AU2003232034A1 - Therapeutic polypeptides, nucleic acids encoding same, and methods of use - Google Patents

Description

WO 03/093432 PCT/USO3/13690 THERAPEUTIC POLYPEPTIDES, NUCLEIC ACIDS ENCODING SAME, AND METHODS OF USE FIELD OF THE INVENTION The present invention relates to both novel polypeptides, and the nucleic acids encoding them as well as polypeptides that are targets of small molecule drugs. Those polypeptides 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. 1 WO 03/093432 PCT/US03/13690 BACKGROUND OF THE INVENTION 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. 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. 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. 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 2 WO 03/093432 PCT/US03/13690 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. 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, protein-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. 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 ofmacromolecule. 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. 3 WO 03/093432 PCT/US03/13690 Antibodies are multichain proteins that bind specifically to a given antigen, and bind poorly, or not at all, to substances deemed not to be cognate antigens. Antibodies are comprised of two short chains termed light chains and two long chains termed heavy chains. These chains are constituted of immunoglobulin domains, of which generally there are two classes: one variable domain per chain, one constant domain in light chains, and three or more constant domains in heavy chains. The antigen-specific portion of the immunoglobulin molecules resides in the variable domains; the variable domains of one light chain and one heavy chain associate with each other to generate the antigen-binding moiety. Antibodies that bind immunospecifically to a cognate or target antigen bind with high affinities. Accordingly, they are useful in assaying specifically for the presence of the antigen in a sample. In addition, they have the potential of inactivating the activity of the antigen. Therefore there is a need to assay for the level of a protein effector of interest in a biological sample from such a subject, and to compare this level with that characteristic of a nonpathological condition. In particular, there is a need for such an assay based on the use of an antibody that binds immunospecifically to the antigen. There further is a need to inhibit the activity of the protein effector in cases where a pathological condition arises from elevated or excessive levels of the effector based on the use of an antibody that binds immunospecifically to the effector. Thus, there is a need for the antibody as a product of manufacture. There further is a need for a method of treatment of a pathological condition brought on by an elevated or excessive level of the protein effector of interest based on administering the antibody to the subject. SUMMARY OF THE INVENTION The invention is based in part upon the discovery of isolated polypeptides including amino acid sequences selected from mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174. The novel nucleic acids and polypeptides are referred to herein as NOV1 a, NOVIb, NOVIc, NOVld, NOV2a, NOV2b, NOV2c, NOV2d, NOV3a, NOV3b, etc. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as "NOVX" nucleic acid or polypeptide sequences. The invention also is based in part upon variants 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 I and 174, 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 4 WO 03/093432 PCT/US03/13690 mature form are so changed. In another embodiment, the invention includes the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174. In another embodiment, the invention also comprises variants of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 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 involves fragments of any of the mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, or any other amino acid sequence selected from this group. The invention also comprises fragments from these groups in which up to 15% of the residues are changed. In another embodiment, the invention encompasses polypeptides that are naturally occurring allelic variants of the sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174. These allelic variants include amino acid sequences that are the translations of nucleic acid sequences differing by a single nucleotide from nucleic acid sequences selected from the group consisting of SEQ ID NOS: 2n-1, wherein n is an integer between 1 and 174. The variant polypeptide where any amino acid changed in the chosen sequence is changed to provide a conservative substitution. In another embodiment, the invention comprises a pharmaceutical composition involving a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 and a pharmaceutically acceptable carrier. In another embodiment, the invention involves a kit, including, in one or more containers, this pharmaceutical composition. In another embodiment, the invention includes the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease being selected from a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 wherein said therapeutic is the polypeptide selected from this group. In another embodiment, the invention comprises a method for determining the presence or amount of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a sample, the method involving providing the sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody 5 WO 03/093432 PCT/US03/13690 bound to the polypeptide, thereby determining the presence or amount of polypeptide in the sample. In another embodiment, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a first mammalian subject, the method involving measuring the level of expression ofthe polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in this sample 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. In another embodiment, the invention involves a method of identifying an agent that binds to a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. The agent could be a cellular receptor or a downstream effector. In another embodiment, the invention involves 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 polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including providing a cell expressing the polypeptide of the invention 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 embodiment, the invention involves a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of the invention, wherein the test animal recombinantly expresses the polypeptide of the 6 WO 03/093432 PCT/US03/13690 invention; measuring the activity of the polypeptide in the test animal after administering the test compound; and comparing the activity of the protein in the test animal with the activity of the polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the 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 polypeptide of the invention. The recombinant test animal could express a test protein transgene or express the transgene under the control of a promoter at an increased level relative to a wild-type test animal The promoter may or may not b the native gene promoter of the transgene. In another embodiment, the invention involves a method for modulating the activity of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including introducing a cell sample expressing the 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 involves a method of treating or preventing a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174, the method including administering the polypeptide to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject. The subject could be human. In another embodiment, the invention involves a method of treating a pathological state in a mammal, the method including administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174 or a biologically active fragment thereof. In another embodiment, the invention involves an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174; 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 174 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; the amino acid sequence selected 7 WO 03/093432 PCT/US03/13690 from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174; 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 174, 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; 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 174 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; and the complement of any of the nucleic acid molecules. In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the invention involves an isolated nucleic acid molecule including a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 2n-1, wherein n is an integer between 1 and 174. In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of the nucleotide sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174; a nucleotide sequence wherein one or more nucleotides in the nucleotide 8 WO 03/093432 PCT/US03/13690 sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174 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; 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 174; and 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 174 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 an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the 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 174, or a complement of the nucleotide sequence. In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174, wherein the nucleic acid molecule has a nucleotide sequence in which any nucleotide specified in the coding sequence of the chosen 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 in the chosen coding sequence are so changed, an isolated second polynucleotide that is a complement of the first polynucleotide, or a fragment of any of them. In another embodiment, the invention includes a vector involving the nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between I and 174. This vector can have a promoter operably linked to the nucleic acid molecule. This vector can be located within a cell. In another embodiment, the invention involves a method for determining the presence or amount of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the 9 WO 03/093432 PCT/US03/13690 amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a sample, the method including 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 nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in the sample. The presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type. The cell type can be cancerous. In another embodiment, the invention involves a method for determining the presence of or predisposition for a disease associated with altered levels of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 174 in a first mammalian subject, the method including measuring the amount of the 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 the 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. The invention further provides an antibody that binds immunospecifically to a NOVX polypeptide. The NOVX antibody may be monoclonal, humanized, or a fully human antibody. Preferably, the antibody has a dissociation constant for the binding of the NOVX polypeptide to the antibody less than 1 x 10 -9 M. More preferably, the NOVX antibody neutralizes the activity of the NOVX polypeptide. In a further aspect, the invention provides for the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, associated with a NOVX polypeptide. Preferably the therapeutic is a NOVX antibody. In yet a further aspect, the invention provides a method of treating or preventing a NOVX-associated disorder, a method of treating a pathological state in a mammal, and a method of treating or preventing a pathology associated with a polypeptide by administering a NOVX antibody to a subject in an amount sufficient to treat or prevent the disorder. 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 10 WO 03/093432 PCT/US03/13690 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 are not intended to be limiting. Other features and advantages of the invention will be apparent from the following detailed description and claims. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a bar diagram showing the activation of 786-0 epithelial cell BrdU incorporation by CG51051-06 protein. DETAILED DESCRIPTION OF THE INVENTION 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. SEQUENCES AND CORRESPONDING SEQ ID NUMBERS SEQ ID SEQ ID NOVX Internal NO NO Homology Assignment Identification (nucleic (amino Homoo acid) acid) NOVla CG103910-02 1 2 Bone morphogenetic protein 7 (Osteogenic protein 1) - Homo sapiens NOVlb CG103910-03 3 4 Bone morphogenetic protein 7 (Osteogenic protein 1) - Homo sapiens NOVIc CG103910-01 5 6 Bone morphogenetic protein 7 .. ... .. (Osteogenic protein 1)- Homo sapiens NOVId CG103910-04 7 8 Bone morphogenetic protein 7 ......... ..... . .(Osteogenic protein 1) - Homo sapiens NOVle 11382317 9 10 Bone morphogenetic protein 7 S(Osteogenic protein 1) -Homo sapiens NOV2a CG106298-02 11 12 Complement factor H-related protein 4 ............ _........ . ...... precursor (FHR-4) - Homo sapiens NOV2b 'CG106298-01 13 14 Complement factor H-related protein 4 precursor (FHR-4) - Homo sapiens NOV3a CG110590-02 15 16 Neuralin precursor (Ventroptin) - Homo sapiens 11 WO 03/093432 PCT/USO3/13690 NOV3b CG110590-01 17 18 Neuralin precursor (Ventroptin) - Homo sapiens NOV3c 13382325 19 20 Neuralin precursor (Ventroptin) - Homo sapiens NOV3d 13382326 21 22 Neuralin precursor (Ventroptin) - Homo .............. .... .... sap ien s NOV4a CG114555-01 23 24 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose transporter type 9) - Homo sapiens NOV4b 247847074 25 26 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose transporter type 9) - Homo sapiens NOV4c 247847070 27 28 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose transporter type 9) - Homo sapiens NOV4d 247847055 29 30 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose ....... .. ......... transporter type 9) - Homo sapiens NOV4e 247847059 31 32 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose . ....... .. .. ... .. .. r-p.transporter type 9) - Homo sapiens NOV4f 247847047 33 34 Solute carrier family 2, facilitated _ glucose transporter, member 9 (Glucose .transporter type 9) - Homo sapiens NOV4g CG114555-02 35 36 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose ............. ........... transporter type 9) - Homo sapiens NOV4h CG114555-03 37 38 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose transporter type 9) - Homo sapiens NOV4i CG1 14555-04 39 40 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose ......... ____transporter type 9) - Homo sapiens NOV4j 13379365 41 42 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose transporter type 9) - Homo sapiens NOV4k 13379364 43 44 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose transporter type 9) - Homo sapiens NOV41 13379363 45 46 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose ................... ________transporter type 9) - Homo sapiens NOV4m 13379362 47 48 Solute carrier family 2, facilitated glucose transporter, member 9 (Glucose transporter type 9) - Homo sapiens NOV4n 13379620 49 50 Solute carrier family 2, facilitated g lucose transporter, member 9 (Glucose 12 WO 03/093432 PCT/US03/13690 transporter type 9) - Homo sapiens NOV5a CG181662-01 51 52 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5b CG181662-02 53 54 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5c 307686795 55 56 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5d CG181662-03 57 58 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5e CG181662-04 59 60 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5f 13382357 61 62 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5g 13377970 63 64 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5h 13378241 65 66 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5i 13377901 67 68 Protein farnesyltransferase alpha subunit (EC 2.5.1 .-) (CAAX farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) Homo sapiens NOV5j 13377900 6970 Protein farnesyltransferase alpha subunit (EC 2.5.1.-) (CAAX farnesyltransferase alpha subunit) (RAS proteins 13 WO 03/093432 PCT/US03/13690 prenyltransferase alpha) (FTase-alpha) Ho m o sapiens NOV6a CG182223-01 71 72 Human neurotransmission-associated protein NTRAN8 - Homo sapiens NOV7a CG183585-01 73 74 Adult male liver tumor cDNA, RIKEN full-length enriched library, clone:C730027017 product:hypothetical protein, full insert sequence - Mus musculus NOV8a CG183860-01 75 76 Human secreted protein HNTNC20 Homo sapiens NOV9a CG184416-01 77 78 MP-23 (MIFR/FEMALYSIN) (DJ283E3.2.1) (Matrix metalloproteinase MMP21/22A (MIFR1)) (Matrix _metalloproteinase 23B) - Homo sapiens NOV10a CG185200-01 79 80 Human secreted/transmembrane protein, SPRO 1377 - Homo sapiens NOV10b CG185200-02 81 82 Human secreted/transmembrane protein, PRO1377 - Homo sapiens NOV1 la CG50513-01 83 84 central nervous system protein #236 Homo sapiens NOV1 lb 273654175 85 86 central nervous system protein #236 Homo sapiens NOV1I c CG50513-02 87 88 central nervous system protein #236 Homo sapiens NOVl ld CG50513-03 89 90 central nervous system protein #236 Homo sapiens NOV1 le CG50513-04 91 92 central nervous system protein #236 Homo sapiens NOV11 f CG50513-05 93 94 central nervous system protein #236 Homo sapiens NOV1 g CG50513-06 95 96 central nervous system protein #236 ........ __Homo sapiens NOV1 lh CG50513-07 97 98 central nervous system protein #236 Homo sapiens NOV11i 13376798 99 100 central nervous system protein #236 ...... .. Homo sapiens NOVI j 13376799 101 102 central nervous system protein #236 Homo sapiens NOV12a CG50949-03 103 104 Membrane-type mosaic serine protease Homo sapiens NOV12b 197192399 105 106 Membrane-type mosaic serine protease Homo sapiens NOV12c 257499999 107 108 Membrane-type mosaic serine protease Homo sapiens NOV12d 257450010 109 110 Membrane-type mosaic serine protease 14 WO 03/093432 PCT/USO3/13690 ______ ____ _ _Homo sapiens NOV12e 252417780 111 112 Membrane-type mosaic serine protease ............ . . .1111Homo sapiens NOV12f 1252417791 113 114 Membrane-type mosaic serine protease Homo sapiens NOV12g 252417821 115 116 Membrane-type mosaic serine protease Homo sapiens NOV12h 252417840 117 118 Membrane-type mosaic serine protease SHomo sapiens NOV12i 257474313 119 120 Membrane-type mosaic serine protease Homo sapiens NOV12j 257474324 121 122 Membrane-type mosaic serine protease ....... ._ _ ..- Homo sapiens NOV12k CG50949-06 123 124 Membrane-type mosaic serine protease Homo sapiens NOV121 268669017 125 126 Membrane-type mosaic serine protease Homo sapiens NOV12m CG50949-05 127 128 Membrane-type mosaic serine protease Homo sapiens NOV12n 317431859 129 130 Membrane-type mosaic serine protease Homo sapiens NOV12o CG50949-01 131 132 Membrane-type mosaic serine protease Homo sapiens NOV12p CG50949-02 133 134 Membrane-type mosaic serine protease Homo sapiens NOV12q CG50949-04 135 136 Membrane-type mosaic serine protease Homo sapiens NOV12r CG50949-07 137 138 Membrane-type mosaic serine protease Homo sapiens NOV12s 13374729 139 140 Membrane-type mosaic serine protease Homo sapiens NOV12t 13374730 141 142 Membrane-type mosaic serine protease Homo sapiens NOV12u 13374731 143 144 Membrane-type mosaic serine protease Homo sapiens NOV13a CG51018-01 145 146 Matrilin-2 precursor - Homo sapiens NOV13b 274051273 147 148 Matrilin-2 precursor - Homo sapiens NOV13c 274051251 149 150 Matrilin-2 precursor - Homo sapiens NOV13d 274051253 151 152 Matrilin-2 precursor - Homo sapiens NOV13e 306562753 153 154 Matrilin-2 precursor - Homo sapiens NOV13f CG51018-02 155 156 Matrilin-2 precursor - Homo sapiens NOV13g CG51018-03 157 158 Matrilin-2 precursor - Homo sapiens NOV13h .1 337 4217 159 160 Matrilin-2 precursor - Homo sapiens NOV14a CG51051-07 161 162 Netrin-Gld - Mus musculus NOV14b 1CG51051-14 1163 164 Netrin-Gld - Mus musculus 15 WO 03/093432 PCT/USO3/13690 NOV14c 254537195 165 166 Netrin-Gld - Mus musculus NOV14d 254537282 167 168 Netrin-Gld - Mus musculus NOV14e CG51051-09 169 170 Netrin-G I d -Mus musculus NOV14f 304965116 171 172 Netrin-Gld - Mus musculus NOVl4g 273711018 173 174 Netrin-GId - Mus musculus NOV14h 273711053 175 176 Netrin-Gld -Mus musculus NOV14i 274051275 177 178 Netrin-Gld - Mus musculus NOVI4j CG51051-01 179 180 Netrin-Gld- Mus musculus NOV14k CG51051-02 181 1182 Netrin-G Id - Mus musculus NOV141 CG51051-03 183 184 Netrin-Gld- Mus musculus NOV14m CG51051-04 185 186 Netrin-G d - Mus musculus OV14n CG5105.1-05 187 188 Netrin-Gid - Mus musculus NOV14o CG51051-06 189 190 Netrin-Gld - Mus musculus N ov lcp ............ co9 51051:0 S ~~ ~~~~~...........! .............................. 17. ............ trn Q d -M s us u s NOV14p CG51051-08 191 192 Netrin-Gld - Mus musculus NOV14q CG51051-10 193 194 Netrin-G1d - Mus musculus NOV14r CG51051-11 195 196 Netrin-GId - Mus minusculus NOV14s CG51051-12 197 198 Netrin-Gld - Mus musculus NOV14t CG51051-13 199 200 Netrin-Gld - Mus musculus NOV14u CG51051-15 201 202 Netrin-Gld -Mus musculus NOV14v CG51051-16 203 204 Netrin-Gld- Mus musculus NOV14w 13380736 205 206 Netrin-Gld - Mus musculus NOV14x 13380734 207 208 Netrin-Gld - Mus musculus NOV14y 13382329 [209 210 Netrin-Gld -Mus musculus NOV15a. CG52261-01 211 212 Netrin-Gld - Mus miusculus NOV15b 268667469 213 214 Netrin-Gld - Mus musculus NOV15c CG52261-02 215 216 Netrin-Gld - Mus musculus NOV15d 13382342 217 218 Netrin-Gld - Mus musculus NOV15e 13382341 219 220 Netrin-Gld - Mus musculus NOV16a CG52414-02 221 222 Epidermal growth factor receptor-related Sp.rotein homolog - Mus musculus NOV16b 305262879 223 224 Epidermal growth factor receptor-related protein homolog - Mus musculus NOV16c 319073326 225 [226 Epidermal growth factor receptor-related Protein homolog - Mus musculus NOV16d CG52414-01 227 228 Epidermal growth factor receptor-related _protein homolog - Mus musculus NOV16e CG52414-03 229 230 Epidermal growth factor receptor-related protein homolog -Mus musculus NOV16f 13379509 231 232 Epidermal growth factor receptor-related _protein homolog - Mus musculus NOV16g 13381817 233 234 Epidermal growth factor receptor-related protein homolog - Mus musculus NOV16h 13382069 235 236 [Epidermal growth factor receptor-related 16 WO 03/093432 PCT/US03/13690 ............ protein homolog -Mus musculus NOV16i 13381560 237 238 Epidermal growth factor receptor-related S____ protein homolog - Mus musculus NOV17a CG52643-02 239 240 Human follistatin-related protein NOV17b 259341359 241 242 . Human follistatin-related protein NOV17c 268824728 243 244 Human follistatin-related protein NOV17d 268825987 245 246 Human follistatin-related protein NOV17e 268825997 247 248 Human follistatin-related protein NOV17f 275698334 249 250 Human follistatin-related protein NOV17g CG52643-04 251 252 Hrluman follistatin-related protein NOV17h 301380586 1253 . 254 Human follistatin-related protein NOV17i 289087852 255 256 Human follistatin-related protein NOV17j 289081920 257 258 Human follistatin-related protein 1 .1 -... 1...." "-. --1-. ...... . NOV17k 289098038 259 260 Human follistatin-related protein NOV171 311060818 261 262 Human follistatin-related protein NOV17m 311885703 263 264 Human follistatin-related protein NOV17n CG52643-01 265 266 Human follistatin-related protein NOV17o CG52643-03 267 268 Human follistatin-related protein NOV17p CG52643-05 269 270 Human follistatin-related protein NOV17q CG52643-06 271 272 Human follistatin-related protein NOV17r 13382322 273 274 Human follistatin-related protein NOV 17s 13382324 275 276 Human follistatin-related protein NOV17t 13381678 277 278 Human follistatin-related protein NOV 18a CG53270-01 279 280 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens NOV18b 274089779 281 282 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens NOV18c CG53270-02 283 284 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens NOV18d 13382344 285 286 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens NOV18e 13382345 287 288 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens NOV18f 13376391 289 290 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens NOV18g 13376390 291 292 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens 17 WO 03/093432 PCT/US03/13690 NOV18h 13376389 293 294 Serine/threonine kinase FKSG81 (Testis specific serine/threonine kinase 1) Homo sapiens NOVI9a CG54254-04 295 296 Fibronectin leucine rich transmembrane protein NOV19b 247846813 297 298 Fibronectin leucine rich transmembrane protein NOV19c 247846825 299 300 Fibronectin leucine rich transmembrane _____ ___ _ I protein NOVI9d 247846967 301 302 Fibronectin leucine rich transmembrane protein NOV19e J283841186 303 304 Fibronectin leucine rich transmembrane . ........... . . .................. protein NOV19f CG54254-01 305 306 Fibronectin leucine rich transmembrane protein NOV9g CG54254-02 307 308 Fibronectin leucine rich transmembrane protein NOV19h CG54254-03 309 310 Fibronectin leucine rich transmembrane protein NOV19i CG54254-05 311 312 Fibronectin leucine rich transmembrane protein NOV19j CG54254-06 313 314 Fibronectin leucine rich transmembrane protemin NOV19k CG54254-07 315 316 Fibronectin leucine rich transmembrane protein NOV191 13375078 317 318 Fibronectin leucine rich transmembrane protein NOV 19m 13376406 19 320 Fibronectin leucine rich transmembrane protem NOV19n 13375079 321 322 Fibronectin leucinerih transmembrane protein NOV19o 13376405 323 324 Fibronectin leucine rich transmembrane protein NOV20a CG96778-02 325 326 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC 1.3.99.3) (MCAD) - Homo sapiens NOV20b CG96778-01 327 328 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC 1.3.99.3) (MCAD) -Homo sapiens NOV20c 276657466 329 330 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC 1.3.99.3) (MCAD) - Homo sapiens NOV20d 276657530 331 332 Acyl-CoA dehydrogenase, medium-chain _ _ _specific, mitochondrial precursor (EC . .399.3)(MCAD)- Homo sapiens NOV20e 276657538 333 334 Acyl-CoA dehydrogenase, medium-chain 18 WO 03/093432 PCT/US03/13690 specific, mitochondrial precursor (EC ................. 1.3.99.3) (MCAD) - Homo sapiens NOV20f 27665766 335 336 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC 1.3.99.3) (MCAD) - Homo sapiens NOV20g CG96778-03 337 338 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC 1.3.99.3) (MCAD) - Homo sapiens NOV20h 13382351 339 340 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC 1.3.99.3) (MCAD) - Homo sapiens NOV20i 13382352 341 342 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC ._ _ ._ ...... 1.3.99.3) (MCAD) - Homo sapiens NOV20j 13382353 343 344 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC ......... 1...... .. 1.3.99.3 ) (MCAD) - Homo sapiens NOV20k 13382354 345 346 Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial precursor (EC 1.3.99.3) (MCAD) - Homo sapiens NOV201 12252113 347 348 Acyl-CoA dehydrogenase, medium-chain S specific, mitochondrial precursor (EC 1.49.3 (MCAD) - Homo sapiens 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. 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), vascular calcification, fibrosis, 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, osteoarthritis, rheumatoid arthritis, osteochondrodysplasia, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, glomerulonephritis, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, psoriasis, skin disorders, graft versus host disease, AIDS, bronchial asthma, lupus, Crohn's 19 WO 03/093432 PCT/US03/13690 disease; inflammatory bowel disease, ulcerative colitis, multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, schizophrenia, depression, asthma, emphysema, allergies, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation, neuroprotection, fertility, or regeneration (in vitro and in vivo). 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. 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. 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. 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. Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein. NOVX clones 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 20 WO 03/093432 PCT/US03/13690 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. 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. 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. 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 174; (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 174, 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 174; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between I and 174 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). In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino 21 WO 03/093432 PCT/US03/13690 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 174; (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 174 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 174; (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 174, 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 174 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. 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 174; (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 174 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 174; 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 174 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. NOVX Nucleic Acids and Polypeptides 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 22 WO 03/093432 PCT/US03/13690 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. 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 I 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+I 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. 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 23 WO 03/093432 PCT/US03/13690 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. 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. 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 174, 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 174, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORY MANUAL 2 nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989; and Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993.) 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. 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 eDNA 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 24 WO 03/093432 PCT/US03/13690 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 174, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes. 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 174, 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 174, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174, 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 174, thereby forming a stable duplex. 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. 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. 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 25 WO 03/093432 PCT/US03/13690 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. 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. 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., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, NY, 1993, and below. 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 26 WO 03/093432 PCT/US03/13690 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 174, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below. 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 bonafide 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. 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 174; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174; or of a naturally occurring mutant of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174. 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. "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 27 WO 03/093432 PCT/US03/13690 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 174, 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. NOVX Single Nucleotide Polymorphisms 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. 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. Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have 28 WO 03/093432 PCT/US03/13690 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's human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools T M program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed. 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 (Alderborn et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000). 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. NOVX Nucleic Acid and Polypeptide Variants 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 174, 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 I and 174. 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 174. In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174, 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, 29 WO 03/093432 PCT/US03/13690 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. 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 174, 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. 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 174. 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. 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. 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 oC 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 30 WO 03/093432 PCT/US03/13690 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 oC for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60 oC for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide. Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & 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 6X SSC, 50 mM Tris-HCI (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 0 C, followed by one or more washes in 0.2X SSC, 0.01% BSA at 50 0 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 174, 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). 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 174, 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 6X SSC, 5X Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55 oC, followed by one or more washes in IX SSC, 0.1% SDS at 37 oC. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Krieger, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY. 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 174, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are 31 WO 03/093432 PCT/US03/13690 hybridization in 35% formamide, 5X SSC, 50 mM Tris-HCI (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/mi denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40 0 C, followed by one or more washes in 2X 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, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981. Proc NatlAcadSci USA 78: 6789-6792. Conservative Mutations 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 174, 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 174. 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 predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-laknown within the art. 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 174, 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 174. 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 174; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 174; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 174; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein 32 WO 03/093432 PCT/US03/13690 n is an integer between 1 and 174; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 174. 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 174, 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 174, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein. Mutations can be introduced any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, 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 predicted 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 174, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined. 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, 33 WO 03/093432 PCT/US03/13690 NEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code. 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). 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). Interfering RNA 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 W002/29858, 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. 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 & 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. 34 WO 03/093432 PCT/USO3/13690 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. 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. 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 HIl. One example of a vector system is the GeneSuppressor m 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' 35 WO 03/093432 PCT/US03/13690 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. 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. 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 mRnNAs 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. 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. 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 36 WO 03/093432 PCT/US03/13690 would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene. 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. 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(N1 9)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 & 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. 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' (N1 9)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. 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 37 WO 03/093432 PCT/US03/13690 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 Vg 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 oftransfection 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. For a control experiment, transfection of 0.84 pg single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 pg antisense siRNA has a weak silencing effect when compared to 0.84 pg 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. 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, 38 WO 03/093432 PCT/US03/13690 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. 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. 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. 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'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 39 WO 03/093432 PCT/US03/13690 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. 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. Production of RNAs 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 gM) in 10 mM Tris-HCI (pH 7.5) with 20 mM NaCI were heated to 950 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). Lysate Preparation Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer's directions. dsRNA is incubated in the lysate at 30o 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 mnRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis. 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 X 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. 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 40 WO 03/093432 PCT/US03/13690 each assay. The sequence of these 21-23 mers is then determined using standard nucleic acid sequencing techniques. RNA Preparation 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, & Tuschl, Genes & Dev. 15, 188-200 (2001)), followed by Sep-Pak C18 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)). These RNAs (20 jtM) single strands are incubated in annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate) for 1 min at 900 C followed by 1 h at 370 C. Cell Culture 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 X 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. 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. Antisense Nucleic Acids 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 174, or 41 WO 03/093432 PCT/US03/13690 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 174, 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 174, are additionally provided. 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). 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 ofNOVX 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). 42 WO 03/093432 PCT/US03/13690 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-methyleytosine, 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). 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 mRNPA 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. 43 WO 03/093432 PCT/US03/13690 In yet another embodiment, the antisense nucleic acid molecule of the invention is an c-anomeric nucleic acid molecule. An c-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual (-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. Ribozymes and PNA Moieties 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. 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 eDNA disclosed herein (i.e., SEQ ID NO:2n-1, wherein n is an integer between 1 and 174). 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. Patent 4,987,071 to Cech, et al. and U.S. Patent 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. 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. YAcad. Sci. 660: 27-36; Maher, 1992. Bioassays 14: 807-15. 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 44 WO 03/093432 PCT/US03/13690 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'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93: 14670-14675. 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., SI 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'Keefe, et al., 1996. supra). 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. NuclAcids 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. NuclAcidRes 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, 45 WO 03/093432 PCT/US03/13690 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. 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. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like. NOVX Polypeptides 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 174. 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 174, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof. 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. 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. 46 WO 03/093432 PCT/US03/13690 Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques. 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. The language "substantially free of chemical precursors or other chemicals" includes preparations of NOVX proteins in which the protein is separated from chemical 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. 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 174) 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. 47 WO 03/093432 PCT/US03/13690 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. In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 174. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 174, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 174, 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 174, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between I and 174. Determining Homology Between Two or More Sequences 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"). 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. JMol 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 174. 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 48 WO 03/093432 PCT/US03/13690 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. Chimeric and Fusion Proteins 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 174, 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. 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. 49 WO 03/093432 PCT/US03/13690 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. In yet another embodiment, the fusion protein is a NOVX-inununoglobulin 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. 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-fi-ame 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.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion 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. 50 WO 03/093432 PCT/US03/13690 NOVX Agonists and Antagonists 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. 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. 51 WO 03/093432 PCT/US03/13690 Polypeptide Libraries 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 S 1 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. 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. Anti-NOVX Antibodies 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, Fab, Fab' and F(ab') 2 fragments, and an Fab expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ 52 WO 03/093432 PCT/US03/13690 from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgGj, 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. 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 174, 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. 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. 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 53 WO 03/093432 PCT/US03/13690 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 (KD) is 1 pM, preferably _ 100 nM, more preferably < 10 nM, and most preferably < 100 pM to about 1 pM, as measured by assays including radioligand binding assays or similar assays known to skilled artisans. 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. 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, NY, incorporated herein by reference). Some of these antibodies are discussed below. Polyclonal Antibodies 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 innmmunogenic 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'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). 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 54 WO 03/093432 PCT/US03/13690 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 (April 17, 2000), pp. 25-28). Monoclonal Antibodies 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. 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. 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, Monoclonal Antibodies: Principles and Practice, 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. 55 WO 03/093432 PCT/US03/13690 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, California and the American Type Culture Collection, Manassas, Virginia. 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). 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. 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's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal. 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. The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Patent 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 56 WO 03/093432 PCT/US03/13690 vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce inunummnoglobulin 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. Patent 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. Humanized Antibodies 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 huinans 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. Patent 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 (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)). 57 WO 03/093432 PCT/US03/13690 Human Antibodies 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: MONOCLONAL ANTIBODIES AND CANCER THERAPY, 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: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). 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. Patent 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)). Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal'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'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 58 WO 03/093432 PCT/US03/13690 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 TM as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human inumnunoglobulins. 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. 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. Patent 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. A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Patent 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. 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. Fab Fragments and Single Chain Antibodies 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. Patent No. 4,946,778). In addition, methods can be adapted for the construction of Fab expression 59 WO 03/093432 PCT/US03/13690 libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification ofmonoclonal Fab 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 Fab fragment generated by reducing the disulfide bridges of an F(ab')2 fragment; (iii) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) Fv fragments. 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. 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 hybridomnas (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 13 May 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991). 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 (CHI) 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). 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 60 WO 03/093432 PCT/US03/13690 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. 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. 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. 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. 61 WO 03/093432 PCT/US03/13690 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 1 ) connected to a light-chain variable domain (VL) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH 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). Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991). 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 (FcyR), such as FcyRI (CD64), FcyRII (CD32) and FcyRIII (CD 16) 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). Heteroconjugate Antibodies 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. Patent No. 4,676,980), and for treatment 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. Patent No. 4,676,980. 62 WO 03/093432 PCT/US03/13690 Effector Function Engineering 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 Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989). Immunoconjugates 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). 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 2 12 Bi, 131 a 31 n, 90Y, and 1 86 Re. 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), 63 WO 03/093432 PCT/US03/13690 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. 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. Immunoliposomes 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. Patent No. 5,013,556. 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). Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention 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 anNOVX 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 64 WO 03/093432 PCT/US03/13690 NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein. 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"). 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, j3-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 1251, 1311, 35 S or 3 H. Antibody Therapeutics Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed 65 WO 03/093432 PCT/US03/13690 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. 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. 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. Pharmaceutical Compositions of Antibodies 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 66 WO 03/093432 PCT/US03/13690 Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York. 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. 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. The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes. 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 y ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT m (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 67 WO 03/093432 PCT/US03/13690 release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. ELISA Assay 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., Fab 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, NJ, 1995; "Immunoassay", E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, CA, 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. 68 WO 03/093432 PCT/US03/13690 NOVX Recombinant Expression Vectors and Host Cells 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, expression vectors of utility 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. 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). 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, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 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 69 WO 03/093432 PCT/US03/13690 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.). 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, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 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. 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 pRITS (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein. Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET 1ld (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89). 70 WO 03/093432 PCT/US03/13690 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, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 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. In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSecl (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.). 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). 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'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., MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989. 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. 71 WO 03/093432 PCT/US03/13690 8: 729-733) and immunoglobulins (Banerji, 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 oc-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546). 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. 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. 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. 72 WO 03/093432 PCT/US03/13690 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. (MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals. 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). 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. Transgenic NOVX Animals 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 73 WO 03/093432 PCT/US03/13690 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. 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 eDNA sequences, i.e., any one of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174, 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. Patent Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: MANIPULATING THE MOUSE EMBRYO, 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. 74 WO 03/093432 PCT/US03/13690 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 174), 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 174, 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). 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. 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: TERATOCARCINOMAS AND EMBRYONIC STEM CELLS: A PRACTICAL APPROACH, 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: 75 WO 03/093432 PCT/US03/13690 823-829; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169. 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'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. 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 Go 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. Pharmaceutical Compositions 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 antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington'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's solutions, dextrose solution, and 5% 76 WO 03/093432 PCT/US03/13690 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. 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. 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 T M (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 77 WO 03/093432 PCT/US03/13690 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. 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. 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. 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. Systemic administration can also be by transmucosal or transdennal 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 78 WO 03/093432 PCT/US03/13690 sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art. 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. 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. Patent No. 4,522,811. 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. 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. Patent 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. 79 WO 03/093432 PCT/US03/13690 The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration. Screening and Detection Methods 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. The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra. Screening Assays 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. 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 80 WO 03/093432 PCT/US03/13690 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. 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. 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. US.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. 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. Patent No. 5,223,409), spores (Ladner, U.S. Patent 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. US.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. PatentNo. 5,233,409.). 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 1251 35S, 14C, 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 81 WO 03/093432 PCT/US03/13690 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. 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. 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 82 WO 03/093432 PCT/US03/13690 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. In yet another embodiment, an assay of the invention is a cell-fi-ee 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-active 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. 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. 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. 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 83 WO 03/093432 PCT/US03/13690 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-l1-propane sulfonate (CHAPSO). In more than one embodiment of the above assay methods of the invention, it ffiay be desirable to inummobilize 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. 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 84 WO 03/093432 PCT/US03/13690 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. 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 ofNOVX 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 ofNOVX 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 ofNOVX 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. 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. Patent 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. 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 85 WO 03/093432 PCT/US03/13690 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. The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein. Detection Assays Portions or fragments of the eDNA 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. Chromosome Mapping 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 174, 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. 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. 86 WO 03/093432 PCT/US03/13690 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'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. 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. 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., HUMAN CHROMOSOMES: A MANUAL OF BASIC TECHNIQUES (Pergamon Press, New York 1988). 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. 87 WO 03/093432 PCT/US03/13690 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, MENDELIAN INHERITANCE IN MAN, 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. 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. Tissue Typing The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual'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. Patent No. 5,272,057). 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'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's DNA and subsequently sequence it. 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 88 WO 03/093432 PCT/US03/13690 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). 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 174, are used, a more appropriate number of primers for positive individual identification would be 500-2,000. Predictive Medicine 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's Disease, Parkinson'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. 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"). 89 WO 03/093432 PCT/US03/13690 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.) 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. These and other agents are described in further detail in the following sections. Diagnostic Assays 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 174, 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. 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., Fab 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 90 WO 03/093432 PCT/US03/13690 hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, 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. 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. 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. 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. Prognostic Assays 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., 91 WO 03/093432 PCT/US03/13690 mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at risk of 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. 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). 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 92 WO 03/093432 PCT/US03/13690 means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells. 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. Patent 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. 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); QP3 Replicase (see, Lizardi, et al, 1988. BioTechnology 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. 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. Patent No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site. 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 93 WO 03/093432 PCT/US03/13690 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. 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. Biochemn. Biotechnol. 38: 147-159). 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 RNAJDNA 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 S1 nuclease to enzymatically digesting the mismatched regions. In otherembodiments, 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. 94 WO 03/093432 PCT/US03/13690 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. 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. Patent No. 5,459,039. 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. 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. 95 WO 03/093432 PCT/US03/13690 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. 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. 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. 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. Pharmacogenomies 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 96 WO 03/093432 PCT/US03/13690 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. In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual'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'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. 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. 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 97 WO 03/093432 PCT/US03/13690 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. 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'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. Monitoring of Effects During Clinical Trials 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. 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 98 WO 03/093432 PCT/US03/13690 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. 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. Methods of Treatment 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. These methods of treatment will be discussed more fully, below. 99 WO 03/093432 PCT/US03/13690 Diseases and Disorders 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 homrnologs 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., Capecehi, 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. 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. 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 andlor 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, irununoassays (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). Prophylactic Methods 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. 100 WO 03/093432 PCT/US03/13690 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. Therapeutic Methods 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. 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). 101 WO 03/093432 PCT/US03/13690 Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia). Determination of the Biological Effect of the Therapeutic 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. In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient'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. Prophylactic and Therapeutic Uses of the Compositions of the Invention 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. 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. 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. The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. 102 WO 03/093432 PCT/US03/13690 EXAMPLES Example A: Polynucleotide and Polypeptide Sequences, and Homology Data Example 1. The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table IA. Table 1A. NOVI Sequence Analysis NOV1a, CG103910-02 SEQ ID NO: 1 1224 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1041 ATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCT GCTGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCC TCCGCAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCG CGCCCGCACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGC GGTGGAGGAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCC AGGGCCCCCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTC GTCAACCTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGA TCTTTCCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCC GGGAACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGG GAATCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGA CATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGG AGACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAAC AAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGG GAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACG TGGCAGGTCCACTTCATCAACCCGGAAACGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGC CATCTCCGTCCTCTACTTCGATGACAGCTCCAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCC GGGCCTGTGGCTGCCACTAGCTCCTCCGAGAATTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTC CATTGCTCGCCTTGGCCAGGAACCAGCAGACCAACTGCCTTTTGTGAGACCTTCCCCTCdCTATCCCC NOVia, CG103910-02 SEQ ID NO: 2 1347 aa MW at 39545.6kD Protein Sequence MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILSILGLPHRP RPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQVLQEHLGR ESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPRHNLGLQLSVETLDGQSINPKLAGLIGRHGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEALRMANVAGPLHQPGNGAQALLCAHAAQC HLRPLLR NOVIb, CC103910-03 SEQ ID NO: 3 1226 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 976 ATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCT GCTGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCC TCCGCAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCG CGCCCGCACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGC GGTGGAGGAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCC AGGGCCCCCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTC GTCAACCTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGA TCTTTCCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCC GGGAACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGG GAATCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGA CATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGG AGACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGOCCTGATTOGGCGGCACGGGCCCCAGAAC AAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGG GAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACG 103 WO 03/093432 PCT/US03/13690 TGGCAGGACTGGATCATCGCGCCTGAAGGCTACGCCGCCTACTACTGTGAGGGGGAGTGTGCCTTCCC TCTGAACTCCTACATGAACGCCACCAACCACGCCATCGTGCAGACGCTGGTCCACTTCATCAACCCGG AAACGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCTATGCCATCTCCGTCCTCTACTTCGATGAC AGTTCCAACGTCATCCTGAAGAAATACAGATACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCT cc NOVIb, CGl03910-03 SEQ IDNO: 41325aa W at 37269.9kD Protein Sequence MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILSILGLPHRP RPHLQGKKNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQVLQEHLGR ESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPRHNLGLQLSVETLDGQSINPKLAGLIGRHGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEALRMANVAGLDHRA NOVc, CG103910-01 SEO ID NO: 5 1878 bp DNA Sequence ORF Start: ATG at 123 ORF Stop: TAG at 1418 GGGCGCAGCGGGGCCCGTCTGCAGCAAGTGACCGACGGCCGGGACGGCCGCCTGCCCCCTCTGCCACC TGGGGCGGTGCGGGCCCGGAGCCCGGAGCCCGGGTAGCGCGTAGAGCCGGCGCGATGCACGTGCGCTC ACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCTGCTGCGCTCCGCCC TGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTCATCCACCGGCGCCTCCGCAGCCAGGAG CGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCGCGCCCGCACCTCCA GGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGCGGTGGAGGAGGGCG GCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCCAGGGCCCCCCTCTG GCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTCGTCAACCTCGTGGA ACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGATCTTTCCAAGATCC CAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCCGGGAACGCTTCGAC AATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGGGAATCGGATCTCTT CCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGACATCACAGCCACCA GCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGGAGACGCTGGATGGG CAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAACAAGCAGCCCTTCAT GGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGGGAGCAAACAGCGCA GCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACGTGGCAGAGAACAGC AGCAGCGACCAGAGGCAGGCCTGTAAGAAGCACGACTGTATGTCAGCTTCCGAGACCTGGGCTGGCA GGACTGGATCATCGCGCCTGAAGGCTACGCCGCCTACTACTGTGAGGGGGAGTGTGCCTTCCCTCTGA ACTCCTACATGAACGCCACCAACCACGCCATCGTGCAGACGCTGGTCCACTTCATCAACCCGGAAACG GTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGCCATCTCCGTCCTCTACTTCGATGACAGCTC CAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCTCCGAG AATTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTCCATTGCTCGCCTTGGCCAGGAACCAGCAGA CCAACTGCCTTTTGTGAGACCTTCCCCTCCCTATCCCCAACTTTAAAGGTGTGAGAGTATTAGGAAAC ATGAGCAGCATATGGCTTTTGATCAGTTTTTCAGTGGCAGCATCCAATGAACAAGATCCTACAAGCTG TGCAGGCAAAACCTAGCAGGAAAAAAAAACAACGCATAAAGAAAA ATGGCCGGGCCAGGTCATTGGCT GGGAAGTCTCAGCCATGCACGGACTCGTTTCCAGAGGTAATTATGAGCGCCTACCAGCCAGGCCACCC AGCCGTGGGAGGAAGGGGGCGTGGCAAGGGGTGGGCACATTGGTGTCTGTGCGAAAGGAAAATTGACC CGGAAGTTCCTGTAATAAATGTCACAATAAAACGAATGAATG NOV1c, CG103910-01 SEQ ID NO: 6 431 aa MWat49312.4kD Protein Sequence MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILSILGLPHRP RPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQVLQEHLGR ESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPRHNLGLQLSVETLDGQSINPKLAGLIGRHGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEALRMANVAENSSSDQRQACKKHELYVSFR DLGWQDWIIAPEGYAAYYCEGECAFPLNSYMNATNAIVQTLVHFINPETVPKPCCAPTQLNAISVLY FDDS SNVILKKYRNMVVRACGCH NOVd, CG103910-04 SEQ ID NO: 7 997 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: end of sequence CACCGGATCCACCATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGG 104 WO 03/093432 PCT/US03/13690 CACCCCTGTTCCTGCTGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACGAGGTGCACTCGAGCTTC ATCCACCGGCGCCTCCGCAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTT GCCCCACCGCCCGCGCCCGCACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGT ACAACGCCATGGCGGTGGAGGAGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCC GTCTTCAGTACCCAGGGCCCCCCTCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACAT GGTCATGAGCTTCGTCAACCTCGTGGAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAG AGTTCCGGTTTGATCTTTCCAAGATCCCAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTAC AAGGACTACATCCGGGAACGCTTCGACAATGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGA GCACTTGGGCAGGGAATCGGATCTCTTCCTGCTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCT GGCTGGTGTTTGACATCACAGCCACCAGCAACCACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTG CAGCTCTCGGTGGAGACGCTGGATGGGCAGAGCATCAACCCCAAGTTGGCGGGCCTGATTGGGCGGCA CGGGCCCCAGAACAAGCAGCCCTTCATGGTGGCTTTCTTCAAGGCCACGGAGGTCCACTTCCGCAGCA TCCGGTCCACGGGGAGCAAACAGCGCAGCCAGAACCGCTCCAAGACGCCCAAGAACCAGGAAGCCCTG CGGATGGCCAACGTGGCAGGACTGGATCATCGCGCC NOVId, CG103910-04 SEQ ID NO: 8 325 aa MW at Protein Sequence 137269.9kD MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILSILGLPHRP RPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQVLQEHLGR ESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPRHNLGLQLSVETLDGQSINPKLAGLIGRHGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEALRMANVAGLDHRA NOVIe, 13382317 SNP CG103910-02 SEQ IDNO: 9 SNP at position 1193 DNA Sequence ORF Start: ATG at 1 ORF Stop: TGA at 1042 ATGCACGTGCGCTCACTGCGAGCTGCGGCGCCGCACAGCTTCGTGGCGCTCTGGGCACCCCTGTTCCTGC TGCGCTCCGCCCTGGCCGACTTCAGCCTGGACAACOAGGTGCACTCGAGCTTCATCCACCGGCGCCTCCG CAGCCAGGAGCGGCGGGAGATGCAGCGCGAGATCCTCTCCATTTTGGGCTTGCCCCACCGCCCGCGCCCG CACCTCCAGGGCAAGCACAACTCGGCACCCATGTTCATGCTGGACCTGTACAACGCCATGGCGGTGGAGG AGGGCGGCGGGCCCGGCGGCCAGGGCTTCTCCTACCCCTACAAGGCCGTCTTCAGTACCCAGGGCCCCCC TCTGGCCAGCCTGCAAGATAGCCATTTCCTCACCGACGCCGACATGGTCATGAGCTTCGTCAACCTCGTG GAACATGACAAGGAATTCTTCCACCCACGCTACCACCATCGAGAGTTCCGGTTTGATCTTTCCAAGATCC CAGAAGGGGAAGCTGTCACGGCAGCCGAATTCCGGATCTACAAGGACTACATCCGGGAACGCTTCGACAA TGAGACGTTCCGGATCAGCGTTTATCAGGTGCTCCAGGAGCACTTGGGCAGGGAATCGGATCTCTTCCTG CTCGACAGCCGTACCCTCTGGGCCTCGGAGGAGGGCTGGCTGGTGTTTGACATCACAGCCACCAGCAACC ACTGGGTGGTCAATCCGCGGCACAACCTGGGCCTGCAGCTCTCGGTGGAGACGCTGGATGGGCAGAGCAT CAACCCCAAGTTGGCGGGCCTGATTGGGCGGCACGGGCCCCAGAACAAGCAGCCCTTCATGGTGGCTTTC TTCAAGGCCACGGAGGTCCACTTCCGCAGCATCCGGTCCACGGGGAGCAAACAGCGCAGCCAGAACCGCT CCAAGACGCCCAAGAACCAGGAAGCCCTGCGGATGGCCAACGTGGCAGGTCCACTTCATCAACCCGGAAA CGGTGCCCAAGCCCTGCTGTGCGCCCACGCAGCTCAATGCCATCTCCGTCCTCTACTTCGATGACAGCTC CAACGTCATCCTGAAGAAATACAGAAACATGGTGGTCCGGGCCTGTGGCTGCCACTAGCTCCTCCGAGAA TTCAGACCCTTTGGGGCCAAGTTTTTCTGGATCCTCCATTGCTCGCCTTGGCCAGGAACCAGCAGACCAA CTCCCTTTTGTGAGACCTTCCCCTCCCTATCCCC NOVie, 13382317 SNP CG103910-02 SEQ ID NO: 10325 aa SNP: No change in Protein Sequence Protein sequence MEVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILSILGLPHRP RPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLASLQDSHFLTDADMVMSF VNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDYIRERFDNETFRISVYQVLQEHLGR ESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPRHNLGLQLSVETLDGQSINPKLAGLIGRGPQN KQPFMVAFFKATEVHFRSIRSTGSKQRSQNRSKTPKNQEALRMANVAGPLHQPGNGAQALLCARAAQC HLRPLLR A ClustaIW comparison of the above protein sequences yields the following sequence alignment shown in Table IB. 105 WO 03/093432 PCT/US03/13690 Table lB. Comparison of the NOV1 protein sequences. NOVIa MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS NOVIb MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS NOVIc MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS NOVId MHVRSLRAAAPHSFVALWAPLFLLRSALADFSLDNEVHSSFIHRRLRSQERREMQREILS NOV1a ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS NOV1b ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS NOVIc ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS NOVId ILGLPHRPRPHLQGKHNSAPMFMLDLYNAMAVEEGGGPGGQGFSYPYKAVFSTQGPPLAS NOVIa LQDSHFLTDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY NOVIb LQDSHFLTDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY NOVic LQDSHFLTDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY NOVId LQDSHFLTDADMVMSFVNLVEHDKEFFHPRYHHREFRFDLSKIPEGEAVTAAEFRIYKDY NOVIa IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR NOVIb IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR NOVIc IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR NOVId IRERFDNETFRISVYQVLQEHLGRESDLFLLDSRTLWASEEGWLVFDITATSNHWVVNPR NOVIa HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPFMVAFFKATEVHFRSIRSTGSKQRS NOVIb HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPFMVAFFKATEVHFRSIRSTGSKQRS NOVIc HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPFMVAFFKATEVHFRSIRSTGSKQRS NOVId HNLGLQLSVETLDGQSINPKLAGLIGRHGPQNKQPFMVAFFKATEVHFRSIRSTGSKQRS NOVIa QNRSKTPKNQEALRMANVAG----PLHQPGN--------------------- GAQALLCA NOVIb QNRSKTPKNQEALRMANVAG----LDHRA------------------------------ NOVIc QNRSKTPKNQEALRMANVAENSSSDQRQACKKHELYVSFRDLGWQDWIIAPEGYAAYYCE NOV1d QNRSKTPKNQEALRMANVAG---LDHRA------------------------------- NOVIa HAAQCHLRPLLR------------------------------------------------- NOV1b ----------------------------------------------------------- NOV1c GECAFPLNSYMNATNHAIVQTLVHFINPETVPKPCCAPTQLNAISVLYFDDSSNVILKKY NOV1d ----------------------------------------------------------- NOVIa

