat gcc ttc cag cag gaa gcc cag acc      529 
Thr Leu Val Gln Asp Leu Ala Asn Ala Phe Gln Gln Glu Ala Gln Thr 
            160                 165                 170 

tca ggg aag gaa cgc ctt ctt ctg agt gca gcg gtt cca gct ggg cag      577 
Ser Gly Lys Glu Arg Leu Leu Leu Ser Ala Ala Val Pro Ala Gly Gln 
        175                 180                 185 

acc tat gtg gat gct gga tac gag gtg gac aaa atc gcc cag aac ctg      625 
Thr Tyr Val Asp Ala Gly Tyr Glu Val Asp Lys Ile Ala Gln Asn Leu 
    190                 195                 200 

gat ttt gtc aac ctt atg gcc tac gac ttc cat ggc tct tgg gag aag      673 
Asp Phe Val Asn Leu Met Ala Tyr Asp Phe His Gly Ser Trp Glu Lys 
205                 210                 215                 220 

gtc acg gga cat aac agc ccc ctc tac aag agg caa gaa gag agt ggt      721 
Val Thr Gly His Asn Ser Pro Leu Tyr Lys Arg Gln Glu Glu Ser Gly 
                225                 230                 235 

gca gca gcc agc ctc aac gtg gat gct gct gtg caa cag tgg ctg cag      769 
Ala Ala Ala Ser Leu Asn Val Asp Ala Ala Val Gln Gln Trp Leu Gln 
            240                 245                 250 

aag ggg acc cct gcc agc aag ctg atc ctt ggc atg cct acc tac gga      817 
Lys Gly Thr Pro Ala Ser Lys Leu Ile Leu Gly Met Pro Thr Tyr Gly 
        255                 260                 265 

cgc tcc ttc aca ctg gcc tcc tca tca gac acc aga gtg ggg gcc cca      865 
Arg Ser Phe Thr Leu Ala Ser Ser Ser Asp Thr Arg Val Gly Ala Pro 
    270                 275                 280 

gcc aca ggg tct ggc act cca ggc ccc ttc acc aag gaa gga ggg atg      913 
Ala Thr Gly Ser Gly Thr Pro Gly Pro Phe Thr Lys Glu Gly Gly Met 
285                 290                 295                 300 

ctg gcc tac tat gaa gtc tgc tcc tgg aag ggg gcc acc aaa cag aga      961 
Leu Ala Tyr Tyr Glu Val Cys Ser Trp Lys Gly Ala Thr Lys Gln Arg 
                305                 310                 315 

atc cag gat cag aag gtg ccc tac atc ttc cgg gac aac cag tgg gtg     1009 
Ile Gln Asp Gln Lys Val Pro Tyr Ile Phe Arg Asp Asn Gln Trp Val 
            320                 325                 330 

ggc ttt gat gat gtg gag agc ttc aaa acc aag gtc agc tat ctg aag     1057 
Gly Phe Asp Asp Val Glu Ser Phe Lys Thr Lys Val Ser Tyr Leu Lys 
        335                 340                 345 

cag aag gga ctg ggc ggg gcc atg gtc tgg gca ctg gac tta gat gac     1105 
Gln Lys Gly Leu Gly Gly Ala Met Val Trp Ala Leu Asp Leu Asp Asp 
    350                 355                 360 

ttt gcc ggc ttc tcc tgc aac cag ggc cga tac ccc ctc atc cag acg     1153 
Phe Ala Gly Phe Ser Cys Asn Gln Gly Arg Tyr Pro Leu Ile Gln Thr 
365                 370                 375                 380 

cta cgg cag gaa ctg agc acc cca gag ctt gaa gtt cca aaa cca ggt     1201 
Leu Arg Gln Glu Leu Ser Thr Pro Glu Leu Glu Val Pro Lys Pro Gly 
                385                 390                 395 

cag ccc tct gaa cct gag cat ggc ccc agc cct gga caa gac acg ttc     1249 
Gln Pro Ser Glu Pro Glu His Gly Pro Ser Pro Gly Gln Asp Thr Phe 
            400                 405                 410 

tgc cag ggc aaa gct gat ggg ctc tat ccc aat cct cgg gaa cgg tcc     1297 
Cys Gln Gly Lys Ala Asp Gly Leu Tyr Pro Asn Pro Arg Glu Arg Ser 
        415                 420                 425 

agc ttc tac agc tgt gca gcg ggg cgg ctg ttc cag caa agc tgc ccg     1345 
Ser Phe Tyr Ser Cys Ala Ala Gly Arg Leu Phe Gln Gln Ser Cys Pro 
    430                 435                 440 

aca ggc ctg gtg ttc agc aac tcc tgc aaa tgc tgc acc tgg aat         1390 
Thr Gly Leu Val Phe Ser Asn Ser Cys Lys Cys Cys Thr Trp Asn 
445                 450                 455 

gtcgacggc                                                           1399 

 
           
             38  
             459  
             PRT  
             Homo sapiens  
           
            38 

Met Val Arg Ser Val Ala Trp Ala Gly Phe Met Val Leu Leu Met Ile 
1               5                   10                  15 

Pro Trp Gly Ser Ala Ala Lys Leu Val Cys Tyr Phe Thr Asn Trp Ala 
            20                  25                  30 

Gln Tyr Arg Gln Gly Glu Ala Arg Phe Leu Pro Lys Asp Leu Asp Pro 
        35                  40                  45 

Ser Leu Cys Thr His Leu Ile Tyr Ala Phe Ala Gly Met Thr Asn His 
    50                  55                  60 

Gln Leu Ser Thr Thr Glu Trp Asn Asp Glu Thr Leu Tyr Gln Glu Phe 
65                  70                  75                  80 

Asn Gly Leu Lys Lys Met Asn Pro Lys Leu Lys Thr Leu Leu Ala Ile 
                85                  90                  95 

Gly Gly Trp Asn Phe Gly Thr Gln Lys Phe Thr Asp Met Val Ala Thr 
            100                 105                 110 

Ala Asn Asn Arg Gln Thr Phe Val Asn Ser Ala Ile Arg Phe Leu Arg 
        115                 120                 125 

Lys Tyr Ser Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Ser 
    130                 135                 140 

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

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

Arg Leu Leu Leu Ser Ala Ala Val Pro Ala Gly Gln Thr Tyr Val Asp 
            180                 185                 190 

Ala Gly Tyr Glu Val Asp Lys Ile Ala Gln Asn Leu Asp Phe Val Asn 
        195                 200                 205 

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

Asn Ser Pro Leu Tyr Lys Arg Gln Glu Glu Ser Gly Ala Ala Ala Ser 
225                 230                 235                 240 

Leu Asn Val Asp Ala Ala Val Gln Gln Trp Leu Gln Lys Gly Thr Pro 
                245                 250                 255 