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NOVIb ---------- NOVIc RNMVVRACGCH NOVId --------- NOVIa (SEQ ID NO: 2) NOVIb (SEQ ID NO: 4) NOV1c (SEQ ID NO: 6) NOVId (SEQ ID NO: 8) Further analysis of the NOV1 a protein yielded the following properties shown in Table I C. Table 1C. Protein Sequence Properties NOVia SignalP analysis: Cleavage site between residues 30 and 31 PSORT II analysis: PSG: a new signal peptide prediction method 106 WO 03/093432 PCT/US03/13690 N-region: length 7; pos.chg 2; neg.chg 0 H-region: length 17; peak value 9.51 PSG score: 5.11 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 0.94 possible cleavage site: between 29 and 30 >>> Seems to have a cleavable signal peptide (1 to 29) ALOM: Klein et al's method for TM region allocation Init position for calculation: 30 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 6.10 (at 124) ALOM score: 6.10 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 14 Charge difference: -5.5 C(-1.5) - N( 4.0) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 3 Hyd Moment(75): 6.00 Hyd Moment(95): 9.57 G content: 0 D/E content: 1 S/T content: 3 Score: -0.96 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 35 LRSIAL NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 11.5% NLS Score: -0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: HVRS 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 107 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 44.4 %: extracellular, including cell wall 22.2 %: Golgi 11.1 %: vacuolar 11.1 %: nuclear 11.1 %: endoplasmic reticulum >> prediction for CG103910-02 is exc (k=9) A search of the NOVIa 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. 108 WO 03/093432 PCT/USO3/13690 Table 1D. Geneseq Results for NOVla NOVia Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region ABU56730 Lung cancer-associated polypeptide 1..319 319/319 (100%) 0.0 #323 - Unidentified, 431 aa. 1..319 319/319 (100%) [WO200286443-A2, 31-OCT-2002] AAU97017 Human osteogenic protein (OP-1) - 1..319 319/319 (100%) 0.0 Homo sapiens, 431 aa. 1..319 319/319 (100%) [US2002049159-A1, 25-APR-2002] AAE25993 Human osteogenic protein 1 (hOP- 1..319 319/319 (100%) 0.0 1) - Homo sapiens, 431 aa. 1..319 319/319 (100%) [US6407060-B1, 18-JUN-2002] ABB82416 Human osteogenic protein-1 (OP-1) 1..319 319/319 (100%) 0.0 - Homo sapiens, 431 aa. 1..319 319/319 (100%) [WO200270029-A2, 12-SEP-2002] AAB37614 Human OP-1 - Homo sapiens, 431 1..319 319/319(100%) 0.0 aa. [WO200066620-A2, 09-NOV- 1.319 319/319 (100%) 2000] In a BLAST search of public sequence databases, the NOV 1 a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E. 109 WO 03/093432 PCT/USO3/13690 Table 1E. Public BLASTP Results for NOVla Protein NOVla Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value Residues Portion Q9BTB3 Similar to bone morphogenetic 1..319 319/319 (100%) 0.0 protein 7 (Osteogenic protein 1) - 1..319 319/319 (100%) Homo sapiens (Human), 412 aa. P 18075 Bone morphogenetic protein 7 1..319 319/319 (100%) 0.0 precursor (BMP-7) (Osteogenic 1..319 319/319 (100%) protein 1) (OP-1) - Homo sapiens (Human), 431 aa. P23359 Bone morphogenetic protein 7 1..319 309/319 (96%) e-180 precursor (BMP-7) (Osteogenic 1..318 313/319 (97%) protein 1) (OP-1) - Mus musculus (Mouse), 430 aa. JQ1184 osteogenic protein 1 precursor - 1..319 308/319 (96%) e-179 mouse, 430 aa. 1..318 312/319 (97%) Q91I8T6 Bone morphogenetic protein 7 - 39..319 246/285 (86%) e-143 Gallus gallus (Chicken), 398 aa 2..286 264/285 (92%) (fragment). PFam analysis predicts that the NOVIa protein contains the domains shown in the Table 1F. Table 1F. Domain Analysis of NOVIa Identities/ Pfam Domain NOVla Match Region Similarities Expect Value for the Matched Region TGFbpropeptide 37..281 104/269 (39%) 3e-100 223/269 (83%) Example 2. The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A. Table 2A. NOV2 Sequence Analysis NOV2a, CG106298-02 ISEQ ID NO: 11 1162bp DNA Sequence ORF Sat 19 top: at 832 CTACTGAGAATATCTAACATGTTGTTACTAATCAATGTCATTCTGACCTTGTGGGTTTCCTGTGCTAA TGGACAAGTGAAACCTTGTGATTTTCCAGACATTAAACATGGAGGTCTATTTCATGAGAATATGCGTA 110 WO 03/093432 PCT/US03/13690 GACCATACTTTCCAGTAGCTGTAGGACAATCTTACTCCTATTACTGTGACCAAAATTTTGTGACTCCT TCAGGAAGTTACTGGGATTACATTCACTGCACACAAGATGGGTGGTTGCCAACAGTCCCATGCCTCAG AACATGCTCAAAATCAGATATAGAAATTGAAAATGGATTCATTTCTGAATCTTCCTCTATTTATATTT TAATAAAGAAATACAATATAAATGTAAACCAGGATATGCAACAGCAGATGGAAATTCTTCAGGTTCA ATTACATGTTTGCAAAATGGATGGTCAGCACAACCAATTTGCATTAAATTTTGTGATATGCCTGTTTT TGAGAATTCCAGAGCCAAGAGTAATGGCATGCGGTTTAAGCTCCATGACACATTGGACTACGAATGCT ACGATGGATATGAAATCAGTTATGGAAACACCACAGGTTCCATAGTGTGTGGTGAAGATGGGTGGTCC CATTTCCCAACATGTTATAATTCTTCAGAAAAGTGTGGGCCTCCTCCACCTATTAGCAATGGTGATAC CACCTCCTTTCTACTAAAAGTGTATGTGCCACAGTCAAGAGTCGAGTACCAATGCCAGTCCTACTATG AACTTCAGGGTTCTAATTATGTAACATGTAGTAATGGAGAGTGGTCGGAACCACCAAGATGCATACGT ATCCACTTCTGCAGATGATCATGTCCAAGTTTGAGCTCCAAACTATGCAAGTGGCAAGACTGAAGAAG AAATTAGTATCCTCAAATCAAAATAGTTTACAAGTATCTTCAAACTTGATTTCATAGAAAAGTGTTAG GTTTCAGAGATAAATTCTGAGTCTCAAATTTGATTGAATGGGGAGATGGACACTCCTAAGATGGGTTT CACAGCAAAAGCATTACCTCTTCTCACAATCAAGAACAGGAAAGGATTATAATTATCTGAAGTATAAG ATCAGTTCCATGATACAAGCAAGACTTTCAGTCTTCAAAACTAAAGAAGCAAAGAGCATTCAAGCACA GAATTC NOV2a, CG106298-02 SEQ ID NO: 12 271 aa MW at 30635.1kD Protein Sequence MLLLINVILTLWVSCANGQVKPCDFPDIKHGGLFHNMRRPYFPVAVGQSYSYYCDQNFVTPSGSYWD YIHCTQDGWLPTVPCLRTCSKSDIEIENGFISESSSIYILNKEIQYKCKPGYATADGNSSGSITCLQN GWSAQPICIKFCDMPVFENSRAKSNGMRFKLHDTLDYECYDGYEISYGNTTGSIVCGEDGWSHFPTCY NSSEKCGPPPPISNGDTTSFLLKVYVPQSRVEYQCQSYYELQGSNYVTCSNGEWSEPPRCIRIHFCR NOV2b, CG106298-01 SEQ ID NO: 13 2033 bp DNA equ Start: ATG at78 OR TAA at 1812 AATAATAATGAAAGATTTCAAACCCCAAACAGTGCAACTGAAACTTTTGCATTACTATACTACTGAGA ATATCTAACATGTTGTTACTAATCAATGTCATTCTGACCTTGTGGGTTTCCTGTGCTAATGGACAAGA AGTGAAACCTTGTGATTTTCCAGAAATTCAACATGGAGGTCTATATTATAAGAGTTTGCGTAGACTAT ACTTTCCAGCAGCTGCAGGACAATCTTATTCCTATTACTGTGATCAAAATTTTGTGACTCCTTCAGGA AGTTACTGGGATTACATTCATTGCACACAAGATGGTTGGTCACCAACGGTCCCATGCCTCAGAACATG CTCAAAATCAGATGTAGAAATTGAAAATGGATTCATTTCTGAATCTTCCTCTATTTATATTTTAAATG AAGAAACACAATATAATTGTAAACCAGGATATGCAACAGCAGATGGAAATTCTTCAGGATCAATTACA TGTTTGCAAAATGGATGGTCAACACAACCAATTTGCATTAAATTTTGTGATATGCCTGTTTTTGAGAA TTCCAGAGCCAAGAGTAATGGCATGTGGTTTAAGCTCCATGACACATTGGACTATGAATGCTATGATG GATATGAAAGCAGTTATGGAAACACCACAGATTCCATAGTGTGTGGTGAAGATGGCTGGTCCCATTTG CCAACATGCTATAATTCTTCAGAAAGCTGTGGGCCTCCTCCACCTATTAGCAATGGAGATACCACGTC CTTCCCGCAAAAAGTGTATCTGCCATGGTCAAGAGTCGAGTACCAGTGCCAGTCCTACTATGAACTTC AGGGTTCTAAATATGTAACATGTAGTAATGGAGACTGGTCAGAACCACCAAGATGCATATCAATGAAA CCTTGTGAGTTTCCAGAAATTCAACATGGACATCTATATTATGAGAATACGCGTAGACCATACTTTCC AGTAGCTACAGGACAATCTTACTCCTATTACTGTGACCAAAATTTTGTGACTCCTTCAGGAAGTTACT GGGATTACATTCACTGCACACAAGATGGGTGGTTGCCAACAGTCCCATGCCTCAGAACATGCTCAAAA TCAGATATAGAAATTGAAAATGGATTCATTTCTGAATCTTCCTCTATTTATATTTTAAATAAAGAAAT ACAATATAAATGTAAACCAGGATATGCAACAGCAGATGGAAATTCTTCAGGTTCAATTACATGTTTGC AAAATGGATGGTCAGCACAACCAATTTGCATTAAATTTTGTGATATGCCTGTTTTTGAGAATTCCAGA GCCAAGAGTAATGGCATGCGGTTTAAGCTCCATGACACATTGGACTACGAATGCTACGATGGATATGA AATCAGTTATGGAAACACCACAGGTTCCATAGTGTGTGGTGAAGATGGGTGGTCCCATTTCCCAACAT GTTATAATTCTTCAGAAAAGTGTGGGCCTCCTCCACCTATTAGCAATGGTGATACCACCTCCTTTCTA CTAAAAGTGTATGTGCCACAGTCAAGAGTCGAGTACCAATGCCAGTCCTACTATGAACTTCAGGGTTC TAATTATGTAACATGTAGTAATGGAGAGTGGTCGGAACCACCAAGATGCATACATCCATGTATAATAA CTGAAGAAAACATGAATAAAAATAACATACAGTTAAAAGGAAAAAGTGACATAAAATATTATGCAAAA ACAGGGGATACCATTGAATTTATGTGTAAATTGGGATATAATGCGAATACATCAGTTCTATCATTTCA AGCAGTGTGTAGGGAAGGCATAGTGGAATACCCCAGATGCGAATAAGGCAGCATTGTTACCCTAAATG TATGTCCAACTTCCACTTCTCACTCTTATGGTCTCAAAGCTTGCAAAGATAGCTTCTGATATTGTTGT AATTTCTACTTTATTTCAAAGAAAATTAATATAATAGTTTCAATTTGCAACTTAATATGTTCTCAAAA ATATGTTAAAACAAACTAAATTATTGCTTATGCTTGTACTAAAATAATAAAAACTACCCTT NOV2b, CG106298-01 SEQ ID NO: 14 578 aa MW at 65309.OkD Protein Sequence 111 WO 03/093432 PCT/US03/13690 MLLLINVILTLWVSCANGQEVKPCDFPEIQHGGLYYKSLRRLYFPAAAGQSYSYYCDQNFVTPSGSYW DYIHCTQDGWSPTVPCLRTCSKSDVEIENGFISESSSIYILNEETQYNCKPGYATADGNSSGSITCLQ NGWSTQPICIKFCDMPVFENSRAKSNGMWFKLHDTLDYECYDGYESSYGNTTDSIVCGEDGWSHLPTC YNSSESCGPPPPISNGDTTSFPQKVYLPWSRVEYQCQSYYELQGSKYVTCSNGDWSEPPRCISMKPCE FPEIQHGHLYYENTRRPYFPVATGQSYSYYCDQNFVTPSGSYWDYIHCTQDGWLPTVPCLRTCSKSDI EIENGFISESSSIYILNKEIQYKCKPGYATADGNSSGSITCLQNGWSAQPICIKFCDMPVFENSRAKS NGMRFKLHDTLDYECYDGYEISYGNTTGSIVCGEDGWSHFPTCYNSSEKCGPPPPISNGDTTSFLLKV YVPQSRVEYQCQSYYELQGSNYVTCSNGEWSEPPRCIHPCIITEENMNKNNIQLKGKSDIKYYAKTGD TIEFMCKLGYNANTSVLSFQAVCREGIVEYPRCE A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 2B. Table 2B. Comparison of the NOV2 protein sequences. NOV2a MLLLINVILTLWVSCANGQ-VKPCDFPDIKHGGLFHENMRRPYFPVAVGQSYSYYCDQNF NOV2b MLLLINVILTLWVSCANGQEVKPCDFPEIQHGGLYYKSLRRLYFPAAAGQSYSYYCDQNF NOV2a VTPSGSYWDYIHCTQDGWLPTVPCLRTCSKSDIEIENGFISESSSIYILNKEIQYKCKPG NOV2b VTPSGSYWDYIHCTQDGWSPTVPCLRTCSKSDVEIENGFISESSSIYILNEETQYNCKPG NOV2a YATADGNSSGSITCLQNGWSAQPICIKFCDMPVFENSRAKSNGMRFKLHDTLDYECYDGY NOV2b YATADGNSSGSITCLQNGWSTQPICIKFCDMPVFENSRAKSNGMWFKLHDTLDYECYDGY NOV2a EISYGNTTGSIVCGEDGWSHFPTCYNSSEKCGPPPPISNGDTTSFLLKVYVPQSRVEYQC NOV2b ESSYGNTTDSIVCGEDGWSHLPTCYNSSESCGPPPPISNGDTTSFPQKVYLPWSRVEYQC NOV2a QSYYELQGSNYVTCSNGEWSEPPRCIRIHFCR--------------------------- NOV2b QSYYELQGSKYVTCSNGDWSEPPRCISMKPCEFPEIQHGHLYYENTRRPYFPVATGQSYS NOV2a --------------------------------------------------