Ala Ser Lys Leu Ile Leu Gly Met Pro Thr Tyr Gly Arg Ser Phe Thr 
            260                 265                 270 

Leu Ala Ser Ser Ser Asp Thr Arg Val Gly Ala Pro Ala Thr Gly Ser 
        275                 280                 285 

Gly Thr Pro Gly Pro Phe Thr Lys Glu Gly Gly Met Leu Ala Tyr Tyr 
    290                 295                 300 

Glu Val Cys Ser Trp Lys Gly Ala Thr Lys Gln Arg Ile Gln Asp Gln 
305                 310                 315                 320 

Lys Val Pro Tyr Ile Phe Arg Asp Asn Gln Trp Val Gly Phe Asp Asp 
                325                 330                 335 

Val Glu Ser Phe Lys Thr Lys Val Ser Tyr Leu Lys Gln Lys Gly Leu 
            340                 345                 350 

Gly Gly Ala Met Val Trp Ala Leu Asp Leu Asp Asp Phe Ala Gly Phe 
        355                 360                 365 

Ser Cys Asn Gln Gly Arg Tyr Pro Leu Ile Gln Thr Leu Arg Gln Glu 
    370                 375                 380 

Leu Ser Thr Pro Glu Leu Glu Val Pro Lys Pro Gly Gln Pro Ser Glu 
385                 390                 395                 400 

Pro Glu His Gly Pro Ser Pro Gly Gln Asp Thr Phe Cys Gln Gly Lys 
                405                 410                 415 

Ala Asp Gly Leu Tyr Pro Asn Pro Arg Glu Arg Ser Ser Phe Tyr Ser 
            420                 425                 430 

Cys Ala Ala Gly Arg Leu Phe Gln Gln Ser Cys Pro Thr Gly Leu Val 
        435                 440                 445 

Phe Ser Asn Ser Cys Lys Cys Cys Thr Trp Asn 
    450                 455 

 
           
             39  
             1043  
             DNA  
             Homo sapiens  
             
               CDS  
               (30)..(983)  
             
           
            39 

tgggctgcag cctgccgctg agctgcatc atg gtg cgg tct gtg gcc tgg gca       53 
                                Met Val Arg Ser Val Ala Trp Ala 
                                1               5 

ggt ttc atg gtc ctg ctg atg atc cca tgg ggc tct gct gca aaa ctg      101 
Gly Phe Met Val Leu Leu Met Ile Pro Trp Gly Ser Ala Ala Lys Leu 
    10                  15                  20 

gtc tgc tac ttc acc aac tgg gcc cag tac aga cag ggg gag gct cgc      149 
Val Cys Tyr Phe Thr Asn Trp Ala Gln Tyr Arg Gln Gly Glu Ala Arg 
25                  30                  35                  40 

ttc ctg ccc aag gac ttg gac ccc agc ctt tgc acc cac ctc atc tac      197 
Phe Leu Pro Lys Asp Leu Asp Pro Ser Leu Cys Thr His Leu Ile Tyr 
                45                  50                  55 

gcc ttc gct ggc atg acc aac cac cag ctg agc acc act gag tgg aat      245 
Ala Phe Ala Gly Met Thr Asn His Gln Leu Ser Thr Thr Glu Trp Asn 
            60                  65                  70 

gac gag act ctc tac cag gag ttc aat ggc ctg aag aag atg ttc aca      293 
Asp Glu Thr Leu Tyr Gln Glu Phe Asn Gly Leu Lys Lys Met Phe Thr 
        75                  80                  85 

gat atg gta gcc acg gcc aac aac cgt cag acc ttt gtc aac tcg gcc      341 
Asp Met Val Ala Thr Ala Asn Asn Arg Gln Thr Phe Val Asn Ser Ala 
    90                  95                  100 

atc agg ttt ctg cgc aaa tac agc ttt gac ggc ctt gac ctt gac tgg      389 
Ile Arg Phe Leu Arg Lys Tyr Ser Phe Asp Gly Leu Asp Leu Asp Trp 
105                 110                 115                 120 

gag tac cca gga agc cag ggg agc cct gcc gta gac aag gag cgc ttc      437 
Glu Tyr Pro Gly Ser Gln Gly Ser Pro Ala Val Asp Lys Glu Arg Phe 
                125                 130                 135 

aca acc ctg gta cag gac ttg gcc aat gcc ttc cag cag gaa gcc cag      485 
Thr Thr Leu Val Gln Asp Leu Ala Asn Ala Phe Gln Gln Glu Ala Gln 
            140                 145                 150 

acc tca ggg aag gaa cgc ctt ctt ctg agt gca gcg gtt cca gct ggg      533 
Thr Ser Gly Lys Glu Arg Leu Leu Leu Ser Ala Ala Val Pro Ala Gly 
        155                 160                 165 

cag acc tat gtg gat gct gga tac gag gtg gac aaa atc gcc cag aac      581 
Gln Thr Tyr Val Asp Ala Gly Tyr Glu Val Asp Lys Ile Ala Gln Asn 
    170                 175                 180 

ctg gat ttt gtc aac ctt atg gcc tac gac ttc cat ggc tct tgg gag      629 
Leu Asp Phe Val Asn Leu Met Ala Tyr Asp Phe His Gly Ser Trp Glu 
185                 190                 195                 200 

aag gtc acg gga cat aac agc ccc ctc tac aag agg caa gaa gag agt      677 
Lys Val Thr Gly His Asn Ser Pro Leu Tyr Lys Arg Gln Glu Glu Ser 
                205                 210                 215 

ggt gca gca gcc agc ctc aac gtg ggc cga tac ccc ctc atc cag acg      725 
Gly Ala Ala Ala Ser Leu Asn Val Gly Arg Tyr Pro Leu Ile Gln Thr 
            220                 225                 230 

cta cgg cag gaa ctg agt ctt cca tac ttg cct tca ggc acc cca gag      773 
Leu Arg Gln Glu Leu Ser Leu Pro Tyr Leu Pro Ser Gly Thr Pro Glu 
        235                 240                 245 

ctt gaa gtt cca aaa cca ggt cag ccc tct gaa cct gag cat ggc ccc      821 
Leu Glu Val Pro Lys Pro Gly Gln Pro Ser Glu Pro Glu His Gly Pro 
    250                 255                 260 

agc cct gga caa gac acg ttc tgc cag ggc aaa gct gat ggg ctc tat      869 
Ser Pro Gly Gln Asp Thr Phe Cys Gln Gly Lys Ala Asp Gly Leu Tyr 
265                 270                 275                 280 

ccc aat cct cgg gaa cgg tcc agc ttc tac agc tgt gca gcg ggg cgg      917 
Pro Asn Pro Arg Glu Arg Ser Ser Phe Tyr Ser Cys Ala Ala Gly Arg 
                285                 290                 295 

ctg ttc cag caa agc tgc ccg aca ggc ctg gtg ttc agc aac tcc tgc      965 
Leu Phe Gln Gln Ser Cys Pro Thr Gly Leu Val Phe Ser Asn Ser Cys 
            300                 305                 310 

aaa tgc tgc acc tgg aat tgagtcgcta aagcccctcc agtcccagct            1013 
Lys Cys Cys Thr Trp Asn 
        315 

ttgaggctgg gcccaggatc actctacagc                                    1043 

 
           
             40  
             318  
             PRT  
             Homo sapiens  
           
            40 

Met Val Arg Ser Val Ala Trp Ala Gly Phe Met Val Leu Leu Met Ile 
1               5                   10                  15 

Pro Trp Gly Ser Ala Ala Lys Leu Val Cys Tyr Phe Thr Asn Trp Ala 
            20                  25                  30 

Gln Tyr Arg Gln Gly Glu Ala Arg Phe Leu Pro Lys Asp Leu Asp Pro 
        35                  40                  45 

Ser Leu Cys Thr His Leu Ile Tyr Ala Phe Ala Gly Met Thr Asn His 
    50                  55                  60 

Gln Leu Ser Thr Thr Glu Trp Asn Asp Glu Thr Leu Tyr Gln Glu Phe 
65                  70                  75                  80 

Asn Gly Leu Lys Lys Met Phe Thr Asp Met Val Ala Thr Ala Asn Asn 
                85                  90                  95 

Arg Gln Thr Phe Val Asn Ser Ala Ile Arg Phe Leu Arg Lys Tyr Ser 
            100                 105                 110 

Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Ser Gln Gly Ser 
        115                 120                 125 

Pro Ala Val Asp Lys Glu Arg Phe Thr Thr Leu Val Gln Asp Leu Ala 
    130                 135                 140 

Asn Ala Phe Gln Gln Glu Ala Gln Thr Ser Gly Lys Glu Arg Leu Leu 
145                 150                 155                 160 

Leu Ser Ala Ala Val Pro Ala Gly Gln Thr Tyr Val Asp Ala Gly Tyr 
                165                 170                 175 

Glu Val Asp Lys Ile Ala Gln Asn Leu Asp Phe Val Asn Leu Met Ala 
            180                 185                 190 

Tyr Asp Phe His Gly Ser Trp Glu Lys Val Thr Gly His Asn Ser Pro 
        195                 200                 205 

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

Gly Arg Tyr Pro Leu Ile Gln Thr Leu Arg Gln Glu Leu Ser Leu Pro 
225                 230                 235                 240 

Tyr Leu Pro Ser Gly Thr Pro Glu Leu Glu Val Pro Lys Pro Gly Gln 
                245                 250                 255 

Pro Ser Glu Pro Glu His Gly Pro Ser Pro Gly Gln Asp Thr Phe Cys 
            260                 265                 270 

Gln Gly Lys Ala Asp Gly Leu Tyr Pro Asn Pro Arg Glu Arg Ser Ser 
        275                 280                 285 

Phe Tyr Ser Cys Ala Ala Gly Arg Leu Phe Gln Gln Ser Cys Pro Thr 
    290                 295                 300 

Gly Leu Val Phe Ser Asn Ser Cys Lys Cys Cys Thr Trp Asn 
305                 310                 315 

 
           
             41  
             1546  
             DNA  
             Homo sapiens  
             
               CDS  
               (13)..(1323)  
             
           
            41 

ctgagctgca tc atg gtg cgg tct gtg gcc tgg gca ggt ttc atg gtc ctg     51 
              Met Val Arg Ser Val Ala Trp Ala Gly Phe Met Val Leu 
              1               5                   10 

ctg atg atc cca tgg ggc tct gct gca aaa ctg gtc tgc tac ttc acc       99 
Leu Met Ile Pro Trp Gly Ser Ala Ala Lys Leu Val Cys Tyr Phe Thr 
    15                  20                  25 

aac tgg gcc cag tac aga cag ggg gag gct cgc ttc ctg ccc aag gac      147 
Asn Trp Ala Gln Tyr Arg Gln Gly Glu Ala Arg Phe Leu Pro Lys Asp 
30                  35                  40                  45 

ttg gac ccc agc ctt tgc acc cac ctc atc tac gcc ttc gct ggc atg      195 
Leu Asp Pro Ser Leu Cys Thr His Leu Ile Tyr Ala Phe Ala Gly Met 
                50                  55                  60 

acc aac cac cag ctg agc acc act gag tgg aat gac gag act ctc tac      243 
Thr Asn His Gln Leu Ser Thr Thr Glu Trp Asn Asp Glu Thr Leu Tyr 
            65                  70                  75 

cag gag ttc aat ggc ctg aag aag atg aat ccc aag ctg aag acc ctg      291 
Gln Glu Phe Asn Gly Leu Lys Lys Met Asn Pro Lys Leu Lys Thr Leu 
        80                  85                  90 

tta gcc atc gga ggc tgg aat ttc ggc act cag aag ttc aca gat atg      339 
Leu Ala Ile Gly Gly Trp Asn Phe Gly Thr Gln Lys Phe Thr Asp Met 
    95                  100                 105 

gta gcc acg gcc aac aac cgt cag acc ttt gtc aac tcg gcc atc agg      387 
Val Ala Thr Ala Asn Asn Arg Gln Thr Phe Val Asn Ser Ala Ile Arg 
110                 115                 120                 125 

ttt ctg cgc aaa tac agc ttt gac ggc ctt gac ctt gac tgg gag tac      435 
Phe Leu Arg Lys Tyr Ser Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr 
                130                 135                 140 

cca gga agc cag ggg agc cct gcc gta gac aag gag cgc ttc aca acc      483 
Pro Gly Ser Gln Gly Ser Pro Ala Val Asp Lys Glu Arg Phe Thr Thr 
            145                 150                 155 

ctg gta cag gac ttg gcc aat gcc ttc cag cag gaa gcc cag acc tca      531 
Leu Val Gln Asp Leu Ala Asn Ala Phe Gln Gln Glu Ala Gln Thr Ser 
        160                 165                 170 

ggg aag gaa cgc ctt ctt ctg agt gca gcg gtt cca gct ggg cag acc      579 
Gly Lys Glu Arg Leu Leu Leu Ser Ala Ala Val Pro Ala Gly Gln Thr 
    175                 180                 185 

tat gtg gat gct gga tac gag gtg gac aaa atc gcc cag aac ctg gat      627 
Tyr Val Asp Ala Gly Tyr Glu Val Asp Lys Ile Ala Gln Asn Leu Asp 
190                 195                 200                 205 

ttt gtc aac ctt atg gcc tac gac ttc cat ggc tct tgg gag aag gtc      675 
Phe Val Asn Leu Met Ala Tyr Asp Phe His Gly Ser Trp Glu Lys Val 
                210                 215                 220 