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NOV2b YYCDQNFVTPSGSYWDYIHCTQDGWLPTVPCLRTCSKSDIEIENGFISESSSIYILNKEI NOV2a ---------------------------------------------------- NOV2b QYKCKPGYATADGNSSGSITCLQNGWSAQPICIKFCDMPVFENSRAKSNGMRFKLHDTLD NOV2a ------------------------------------------------- NOV2b YECYDGYEISYGNTTGSIVCGEDGWSHFPTCYNSSEKCGPPPPISNGDTTSFLLKVYVPQ NOV2a ------------------------------------------------- NOV2b SRVEYQCQSYYELQGSNYVTCSNGEWSEPPRCIHPCIITEENMNKNNIQLKGKSDIKYYA NOV2a ------------------------------------- NOV2b KTGDTIEFMCKLGYNANTSVLSFQAVCREGIVEYPRCE NOV2a (SEQ ID NO: 12) NOV2b (SEQ ID NO: 14) 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 19 and 20 112 WO 03/093432 PCT/US03/13690 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 20; peak value 9.20 PSG score: 4.80 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 1.38 possible cleavage site: between 18 and 19 >>> Seems to have a cleavable signal peptide (1 to 18) ALOM: Klein et al's method for TM region allocation Init position for calculation: 19 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPHERAL Likelihood = 8.27 (at 137) ALOM score: 8.27 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 9 Charge difference: 0.0 C( 1.0) - N( 1.0) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.43 Hyd Moment(95): 4.91 G content: 1 D/E content: 1 S/T content: 2 Score: -5.38 Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 7.4% 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 113 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 44.4 %: extracellular, including cell wall 33.3 %: nuclear 22.2 %: mitochondrial >> prediction for CG106298-02 is exc (k=9) 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. 114 WO 03/093432 PCT/USO3/13690 Table 2D. Geneseq Results for NOV2a NOV2a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAY09065 Human complement factor H 12..265 241/263 (91%) e-152 homolog protein - Homo sapiens, 578 251..513 250/263 (94%) aa. [WO9918200-A1, 15-APR-1999] ABU07436 Protein differentially regulated in 10..253 135/303 (44%) 9e-68 prostate cancer #39 - Homo sapiens, 312..611 171/303 (55%) 1231 aa. [WO200281638-A2, 17 OCT-2002] AAB43738 Human cancer associated protein 1..265 108/270 (40%) 2e-56 sequence SEQ ID NO:1183 - Homo 13..275 154/270 (57%) sapiens, 342 aa. [WO200055350-A1, 21-SEP-2000] ABB80571 Human sbg614126complfH protein 1..265 113/269 (42%) 2e-56 #2 - Homo sapiens, 327 aa. 1..262 154/269 (57%) [WO200222802-A1, 21-MAR-2002] ABB80570 Human sbg614126complfH protein 23..265 102/247 (41%) 5e-51 #1 - Homo sapiens, 364 aa. 60..299 141/247 (56%) [WO200222802-A1, 21-MAR-2002] 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. 115 WO 03/093432 PCT/USO3/13690 Table 2E. Public BLASTP Results for NOV2a Protein NOV2a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value Residues Portion Q92496 Complement factor H-related protein 1..265 255/266 (95%) e-160 4 precursor (FHR-4) - Homo sapiens 1..266 262/266 (97%) (Human), 331 aa. Q02985 Complement factor H-related protein 1..265 172/270 (63%) e-101 3 precursor (FHR-3) (H factor-like 1..265 198/270 (72%) protein 3) (DOWNI16) - Homo sapiens (Human), 330 aa. A45222 complement factor H-related protein 1..265 173/269 (64%) e-101 DOWN16 precursor - human, 331 aa. 1..266 196/269 (72%) Q8R018 Hypothetical 58.1 kDa protein - Mus 10.,270 150/320 (46%) 6e-81 musculus (Mouse), 509 aa. 130..447 181/320 (55%) Q61407 Complement factor H-related protein - 10..270 150/320 (46%) 6e-81 Mus musculus'(Mouse), 452 aa 73.390 181/320 (55%) (fragment). PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F. Table 2F. Domain Analysis of NOV2a Identities/ Pfam Domain NOV2a Match Region Similarities Expect Value for the Matched Region Sushi 23..83 17/69 (25%) 1.2e-08 47/69(68%) Sushi 87..144 22/68 (32%) 2.2e-12 45/68 (66%) Sushi 148..203 22/66 (33%) 3.9e-08 44/66 (67%) Sushi 210..264 23/65 (35%) 5.4e-15 42/65 (65%) 116 WO 03/093432 PCT/US03/13690 Example 3. The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A. Table 3A. NOV3 Sequence Analysis NOV3a, CGl10590-02 SEQ ID NO: 15 1487 bp DNA Sequence ORF Start: ATGat 112 ORF Stop: TGA at 1303 GGAGAAGGCCAGTGCCCAGGTTAGTGAGCAGTGCCCGGCGCCCGCTTCCCTCACCTCCTTTTCCAGCC TTTGCACAGCTTGAAGGTTCTGTCACCTTTTGCAGTGGTCCAAATGAGAAAAAAGTGGAAAATGGGAG GCATGAAATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAAGGAGGCAAAACAGAGCAAGTAAAA. CATTCAGAGACATATTGCATGTTTCAAGACAAGAAGTACAGAGTGGGTGAGAGATGGCATCCTTACCT GGAACCTTATGGGTTGGTTTACTGCGTGAACTGCATCTGCTCAGAGAATGGGAATGTGCTTTGCAGCC GAGTCAGATGTCCAAATGTTCATTGCCTTTCTCCTGTGCATATTCCTCATCTGTGCTGCCCTCGCTGC CCAGACTCCTTACCCCCAGTGAACAATAAGGTGACCAGCAAGTCTTGCGAGTACAATGGGACAACTTA CCAACATGGAGAGCTGTTCGTAGCTGAAGGGCTCTTTCAGAATCGGCAACCCAATCAATGCACCCAGT GCAGCTGTTCGGAGGGAAACGTGTATTGTGGTCTCAAGACTTGCCCCAAATTAACCTGTGCCTTCCCA GTCTCTGTTCCAGATTCCTGCTGCCGGGTATGCAGAGGAGATGGAGAACTGTCATGGGAACATTCTGA TGGTGATATCTTCCGGCAACCTGCCAACAGAGAAGCAAGACATTCTTACCACCGCTCTCACTATGATC CTCCACCAAGCCGACAGGCTGGAGGTCTGTCCCGCTTTCCTGGGGCCAGAAGTCACCGGGGAGCTCTT ATGGATTCCCAGCAAGCATCAGGAACCATTGTGCAAATTGTCATCAATAACAAACACAAGCATGGACA AGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGAGTCCTGGCACCCAAACCTCCGGGCATTTG GCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAGCAAGAGTGTAAGAAAATCCACTGCCCC AATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAAATGCTGCAAGGTGTGTCCAGGTAAAAA AGCAAAAGAACTTCCAGGCCAAAGCTTTGACAATAAAGGATACTTCTGCGGGGAAGAAACGATGCCTG TGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACCAGAAAAATAGCACTGGAGACTGAGAGACCA CCTCAGGCATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTGAGGAGCTTCCTCAC TTCAAGCTGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAAGCTCAGATCAG CCAGATGTGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTACCTGGAGA GATCTGAAAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAA NOV3a, CG1 10590-02 SEQ ID NO: 16 397 aa MW at 44841.9kD Protein Sequence MRKKWKMGGMYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERWHPYLEPYGLVYCVNCICS ENGNVLCSRVRCPNVHCLSPVHIPHLCCPRCPDSLPPVNNKVTSKSCEYNGTTYQHGELFVAEGLFQN RQPNQCTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELSWEHSDGDIFRQPANREARH SYHRSHYDPPPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINNKHKHGQVCVSNGKTYSHGES WHPNLRAFGIVECVLCTCNVTKQECKKIHCPNRYPCKYPQKIDGKCCKVCPGKKAKELPGQSFDNKGY FCGEETMPVYESVFMEDGETTRKIALETERPPQAFSSTSILRRSPRGCLRSFLTSSW NOV3b, CG110590-01 SEQ ID NO: 17 1440bp DNA Sequence RF Start: ATG at 18 PJOR Stop: TAG at 1374 TGAGAAAAGTGGAAAATGGGAGGCATG AATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAA GGAGGCAAAACAGAGCAAGTAAAACATTCAGAGACATATTGCATGTTTCAAGACAAGAAGTACAGAGT GGGTGAGAGATGGCATCCTTACCTGGAACCTTATGGGTTGGTTTACTGCGTGAACTGCATCTGCTCAG AGAATGGGAATGTGCTTTGCAGCCGAGTCAGATGTCCAAATGTTCATTGCCTTTCTCCTGTGCATATT CCTCATCTGTGCTGCCCTCGCTGCCCAGAAGACTCCTTACCCCCAGTGAACAATAAGGTGACCAGCAA GTCTTGCGAGTACAATGGGACAACTTACCAACATGGAGAGCTGTTCGTAGCTGAAGGGCTCTTTCAGA ATCGGCAACCCAATCAATGCACCCAGTGCAGCTGTTCGGAGGGAAACGTGTATTGTGGTCTCAAGACT TGCCCCAAATTAACCTGTGCCTTCCCAGTCTCTGTTCCAGATTCCTGCTGCCGGGTATGCAGAGGAGA TGGAGAACTGTCATGGGAACATTCTOATGGTATATCTTCCGGCAACCTGCCAACAGAGAAGCAAGAC ATTCTTACCACCGCTCTCACTATGATCCTCCACCAAGCCGACAGGCTGGAGGTCTGTCCCGCTTTCCT GGGGCCAGAAGTCACCGGGGAGCTCTTATGGATTCCCAGCAAGCATCAGGAACCATTGTGCAAATTGT CATCAATAACAAACACAAGCATGGACAAGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGAGT CCTGGCACCCAAACCTCCGGGCATTTGGCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAG CAAGAGTGTAAGAAAATCCACTGCCCCAATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAA 117 WO 03/093432 PCT/US03/13690 ATGCTGCAAGGTGTGTCCAGGTAAAAAAGCAAAAGAAGAACTTCCAGGCCAAAGCTTTGACAATAAAG GCTACTTCTGCGGGGAAGAAACGATGCCTGTGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACC AGAAAAATAGCACTGGAGACTGAGAGACCACCTCAGGTAGAGGTCCACGTTTGGACTATTCGAAAGGG CATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTGAGGAGCTTCCTCACTTCAAGC TGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAAGCTCAGATCAGCCAGATG TGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTACCTGGAGAGATCTGA AAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAAAACTCAAGCTGCAGCT GGACTGCAGGCT NOV3b, CGI 10590-01 SEQ ID NO: 18 452 aa MW at 51425.5kD Protein Sequence MGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERWHPYLEPYGLVYCVNCICSENGNVL CSRVRCPNVHCLSPVHIPHLCCPRCPEDSLPPVNNKVTSKSCEYNGTTYQHGELFVAEGLFQNRQPNQ CTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELSWEHSDGDIFRQPANREARHSYHRS HYDPPPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNL RAFGIVECVLCTCNVTKQECKKIHCPNRYPCKYPQKIDGKCCKVCPGKKAKEELPGQSFDNKGYFCGE ETMPVYESVFMEDGETTRKIALETERPPQVEVHVWTIRKGILQMFHIEKISKRMFEELPHFKLVTRTT LSQWKIFTEGEAQISQMCSSRVCRTELEDLVKVLYLERSEKGHC NOV3c, 13382325 SNP SEQ ID NO: 19 1487 bp, SNP: T/C at CG110590-02 'position 454 DNA Sequence ORF Start: ATG at 112 jORF Stop: 1303 GGAGAAGGCCAGTGCCCAGGTTAGTGAGCAGTGCCCGGCGCCCGCTTCCCTCACCTCCTTTTCCAGCCTTT GCACAGCTTGAAGGTTCTGTCACCTTTTGCAGTGGTCCAAATGAGAAAAAAGTGGAAAATGGGAGGCATGA AATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAAGGAGGCAAAACAGAGCAAGTAAAACATTCAGAG ACATATTGCATGTTTCAAGACAAGAAGTACAGAGTGGGTGAGAGATGGCATCCTTACCTGGAACCTTATGG GTTGGTTTACTGCGTGAACTGCATCTGCTCAGAGAATOGGAATGTGCTTTGCAGCCGAGTCAGATGTCCAA ATGTTCATTGCCTTTCTCCTGTGCATATTCCTCATCTGTGCTGCCCTCGCTGCCCAGACTCCTTACCCCCA GTGAACAATAAGGTGACCAGCAAGTCTCGCGAGTACAATGGGACAACTTACCAACATGGAGAGCTGTTCGT AGCTGAAGGGCTCTTTCAGAATCGGCAACCCAATCAATGCACCCAGTGCAGCTGTTCGGAGGGAAACGTGT ATTGTGGTCTCAAGACTTGCCCCAAATTAACCTGTGCCTTCCCAGTCTCTGTTCCAGATTCCTGCTGCCGG GTATGCAGAGGAGATGGAGAACTGTCATGGGAACATTCTGATGGTGATATCTTCCGGCAACCTGCCAACAG AGAAGCAAGACATTCTTACCACCGCTCTCACTATGATCCTCCACCAAGCCGACAGGCTGGAGGTCTGTCCC GCTTTCCTGGGCCAGAAGTCACCGGGGAGCTCTTATGGATTCCCAGCAAGCATCAGGAACCATTGTGCAA ATTGTCATCAATAACAAACACAAGCATGGACAAGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGA GTCCTGGCACCCAAACCTCCGGGCATTTGGCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAGC AAGAGTGTAAGAAAATCCACTGCCCCAATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAAATGC TGCAAGGTGTGTCCAGGTAAAAAAGCAAAAGAACTTCCAGGCCAAAGCTTTGACAATAAAGGATACTTCTG CGGGGAAGAAACGATGCCTGTGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACCAGAAAAATAGCAC TGGAGACTGAGAGACCACCTCAGGCATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTG AGGAGCTTCCTCACTTCAAGCTGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAA GCTCAGATCAGCCAGATGTGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTA CCTGGAGAGATCTGAAAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAA NOV3c, 13382325 SNP SEQ ID NO: 20 397 aa SNP: Cys to Arg at 115 CG1 10590-02 Protein Sequence MRKKWKMGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERWHPYLEPYGLVYCVNCICSENG NVLCSRVRCPNVHCLSPVHIPHLCCPRCPDSLPPVNNKVTSKSREYNGTTYQHGELFVAEGLFQNRQPNQC TQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELSWEHSDGDIFRQPANREARHSYHRSHYDP PPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNLRAFGIVE CVLCTCNVTKQECKKIHCPNRYPCKYPQKIDGKCCKVCPGKKAKELPGQSFDNKGYFCGEETMPVYESVFM EDGETTRKIALETERPPQAFSSTSILRRSPRGCLRSFLTSSW NOV3d, 13382326 SNP SEQ ID NO: 21 1440 bp SNP: A/G at CG110590-02 756 DNA Sequence ORF Start: ATG at ORF Stop: end of .112 Isequence 118 WO 03/093432 PCT/US03/13690 GGAGAAGGCCAGTGCCCAGGTTAGTGAGCAGTGCCCGGCGCCCGCTTCCCTCACCTCCTTTTCCAGCCTTT GCACAGCTTGAAGGTTCTGTCACCTTTTGCAGTGGTCCAAATGAGAAAAAAGTGGAAAATGGGAGGCATGA AATACATCTTTTCGTTGTTGTTCTTTCTTTTGCTAGAAGGAGGCAAAACAGAGCAAGTAAAACATTCAGAG ACATATTGCATGTTTCAAGACAAGAAGTACAGAGTGGGTGAGAGATGGCATCCTTACCTGGAACCTTATGG GTTGGTTTACTGCGTGAACTGCATCTGCTCAGAGAATGGGAATGTGCTTTGCAGCCGAGTCAGATGTCCAA ATGTTCATTGCCTTTCTCCTGTGCATATTCCTCATCTGTGCTGCCCTCGCTGCCCAGACTCCTTACCCCCA GTGAACAATAAGGTGACCAGCAAGTCTTGCGAGTACAATGGGACAACTTACCAACATGGAGAGCTGTTCGT AGCTGAAGGGCTCTTTCAGAATCGGCAACCCAATCAATGCACCCAGTGCAGCTGTTCGGAGGGAAACGTGT ATTGTGGTCTCAAGACTTGCCCCAAATTAACCTGTGCCTTCCCAGTCTCTGTTCCAGATTCCTGCTGCCGG GTATGCAGAGGAGATGGAGAACTGTCATGGGAACATTCTGATGGTGATATCTTCCGGCAACCTGCCAACAG AGAAGCAAGACATTCTTACCACCGCTCTCACTATGATCCTCCACCGAGCCGACAGGCTGGAGGTCTGTCCC GCTTTCCTGGGGCCAGAAGTCACCGGGGAGCTCTTATGGATTCCCAGCAAGCATCAGGAACCATTGTGCAA ATTGTCATCAATAACAAACACAAGCATGGACAAGTGTGTGTTTCCAATGGAAAGACCTATTCTCATGGCGA GTCCTGGCACCCAAACCTCCGGGCATTTGGCATTGTGGAGTGTGTGCTATGTACTTGTAATGTCACCAAGC AAGAGTGTAAGAAAATCCACTGCCCCAATCGATACCCCTGCAAGTATCCTCAAAAAATAGACGGAAAATGC TGCAAGGTGTGTCCAGGTAAAAAAGCAAAAGAACTTCCAGGCCAAAGCTTTGACAATAAAGGATACTTCTG CGGGGAAGAAACGATGCCTGTGTATGAGTCTGTATTCATGGAGGATGGGGAGACAACCAGAAAAATAGCAC TGGAGACTGAGAGACCACCTCAGGCATTCTCCAGCACTTCCATATTGAGAAGATCTCCAAGAGGATGTTTG AGGAGCTTCCTCACTTCAAGCTGGTGACCAGAACAACCCTGAGCCAGTGGAAGATCTTCACCGAAGGAGAA GCTCAGATCAGCCAGATGTGTTCAAGTCGTGTATGCAGAACAGAGCTTGAAGATTTAGTCAAGGTTTTGTA CCTGGAGAGATCTGAAAAGGGCCACTGTTAGGCAAGACAGACAGTATTGGATAGGGTAAAGCAAGAA NOV3d, 13382326 SNP SEQ ID NO: 22 397 aa SNP: No change in protein CGI 10590-02. sequence Protein Sequence -1 MRKKWKMGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERWHPYLEPYGLVYCVNCICSENG NVLCSRVRCPNVHCLSPVHIPHLCCPRCPDSLPPVNNKVTSKSCEYNGTTYQHGELFVAEGLFQNRQPNQC TQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCRGDGELSWEHSDGDIFRQPANREARHSYHRSHYDP PPSRQAGGLSRFPGARSHRGALMDSQQASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNLRAFGIVE CVLCTCNVTKQECKKIHCPNRYPCKYPQKIDGKCCKVCPGKKAKELPGQSFDNKGYFCGEETMPVYESVFM EDGETTRKIALETERPPQAFSSTSILRRSPRGCLRSFLTSSW A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 3B. 119 WO 03/093432 PCT/US03/13690 Table 3B. Comparison of the NOV3 protein sequences. NOV3a MRKKWKMGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERWHPYLEPYGLV NOV3b ------ MGGMKYIFSLLFFLLLEGGKTEQVKHSETYCMFQDKKYRVGERWHPYLEPYGLV NOV3a YCVNCICSENGNVLCSRVRCPNVHCLSPVHIPHLCCPRCP-DSLPPVNNKVTSKSCEYNG NOV3b YCVNCICSENGNVLCSRVRCPNVHCLSPVHIPHLCCPRCPEDSLPPVNNKVTSKSCEYNG NOV3a TTYQHGELFVAEGLFQNRQPNQCTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCR NOV3b TTYQHGELFVAEGLFQNRQPNQCTQCSCSEGNVYCGLKTCPKLTCAFPVSVPDSCCRVCR NOV3a GDGELSWEHSDGDIFRQPANREARHSYHRSHYDPPPSRQAGGLSRFPGARSHRGALMDSQ NOV3b GDGELSWEHSDGDIFRQPANREARHSYHRSHYDPPPSRQAGGLSRFPGARSHRGALMDSQ NOV3a QASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNLRAFGIVECVLCTCNVTKQECKK NOV3b QASGTIVQIVINNKHKHGQVCVSNGKTYSHGESWHPNLRAFGIVECVLCTCNVTKQECKK NOV3a IHCPNRYPCKYPQKIDGKCCKVCPGKKAK-ELPGQSFDNKGYFCGEETMPVYESVFMEDG NOV3b IHCPNRYPCKYPQKIDGKCCKVCPGKKAKEELPGQSFDNKGYFCGEETMPVYESVFMEDG NOV3a ETTRKIALETERPP-------------- QAFSSTSILRRS---- PRGCLRS-FLTSSW- NOV3b ETTRKIALETERPPQVEVHVWTIRKGILQHFHIEKISKRMFEELPHFKLVTRTTLSQWKI NOV3a ------------------------------------- NOV3b FTEGEAQISQMCSSRVCRTELEDLVKVLYLERSEKGHC NOV3a (SEQ ID NO: 16) NOV3b (SEQ ID NO: 18) Further analysis of the NOV3a protein yielded the following properties shown in Table 3C. Table 3C. Protein Sequence Properties NOV3a SignalP analysis: Cleavage site between residues 28 and 29 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 11; pos.chg 5; neg.chg 0 H-region: length 11; peak value 12.14 PSG score: 7.74 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -1.64 possible cleavage site: between 27 and 28 >>> Seems to have a cleavable signal peptide (1 to 27) ALOM: Klein et al's method for TM region allocation Init position for calculation: 28 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed 120 WO 03/093432 PCT/US03/13690 PERIPHERAL Likelihood = 1.80 (at 277) ALOM score: 1.80 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 13 Charge difference: -6.5 C(-0.5) - N( 6.0) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 6.12 Hyd Moment(95): 9.66 G content: 2 D/E content: 1 S/T content: 1 Score: -4.32 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 12 MRKIKW NUCDISC: discrimination of nuclear localization signals pat4: none pat7: PGKKAKE (4) at 323 bipartite: none content of basic residues: 13.1% NLS Score: -0.13 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: RKKW 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 121 WO 03/093432 PCT/US03/13690 checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 66.7 %: extracellular, including cell wall 11.1%: mitochondrial 11.1 %: vacuolar 11.1 %: nuclear >> prediction for CG110590-02 is exc (k=9) A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3D. Table 3D. Geneseq Results for NOV3a NOV3a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAY53035 Human secreted protein clone 1..373 373/374 (99%) 0.0 dw665_4 protein sequence SEQ ID 1..374 373/374 (99%) NO:76 - Homo sapiens, 457 aa. [WO9957132-A1, 11-NOV-1999] AAY82777 Human chordin related protein (Clone 1..373 373/374 (99%) 0.0 dw665_4) - Homo sapiens, 457 aa. 1..374 373/374 (99%) [WO200009551-A1, 24-FEB-2000] AAM39408 Human polypeptide SEQ ID NO 2553 1..373 371/375 (98%) 0.0 - Homo sapiens, 458 aa. 1..375 372/375 (98%) [WO200153312-Al1, 26-JUL-2001] AAB65027 Gene #1 associated peptide #2 - 1..373 368/374 (98%) 0.0 Homo sapiens, 489 aa. 37..406 369/374 (98%) [W0200075375-A1, 14-DEC-2000] .......... AAB64993 Human secreted protein #1 - Homo 1..373 368/374 (98%) 0.0 sapiens, 453 aa. [WO200075375-A1, 1..370 369/374 (98%) 14-DEC-2000]_. . 122 WO 03/093432 PCT/US03/13690 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 3E. Table 3E. Public BLASTP Results for NOV3a Protein NOV3a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value Residues Portion Q9BU40 Neuralin precursor (Ventroptin) - 7..373 367/367 (100%) 0.0 Homo sapiens (Human), 450 aa. 1..367 367/367 (100%) CAC43868 Sequence 7 from Patent 7..373 367/369 (99%) 0.0 WO0 142465 precursor - Homo 1..369 367/369 (99%) sapiens (Human), 452 aa. CAC43869 Sequence 11 from Patent 7..373 362/368 (98%) 0.0 WO0142465 precursor - Homo 1..364 363/368 (98%) sapiens (Human), 447 aa (fragment). Q920C1 Neuralin precursor (Ventroptin) - 7.373 334/368 (90%) 0.0 Mus musculus (Mouse), 447 aa. 1.364 351/368 (94%) CAC43867 Sequence 4 from Patent 7..377 327/372 (87%) 0.0 WO0142465 precursor - Rattus 1..368 346/372 (92%) _ _ norvegicus (Rat), 382 aa. PFamn analysis predicts that the NOV3a protein contains the domains shown in the Table 3F. Table 3F. Domain Analysis of NOV3a Identities/ Pfam Domain NOV3a Match Region Similarities Expect Value for the Matched Region Vwc 37..99 25/84 (30%) 1.5e-10 39/84 (46%) Vwc 115..178 26/90 (29%) 8e-09 48/90 (53%) Vwc 260..322 27/84 (32%) 1.5e-11 41/84 (49%) 123 WO 03/093432 PCT/US03/13690 Example 4. The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A. Table 4A. NOV4 Sequence Analysis NOV4a, CG114555-01 SEQ ID NO: 23 1710 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: TAA at 1534 GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG ATGACACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGAAAGAAGGCA TGGACGTCCAATAGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCG GTGGACTTGTGGGGACATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTG GCCAATAATGGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGA AATGCTCATCGTGGGACGCTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGT ACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGC ATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATA CCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCAGCTOCTGAGCCTTCCCTTTCTCCCGGACAGCC CACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGT AAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCT GGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCA TGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAA.CAGCATCTTTGGAAAAGCT GGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGT CTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGG GCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTG AGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGC TCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTA GTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAG AACCTATGCAGAAATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCG ACTCAGCTGTCACTGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAAT TATGTCAAAAACAGGATTGTCTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTAT TGGGAAGCTTAAATGAATTGAAGCTATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGT ACTAATCTAA NOV4a, CG114555-01 SEQ ID NO: 24 507 aa M at 55327.3kD MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRRYIKAFYNESWERRHGRPI DPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAFEMLIV GRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGV IVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVL ELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGL VIEHLGRRPLLIGGFGLMGLFFGTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEF FQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAE ISQAFSKRNKAYPPEEKIDSAVTDGKINGRP NTYV4b, 247847074 ISEQ ID K): 25 1203 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence TTGTACAAAAAAGCAGGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAA TAATGGGTTTGCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGC TCATCGTGGGACGTTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTC AGTGAGATCTCACCCAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGG CGTGTTCACTGGGCAGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGT TTGGAGTGATTGTGGTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGC TACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGC AGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGT 124 WO 03/093432 PCT/US03/13690 CCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCC TGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGAT CCCTCCGGCAARGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCT CTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTC TTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTAT CGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTG GTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCC AACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTT TGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCT ATGCAGAAATCAGCCAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC NOV4b, 247847074 SEQ ID NO: 26 401 aa fW at 43391.7kD Protein Sequence LYKKAGSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYL SEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPR YLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMA CYQLCGLNAIWFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLS NFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA NOV4c, 247847070 ISEQ ID NO: 27 111087 bp DNA Sequence ORF Start: at 1 JORF Stop: end of sequence GGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGT TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACC CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACATTTCCCAAG AGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG TGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGA TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGACCACGCCCCC TGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGG CATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAG GCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGAC ACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCC TGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC NOV4c, 247847070 SEQ ID NO: 28 362 aa JMW at 39164.5kD Protein Sequence GSAAA.PFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISP KEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLE KHNEARAVKAFQTFLGKADISQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLC GLNAIWFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSDHAPWVPYLSIVGILAIIASFCSGPGG IPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLP ETKNRTYABISQAFLEGKGGRA NOV4d, 247847055 SEQ ID NO: 29 1189 bp DNA SequenceORF Start: at 1 ORF Stop: end of sequence GGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGC TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACC CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAG 1AGGTAGAGGAGGTCCTGGCTGAGAGCCACGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG 125 WO 03/093432 PCT/US03/13690 CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG TGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGA TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATT GAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCT CACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGG CCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAG CAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGG GCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTA TCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGC CAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC NOV4d, 247847055 SEQ ID NO: 30 396 aa MW at 42768.9kD Protein Sequence M t GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAEMLIVGRIMGIDGGVALSVLPMYLSEISP KEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLE KHNEARAVKAFQTFLGKADVSQEVEEVLAESHVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLC GLNAIWFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTL TITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAPIIAGTVNWLSNFAVG LLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA NO4e, 247847059 SEQ ID NO: 31 1189b DNA Sequence ORF Start: at 1 ORF Stop: end of sequence GGCTCCGCGGCCGCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGC TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACC CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACATTTCCCAAG AGGTAGAGGAGOTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG TGGCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGA TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATT GAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCT CACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGG CCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAG CAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGG GCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTA TCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGC CAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC NOV4e, 247847059 SEQ ID NO: 32 396 aa ;MW at 42801.9kD Protein Sequence GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFMLIVGRFIMGIDGGVALSVLPMYLSEISP *KEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLE KHNEARAVKAFQTFLGKADISQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLC GLNAIWFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVPSOLVIEHLGRRPLLIGGFGLMGLPFGTL TITLTLQDHAPWVPYLSIVGILAI!ASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVG LLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA NOV4f, 247847047 }SEQIDNO:33 J1189bp DNA Sequence IORF Start: at I JORF Stop: end of sequence GGCTCCGCGGCCGCCCCCTTCACCGGTACCAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAA TTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGC TTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATOTACCTCAGTGAGATCTCACC CAAGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGC AGCTTCTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTG GTCCCTGCCGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGA 126 WO 03/093432 PCT/US03/13690 GAAGCACAACGAGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAG AGGTAGAGGAGGTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTG CTGAGAGCTCCCTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTG TGOCCTCAATGCAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGA TCCCATACGTCACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATT GAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCT CACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGG CCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAG CAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGG GCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTA TCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGC CAGGCATTTCTCGAGGGCAAGGGTGGGCGCGCC NOV4f, 247847047 SEQ ID NO: 34 396 aa MW at 42803.9kD Protein Sequence GSAAAPFTGTRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISP KEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLE KHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLC GLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTL TITLTLQDRAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVG LLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFLEGKGGRA NOV4g, CG114555-02 ISEQ ID NO: 35 .1682 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: TAA at 1634 GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG ATGACACCAGCCACGCCAGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGTCCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGGACTGGTCCTGCTCGCTCCTCGTGGCCTCCCTCGCGGGCGC CTTCGGCTCCCCCTTCCTCTACGGCTACAACCTGTCGGTGGTGAATGCCCCCACCCCGTACATCAAGG CCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAATAGACCCAGACACTCTGACTCTGCTC TGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGACATTAATTGTGAAGATGATTGG AAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAATTTCTGCTGCATTGCTGA TGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAGATGCTCATCGTGGGACGCTTCATCATGGGCATAGAT GGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTC TCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCG AGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCAG CTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAG AGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGG CTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTC CGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTG GTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGA GTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGA CCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGGCCCTCACCATCACGCTGACCCT GCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCT GCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCT GCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCAT TCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATCTACC TGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTTCCAAAAGG AACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGATGGTAAGATAAATGGAAGGCC TTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTG NOV4g, CG1 14555-02 SEQ ID NO: 36 MW at 58796.3kD Protein Sequence MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRRKDWSCSLLVASLAGAFGSP FLYGYNLSVVNAPTPYIKAFYNESWERRHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLG RKHTLLANNGFAISAALLMACSLQAGAEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQV TAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKA FQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFYTN SIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGALTITLTLQDHA 127 WO 03/093432 PCT/US03/13690 PWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVGLLFPFIQKSL DTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKINGRP NOV4h, CGI14555-03 {EQ ID NO: 37 j1757 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: TAA at 1709 GTCACTGAGACCCATGGCAAGGAAGCAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG ATGACACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGCAGCCTCTACGGAGCACCTCCTCTGCAGCAGGCTCCTCAAC AACATATGTGGCCAGTGCTGCTATTAAGATCCCATTTCACAGGTGGGCAAGCTTAGCCCCAGAAAAGT CAAGTCACTTGCTCAGACTCCTACAGCTGAGGGGACTGGCCCTGGAGGTAAAGCTGATATCACTTGGC TCAAAGCCCCAAAGCTCTATCTCGTGGCTGGTGGCACTAGAGGAGACAAACGAGATTGGCAGAGACTG GTCCTGCTCGCTCCTCGTGGCCTCCCTCGCGGGCGCCTTCGGCTCCTCCTTCCTCTACGGCTACAACC TGTCGGTGGTGAATGCCCCCACCCCGCACACTTTGCTGGCCAATAATGGGTTTGCAATTTCTGCTGCA TTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCATCATGGG CATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCC GTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGC CTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGT TGTCCAGCTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACG AGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAG GTCCTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCC CTACGTCCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATG CAATTTGGTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTC ACCTTGAGTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGG ACGGAGACCCCTCCTCATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGGCCCTCACCATCACGC TGACCCTGCAGGACCACGCCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCC TCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCG GCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCC CATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCT ATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTTC CAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGATGGTAAGATAAATG GAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTG NOV4h, CG114555-03 SEQ IDNO: 38 565 aa JMW at 61112.6kD Protein Sequence MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKQPLRSTSSAAGSSTTYVA SAAIKIPFHRWASLAPEKSSHLLRLLQLRGLALEVKLISLGSKPQSSISWLVALEETNEIGRDWSCSL LVASLAGAFGSSFLYGYNLSVVNAPTPHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGIDGG VALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLL SLPFLLDSPRYLLLEKHNEARAVKAPQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRW QVVTVIVTMACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPL LIGGFGLMGLFFGALTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAF IIAGTVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNK AYPPEEKIDSAVTDGKINGRP NOV4i, CG114555-04 ISEQ ID NO: 39 11502 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: TAA at 1454 GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAG ATGACACCAGCCACGCCAGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGTCCACCTGAGGAGT GGGGTGCCAGGTGGAAGGAGAAGAAAGGACTGGTCCTGCTCGCTCCTCGTGGCCTCCCTCGCGGGCGC CTTCGGCTCCCCCTTCCTCTACGGCTACAACCTGTCGGTGGTGAATGCCCCCACCCCGTACATCAAGG CCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAATAGACCCAGACACTCTGACTCTGCTC TGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGACATTAATTGTGAAGATGATTGG AAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAATTTCTGCTGCATTGCTGA TGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAGATGCTCATCGTGGGACGCTTCATCATGGGCATAGAT GGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGATCCGTGGCTC TCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCTGCCCG AGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCAG CTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAG 128 WO 03/093432 PCT/US03/13690 AGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGG CTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTC CGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTG GTTCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGA GTACAGGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGCATCCCGTTCATCTTGACTGGTGAGTTC TTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTCCAACTTTGC TGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGCTACAA TTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGAA ATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCAC TGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACA GGATTG NOV4i, CG114555-04 SEQ ID NO: 40 480 aa MW at 52522.9kD Protein Sequence MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRRKDWSCSLLVASLAGAFGSP FLYGYNLSVVNAPTPYIKAFYNESWERRHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLG RKHTLLANNGFAISAA.LLMACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQV TAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKA FQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFYTN SIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGIPFILTGEFFQQSQRPAAFIIAGTVNWLSNFAVGLL FPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKI NGRP NOV4j, 13379365 SNP in SEQ ID NO: 41 SNP G/A at position 86 CGl 14555-01 ORF Start: ATG at 14 ORF Stop: TAA at 1535 DNA Sequence GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA CACCAGCCACGCCAGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT AGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC ATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT CCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT GCCCGAGCTGCTGGGAAAGGAGAGTACCTOGCCATACCTGTTTOGAGTGATTGTGGTCCCTGCCGTTGTCCA GCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTC CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTA GTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACC TATGCAGAAATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCT GTCACTGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAAC AGGATTGTCTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGA ATTGAAGCTATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA NOV4j, 13379365 SNP in SEQ ID NO: 42 507aa SNP: Gly to CG114555-01 Arg at position Protein Sequence 25 MARKQNRNSKELGLVPLTDDTSHARPPGPORALLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPIDPDT LTLLWSVTVSIRAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAFEMLITVGRFI:MGID! GGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSL PFLPDSPRYLLLEKHNEARAVKAFQTFLGRADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVI 129 WO 03/093432 PCT/US03/13690 VTMACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAIIAGTVNWLSNFAV GLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKIN GRP NOV4k, 13379364 SNP in SEQ ID NO:43 SNP: G/A at position 97 CG114555-01 ORF Start: ATG at 14 ORF Stop: TAA at 1535 DNA Sequence GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA CACCAGCCACGCCGGGCCTCCAGGACCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT AGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC ATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT CCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT GCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCA GCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTC CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGC TACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGA AATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGA TGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTGT CTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGAATTGAAGC TATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA NOV4k, 13379364 SNP SEQ ID NO: 507 aa SNP: Gly to Gly at position 28 CG114555-01 44 Protein Sequence MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPIDPDT LTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGID GGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSL PFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVI VTMACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAPIIAGTVNWLSNFAV GLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKIN GRP NOV41, 13379363 SNP CGl 14555-01 SEQ ID NO5 SNP: A/G at position 289 DNA Sequence ORF Start: ATG at ORF Stop: TAA at 1535 position 14 GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA CACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT AGACCCAGACACTCTGACTCTGCTCTGGTCTOTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC GTTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT CCGTGGCTCTCTGGGGCAGGTGACTOCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT GCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCA 130 WO 03/093432 PCT/US03/13690 GCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTC CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGC TACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGA AATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGA TGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTGT CTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGAATTGAAGC TATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA NOV41, 13379363 SNP SEQ ID NO: 507 SNP: no change in the protein CG14555-01 46 aa sequence Protein Sequence MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPIDPDT LTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLMACSLQAGAFEMLIVGRFIMGID GGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSL PFLPDSPRYLLLEKHNEARAVKAFQTFLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVI VTMACYQLCGLNAIWFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGL FFGTLTITLTLQDHAPWVPYLS IVGILAI IASFCSGPGGI PFILTGEFFQQSQRPAAFIIAGTVWLSNFAV GLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSAVTDGKIN GRP NOV4m, 13379362 SNP CG1 14555-01 SEQ ID NO: 47 SNP: C/T at position 672 DNA Sequence ORF Start: ATG at ORF Stop: TAA at 1535 position 14L GTCACTGAGACCCATGGCAAGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATGA CACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTGCC AGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGGAAAGAAGGCATGGACGTCCAAT AGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGGGGAC ATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTTGCAAT TTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACGCTTCAT CATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCAAGGAGAT CCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTTCTGGGCCT GCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGCCGTTGTCCA GCTGCTGAGCCTTCCCTTTCTCCTGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACAACGAGGCAAGAGC TGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGACGTTTCCCAAGAGGTAGAGGAGGTCCTGGCTGAGAG CCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGTCCGCTGGCAGGT GGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGTTCTATACCAACAG CATCTTTGGAAAAGCTGGGATCCCTCTGGCAAAGATCCCATACGTCACCTTGAGTACAGGGGGCATCGAGAC TTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCTCATTGGTGGCTTTGG GCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACGCCCCCTGGGTCCCCTA CCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGTGGCATCCCGTTCATCTT GACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGGCACCGTCAACTGGCTCTC CAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCTACTGTTTCCTAGTCTTTGC TACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACCAAAAACAGAACCTATGCAGA AATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAAAATCGACTCAGCTGTCACTGA TGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACAATTATGTCAAAAACAGGATTGT CTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATTGGGAAGCTTAAATGAATTGAAGC TATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTAATCTAA NOV4m, 13379362 SEQ ID NO: 48 507 aa SNP: Pro to Leu at position 220 SNP CG114555-01 131 WO 03/093432 PCT/t1S03/13690 Protein Sequence MARKQNRNSKELGLVPLTDDTSHAGPPGPGRAIJLECDHLRSGVPGGRRRKYIKAFYNESWERRHGRPIDPD TLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANSNGFAISAALLMACSLQAGAFEMLIVGRFIMG IDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTGQLLGLPELLGKESTWPYLFGVIVVPAVVQL LSLPFLLDSPRYLLLEKHEARAVKAFQTFLGKADJVSQEVEEVLAESRVQRS IRLVSVLELLRAPYVRWQV .VTVIVTMACYQLCGLNAIWFYTNS IFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGF GLMGLFFGTLTITLTLQDIIAPNVPYLSIVGILAI ASFCSGPGGIPFILTGEFFQQSQRPAAFIIAGTVNW LSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFSKRNKAYPPEEKIDSA VTDGKINGRP NOV~n, 13379620 NP- 7SEQ ID NO: 49 ........ ISNP: TIC at position 963 .. CGI 14555-01 lORF Start: ATG a, ORF Stop: TAA at 15 35 DNA Sequence position 14 GTATGAG-ACCCATGGC1AGGAAACAAAATAGGAATTCCAAGGAACTGGGCCTAGTTCCCCTCACAGATG ACACCAGCCACGCCGGGCCTCCAGGGCCAGGGAGGGCACTGCTGGAGTGTGACCACCTGAGGAGTGGGGTG CCAGGTGGAAGGAGAAGAAAGTACATCAAGGCCTTTTACAATGAGTCATGGAAAGAAOGCATGGACGTCC AATAGACCCAGACACTCTGACTCTGCTCTGGTCTGTGACTGTGTCCATATTCGCCATCGGTGGACTTGTGG GGACATTAATTGTGAAGATGATTGGAAAGGTTCTTGGGAGGAAGCACACTTTGCTGGCCAATAATGGGTTT GCAATTTCTGCTGCATTGCTGATGGCCTGCTCGCTCCAGGCAGGAGCCTTTGAAATGCTCATCGTGGGACG CTTCATCATGGGCATAGATGGAGGCGTCGCCCTCAGTGTGCTCCCCATGTACCTCAGTGAGATCTCACCCA AGGAGATCCGTGGCTCTCTGGGGCAGGTGACTGCCATCTTTATCTGCATTGGCGTGTTCACTGGGCAGCTT CTGGGCCTGCCCGAGCTGCTGGGAAAGGAGAGTACCTGGCCATACCTGTTTGGAGTGATTGTGGTCCCTGC CGTTGTCCAGCTGCTGAGCCTTCCCTTTCTCCCGGACAGCCCACGCTACCTGCTCTTGGAGAAGCACACG AGGCAAGAGCTGTGAAAGCCTTCCAAACGTTCTTGGGTAAAGCAGAkCGTTTCCCAAGAGGTAGAGGAGGTC CTGGCTGAGAGCCGCGTGCAGAGGAGCATCCGCCTGGTGTCCGTGCTGGAGCTGCTGAGAGCTCCCTACGT CCGCTGGCAGGTGGTCACCGTGATTGTCACCATGGCCTGCTACCAGCTCTGTGGCCTCAATGCAATTTGGT TCTATACCAACAGCATCTTTGGAAAAGCTGGGATCCCTCCGGCAAAGATCCCATACGTCACCTTGAGTACA GGGGGCATCGAGACTTTGGCTGCCGTCTTCTCTGGTTTGGTCATTGAGCACCTGGGACGGAGACCCCTCCT CATTGGTGGCTTTGGGCTCATGGGCCTCTTCTTTGGGACCCTCACCATCACGCTGACCCTGCAGGACCACG CCCCCTGGGTCCCCTACCTGAGTATCGTGGGCATTCTGGCCATCATCGCCTCTTTCTGCAGTGGGCCAGGT GGCATCCCGTTCATCTTGACTGGTGAGTTCTTCCAGCAATCTCAGCGGCCGGCTGCCTTCATCATTGCAGG CACCGTCAACTGGCTCTCCAACTTTGCTGTTGGGCTCCTCTTCCCATTCATTCAGAAAAGTCTGGACACCT ACTGTTTCCTAGTCTTTGCTACAATTTGTATCACAGGTGCTATCTACCTGTATTTTGTGCTGCCTGAGACC AAAAACAGAACCTATGCAGAAATCAGCCAGGCATTTTCCAAAAGGAACAAAGCATACCCACCAGAAGAGAA AATCGACTCAGCTGTCACTGATGGTAAGATAAATGGAAGGCCTTAACAAGTTTCCTCCTCCACGTTGGACA ATTATGTCAAAAACAGGATTGTCTACATGGATGATCTCACTTTTCAGGAAACTTAAAATTTACCCATTATT GGGAAGCTTAATGAATTGAAGCTATGCAAGTCTTTTATATTATTAAATATTTAAAAGTAAACCTGTACTA ATCTAA MRQPSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKYIKAFYNESWE RRHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAI SAALLM ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFTG QLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQTFL GKAflVSQEVEEVLAESRVQRS IRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAIWFY TSSIFGK-AGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFFGTLT ITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFXIIAGTVNWL SNFAVGLLPFIQKSLDTYCFLVATICITGAIYLYFVLPETNTYAEI SQAFSKRNKAY PPEEKIDSAVTDGKINGRP A ClustaiW comparison of the above protein sequences yields the following sequence alignent shown in Table 4B. 132 WO 03/093432 PCT/US03/13690 Table 4B. Comparison of the NOV4 protein sequences. NOV4a MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRK--------- NOV4b ----------------------------------------------------------- NOV4c ----------------------------------------------------------- NOV4d ----------------------------------------------------------- NOV4e ----------------------------------------------------------- NOV4f ----------------------------------------------------------- NOV4g MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRRKDW------- NOV4h MARKQNRNSKELGLVPLTDDTSHAGPPGPGRALLECDHLRSGVPGGRRRKQPLRSTSSAA NOV4i MARKQNRNSKELGLVPLTDDTSHARPPGPGRALLECVHLRSGVPGGRRRKDW------- NOV4a ------------------------------------------------YIKAFYNESWER NOV4b ----------------------------------------------------------- NOV4c ----------------------------------------------------------- NOV4d ----------------------------------------------------------- NOV4e ----------------------------------------------------------- NOV4f ----------------------------------------------------------- NOV4g --------- SCSLLV-----ASLAGAFGSPFLYGYNLS ----VVNAPTPYIKAFYNESWER NOV4h GSSTTYVASAAIKIPFHRWASLAPEKSSHLLRLLQLRGLALEVKLISLGSKPQSSISWLV NOV4i --------SCSLLV-----ASLAGAFGSPFLYGYNLS---- VVNAPTPYIKAFYNESWER NOV4a RHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLM NOV4b --------------------------LYKKAGSAAAPFTGTRKHTLLANNGFAISAALLM NOV4c ------------------------------ GSAAAPFTGTRKHTLLANNGFAISAALLM NOV4d ------------------------------ GSAAAPFTGTRKHTLLANNGFAISAALLM NOV4e ------------------------------ GSAAAPFTGTRKHTLLANNGFAISAALLM NOV4f ------------------------------ GSAAAPFTGTRKHTLLANNGFAISAALLM NOV4g RHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLM NOV4h ALEETNEIGRDWSCSLLVASLAGAFGSSFLYGYNLSVVNAPTPHTLLANNGFAISAALLM NOV4i RHGRPIDPDTLTLLWSVTVSIFAIGGLVGTLIVKMIGKVLGRKHTLLANNGFAISAALLM NOV4a ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4b ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4c ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4d ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4e ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4f ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4g ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4h ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4i ACSLQAGAFEMLIVGRFIMGIDGGVALSVLPMYLSEISPKEIRGSLGQVTAIFICIGVFT NOV4a GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4b GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4c GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4d GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4e GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4f GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLPDSPRYLLLEKHNEARAVKAFQT NOV4g GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKAFQT NOV4h GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKAFQT NOV4i GQLLGLPELLGKESTWPYLFGVIVVPAVVQLLSLPFLLDSPRYLLLEKHNEARAVKAFQT NOV4a FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4b FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4c FLGKADISQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4d FLGKADVSQEVEEVLAESHVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4e FLGKADISQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI 133 WO 03/093432 PCT/US03/13690 NOV4f FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4g FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4h FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4i FLGKADVSQEVEEVLAESRVQRSIRLVSVLELLRAPYVRWQVVTVIVTMACYQLCGLNAI NOV4a WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4b WFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4c WFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFS----------------------- NOV4d WFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4e WFYTNSIFGKAGIPPAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4f WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4g WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4h WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFSGLVIEHLGRRPLLIGGFGLMGLFF NOV4i WFYTNSIFGKAGIPLAKIPYVTLSTGGIETLAAVFS---------------------- NOV4a GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4b GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4c ----------DHAPWVPYLSIVGILATIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4d GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4e GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4f GTLTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4g GALTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGOIPFILTGEFFQQSQRPAAFIIAG NOV4h GALTITLTLQDHAPWVPYLSIVGILAIIASFCSGPGGIPFILTGEFFQQSQRPAAFIIAG NOV4i ----------------------------------- GIPFILTGEFFQQSQRPAAFIIAG NOV4a TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS NOV4b TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4c TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4d TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4e TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4f TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFL NOV4g TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS NOV4h TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS NOV4i TVNWLSNFAVGLLFPFIQKSLDTYCFLVFATICITGAIYLYFVLPETKNRTYAEISQAFS NOV4a KRNKAYPPEEKIDSAVTDGKINGRP NOV4b E----------------- GKG-GRA NOV4c E----------------- GKG-GRA NOV4d E-----------------GKG-GRA NOV4e E -----------------GKG-GRA NOV4f E -----------------GKG-GRA NOV4g KRNKAYPPEEKIDSAVTDGKINGRP NOV4h KRNKAYPPEEKIDSAVTDGKINGRP NOV4i KRNKAYPPEEKIDSAVTDGKINGRP NOV4a (SEQ ID NO: 24) NOV4b (SEQ ID NO: 26) NOV4c (SEQ ID NO: 28) NOV4d (SEQ ID NO: 30) NOV4e (SEQ ID NO: 32) NOV4f (SEQ ID NO: 34) NOV4g (SEQ ID NO: 33) NOV4h (SEQ ID NO: 38) NOV4i (SEQ ID NO: 40) 134 WO 03/093432 PCT/US03/13690 Further analysis of the NOV4a protein yielded the following properties shown in Table 4C. Table 4C. Protein Sequence Properties NOV4a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 11; pos.chg 4; neg.chg 1 H-region: length 7; peak value 1.99 PSG score: -2.41 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -4.97 possible cleavage site: between 24 and 25 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 9 INTEGRAL Likelihood = -6.48 Transmembrane 79 - 95 INTEGRAL Likelihood = -1.75 Transmembrane 120 - 136 INTEGRAL Likelihood = 0.47 Transmembrane 140 - 156 INTEGRAL Likelihood = -3.40 Transmembrane 171 - 187 INTEGRAL Likelihood = -5.73 Transmembrane 200 - 216 INTEGRAL Likelihood = -0.32 Transmembrane 283 - 299 INTEGRAL Likelihood = -2.23 Transmembrane 351 - 367 INTEGRAL Likelihood = -5.89 Transmembrane 378 - 394 INTEGRAL Likelihood = -5.26 Transmembrane 449 - 465 PERIPHERAL Likelihood = 1.01 (at 419) ALOM score: -6.48 (number of TMSs: 9) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 86 Charge difference: 5.0 C( 4.5) - N(-0.5) C > N: C-terminal side will be inside >>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 10.97 Hyd Moment(95): 13.25 G content: 1 D/E content: 2 S/T content: 2 Score: -3.59 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 17 NRNISK NUCDISC: discrimination of nuclear localization signals pat4: RRRK (5) at 47 pat7: PGGRRRK (5) at 44 bipartite: none content of basic residues: 9.1% NLS Score: 0.27 135 WO 03/093432 PCT/US03/13690 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: ARKQ 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's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 66.7 %: endoplasmic reticulum 11.1 %: vacuolar 11.1 %: mitochondrial 11.1 %: Golgi >> prediction for CG114555-01 is end (k=9) 136 WO 03/093432 PCT/US03/13690 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 4D. 137 WO 03/093432 PCT/USO3/13690 Table 4D. Geneseq Results for NOV4a NOV4a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAM79422 Human protein SEQ ID NO 3068 - 1..507 506/540 (93%) 0.0 Homo sapiens, 558 aa. 19..558 506/540 (93%) [WO200157190-A2,09-AUG-2001] ABB 11910 Human GLUT9 homologue, SEQ ID 1..507 506/540 (93%) 0.0 NO:2280 - Homo sapiens, 558 aa. 19..558 506/540 (93%) [WO200157188-A2, 09-AUG-2001] AAM41316 Human polypeptide SEQ ID NO 1..507 505/540 (93%) 0.0 6247 - Homo sapiens, 558 aa. 19..558 505/540 (93%) ....... [WO200153312-A1, 26-JUL-2001] AAE16788 Human transporter and ion channel- 1..504 500/537 (93%) 0.0 25 (TRICH-25) protein - Homo 1..537 501/537 (93%) sapiens, 537 aa. [WO200192304-A2, 06-DEC-2001] AAE14611 Human glucose transporter protein 1..500 498/533 (93%) 0.0 GLUTX - Homo sapiens, 563 aa. 1..533 498/533 (93%) [US6346374-B 1, 12-FEB-2002] 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 4E. 138 WO 03/093432 PCT/US03/13690 Table 4E. Public BLASTP Results for NOV4a Protein NOV4a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Accession Protein/Organism/LengthMah thMthe Vlu Number Match the Matched Value Residues Portion Q9NRMO Solute carrier family 2, facilitated 1..507 506/540 (93%) 0.0 glucose transporter, member 9 1..540 506/540 (93%) (Glucose transporter type 9) - Homo sapiens (Human), 540 aa. Q8WV30 Similar to solute carrier family 2 51..507 457/457 (100%) 0.0 (Facilitated glucose transporter), 55..511 457/457 (100%) member 9 - Homo sapiens (Human), 511 aa. P22732 Solute carrier family 2, facilitated 52..494 202/446 (45%) e-112 glucose transporter, member 5 46..491 291/446 (64%) (Glucose transporter type 5, small intestine) (Fructose transporter) Homo sapiens (Human), 501 aa. G02864 fructose transporter - human, 481 aa. 52..494 201/446 (45%) e-111 26..471 290/446 (64%) Q8R1N7 Similar to solute carrier family 2 50..493 201/447 (44%) e-111 (Facilitated glucose transporter), 43..489 290/447 (63%) member 5 - Mus musulus (Mouse), 501 aa. PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F. Table 4F. Domain Analysis of NOV4a Identities/ Pfam Domain NOV4a Match Region Similarities Expect Value for the Matched Region sugartr 33..481 150/488 (31%) 9.1le-95 332/488 (68%) 139 WO 03/093432 PCT/t1S03/13690 Example 5. The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A. Table 5A. NOV5 Sequence Analysis NOV5a, CGI81662-01 SEQ ID NO: 5 1 1492 bp DNA Sequence IOUE Start: ATG at 4 .ORF Stop: TAA at 940 GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACC CCGCCGCCCCCGCCCACGACCAGAGGTGGCGGCGG AAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGG CATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAGGATCTACATGAGGAAATGACTACATCACTGC AATAATTGAGGAGCAGCCCAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGATGGCTAA GAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTATCAGGATGCAAGATTATCATGeC TGGCAGCATCGACATGGGTTATTCAGGAATTTAAACTTTGGGATATGAGCTGCAGTATGTGGACCA ACTTCTGAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCA CTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTA CCACATAATGAAGTGCATGGACTATTTGAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCC TATCTGTTAATCATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTATTGCCTTTCTTG TGGATATCTATGAAGACATGCTAGAAATCAGTGTGACA GAGACATTCTTATAAGCATTA GAGTTATGTGAATCCTAGCTAGA-AGGACACTATAAGAAGGATATTGGAGATACATTGGAAG ATCCCTTCAAGCAACACAGCACAGAAATGACTCACCAACAALTGTACAGCATACACCATCCAG AAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCC TTCCCTTTGCCTGTGGTGTAAAAGTGCATCACACAGGTATTGCTTTTTACAAGACTGATGCTCCTT GGGTGCTGCTGCTACTCAGACTAGCTCTAGTAATGTGATTCTTCTGCAGTCATTGGATGGGA GGAGAGAAAAGTCCCATAAAGGACTTTTGTAGTCTTATCACATATATCTAATCCCTTAGCAT CAGCTCCTCCCTCAGTGGTACATGCGTCAAGATTTGTAGCAGT\ATAACTGCAGGTCACTTGTATGTA ATGGATGTGAGGTAGCCGAAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCT ATAGCTGTATCTAAc NOV5a, CG181662-01 'SEQ ID NO: 52 1312 1Mw at 36492.6kD Protein Sequence MAATEGVGE AGGEPGQPAQPPPQPHPPPPQQQHKEEMAAGEAVASPMDDGFVSLDSPSYVLYRH FRRVLLKSLQKDLHEEMtYITAIIEQIKNYQVWHHRRVLVEWLRDPSQELEFIAfILNQDKNYI-IW QHRQWVIQEFKLWDNELQYVDQLLKEDV1NNSVWNQRYFVISNTTGYND1RAVLEREVQYTLEMIXLVP HESAWNLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALE LCEILAKcEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5b, CG181662-02 SEQ ID NO: 53 147b DNA Sequence OR tr:AGa 7,JORLF Stop: TAA at 953 CGGCCGCGTCGACGAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGCGAGCCCGGGC AGCCGGCGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGAGAGATGGCG GCCGAGGCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTA TGTCCTATACAGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGATGA ACTACATCACTGCAATAATTGAGGAGCAGCCCAAACTATCAGTTTGGCATCATAGGCGAGTATTA GTGGAATGGCTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCA GAATTATCATGCCTGGCAGCATCGACAATGGGTTATTCAGGATTTAAACTTTGGGATATGAGCTGC AGTATGTGGACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCA~AAGATACTTCaTT ATTTCTAACACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGJX.2AT GATTAAACTAGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTC TTTCCAAATATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTA ATTGCCTTTCTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAGGAAGACATTCT TAATAAAGCATTAGAGTTATGTGAAATCCTAGCTAAGAAAAGGACACTATAAGAAAGGAATATTGGA GATACATTGGAAGATCCCTTCAAGCAACACGCACAGAATGACTCACCAACAAATGTACAGCAA TAACACCATCCAGAAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCAC 140 WO 03/093432 PCT/US03/13690 ACGAGAGTGGTCCTTCCCTTTGCCTGTGGTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGA ACTGATGCTCCTTGGGTGCTGCTGCTACTCAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAtAG TCATTGGATGGGAGGAGGAAGAAAAAGTCCCATAAAGGAACTTTTGTAGTCTTATCAACATATAATCT AATCCCTTAGCATCAGCTCCTCCCTCAGTGGTACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGG TCACTTGTATGTAATGGATGTGAGGTAGCCGAAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCA TCAGAGCTGGTCTGCACACTCACATTATCTTGCTATCACTGTAACCAACTAATGCCAAAAGAACGGTT TTGTAATAAAATTATAGCTOTATCTAAAAACAAAAAAAAAAAAAAAAAACCAAAAAAT NOV5b, CG181662-02 SEQ ID NO: 54 312 aa MW at 36492.6kD Protein Sequence a MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRH FRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHAW QHRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVP HNESAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALE LCEILAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5c, 307686795 SEQ ID NO: 55 1487 bp DNA Sequence ORF Start: at 2 ORF Stop: TAA at 953 CGGCCGCGTCGACGAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGC AGCCGGCGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCG GCCGAGGCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTA TGTCCTATACAGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGA ACTACATCACTGCAATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTA GTGGAATGGCTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAA GAATTATCATGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGC AGTATGTGGACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTT ATTTCTAACACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAAT GATTAAACTAGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTC TTTCCAAATATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTA ATTGCCTTTCTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCT TAATAAAGCATTAGAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGA GATACATTGGAAGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAA TAACACCATCCAGAAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCAC ACGAGAGTGGTCCTTCCCTTTGCCTGTOGTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGA ACTGATGCTCCTTGGGTGCTGCTGCTACTCAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAG TCATTGGATGGGAGGAGGAAGAAAAAGTCCCATAAAGGAACTTTTGTAGTCTTATCAACATATAATCT AATCCCTTAGCATCAGCTCCTCCCTCAGTGGTACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGG TCACTTGTATGTAATGGATGTGAGGTAGCCGAAGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCA TCAGAGCTGGTCTGCACACTCACATTATCTTGCTATCACTGTAACCAACTAATGCCAAAAGAACGGTT TTGTAATAAAATTATAGCTGTATCTAAAAACAAAAAAAAAAAAAAAAAACCAAAAAAAT NOV5c, 307686795 SEQ ID NO: 56 317 aa (MW at 37049.2kD Protein Sequence GRVDEMAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSY VLYRHFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAK NYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEM IKLVPHNESAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLEMQCDNKEDIL NKALELCEILAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5d, CG181662-03 SEQ ID NO: 57 1344 bp DNA Sequence ORF Start: ATG at 17 IORF Stop: TAA at 1154 TCGGTCCGCAGCCGAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGC AGCCGGCGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCG GCCGAGGCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTA TGTCCTGTACAGGGACAGAGCAGAATGGGCTGATATAGATCCGGTGCCGCAGAATGATGGCCCCAATC CCGTGGTCCAGATCATTTATAGTGACAAATTTAGAGATGTTTATGATTACTTCCGAGCTGTCCTGCAG CGTGATGAAAGAAGTGAACGAGCTTTTAAGCTAACCCGGGATGCTATTGAGTTAAATGCAGCCAATTA TACAGTGTGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACT 141 WO 03/093432 PCT/US03/13690 ACATCACTGCAATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTG GAATGGCTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAA TTATCATGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGT ATGTGGACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATT TCTAACACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGAT TAAACTAGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTT CCAAATATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATT GCCTTTCTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAA TAAAGCATTAGAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGAT ACATTGGAAGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAA CACCATCCAGAAGAACTTGATGGAATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACG AGAGTTCCTTCCCTTTTGTGGTGTAAAAGTGCATCACACAGGTATTGCTTTTTACAGACTGATGCTCC TTGGTGCTGCTGCATCTATCTCAGACTAGCTCTAGTATGTGATCTCTAAGCA NOV5d, CGl81662-03 SEQ ID NO: 58 379 aa MW at 44408.2kD Protein Sequence MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRD RAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSERAFKLTRDAIELNAANYTVWHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHAWQ HRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPH NESAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALEL CEILAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5e, CG181662-04 ISEQ ID NO: 59 11156 bp DNA Sequence ORF Start: ATG at 11 ORF Stop: end of sequence CACCGGATCCATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGG CGCAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAG GCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCT GTACAGGGACAGAGCAGAATGGGCTGATATAGATCCGGTGCCGCAGAATGATGGCCCCAATCCCGTGG TCCAGATCATTTATAGTGACAAATTTAGAGATGTTTATGATTACTTCCGAGCTGTCCTGCAGCGTGAT GAAAGAAGTGAACGAGCTTTTAAGCTAACCCGGGATGCTATTGAGTTAAATGCAGCCAATTATACAGT GTGGCATTTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCA CTGCAATAATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGG CTAAGAGATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCA TGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGG ACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAAC ACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACT AGTACCACATAATGAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAAT ATCCTAATCTGTTAAATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTT CTTGTGGATATCTATGAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGC ATTAGAGTTATGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTG GAAGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAA NOV5e, CG181662-04 SEQ ID NO: 60 3 179 aal MW Ia t 44408.2kD Protein Sequence MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRD RAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSERAFKLTRDAIELNAANYTVWHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDARNYHAWQ HRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPH NESAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALEL CEILAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5f, 13382357 SNP CG181662-01 SEQ ID NO: 1492 bp, SNP at position DNA Sequence 61 310 C/T ORF Start: ORF Stop: TAA at 940 ATG at 4 GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA 142 WO 03/093432 PCT/US03/13690 GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGTATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA AGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC TATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAA CAAA NOV5f, 13 3823 57 SNP CGl181662- :SEQ ID NO: 312 aa SNP: His to Tyr at 01 62 position 103 Protein SequenceI MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVLLKSLQKDLHEEMMYITAIIEEQPKNYQVWYHRRVLVEWLRDPSQELEFIADILNQDANYAWQH RQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5g, 13377970 SNP CG181662-01 SEQ ID 1492 bp, SNP at position DNA Sequence 'NO: 63 457 G/C ORF Start: ORF Stop: TAA at 940 _ATG at 4 GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATCAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA AGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC TATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA CAAA NOV5a, 13377970 SNP SEQ ID NO: 64 312 ]SNP: Glu to Gln at 143 WO 03/093432 PCT/US03/13690 CG181662-01 aa Jposition 152 Protein Sequence MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHAWQH RQWVIQEFKLWDNQLQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5h, 13378241 SNP CG181662-01 SEQ ID 1492 bp, SNP at position DNA Sequence NO: 65 729 C/A ORF Start: ORF Stop: TAA at 940 ATG at 4 GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCATACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG GTGTAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA AGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC TATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA CAAA NOV5h, 13378241 SNP CGl81662-01 SEQ ID 312 'SNP: no change in the Protein Sequence NO:a66 protein sequence MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHAWQH RQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5i, 13377901 SNP CG181662-01 SEQ ID 1492 bp, SNP at position DNA Sequence INO: 67 11330 G/T ORF ORF Stop: TAA at 940 Start: ATG at 4 GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA GCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCGCCCTCCTATGTCCTATACAGGCAT TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC 144 WO 03/093432 PCT/US03/13690 AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA AGTTTGGTTCAGTAAGCATGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC TATCACTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA CAAA NOV5i, 13377901 SNP CG181662-01 SEQ ID NO: 68 312 aa SNP: Not in coding Protein Sequence region MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDSPSYVLYRHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHAWQH RQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ NOV5j, 13377900 SNP CG181662-01 SEQ ID 1492 bp, SNP at position DNA Sequence NO: 69 111385 A/C [ORF Start: ORF Stop: TAA at 940 JATG at 4 GAGATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCGCAACCC CCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCGGCCGAGGCTGGGGAA TTCCGGAGAGTTCTTTTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATA ATTGAGGAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGAGAT CCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTATCATGCCTGGCAG CATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTGCAGTATGTGGACCAACTTCTG AAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGATACTTCGTTATTTCTAACACCACTGGCTAC AATGATCGTGCTGTATTGGAGAGAGAAGTCCAATACACTCTGGAAATGATTAAACTAGTACCACATAAT GAAAGTGCATGGAACTATTTGAAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTA AATCAATTACTTGATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTAT GAAGACATGCTAGAAAATCAGTGTGACATAAGGAAGACATTCTTAATAAAGCATTAGAGTTATGTGAA ATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGAAGATCCCTTCAAAGC AAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAACACCATCCAGAAGAACTTGATGGA ATGCTTTTATTTTTTATTAAGGGACCCTGCAGGAGTTTCACACGAGAGTGGTCCTTCCCTTTGCCTGTG GTGTAAAAGTGCATCACACAGGTATTGCTTTTTAACAAGAACTGATGCTCCTTGGGTGCTGCTGCTACT CAGACTAGCTCTAAGTAATGTGATTCTTCTAAAGCAAAGTCATTGGATGGGAGGAGGAAGAAAAAGTCC CATAAAGGAACTTTTGTAGTCTTATCAACATATAATCTAATCCCTTAGCATCAGCTCCTCCCTCAGTGG TACATGCGTCAAGATTTGTAGCAGTAATAACTGCAGGTCACTTGTATGTAATGGATGTGAGGTAGCCGA AGTTTGGTTCAGTAAGCAGGGAATACAGTCGTTCCATCAGAGCTGGTCTGCACACTCACATTATCTTGC TATCCCTGTAACCAACTAATGCCAAAAGAACGGTTTTGTAATAAAATTATAGCTGTATCTAAAAAAAAA AAACAAA NOV5j, 13377900 SNP CGl81662-01 SEQ ID NO: 70 312 aa SNP: Not in coding Protein Sequence region MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASP PMDDGFVSLDSPSYVLYRHF RRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLRDPSQELEFIADILNQDAKNYHAWQH RQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNE SAWNYLKGILQDRGLSKYPNLLNQLLDLQPSHSSPYLIAPLVDIYEDMLENQCDNKEDILNKALELCEI LAKEKDTIRKEYWRYIGRSLQSKHSTENDSPTNVQQ 145 WO 03/093432 PCT/US03/13690 A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 5B. Table 5B. Comparison of the NOV5 protein sequences. NOV5a .----- MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF NOV5b .----- MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF NOVSc GRVDEMAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF NOV5d -----MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF NOV5e ----- MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGF NOV5a VSLDSPSYVLYR----------------------------------------------- NOV5b VSLDSPSYVLYR----- ---------------------------------------------- NOV5c VSLDSPSYVLYR ----------------------------------------------- NOV5d VSLDSPSYVLYRDRAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSER NOV5e VSLDSPSYVLYRDRAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSER NOV5a --------------------- HFRRVLLKSLQKDLHEEMNYITATIEEQPKNYQVWHHRRVL NOV5b --------------------- HFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVL NOV5c --------------------- HFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVL NOV5d AFKLTRDAIELNAANYTVWHFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVL NOV5e AFKLTRDAIELNAANYTVWHFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVL NOV5a VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS NOV5b VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS NOV5c VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS NOV5d VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS NOV5e VEWLRDPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNS NOV5a VWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNL NOV5b VWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNL NOV5c VWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNL NOV5d VWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNL NOV5e VWNQRYFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNL NOV5a LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY NOV5b LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY NOV5c LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY NOV5d LNQLLDLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY NOV5e LNQLLDLQPSHSSPYLIAELVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEY NOV5a WRYIGRSLQSKHSTENDSPTNVQQ NOV5b WRYIGRSLQSKHSTENDSPTNVQQ NOV5c WRYIGRSLQSKHSTENDSPTNVQQ NOV5d WRYIGRSLQSKHSTENDSPTNVQQ NOV5e WRYIGRSLQSKHSTENDSPTNVQQ NOV5a (SEQ ID NO: 52) NOV5b (SEQ ID NO: 54) NOV5c (SEQ ID NO: 56) NOV5d (SEQ ID NO: 58) NOV5e (SEQ ID NO: 60) Further analysis of the NOV5a protein yielded the following properties shown in Table 5C. 146 WO 03/093432 PCT/US03/13690 Table 5C. Protein Sequence Properties NOV5a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 9; pos.chg 0; neg.chg 2 H-region: length 5; peak value 0.00 PSG score: -4.40 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -11.19 possible cleavage site: between 13 and 14 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 = 6.42 (at 240) ALOM score: 6.42 (number of TMSs: 0) MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 6.27 Hyd Moment(95): 4.56 G content: 2 D/E content: 2 S/T content: 1 Score: -7.86 Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found 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 147 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5 COIL: Lupas's algorithm to detect coiled-coil regions 249 D 0.58 250 I 0.58 251 Y 0.82 252 E 0.82 253 D 0.93 254 M 0.93 255 L 0.97 256 E 0.97 257 N 0.97 258 Q 0.97 259 C 0.97 260 D 0.97 261 N 0.97 262 K 0.97 263 E 0.97 264 D 0.97 265 I 0.97 266 L 0.97 267 N 0.97 268 K 0.97 269 A 0.97 270 L 0.97 271 E 0.97 272 L 0.97 273 C 0.97 274 E 0.97 275 I 0.97 276 L 0.97 277 A 0.97 278 K 0.97 279 E 0.97 280 K 0.97 281 D 0.97 282 T 0.97 283 I 0.86 284 R 0.70 285 K 0.70 148 WO 03/093432 PCT/US03/13690 286 E 0.70 287 Y 0.70 total: 39 residues Final Results (k = 9/23): 78.3 %: nuclear 8.7 %: mitochondrial 8.7 %: cytoplasmic 4.3 %: peroxisomal >> prediction for CG181662-01 is nuc (k=23) 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 5D. Table 5D. Geneseq Results for NOV5a NOVSa Identities/ Geneseq Protein/Organism/Lenigth [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAB58384 Lung cancer associated polypeptide 1..312 278/380 (73%) e-152 sequence SEQ ID 722 - Homo 16..394 289/380 (75%) Sapiens, 394 aa. [WO200055180-A2, 21-SEP-2000] ABB08436 Protein sequence 2 relative to the 1..312 278/380 (73%) e-152 farnesyltransferase of the invention - 1..379 289/380 (75%) Unidentified, 379 aa. [KR98075770 A, 16-NOV-1998] AAU77150 Human geranylgeranyltransferase 1..312 278/380 (73%) e-152 type I related protein #2 - 1..379 289/380 (75%) Unidentified, 380 aa. [KR98075771 A, 16-NOV-1998] AAW04431 Human farnesyl transferase enzyme 1..312 278/380 (73%) e-152 alpha subunit - Homo sapiens, 379 1..379 289/380 (75%) aa. [WO9634113-A2, 31-OCT-1996] AAR77841 Human farnesyl protein transferase 1..312 278/380 (73%) e-152 alpha subunit - Homo sapiens, 379 1..379 289/380 (75%) aa. [US5420245-A, 30-MAY-1995] 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 5E. 149 WO 03/093432 PCT/US03/13690 Table 5E. Public BLASTP Results for NOV5a Protein NOV5a Identities/ Protein Residues/; Similarities for Expect Accession Protein/Organism/Length Residues Similarities for Expect Number Match the Matched Value Residues Portion P49354 Protein farnesyltransferase alpha 1.312 278/380 (73%) e-152 subunit (EC 2.5.1.