acg gga cat aac agc ccc ctc tac aag agg caa gaa gag agt ggt gca      723 
Thr Gly His Asn Ser Pro Leu Tyr Lys Arg Gln Glu Glu Ser Gly Ala 
            225                 230                 235 

gca gcc agc ctc aac gtg gat gct gct gtg caa cag tgg ctg cag aag      771 
Ala Ala Ser Leu Asn Val Asp Ala Ala Val Gln Gln Trp Leu Gln Lys 
        240                 245                 250 

ggg acc cct gcc agc aag ctg atc ctt ggc atg cct acc tac gga cgc      819 
Gly Thr Pro Ala Ser Lys Leu Ile Leu Gly Met Pro Thr Tyr Gly Arg 
    255                 260                 265 

tcc ttc aca ctg gcc tcc tca tca gac acc aga gtg ggg gcc cca gcc      867 
Ser Phe Thr Leu Ala Ser Ser Ser Asp Thr Arg Val Gly Ala Pro Ala 
270                 275                 280                 285 

aca ggg tct ggc act cca ggc ccc ttc acc aag gaa gga ggg atg ctg      915 
Thr Gly Ser Gly Thr Pro Gly Pro Phe Thr Lys Glu Gly Gly Met Leu 
                290                 295                 300 

gcc tac tat gaa gtc tgc tcc tgg aag ggg gcc acc aaa cag aga atc      963 
Ala Tyr Tyr Glu Val Cys Ser Trp Lys Gly Ala Thr Lys Gln Arg Ile 
            305                 310                 315 

cag gat cag aag gtg ccc tac atc ttc cgg gac aac cag tgg gtg ggc     1011 
Gln Asp Gln Lys Val Pro Tyr Ile Phe Arg Asp Asn Gln Trp Val Gly 
        320                 325                 330 

ttt gat gat gtg gag agc ttc aaa acc aag ggc cga tac ccc ctc atc     1059 
Phe Asp Asp Val Glu Ser Phe Lys Thr Lys Gly Arg Tyr Pro Leu Ile 
    335                 340                 345 

cag acg cta cgg cag gaa ctg agt ctt cca tac ttg cct tca ggc acc     1107 
Gln Thr Leu Arg Gln Glu Leu Ser Leu Pro Tyr Leu Pro Ser Gly Thr 
350                 355                 360                 365 

cca gag ctt gaa gtt cca aaa cca ggt cag ccc tct gaa cct gag cat     1155 
Pro Glu Leu Glu Val Pro Lys Pro Gly Gln Pro Ser Glu Pro Glu His 
                370                 375                 380 

ggc ccc agc cct gga caa gac acg ttc tgc cag ggc aaa gct gat ggg     1203 
Gly Pro Ser Pro Gly Gln Asp Thr Phe Cys Gln Gly Lys Ala Asp Gly 
            385                 390                 395 

ctc tat ccc aat cct cgg gaa cgg tcc agc ttc tac agc tgt gca gcg     1251 
Leu Tyr Pro Asn Pro Arg Glu Arg Ser Ser Phe Tyr Ser Cys Ala Ala 
        400                 405                 410 

ggg cgg ctg ttc cag caa agc tgc ccg aca ggc ctg gtg ttc agc aac     1299 
Gly Arg Leu Phe Gln Gln Ser Cys Pro Thr Gly Leu Val Phe Ser Asn 
    415                 420                 425 

tcc tgc aaa tgc tgc acc tgg aat tgagtcgtaa agcccctcca gtccagcttt    1353 
Ser Cys Lys Cys Cys Thr Trp Asn 
430                 435 

gaggctgggc ccaggatcac tctacagcct gcctcctggg ttttcctggg ggccgcaatc   1413 

tggctcctgc aggcctttct gtggtcttcc tttatccagg ctttctgctc tcagccttgc   1473 

cttccttttt tctgggtctc ctgggctgcc cctttcactt gcaaaataaa tctttggttt   1533 

gtgcccctct tca                                                      1546 

 
           
             42  
             437  
             PRT  
             Homo sapiens  
           
            42 

Met Val Arg Ser Val Ala Trp Ala Gly Phe Met Val Leu Leu Met Ile 
1               5                   10                  15 

Pro Trp Gly Ser Ala Ala Lys Leu Val Cys Tyr Phe Thr Asn Trp Ala 
            20                  25                  30 

Gln Tyr Arg Gln Gly Glu Ala Arg Phe Leu Pro Lys Asp Leu Asp Pro 
        35                  40                  45 

Ser Leu Cys Thr His Leu Ile Tyr Ala Phe Ala Gly Met Thr Asn His 
    50                  55                  60 

Gln Leu Ser Thr Thr Glu Trp Asn Asp Glu Thr Leu Tyr Gln Glu Phe 
65                  70                  75                  80 

Asn Gly Leu Lys Lys Met Asn Pro Lys Leu Lys Thr Leu Leu Ala Ile 
                85                  90                  95 

Gly Gly Trp Asn Phe Gly Thr Gln Lys Phe Thr Asp Met Val Ala Thr 
            100                 105                 110 

Ala Asn Asn Arg Gln Thr Phe Val Asn Ser Ala Ile Arg Phe Leu Arg 
        115                 120                 125 

Lys Tyr Ser Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Ser 
    130                 135                 140 

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

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

Arg Leu Leu Leu Ser Ala Ala Val Pro Ala Gly Gln Thr Tyr Val Asp 
            180                 185                 190 

Ala Gly Tyr Glu Val Asp Lys Ile Ala Gln Asn Leu Asp Phe Val Asn 
        195                 200                 205 

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

Asn Ser Pro Leu Tyr Lys Arg Gln Glu Glu Ser Gly Ala Ala Ala Ser 
225                 230                 235                 240 

Leu Asn Val Asp Ala Ala Val Gln Gln Trp Leu Gln Lys Gly Thr Pro 
                245                 250                 255 

Ala Ser Lys Leu Ile Leu Gly Met Pro Thr Tyr Gly Arg Ser Phe Thr 
            260                 265                 270 

Leu Ala Ser Ser Ser Asp Thr Arg Val Gly Ala Pro Ala Thr Gly Ser 
        275                 280                 285 

Gly Thr Pro Gly Pro Phe Thr Lys Glu Gly Gly Met Leu Ala Tyr Tyr 
    290                 295                 300 

Glu Val Cys Ser Trp Lys Gly Ala Thr Lys Gln Arg Ile Gln Asp Gln 
305                 310                 315                 320 

Lys Val Pro Tyr Ile Phe Arg Asp Asn Gln Trp Val Gly Phe Asp Asp 
                325                 330                 335 

Val Glu Ser Phe Lys Thr Lys Gly Arg Tyr Pro Leu Ile Gln Thr Leu 
            340                 345                 350 

Arg Gln Glu Leu Ser Leu Pro Tyr Leu Pro Ser Gly Thr Pro Glu Leu 
        355                 360                 365 

Glu Val Pro Lys Pro Gly Gln Pro Ser Glu Pro Glu His Gly Pro Ser 
    370                 375                 380 

Pro Gly Gln Asp Thr Phe Cys Gln Gly Lys Ala Asp Gly Leu Tyr Pro 
385                 390                 395                 400 

Asn Pro Arg Glu Arg Ser Ser Phe Tyr Ser Cys Ala Ala Gly Arg Leu 
                405                 410                 415 

Phe Gln Gln Ser Cys Pro Thr Gly Leu Val Phe Ser Asn Ser Cys Lys 
            420                 425                 430 

Cys Cys Thr Trp Asn 
        435 

 
           
             43  
             1380  
             DNA  
             Homo sapiens  
             
               CDS  
               (3)..(1343)  
             
           
            43 

gc tct gca tac aaa ctg gtc tgc tac ttc acc aac tgg gcc cag tac        47 
   Ser Ala Tyr Lys Leu Val Cys Tyr Phe Thr Asn Trp Ala Gln Tyr 
   1               5                   10                  15 

aga cag ggg gag gct cgc ttc ctg ccc aag gac ttg gac ccc agc ctt       95 
Arg Gln Gly Glu Ala Arg Phe Leu Pro Lys Asp Leu Asp Pro Ser Leu 
                20                  25                  30 

tgc acc cac ctc atc tac gcc ttc gct ggc atg acc aac cac cag ctg      143 
Cys Thr His Leu Ile Tyr Ala Phe Ala Gly Met Thr Asn His Gln Leu 
            35                  40                  45 

agc acc act gag tgg aat gac gag act ctc tac cag gag ttc aat ggc      191 
Ser Thr Thr Glu Trp Asn Asp Glu Thr Leu Tyr Gln Glu Phe Asn Gly 
        50                  55                  60 

ctg aag aag atg aat ccc aag ctg aag acc ctg tta gcc atc gga ggc      239 
Leu Lys Lys Met Asn Pro Lys Leu Lys Thr Leu Leu Ala Ile Gly Gly 
    65                  70                  75 

tgg aat ttc agc act cag aag ttc aca gat atg gta gcc acg gcc aac      287 
Trp Asn Phe Ser Thr Gln Lys Phe Thr Asp Met Val Ala Thr Ala Asn 
80                  85                  90                  95 

aac cgt cag acc ttt gtc aac tcg gcc atc agg ttt ctg cgc aaa tac      335 
Asn Arg Gln Thr Phe Val Asn Ser Ala Ile Arg Phe Leu Arg Lys Tyr 
                100                 105                 110 

agc ttt gac ggc ctt gac ctt gac tgg gag tac cca gga agc cag ggg      383 
Ser Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Ser Gln Gly 
            115                 120                 125 

agc cct gcc gta gac aag gag cgc ttc aca acc ctg gta cag gac ttg      431 
Ser Pro Ala Val Asp Lys Glu Arg Phe Thr Thr Leu Val Gln Asp Leu 
        130                 135                 140 

gcc aat gcc ttc cag cag gaa gcc cag acc tca ggg aag gaa cgc ctt      479 
Ala Asn Ala Phe Gln Gln Glu Ala Gln Thr Ser Gly Lys Glu Arg Leu 
    145                 150                 155 

ctt ctg agt gca gcg gtt cca gct ggg cag acc tat gtg gat gct gga      527 
Leu Leu Ser Ala Ala Val Pro Ala Gly Gln Thr Tyr Val Asp Ala Gly 
160                 165                 170                 175 

tac gag gtg gac aaa atc gcc cag aac ctg gat ttt gtc aac ctt atg      575 
Tyr Glu Val Asp Lys Ile Ala Gln Asn Leu Asp Phe Val Asn Leu Met 
                180                 185                 190 

gcc tac gac ttc cat ggc tct tgg gag aag gtc acg gga cat aac agc      623 
Ala Tyr Asp Phe His Gly Ser Trp Glu Lys Val Thr Gly His Asn Ser 
            195                 200                 205 

ccc ctc tac aag agg caa gaa gag agt ggt gca gca gcc agc ctc aac      671 
Pro Leu Tyr Lys Arg Gln Glu Glu Ser Gly Ala Ala Ala Ser Leu Asn 
        210                 215                 220 

gtg gat gct gct gtg caa cag tgg ctg cag aag ggg acc cct gcc agc      719 
Val Asp Ala Ala Val Gln Gln Trp Leu Gln Lys Gly Thr Pro Ala Ser 
    225                 230                 235 

aag ctg atc ctt ggc atg cct acc tac gga cgc tcc ttc aca ctg gcc      767 
Lys Leu Ile Leu Gly Met Pro Thr Tyr Gly Arg Ser Phe Thr Leu Ala 
240                 245                 250                 255 

tcc tca tca gac acc aga gtg ggg gcc cca gcc aca ggg tct ggc act      815 
Ser Ser Ser Asp Thr Arg Val Gly Ala Pro Ala Thr Gly Ser Gly Thr 
                260                 265                 270 

cca ggc ccc ttc acc aag gaa gga ggg atg ctg gcc tac tat gaa gtc      863 
Pro Gly Pro Phe Thr Lys Glu Gly Gly Met Leu Ala Tyr Tyr Glu Val 
            275                 280                 285 

tgc tcc tgg aag ggg gcc acc aaa cag aga atc cag gat cag aag gtg      911 
Cys Ser Trp Lys Gly Ala Thr Lys Gln Arg Ile Gln Asp Gln Lys Val 
        290                 295                 300 

ccc tac atc ttc cgg gac aac cag tgg gtg ggc ttt gat gat gtg gag      959 
Pro Tyr Ile Phe Arg Asp Asn Gln Trp Val Gly Phe Asp Asp Val Glu 
    305                 310                 315 

agc ttc aaa acc aag gtc agc tat ctg aag cag aag gga ctg ggc ggg     1007 
Ser Phe Lys Thr Lys Val Ser Tyr Leu Lys Gln Lys Gly Leu Gly Gly 
320                 325                 330                 335 

gcc atg gtc tgg gca ctg gac tta gat gac ttt gcc ggc ttc tcc tgc     1055 
Ala Met Val Trp Ala Leu Asp Leu Asp Asp Phe Ala Gly Phe Ser Cys 
                340                 345                 350 

aac cag ggc cga tac ccc ctc atc cag acg cta cgg cag gaa ctg agt     1103 
Asn Gln Gly Arg Tyr Pro Leu Ile Gln Thr Leu Arg Gln Glu Leu Ser 
            355                 360                 365 