-) (CAAX 1..379 289/380 (75%) farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) - Homo sapiens (Human), 379 aa. P29702 Protein farnesyltransferase alpha 56..312 242/257 (94%) e-143 subunit (EC 2.5.1.-) (CAAX 85..340 251/257 (97%) famesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) - Bos taurus (Bovine), 340 aa (fragment). Q04631 Protein farnesyltransferase alpha 1..310 258/378 (68%) e-139 subunit (EC 2.5.1.-) (CAAX 1.377 277/378 (73%) farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) - Rattus norvegicus (Rat), 377 aa. Q61239 Protein farnesyltransferase alpha 1.310 256/378 (67%) e-139 subunit (EC 2.5.1.-) (CAAX 1.377 277/378 (72%) farnesyltransferase alpha subunit) (RAS proteins prenyltransferase alpha) (FTase-alpha) - Mus musculus (Mouse), 377 aa. Q921F7 Similar to farnesyltransferase, CAAX 1..310 255/378 (67%) e-138 box, alpha - Mus musculus (Mouse), 1..377 277/378 (72%) 377 aa. PFam analysis predicts that the NOV5a-protein contains the domains shown in the Table SF. 150 WO 03/093432 PCT/US03/13690 Table 5F. Domain Analysis of NOV5a Identities/ Pfam Domain NOV5a Match Region Similarities Expect Value for the Matched Region PPTA 83..113 12/31 (39%) 3.3e-11 28/31 (90%) PPTA 117..147 12/31 (39%) 4e-12 29/31 (94%) PPTA 151..181 9/31 (29%) 2.8e-09 29/31 (94%) PPTA 191..221 15/31 (48%) 1.7e-09 28/31 (90%) Example 6. The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A. Table 6A. NOV6 Sequence Analysis NOV6a, CG182223-01 SEQ ID NO: 71 4683 bp DNA Sequence IORF Start: ATG at 7 ORF Stop: TAA at 4588 GTCAAAATGAGTCTGCTGATGTTTACACAACTACTGCTCTGTGGATTTTTATATGTTCGGGTTGATGG ATCGCGTCTTCGCCAGGAGGACTTTCCCCCGCGGATTGTGGAGCATCCTTCCGATGTCATCGTCTCTA AGGGCGAGCCCACGACTCTGAACTGCAAGGCGGAGGGCCGGCCAACGCCCACCATTGAGTGGTACAAA GATGGGGAGCGAGTGGAGACTGACAAGGACGATCCCCGGTCCCACAGGATGCTTCTGCCCAGCGGATC CTTATTCTTCTTGCGCATCGTGCACGGGCGCAGGAGTAAACCTGATGAAGGAAGCTACGTTTGTGTTG CGAGGAACTATCTTGGTGAAGCAGTGAGTCGAAATGCGTCTCTGGAAGTGGCATTGTTACGAGATGAC TTCCGACAAAACCCCACAGATGTTGTAGTGGCAGCTGGAGAGCCTGCAATCCTGGAGTGCCAGCCTCC CCGGGGACACCCAGAACCCACCATCTACTGGAAAAAAGACAAAGTTCGAATTGATGACAAGGAAGAAA GAATAAGTATCCGTGGTGGAAAACTGATGATCTCCAATACCAGGAAAAGTGATGCAGGGATGTATACT TGTGTTGGTACCAATATGGTGGGAGAAAGGGACAGTGACCCAGCAGAGCTGACTGTCTTTGAACGACC CACATTTCTCAGGAGGCCAATTAACCAGGTGGTACTGGAGGAAGAAGCTGTAGAATTTCGTTGTCAAG TCCAAGGAGATCCTCAACCAACTGTGAGGTGGAAAAAGGATGATGCAGACTTGCCAAGAGGAAGGTAT GACATCAAAGACGATTACACACTAAGAATTAAAAAGACCATGAGTACAGATGAAGGCACCTATATGTG TATTGCTGAGAATCGGGTTGGAAAAATGGAAGCCTCTGCTACACTCACCGTCCGAGCTCCCCCACAGT TTGTGGTTCGGCCAAGAGATCAGATTGTTGCTCAAGGTCGAACAGTGACATTTCCCTGTGAAACTAAA GGAAACCCACAGCCAGCTGTTTTTTGGCAGAAAGAAGGCAGCCAGAACCTACTTTTCCCAAACCAACC CCAGCAGCCCAACAGTAGATGCTCAGTGTCACCAACTGGAGACCTCACAATCACCAACATTCAACGTT CCGACGCGGGTTACTACATCTGCCAGGCTTTAACTGTGGCAGGAAGCATTTTAGCAAAAGCTCAACTG GAGGTTACTGATGTTTTGACAGATAGACCTCCACCTATAATTCTACAAGGCCCAGCCAACCAAACGCT GGCAGTGGATGGTACAGCGTTACTGAAATGTAAAGCCACTGGTGATCCTCTTCCTGTAATTAGCTGGT TAAAGGAGGGATTTACTTTTCCGGGTAGAGATCCAAGAGCAACAATTCAAGAGCAAGGCACACTGCAG ATTAAGAATTTACGGATTTCTGATACTGGCACTTATACTTGTGTGGCTACAAGTTCAAGTGGAGAGAC TTCCTGGAGTGCAGTGCTGGATGTGACAGAGTCTGGAGCAACAATCAGTAAAAACTATGATTTAAGTG ACCTGCCAGGGCCACCATCCAAACCGCAGGTCACTGATGTTACTAAGAACAGTGTCACCTTGTCCTGG CAGCCAGGTACCCCTGGAACCCTTCCAGCAAGTGCATATATCATTGAGGCTTTCAGCCAATCAGTGAG CAACAGCTGGCAGACCGTGGCAAACCATGTAAAGACCACCCTCTATACTGTAAGAGGACTGCGGCCCA 151 WO 03/093432 PCT/US03/13690 ATACAATCTACTTATTCATGGTCAGAGCGATCAACCCCCAAGGTCTCAGTGACCCAAGTCCCATGTCA GATCCTGTGCGCACACAAGATATCAGCCCACCAGCACAAGGAGTGGACCACAGGCAAGTGCAGAAAGA GCTAGGAGATGTCCTTGTCCGTCTTCATAATCCAGTTGTGCTGACTCCCACCACGGTTCAGGTCACAT GGACGGTTGATCGCCAACCCCAGTTTATCCAAGGCTACCGAGTGATGTATCGTCAGACTTCAGGTC!TG CAGGCGACATCTTCGTGGCAGAATTTAGATGCCAAAGTCC!CGACTGAACGAAGTGCTGTCTTAGTCAA CCTGAAAAAGGGGGTGACTTATGAAATTAAAGTACGGCCATATTTTAATGAGTTCCAAGGAATGGATA GTGAATCTA2AAACGGTTCGTACTACTGAAGAAGCCCCAAGTGCCCCACCACAGTCTGTCACTGTACTG ACAGTTGGAAGCTACAATAGCACAAGTATTAGTGTTTCCTGGGATCCTCCTCCTCCAGATCACCAGAA TGGAATTATCCAAGAATACAAGATCTGGTGTCTAGGAAATGAAACGCGATTCCATATCAACAAAACTG TGGATGCAGCCATTCGGTCCGTAATAATTGGTGGATTATTCCCAGGTATTCAATACCGGGTAGAGGTT GCAGCTAGTACCAGTGCAGGGGTTGGAGTAAAGAGTGAGCCACAGCCAATAATAATAGGGAGACGCAA TGAAGTTGTCATTACTGAAAACAATAACAGCATAACTGAGCAAATCACTGATGTGGTGAAGCAACCAG CCTTTATAGCTGGTATTGGTGGTGCCTGCTGGGTAATTCTGATGGGTTTTAGCATATGGTTGTATTGG CGAAGAAAGAAGAGGAAGGGACTCAGTAATTATGCTTTTTCTTTTTTCATAGTTACGTTTCAAAGAGG AGATGGAGGACTAATGAGCAATGGAAGCCGTCCAGGTCTTCTCAATGCTGGTGATCCCAGCTATCCAT GGCTTGCTGATTCTTGGCCAGCCACGAGCTTGCCAGTAAATAATAGCAACAGTGGCCCAAATGAGATT GGAAATTTTGGCCGTGGAGATGTGCTGCCACCAGTTCCAGGCCAGGGGATALAACAGCAACGATGCT CTCAGATGGAGCCATTTATAGTAGCATTGACTTCACTACCAAAACCAGTTACAACAGTTCCAGCCAA TAACACAGGCTACCCCATATGCCACGACACAGATCTTGCATTCCAACAGCATACATGAATTGGCTGTC GATCTGCCTGATCCACAATGGAAAAGCTCAATTCAGCAAAAAACAGATCTGATGGGATTTGGTTATTC TCTACCTGATCAGAACAAAGGTAACAATTTACTTTACATTCCTGACTACCGATTGGCTGAGGGATTGT CTAATAGAATGCCACACAACCAGTCTCAGGATTTCAGCACCACCAGCTCTCACACAGCTCAGAAGG AGTGGCAGTCTTTCAGGTGGGAAAGGTGGAXA1AAGAAGAAAAATAAA~AACTCTTCTAAACCACAGAA AAACAATGGATCCACTTGGGCCAATGTCCCTCTACCTCCCCCCCCAGTCCAGCCCCTTCCTGGCACGG AGCTGGAACACTATGCAGTGGAACAACAAGAAAATGGGTATGACAGTGATAGCTGGTGCCCACCATTG CCAGTACAAACTTACTTACACCAGGTCTGGAAGATGAACTGGAAGAAGATGATGATAGGGTCCCAAC ACCTCCTGTTCGAGGCGTGGCTTCTTCTCCTGCTATCTCCTTTGGACAGCAGTCCACTGCAACTCTTA CTCCATCCCCACGGGAAGAGATGCAACCCATGCTGCAGGCTCACCTGGATGAGTTGACAAGAGCCTAT CAGTTTGATATAGCAAA-ACA7AACATGGCACATTCAAAGCAATAATCAACCTCCACAGCCTCCAGTTCC ACCGTTAGGTTATGTGTCTGGAGCCTTGATTTCTGATTTGGAAACGGATGTTGCAGATGATGATGCCG ACGACGAAGAGGAAGCTTTAGAAATCCCCAGGCCCCTGAGAGCACTGGACCAGACTCCTGGATCCAGC ATGGACAATCTAGACAGCTCTGTGACAGGTAACGGAAGACCTCGACCTACCAGCCCATTTTCTACTGA CAGTAACACCAGTGCAGCCCTGAGTCAAAGTCAGAGGCCTCGGCCCACTAAAAAA-CACAAGGGAGGGC GGATGGACCAACAACCAGCATTGCCTCATCGAAGGGAAGGAATGACAGATGA.TCTTCCACCACCACCA GATCCCCCGCCAGGTCAGGGTTTAAGGCAGCAAATAGGCCCGAGCCAGCAGGCTGGTAACGTGGAAAA CTCAGCAGAGAGAAAAGGAAGCTCTCTAGAGAGACAACATGCATCCAGCTTAGAAGACACAAAGAGCT CATTGGATTGTCCAGCTAGAACCTCCCTAGAGTGGCAGCGACAAACCCAGGAATGGATAAGCTCCACA GAACGACAAGAAGATATACGGAAAGCCCCACACAAACAAGGTTTTTCAGAGGAGGCCTTGGTGCCCTA TAGCAAGCCCAGTTTCCCATCTCCAGGTGGCCACAGCTCATCAkGGAACAGCTTCTTCTAAGGGATCCA CTGGACCTAGGAAAACCGAGGTGTTGAGAGCAGGCC-ACCAGCGCAATGCCAGCGACCTTCTTGACATA GGATATATGGGCTCCAACAGTCAAGGACAGTTTACAGGTGAATTATGTAAGTGCTTAGGTCATTTAAA AGGCTATCGTGATTCAGAAAGAATCTTGGGTTAATAACATTGCCACATTAAACAAATTTCAGATTAAT AGAAAACTTGCTCTGTTACAAAAACAATCAATTGCAATTTTCAACAAGTTTGGTCATAA NOV6a, CGI82223-01 SEQ ID NO: 72 j57a MWat 167842.2kD Protein Sequence 157 MSLLMFTQLLLCGFLYVRVDGSRLRQEDFPPRIVEIPSDVIVSKGEPTTLNCKAEGRPTPTIEWYKDG ERVETDICDDPRSHRMLLPSGSLFFLRIVHGRRSKPDEGSYVCVARflYLGEAVSRNASLEVALLRDDFR QNPTDVVVAAGEPAILECQPPRGHPEPTIYWKKDKVRIDDKEERIS IRGGKLMISNTRKSDAGMYTCV GTNMVGERDSDPAELTVFERPTFLRRPINQVVLEEAVEFRCQVQGDPQPTVRWKKDDADLPRGRYDI KDDYTLRIKKTMSTDEGTYMCIAENRVGKMFEASATLTVRAPPQFVVRPRDQIVAQGRTVTFPCETKGN PQPAVFWQKEGSQNLLFPNQPQQPNSRCSVSPTGDLTITNIQ-SDAGYYICQALTVAGS ILAKAQLEV TDVLTDRPPPI ILQGPANQTLAVDGTALLKCKATGDPLPVISWLKEGFTFPGRflPRATIQEQGTLQIK NLRISDTGTYTCVATSSSGETSWSAVLDVTESGATISKNYDLSDLPGPPSKPQVTDVTKNSVTLSWQP GTPGTLPASAYIIEAFSQSVSNSWQTVNHVKTTLYTVRGLPNTIYLFMVRAIN'PQGLSDPSPMSDP VRTQDI SPPAQGVDHRQVQKELGDVLVRLHNPVVLTPTTVQVTWTVDRQPQFIQGYRVMYRQTSGLQA TSSWQNLDAKVPTERSAVLVNLKKGVTYEIKVRPYFNBFQGMDSESKTVRTTEEAPSAPPQSVTVLTV' GSYNSTSISVSDPPPPDHQN'GI IQEYKIWCLGNETRFHINKTVDAAIRSVIIGGLFPGIQYRVEVAA S TSAGVGVKSEPQPI IIGRRNEVVITENNNSITEQITDVVKQPAFIAGIGGACWVILMGFSIWLYWRR 152 WO 03/093432 PCT/US03/13690 KKRKGLSNYAFSFFIVTFQRGDGGLMSNGSRPGLLNAGDPSYPWLADSWPATSLPVNNSNSGPNEIGN FGRGDVLPPVPGQGDKTATMLSDGAIYSSIDFTTKTSYNSSSQITQATPYATTQILHSNSIHELAVDL PDPQWKSSIQQKTDLMGFGYSLPDQNKGNNLLYIPDYRLAEGLSNRMPHNQSQDFSTTSSHNSSERSG SLSGGKGGKKKKNKNSSKPQKNNGSTWANVPLPPPPVQPLPGTELEHYAVEQQENGYDSDSWCPPLPV QTYLHQGLEDELEEDDDRVPTPPVRGVASSPAISFGQQSTATLTPSPREEMQPMLQAHLDELTRAYQF DIAKQTWHIIQSNNQPPQPPVPPLGYVSGALISDLETDVADDDADDEEEALEIPRPLRALDQTPGSSMD NLDSSVTGNGRPRPTSPFSTDSNTSAALSQSQRPRPTKKHKGGRMDQQPALPHRREGMTDDLPPPPDP PPGQGLRQQIGPSQQAGNVENSAERKGSSLERQHASSLEDTKSSLDCPARTSLEWQRQTQEWISSTER QEDIRKAPHKQGFSEEALVPYSKPSFPSPGGHSSSGTASSKGSTGPRKTEVLRAGHQRNASDLLDIGY MGSNSQGQFTGELCKCLGHLKGYRDSERILG Further analysis of the NOV6a protein yielded the following properties shown in Table 6B. Table 6B. Protein Sequence Properties NOV6a SignalP analysis: Cleavage site between residues 22 and 23 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 0; pos.chg 0; neg.chg 0 E-region: length 17; peak value 9.00 PSG score: 4.60 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.73 possible cleavage site: between 15 and 16 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 2 INTEGRAL Likelihood = -2.81 Transmembrane 1 - 17 INTEGRAL Likelihood = -3.98 Transmembrane 860 - 876 PERIPHERAL Likelihood = 1.01 (at 792) ALOM score: -3.98 (number of TMSs: 2) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 8 Charge difference: 0.0 C( 1.0) - N( 1.0) N >= C: N-terminal side will be inside >>> membrane topology: type 3a MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 4.50 Hyd Moment(95): 2.47 G content: 1 D/E content: 1 S/T content: 2 Score: -4.61 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 28 VRVIDG NUCDISC: discrimination of nuclear localization signals 153 WO 03/093432 PCT/US03/13690 pat4: RRKK (5) at 883 pat4: RKKR (5) at 884 pat4: KKRK (5) at 885 pat4: KKKK (5) at 1097 pat4: KKHK (3) at 1330 pat7: PTVRWKK (3) at 254 pat7: PTKKHKG (4) at 1328 bipartite: none content of basic residues: 10.3% NLS Score: 1.57 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 39.1 %: mitochondrial 34.8 %: nuclear 17.4 %: endoplasmic reticulum 154 WO 03/093432 PCT/US03/13690 4.3 %: cytoplasmic 4.3 %: peroxisomal >> prediction for CG182223-01 is mit (k=23) 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 6C. Table 6C. Geneseq Results for NOV6a NOV6a Identities/ Geneseq Protein/OrganismlLength Residues/ Similarities for Expect Identifier [Patent #, Date] Match the Matched Value Residues Region AAO19185 Human neurotransmission- 1..1509 1501/1520 (98%) 0.0 associated protein NTRAN8 - 1..1515 1501/1520 (98%) Homo sapiens, 1515 aa. [WO200266646-A2, 29-AUG 2002] AA019179 Human neurotransmission- 1..1400 1356/1413 (95%) 0.0 associated protein NTRAN2 - 1..1405 1361/1413 (95%) Homo sapiens, 1422 aa. [WO200266646-A2, 29-AUG 2002] ABU04094 Human expressed protein tag 21..1495 819/1610 (50%) 0.0 (EPT) #760 - Homo sapiens, 1651 58..1634 1040/1610 (63%) aa. [WO200278524-A2, 10-OCT 2002] ABU04093 Human expressed protein tag 21..1495 819/1610 (50%) 0.0 (EPT) #759 - Homo sapiens, 1651 58..1634 1040/1610 (63%) aa. [WO200278524-A2, 10-OCT 20021 ABU04092 Human expressed protein tag 21..1495 819/1610 (50%) 0.0 (EPT) #758 - Homo sapiens, 1651 58..1634 1040/1610 (63%) aa. [WO200278524-A2, 10-OCT 2002] 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 6D. 155 WO 03/093432 PCT/US03/13690 Table 6D. Public BLASTP Results for NOV6a Protein NOV6a Identities/ Residues/!xpc Accession Protein/Organism/Length Residues/ Similarities for the Expect Match Value Number Residues Matched Portion Residues Q9HCK4 Hypothetical protein KIAA1568 - 1..1400 1316/1408 (93%) 0.0 Homo sapiens (Human), 1380 aa 3..1361 1321/1408 (93%) (fragment). Q90Z70 Roundabout2 - Brachydanio rerio 7.. 1509 1152/1525 (75%) 0.0 (Zebrafish) (Danio rerio), 1513 aa. 5..1513 1294/1525 (84%) Q9QZI3 Robo2 - Rattus norvegicus (Rat), 1..1053 974/1056 (92%) 0.0 1060 aa (fragment). 1..1050 1001/1056 (94%) Q8UVD7 Roundabout-1 - Xenopus laevis 10..1495 826/1620 (50%) 0.0 (African clawed frog), 1614 aa. 10..1598 1060/1620 (64%) Q9Y6N7 Roundabout 1 - Homo sapiens 21..1495 819/1610 (50%) 0.0 (Human), 1651 aa. 58..1634 1040/1610 (63%) PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E. Table 6E. Domain Analysis of NOV6a Identities/ Pfam Domain NOV6a Match Region Similarities Expect Value for the Matched Region ig 45..112 17/71 (24%) 6.2e-06 52/71 (73%) ig 147..205 16/61 (26%) 8.2e-06 42/61 (69%) ig 239..295 17/60 (28%) 1.6e-08 44/60 (73%) ig 328..393 17/69 (25%) 7.6e-09 51/69 (74%) ig 432..490 17/62(27%) 1.8e-08 46/62 (74%) fn3 522..607 33/88 (38%) 3.2e-17 64/88 (73%) fn3 638..724 24/90 (27%) 0.0086 63/90 (70%) fn3 736..826 33/93 (35%) 3.5e-14 64/93 (69%) 156 WO 03/093432 PCT/tUS03/13690 Example 7. The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A. Table 7A. NOV7 Sequence Analysis NOV7a, CG183585-01 ISEQIDNO:73 1385 bp DNA Sequence JORF Start: ATG at 145 JORF Stop: TAG at 1264 CTTGTATATATAATGGTAGACTGTAAAGGGTACCTTCCCCACCTGATATTCTGGAATGTCAGTTTGTA GGTGGAGATTGCGACTTCTTTTTCCTTAGCAGAGCCAAGCTCCATTCAGCTGGTTACCACTTTGTGGG TGTCTTTAATGAAGCTTATAAATGGCAGGAAGCAAACATTCCCGTGGTTTGGCATGGATATTGGTGGA ACCCTGGTTAAGTTGGTTTACTTTGAACCGAAGGATATCACGGCAGAAGAAGAGCAGGAAGAAGTGGA GAACCTGAAGAGCATCCGGAAGTATTTGACTTCTAATACTGCTTATGGGAAAACTGGGATCCGAGACG TCCACCTGGAACTGAAAAACCTGACCATGTGTGGACGCAAAGGGAACCTGCACTTCATCCGCTTTCCC AGCTGTGCCATGCACAGGTTCATTCAGATGGGCAGCGAGAAGAACTTCTCTAGCCTTCACACCACCCT CTGTGCCACAGGAGGCGGGGCTTTCAAATTCGAAGAGGACTTCAGAATGATTGCTGACCTGCAGCTGC ATAAACTGGATGAACTGGACTGTCTGATTCAGGGCCTGCTTTATGTCGACTCTGTTGGCTTCAACGGC AAGCCAGAATGTTACTATTTTGAAAATCCCACAAATCCTGAATTGTGTCAAAAAAAGCCGTACTGCCT TGATAACCCATACCCTATGTTGCTGGTTAACATGGGCTCAGGTGTCAGCATTCTAGCCGTGTACTCCA AGGACAACTATAAAAGAGTTACAGGGACCAGTCTTGGAGGTGGAACATTCCTAGGCCTATGTTGCTTG CTGACTGGTTGTGAGACCTTTGAAGAAGCTCTGGAAATGGCAGCTAAAGGCGACAGCACCAATGTTGA TAAACTGGTGAAGGACATTTACGGAGGAGACTATGAACGATTTGGCCTTCAAGGATCTGCTGTAGCAT CAAGCTTGGGCAACATGATGAGTAAAGAAAAGCGAGATTCCATCAGCAAGGAAGACCTCGCCCGGGCC ACATTGGTCACCATCACCAACAACATTGGCTCCATTGCTCGGATGTGTGCGTTGAATGAGAACATAGA CAGAGTTGTGTTTGTTGGAAATTTTCTCAGAATCAATATGGTCTCCATGAAGCTGCTGGCATATGCCA TGGATTTTTGGTCCAAAGGACAACTGAAAGCTCTGTTTTTGGAACATGAGGGTTATTTTGGAGCCGTT GGGGCACTGTTGGAACTGTTCAAAATGACTGATGATAAGTAGAGACGAGCAGTGGAGGAAACAGCCTC CCAAAAGGACAGAGAACTAAAAAATTGCTGCTGGAGAAGGTGAAAGTCGCTTTGGGACGGAAGCCAAG CCATTATGGCAGATGAACCTGCTGG NOV7a, CG183585-01 SEQ ID NO: 74 373 aa IMW at 41664.6kD Protein Sequence MKLINGRKQTFPWFGMDIGGTLVKLVYFEPKDITAEEEQEEVENLKSIRKYLTSNTAYGKTGIRDVHL ELKNLTMCGRKGNLHFIRFPSCAMHRFIQMGSEKNFSSLHTTLCATGGGAFKFEEDFRMIADLQLHKL DELDCLIQGLLYVDSVGFNGKPECYYFENPTNPELCQKKPYCLDNPYPMLLVNMGSGVSILAVYSKDN YKRVTGTSLGGGTFLGLCCLLTGCETFEEALEM.AIKGDSTNVDKLVKDIYGGDYERFGLQGSAVASSL GNMMSKEKRDS ISKEDLARATLVTITNNIGSIARMCALNENIDRVVFVGNFLRINMVSMKLLAYAMDF WSKGQLKALFLEHEGYFGAVGALLELFKMTDDK Further analysis of the NOV7a protein yielded the following properties shown in Table 7B. Table 7B. Protein Sequence Properties NOV7a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 8; pos.chg 3; neg.chg 0 H-region: length 8; peak value 5.54 PSG score: 1.14 GvH: von Heijne's method for signal seq. recognition 157 WO 03/093432 PCT/US03/13690 GvH score (threshold: -2.1): -10.98 possible cleavage site: between 59 and 60 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 = 0.95 (at 212) ALOM score: 0.42 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 6 Charge difference: -2.0 C( 1.0) - N( 3.0) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 10.35 Hyd Moment(95): 1.52 G content: 2 D/E content: 1 S/T content: 1 Score: -4.69 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 17 GRKIQT NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 11.3% 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 158 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 60.9 %: cytoplasmic 21.7 %: nuclear 17.4 %: mitochondrial >> prediction for CG183585-01 is cyt (k=23) 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 7C. Table 7C. Geneseq Results for NOV7a NOV7a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAE24134 Human kinase (PKIN)-5 protein - 1..373 371/373 (99%) 0.0 Homo sapiens, 373 aa. 1..373 372/373 (99%) [WO200233099-A2, 25-APR-2002] AAE21720 Human PKIN-15 protein - Homo 7..369 297/363 (81%) e-178 sapiens, 447 aa. [WO200218557- 84..446 332/363 (90%) A2, 07-MAR-2002] AAM40613 Human polypeptide SEQ ID NO 7..369 297/363 (81%) e-178 5544 - Homo sapiens, 460 aa. 97..459 332/363 (90%) [WO200153312-A1, 26-JUL-2001] AAM38827 Human polypeptide SEQ ID NO 7..369 296/363 (81%) e-178 1972 - Homo sapiens, 447 aa. 84..446 331/363 (90%) [WO200153312-A1, 26-JUL-2001] AAB94366 Human protein sequence SEQ ID 1..366 291/366 (79%) e-173 NO: 1499 - Homo aniens 370 aa. 1..366 330/366 (89%). 159 WO 03/093432 PCT/US03/13690 [EP 1074617-A2, 07-FEB-200 1 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 7D. Table 7D. Public BLASTP Results for NOV7a NOV7a Identities/ Protein i ProteinResidues/ Similarities for Expect Accession Protein/Organism/Length Number Match the Matched Value Residues Portion SBAC34132 Adult male liver tumor eDNA, RIKEN 1..371 365/371 (98%) 0.0 full-length enriched library, 1..371 369/371 (99%) clone:C730027017 product:hypothetical protein, full insert sequence - Mus musculus (Mouse), 373 aa. Q8TEO4 Pantothenate kinase 1 (EC 2.7.1.33) 2..373 365/374 (97%) 0.0 (Pantothenic acid kinase 1) (hPanK1) 225..598 368/374 (97%) (hPanK) - Homo sapiens (Human), 598 aa. Q8K4K6 Pantothenate kinase 1 (EC 2.7.1.33) 2..371 359/372 (96%) 0.0 (Pantothenic acid kinase 1) (mPankl) 175..546 365/372 (97%) (mPank) - Mus musculus (Mouse), 548 aa. Q9BZ23 Pantothenate kinase 2 (EC 2.7.1.33) 7..369 297/363 (81%) e-178 (Pantothenic acid kinase 2) (hPANK2) 207..569 332/363 (90%) - Homo sapiens (Human), 570 aa. Q9H999 Pantothenate kinase 3 (EC 2.7.1.33) 1 ..366 291/366 (79%) 1e-173 (Pantothenic acid kinase 3) (hPanK3) - 1..366 330/366 (89%) Homo sapiens (Human), 370 aa. PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7E. Table 7E. Domain Analysis of NOV7a Identities/ Pfam Domain NOV7a Match Region Similarities Expect Value for the Matched Region Fumble 12..367 196/401 (49%) 2.3e-234 346/401 (86%) ..... 160 WO 03/093432 PCT/US03/13690 Example 8. The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A. Table 8A. NOV8 Sequence Analysis NOV8a, CG183860-01 ISEQ ID NO: 75 1858 bp DNA Sequence OR-F Start: ATG at 72 ORF Stop: TGA at 786 CAGGTAGCCCGGCTCAGCCCTTCGCTTTCCAGCTGCGTCCTGCTCCCGGCCGCCCAGGGAGCCCAGTG GCGATGAGGGCACTGCTGGCGCTTTGCCTTCTCCTTGGCTGGCTGCGCTGGGGCCCGGCGGGCGCCCA GCAGTCCGGAGAGTACTGCCACGGCTGGGTGGACGTGCAGGGCAACTACCACGAGGGCTTCCAGTGCC CAGAGGACTTCGACACGCTGGACGCTACCATCTGCTGCGGCTCCTGCGCGCTCCGCTACTGTTGCGCC GCGGTCGACGCCAGGCTGGAGCAGGGCGGCTGCACCAACGACCGCCGCGAACTGGAGCACCCAGGCAT CACTGCGCAGCCTGTCTACGTCCCCTTTCTCATCGTCGGCTCCATCTTCATTGCGTTCATCATCCTGG GCTCTGTAGTGGCTATTTATTGTTGCACCTGTTTGAGACCCAAGGAGCCCTCGCAGCAGCCAATCCGC TTCTCACTCCGCAGCTATCAGACAGAGACCCTGCCCATGATCCTGACCTCCACCAGCCCCAGGGCACC CTCCCGGCAGTCCAGCACAGCCACGAGCTCCAGCTCCACAGGCGGCTCCATCCGCAGGTTCTCCTTTG CCAGGGCTGAGCCGGGCTGCCTGGTGCCCTCACCGCCCCCGCCATACACCACCAGCCACTCAATCCAC CTGGCTCAGCCATCTGGTTTCCTGGTGTCACCCCAGTATTTCGCTTACCCCCTCCAGCAGGAGCCCCC ACTGCCTGGGAAGAGCTGTCCAGACTTCAGTTCCAGTTGACACGCCCAGGCCATGAATCCACAACTCA GTCAGATGGCAGACAGGTGGAGCCCTGCTCCCATTGCCACATGCAATTCTGAGAAAATTTCCCTTGTA ACTGATCAGTGTCATGGAGGAGCATGCTAGGAAAACACAGCACCTTCTAATTTGAAAGTTCCTGTCTC CAATCACAGAAAGGCTAAACCAGAGAACTGTTTTCTGGTTTTGCAAACATGTGATCATTACATTTCAA TCTATGCTACTTTTATTCAAAATATGCAGCAGTTTACTTTAAAGTTGCAAACTGGCTAAAAACGTTT TACTGGACATTCAGCTATATTGCTTAGAAAAGGGCTACATGTTTCTTTTTCATATAAGTTGTTCATTG AGTTATGATAGGAATATATTCATAAATAAGCAAAGAAAAATACCTAATTGTAATTATCAAAGGTTCAC TTAAAAAAATTAACTATTAGGTAAACTTAAGGGGGCAGTGAAAAATCTATTTATGATTTCGGGAGTAA CCTAACCATGAATAATATTAGCATAATGAGAACATTTACTTTTTAAATAAATAACTAAATTTTGTTTA CAATATGAGTTTTTCCAGAATACAAGGTTTCAATAATCACATGAGGAGTTTAAAGTTTTAAATATATA CTCAGACATTCATTGTAACACAGAGTGTATGTAAAATCATTTCCCCCACTCACTGGAGGGAGTATTTA TTGCAGACTTTTTGTTCAGCAACATTTAGTGTTTCAGTGAAAGTTGGACAGTTGGGGCTTAAAACATT TATTTGTAAAATGAGCTATGTTCAAATGTAAATATTTGTAATTTAATGTATTTACCACATTGACTGTA CTAATTATTTAGTAGTCATACTGTAATTTTTATGTTAATAATAACTGGAGTTCAAAGTCTAGCTATTG GTATAATCATCTAATATTATATATATCTCCAGTGCCCCTGAATTTTATGTTTGATGACTATATATTTG GGCATATATCTTGTTGGATTAGAATAAATAAAACACTTTATATTTTCATGAACTCTAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAGGG NOV8a, CG183860-01 SEQ ID NO: 76 238 aa MW at 25860. 1kD Protein Sequence I MRALLALCLLLGWLRWGPAGAQQSGEYCHGWVDVQGNYHEGFQCPEDFDTLDATICCGSCALRYCCAA VDARLEQGGCTNDRRELEHPGITAQPVYVPFLIVGSIFIAFIILGSVVAIYCCTCLRPKEPSQQPIRF SLRSYQTETLPMILTSTSPRAPSRQSSTATSSSSTGGSIRRFSPARAEPGCLVPSPPPPYTTSHSIHL AQPSGFLVSPQYFAYPLQQEPPLPGKSCPDFSSS Further analysis of the NOV8a protein yielded the following properties shown in Table 8B. Table SB. Protein Sequence Properties NOV8a SignalP analysis: Cleavage site between residues 22 and 23 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 2; pos.chg 1; neg.chg 0 161 WO 03/093432 PCT/US03/13690 H-region: length 12; peak value 10.66 PSG score: 6.26 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 1.27 possible cleavage site: between 21 and 22 >>> Seems to have a cleavable signal peptide (1 to 21) ALOM: Klein et al's method for TM region allocation Init position for calculation: 22 Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood =-11.04 Transmembrane 100 - 116 PERIPHERAL Likelihood = 1.27 (at 53) ALOM score: -11.04 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 10 Charge difference: -1.5 C( 0.5) - N( 2.0) N >= C: N-terminal side will be inside >>> membrane topology: type la (cytoplasmic tail 117 to 238) MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 6.25 Hyd Moment(95): 8.60 G content: 4 D/E content: 1 S/T content: 1 Score: -4.46 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 25 LRWIGP NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 6.7% NLS Score: -0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: RALL 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 162 WO 03/093432 PCT/US03/13690 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: 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 89 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 44.4 %: extracellular, including cell wall 22.2 %: Golgi 22.2 %: endoplasmic reticulum 11.1 %: plasma membrane > prediction for CG183860-01 is exo (k=9) 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 SC. 163 WO 03/093432 PCT/US03/13690 Table 8C. Geneseq Results for NOV8a NOV8a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAY86234 Human secreted protein HNTNC20, 1..195 179/195 (91%) e-103 SEQ ID NO:149 - Homo sapiens, 219 1..195 179/195 (91%) aa. [WO9966041-A1, 23-DEC-1999] ABU56619 Lung cancer-associated polypeptide 19..212 107/204 (52%) 2e-51 #212 - Unidentified, 295 aa. 29..226 136/204 (66%) [WO200286443-A2, 31-OCT-2002] ABB85001 Human PRO28631 protein sequence 19..212 107/204 (52%) 2e-51 SEQ ID NO:370 - Homo sapiens, 295 29..226 136/204 (66%) aa. [WO200200690-A2, 03-JAN 2002] ABB95607 Human angiogenesis related protein 19..212 107/204 (52%) 2e-51 PRO28631 SEQ ID NO: 370 - Homo 29..226 136/204 (66%) sapiens, 295 aa. [WO200208284-A2, 31-JAN-2002] ABG61896 Prostate cancer-associated protein #97 13..84 48/72 (66%) 3e-25 - Mammalia, 582 aa. 243..314 56/72 (77%) [WO200230268-A2, 18-APR-2002] 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 8D. 164 WO 03/093432 PCT/USO3/13690 Table 8D. Public BLASTP Results for NOV8a NOV8a Identities/ Protein Accession Protein/Organism/Length Residues/ Similarities for Expect Accession Protein/Organism/Length Number Match the Matched Value Nume Residues Portion Q8C5V3 Hypothetical protein - Mus 79..238 149/160 (93%) 4e-83 musculus (Mouse), 160 aa 1..160 153/160 (95%) (fragment). Q96EQ5 Hypothetical protein - Homo 96..238 143/143 (100%) 3e-79 sapiens (Human), 144 aa 2..144 143/143 (100%) (fragment). Q8QZV2 Hypothetical protein -Mus 2..212 114/221 (51%) le-51 musculus (Mouse), 295 aa. 15..226 142/221 (63%) Q8BN61 Hypothetical protein -Mus 2..212 113/221 (51%) le-50 musculus (Mouse), 295 aa. 15..226 141/221 (63%) CAC51150 Sequence 26 from Patent 24.. 196 44/183 (24%) 6e-06 WOO 149728 -Homo sapiens 27.. 187 76/183 (41%) (Human), 197 aa. Example 9. The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A. Table 9A. NOV9 Sequence Analysis NOV9a, CG184416-01 SEQ ID NO: 77 132 bp DNA Sequence ORF Start: ATG at 39 ORF Stop: TGA at 1284 CTGCCCCATGCAGCCCTGAGCCCCACAGCAAGTCTGCCATGGGCCGCGGGGCCCGTGTCCCCTCGGAG GCCCCGGGGGCAGGCGTCGAGCGCCGCTGGCTTGGAGCCGCGCTGGTCGCCCTGTGCCTCCTCCCCGC GCTGGTGCTGCTGGCCCGGCTGGGGGCCCCGGCGGTGCCGGCCTGGAGCGCAGCGCAGGGAGACGTCG CTGCGCTGGGCCTCTCGGCGGTCCCCCCCACCCGGGTCCCGGGCCCACTGGCCCCCCGCAGACGCCGC TACACGCTGACTCCAGCCAGGCTGCGCTGGGACCACTTCAACCTCACCTACAGGATCCTCTCCTTCCC GCGGAACCTGCTGAGCCCGCGGGAGACGCGGCGGGCCCTAGCTGCCGCCTTCCGCATGTGGAGCGACG TGTCCCCCTTCAGCTTCCGCGAGGTGGCCCCCGAGCAGCCCAGCGACCTCCGGATAGGCTTCTACCCG ATCAACCACACGGACTGCCTGGTCTCCGCGCTGCACCACTGCTTCGACGGCCCCACGGGGGAGCTGGC CCACGCCTTCTTCCCCCCGCACGGCGGCATCCACTTCGACGACAGCGAGTACTGGGTCCTGGGCCCCA CGCGCTACAGCTGGAAGAAAGGCGTGTGGCTCACGGACCTGGTGCACGTGGCGGCCCACGAGATCGGC CACGCGCTGGGCCTGATGCACTCACAACACGGCCGGGCGCTCATGCACCTGAACGCCACGCTGCGCGG CTGGAAGGCGTTGTCCCAGGACGAGCTGTGGGGGCTGCACCGGCTCTACGGTGAGTCCCTTTGTCGGG CGGGAGGGCGGGGACCGGGCGGTCCTGAGCCAGGCGTOCTCCCCACGCTCCCGATAGGATGCCTCGAC AGGCTGTTCGTGTGCGCGTCCTGGGCGCGGAGGGGCTTCTGCGACGCTCGCCGGCGGCTCATGAAGAG GCTCTGCCCCAGCAGCTGCGACTTCTGCTACGAATTCCCCTTCCCCACGGTGGCCACCACCCCACCGC CCCCCAGGACCAAAACCAGGCTGGTGCCCGAGGGCAGGAACGTGACCTTCCGCTGCGGCCAGAAGATC CTCCACAAGAAAGGGAAAGTGTACTGGTACAAGGACCAGGAGCCCCTGGAGTTCTCCTACCCCGGCTA CCTGGCCCTGGGCGAGGCGCACCTGAGCATCATCGCCAACGCCGTCAATGAGGGCACCTACACCTGCG TGGTGCGCCGCCAGCAGCGCGTGCTGACCACCTACTCCTGGCGAGTCCGTGTGCGGGGCTGAGCCCGG 165 WO 03/093432 PCT/US03/13690 CTGATAAAGCACTTTCTCTCTGAAAAAAA NOV9a, CG184416-01 SEQ ID NO: 78 415 aa MW at 46304.OkD Protein Sequence MGRGARVPSEAPGAGVERRWLGAALVALCLLPALVLLARLGAPAVPAWSAAQGDVAALGLSAVPPTRV PGPLAPRRRRYTLTPARLRWDHFNLTYRILSFPRNLLSPRETRRALAAAFRMWSDVSPFSFREVAPEQ PSDLRIGFYPINHTDCLVSALHHCFDGPTGELAHAFFPPHGGIHFDDSEYWVLGPTRYSWKKGVWLTD LVHVAAHEIGHALGLMHSQHGRALMHLNATLRGWKALSQDELWGLHRLYGESLCRAGGRGPGGPEPGV LPTLPIGCLDRLFVCASWARRGFCDARRRLMKRLCPSSCDFCYEFPFPTVATTPPPPRTKTRLVPEGR NVTFRCGQKILHKKGKVYWYKDQEPLEFSYPGYLALGEAHLS I IANAVNEGTYTCVVRRQQRVLTTYS WRVRVRG Further analysis of the NOV9a protein yielded the following properties shown in Table 9B. Table 9B. Protein Sequence Properties NOV9a SignalP analysis: Cleavage site between residues 45 and 46 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 10; pos.chg 2; neg.chg 1 H-region: length 6; peak value -6.74 PSG score: -11.14 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 1.31 possible cleavage site: between 37 and 38 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 =-10.40 Transmembrane 21 - 37 PERIPHERAL Likelihood = 0.79 (at 272) ALOM score: -10.40 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 28 Charge difference: 0.0 C( 1.0) - N( 1.0) N >= C: N-terminal side will be inside >>> membrane topology: type 2 (cytoplasmic tail 1 to 21) MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 4.37 Hyd Moment(95): 11.61 G content: 4 D/E content: 2 S/T content: 1 Score: -6.42 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 16 ARVjPS 166 WO 03/093432 PCT/US03/13690 NUCDISC: discrimination of nuclear localization signals pat4: PRRR (4) at 74 pat4: RRRR (5) at 75 pat7: PLAPRRR (3) at 71 pat7: PRRRRYT (5) at 74 bipartite: RRQQRVLTTYSWRVRVR at 398 content of basic residues: 12.8% NLS Score: 1.27 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: GRGA none SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: none VAC: possible vacuolar targeting motif: found TLPI at 275 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's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 39.1 %: mitochondrial 167 WO 03/093432 PCT/US03/13690 30.4 %: cytoplasmic 8.7 %: vacuolar 8.7 %: endoplasmic reticulum 4.3 %: Golgi 4.3%: vesicles of secretory system 4.3%: nuclear >> prediction for CG184416-01 is mit (k=23) 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 9C. Table 9C. Geneseq Results for NOV9a NOV9a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region ABG72777 Human matrix metalloproteinase 23 1..415 390/415 (93%) 0.0 (MMP23) protein - Homo sapiens, 1..390 390/415 (93%) 390 aa. [WO200285285-A2, 31-OCT 20021 AAB84622 Amino acid sequence of matrix 1..415 390/415 (93%) 0.0 metalloproteinase-21 - Homo sapiens, 1..390 390/415 (93%) 390 aa. [WO200149309-A2, 12-JUL 2001] AAE10430 Human matrix metalloprotinase-22P 1..415 390/415 (93%) 0.0 (MMP-22P) protein - Homo sapiens, 1..390 390/415 (93%) 390 aa. [WO200166766-A2, 13-SEP 2001] AAY78585 Metalloprotease in the female 1..415 390/415 (93%) 0.0 reproductive tract protein sequence - 1..390 390/415 (93%) Homo sapiens, 390 aa. [JP2000014387-A, 18-JAN-2000] AAY78353 Rat metalloproteinase protein 1..414 327/417 (78%) 0.0 sequence SEQ ID NO:2 - Rattus 1..390 344/417 (82%) norvegicus, 391 aa. [JP2000014386 A, 18-JAN-2000] 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 9D. 168 WO 03/093432 PCT/US03/13690 Table 9D. Public BLASTP Results for NOV9a SNOV9a Identities/ Protemn Residues/ Similarities for Expect Accession Protein/Organism/Length Match the Matched Value Match the Matched Value Number. Number Residues Portion Q9UBR9 MMP-23 (MIFR/FEMALYSIN) 1..415 390/415 (93%) 0.0 (DJ283E3.2.1) (Matrix 1..390 390/415 (93%) metalloproteinase MMP21/22A (MIFR1)) (Matrix metalloproteinase 23B) - Homo sapiens (Human), 390 aa. 075900 Metalloprotease mmp21/22A - Homo 1..415 389/415 (93%) 0.0 Sapiens (Human), 390 aa. 1..390 389/415 (93%) 088676 cAMP metalloproteinase - Mus 1 ..414 328/416 (78%) 0.0 musculus (Mouse), 391 aa. 1..390 345/416 (82%) 088272 MIFR- Rattus norvegicus (Rat), 391 1..414 327/417 (78%) 0.0 aa. 1..390 344/417 (82%) 075894 Metalloprotease isoform C 149.398 250/250 (100%) e-156 (Metalloprotease MMP21/22C) - 1..250 250/250 (100%) Homo sapiens (Human), 250 aa (fragment). PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E. Table 9E. Domain Analysis of NOV9a Identities/ Pfam Domain NOV9a Match Region Similarities Expect Value for the Matched Region Peptidase M10 81..192 43/115 (37%) 1.9e-23 74/115 (64%) ShTK 279..315 16/44 (36%) 3.4e-09 27/44 (61%) ig 339..397 17/61(28%) 0.00051 39/61 (64%) 169 WO 03/093432 PCT/US03/13690 Example 10. The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10 A. Table 1OA.NOy1 Sequence Analysis NOV10a, CG185200-01 SEQ ID NO: 79 .2050 bp DNA Sequence IORF Start: ATG at 66 ORF Stop: TAA at 918 AGCACCATTTAAGCCACTGGGAAATTTGTTGTCTAGTGGTTGTGGGTGAATAAAGGAGGGCAGAATG GATGATTTCATCTCCATTAGCCTGCTGTCTCTGCTATGTTGGTGGGATGTTACGTGGCCGGAATCAT TCCCTTGGCTGTTAATTTCTCAGAGGAACGACTGAAGCTGGTGACTGTTTTGGGTGCTGGCCTTCTCT GTGGAACTGCTCTGGCAGTCATCGTGCCTGAAGGAGTACATGCCCTTTATGAAGATATTCTTGAGGOGA AAACACCACCAAGCAAGTGAAACACATAA.TGTGATTGCATCAGACAAAGCAGCAGAAAAATCAGTTGT CCATGAACATGAGCACAGCCACGACCACACACAGCTGCATGCCTATATTGGTGTTTCCCTCGTTCTGG GCTTCGTTTTCATGTTGCTGGTGGACCAGATTGGTAACTCCCATGTGCATTCTACTGACGCTGATGGT GTTGCTTTGGGAGCAGCAGCATCTACTTCACAGACCAGTGTCCAGTTAATTGTGTTTGTGGCAATCAT GCTACATAAGGCACCAGCTGCTTTTGGACTGGTTTCCTTCTTGATGCATGCTGGCTTAGAGCGGAATC GAATCAGAAAGCACTTGCTGGTCTTTGCATTGGCAGCACCAGTTACGTCCATGGTGACATACTTAGGA CTGAGTAAGAGCAGTAAAGAAGCCCTTTCAGAGGTGAACGCCACGGGAGTGGCCATGCTTTTCTCTGC CGGGACATTTCTTTATGTTGCCACAGTACATGTCCTCCCTGAGGTGGGCGGAATAGGGCACAGCCACA AGCCCGATGCCACGGGAGGGAGAGGCCTCAGCCGCCTGGAAGTGGCAGCCCTGGTTCTGGGTTGCCTC ATCCCTCTCATCCTGTCAGTAGGACACCAGCATTAAATGTTCAAGGTCCAGCCTTGGTCCAGGGCCGT TTGCCATCCAGTGAGAACAGCCGGCACGTGACAGCTACTCACTTCCTCAGTCTCTTGTCTCACCTTGC GCATCTCTACATGTATTCCTAGAGTCCAGAGGGGAGGTGAGGTTAAAACCTGAGTAATGGAAAAGCTT TTAGAGTAGAAACACATTTACGTTGCAGTTAGCTATAGACATCCCATTGTGTTATCTTTTAAAAGGCC CTTGACATTTTGCGTTTTAATATTTCTCTTAACCCTATTCTCAGGGAAGATGGAATTTAGTTTTAAGG AAAAGAGGAGAACTTCATACTCACAATGAATAGTGATTATGAAAATACAGTGTTCTGTAATTAAGCT ATGTCTCTTTCTTCTTAGTTTAGAGGCTCTGCTACTTTATCCATTGATTTTTAACATGGTTCCCACCA TGTAAGACTGGTGCTTTAGCATCTATGCCACATGCGTTGATGGAAGGTCATAGCACCCACTCACTTAG ATGCTAAAGGTGATTCTAGTTAATCTGGGATTAGGGTCAGGAAAATGATAGCAAGACACATTGAAAGC TCTCTTTATACTCAAAAGAGATATCCATTGAAAAGGGATGTCTAGAGGGATTTAAACAGCTCCTTTGG CACGTGCCTCTCTGAATCCAGCCTGCCATTCCATCAAATGGAGCAGGAGAGGTGGGAGGAGCTTCTAA AGAGGTGACTGGTATTTTGTAGCATTCCTTGTCAAGTTCTCCTTTGCAGAATACCTGTCTCCACATTC CTAGAGAGGAGCCAAGTTCTAGTAGTTTCAGTTCTAGGCTTTCCTTCAAGAACAGTCAGATCACAAAG TGTCTTTGGAAATTAAGGGATATTAAATTTTAAGTGATTTTTGGATGGTTATTGATATCTTTGTAGTA GCTTTTTTTAAAAGACTACCAAAATGTATGGTTGTCCTTTTTTTTTGTTTTTTTTTTTTTTAATTATT TCTCTTAGCAGATCAGCAATCCCTCTAGGGACCTAAATACTAGGTCAGCTTTGGCGACACTGTGTCTT CTCACATAACCACCTGTAGCAAGATGGATCATAAATGAGAAGTGTTTGCCTATTGATTTAAGCTTAT TGGAATCATG NOV10a, CG185200-01 SEQ ID NO: 80 284 aa MW at 29900.4kD Protein Sequence MDDFISISLLSLAMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVHALYEDILE GKHHQASETHNVIASDKAAEKSVVHEHEHSHDHTQLHAYIGVSLVLGFVFMLLVDQIGNSHVHSTDAD GVALGAAASTSQTSVQLIVFVAIMLHKAPAAFGLVSFLMHAGLERNRIRKHLLVFALAAPVTSMVTYL GLSKSSKEALSEVNATGVAMLFSAGTFLYVATVHVLPEVGGIGHSHKPDATGGRGLSRLEVAALVLGC LIPLILSVGHQH NOVIOb, CG185200-02 SEQ IDNO: 81 1120 bp DNA Sequence ORF Start: ATG at 94 ORF Stop: TAA at 1015 GGAACCACCACACCTGTTTAAAGAACCTAAGCACCATTTAAAGCCACTGGAAATTTGTTGTCTAGTGG TTGTGGGTGAATAAAGGAGGGCAGAATGGATGATTTCATCTCCATTAGCCTGCTGTCTCTGGCTATGT TGGTGGGATGTTACGTGGCCGGAATCATTCCCTTGGCTGTTAATTTCTCAGAGGAACGACTGAAGCTG GTGACTGTTTTGGGTGCTGGCCTTCTCTGTGGAACTGCTCTGGCAGTCATCGTGCCTGAAGGAGTACA TGCCCTTTATGAAGATATTCTTGAGGGAAAACACCACCAAGCAAGTGAAACACATAATGTGATTGCAT CAGACAAAGCAGCAGAAAAATCAGTTGTCCATGAACATGAGCACAGCCACGACCACACACAGCTGCAT 170 WO 03/093432 PCT/US03/13690 GCCTATATTGGTGTTTCCCTCGTTCTGGGCTTCGTTTTCATGTTGCTGGTGGACCAGATTGGTAACTC CCATGTGCATTCTACTGACGATCCAGAAGCAGCAAGGTCTAGCAATTCCAAAATCACCACCACGCTGG GTCTGGTTGTCCATGCTGCAGCTGATGGTGTTGCTTTGGGAGCAGCAGCATCTACTTCACAGACCAGT GTCCAGTTAATTGTGTTTGTGGCAATCATGCTACATAAGGCACCAGCTGCTTTTGGACTGGTTTCCTT CTTGATGCATGCTGGCTTAGAGCGGAATCGAATCAGAAAGCACTTGCTGGTCTTTGCATTGGCAGCAC CAGTTATGTCCATGGTGACATACTTAGGACTGAGTAAGAGCAGTAAAGAAGCCCTTTCAGAGGTGAAC GCCACGGGAGTGGCCATGCTTTTCTCTGCCGGGACATTTCTTTATGTTGCCACAGTACATGTCCTCCC TGAGGTGGGCGGAATAGGGCACAGCCACAAGCCCGATGCCGCGGGAGGGAGAGGCCTCAGCCGCCTGG AAGTGGCAGCCCTGGTTCTGGGTTGCCTCATCCCTCTCATCCTGTCAGTAGGACACCAGCATTAAATG TTCAAGGTCCAGCCTTGGTCCAGGGCCGTTTGCCATCCAGTGAGAACAGCCGGCACGTGACAGCTACT CACTTCCTCAGTCTCTTGTCTCACCTAAGGCG NOV10b, CG185200-02 ISEQD NO8 at 32221.0kD Protein Sequence MDDFISISLLSLAMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVHALYEDILE GKHHQASETHNVIASDKAAEKSVVHEHEHSHDHTQLHAYIGVSLVLGFVFMLLVDQIGNSHVHSTDDP EAARSSNSKITTTLGLVVHAAADGVALGAAASTSQTSVQLIVFVAIMLHKAPAAFGLVSFLMHAGLER NRIRKHLLVFALAAPVMSMVTYLGLSKSSKEALSEVNATGVAMLFSAGTFLYVATVHVLPEVGGIGHS HKPDAAGGRGLSRLEVAALVLGCLIPLILSVGHQH A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 10OB. Table 10B. Comparison of the NOV10 protein sequences. NOV10a MDDFISISLLSLAMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVH NOV10b MDDFISISLLSLAMLVGCYVAGIIPLAVNFSEERLKLVTVLGAGLLCGTALAVIVPEGVH NOV10a ALYEDILEGKHHQASETHNVIASDKAAEKSVVHEHEHSHDHTQLHAYIGVSLVLGFVFML NOVI0b ALYEDILEGKHHQASETHNVIASDKAAEKSVVHEHEHSHDHTQLHAYIGVSLVLGFVFML NOV10a LVDQIGNSHVHSTD-- -----------------------ADGVALGAAASTSQTSVQLIVFV NOV10b LVDQIGNSHVHSTDDPEAARSSNSKITTTLGLVVHAAADGVALGAAASTSQTSVQLIVFV NOV10a AIMLHKAPAAFGLVSFLMHAGLERNRIRKHLLVFALAAPVTSMVTYLGLSKSSKEALSEV NOVI0b AIMLHKAPAAFGLVSFLMHAGLERNRIRKHLLVFALAAPVMSMVTYLGLSKSSKEALSEV NOV10a NATGVAMLFSAGTFLYVATVHVLPEVGGIGHSHKPDATGGRGLSRLEVAALVLGCLIPLI NOVI0b NATGVAMLFSAGTFLYVATVHVLPEVGGIGHSHKPDAAGGRGLSRLEVAALVLGCLIPLI NOV10a LSVGHQH NOV10b LSVGHQH NOV10a (SEQ ID NO: 80) NOV10b (SEQ ID NO: 82) Further analysis of the NOV 10 a protein yielded the following properties shown in Table 10C. Table 10C. Protein Sequence Properties NOV10a SignalP analysis: Cleavage site between residues 62 and 63 PSORT II analysis: 171 WO 03/093432 PCT/US03/13690 PSG: a new signal peptide prediction method N-region: length 3; pos.chg 0; neg.chg 2 H-region: length 28; peak value 0.00 PSG score: -4.40 