ctt cca tac ttg cct tca ggc acc cca gag ctt gaa gtt cca aaa cca     1151 
Leu Pro Tyr Leu Pro Ser Gly Thr Pro Glu Leu Glu Val Pro Lys Pro 
        370                 375                 380 

ggt cag ccc tct gaa cct gag cat ggc ccc agc cct gga caa gac acg     1199 
Gly Gln Pro Ser Glu Pro Glu His Gly Pro Ser Pro Gly Gln Asp Thr 
    385                 390                 395 

ttc tgc cag ggc aaa gct gat ggg ctc tat ccc aat cct cgg gaa cgg     1247 
Phe Cys Gln Gly Lys Ala Asp Gly Leu Tyr Pro Asn Pro Arg Glu Arg 
400                 405                 410                 415 

tcc agc ttc tac agc tgt gca gcg ggg cgg ctg ttc cag caa agc tgc     1295 
Ser Ser Phe Tyr Ser Cys Ala Ala Gly Arg Leu Phe Gln Gln Ser Cys 
                420                 425                 430 

ccg aca ggc ctg gtg ttc agc aac tcc tgc aaa tgc tgc acc tgg aat     1343 
Pro Thr Gly Leu Val Phe Ser Asn Ser Cys Lys Cys Cys Thr Trp Asn 
            435                 440                 445 

tgagtcgcta aagcccctcc agtcccagct ttgaggc                            1380 

 
           
             44  
             447  
             PRT  
             Homo sapiens  
           
            44 

Ser Ala Tyr Lys Leu Val Cys Tyr Phe Thr Asn Trp Ala Gln Tyr Arg 
1               5                   10                  15 

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

Thr His Leu Ile Tyr Ala Phe Ala Gly Met Thr Asn His Gln Leu Ser 
        35                  40                  45 

Thr Thr Glu Trp Asn Asp Glu Thr Leu Tyr Gln Glu Phe Asn Gly Leu 
    50                  55                  60 

Lys Lys Met Asn Pro Lys Leu Lys Thr Leu Leu Ala Ile Gly Gly Trp 
65                  70                  75                  80 

Asn Phe Ser Thr Gln Lys Phe Thr Asp Met Val Ala Thr Ala Asn Asn 
                85                  90                  95 

Arg Gln Thr Phe Val Asn Ser Ala Ile Arg Phe Leu Arg Lys Tyr Ser 
            100                 105                 110 

Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Ser Gln Gly Ser 
        115                 120                 125 

Pro Ala Val Asp Lys Glu Arg Phe Thr Thr Leu Val Gln Asp Leu Ala 
    130                 135                 140 

Asn Ala Phe Gln Gln Glu Ala Gln Thr Ser Gly Lys Glu Arg Leu Leu 
145                 150                 155                 160 

Leu Ser Ala Ala Val Pro Ala Gly Gln Thr Tyr Val Asp Ala Gly Tyr 
                165                 170                 175 

Glu Val Asp Lys Ile Ala Gln Asn Leu Asp Phe Val Asn Leu Met Ala 
            180                 185                 190 

Tyr Asp Phe His Gly Ser Trp Glu Lys Val Thr Gly His Asn Ser Pro 
        195                 200                 205 

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

Asp Ala Ala Val Gln Gln Trp Leu Gln Lys Gly Thr Pro Ala Ser Lys 
225                 230                 235                 240 

Leu Ile Leu Gly Met Pro Thr Tyr Gly Arg Ser Phe Thr Leu Ala Ser 
                245                 250                 255 

Ser Ser Asp Thr Arg Val Gly Ala Pro Ala Thr Gly Ser Gly Thr Pro 
            260                 265                 270 

Gly Pro Phe Thr Lys Glu Gly Gly Met Leu Ala Tyr Tyr Glu Val Cys 
        275                 280                 285 

Ser Trp Lys Gly Ala Thr Lys Gln Arg Ile Gln Asp Gln Lys Val Pro 
    290                 295                 300 

Tyr Ile Phe Arg Asp Asn Gln Trp Val Gly Phe Asp Asp Val Glu Ser 
305                 310                 315                 320 

Phe Lys Thr Lys Val Ser Tyr Leu Lys Gln Lys Gly Leu Gly Gly Ala 
                325                 330                 335 

Met Val Trp Ala Leu Asp Leu Asp Asp Phe Ala Gly Phe Ser Cys Asn 
            340                 345                 350 

Gln Gly Arg Tyr Pro Leu Ile Gln Thr Leu Arg Gln Glu Leu Ser Leu 
        355                 360                 365 

Pro Tyr Leu Pro Ser Gly Thr Pro Glu Leu Glu Val Pro Lys Pro Gly 
    370                 375                 380 

Gln Pro Ser Glu Pro Glu His Gly Pro Ser Pro Gly Gln Asp Thr Phe 
385                 390                 395                 400 

Cys Gln Gly Lys Ala Asp Gly Leu Tyr Pro Asn Pro Arg Glu Arg Ser 
                405                 410                 415 

Ser Phe Tyr Ser Cys Ala Ala Gly Arg Leu Phe Gln Gln Ser Cys Pro 
            420                 425                 430 

Thr Gly Leu Val Phe Ser Asn Ser Cys Lys Cys Cys Thr Trp Asn 
        435                 440                 445 

 
           
             45  
             1599  
             DNA  
             Homo sapiens  
             
               CDS  
               (37)..(1377)  
             
           
            45 

ttttgtatgg gctgcagcct gccgctgagc tgcatc atg gtg cgg tct gtg gcc       54 
                                        Met Val Arg Ser Val Ala 
                                        1               5 

tgg gca ggt ttc atg gtc ctg ctg atg atc cca tgg ggc tct gct gca      102 
Trp Ala Gly Phe Met Val Leu Leu Met Ile Pro Trp Gly Ser Ala Ala 
            10                  15                  20 

aaa ctg gtc tgc tac ttc acc aac tgg gcc cag tac aga cag ggg gag      150 
Lys Leu Val Cys Tyr Phe Thr Asn Trp Ala Gln Tyr Arg Gln Gly Glu 
        25                  30                  35 

gct cgc ttc ctg ccc aag gac ttg gac ccc agc ctt tgc acc cac ctc      198 
Ala Arg Phe Leu Pro Lys Asp Leu Asp Pro Ser Leu Cys Thr His Leu 
    40                  45                  50 

atc tac gcc ttc gct ggc atg acc aac cac cag ctg agc acc act gag      246 
Ile Tyr Ala Phe Ala Gly Met Thr Asn His Gln Leu Ser Thr Thr Glu 
55                  60                  65                  70 

tgg aat gac gag act ctc tac cag gag ttc aat ggc ctg aag aag atg      294 
Trp Asn Asp Glu Thr Leu Tyr Gln Glu Phe Asn Gly Leu Lys Lys Met 
                75                  80                  85 

ttc aca gat atg gta gcc acg gcc aac aac cgt cag acc ttt gtc aac      342 
Phe Thr Asp Met Val Ala Thr Ala Asn Asn Arg Gln Thr Phe Val Asn 
            90                  95                  100 

tcg gcc atc agg ttt ctg cgc aaa tac agc ttt gac ggc ctt gac ctt      390 
Ser Ala Ile Arg Phe Leu Arg Lys Tyr Ser Phe Asp Gly Leu Asp Leu 
        105                 110                 115 

gac tgg gag tac cca gga agc cag ggg agc cct gcc gta gac aag gag      438 
Asp Trp Glu Tyr Pro Gly Ser Gln Gly Ser Pro Ala Val Asp Lys Glu 
    120                 125                 130 

cgc ttc aca acc ctg gta cag gac ttg gcc aat gcc ttc cag cag gaa      486 
Arg Phe Thr Thr Leu Val Gln Asp Leu Ala Asn Ala Phe Gln Gln Glu 
135                 140                 145                 150 

gcc cag acc tca ggg aag gaa cgc ctt ctt ctg agt gca gcg gtt cca      534 
Ala Gln Thr Ser Gly Lys Glu Arg Leu Leu Leu Ser Ala Ala Val Pro 
                155                 160                 165 

gct ggg cag acc tat gtg gat gct gga tac gag gtg gac aaa atc gcc      582 
Ala Gly Gln Thr Tyr Val Asp Ala Gly Tyr Glu Val Asp Lys Ile Ala 
            170                 175                 180 

cag aac ctg gat ttt gtc aac ctt atg gcc tac gac ttc cat ggc tct      630 
Gln Asn Leu Asp Phe Val Asn Leu Met Ala Tyr Asp Phe His Gly Ser 
        185                 190                 195 

tgg gag aag gtc acg gga cat aac agc ccc ctc tac aag agg caa gaa      678 
Trp Glu Lys Val Thr Gly His Asn Ser Pro Leu Tyr Lys Arg Gln Glu 
    200                 205                 210 

gag agt ggt gca gca gcc agc ctc aac gtg gat gct gct gtg caa cag      726 
Glu Ser Gly Ala Ala Ala Ser Leu Asn Val Asp Ala Ala Val Gln Gln 
215                 220                 225                 230 

tgg ctg cag aag ggg acc cct gcc agc aag ctg atc ctt ggc atg cct      774 
Trp Leu Gln Lys Gly Thr Pro Ala Ser Lys Leu Ile Leu Gly Met Pro 
                235                 240                 245 

acc tac gga cgc tcc ttc aca ctg gcc tcc tca tca gac acc aga gtg      822 
Thr Tyr Gly Arg Ser Phe Thr Leu Ala Ser Ser Ser Asp Thr Arg Val 
            250                 255                 260 

ggg gcc cca gcc aca ggg tct ggc act cca ggc ccc ttc acc aag gaa      870 
Gly Ala Pro Ala Thr Gly Ser Gly Thr Pro Gly Pro Phe Thr Lys Glu 
        265                 270                 275 

gga ggg atg ctg gcc tac tat gaa gtc tgc tcc tgg aag ggg gcc acc      918 
Gly Gly Met Leu Ala Tyr Tyr Glu Val Cys Ser Trp Lys Gly Ala Thr 
    280                 285                 290 

aaa cag aga atc cag gat cag aag gtg ccc tac atc ttc cgg gac aac      966 
Lys Gln Arg Ile Gln Asp Gln Lys Val Pro Tyr Ile Phe Arg Asp Asn 
295                 300                 305                 310 

cag tgg gtg ggc ttt gat gat gtg gag agc ttc aaa acc aag gtc agc     1014 
Gln Trp Val Gly Phe Asp Asp Val Glu Ser Phe Lys Thr Lys Val Ser 
                315                 320                 325 

tat ctg aag cag aag gga ctg ggc ggg gcc atg gtc tgg gca ctg gac     1062 
Tyr Leu Lys Gln Lys Gly Leu Gly Gly Ala Met Val Trp Ala Leu Asp 
            330                 335                 340 

tta gat gac ttt gcc ggc ttc tcc tgc aac cag ggc cga tac ccc ctc     1110 
Leu Asp Asp Phe Ala Gly Phe Ser Cys Asn Gln Gly Arg Tyr Pro Leu 
        345                 350                 355 

atc cag acg cta cgg cag gaa ctg agt ctt cca tac ttg cct tca ggc     1158 
Ile Gln Thr Leu Arg Gln Glu Leu Ser Leu Pro Tyr Leu Pro Ser Gly 
    360                 365                 370 

acc cca gag ctt gaa gtt cca aaa cca ggt cag ccc tct gaa cct gag     1206 
Thr Pro Glu Leu Glu Val Pro Lys Pro Gly Gln Pro Ser Glu Pro Glu 
375                 380                 385                 390 

cat ggc ccc agc cct gga caa gac acg ttc tgc cag ggc aaa gct gat     1254 
His Gly Pro Ser Pro Gly Gln Asp Thr Phe Cys Gln Gly Lys Ala Asp 
                395                 400                 405 

ggg ctc tat ccc aat cct cgg gaa cgg tcc agc ttc tac agc tgt gca     1302 
Gly Leu Tyr Pro Asn Pro Arg Glu Arg Ser Ser Phe Tyr Ser Cys Ala 
            410                 415                 420 

ggg ggg cgg ctg ttc cag caa agc tgc ccg aca ggc ctg gtg ttc agc     1350 
Gly Gly Arg Leu Phe Gln Gln Ser Cys Pro Thr Gly Leu Val Phe Ser 
        425                 430                 435 

aac tcc tgc aaa tgc tgc acc tgg aat tgagtcgcta aagcccctcc           1397 
Asn Ser Cys Lys Cys Cys Thr Trp Asn 
    440                 445 

agtcccagct ttgaggctgg gcccaggatc actctacagc ctgcctcctg ggttttccct   1457 

gggggccgca atctggctcc tgcaggcctt tctgtggtct tcctttatcc aggctttctg   1517 

ctctcagcct tgccttcctt ttttctgggt ctcctgggct gcccctttca cttgcaaaat   1577 

aaatctttgg tttgtgcccc tc                                            1599 

 
           
             46  
             447  
             PRT  
             Homo sapiens  
           
            46 

Met Val Arg Ser Val Ala Trp Ala Gly Phe Met Val Leu Leu Met Ile 
1               5                   10                  15 

Pro Trp Gly Ser Ala Ala Lys Leu Val Cys Tyr Phe Thr Asn Trp Ala 
            20                  25                  30 

Gln Tyr Arg Gln Gly Glu Ala Arg Phe Leu Pro Lys Asp Leu Asp Pro 
        35                  40                  45 