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -1.40 possible cleavage site: between 52 and 53 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 7 INTEGRAL Likelihood = -6.48 Transmembrane 12 - 28 INTEGRAL Likelihood = -5.68 Transmembrane 38 - 54 INTEGRAL Likelihood = -8.49 Transmembrane 106 - 122 INTEGRAL Likelihood = -1.97 Transmembrane 153 - 169 INTEGRAL Likelihood = -3.13 Transmembrane 188 - 204 INTEGRAL Likelihood = -1.01 Transmembrane 221 - 237 INTEGRAL Likelihood = -8.81 Transmembrane 265 - 281 PERIPHERAL Likelihood = 9.18 (at 135) ALOM score: -8.81 (number of TMSs: 7) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 19 Charge difference: 1.0 C( 0.0) - N(-1.0) C > N: C-terminal side will be inside >>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 8.48 Hyd Moment(95): 7.98 G content: 0 D/E content: 2 S/T content: 0 Score: -6.50 Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 5.3% 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 172 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 55.6 %: endoplasmic reticulum 11.1 %: Golgi 11.1 %: vacuolar 11.1 %: vesicles of secretory system 11.1 %: mitochondrial >> prediction for CG185200-01 is end (k=9) A search of the NOVIOa protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10D. 173 WO 03/093432 PCT/US03/13690 Table 10D. Geneseq Results for NOV10a NOV10a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAB93646 Human protein sequence SEQ ID 1..284 284/307 (92%) e-154 NO:13148 - Homo sapiens, 307 aa. 1..307 284/307 (92%) [EP1074617-A2, 07-FEB-2001] ABU57061 Human PRO polypeptide #131 - 1..284 283/307 (92%) e-153 Homo sapiens, 307 aa. 1.307 283/307 (92%) [US2003027280-Al, 06-FEB-2003] ABU56066 Human secreted/transmembrane 1..284 283/307 (92%) e-153 protein, PRO 1377 - Homo sapiens, 1..307 283/307 (92%) 307 aa. [US2003022298-A1, 30 JAN-2003] ABU10640 Human secreted/transmembrane 1..284 283/307 (92%) e-153 protein #131 - Homo sapiens, 307 aa. 1..307 283/307 (92%) [US2002127584-Al, 12-SEP-2002] AAB66116 Protein of the invention #28 - 1..284 283/307 (92%) e-153 Unidentified, 307 aa. 1..307 283/307 (92%) [WO200078961-A1, 28-DEC-2000] In a BLAST search of public sequence databases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10E. 174 WO 03/093432 PCT/US03/13690 Table 10E. Public BLASTP Results for NOV10a Protein NOV10a Identitiesf ProteinResidues/ Similarities for Expect Accession Protein/Organism/Length Match the Matched Value Number Nume Residues Portion Q9NUM3 Hypothetical protein FLJ11274 - 1 ..284 284/307 (92%) e-154 Homo sapiens (Human), 307 aa. 1..307 284/307 (92%) AAH47682 Hypothetical protein - Homo 1..284 283/307 (92%) e-153 sapiens (Human), 307 aa. 1..307 283/307 (92%) Q8BFUI CDNA FLJ11274 FIS - Mus 1..284 266/308 (86%) e-143 musculus (Mouse), 308 aa. 1..308 275/308 (88%) Q95JP5 Hypothetical 25.0 kDa protein - 130..284 149/155 (96%) 2e-76 Macaca fascicularis (Crab eating 82..235 152/155 (97%) macaque) (Cynomolgus monkey), 235 aa. AAH44279 Hypothetical protein - Xenopus 1..281 154/308 (50%) 7e-69 laevis (African clawed frog), 303 aa. 1..299 197/308 (63%) PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10F. Table 10F. Domain Analysis of NOV10a Identities/ Pfam Domain NOV10a Match Region Similarities Expect Value for the Matched Region Zip 4..279 78/407 (19%) 2.1e-34 214/407 (53%) Example 11. The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11 A. Table lA. NOV11 Sequence Analysis NOV11a, CG50513-01 SEQ ID NO: 83 11598 bp DNA Sequence ORF Start: at 1 IORF Stop: TGA at 1354 AAACAGCCACTTGTTTCATCCCACCTGGGCATTAGGTTGACTTCAAAGATGCCTCAGTTACTGCAAAA CATTAATGGGATCATCGAGGCCTTCAGGCGCTATGCAAGGACGGAGGGCAACTGCACAGCGCTCACCC GAGGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATTGTGAAACCCCACGATCCAGCA ACTGTGGATGAGGTCCTGCGTCTGCTGGATGAAGACCACACAGGGACTGTGGAATTCAAGGAATTCCT GGTCTTAGTGTTTAAAGTTGCCCAGGCCTGTTTCAAGACACTGAGCGAGAGTGCTGAGGGAGCCTGCG GCTCTCAAGAGTCTGGAAGCCTCCACTCTGGGGCCTCGCAGGAGCTGGGCGAAGGACAGAGAAGTGGC 175 WO 03/093432 PCT/US03/13690 ACTGAAGTGGGAAGGGCGGGGAAAGGGCAGCATTATGAGGGGAGCAGCCACAGACAGAGCCAGCAGGG TTCCAGAGGGCAGAACAGGCCTGGGGTTCAGACCCAGGGTCAGGCCACTGGCTCTGCGTGGGTCAGCA GCTATGACAGGCAAGCTGAGTCCCAGAGCCAGGAAAGAATAAGCCCGCAGATACAACTCTCTGGGCAG ACAGAGCAGACCCAGAAAGCTGGAGAAGGCAAGAGGAATCAGACAACAGAGATGAGGCCAGAGAGACA GCCACAGACCAGGGAACAGGACAGAGCCCACCAGACAGGTGAGACTGTGACTGGATCTGGAACTCAGA CCCAGGCAGGTGCCACCCAGACTGTGGAGCAGGACAGCAGCCACCAGACAGGAAGCACCAGCACCCAG ACACAGGAGTCCACCAATGGCCAGAACAGAGGGACTGAGATCCACGGTCAAGGCAGGAGCCAGACCAG CCAGGCTGTGACAGGAGGACACACTCAGATACAGGCAGGGTCACACACCGAGACTGTGGAGCAGGACA GAAGCCAAACTGTAAGCCACGGAGGGGCTAGAGAACAGGGACAGACCCAGACGCAGCCAGGCAGTGGT CAAAGATGGATGCAAGTGAGCAACCCTGAGGCAGGAGAGACAGTACCGGGAGGACAGGCCCAGACTGG GGCAAGCACTGAGTCAGGAAGGCAGGAGTGGAGCAGCACTCACCCAAGGCGCTGTGTGACAGAAGGGC AGGGAGACAGACAGCCCACAGTGGTTGGTGAGGAATGGGTTGATGACCACTCAAGGGAGACAGTGATC CTCAGGCTGGACCAGGGCAACTTGCATACCAGTGTTTCCTCAGCACAGGGCCAGGATGCAGCCCAGTC AGAAGAGAAGCGAGGCATCACAGCTAGAGAGCTGTATTCCTACTTGAGAAGCACCAAGCCATGACTTC CCCGACTCCAATGTCCAGTACTGGAAGAAGACAGCTGGAGAGAGTTTGGCTTGTCCTGCATGGCCAAT CCAGTGGGTGCATCCCTGGACATCAGCTCTTCATTATGCAGCTTCCCTTTTAGGTCTTTCTCAATGAG ATAATTTCTGCAAGGAGCTTTCTATCCTGAACTCTTCTTTCTTACCTGCTTTGCGGTGCAGACCCTCT CAGGAGCAGGAAGACTCAGAACAAGTCACCCCTT NOVI la, CG50513-01 SEQ ID NO: 84 451 aa MWat4898.6kD Protein Sequence KQPLVSSHLGIRLTSKMPQLLQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKPHDPA TVDEVLRLLDEDHTGTVEFKEFLVLVFKVAQACFKTLSESAEGACGSQESGSLHSGASQELGEGQRSG TEVGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQTQGQATGSAWVSSYDRQAESQSQERISPQIQLSGQ TEQTQKAGEGKRNQTTEMRPERQPQTREQDRAHQTGETVTGSGTQTQAGATQTVEQDSSHQTGSTSTQ TQESTNGQNRGTEIHGQGRSQTSQAVTGGHTQIQAGSHTETVEQDRSQTVSHGGAREQGQTQTQPGSG QRWMQVSNPEAGETVPGGQAQTGASTESGRQEWSSTHPRRCVTEGQGDRQPTVVGEEWVDDHSRETVI LRLDQGNLHTSVSSAQGQDAAQSEEKRGITARELYSYLRSTKP NOV11b, 273654175 ISEQ ID NO: 85 1151 bp DNA Sequence ORF Start: at 2 JORF Stop: at End of Sequence ACCGGATCCTTACTGCAAAACATTAATGGGATCATCGAGGCCTTCAGGCGCTATCAAGGACGGAGG GCAACTGCACAGCGCTCACCCGAGGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATT GTGAAACTCGAGGGC NOV11 b, 273654175 SEQ ID NO: 86 50 aa MW at 5608.3kD Protein Sequence I _I TGSLLQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKLEG NOVl Ic, CG50513-02 SEQ ID NO: 87 1039 bp DNA Sequence ORF Start: atI ORF Stop: end of sequence GTCAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCC CTGTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGA CCCGAGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAAAG CCCCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAGAATGGCAGCA GTGTTCCAGGACTTGTGGCGGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATG GCAGCTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCAAGGCATCGTCTCACAAGTCCTGTGCC AGGACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGG AATCCAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCAAAGGTCGGCGCATCCCCCTCAGTGAGA TGATGTGCAGGGATCTACCAGGGTTCCCTCTTGTAAGATCTTGCCAGATGCCTGAGTGCAGTAAAATC AAATCAGAGATGAAGACAAAACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACAT TCAGACAAGGGAAGAGAAGCGTATTAACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCCAACACAT CCGTGATTATTAAGTGCCCAGTGCGACGATTCCAGAAATCTCTGATCCAGTGGGAGAAGGATGGCCGT TGCCTGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAAATCCACGGTCTTGCTGC CCCCGACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAACAGGTGTGCTCAAGCTCATTG GTACTGACAACCGGCTCATTGCACGCCCAACCCTCANGGAGCCTATGAGGGAATATCCTGGGATGGAC CACAACGAAGCCAATAGTT NOV1 Ic, CG50513-02 SEQ ID NO: 88 346 aa MW at 38248.6kD 176 WO 03/093432 PCT/t1S03/13690 ~Protein Sequence.1 VNDSLCDMVHRPPAMSQACNTEPCPPRWIWGSWGPCSATCGVGIQTRDVYCLHPGETPAPPEECRDEK PHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQNPRRVTCRQLLTDGSFLNLSDELCQGPKASSHKSC!A RTDCPPHLAVGDWSKCSVS CGVGIQRRKQVCQRLA74KGRRIPLSEMMCRDLPGFPLVRSCQMPECSKI KSEMKTKLGEQGPQILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVI IKCPVRRFQKSLIQWEKDGR CLQNSKRLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETGVLKLIGTDNRLIAP.PTLXEPMREYPGMD NOVIlId, CG50513-03 ISEQ ID NO: 89633b DNA Sequence JORF.Start: ATO at 425 JO.RF Stop.: TAA at 4268 TATAATTATTAATAGAGACCTTTCAAAGGACAAATTCTGTGAAATAAAGTGGTTTTCTGAAGAGCCTA CTAATAGGACAGTGTGTTAATATCACTAATAAGAGAGThATGATTATAAAAAGGAATAAATTTATTGA AATTGCAAGATACTTTTCTCCTTTGATTAATATACTGCTAGTTTAGTTTTCTACATTTTCAAATAGAA CTGGGGAATTTGTGTCGTAGATATTCTTGACAACTAAAGAGATGGTGGCTGAATTTTTGGGAATGGTT GATAAACTTGATATTTTTAGTTTCCAATTTGGAAGAGCTCTGTCTCTTGGGATGTCAAATATTATAT TCGTCAATTAATGAATGTGTTAATTTATTATAGAAATGATATTCTCACAATGATTTCATTTGTAaTGA TGGATTTAAAGAGATAATG;CCCTATOACCACTTCCAACCTCTTCCTCGCTGGGAACATAATCCTTGGA CTGCATGTTCCGTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTGTGTGTGTAAGGAATCCATG CATGGAGAGATATTGCAGGTGGAAGAATGGAAGTGCATGTACGCACCCAAACCCAAGGTTATGCAC TTGTAATCTGTTTGATTGCCCCAAGTGGATTGCCATGGAGTGGTCTCAGTGCACAGTGACTTGTGGCC GAGGGTTACGGTACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCATGTTGGGGGCTGCAATCCA CAACTGAAGTTACACATCAAAAAGATGTGTCATTCCCATCCCGTGTTATAAACCALGAAAAG TCCAGTGGAAGCAAAATTGCCTTGGCTG~aAACAAGCACAAGAACTAGAAGAGACCAGATAGCACAG AAGAACCAACGTTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTGTGGGCCGGGTGTGCAGGTC CGTGAGGTGAAGTGCCGTGTGCTCCTCACATTCACGCAGACTGAGACTGAGCTGCCCGAGGAAGAGTG TGAAGGCCCCAAGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGTGATGAGAGCCCGGCCTCCC GAGAGCTAGACATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTGGGAGTACGCTGGGTTCACC CCTTGCACAGCAACATGCGTGGGAGGCCATCAAGAAGCCATAGCAGTGTGCTTACATATCCAGACCCA GCAGACAGTCAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACA CAGAGCCCTGTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGA ATTCAGACCCGAGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGA TGAAAAGCCCCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAGAAT GGCAGCAGTGTTCCAGGACTTGTGGCGGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTA ACGGATGGCGCTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCAAiGGCATCGTCTCACAAGTC CTGTGCCAGGACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTG GTGTTGGAATCCAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCAAAGGTCGGCGCATCCCCCTC AGTGAGATGATGTGCAGGGATCTACCAGGGTTCCCTCTTGTAAGATCTTGCCAGATGCCTGAGTGCAG TAAATCAATCAGAGATGAAGACAAAACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAG TCTACATTCAGACAAGGGAAGAGAAGCGTATTAACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCC AACACATCCGTGATTATTAAGTGCCCCGTGCGACGATTCCAGAAkATCTCTGATCCAGTGGGAGAAGGA TGGCCGTTGCCTGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAAATCCACGGTC TTGCTGCCCCCGACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAACAGTTGTGCTCAG CTCATTGGTACTGACAACCGGCTCATCGCACGCCCAGCCCTCAGGGAGCCTATGAGGGAATATCCTGG GATGGACCACAGCGAAGCCAATAGTTTGGGAGTCACATGGCACAXAATGAGGCAAATGTGGAATAACA AAAATGACCTTTATCTGGATGATGACCACATTAGTAACCAGCCTTTCTTGAGAGCTCTGTTAGGCCAC TGCAGCAATTCTGCAGGAAGCACCAACTCCTGGGAGTTGAAGAATAAGCAGTTTGAAGCAGCAGTTAA ACAAGGAGCATATAGCATGGATACAGCCCAGTTTGATGAGCTGATAAGAA ACATGAGTCAGCTCATGG AAACCGGAGAGGTCAGCGATGATCTTGCGTCCCAGCTGATATATCAGCTGGTGGCCGAATTAGCCAAG GCACAGCCAACACACATGCAGTGGCGGGGCATCCAGGAAGAGACACCTCCTGCTGCTCAGCTCAGAGG GGAAACAGGGAGTGTGTCCCAAAGCTCGCATGCAAAAAACTCAGGCAAGCTGACATTCAAGCCGAAAG GACCTGTTCTCATGAGGCAAGCCAACCTCCCTCATTTCATTTAATAAAACAATAAATTCCAGGATT GGAAATACAGTATACATTACAAAAAGGACAGAGGTCATCAATATACTGTGTGACCTTATTACCCCCAG TGAGGCCACATATACATGGACCALAGGATGGAACCTTGTTACAGCCCTCAGTAAAAATAATTTTGGATG GAACTGGGAAGATACAGATACAGAATCCTACAAGGAAAGAACAAGGCATATATGAATGTTCTGTAGCT AATCATCTTGGTTCAGATGTGGAAAGTTCTTCTGTGCTGTATGCAGAGGCACCTGTCATCTTGTCTGT TGAAAGAAATATCACCAAACCAGAGCACAACCATCTGTCTGTTGTGGTTGGAGGCATCGTGGAGGCAG CCCTTGGAGCAAACGTGACAATCCGATGTCCTGTAAAAGGTGTCCCTCAGCCTAATATAACTTGGTTG AAGAGAGGAGGATCTCTGAGTGL3CAATGTTTCCTTGCTTTTCAATGGATCCCTGTTGTTGCAGAATGT 177 WO 03/093432 PCT/11S03/13690 TTCCCTTGAAATGAGGAACCTACGTCTGCATAGCCACCAATGCTCTTGGAAGGCAGTGGCAACAT CTGTACTCCACTTGCTGGAACGAAGATGGCCAGAGAGTAGAATCGTATTTCTGCGGACATAAAG TACATTCTCCAGGCACCAACACTAGAACCACAGCAATGACCCAACAGGAGAACCCCCGCCTCAAGA GCCTTTTTGGGAGCCTGGTAACTGGTCACATTGTTCTGCCACCTGTGGTCATTTGGGAGCCCGCATTC .AGAGACCCCAGTGTGTGATGGCCAATGGGCAGGAAGTGAGTGAGGCCCTGTGTGATCACCTCCAGAAG CCACTGGCTGGGTTTGAGCCCTGTAACATCCGGGACTGCCCAGCGAGGTGGTTCACAAGTGTGTGGTC ACAGTGCTCTGTGTCTTGCGGTGAAGGATACCACAGTCGGCAGGTGACGTGCAAGCGGACAAAAGCCA ATGGAACTGTGCAGGTGGTGTCTCCAAGAGCATGTGCCCCTAAAGACCGGCCTCTGGGAAGAACCA TGTTTTGGTCATCCATGTGTTCAGTGGGAACCAGGGAACCGGTGTCCTGGACGTTGCATGGGCCGTGC TGTGAGGATGCAGCAGCGTCACACAGCTTGTCAACACAACAGCTCTGACTCCAACTGTATGACAGAA AGAGACCCACCTTAAGAAGGAACTGCACATCAGGGGCCTGTGATGTGTGTTGGCACACAGGCCCTTGG AAGCCCTGTACAGCAGCCTGTGGCAGGGGTTTCCAGTCTCGGAXAGTCGACTGTATCCACACAAGGAG TTGCAAACCTGTGGCCAAGAGACACTGTGTACAGAAAAAGAAACCAATTTCCTGGCGGCACTGTCTTG GGCCCTCCTGTGATAGAGACTGCACAGACACAACTCACTACTGTATGTTTGTAAAACATCTTAATTTG TGTTCTCTAGACCGCTACAAACAAAGGTGCTGCCAGTCATGTCAAGAGGGATAAACCTTTGGAGGGGT CATGATGCTGCTGTGAAGATAAAAGTAGATATAAAGCTCTTTTCCCCATGTCGCTGATTCAAAC ATGTATTTCTTAAZAAGACTAG3ATTCTATGGATCAAACAGAGGTTGATGCAAAAACACCACTGTTAAGG TGTAAAGTGAATTTTCCAATGGTAGTTTTATATTCCAATTTTTTAAATGATGTATTCAAGGATGAA CAAAATACTATAGCATGCATGCCACTGCACTTGGGACCTCATCATGTCAGTTGAATCGAGAALTCACC AAGATTATGAGTGCATCCTCACGTGCTGCCTCTTTCCTGTGATATGTAGACTAGCACAGAGTGGTACA TCCTAAAAACTTGGGAAACACAGCAACCCATGACTTCCTCTTCTCTCAAGTTGCAGGTTTTCAACAGT TTTATAAGGTATTTGCATTTTAGAAGCTCTGGCCAGTAGTTGTTAAGATGTTGGCATTAATGGCATTT TCATAGATCCTTGGTTTAGTCTGTGAAAAAGAA-ACCATCTCTCTGGATAGGCTGTCACACTGACTGAC CTAAGGGTTCATGGAGCATGGCATCTTGTCCTTGCTTTTAGAACACCCATGGAAGAAAACACAGAGT AGATATTGCTGTCATTTATACACTACAGAAATTTATCTATGACCTAATGAGGCATCTCGGAGTCAA AGAAGAGGGAAAGTTAACCTTTTCTACTGATTTCGTAGTATATTCAGAGCTTTCTTTTAAGAGCTGTG AATGAAACTTTTTCTAAGCACTATTCTATTGCACACAAACAGAAAACCAAAGCCTTATTAGACCTAT, TTTCTAGATTCTAACTATTGAATAAGAGALCAAAG AAAGTGTAA ATTTTGAAATGTTGCGTTTATATCA GTGACTTAGGTTAGA.AGTTACACTAAGGACCAGGGGTTGGAATCAGAATTTAGTTTAAGATTTGAGGA AAAGGcGTAAGGGTTAGTTTCAGTTTTAGGATTAGAGCTAGAATTGGGTTAGGTGAGAAAGAAAGTTAA GGTTAAGGCTAGAGTTGTCTTTAAGGGTTAGGGTTAGGACCAGGTTAGGTCAGGGTTGGATTGGGTTT AGATTGGGGCCAGTGCTGGTGTTAGTGATAGTGTCAGGATGGAGGTTAGGTTTGGAGTAAGCGTTGTT GCTGAAGTGAGTTCAGGCTAGCATTAAATTGTA1AGTTCTGATAGCTGATTTGGTTATGGGGTCTTTCCC CTGTATACTACCAGTTGTGTCTTTAGATGGCACACAAGTCCAAATAAGTGGTCATACTTCTTTATTCA GGGTCTCAGCTGCCTGTACACCTGCTGCCTACATCTTCTTGGCAACAAAGTTACCTGCCACAGGCTCT GCTGAGCCTAGTTCCTGGTCAGTAATAACTGAACAGTGCATTTTGGCTTTGGATGTGTCTGTGGACAA GCTTGCTGAGTTTCTCTACCATATTCTGAGCACACGGTCTCTTTTGTTCTAATTTCAGCTTCACTGAC ACTGGGTTGAGCACTACTGTATGTGGAGGGTTTGGTGATTGGGAATGGATGGGGGACAGTGAGGAGGA CACACCAGCCCATTAGTTGTTAATCATCAATCACATCTGATTGTTGAAGGTTATTAAATTAAAAGAAA GATCATTTGTAACATACTCTTTGTATATATTTATTATATGAAAGGTGCAATATTTTATTTTGTACAGT ATGTAATAAAGACATGGGACATATATTTTTCTTATTAACAAAATTTCATATTAAATTGCTTCACTTTG TATTTAAAGTTAAAAGTTACTATTTTTCATTTGCTATTGTACTTTCATTGTTGTCATTCATTGACAT TCCTGTGTACTGTATTTTACTACTGTTTTTATAACATGAGAGTTAATGTTTCTGTTTCATGATCCTTA TGTAATTCAGAAALTAAATTTACTTTGATTATTCAGTGGCATCCTTAT NOV1Ild, CG50513-03 0SQIDN: 9011281 aa 1MW at 142825.9kD PoenSequence I MPYDHFQPLPRWEHNPWTACSVSCGGGIQR'RSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFD CPEWAMEWSQCTVTCGRGLRYRVLCNHRGEHJGGCNPQLLHIKEECVIPIPCYKPKEKSPVEAK LPLQQLERAEPFPPSCTCGGQRVCVLFQEEPECGK PTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATCVGGHQAIAVCLHIQTQQVN SLCDMVRPPAMSQACNTEPCPPRWHVGSWGPCSATCGVGIQTVCLHPGETPAPPEECRDEKPR LQACNQFDCPPGWHIEEWQQCSRTCGGGTQNRRVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTD CPPHLAVGDWSKCSVSCGVGIQRRKQVCQRLAAU(GRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSE MKTKLGEQGPQILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEYIDGRCLQ NSRGTSSKHLADGYCASQEVLLGDRIRARPRYGDS 178 WO 03/093432 PCT/t1S03/13690 SQSSHA.KNSGKLTFKPKGPVLMRQSQPPS ISFNKTINSRIGNTVYITKRTBVINILCDLITPSEATYT WTKDGTLLQPSVKI ILDGTGKIQIQNPTRKEQGIYECSVANHLGSDVESSSVLYAEAPVILSVEPNIT KPEHNHLSVVVGGIVEAALGANVTIRCPVKGVPQPNqITWLKRGGSLSGNVSLLFNGSLLLQNVSLENE GTYVCIATNALGKAVATSVLHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPPWEP GNWSHCSATCGHLGARIQRPQCVMANGQEVSEAIJCDHLQKPLAGFEPCNIRDCPARWFTSVWSQCSVS CGEGYHSRQVTCKRTKANGTVQVSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRCMGRAXVRQQ RIITACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGPWKPCTAACGRGFQSRKVD)CIHTRSCKPVA KRHCVQKKKPISWRHCLGPS CDRDCTDTTHYCMFVKHLI'LCSLDRYKQRCCQSCQEG NOVI le, CG50513-04 SEQ ID NO:- 91 17260 bp DNA Sequence ORF Star: ATG at16ORF Stop: TAA at 5209 CGCACGAGGTGTTGACGGGCGGCTTCTGCCAACTTCTCCCCAGCGCGCGCCGAGCCCGCGCGGCCCCG GGGCTGCACGTCCCAGATACTTCTGCGGCGCAAGGCTACAACTGAGACCCGGAGGAGACTAGACCCCA TGGCTTCCTGGACGAGCCCCTGGTGGGTGCTGATAGGGATGGTCTTCATGCACTCTCCCCTCCCGCAG ACCACAGCTGAGAAATCTCCTGGAGCCTATTTCCTTCCCGAGTTTGCACTTTCTCCTCAGGGAAGTTT TCTGGAAGACACAACAGGGGAGCAGTTCCTCACTTATCGCTATGATGACCAGACCTCAAGAAACACTC GTTCAGATGAAGACAAAGATGGCAACTGGGATGCTTGGGGCGACTGGAGTGACTGCTCCCGGACCTGT GGGGGAGGAGCATCATATTCTCTGCGGAGATGTTTGACTGGAAGGAATTGTGAAGGGCAGAACATTCG GTACAAGACATGCAGCAATCATGACTGCCCTCCAGATGCAGAAGATTTCAGAGCCCAGCAGTGCTCAG CCTACAATGATGTCCAGTATCAGGGGCATTACTATGAATGGCTTCCACGATATAATGATCCTGCTGCC CCGTGTGCACTCAAGTGTCATGCACAAGGACAAAA.CTTGGTGGTGGAGCTGGCACCTAAGGTACTGGA TGGAACTCGTTGCAACACGGACTCCTTGGACATGTGTATCAGTGGCATCTGTCAGGCAGTGGGCTGCG ATCGGCAACTGGGAAGCAATGCCAAGGAGGACAACTGTGGAGTCTGTGCCGGCGATGGCTCCACCTGC AGGCTTGTACGGGGACAATCAAGTCACACGTTTCTCCTGAAAAAAGAGAAGAAAATGTAATTGCTGT TCCTTTGGGAAGTCGAAGTGTGAGAATTACAGTGAAAGGACCTGCCCACCTCTTTATTGAATCAAAAA CACTTCAAGGAAGCAAGGAGAACACAGCTTTAACAGCCCCGGCGTCTTTGTCGTAGAAAACACAACA GTGGAATTTCAGAGGGGCTCCGAGAGGCAAACTTTTAAGATTCCAGGACCTCTGATGGCTGATTTCAT CTTCAAGACCAGGTACACTGCAGCCAAAGACAGCGTGGTTCAGTTCTTCTTTTACCAGCCCATCAGTC ATCAGTGGAGACAAACTGACTTCTTTCCCTGCACTGTGACGTGTGGAGGAGGTTATCAGCTCAATTCT GCTGAATGTGTGGATATCCGCTTGAAGAGGGTAGTTCCTGACCATTATTGTCACTACTACCCTGAAA7 TGTAAACCAACCAAAACTGAAGGAATGCAGCATGGATCCCTGCCCATCAAGTGATGGATTTAAAG AGATAATGCCCTATGACCACTTCCAACCTCTTCCTCGCTGGGAACATAATCCTTGGACTGCATGTTCC GTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTGTGTGTGTAGAGGAATCCATGCATGGAGAGAT ATTGCAGGTGGAGAATGGAAGTGCATGTACGCACCCAAACCCAAGGT ATGCAAACTTGTAATCTGT TTGATTGCCCCAAGTGGATTGCCATGGAGTGGTCTCAGTGCACAGTGACTTGTGGCCGAGGGTTACGG TACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCATGTTGGGGGCTGCAATCCACAACTGAAGTT ACACATCAAAGAAGAATGTGTCATTCCCATCCCGTGTTATAAACCAAAAGAAAAAGTCCAGTGGAAG CAAAATTGCCTTGGCTGAAACAAGCACAAGAACTAGAAGAGACCAGAATAGCAACAGAAGAACCAALCG TTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTGTGGGCCGGGTGTGCAGGTCCGTGAGGTGAA GTGCCGTGTGCTCCTCACATTCACGCAGACTGAGACTGAGCTGCCCGAGGAAGAGTGTGAAGGCCCCA AGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGTGATGAGAGCCCGGCCTCCCGAGAGCTAGAC ATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTGGGAGTACGCTGGGTTCACCCCTTGCACAGC AACATGCGTGGGAGGCCATCAAGAAGCCATAGCAGTGTGCTTACATATCCAGACCCAGCADGACAGTCA ATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCCCTGT CCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGACCCG AGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAAAGCCCC ATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAOAATGGCAGCAGTGT TCCAGGACTTGTGGCGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATGGCAG CTTTTTGAATCTCTCAGATGAATTGTGCCAAGQACCCAAGGCATCGTCTCACAAGTCCTGTGCCAGGA CAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGGAATC CAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCAGCCA.AGGTCGGCGCATCCCCCTCAGTGAGATGAT GTGCAGGGATCTACCAGGGTTCCCTCTTGTAAGATCTTGCCAGATGCCTGAGTGCAGTAAAATCAAAT CAGAGATGAAGACAAALACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACATTCAG ACAGGGAGAGAGCGTATTACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCCAACACATCCGT GATTATTAAGTGCCCCGTGCGACGATTCCAGAAATCTCTGATCCAGTGGGAGAAGGATGGCCGTTGCC TGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAAATCCACGGTCTTGCTGCCCCC GACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAAC!AGTTGTGCTCAAGCTCATTGGTAC TGACAACCGGCTCATCGCACGCCCAGCCCTCAGGGAGCCTATGAGGGAATATCCTGGGATGGACCACA 179 WO 03/093432 PCT1US03113690 GCGAAGCCAATAGTTTGGGAGTCACATGGCACAAAATGAGGCAAATGTGGAATAACAAAAATGACCTT TATCTGGATGATGACCACATTAGTAACCAGCCTTTCTTGAGAGCTCTGTTAGGCCACTO3CAGCAATTC TGCAGGAAGCACCAACTCCTGGGAGTTGAAGAATAAGCAGTTTGAAGCAGCAGTTAAACAAGGAGCAT ATAGCATGGATACAGCCCAGTTTGATGAGCTGATAAGAAACATGAGTCAGCTCATGGAA-ACCGGAGAG GTCAGCGATGATCTTGCGTCCCAGCTGATATATCAGCTGGTGGCCGAATTAGCCAAGGCACAGCCAAC ACACATGCAGTGGCGGGGCATCCAGGAAGAGACACCTCCTGCTGCTCAGCTCAGAGGGGAAACAGGGA GTGTGTCCCAAAGCTCGCATGCAAAAAACTCAGGCAAGCTGACATTCAAGCCGAAAGGACCTGTTCTC ATGAOGCAAAGCCAACCTCCCTCAATTTCATTTAATAAAACAATAAATTCCAGGATTGGAAATACAGT ATACATTACA-AA7AAGGACAGAGGTCATCAATATACTGTGTGACCTTATTACCCCCAGTGAGGCCACAT ATACATGGACCAAGGATGGAACCTTGTTACAGCCCTCAGTAAA.ATAATTTTGGATGGAACTGGGAAG ATACAGATACAGAATCCTACAAGGAAAGAACAAGGCATATATGAATGTTCTGTAGCTAATCATCTTGG TTCAGATGTGGAAAGTTCTTCTGTGCTGTATGCAGAGGCACCTGTCATCTTGTCTGTTGAAAGAAATA TCACCAAACCAGAGCACAACCATCTGTCTGTTGTGGTTGGAGGCATCGTGGAGGCAGCCCTTGGAGCA AACGTGACAATCCGATGTCCTGTAAAAGGTGTCCCTCAGCCTAATATAACTTGGTTAAGAGAGGAGG ATCTCTGAGTGGCAATGTTTCCTTGCTTTTCAATGGATCCCTGTTGTTGCAGAATGTTTCCCTTGAAA ATGAAGGAACCTACGTCTGCATAGCCACCAATGCTCTTGGA-AAGGCAGTGGCAACATCTGTATTCCAC TTGCTGGAACGAAGATGGCCAGAGAGTAGAATCGTATTTCTGCAAGGACATAAAAAGTACATTCTCCA GGCACCAACACTAGAACCAACAGCAATGACCCAACAGGAGAACCCCCGCCTCAAGAGCCTTTTTGGG AGCCTGGTAACTGGTCACATTGTTCTGCCACCTGTGGTCATTTGGGAGCCCGCATTCAGAGACCCCAG TGTGTGATGGCCAATGGGCAGGAAGTGAGTGAGGCCCTGTGTGATCACCTCCAGAAGCCACTGGCTGG GTTTGAGCCCTGTAACATCCGGGACTGCCCAGCGAGGTGGTTCACAGTGTGTGGTCACAGTGCTCTG TGTCTTGCGGTGAAGGATACCACAGTCGGCAGGTGACGTGCAAGCGGACAAAAGCCAATGGAACTGTG CAGGTGGTGTCTCCAAGAGCATGTGCCCCTAAAGACCGGCCTCTGGGAAGAAAACCATGTTTTGGTCA TCCATGTGTTCAGTGGGAACCAGGGAACCGGTGTCCTGGACGTTGCATGGGCCGTGCTGTGAGGATGC AGCAGCGTCACACAGCTTGTCAACACAAQAGCTCTGACTCCAA-CTGTGATGACAGAAAGAGACCCACC TTAAGAAXGGAACTGCACATCAGGGGCCTGTGATGTGTGTTGGCACACAGGCCCTTGGAA-GCCCTGTAC AGCAGCCTGTGGCAGGGGTTTCCAGTCTCGGAAAGTCGACTGTATCCACACAAGGAGTTGCAAACCTG TGGCCAALGAGACACTGTGTACAGAAAAAGAAACCAATTTCCTGGCGGCACTGTCTTGGGCCCTCCTGT GATAGAGACTGCACAG-ACACAACTCACTACTGTATGTTTGTAAAACATCTTAATTTGTGTTCTCTAGA CCGCTACAAACAAAGGTGCTGCCAGTCATGTCAAGAGGGATAACCTTTGGAGGGGTCATGATGCTGC TGTGAAGATAAAAGTAGAATATAAA&AGCTCTTTTCCCCATGTCGCTGATTCAAAAACATGTATTTCTT AAAAGACTAGATTCTATGGATCAAACAGAGGTTGATGCA~AAACACCACTGTTAAGGTGTAAAGTGAA ATTTTCCAATGGTAGTTTTATATTCCAATTTTTTAAAATGATGTATTCAAGGATGAACAAAATACTAT AGCATGCATGCCACTGCACTTGGGACCTCATCATGTCAGTTGAXTCGAGAAATCACCAAGATTATGAG TGCATCCTCACGTGCTGCCTCTTTCCTGTGATATGTAGACTAGCACAGAGTGGTACATCCTAAAAACT TGGGAALACACAGCAACCCATGACTTCCTCTTCTCTCAAGTTGCAGGTTTTCAACAGTTTTATAALGGTA TTTGCATTTTAGAAGCTCTGGCCAGTAGTTGTTAAGATGTTGGCATTAATGGCATTTTCATAGATCCT TGGTTTAGTCTGTGAAAAAGAAACCATCTCTCTGGATAGGCTGTCACACTGACTGACCTAAGGGTTCA TGGAAGCATGGCATCTTGTCCTTGCTTTTAGAACACCCATGGAAGAAAACACAGAGTAGATATTGCTG TCATTTATACAACTACAGAAATTTATCTATGACCTAATGAGGCATCTCGGAAGTCAAAGAAGAGGGAA AGTTAACCTTTTCTACTGATTTCGTAGTATATTCAGAGCTTTCTTTTAAGAGCTGTGAATGAAACTTT TTCTAAGCACTATTCTATTGCACACAAACAGAAAACCAAAGCCTTATTAGACCTAATTTATGCATAAA GTAGTATTCCTGAGAACTTTATTTTGGAAAATTTATAAGAAAGTAATCCAAATAAGAAACACGATAGT TGAAAATAATTTTTATAGTAAATAATTGTTTTGGGCTGATTTTTCAGTAAATCCAAAGTGACTTAGGT TAGAAGTTACACTAAGGACCAGGGGTTGGAATCAGAATTTAGTTTAAGATTTGAGGAAAAGGGTAAGG GTTAGTTTCAGTTTTAGGATTAGAGCTAGAA.TTGGGTTAGGTGAGTAjAGAGTTAAGGTTAAGGCTA GAGTTGTCTTTA2AGGGTTAGGGTTAGGACCAGGTTAGGTCAGGGTTGGATTGGGTTTAGATTGGGGCC AGTGCTGGTGTTAGTGATAGTGTCAGGATGGAGGTTAGGTTTGGAGTAAGCGTTGTTGCTGAAGTGAG TTCAGGCTAGCATTAAATTGTAAGTTCTGAAGCTGATTTGGTTATGGGGTCTTTCCCCTGTATACTAC CAGTTGTGTCTTTAGATGGCACACAAGTCCAAATAAGTGGTCATACTTCTTTATTCAGGGTCTCAGCT GCCTGTACACCTGCTGCCTACATCTTCTTGGCAACAAAGTTACCTGCCACAGGCTCTGCTGAGCCTAG TTCCTGGTCAGTAATAACTGJACAGTGCATTTTGGCTTTGGATGTGTCTGTGGACAAGCTTGCTGAGT TTCTCTACCATATTCTGAGCACACGGTCTCTTTTGTTCTAACTTCAGCTTCACTGACACTGGGTTGAG CACTACTGTATGTGGAGGGTTTGGTGATTGGGAATGGATGGGGGACAGTGAGGAGGACACACCAGCCC ATTAGTTGTTAATCATCATCACATCTGATTGTTGAAGGTTATTAAATTA-ZiAAGAAAGATCATTTGTA ACATACTCTTTGTATATATTTATTATATGAAAGGTGCAATATTTTATTTTGTACAGTATGTAATAAAG ACATGGGACATATATTTTTCTTATTAACAAAATTTCATATTA-AATTGCTTCACTTTGTATTTAAAGTT AAAAGTTACTATTTTTCATTTGCTATTGTACTTTCATTGTTGTCATTCAATTGACATTCCTGTGTACT 180 WO 03/093432 PCT1US03113690 GATTTTACTACTGTTTTTATAACTGAGAGTTAATGTTTCTGTTTCATGATCCTTATGTATTCAGAJ NOVi le, CG50513-04 JSEQ ID NO:92 1691aa MWatl88743.8kD Protein Sequence [vASWTS PWWVLIGMVFMHS PLPQTTAEKSPGAYFLPEFALSPQGSFLEDTTGEQIJTYRYDDQTSRNT RSDEDKDGNWDAWGDWSDCSRTCGGASYSIRRCLTG3RNCEGQNIRYECTCSNHDCPPDAEDFRAQQCS AYNDVQYQGHYYEWLP2RYNDPAAPCALKCHAGQNLVVELAPKVLDGTRCNTDSLDMCISGICQAVGC DRQLGSNAKEDNCGVCAGDGSTCRLVRGQSIKSHvsPEKREENVIAVPLGSRSVRITVKGPAHLFIESK TLQGSKGEHSFNySPGVFVVENTTVEFQRGS ERQTFKIPGPLMADFI FKTRYTAAKDSWVQFFFYQPIS HQWRQTDFFPCTVTCGGGYQLrSAECVDaRLKRVVPDHYCHYYPENVKPKPKLKECSMDPCPSSDGFK EIMPYDHFQPLPRWEHNrPWTACSVSCGGGIQRRSFVCVEES{HGEILQVEEWKCMYAPKPKVMQTCL FDCPKWIAMEWSQCTVTCGRGLRYRLCIRGEHVGGCNPQLKLHIKEECVIPIPCYKPKKSPVE A2KLPWLKQAQELEETRIATEEPTIPEPWSACSTTCGPGVQVREVKCRVLLTFTQTETELPEEECEGP KLPTERPCLLEACDESr'ASRELDIPLPEDSETTYDWEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTV NDSLCDMVHRPASQACNTEPCPPRWHVGSWGPCSA TCGVGIQTRDVYCLHPGETPAPPEECRDEKP HALQACNQFDCPPGWHIEEWQQCSRTCGGGTQNRRVTCRQLLTDGS FLNLSDELCQGPKASSHKSCAR TDCPPHLAVGDWSKCSVSCGVGIQRRKQVCQRLAAKGRRI PLSEMMCRDLPGFPLVRSCQMPECSKIK SEMKTKLGEQGPQILSVQRVYIQTREEKRINIJTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRC LQNSKRLGITKSGSLKIHGLAAPDIGVYRC JAGSAQETVVLKLIGTDNRLIAPALREPMREYPGMDH SEASLGVTWHKRQMNNKNDLYLDDDHISNQPFLRALLGHCSNSAC2STNSWELKNIQFEAVKQGA YSMDTAQFDELIRMSQLMETGEVSDDLASQLIYQLVAELAKJAQPTHMQWRGIQEETPPAJAQLRGETG SVSQSSHAXNSGKLTFRPKGPVLMRQSQPPS ISFNKTINSRIGNTVYITKRTEVINILCDLITPSEAT YTWTKDGTLLQPSVIILDGTGKIQIQNPTRKEQGIYECSVAHLGSDVESSSVLYAEAPVILSVERN ITKPENHLSVVVGGIVEAALGANVTIRCPVKGVPQPNITWLKRGGSLSGNVSLLFNGSLLLQNVSLE NEGTYVCIATNALGKAVATSVFHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFW EPGNWSIICSATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPAWFTSVWSQCS VSCGEGYHSRQVTCKRTKANGTVQVVSPRCAPKDRPLGRKPCFGHPCVQWEPGNRCPGRCMGRAVRMV QQRH-TACQHNSSDSNCDDRKPPTLRRNCTSGACDVCWHTGPWKPCTAACGRGFQSRKVDCIHTRSCKP VAKRHCVQKKKPISWRIICLGPSCDRDCTDTTHiYCMFVKLNLSLDRYKQRCCQS CQEG NOVI If, CG50513-05 {SEQ ID NO: 93 16294 bp DNA Sequence lORF Start: ATG at 416 IORE Stop: TAA at 4259 TATGGCTTAAGCATCGG-AAATGTTTAGGCATAAG CATTTATTATAAGGGATATAAAAGAAATATAATCA ATACTTTTCTCCTTTGATTAATATACTGCTAGTTTAGTTTTCTACATTTTCATAGACTGGGGAAT TTGTGTCGTAGATATTCTTGACACTAGAGATGGTGGCTGATTTTTGGGAATGGTTGATACACT TGATATTTTTAGTTTCCAATTTGGAAGAGCTCTGTCTCTTGGGATGTCAAATATTATATTCGTCATT AATGAATGTGTTAATTTATTATAGATGATATTCTCACATGATTTCATTTGTAGTQATGGATTTAA AGAGATAATGCCCTATGACCACTTCCAACCTCTTCCTCGCTGGGAACATATCCTTGGACTGCATGTT CCGTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTTGTGTGTAGAGGAATCCATGCA'GGAGAG ATTGAGGAGAGAGGAGAGACAACA(GTTCACTTAC GTTTGATTGCCCCAAGTGGATTGCCATGGAGTGGTCTCAGTGCACAGTGACTTGTGGCCGAGGGTTAC GGTACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCATGTTGCGGGCTGCAATCCACAACTGAAG TTCCTAAAGAGGCTCCTCGGTTACAAGAa GCATG AGAATGCTGTAAAGAAGACAAGGCAATGACGAACA CGTTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTGTGGGCCGGGTGTGCAGGTCCGTGAGGTG AAGTGCCGTGTGCTCCTCACATTCACGCAGACTGAGACTGAGCTGCCCGAGGAAGAGTGTGAAGGCCC CAAGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGTGATGAGAGCCCGGCCTCCCGAGAGCTAG' ACATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTGGGAGTACCCTGGGTTCACCCCTTGCACA GCAALCATGCGTGGGAGGCCATCAAGAALGCCATAGCAGTGTGCTTACATATCCAGACCCAGCAGAC'AGT CAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCCCT GTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGACC CGAGATGTGTACTGCCTGCACCCAGGGAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAACC CCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCTGGCTGGCACATTGAAGAATGGCAGCAGT GTTCCAGcGACTTGTGGCGGGGGAACTCAGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATGGC AGCTTTTTGAATCTCTCAGATGAATTGTGCCAAGGACCCAAGGCATCGTCTCACAAGTCCTGTGCCAG GACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGGAA 181 WO 03/093432 PCT1US03113690 TCAAAGAGAGGGCAAGTGACAAGCGGACCCCGGGT ATGTGCAGGGATCTACCAGGGCTCCCTCTTGTAAGATTTGCCAGATGCCTGAGTGCAGTAAATCAA ATCAGAGATGAAGACAAAACTTGGTGAGCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACATTC AGACAAGGGAAGAGAAGCGTATTAACCTGACCATTGGTAGCAGAGCCTATTTGCTGCCCAACACATCC GTGATTATTAAGTGCCCAGTGCGACGATTCCAGAAATCTCTGATCCAGTGGAG7AGGATOGCCGTTG CCTGCAGAACTCCAAACGGCTTGGCATCACCAAGTCAGGCTCACTAAAJATCCACGGTCTTGCTGCCC CCGACATCGGCGTGTACCGGTGCATTGCAGGCTCTGCACAGGAAACAGTTGTGCTCAAGCTCATTGGT .ACTGACAACCGGCTCATCGCACGCCCAGCCCTCAGGGAGCCTATGAGGGAATATCCTGGGATGGACCA CACAGCAATTGATAAGCCAAGGCATTGAACA-AGC TTTATCTGGATGATGACCACATTAGTAACCAGCCTTTCTTGAGAGCTCTGTTAGGCCACT(3CAGCAAT TCTGCAGGAAGCACCAACTCCTGGGAGTTGAAGAATAAGCAGTTTGAACAGCAGTTAAAJAGAGC ATTGAGAAACCGTGTACGAAGACTATACCTGACGA AGGTCAGCGATGATCTTGCGTCCCAGCTGATATATCAGCTGGTGGCCOAATTAGCCAAGGCACAGCCA ACACACATGCAGTGGCGGGGCATCCAGGAAGAGACACCTCCTGCTGCTCAGCTCAGAGGGAACAG GAGTGTCCCAAAGCTCGCATGCAAAAAACTCAGGCAAGTGACATTCAGCCGAGGACCTGTTC TCATGAGGCAAAGCCAACCTCCCTCATTTCATTTAATAACAATAATTCCAGGATrGAATAcA GTATACATTACA74AAAGGACAGAGGTCATCIATATACTGTGTGACCTTATTACCCCCAGTGAGGCCAC ATATACATGGACCAAGGATGGAACCTTGTTACAGCCCTCAGTAATAATTTTGGATGGACTGGGA AGATACAGATACAGAATCCTACAAGGAGACAAGGCATATATGAJATGTTCTGTAGCTAATCATCTT GGTTCAGATGTGGAAAGTTCTTCTGTGCT GTATGCAGAGGCACCTGTCATCTTGTCTGTTGJAGA TATCACCAAACCAGAGCACAACCATCTGTCTGTTGTGGTTGGAGGCATCJTGGAGGCAGCCCTTGGAG CAAACGTGACAATCCGATGTCCTGTAAAAGGTGTCCCTCAGCCTAATATACTTGGTTGAGAGAGGA GGATCTCTGAGTGGCAATGTTTCCTTGCTTTTCAATGGATCCCTGTTGTTGCAGAATGTTTCCCTTGA .AATGAAGGAACCTACGTCTGCATAGCCACCAATGCTCTTGGAGGCAGTGGCAACATCTGTACTCC ACTTGCTGGAACGAAGATGGCCAGAGAGTAGAATCGTATTTCTGCA-7GGACATAAAAGTACATTCTC CAGGCA.CCACACTAGAACCACAGCAATGACCCACAGGAGAACCCCCGCCTCAAGAGCCTTTTTG GGAGCCTGGTAACTGGTCACATTGTTCTGCCACCTGTGGTCATTTGGGAGCCCGCATTCAGAGACCCC AGTGTGTGATGGCCATGGGCAGGAAGTGATGAGGCCCTGTGTGATCACCTCCAGAAGCCACTGGCT GGGTTTGAGCCCTGTAACATCCGGGACTGCCCAGCGAGGTGGTTCACAAGTGTGTGGTCACAGTGCTC TGGCTCGGAGTCAATGCGGGCTCACGCAACATGAT TGCAGGTGGTGTCTCCAAGAGCATGTGCCCCTAAGACCGGCCTCTGGGAGA XJCCATGTTTTGGT CATCCATGTGTTCAGTGGGAACCAGGGAACCGGTGTCCTGGACGTTGCATGGGCCGTGCTGTGAGGAT GCAGCAGCGTCACACAGCTTGTCAACACAACAGCTCTGACTCCACTGTGATGACAGAGAGACCCA CCTTA GAAGGAACTGCACATCAGGGGCCTGTGATGTGTGTTGGCACACAGGCCCTTGGAAGCCCTGT ACAGCAGCCTGTGGCAGGTTTCCATCTCGCAGTCGACTGTATCCACACAGGAGTTGCAACC TGTGGCCAAGAGACACTGTGTACAGAAkAAAGAAACCAATTTCCTGGCGGCACTGTCTTGGGCCCTCCT GTGATAGAGACTGCACAGACACACTCACTACTGTATGTTTGTAJA3ACATCTTATTTGTGTTCTCTA GACCAAAAAGGTCATAGCAGGGTACTTGGGTAGTC GCTGTGAAGATAAAAGTAGAATATAAAAGCTCTTTTCCCCATGTCGCTGATTCAAAAACATGTATTTC TTAAAAGACTAGATTCTATGGATCAAACAGAGGTTGATGCAAAAACACCACTGTTAAGGTGTAGTG AGTGCATCCTCACGTGCTGCCTCTTTCCTGTGATATGTAGACTAGCACAGAGTGGTACATCCTAAAAA CTTGGGAAACACAGCAACCCATGACTTCCTCTTCTCTCAAGTTGCAGGTTTTCAACAGTTTTATAAGG TATTTGCATTTTAGAAGCTCTGGCCAGTAGTTGTTAAGATGTTGGCATTAATGGCATTTTCATAGATC CTTGGTTTAGTCTGTGAAJAGAAACCATCTCTCTGGATAGGCTGTCACACTGACTGACCTAAGGGTT CATGGAAGCATGQCATCTTGTCCTTGCTTTTAGAACACCCATGGAGAAAACACAGAGTAGATATTGC TGTCATTTATACAACTACAGAATTTATCTATGACCTAATGAGGCATCTCGGAAGTCAAAGAAGAGGG AAAGTTAACCTTTTCTACTGATTTCGTAGTATATTCAGAGCTTTCTTTTAGAGCTGTGAATGAAACT TTTTCTAAOCACTATTCTATTGCACACAAACAGAAACCAAGCCTTATTAGACCTAATTTATGCATA AATGATCGGATTTTGAATTAAGAGATCATAAAAGT GTTG-AAATAATTTTTATGTAAATAATTGTTTTGGGCTGATTTTTCAGTAAATCCAAAGTGACTTAG GTTAGAAGTTACACTAAGGACCAGGGGTTGGAATCAGAATTTAGTTTAAGATTTGAGGAJAAGGGTA GGGTTAGTTTCAGTTTTAGGATTAGAGCTAGAATTGGGTTAGGTAGAAAGAAAGTTAAGGTTAAGGC TAGAGTTGTCTTTAAGGGTTAGGGTTAGGACCAGGTTAGGTCAGGGTTGGATTGGGTTTAGATTGGGG CCAGTGCTGGTGTTAGTGATAGTGTCAGGATGGAGGTTACGTTTGGACTAAGCGTTGTTGCTGAAGTG AGTTCAGGCTAGCATTAAATTGTAAGTTCTGAAGCTGATTTGGTTATGGGGTCTTTCCCCTGTATACT ACCATT GTGTCTTTAGATGGCACACAAGTCCAAATAAGTGGTCATACTTCTTTATTCAGGGTCTCAG 182 WO 03/093432 PCT1US03113690 CTGCCTGTACACCTGCTGCCTACATCTTCTTGGCAACAAAGTTACCTGCCACAGGCTCTGCTGAGC AGTTCCTGGTCAGTAATAACTGAACAGTGCATTTTGGCTTTGGATGTGTCTGTGGACAAGCTTGCTGA GTTTCTCTACCATATTCTGAGCACACGGTCTCTTTTGTTCTAATTTCAGCTTCACTGACACTGGGTTG AGCACTACTGTATGTGGAGGGTTTGGTGATTGGGATGGATGGGGGACAGTGAGGAGGACACACCAGC CCATTAGTTGTTAATCATCAATCACATCTGATTGTTGAAGGTTATTAATTAAAAGAAAGATCATTTG TACATACTCTTTGTATATATTTATTATATGAGGTGCATATTTTATTTTGTACAGTATGTATJA AGACATGGGACATATATTTTTCTTATTAACAAATTTCATATTAAATTGCTTCACTTTGTATTTAAAG TTAAAAGTTACTATTTTTCATTTGCTATTGTACTTTCATTGTTGTCATTCATTGACTTCCTGTGTA CTGTATTTTACTACTGTTTTTATA2ACATGAGAGTTAATGTTTCTGTTTCATGATCCTTATGTAATTCA GAAATAAATTTACTTTGATTATTCAGTGGCATCCTTAT fNOVIIf, CG50513-05 ISEQ ID NO: 941281 aa MWat 142791.9kD jProtein Sequence MPYDHBFQPLPRWEHPTACSVSCGGGIQRRSFVCVEESMGEILQVEEWRCMYAPKPKVMQTCNLFD CPKWIAMEWSQCTVTCGRGLRYRVLCINHRGEHVGGCNPQLKLHIIEECVIPIPCYKPKEKSPVIEJK LPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQTETELPEEECEGPKI. PTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATVGGHQEAIAVCLHIQTQQTVND SLCDMVHRPPAMSQACNTEPCPPRWHVGSWGPCSATCGVGIQTRDVYCLHPGETPAPPEECRDEKPA LQACNQFDCPPGWHIEEWQQCSRTCGGGTQVTCRQLLTDGSFLNLSDLCQGPASSKSATD CPPHLAVGDWSKCSVSCGVGIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGLPLVRSCQMPECSKIKSE MKTKLGEQGPQILSVQRVYIQTREEKRINjLTIGSRAYLLPNTSVI IKCPVRRFQKSLIQWEKDGRCLQ NSRGTSSKHLADGYCASQEVLLGDRIRARPRYGDS ANSLGVTWHKMRQMWNDLYLDDDHISNQPLRALLGHCSNSAGSTNSELJKQFEAAVKQGAYS MDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQWRGIQEETPPAAQLRGETGSV SQSSHAKNSGKLTFKPKGPVLMRQSQPPS ISFNKTINSRIGNTVYITKRTEVINILCDLITPSE-ATYT WTKDGTLLJQPSVKI ILDGTGKIQIQNPTRKEQGIYECSVANELGSDVESS SVLYAEAPVILSVENIT KPELSVVGGIVEAAGANVTIRCPVKGVPQPNITWLKRGGSJSGNVSLLFNGSLLLQNVSLENE GTYVCIATNALGKAVATSVLHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFWEP GNWSHCSATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNRDCPARWFTSVqSQCSVS CGEGYHSRQVTCKRTKANGTVQVSPRACAPKDRPLGRKPCFGHPCVQWEGNRCPGRCMG.AVRM1QQ RHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGPWKPCTAACGRGFQSRKVDCIHTRSCKPVA KRHCVQKKKPISWRHCLGPSCDRDCTDTTHYCMFVKHLNLCSLDRYKQRCCQSCQEG NOVI Ig, CG50513-06 ISQID NO: 95 2912 bp DNA SequenceJORF Start: ATO t98jR Stop: TAA at 28 76 CAGCTTTAACAGCCCCGGCGTCTTTGTCGTAGAAACACAA.CAGTGGATTTTAGAGGGGCTCCGAGA GGCAAACTTTTAAGATTCCAGGCCCTTTGATGGCTGATTTCATCTTCAAGACCAGGTACACTGCAGCC AAAGACAGCGTGGTTCAGTTCTTCTTTTACCAGCCCATCAGTCATCAGTGGAGACAAACTGACTTCTT TCCCTGCACTGTGACGTGTGGAGGAGGTTATCAGCTCAATTCTGCTGATGTGTGGATATCCGCTTGA AGGGATCTACTATTATCACTAATTAACAACAkCGA GAATGCAGCATGGATCCCTGCCCATCAAGTGATGGATTTA.GAGATAATGCCCTATGACCACTTCCA ACCTCTTCCTCGCTGGGAACTATCCTTGGACTGCATGTTCCGTGTCCTGTGGAGGAGGGATTCAGA GACGGAGCTTTGTGTGTGTAGAGGAATCCATGCATGGAGAGATATTGCAGGTGGAGATGGA.JGTGC ATGTACGCACCCAAACCCAAGGTTATGCAAACTTGTAATCTGTTTGATTGCCCCAAGTGGATTGCCAT GGAGTGGTCTCAGTGCACAGTGACTTGTGGCCGAGGGTTACGGTACCGGGTTGTTCTGTGTATTACC ACCGCGGAGAGCATGTTGGGGGCTGCAATCr-CAACTGAAGTTACACATCAGX2GAATGTGTCATT CCCATCCCGTGTTATAAACCAAAAGAAAAAGTCCAGTGGAAGCAAATTGCCTTGGCTGAACAGC ACAAGAACTAGAAGAGACCAGAATAGCAACAGA7AGAACCAAQCGTTCATTCCAGAAC!CCTGGTCAGCCT GCAGTACCACGTGTGGGCCGGGTGTGCAGGTCCGTGAGGTGAAGTGCCGTGTGCTCCTCACATTCACG CAGACTGAGACTGAGCTGCCCGAGGAAGAGTGTGAAGGCCCCAAGCTGCCCACCGAACGGCCCTGCCT CCTGGAAGCATGTGATQAGAGCCCGGCCTCCCGAGAGCTAGACATCCCTCTCCCTGAGGACAGTGAGA CGACTTACGACTGGGAGTACGCTGGGTTCACCCCTTGCACAGCACATGCGTGGGAGGCCATCAG GCCATAGCAGTGTGCTTACATATCCAGACCCAGCAGACAGTCAATGACAGCTTGTGTGATATGGTCCA CCGTCCTCCAGCCATGAGCCAGGCCTGTAACACAGAGCCCTGTCCCCCCAGGTGGCATGTGGGCTCTT GGGGGCCCTGCTCAGCTACCTGTGGAGTTGGAATTCAGACCCGAGATGTGTACTGCCTGCACCCAGGG CAGACCCCTGCCCCTCCTGAGGAGTGCCGAGATGAAAAGCCCCATGCTTTACAAGCATGCAATCAGTT TGACTGCCCTCCTGGCTGGCACATTGAAGAATGGCAGCAGTGTTCCAGGACTTGTGGCGGGGGAC TC AGAACAGAAGAGTCACCTGTCGGCAGCTGCTAACGGATGGCAGCTTTTTGAATCTCTCAGATGAATTG 183 WO 03/093432 PCT1US03113690 TGCCAAOGACCCAAGGCATCGTCTCACAAGTCCTGTGCCAGGACAGACTGTCCTCCAOATTTAGCTGT GGGAGACTGGTCGAAGTGTTCTGTCAGTTGTGGTGTTGGAATCCAGAGAAGAAAGCAGGTGTGTCAAA GGCTGGCAGCCAAAGGTCGGCGCATCCCCCTCAGTGAGATGATGTGCAGGGATCTACCAGGGTTCCCT CTTGTAAGATCTTGCCAGATGCCTGAGTGCAGTAAAATCAAATCAGAGATGAAGACAAAACTTGGTGA GCAGGGTCCGCAGATCCTCAGTGTCCAGAGAGTCTACATTCAGACAAGGGAAGAGAAGCGTATTA.ACC TGACCATTGTAGCAGAGCCTATTTGCTGCCCAACACATCCGTGATTATTAAGTGCCCAGTGCGACGA TTCCAGAAATCTCTGATCCAGTGGGAGAAGGATGGCCGTTOCCTGCAGAACTCCAAACGGCTTGGCAT CACCAAGTCAGGCTCACTAI4AAATCCACGGTCTTGCTGCCCCCGACATCGGCGTGTACCGGTGCATTG CAGGCTCTGCACAGGAAACAGTTGTGCTCAAGCTCATTGGTACTGACAACCGGCTCATCGCACGCCCA GCCCTCAGGGAGCCTATGAGGGAATATCCTGGGATGGACCACAGCGAAGCCAATAGTTTGGGAGTCAC ATGGCACAAAATGAGGCAAATGTGGAATAACAAAAATGACCTTTATCTGGATGATGACCACATTAGTA ACCAGCCTTTCTTGAC3AGCTCTGTTAGGCCACTCAGCAATTCTGCAGGAAGCACCAACTCCTGGGAG TTGAAGAATAAGCAGTTTGAAGCAGCAGTTAAACAAGGAGCATATAGCATGGATACAGCCCAGTTTGA TGAGCTGATAAGAAACATGAGTCAGCTCATGGAAACCGGAGAGGTCAGCGATGATCTTGCGTCCCAGC TGATATATCAGCTGGTGGCCGAATTAGCCAAGGCACAGCCAACACACATGCAGTGGCGGGGCATCCAG GAAGAGACACCTCCTGCTGCTCAGCTCAGAGGGGAAACAGGGAGTGTGTCCCAAAGCTCGCATGCAAA AAACTCAGGCAAGCTGACATTCAAGCCGAAAGGACCTGTTCTCATGAGGCAAAGCCAACCTCCCTCAA TTTCATTTAATAAAACAATAAATTCCAGGATTGgAAATACAGTATACATTACAAAAAGGACAGACGTC ATCAATATACTGTGTGACCTTATTACCCCCAGTGAGGCCACATATACATGGACCAAGGATGGAACCTT GTTACAGCCCTCAGTAAAGTAAGTAAAATAAAA.ATGCAGTATTCATTTTTGCAAAA NOVI11g, CG50513-06 jSEQ IDN:69 . ~ MWat1O4I17.1kD Protein Sequence N:696a~ MADFIFKTRYTAAKDSVVQFFFYQP ISHQWRQTDFFPCTVTCGGGYQLNSAECVDIRLCR;VPDYCH YYPEN~VIPKPKLKECSMPCPSSDGFKcEIMPYDHFQPLPRWEHNPWTACSVSCGGGIQRRSFVCVEES MHGEILQVEEWKCMYAPKPKVMQTCNLFDCPKWIAMEWSQCTVTCGRGLRYRVVLCINHRGEHVGGCN PQLKIJHIKEECVIPIPCYKPKEKSPVEACLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQ VREVKCRVLLTFTQTETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSTTYDWEYAGF TPCTATCVGGHQEAIAVCLHIQTQQTVNlSLCDMVHRPPAMSQACNIEPCPPRWHVGSWGPCSATCGV GIQTRDWCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQNRRVTCRQL

I

4 TDGS FLNLSDELCQGPKAS SHKSCARTDCPPHLAVGDWSKCSVSCGVGIQRRKQVCQRLAAKGRRIP ILSEMrCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ ILSVQRVYIQTREEKRINLTIGSRAYLL PNTSVI IKCPVRRFQKSLIQWEKDGRCLQNSKRLGITICSGSLKIHGLAAPDIGVYRCIAGSAQETVVL Y\ITNLAPLEMEPMRENLVWKRMNKDYDDINPLAL HCSNSAOSTNSWELKKQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELA KAQPTHMQWRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPS ISFNKTINSR IGNTVYITKRTEVINILCDLITPSEATYTWTKDGTLLQPSVK NOVI Ih, CG50513-07 {SEQ ID NO: 97 1377 bp DNA Sequence .- RF Start: at 1 IORF Stop:_end of sequence TGGGAACATAAT -CCTTGGACTGCATGTTCCGTGTCCTGTGGAGGAGGGATTCAGAGACGGAGCTTTGT GTGTGTAGAGGAATCCATGCATGGAGAGATATTGCAGGTGGAAGAATGGAAGTGCATGTACGCACCCA AACCCAAGGTTATGCAAACTTGTAATCTGTTTGATTGCCCCAGTGGATTGCCATGGAGTGGTCTCAG TGCACAOTGACTTGTGGCCGAGGGTTACGGTACCGGGTTGTTCTGTGTATTAACCACCGCGGAGAGCA TGTTGGGGGCTGCAATCCACAACTGAAGTTACACATCAAAGAAGAATGTGTCATTCCCATCCCGTGTT ATAAACCAAAAGAAAAAAGTCCAGTGGAAGCAAAATTGCCTTGGCTGA-AACAAGCACAAGAACTAGAA GAGACCAGAATAGCAACAGAAGAACCAACGTTCATTCCAGAACCCTGGTCAGCCTGCAGTACCACGTG TGGGCCGGGTGTGCAGGTCCGTGAGGTGAAGTGCCGTGTGCTCCTCACATTCACGCAGACCGAGACTG AGCTGCCCGACGAAGAGTGTGAALGGCCCCAAGCTGCCCACCGAACGGCCCTGCCTCCTGGAAGCATGT GATGAGAGCCCGGCCTCCCGAGAGCTAGACATCCCTCTCCCTGAGGACAGTGAGACGACTTACGACTG GGAGTACGCTGGGTTCACCCCTTGCACAGCAACATGCQTGGGAGGCCATCAAGAAGCCATAGCAGTGT GCTTACATATCCAGACCCAGCAGACAGTCAATGACAGCTTGTGTGATATGGTCCACCGTCCTCCAGCC ATGAGCCAGGCCTGTAACACAGAGCCCTGTCCCCCCAGGTGGCATGTGGGCTCTTGGGGGCCCTGCTC AGCTACCTGTGGAGTTGGAATTCAGACCCGAGATGTGTACTGCCTGCACCCAGGGGAGACCCCTGCCC CTCCTGAGGAGTGCCGAGATGAAAAGCCCCATGCTTTACAAGCATGCAATCAGTTTGACTGCCCTCCT GGCTGGCACATTGAAGAATGGCAGCAGTGTTCCAGGACTTGTGGCGGGGGAACTCAG.ACAGAAGAGT CACCTGTCGGCAGCTGCTAACGGATGGCAGCTTTTTGAATCTCTC!AGATGAATTGTGCCAAGGACCCA AGGCATCGTCTCACAAGTCCTGTGCCAGGACAGACTGTCCTCCACATTTAGCTGTGGGAGACTGGTCG 184 WO 03/093432 PCT/USO3/13690 a-GGTTCGTCAGTTGTGGTGTTGGAATCCAGAGAAGAAAGCAGGTGTGTCAAAGGCTGGCACA AGGTCGGCGCATCTCCCTCAGTGAGATGATGTGCAGGGATCTACCAGGGCTCCCTCTTGTAAGATCTT GCCAGATGCCTGACTGC NOVI h, CG50513-07 SEQ ID NO: 98 459 aa (MW at 51217.0kD Protein Sequence WEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTONLFDCPKWIAMEWSQ CTVTCGRGLRYRVVLCINHRGEHVGGCNPQLLHIREECVIPIPCYKPKEKSPVEAKLPWLKQAQELE ETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQTETELPEEECEGPKLPTERPCLLEAC DESPASRELDIPLPEDSETTYDWEYAGFTPCTATCVGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPA MSQACNTEPCPPRWHVGSWGPCSATCGVGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPP GWHIEEWQQCSRTCGGGTQNRRVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPLAVGDWS KCSVSCGVGIQRRKQVCQRLAAKGRRISLSEMMCRDLPGLPLVRSCQMPEC NOVI Ii, 13376798 SNP for SEQ ID NO: 1598 bp SNP: position 58, T/A CG50513-01 99 DNA Sequence ORF Start: at ORF Stop: TGA at 1354 1 AAACAGCCACTTGTTTCATCCCACCTGGGCATTAGGTTGACTTCAAAGATGCCTCAGATACTGCAAAAC ATTAATGGGATCATCGAGGCCTTCAGGCGCTATGCAAGGACGGAGGGCAACTGCACAGCGCTCACCCGA GGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATTGTGAAACCCCACGATCCAGCAACT GTGGATGAGGTCCTGCGTCTGCTGGATGAAGACCACACAGGGACTGTGGAATTCAAGGAATTCCTGGTC TTAGTGTTTAAAGTTGCCCAGGCCTGTTTCAAGACACTGAGCGAGAGTGCTGAGGGAGCCTGCGGCTCT CAAGAGTCTGGAAGCCTCCACTCTGGGGCCTCGCAGGAGCTGGGCGAAGGACAGAGAAGTGGCACTGAA GTGGGAAGGGCGGGGAAAGGGCAGCATTATGAGGGGAGCAGCCACAGACAGAGCCAGCAGGGTTCCAGA GGGCAGAACAGGCCTGGGGTTCAGACCCAGGGTCAGGCCACTGGCTCTGCGTGGGTCAGCAGCTATGAC AGGCAAGCTGAGTCCCAGAGCCAGGAAAGAATAAGCCCGCAGATACAACTCTCTGGGCAGACAGAGCAG ACCCAGAAAGCTGGAGAAGGCAAGAGGAATCAGACAACAGAGATGAGGCCAGAGAGACAGCCACAGACC AGGGAACAGGACAGAGCCCACCAGACAGGTGAGACTGTGACTGGATCTGGAACTCAGACCCAGGCAGGT GCCACCCAGACTGTGGAGCAGGACAGCAGCCACCAGACAGGAAGCACCAGCACCCAGACACAGGAGTCC ACCAATGGCCAGAACAGAGGGACTGAGATCCACGGTCAAGGCAGGAGCCAGACCAGCCAGGCTGTGACA GGAGGACACACTCAGATACAGGCAGGGTCACACACCGAGACTGTGGAGCAGGACAGAAGCCAAACTGTA AGCCACGGAGOGGCTAGAGAACAGGGACAGACCCAGACGCAGCCAGGCAGTGGTCAAAGATGGATGCAA GTGAGCAACCCTGAGGCAGGAGAGACAGTACCGGGAGGACAGGCCCAGACTGGGGCAAGCACTGAGTCA GGAAGGCAGGAGTGGAGCAGCACTCACCCAAGGCGCTGTGTGACAGAAGGGCAGGGAGACAGACAGCCC ACAGTGGTTGGTGAGGAATGGGTTGATGACCACTCAAGGGAGACAGTGATCCTCAGGCTGGACCAGGGC AACTTGCATACCAGTGTTTCCTCAGCACAGGGCCAGGATGCAGCCCAGTCAGAAGAGAAGCGAGGCATC ACAGCTAGAGAGCTGTATTCCTACTTGAGAAGCACCAAGCCATGACTTCCCCGACTCCAATGTCCAGTA CTGGAAGAAGACAGCTGGAGAGAGTTTGGCTTGTCCTGCATGGCCAATCCAGTGGGTGCATCCCTGGAC ATCAGCTCTTCATTATGCAGCTTCCCTTTTAGGTCTTTCTCAATGAGATAATTTCTGQAAGGAGCTTTC TATCCTGAACTCTTCTTTCTTACCTGCTTTGCGGTGCAGACCCTCTCAGGAGCAGGAAGACTCAGAACA AGTCACCCCTT NOV1Ii, 13376798 SNP for SEQ ID NO: 451 aa SNP: Leu to Ile at CG50513-01 100 position 20 Protein Sequence KQPLVSSHLGIRLTSKMPQILQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKPHDPAT VDEVLRLLDEDHTGTVEFKEFLVLVFKVAQACFKTLSESAEGACGSQESGSLHSGASQELGEGQRSGTE VGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQTQGQATGSAWVSSYDRQAESQSQERISPQIQLSGQTEQ TQKAGEGKRNQTTEMRPERQPQTREQDRAKQTGETVTGSGTQTQAGATQTVEQDSSHQTGSTSTQTQES TNGQNRGTEIHGQGRSQTSQAVTGGHTQIQAGSKTETVEQDRSQTVSHGGAREQGQTQTQPGSGQRWMQ VSNPEAGETVPGGQAQTGASTESGRQEWSSTRPRRCVTEGQGDRQPTVVGEEWVDDHSRETVILRLDQG NLHTSVSSAQGQDAAQSEEKRGITARELYSYLRSTKP . .fP ~ . .. .. .... NOVll1j, 13 376799 SNP for SEQ ID NO: 1598 bp, SNP: T/C at position CG50513-01 101 1516 DNA Sequence Start: atf 1 RF Stop: TGA at 1354 AAACAGCCACTTGTTTCATCCCACCTGGGCATTAGGTTGACTTCAAAGATGCCTCAGTTACTGCAAAAC 185 WO 03/093432 PCT/US03/13690 ATTAATGGGATCATCGAGGCCTTCAGGCGCTATGCAAGGACGGAGGGCAACTGCACAGCGCTCACCCGA GGGGAGCTGAAAAGACTCTTGGAGCAAGAGTTTGCCGATGTGATTGTGAAACCCCACGATCCAGCAACT GTGGATGAGGTCCTGCGTCTGCTGGATGAAGACCACACAGGGACTGTGGAATTCAAGGAATTCCTGGTC TTAGTGTTTAAAGTTGCCCAGGCCTGTTTCAAGACACTGAGCGAGAGTGCTGAGGGAGCCTGCGGCTCT CAAGAGTCTGGAAGCCTCCACTCTGGGGCCTCGCAGGAGCTGGGCGAAGGACAGAGAAGTGGCACTGAA GTGGGAAGGGCGGGGAAAGGGCAGCATTATGAGGGGAGCAGCCACAGACAGAGCCAGCAGGGTTCCAGA GGGCAGAACAGGCCTGGGGTTCAGACCCAGGGTCAGGCCACTGGCTCTGCGTGGGTCAGCAGCTATGAC AGGCAAGCTGAGTCCCAGAGCCAGGAAAGAATAAGCCCGCAGATACAACTCTCTGGGCAGACAGAGCAG ACCCAGAAAGCTGGAGAAGGCAAGAGGAATCAGACAACAGAGATGAGGCCAGAGAGACAGCCACAGACC AGGGAACAGGACAGAGCCCACCAGACAGGTGAGACTGTGACTGGATCTGGAACTCAGACCCAGGCAGGT GCCACCCAGACTGTGGAGCAGGACAGCAGCCACCAGACAGGAAGCACCAGCACCCAGACACAGGAGTCC ACCAATGGCCAGAACAGAGGGACTGAGATCCACGGTCAAGGCAGGAGCCAGACCAGCCAGGCTGTGACA GGAGGACACACTCAGATACAGGCAGGGTCACACACCGAGACTGTGGAGCAGGACAGAAGCCAAACTGTA AGCCACGGAGGGGCTAGAGAACAGGGACAGACCCAGACGCAGCCAGGCAGTGGTCAAAGATGGATGCAA GTGAGCAACCCTGAGGCAGGAGAGACAGTACCGGGAGGACAGGCCCAGACTGGGGCAAGCACTGAGTCA GGAAGGCAGGAGTGGAGCAGCACTCACCCAAGGCGCTGTGTGACAGAAGGGCAGGGAGACAGACAGCCC ACAGTGGTTGGTGAGGAATGGGTTGATGACCACTCAAGGGAGACAGTGATCCTCAGGCTGGACCAGGGC AACTTGCATACCAGTGTTTCCTCAGCACAGGGCCAGGATGCAGCCCAGTCAGAAGAGAAGCGAGGCATC ACAGCTAGAGAGCTGTATTCCTACTTGAGAAGCACCAAGCCATGACTTCCCCGACTCCAATGTCCAGTA CTGGAAGAAGACAGCTGGAGAGAGTTTGGCTTGTCCTGCATGGCCAATCCAGTGGGTGCATCCCTGGAC ATCAGCTCTTCATTATGCAGCTTCCCTTTTAGGTCTTTCTCAATGAGATAATTTCTGCAAGGAGCTCTC TATCCTGAACTCTTCTTTCTTACCTGCTTTGCGGTGCAGACCCTCTCAGGAGCAGGAAGACTCAGAACA AGTCACCCCTT NOVI j, 13376799 SNP for SEQ ID NO: 102 451 aa SNP: not in coding region CG50513-01 Protein Sequence KQPLVSSHLGIRLTS PQLLQNINGIIEAFRRYARTEGNCTALTRGELKRLLEQEFADVIVKPHDPAT VDEVLRLLDEDHTGTVEFKEFLVLVFKVAQACFKTLSESAEGACGSQESGSLHSGASQELGEGQRSGTE VGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQTQGQATGSAWVSSYDRQAESQSQERISPQIQLSGQTEQ TQKAGEGKRNQTTEMRPERQPQTREQDRAHQTGETVTGSGTQTQAGATQTVEQDSSHQTGSTSTQTQES TNGQNRGTEIHGQGRSQTSQAVTGGHTQIQAGSHTETVEQDRSQTVSHGGAREQGQTQTQPGSGQRWMQ VSNPEAGETVPGGQAQTGASTESGRQEWSSTHPRRCVTEGQGDRQPTVVGEEWVDDHSRETVILRLDQG NLHTSVSSAQGQDAAQSEEKRGITARELYSYLRSTKP A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 1 lB. Table 11B. Comparison of the NOV11 protein sequences. NOV11a -------------- NOV11b -------------- NOV11c ------------ NOVIld ------- - ------- NOVile MASWTSPWWVLIGMVFMHSPLPQTTAEKSPGAYFLPEFA.LSPQGSFLEDTTGEQFLTYRY NOV11f ------------

---

NOV11g ------------- NOV11h ------------

---

NOV11a ------------

---

NOV11b ------------

--

NOV11c ---------- NOV11d ------------------- NOV11e DDQTSRNTRSDEDKDGNWDAWGDWSDCSRTCGGGASYSLRRCLTGRNCEGQNIRYKTCSN NOV11f -------- - -- NOV11g - ---------- 186 WO 03/093432 PCT/US03/13690 NOV11h --------------------------- NOV11a ----------------------- NOV11b ----------------------- NOV11c ----------------------- NOVIld ----------------------- NOV11e HDCPPDAEDFRAQQCSAYNDVQYQGHYYEWLPRYNDPAAPCALKCHAQGQNLVVELAPKV NOV11f ----------------------- NOV11g ------------------------- NOV11h ----------------------- NOV11a ----------------------- NOV11b ------------------------- NOV11c --------------------------- NOVIld --------------------------- NOVIle LDGTRCNTDSLDMCISGICQAVGCDRQLGSNAKEDNCGVCAGDGSTCRLVRGQSKSHVSP NOV11f ---------------------- NOV11g ---------------------- NOV11h --------------------- NOV11a ---------------------- NOV11b --------------------- NOV11c ---------------------- NOV11d ---------------------- NOV11e EKREENVIAVPLGSRSVRITVKGPAHLFIESKTLQGSKGEHSFNSPGVFVVENTTVEFQR NOV11f ----------------------- NOV11g ----------------------- NOV11h ----------------------- NOV11a ----------------------- NOV11b --------------------------- NOV11c --------------------------- NOV11d ---------------------------- NOV11e GSERQTFKIPGPLMADFIFKTRYTAAKDSVVQFFFYQPISHQWRQTDFFPCTVTCGGGYQ NOV11f --------------------------- NOV11g -------------MADFIFKTRYTAAKDSVVQFFFYQPISHQWRQTDFFPCTVTCGGGYQ NOV11h --------------------------- NOV11a ------------------------- NOV11b -------------------------- NOV11c --------------------------- NOV11d -------------------------------------------------- MPYDHFQPLP NOV11e LNSAECVDIRLKRVVPDHYCHYYPENVKPKPKLKECSMDPCPSSDGFKEIMPYDHFQPLP NOV11f -------------------------------------------------- MPYDHFQPLP NOVllg LNSAECVDIRLKRVVPDHYCHYYPENVKPKPKLKECSMDPCPSSDGFKEIMPYDHFQPLP NOV11h -------------------------- NOV11a ----------------------------- NOV11b ---------------------------- NOV11c ----------------------------- NOV11d RWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFDCP NOV11e RWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFDCP NOV11f RWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFDCP NOV11g RWEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFDCP NOV11h -WEHNPWTACSVSCGGGIQRRSFVCVEESMHGEILQVEEWKCMYAPKPKVMQTCNLFDCP NOV11a ------------------------------------------------- 187 WO 03/093432 PCT/US03/13690 NOV11b ----------------------------------------------------------- NOV11c ----------------------------------------------------------- NOVIld KWIAMEWSQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK NOV11e KWIAMEWSQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK NOVIlf KWIAMEWSQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK NOV11g KWIAMEWSQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK NOV11h KWIAMEWSQCTVTCGRGLRYRVVLCINHRGEHVGGCNPQLKLHIKEECVIPIPCYKPKEK NOV11a -----------KQPLVSSHLGIRLTSKMPQLLQNINGIIEAFRRYARTEGNCTALTRGEL NOV11b ---------------------------TGSLLQNINGIIEAFRRYARTEGNCTALTRGEL NOV11c ---------------------------------------------------------- NOV11d SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT NOV11e SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT NOV11f SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT NOV11g SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT NOV11h SPVEAKLPWLKQAQELEETRIATEEPTFIPEPWSACSTTCGPGVQVREVKCRVLLTFTQT NOVila KRLLEQEFADVIVKPHDPATVDEVLRLLDEDHTGTVEFKEFLVLVFKVAQACFKTLSESA NOV11b KRLLEQEFADVIVKLEG- ------------------------------------------ NOV11c --------------------------------------------------------- NOV11d ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATC NOVIle ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATC NOV11f ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATC NOV11g ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATC NOV11h ETELPEEECEGPKLPTERPCLLEACDESPASRELDIPLPEDSETTYDWEYAGFTPCTATC NOV11a EGACGSQESGSLHSGASQELGEGQRSGTEVGRAGKGQHYEGSSHRQSQQGSRGQNRPGVQ NOV11b ----------------------------------------------------------- NOV11c -------------------VNDSLCDMVHRPPAMSQACNTEPCPPRWHVGSWGPCSATCG NOV11d VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGSWGPCSATCG NOV11e VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGSWGPCSATCG NOV11If VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGSWGPCSATCG NOV11g VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGSWGPCSATCG NOV11h VGGHQEAIAVCLHIQTQQTVNDSLCDMVHRPPAMSQACNTEPCPPRWHVGSWGPCSATCG NOVIa TQGQATGSAWVSSYDRQAESQSQERISPQIQLSGQTEQTQKAGEGKRNQTTEMRPERQPQ NOV11b ----------------------------------------------------------- NOV11c VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ NOV11d VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ NOV11e VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ NOV11f VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ NOVlIg VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ NOV11h VGIQTRDVYCLHPGETPAPPEECRDEKPHALQACNQFDCPPGWHIEEWQQCSRTCGGGTQ NOV11a TREQDRAHQTGETVTGSGTQTQAGATQTVEQDSSHQTGSTSTQTQESTNGQNRGTEIHGQ NOV11b ---------------------------------------------------------- NOV11c NR---RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGV NOV11d NR---RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGV NOV11e NR---RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGV NOV11f NR---RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGV NOV11g NR---RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGV NOV11h NR---RVTCRQLLTDGSFLNLSDELCQGPKASSHKSCARTDCPPHLAVGDWSKCSVSCGV NOV11a GRSQTSQAVTGGHTQIQAGSHTETVEQDRSQTVSHGGAREQGQTQTQPGSGQRWMQVSNP NOV11b ---------------------------------------------------------- NOV11c GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ NOV1ld GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ 188 WO 03/093432 PCT/US03/13690 NOV11e GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ NOV11f GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGLPLVRSCQMPECSKIKSEMKTKLGEQGPQ NOVl1g GIQRRKQVCQRLAAKGRRIPLSEMMCRDLPGFPLVRSCQMPECSKIKSEMKTKLGEQGPQ NOV11h GIQRRKQVCQRLAAKGRRISLSEMMCRDLPGLPLVRSCQMPEC---------------- NOV11a EAGETVPGGQAQTGASTESGRQEWSSTHPRRCVTEGQGDRQPTVVGEEWVDDHSRETVIL NOV11b -------------------------- --------- - - NOV11c ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRCLQNSK NOV11d ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRCLQNSK NOVIle ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRCLQNSK NOVIIf ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRCLQNSK NOVIIg ILSVQRVYIQTREEKRINLTIGSRAYLLPNTSVIIKCPVRRFQKSLIQWEKDGRCLQNSK NOV11h ----------------------------------------------- NOV11a RLDQGNLHTSVSSAQGQDAAQSEEKRGITARELYSYLRSTKP--------

--

NOV11b -------------------------------------------- NOV11c RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETGVLKLIGTDNRLIARPTLXEPMREYPG NOV11d RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPG NOVIle RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPG NOV11f RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPG NOVIIg RLGITKSGSLKIHGLAAPDIGVYRCIAGSAQETVVLKLIGTDNRLIARPALREPMREYPG NOV11h ------------------------------------------------ NOVIla ----------------------------------------------- NOV11b --------------------------------------------- NOV11c MDHNEANS----------------------------------------------- NOV11d MDHSEANSLGVTWHKMRQMWNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNSWELKN NOV11e MDHSEANSLGVTWHKMRQMWNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNSWELKN NOVIIf MDHSEANSLGVTWHKMRQMWNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNSWELKN NOViIg MDHSEANSLGVTWHKMRQMWNNKNDLYLDDDHISNQPFLRALLGHCSNSAGSTNSWELKN NOV11h ----------------------------------------------- NOV11a ---------------------------------------------- NOV11b ----------------------------------------------- NOV11c ----------------------------------------------- NOVIlId KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ NOV11e KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ NOV11f KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ NOViIg KQFEAAVKQGAYSMDTAQFDELIRNMSQLMETGEVSDDLASQLIYQLVAELAKAQPTHMQ NOV11h -------------------------------------------------- NOV11a -------------------------------------------------- NOV11b -------------------------------------------------- NOV11c -------------------------------------------------- NOVIld WRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR NOVIle WRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR NOV11f WRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR NOV11g WRGIQEETPPAAQLRGETGSVSQSSHAKNSGKLTFKPKGPVLMRQSQPPSISFNKTINSR NOV11h ---------------------------------------------------- NOV11a -------------------------------------------------- NOV11b --------------------------------------------------- NOV11c -------------------------------------------------- NOV11d IGNTVYITKRTEVINILCDLITPSEATYTWTKDGTLLQPSVKIILDGTGKIQIQNPTRKE NOV11e IGNTVYITKRTEVINILCDLITPSEATYTWTKDGTLLQPSVKIILDGTGKIQIQNPTRKE NOV11f IGNTVYITKRTEVINILCDLITPSEATYTWTKDGTLLQPSVKIILDGTGKIQIQNPTRKE NOV11g IGNTVYITKRTEVINILCDLITPSEATYTWTKDGTLLQPSVK---------------- 189 WO 03/093432 PCT/US03/13690 NOV11h ----------------------------------------------------------- NOVIla ----------------------------------------------------------- NOVIlb ---------------------------------------------------------- NOV11c ----------------------------------------------------------- NOV11d QGIYECSVANHLGSDVESSSVLYAEAPVILSVERNITKPEHNHLSVVVGGIVEAALGANV NOV11e QGIYECSVANHLGSDVESSSVLYAEAPVILSVERNITKPEHNHLSVVVGGIVEAALGANV NOV11f QGIYECSVANHLGSDVESSSVLYAEAPVILSVERNITKPEHNHLSVVVGGIVEAALGANV NOV11g -------------------------------------------------------- NOV11h ----------------------------------------------------------- NOV11a ----------------------------------------------------------- NOV11b ----------------------------------------------------------- NOV11c ----------------------------------------------------------- NOVIId TIRCPVKGVPQPNITWLKRGGSLSGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAV NOV11e TIRCPVKGVPQPNITWLKRGGSLSGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAV NOV11f TIRCPVKGVPQPNITWLKRGGSLSGNVSLLFNGSLLLQNVSLENEGTYVCIATNALGKAV NOV11g ------------------------------------------------------- NOV11h ------------------------------------------------------- NOVIla --------------------------------------------------------- NOV11b ---------------------------------------------------------- NOV11c .---------------------------------------------------------- NOV11d ATSVLHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFWEPGNWSHCS NOV11e ATSVFHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFWEPGNWSHCS NOV11f ATSVLHLLERRWPESRIVFLQGHKKYILQATNTRTNSNDPTGEPPPQEPFWEPGNWSHCS NOVg11 ---------------------------------------------------------- NOV11h ------------------------