Ser Leu Cys Thr His Leu Ile Tyr Ala Phe Ala Gly Met Thr Asn His 
    50                  55                  60 

Gln Leu Ser Thr Thr Glu Trp Asn Asp Glu Thr Leu Tyr Gln Glu Phe 
65                  70                  75                  80 

Asn Gly Leu Lys Lys Met Phe Thr Asp Met Val Ala Thr Ala Asn Asn 
                85                  90                  95 

Arg Gln Thr Phe Val Asn Ser Ala Ile Arg Phe Leu Arg Lys Tyr Ser 
            100                 105                 110 

Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Ser Gln Gly Ser 
        115                 120                 125 

Pro Ala Val Asp Lys Glu Arg Phe Thr Thr Leu Val Gln Asp Leu Ala 
    130                 135                 140 

Asn Ala Phe Gln Gln Glu Ala Gln Thr Ser Gly Lys Glu Arg Leu Leu 
145                 150                 155                 160 

Leu Ser Ala Ala Val Pro Ala Gly Gln Thr Tyr Val Asp Ala Gly Tyr 
                165                 170                 175 

Glu Val Asp Lys Ile Ala Gln Asn Leu Asp Phe Val Asn Leu Met Ala 
            180                 185                 190 

Tyr Asp Phe His Gly Ser Trp Glu Lys Val Thr Gly His Asn Ser Pro 
        195                 200                 205 

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

Asp Ala Ala Val Gln Gln Trp Leu Gln Lys Gly Thr Pro Ala Ser Lys 
225                 230                 235                 240 

Leu Ile Leu Gly Met Pro Thr Tyr Gly Arg Ser Phe Thr Leu Ala Ser 
                245                 250                 255 

Ser Ser Asp Thr Arg Val Gly Ala Pro Ala Thr Gly Ser Gly Thr Pro 
            260                 265                 270 

Gly Pro Phe Thr Lys Glu Gly Gly Met Leu Ala Tyr Tyr Glu Val Cys 
        275                 280                 285 

Ser Trp Lys Gly Ala Thr Lys Gln Arg Ile Gln Asp Gln Lys Val Pro 
    290                 295                 300 

Tyr Ile Phe Arg Asp Asn Gln Trp Val Gly Phe Asp Asp Val Glu Ser 
305                 310                 315                 320 

Phe Lys Thr Lys Val Ser Tyr Leu Lys Gln Lys Gly Leu Gly Gly Ala 
                325                 330                 335 

Met Val Trp Ala Leu Asp Leu Asp Asp Phe Ala Gly Phe Ser Cys Asn 
            340                 345                 350 

Gln Gly Arg Tyr Pro Leu Ile Gln Thr Leu Arg Gln Glu Leu Ser Leu 
        355                 360                 365 

Pro Tyr Leu Pro Ser Gly Thr Pro Glu Leu Glu Val Pro Lys Pro Gly 
    370                 375                 380 

Gln Pro Ser Glu Pro Glu His Gly Pro Ser Pro Gly Gln Asp Thr Phe 
385                 390                 395                 400 

Cys Gln Gly Lys Ala Asp Gly Leu Tyr Pro Asn Pro Arg Glu Arg Ser 
                405                 410                 415 

Ser Phe Tyr Ser Cys Ala Gly Gly Arg Leu Phe Gln Gln Ser Cys Pro 
            420                 425                 430 

Thr Gly Leu Val Phe Ser Asn Ser Cys Lys Cys Cys Thr Trp Asn 
        435                 440                 445 

 
           
             47  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            47 

tgctcagtgc tcagtctcct                                                 20 

 
           
             48  
             25  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            48 

tcaccactcc atgcggaatc tgtct                                           25 

 
           
             49  
             18  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            49 

agtggctcct gcagcttg                                                   18 

 
           
             50  
             21  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            50 

tggttctggg agtttgtcaa t                                               21 

 
           
             51  
             26  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            51 

tctgcttctt ccctgtgagt accagg                                          26 

 
           
             52  
             17  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            52 

caggagctgg gcatctg                                                    17 

 
           
             53  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            53 

tgcagccttt ggtagctaac                                                 20 

 
           
             54  
             27  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            54 

tcgcattctc caattataaa atcagtg                                         27 

 
           
             55  
             19  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            55 

gcaggctctt ctccttgaa                                                  19 

 
           
             56  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            56 

tcctgaggtg tggatgaata ct                                              22 

 
           
             57  
             27  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            57 

tcatcatcta caatggctac cccagtg                                         27 

 
           
             58  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            58 

ccatcttcag tggtgacttc at                                              22 

 
           
             59  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            59 

tcctgaggtg tggatgaata ct                                              22 

 
           
             60  
             27  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            60 

tcatcatcta caatggctac cccagtg                                         27 

 
           
             61  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            61 

ccatcttcag tggtgacttc at                                              22 

 
           
             62  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            62 

ggggaaatga cgctgataat at                                              22 

 
           
             63  
             26  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            63 

tcccctatat atgacctgac tgccat                                          26 

 
           
             64  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            64 

cccaaatagc agtaggcact tt                                              22 

 
           
             65  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            65 

ggggaaatga cgctgataat at                                              22 

 
           
             66  
             26  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            66 

tcccctatat atgacctgac tgccat                                          26 

 
           
             67  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            67 

cccaaatagc agtaggcact tt                                              22 

 
           
             68  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            68 

gaaacagtcg gggaaacact                                                 20 

 
           
             69  
             27  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            69 

ttggtcaaga agacacaaaa cactctc                                         27 

 
           
             70  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            70 

aaaccaaagg cccagaattt                                                 20 

 
           
             71  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            71 

gaaacagtcg gggaaacact                                                 20 

 
           
             72  
             27  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            72 

ttggtcaaga agacacaaaa cactctc                                         27 

 
           
             73  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            73 

aaaccaaagg cccagaattt                                                 20 

 
           
             74  
             23  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            74 

gaccagctcc agtcctatat ctg                                             23 

 
           
             75  
             35  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            75 

tctgtgagac gcttgaatat ccatgtggaa aaata                                35 

 
           
             76  
             16  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            76 

tggggtttgc tggcat                                                     16 

 
           
             77  
             18  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            77 

ctcaacgtgg gccgatac                                                   18 

 
           
             78  
             31  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            78 

tcaggaactg agtcttccat acttgccttc a                                    31 

 
           
             79  
             19  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            79 

ctcaggttca gagggctga                                                  19 

 
           
             80  
             17  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            80 

agtggctgca gaagggg                                                    17 

 
           
             81  
             22  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            81 

ttggcatgcc tacctacgga cg                                              22 

 
           
             82  
             18  
             DNA  
             Artificial Sequence  
             
               Description of Artifical Sequence 
      Primer/Probe  
             
           
            82 

cccccactct ggtgtctg                                                   18