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NOV11a --------------------------------------------------------- NOVIlb --------------------------------------------------------- NOV11c ---------------------------------------------------------- NOV11d ATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPARWFTSVWSQCSV NOV11e ATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPARWFTSVWSQCSV NOV11f ATCGHLGARIQRPQCVMANGQEVSEALCDHLQKPLAGFEPCNIRDCPARWFTSVWSQCSV NOV11g ----------------------------------------------------------- NOV11h ----------------------------------------------------------- NOV11a ----------------------------------------------------------- NOV11b ----------------------------------------------------------- NOV11c ----------------------------------------------------------- NOV11d SCGEGYHSRQVTCKRTKANGTVQVVSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRC NOVIle SCGEGYHSRQVTCKRTKANGTVQVVSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRC NOV11f SCGEGYHSRQVTCKRTKANGTVQVVSPRACAPKDRPLGRKPCFGHPCVQWEPGNRCPGRC NOV11g ----------------------------------------------------------- NOVIh -------------------------------------------------------- NOV11a NOV11b ----------------------------------------------------------- NOV11c ----------------------------------------------------------- NOV11d MGRAVRMQQRHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGPWKPCTAACGRGF NOV11e MGRAVRMQQRHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGPWKPCTAACGRGF NOV11lf MGRAVRMQQRHTACQHNSSDSNCDDRKRPTLRRNCTSGACDVCWHTGPWKPCTAACGRGF NOVg11 ----------------------------------------------------------- NOV11h ----------------------------------------------------------- NOVla ----------------------------------------------------------- 190 WO 03/093432 PCT/US03/13690 NOV11b ----------------------------------------------------------- NOV11c ----------------------------------------------------------- NOV11d QSRKVDCIHTRSCKPVAKRHCVQKKKPISWRHCLGPSCDRDCTDTTHYCMFVKHLNLCSL NOV11le QSRKVDCIHTRSCKPVAKRHCVQKKKPISWRHCLGPSCDRDCTDTTHYCMFVKHLNLCSL NOV11f QSRKVDCIHTRSCKPVAKRHCVQKKKPISWRHCLGPSCDRDCTDTTHYCMFVKHLNLCSL NOV11g ----------------------------------------------------------- NOV11h ----------------------------------------------------------- NOV11a ------------- NOV11b ------------- NOV11c ------------- NOV11d DRYKQRCCQSCQEG NOV11e DRYKQRCCQSCQEG NOV11f DRYKQRCCQSCQEG NOV11g ------------- NOV11h ------------- NOV11a (SEQ ID NO: 84) NOV11b (SEQ ID NO: 86) NOV11c (SEQ ID NO: 88) NOV11d (SEQ ID NO: 90) NOV11e (SEQ ID NO: 92) NOV11f (SEQ ID NO: 94) NOV11g (SEQ ID NO: 96) NOV11h (SEQ ID NO: 98) Further analysis of the NOV11 a protein yielded the following properties shown in Table 11C. 191 WO 03/093432 PCT/US03/13690 Table 11C. Protein Sequence Properties NOV11a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 1; pos.chg 1; neg.chg 0 H-region: length 10; peak value 5.49 PSG score: 1.09 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -10.00 possible cleavage site: between 26 and 27 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 = 0.63 (at 90) ALOM score: 0.63 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 6 Charge difference: 0.5 C( 2.5) - N( 2.0) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 5.65 Hyd Moment(95): 4.29 G content: 2 D/E content: 1 S/T content: 4 Score: -4.11 Gavel: prediction of cleavage sites for mitochondrial preseq R-3 motif at 35 FRRYjA NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 10.0% NLS Score: -0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: KKXX-like motif in the C-terminus: RSTK SKL: peroxisomal targeting signal in the C-terminus: none PTS2: 2nd peroxisomal targeting signal: found RLTSKMPQL at 12 192 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 73.9 %: nuclear 13.0 %: mitochondrial 13.0 %: cytoplasmic >> prediction for CG50513-01 is nuc (k=23) A search of the NOV 11 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 11D. 193 WO 03/093432 PCT/US03/13690 Table 11D. Geneseq Results for NOV11a NOV11a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAB20163 Human protein SECP9 - Homo 17..451 435/435 (100%) 0.0 sapiens, 435 aa. [WO200105971-A2, 1..435 435/435 (100%) 25-JAN-2001] AAB98668 DRC1 protein sequence - 17..451 429/495 (86%) 0.0 Unidentified, 495 aa. [CN1283695- 1..495 429/495 (86%) A, 14-FEB-2001] ABG09718 Novel human diagnostic protein 17..451 429/495 (86%) 0.0 #9709 - Homo sapiens, 495 aa. 1..495 429/495 (86%) [WO200175067-A2, 11-OCT-2001] AAU87326 Novel central nervous system protein 2..336 311/335 (92%) e-177 #236 - Homo sapiens, 335 aa. 1..331 317/335 (93%) [WO200155318-A2, 02-AUG-2001] AAU86940 Human DNA repair and processing 2..102 74/101 (73%) 5e-31 protein, SEQ ID No 28 - Homo 1..101 75/101 (73%) sapiens, 104 aa. [WO200155305-A2, 02-AUG-2001] In a BLAST search of public sequence databases, the NOV1 1a protein was found to have homology to the proteins shown in the BLASTP data in Table 11E. 194 WO 03/093432 PCT/USO3/13690 Table 11E. Public BLASTP Results for NOV11a Protein NOV11a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value Number Residues Portion CAC32430 Sequence 17 from Patent 17..451 435/435 (100%) 0.0 WO0105971 - Homo sapiens 1..435 435/435 (100%) (Human), 435 aa. Q9UBG3 Tumor related protein - Homo 17..451 429/495 (86%) 0.0 sapiens (Human), 495 aa. 1..495 429/495 (86%) Q8N613 Chromosome I open reading 17..451 428/495 (86%) 0.0 frame 10 - Homo sapiens 1..495 428/495 (86%) (Human), 495 aa. P97347 Repetin - Mus musculus (Mouse), 17..391 112/405 (27%) 9e-27 1130 aa. 1..389 186/405 (45%) Q8VHD8 Hornerin - Mus musculus 17..439 100/431 (23%) le-25 .... _(Mouse), 2496 aa. 1..404 179/431 (41%) PFam analysis predicts that the NOV11 la protein contains the domains shown in the Table 11F. Table 11F. Domain Analysis of NOV11a IIdentities/ Pfam Domain NOV11a Match Region Similarities Expect Value for the Matched Region S_100 20..63 16/44 (36%) 2.9e-09 34/44 (77%) efhand 69..97 8/29 (28%) 0.0061 23/29 (79%) Example 12. The NOV 12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A. Table 12A. NOV12 Sequence Analysis NOV12a, CG50949-03 SEQ ID NO: 1032432 bp DNA Sequence ORF Start: ATG at 112 ORF Stop: TAG at 1870 GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTC CTCGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATG CATCTCCAGCAAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCA 195 WO 03/093432 PCT/US03/13690 GGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGC ATCTCCAGCCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCC TCATCCGGCAGGTCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGT TAGAGCAACACCAGTGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGG CCACCAGGGAGAGCCCAGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCG CTCATCGGGTGCGTGCTCCTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCA GGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACG GGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTG CTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTA CTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGG ATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAA TGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGAT CGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCC ACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACC CGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGC AGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCC TCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGA CAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAA GACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGG TCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGC CAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAG CTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCT GGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCC TCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCCTCAGCGTCCCCATATTCGGG GGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGTTTCTTTCCCTGC TTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAAGGGTGGACCTACAGGCCAGGCAGGCAGTTG CTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGGTTGCAATGGACTTTGAAAACGTTTCAGT TTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTTATGCATGGGAATCCGCTCTTCATGGC CTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTGTTGTTGTTGTTGTCTTTTTTTAAA AACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCACCAGAATGCTCCCTGAGAACTA CCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCACTATCATAAAAGAGTATAAAG TAATAAAATAA4TAAAAAGCG NOV12a, CG50949-03 SEQ ID NO: 104 586 aa MTat 63152.3kD Protein Sequence MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGR ASPGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSP ARSAPATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQRESC PKAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAB RTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQ VSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTD EEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLID FKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVY TKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV NOVl2b, 197192399 SEQ ID NO: 105 717 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence TCCCTGTGGATTGGATCCATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAG TCTGCACTTCGGTACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCG CCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAAC CTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGA GGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTG CTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAG ACCAGGGAGACAGATGACAAGACATCCCCCTCCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAA GAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTC GTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAA 196 WO 03/093432 PCT/US03/13690 AGTGACAGAAGTTCTTCCCTGGATTTACAGCCTCGAG NOV12b, 197192399 SBQIDNO: 106 239 1 a MWat 26529.8k1) Protein Sequence SLWIGSIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTPSLNETCWITGFGK TRETDDKTSPSLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRW YLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSLE NOV12c, 257499999 SEQ ID NO:107 '10bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence TCCCTGTGGATTGGATCCATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAG TCTGCACTTCGGTACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCG CCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAAC CTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGA GGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTG CTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAG ACCAGGGAGACAGATGACAAGACATCCCCCTCCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAA GAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTC GTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAA AGTGACAGAAGTTCTTCCCTGGATTTACAGCCTCGAG NOVI2c, 257499999 SEQ ID NO: 108 aa MW at 26529.8kD Protein Sequence SLWIGSIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGK TRETDDKTSPSLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRW YLAGVTSWGTGCGQRNRPGVYTKVTEVLPWIYSLE N(V12d,257450010 :SBQIDNO: 109 1101bp DNA Sequence IORF Start at 1 ORF Stop end of sequence GGATCCACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGG GGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGA.CAAGTCTCTGC TTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTAC TCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCT CCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGOGAGGGGCGCTGGCCTCGGATA GCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGAC GCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAA GGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCA ACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACC CTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTG CTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGC AGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGG ATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGT CTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAA ACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGA TCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACC CAGGGTGCTCGAG NOV12d, 257450010 SEQ 1ID40:110 367aa at40822.7kd Protein Sequence GSTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSY SEKTCQQLGFERSECPSQRYISLQCSHOGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHICGGTLID AQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLT LSAHIHPACLPMHGTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPR MMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEVR SLQQDTAPSRLGTSSGGDPGGAPRVLE 197 WO 03/093432 PCT/US03/13690 NOV12e, 252417780 SEQ ID NO: 111 1203 bp DNA Sequence ORF Start: at ORF Stop: end of sequence ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGA CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCC ACAGGGATTTTGCCAA.CAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGG TCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGG GCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCA CCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTC GTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCC TGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACA TCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATG CATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGA TGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACT ACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGAC TCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGT CACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTC TTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGA ACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC NOV12e, 252417780 SEQ ID NO: 112 401 aa MW at 44688.8kD Protein Sequence TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWND SYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTG RIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLP EAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETD DKTSPFLREVQVNLIDFKKCNDYLVYDSTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGV TSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12f, 252417791 SEQ ID NO: 113 l110 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGA CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGGTCTGAATGCCCTTCCCAGCGGTATA TCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCC TCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCT CATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGG GCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATC ATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCC CCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATG AGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGG GAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTAC CCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGC CTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGC CAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGA GGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAG GAGCACCCAGGGTGCTCGAGGGC NOV12f, 252417791 SEQ ID NO: 114 ]370 aa MW at 41118.OkD Protein Sequence TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWND SYSEKTCQQLGFERSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHICGGTL IDAQWVLTAAHCFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKP LTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPLREVQVNLIDFKKCNDYLVYDSYLT PRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKME VRSLQQDTAPSRLGTSSGGDPGGAPRVLEG 198 WO 03/093432 PCT/US03/13690 NOVl2g, 252417821 SEQ ID N 115 1203 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGA CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCC ACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGG TCTGAATGCCCTTTCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGG GCGGATCGTGGGAGGGGCGCTGGTCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCA CCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTC GTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGOTGTACGCGGGCACCAGCAACCTGCACCAGTTGCC TGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACA TCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATG CATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGA TGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACT ACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGAC TCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGT CACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTC TTCCCTGGATTTACAGCAAGATGGAGGTAAAATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGA ACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC NOV12g, 252417821 SEQ ID NO: 116 401 aa MW at44749.OkD Protein Sequence TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWND SYSEKTCQQLGFESAHRTTEVAHRDFANSPSILRYNSTIQESLHRSECPFQRYISLQCSHCGLRAMTG RIVGGALVSDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLEQLP EAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETD DKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGV TSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEVKSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12h, 252417840 SEQIDNO:117 1203bp DNA Sequence OREF Start: at CIF Stop: end of sequence ACCGGATCCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCT GTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAG TCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACAGGAATGA CTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCC ACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGG TCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGG GCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCA CCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTC GTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCC TGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACA TCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATG CATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGA TGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACT ACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGAC TCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGT CACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTC TTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAGCAGGCTGGGA ACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC NOV12h, 252417840 jSEQ ID NO: 118 4Olaa MWat 44658.8kD Protein Sequence TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNRND SYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTG RIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLP EAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETD DKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGV 199 WO 03/093432 PCT/USO3/13690 TSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12i, 257474313 ISEQ ID NO: 119 11779bp DNA Sequence CRFStart: at I ORF Stop: end of sequence ACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC ACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAG CCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCGCCAGGTCA GCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCTGTACCCAT CCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTACGAGCCTGC CCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCCTCATTGCC CTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCA GAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACG AGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAG TGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTT CGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGAT ACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAA GTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCC AGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTG TACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAG CAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGT CCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGG ATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGT CAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGA TGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGT GAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAA ACCTGGTGTGTACACCAAAGTGACAGAAGTTTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCC TGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGG GTGCTCGAGGGC NOV12i, 257474313 VSEQ ID DNO: 120 593aa jMWat 63798.OkD Protein Sequence TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGT PPGRASPGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPI RSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQ RESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGF ESAHRTTEVAHRDFANSPSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSK WPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINS NYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQV NLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNK PGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12j,257474324 SEQIDNO: 121 1626 bp DNA Sequence RF Start: at 1 ORF Stop: end of sequence ACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC ACCTCCAGGCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCG CCAGGTCAGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCT GTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTAC GAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCC TCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTAC AAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCT CCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAG CTGGGTTTCGAGAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACT 200 WO 03/093432 PCT/US03/13690 GAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGA GTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCC GCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAA CCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGG AGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCT GCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAA GACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCA AGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTT CGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTG GTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCA AAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCA CCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC NOV1:1j, 257474324 SEI5fD1 2 42 MWrat 58367.2kd Protein Sequence _]EQI O 2 TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGT PPGRASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPV AVPIRSSPARSAPATRATRESPGT SLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLK SDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFERSECPSQRYISLQCSHCGL RAMTGRIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGK TRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRW YLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12k, CG50949-06 ISEQ ID NO: 1'3 1780 bp Sequence OR Start: ATG at 14 P Stop: end of sequence CACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC ACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAG CCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCGCCAGGTCA GCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCTGTACCCAT CCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTACGAGCCTGC CCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCCTCATTGCC CTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCA GAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACG AGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAG TGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTOGGTTT CGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGAT ACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAA GTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCC AGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTG TACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAG CAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGT CCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGG ATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGT CAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGA TGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGT GAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAA ACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCC TGCAGCAGGACACTGCACCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGG GTG NOV12k, CG50949-06 SEQ ID NO: 124 586 aa MW at 63152.3kD Protein Sequence MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGR ASPGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSP 201 WO 03/093432 PCT/US03/13690 ARSAPATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQRESC PKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAH RTTEVABRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSCGLRAMTGRIVGGALASDSKWPWQ VSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTD BEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLID FKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVY TKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV NOV121,268669017 SEQ ID NO: 125 1218 bp DNA Sequence ORF Start: at f qn ACCGGATCCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCA AGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGG TTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAG CAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGA CAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAG GAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACT GAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGA GTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCC GCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAA CCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGG AGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCT GCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAA GACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCA AGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTT CGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTG GTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCA AAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCA CCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC NOV121, 268669017 SEQ ID NO: 126146aaM at 45335.5kD Protein Sequence 0a MV TGSQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICS SNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGL RAMTGRIVGGALASDSKWPWQVSLHFGTTICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGK TRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCGDSGGPLVCEQNNRW YLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12m, CG50949-05 ISEQ ID NO: 127 2310 bp DNA Sequence ORF Start: ATG at 88 OR Stop: TAA at 1699 CGCCCGGGCAGGTTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCTCGACATCAGCTAAGCCTGGAGG ACTCTTCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAG CTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCA TCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGC TGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCAGGCAT CTCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGC AGGTCATCATCCGCCAGGTCAGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAAC ACCAGTGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGG AGAGCCCAGTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCC AAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAG GTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTA GCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGG ACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCA GGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGAC TGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTG AGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGC CGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCA ACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAG 202 WO 03/093432 PCT/US03/13690 GAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCC TGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCA AGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTC AAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCT GGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACC AAAGTGACAGAAGTTCTTCCCTGGATTTACACAAGATGGAGAGCGAGGTGCGATTCAGAAAATCCTA ACCAGCTGGCCTGCTGCTCTGCACAGCACCGGCTGCTGTGAAGACTCTGGCCATGGTGACTGGCCATG TGTGGCATCATCTGGGCTAATGGCCACCGGGCACCATCAGACTCCCACCTCCACTGTCTGCTGCCTCT GTGTGTGTGTGTGTGTGTGTGTGTGTGCATATGTGTGCATTGCCACTCTCCCAAGTTTTTCAGAAACC AGCAGAGCTGTCAACTCTTCTCAAAATCCCAGGCTGGAAATTACCTGGAGACAAGAGTTGAGTACCGT GGATGTTCCTACAGGAGTGTCCATAGATGGATGGAGGAGGTGGAGCCCAGAGCCCAAGGAAGAGCTGG GAATTCTTGCTTCTCTGACCCTCACTTACAGACTAGCCCAGTGTGGGCAGATGCCAGCGGCCCAGGTG GCGCCATTGCTGTCCTGGGATGGATCGTGGGTTTTGGTGGATGCAGCTTCCCAGGGCCTGGACCGTCT TCGGTGAAAAGCTGCTCCCGTTGGCTTTATGAGCATCAAGTCCTCACCCAGACCCCCTGCTGGTGCCG TGGATGTCACCAGTCGGACTGTGCTGTGGCTAACCAGGCTGACAACTGAGATGAGGATTCACTGTA NOV12m, CG50949-05 SEQ ID NO: 128 537 aa W at 58084.3kD Prtein Sequence MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGR ASPGRASPAQASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVP IRSSPARSAPATRATRESPVQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKS LLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRS ECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFV TREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMH GQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDS CQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFRKS NOVl2n, 317431859 SEQ ID NO: 129 1707 bp DNA Sequence 10RF Start: at 1 _ ORF Stop: end of sequence ACCGGATCCACCATGGAGAGGGACAGCCACGGGAATGCATCTCCAGCAAGAACACCTTCAGCTGGAG CATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCA GCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCTGGTAC ACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGG CTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGGTCATCATCCGCCAGGTCAGCCTCGGTGACAACC TCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAGTGGGGGCTGTACCCATCCGATCATCTCCTGC CAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCCAGGTACGAGCCTGCCCAAGTTCACCTGGC GGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTCCTCCTCATTGCCCTGGTGGTTTCGCTC ATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCC CAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGA GGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGT AGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCG GACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCC AGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGA CTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGT GAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTG CCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGC AACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGA GGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACC CTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGC AAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTT CAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACC TTCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGC TGGTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACAC CAAAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGAGCGAGGTGCGATTCAGAAAATCCC TCGAGGGC 1 NV12n,317431859 iSEQ ID NO:130 569 aa 'Wat61684.8kD Protein3Sequence 203 WO 03/093432 PCT/US03/13690 TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGT PPGRASPGRASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPA RSAPATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQRESCP KHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHR TTEVAHRDFANSFSILRYNSTIQESLERSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQV SLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDE EDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQVNLIDF KKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVYT KVTEVLPWIYSKMESEVRFRKSLEG NOV12o, CG50949-01 SEQ ID NO: 131 11314 bp DNA Sequence ORF Start: ATGat1 ORF Stop: TAA at 1264 ATGGAGAGCCCAGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCAT CGGGTGCGTGCTCCTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCC ACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTG GTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAA AATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAG AGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTT GCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCC TTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGG GAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATC TGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGA GAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCT CCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGCCCTCATG CGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATGGACAGAC CTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGACAAGACAT CCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTTGGTCTAT GACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCTGCCAGGG AGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACCAGCTGGG GCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCCCTGGATT TACAGCAAGATGGAGAGCGAGGTGCGATTCACAAAATCCTAACCAGCTGGCCTGCTGCTCTGCACAGC ACCGGCTGCTGTGAAGACTCTG NOVI2o C0949-0O1 ]SEQ ID NO: 1. 32,1421 aa Wa 78.k Protein Sequence h~t78.k MESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLI ILFQFWQGHTGIRYKEQRESCPKHAVRCDGV VDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDF ANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHI CGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDDYDIALM RLSKPLTLSAKIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPPLREVQVNLIDFKKCNDYLVY DSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVYTKVTEVLPWI YSKMESEVRFTKS NOV12p, CG50949-02 JSEQ ID NO: 133 1146 bp DNA Sequence ORF Start: at I .ORF Stop: end of sequence TTCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCAGCACGC TGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGGTTTGACT GGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAGCAGCAAC TGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGACAACCGA GGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAGGAAAGCC TCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACTGAGGGCC ATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCA CTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACT GCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCAC CAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGA CTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCC TCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGG GAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATG 204 WO 03/093432 PCT/USO3/13690 CAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGG GCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTG GCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGAC AGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGAGCGAGGTGCGATTCACAAAATCC NOV12p, CG50949-02 SEQ ID NO: 134382 aa MW at 43224.3kD Protein Sequence FQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSN WNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRZYISLQCSHCGLRA MTGRIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLH QLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTR ETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYL AGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFTKS NOV12q,CG50949-04 SEQ ID NO: 135 762bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence ATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGAGTCTGCACTTCGGTACCAC CCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCCGCCCACTGCTTCTTCGTGA CCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAACCTGCACCAGTTGCCTGAG GCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGGAGGACGACTATGACATCGC CCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCTGCTTGCCTCCCCATGCATG GACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAAGACCAGGGAGACAGATGAC AAGACATCCCCCTCCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCAAGAAATGCAATGACTACTT GGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTTCGTGGGGGCAGAGACTCCT GCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGGTACCTGGCAGGTGTCACC AGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAGTGACAGAAGTTCTTCC CTGGATTTACAGC NOV2q, CG50949-04 SEQ ID NO: 136 231 aa MW at 25643.8kD Protein Sequence IVGGALASDSKWPWQVSLHFGTTRICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPE AASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDD KTSPSLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVT SWGTGCGQRNKPGVYTKVTEVLPWIYS NOVI2r, CG50949-07 SEQ ID NO: 137 1219 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence ACCGGATCCCAGTTCTGGCAGGGCCACACAGGGATCAGGTACAAGGAGCAGAGGGAGAGCTGTCCCA AGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAAGAGTGACGAGCTGGGCTGCGTGAGG TTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCCCATCAGTGGCTTCCCATCTGTAG CAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGGGTTTCGAGAGTGCTCACCGGA CAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAGATACAACTCCACCATCCAG GAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAGTGTTCCCACTGCGGACT GAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGTGGCCTTGGCAAGTGA GTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTGGGTGCTCACTGCC GCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCGGGCACCAGCAA CCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACACCGATGAGG AGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACATCCACCCT GCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTTGGCAA GACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACTTCA AGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCTT CGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTG GTACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCA AAGTGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCA CCCAGCAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGCTCGAGGGC NOV12r, CG50949-07 SEQ ID NO: 138 1406 aa MW at 45335.5kD Protein Sequence 205 WO 031093432 PCT/US03/13690 TGSQFWQGHTGIRYKEQRESCPKKAVRCDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICS SNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGL RAMTGRIVGGALASDSKWPWQVSLHFGTTHICGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSN LHQLPEAASIAEIIINSNYTDEEDDYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGK TRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRW YLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12s, 13374729 SNP for SEQID NO: 2432bp SNP: position 902 A/C CG50949-03 1139 DNA Sequence ORF Start: ORF Stop: TAG at 1870 IATG at 112 .GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCT CGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATC TCCAGCAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGG GCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATC TCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGG TCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAG TGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCC AGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTC CTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGT ACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCC CATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCCGCAGCTGG GTTTCGAGAGTOCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAG ATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGT GGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTG GGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCG GGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACA CCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACAT CCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTT GGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACT TCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAG TGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGOTAAGATCCCTGCAGCAGGACACTGCACCCAG CAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCCTCAGCG TCCCCATATTCGGGGGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGT TTCTTTCCCTGCTTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAGGGTGGACCTACAGGCCAGG CAGGCAGTTGCTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGGTTGCAATGGACTTTGAAAAC GTTTCAGTTTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTTATGCATGGGAATCCGCTCTT CATGGCCTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTGTTGTTGTTGTTGTCTTTTTT TAAAAACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCACCAGAATGCTCCCTGAGAAC TACCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCACTATCATAAAAGAGTATAAAG TAATAAAATAATAAAAAGC NOV12s, 13374729 SNP for SEQ ID NO: 586 aa SNP: Gin to Pro at position CG50949-03 140 264 Protein Sequence MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGRAS PGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPARSA PATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVR CDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCPQLGFESARRTTEVAHP DFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHI CGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDDYDIALMRL SKPLTLSAHIHPACLPMHGQTFSLNETCWITGPGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYL TPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVYTKVTEVLDWIYSK1EV 206 WO 03/093432 PCT/USO3/13690 RSLQQDTAPSRLGTSSGGDPGGAPRV NOV12t, 13374730 SNP for SEQ ID NO: 141 2432 bp, SNP: 1313 T/C CG50949-03 OR Start: ATG St TAG at 1870 DNA Sequence 112 GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCT CGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATC TCCAGCAAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGG GCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATC TCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGG TCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAG TGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCC AGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTC CTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGT ACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCC CATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGG GTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAG ATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGT GGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTG GGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCG GGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCACCATCAACAGCAATTACA CCGATGAGGAGGACGACTATGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACAT CCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTT GGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACT TCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAG TGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAG CAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCTCAGCG TCCCCATATTCGGGGGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGT TTCTTTCCCTGCTTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAAGGGTGGACCTACAGGCCAGG CAGGCAGTTGCTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGGTTGCAATGGACTTTGAAAAC GTTTCAGTTTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTTATGCATGGGAATCCGCTCTT CATGGCCTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTGTTGTTGTTGTTGTCTTTTTT TAAAAACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCACCAGAATGCTCCCTGAGAAC TACCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCACTATCATAAAG TAATAAAATAATAAAAAGCGAAAAAAAAAAAAAAAA NOV12t, 13374730 SNP for SEQ ID NO: 586 aa SNP: Ile to Thr at position 401 CG50949-03 142 Protein Sequence MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGRAS PGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPARSA PATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVR CDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHR DFANSFSILRYNSTIQESLHRSECPSQRYISLQCSKCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHI CGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEITINSNYTDEEDDYDIALMRL SKPLTLSAHIHPACLPMHGQTFSERETCWITGFGKTRETDDKTSPFLREVQVNLIDFKKCNDYLVYDSYL TPRNMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSWGTGCGQRNKPGVYTKVTEVLPWIYSKMEV RSLQQDTAPSRLGTSSGGDPGGAPRV NOV12u, 13374731 SNP for SEQ ID NO: 143 2432 bp SNP: 1350 T CG50949-03 ORF Start: ATG at 112 ORF Stop: TAG at 1870 DNA Sequence GGACACTGACATGGACTGAAGGAGTAGAAAACATGCCTGAGAAGCCAGGGGCCAAGATGGATCTTCTCCT 207 WO 03/093432 PCT/US03/13690 CGACATCAGCTAAGCCTGGAGGACTCTCCCCCTCAGAGACCATGGAGAGGGACAGCCACGGGAATGCATC TCCAGCAAGAACACCTTCAGCTGGAGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCAGGCCGG GCATCTCCAGCCCAGGCATCTCCAGCCCAGGCATCTCCAGCTGGGACACCTCCGGGCCGGGCATCTCCAG CCCAGGCATCTCCAGCTGGTACACCTCCAGGCCGGGCATCTCCAGGCCGGGCATCTCCAGCCCAGGCATC TCCAGCCCAGGCATCTCCAGCCCGGGCATCTCCGGCTCTGGCATCACTTTCCAGGTCCTCATCCGGCAGG TCATCATCCGCCAGGTCGGCCTCGGTGACAACCTCCCCAACCAGAGTGTACCTTGTTAGAGCAACACCAG TGGGGGCTGTACCCATCCGATCATCTCCTGCCAGGTCAGCACCAGCAACCAGGGCCACCAGGGAGAGCCC AGGTACGAGCCTGCCCAAGTTCACCTGGCGGGAGGGCCAGAAGCAGCTACCGCTCATCGGGTGCGTGCTC CTCCTCATTGCCCTGGTGGTTTCGCTCATCATCCTCTTCCAGTTCTGGCAGGGCCACACAGGGATCAGGT ACAAGGAGCAGAGGGAGAGCTGTCCCAAGCACGCTGTTCGCTGTGACGGGGTGGTGGACTGCAAGCTGAA GAGTGACGAGCTGGGCTGCGTGAGGTTTGACTGGGACAAGTCTCTGCTTAAAATCTACTCTGGGTCCTCC CATCAGTGGCTTCCCATCTGTAGCAGCAACTGGAATGACTCCTACTCAGAGAAGACCTGCCAGCAGCTGG GTTTCGAGAGTGCTCACCGGACAACCGAGGTTGCCCACAGGGATTTTGCCAACAGCTTCTCAATCTTGAG ATACAACTCCACCATCCAGGAAAGCCTCCACAGGTCTGAATGCCCTTCCCAGCGGTATATCTCCCTCCAG TGTTCCCACTGCGGACTGAGGGCCATGACCGGGCGGATCGTGGGAGGGGCGCTGGCCTCGGATAGCAAGT GGCCTTGGCAAGTGAGTCTGCACTTCGGCACCACCCACATCTGTGGAGGCACGCTCATTGACGCCCAGTG GGTGCTCACTGCCGCCCACTGCTTCTTCGTGACCCGGGAGAAGGTCCTGGAGGGCTGGAAGGTGTACGCG GGCACCAGCAACCTGCACCAGTTGCCTGAGGCAGCCTCCATTGCCGAGATCATCATCAACAGCAATTACA CCGATGAGGAGGACGACTAGGACATCGCCCTCATGCGGCTGTCCAAGCCCCTGACCCTGTCCGCTCACAT CCACCCTGCTTGCCTCCCCATGCATGGACAGACCTTTAGCCTCAATGAGACCTGCTGGATCACAGGCTTT GGCAAGACCAGGGAGACAGATGACAAGACATCCCCCTTCCTCCGGGAGGTGCAGGTCAATCTCATCGACT TCAAGAAATGCAATGACTACTTGGTCTATGACAGTTACCTTACCCCAAGGATGATGTGTGCTGGGGACCT TCGTGGGGGCAGAGACTCCTGCCAGGGAGACAGCGGGGGGCCTCTTGTCTGTGAGCAGAACAACCGCTGG TACCTGGCAGGTGTCACCAGCTGGGGCACAGGCTGTGGCCAGAGAAACAAACCTGGTGTGTACACCAAAG TGACAGAAGTTCTTCCCTGGATTTACAGCAAGATGGAGGTAAGATCCCTGCAGCAGGACACTGCACCCAG CAGGCTGGGAACTTCCTCAGGTGGGGACCCTGGAGGAGCACCCAGGGTGTAGGCAGAGGTCCCCTCAGCG TCCCCATATTCGGGGGGTGTTCTGGACAGGGTCAAATGTGATGCCTGGGGTCAATCCCAGCTGTCTGTGT TTCTTTCCCTGCTTTTCTTCCCTCAGAACAGAGCTCAGCGGGTTGAAAAAGGGTGGACCTACAGGCCAGG CAGGCAGTTGCTGGGCAGATGTTCTCCCAGAAGTATTTTTTTGTGTAAGG TTGCAATGGACTTTGAAAACGTTTCAGTTTCTGCAGAGGATTTTGTGATAGTCTTTGTTATCAAGCATTT ATGCATGGGAATCCGCTCTTCATGGCCTTTCCCAGCTCTGTTTGTTTTAGTCTTTTTGATTTTCTTTTTG TTGTTGTTGTTGTCTTTTTTTAAAAACACAAGTGACTCCATTTTAACTCTGACAACTTTCACAGCTGTCA CCAGAATGCTCCCTGAGAACTACCATTCTTTCCCTTTCCCACTTAAAATATTTCATCAGAACCTCACCAC TATCATAAAAGAGTATAAAGTAATAAAATAATAAAAAGCGA A A A A A A AA NOV12u, 13374731 SNP for SEQ ID NO: 586 aa SNP: Tyr to STOP at position CG50949-03 144 413 Protein Sequence MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASPAQASPAGTPPGRAS PGRASPAQASPAQASPARASPALASLSRSSSGRSSSARSASVTTSPTRVYLVRATPVGAVPIRSSPARSA PATRATRESPGTSLPKFTWREGQKQLPLIGCVLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVR CDGVVDCKLKSDELGCVRFDWDKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHR DFANSFSILRYNSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHI CGGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEEDD* A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 12B. Table 12B. Comparison of the NOV12 protein sequences. NOV12a ----MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP NOV12b ------------------------------------------------------------------ NOV12c ------------------------------------------------------------------ NOV12d ---------------------------------------------------------- NOV22e ---------------------------------------------------------- NOV12f ---------------------------------------------------------- NOV12g ------------------------------------------------------------------ 208 WO 03/093432 PCT/US03/13690 NOV12h ----------------------------------------------------------- NOV12i TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP NOV12j TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP NOV12k ----MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP NOV121 --------------------------------------------------------- NOV12m ---- MERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP NOV12n TGSTMERDSHGNASPARTPSAGASPAQASPAGTPPGRASPAQASPAQASPAGTPPGRASP NOV12o ---------------------------------------------------------- NOV12p --------------------------------------------------------- NOV12q ---------------------------------------------------------- NOV12r --------------------------------------------------------- NOV12a AQASPAGTPPGRASPGRASPAQASPAQAS-----PARASPALASLSRSSSGRSSSARSAS NOV12b --------------------------------------------------------- NOV12c ------------------------------------------------------- NOV12d --------------------------------------------------------- NOV12e --------------------------------------------------------- NOV12f --------------------------------------------------------- NOV12g --------------------------------------------------------- NOV12h --------------------------------------------------------- NOV12i AQASPAGTPPGRASPGRASPAQASPAQAS-----PARASPALASLSRSSSGRSSSARSAS NOV12j AQASPAGTPPGRASP -------------------------ALASLSRSSSGRSSSARSAS NOV12k AQASPAGTPPGRASPGRASPAQASPAQAS-----PARASPALASLSRSSSGRSSSARSAS NOV121 --------------------------------------------------------- NOV12m AQASPAGTPPGRASPGRASPAQASPAQASPAQASPARASPALASLSRSSSGRSSSARSAS NOV12n AQASPAGTPPGRASPGRASPAQAS---------- PARASPALASLSRSSSGRSSSARSAS NOV12o --------------------------------------------------------- NOV12p ----------------------------------------------------- NOV12q --------------------------------------------------------- NOV12r ---------------------------------------------------------- NOV12a VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGC NOV12b --------------------------------------------------------- NOV12c -------------------------------------------------------- NOV12d ---------------------------------------------------------- NOV12e ---------------------------------------------------------- NOV12f ---------------------------------------------------------- NOV12g ---------------------------------------------------------- INOV12h ---------------------------------------------------------- NOV12i VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGC NOV12j VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGC NOV12k VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGC NOV121 --------------------------------------------------------- NOVI2m VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESP-------------------- NOV12n VTTSPTRVYLVRATPVGAVPIRSSPARSAPATRATRESPGTSLPKFTWREGQKQLPLIGC NOV12o ---------------------------------- MESPGTSLPKFTWREGQKQLPLIGC NOV12p -------------------------------------------------------- NOV12q ---------------------------------------------------------- NOV12r --------------------------------------------------------- NOV12a VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12b ------------------------------------------------------- NOV12c ----------------------------------------------------------- NOV12d -------------------GSTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12e -----------------TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12f -----------------TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12g

-----------------

TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW 209 WO 03/093432 PCT/US03/13690 NOV12h -----------------TGSHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12i VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12j VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12k VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV121 ------------TGSQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12m --------------- VQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12n VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12o VLLLIALVVSLIILFQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12p --------------FQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12q ----------------------------------------------------------- NOV12r ------------ TGSQFWQGHTGIRYKEQRESCPKHAVRCDGVVDCKLKSDELGCVRFDW NOV12a DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12b ---------------------------------------------------------- NOV12c ----------------------------------------------------------- NOV12d DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFE--------------------- NOV12e DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12f DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFE--------------------- NOV12g DKSLLKIYSGSSHQWLPTCSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12h DKSLLKIYSGSSHQWLPICSSNRNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12i DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12j DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFE--------------------- NOV12k DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV121 DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12m DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12n DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12o DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12p DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12q ----------------------------------------------------------- NOV12r DKSLLKIYSGSSHQWLPICSSNWNDSYSEKTCQQLGFESAHRTTEVAHRDFANSFSILRY NOV12a NSTIQESLHRSECPSQRYISLQCSECGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12b ----------------------------SLWIGSIVGGALASDSKWPWQVSLHFGTTHIC NOV12c ----------------------------SLWIGSIVGGALASDSKWPWQVSLHFGTTHIC NOV12d ---------RSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12e NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12f ---------RSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12g NSTIQESLHRSECPFQRYISLQCSHCGLRAMTGRIVGGALVSDSKWPWQVSLHFGTTHIC NOV12h NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12i NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12j ---------RSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12k NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV121 NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12m NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12n NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12o NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12p NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12q ----------------------------------- IVGGALASDSKWPWQVSLHFGTTHIC NOV12r NSTIQESLHRSECPSQRYISLQCSHCGLRAMTGRIVGGALASDSKWPWQVSLHFGTTHIC NOV12a GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12b GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12c GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12d GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12e GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12f GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12g GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED 210 WO 03/093432 PCT/US03/13690 NOV12h GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12i GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12j GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12k GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLQLPEAASIAEIIINSNYTDEED NOV121 GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12m GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12n GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12o GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12p GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12q GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12r GGTLIDAQWVLTAAHCFFVTREKVLEGWKVYAGTSNLHQLPEAASIAEIIINSNYTDEED NOV12a DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12b DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPSLREVQ NOV12c DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPSLREVQ NOV12d DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12e DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12f DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12g DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12h DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12i DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12j DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12k DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV121 DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12m DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12n DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12o DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12p DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12q DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPSLREVQ NOV12r DYDIALMRLSKPLTLSAHIHPACLPMHGQTFSLNETCWITGFGKTRETDDKTSPFLREVQ NOV12a VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12b VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12c VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12d VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12e VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLACVTSW NOV12f VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12g VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12h VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12i VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12j VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12k VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV121 VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12m VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12n VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12o VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12p VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12q VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12r VNLIDFKKCNDYLVYDSYLTPRMMCAGDLRGGRDSCQGDSGGPLVCEQNNRWYLAGVTSW NOV12a GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV-- NOV12b GTGCGQRNKPGVYTKVTEVLPWIYSLE------------------------------ NOV12c GTGCGQRNKPGVYTKVTEVLPWIYSLE------------------------------ NOV12d GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLE NOV12e GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12f GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12g GTGCGQRNKPGVYTKVTEVLPWIYSKMEVKSLQQDTAPSRLGTSSGGDFGGAPRVLEG 211 WO 03/093432 PCT/US03/13690 NOV12h GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12i GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12j GTGCGQRNKPGVYTKIVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12k GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRV-- NOV121 GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12m GTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFRKS--------------------- NOV12n GTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFRKSLEG------------------ NOV12o GTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFTKS--------------------- NOV12p GTGCGQRNKPGVYTKVTEVLPWIYSKMESEVRFTKS--------------------- NOV12q GTGCGQRNKPGVYTKVTEVLPWIYS-------------------------------- NOV12r GTGCGQRNKPGVYTKVTEVLPWIYSKMEVRSLQQDTAPSRLGTSSGGDPGGAPRVLEG NOV12a (SEQ ID NO: 104) NOV12b (SEQ ID NO: 106) NOV12c (SEQ ID NO: 108) NOV12d (SEQ ID NO: 110) NOV12e (SEQ ID NO: 112) NOV12f (SEQ ID NO: 114) NOVl2g (SEQ ID NO: 116) NOV12h (SEQ ID NO: 118) NOV12i (SEQ ID NO: 120) NOV12j (SEQ ID NO: 122) NOV12k (SEQ ID NO: 124) NOV121 (SEQ ID NO: 126) NOV12m (SEQ ID NO: 128) NOV12n (SEQ ID NO: 130) NOV12o (SEQ ID NO: 132) NOV12p (SEQ ID NO: 134) NOV12q (SEQ ID NO: 136) NOV12r (SEQ ID NO: 138) Further analysis of the NOV12a protein yielded the following properties shown in Table 12C. Table 12C. Protein Sequence Properties NOV12a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 4; pos.chg 1; neg.chg 2 H-region: length 8; peak value 0.00 PSG score: -4.40 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -6.21 possible cleavage site: between 24 and 25 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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: 1 212 WO 03/093432 PCT/US03/13690 INTEGRAL Likelihood =-15.71 Transmembrane 168 - 184 PERIPHERAL Likelihood = 2.86 (at 354) ALOM score: -15.71 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 175 Charge difference: 0.5 C( 2.5) - N( 2.0) C > N: C-terminal side will be inside >>> membrane topology: type lb (cytoplasmic tail 168 to 586) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 10.42 Hyd Moment(95): 7.40 G content: 0 D/E content: 2 S/T content: 0 Score: -5.39 Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 10.2% NLS Score: -0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: XXRR-like motif in the N-terminus: ERDS 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: too long tail Dileucine motif in the tail: found LL at 173 LL at 174 213 WO 03/093432 PCT/US03/13690 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues -i Final Results (k = 9/23): 69.6 %: nuclear 13.0 %: mitochondrial 4.3 %: vacuolar 4.3 %: plasma membrane 4.3 %: cytoplasmic 4.3 %: vesicles of secretory system >> prediction for CG50949-03 is nuc (k=23) A search of the NOV 12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12D. 214 WO 03/093432 PCT/USO3/13690 Table 12D. Geneseq Results for NOV12a NOV12a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAE01944 Human transmembrane serine 1..568 556/568 (97%) 0.0 protease (Endotheliase 2-L) protein - 1..563 559/568 (97%) Homo sapiens, 688 aa. _______ [WO200136604-A2, 25-MAY-2001].... ..... . .. AAE17238 Human transmembrane serine 1..559 554/559 (99%) 0.0 protease - Homo sapiens, 562 aa. 1..554 554/559 (99%) [WO200196538-A2, 20-DEC-2001] AAE01943 Human transmembrane serine 1..559 554/559 (99%) 0.0 protease (Endotheliase 2-S) protein - 1..554 554/559 (99%) Homo sapiens, 562 aa. [WO200136604-A2, 25-MAY-2001] AAU82746 Amino acid sequence of novel 1..559. 523/564 (92%) 0.0 human protease #45 - Homo sapiens, 1..529 523/564 (92%) 537 aa. [WO200200860-A2, 03 SJAN-2002] AAB85042 Human SER6 protein sequence - 148..559 412/412 (100%) 0.0 Homo sapiens, 421 aa. 2..413 412/412 (100%) [WO200136645-A2, 25-MAY-2001] In a BLAST search of public sequence databases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12E. 215 WO 03/093432 PCT/USO3/13690 Table 12E. Public BLASTP Results for NOV12a NOV12a Identities/ Protein Residues/ Similarities for Expect Accession Protein/Organism/Length Match the Matched Value Number Residues Portion Q9BYE2 Membrane-type mosaic serine 1..586 577/586 (98%) 0.0 protease - Homo sapiens 1..581 579/586 (98%) (Human), 581 aa. CAC41221 Sequence 5 from Patent 1..568 556/568 (97%) 0.0 WO0136604 - Homo sapiens 1..563 559/568 (97%) (Human), 688 aa. .. CAC41220 Sequence 3 from Patent 1..559 554/559 (99%) 0.0 WO0136604 - Homo sapiens 1..554 554/559 (99%) (Human), 562 aa. AAO38062 Transmembrane protease serine 6 1..559 551/559 (98%) 0.0 - Homo sapiens (Human), 558 aa. 1..554 553/559 (98%) Q9BYE1 Mosaic serine protease - Homo 1..559 520/564 (92%) 0.0 sapiens (Human), 537 aa. 1..529 521/564 (92%) . .. PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12F. Table 12F. Domain Analysis of NOV12a Identities/ Pfam Domain NOV12a Match Region Similarities Expect Value for the Matched Region Idlrecepta 202..228 10/43(23%) 0.45 17/43 (40%) SRCR 240..315 17/116(15%) 0.16 52/116 (45%) trypsin 326..554 98/266 (37%) 6.8e-83 187/266 (70%) 216 WO 031093432 PCT/US03/13690 Example 13. The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A. Table 13A. NOV13 Sequence Analysis NOV13a, CG51018-01 SEQ ID NO: 145 3447 bp DNA Sequence iORF Start: ATG at 55 ORF Stop: TGA at 2932 GGTAGCCGACGCGCCGGCCGGCGCGTGACCTTGCCCCTCTTGCTCGCCTTGAAAATGGAAAAGATGCT CGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCCTCCTCCCTGCCGAGGCCAGGCAGCGGTCAC GTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGCAGACGGCCCTTCTGGAGAGTTCC TGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCTCGCAGTGTCAACACCCATGACTA TGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGACATTGGTCCTGATGTCACCCGAG TGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAGTTCTCCCTCAAGACCTTCAAGAGGAAGTCC GAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGCACCATGACTGGGCTGGCCATCCA GTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGGCCCGGCCCCTGAGGGAGAATGTGCCACGGG TCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCGAGGTGGCTGCTAAGGCACGGGAC ACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTCAACACCTTGAAGTCCATTGGGAG TGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCAGATTGAGACGCTGACCTCCGTCT TCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGCATAACTGTGCCCACTTCTGCATC AACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGGCTACATTCTCAACTCGGATCAGACGACTTG CAGAATCCAGGaTCTGTGTGCCATGGAGGACCACAACTGTGAGCAGCTCTGTGTGAATGTGCCGGGCT CCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATGGGAAGAGGTGTGTGGCTGTGGAC TACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAATGCTGATGGCTCCTACCTTTGCCA GTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAACGTGCACAAAGATAGACTACTGTGCCTCAT CTAATCATGGATGTCAGTACGAGTGTGTTAACACAGATGATTCCTATTCCTGCCACTGCCTGAAAGGC TTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGATCAACTACTGTGCACTGAACAAACCGGGCTG TGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTGCCACCGTGGCTACACTCTGGACC CCAATGGCAAACCCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCATGGCTGTGAGCAGCTGTGT CTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTCCTCATCAACGAGGACCTCAAGAC CTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGAATACTCCTGTGTCAACATGGACA GATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAGACGTGTGCAAAATTG GACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTAAGCAGTGAAGATTCGTTTGTGTG CCAGTGCTTTGAAGGTTATATACTCCGTGAAGA GGAAAAACCTGCAGAAGGAAAGATGTCTGCCAAG CTATAGACCATGGCTGTGAACACATTTGTGTGAACAGTGACGACTCATACACGTGCGAGTGCTTGGAG GGATTCCGGCTCACTGAGGATGGOAAACGCTGCCGAATTTCCTCAGGGAAGGATGTCTGCAAATCAAC CCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAAATGTCAGAGGGAT TTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGCCCAATTGACCTGGTCTTTGTG ATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGAAGCAGTTTGTCACTGGAATTAT AGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACACAGGTCCACA CAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAAGCCGTGGCCCACATGAAATAC ATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGAGAGAAGTTTTACCCAAGGAGA AGGGGCCAGGCCCTTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGACGGACGGGCTCAGG ATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACTATGTATGCTGTTGGGGTAGGA AAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAACAAGCATCTCTTCTATGCCGA AGACTTCAGCACAATGGATGAGATAAGTGAAAACTCAAGAAAGGCATCTGTGAAGCTCTAGAAGACT CCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCAACAGCCAACAGAATCTGAG CCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTGCAGTGCAACACAGATATCTGTT TGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACAAAACCTTCAGGAAGCCCTT TGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAACCTTGCAAACGAAGAA GTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCTGGAAAATCGCCTGAG ATACAGATGAAGATTAGAAATCGCGACACATTTGTAGTCATTGTATCACGGATTACAATGAACGCAGT GCAGAGCCCCAAAGCTCAGGCTATTGTTAAATCAATAATGTTGTGAAGTAAAACAATCAGTACTGAGA AACCTGGTTTGCCACAGAACAAAGACAAGAAGTATACACTAACTTGTATAAATTTATCTAGGAAAAAA ATCCTTCAGAATTCTAAGATGAATTTACCAGGTGAGAATGAATAAGCTATGCAAGGTATTTTGTAATA TACTGTGGACACAACTTGCTTCTGCCTCATCCTGCCTTAGTGTGCAATCTCATTTGACTATACGATAA 217 WO 03/093432 PCT1US03113690 AGTTTGCACAGTCTTACTTCTGTAGACACTGGCCATAGGAUXJATGCTGTTTTTTTGTACTGGACTTTA CCTTGATATATGTATATGGATGTATGCATAATCATAGGACATATGTACTTGTGGAACAGTTGGAT NOV13a, C051018-011' .JSEQ ID NO: 146 99aa ~W170.k Protein Sequence ~5 a MELMLAGCFLLILGQIVLLpAEARQRSRGRS ISRGRHARTliPQTALLESSCENKRADLVFIIDSSRSV NTHDYAKVKEPIVDILQFLDIGPDVTRVGLLQYGSTVK3NEPSLKTFI{RKSEVEPAVKRMRHLSTGTMT GLIYLIFEEAPRNPVMVDGPDVEAKRTIIAGGVFT KSGEHDVLAFQELSFKLTAMSLHCHCNPSVRKGIN DQTTCRIQDLCAMEDHNCEQLCVNVPGS FVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECvNADG SYLCQCIIEGFALNPDEKTCTKIDYCASSNHGCQYECNTDDSYSCHCLKGFTLNPDKICTCRRINYCAL NKPGCEUECVNMEESYYCRCHRGYTLDPNGKPCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLIN EDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDflGCEH8CVSSE DSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLTEDCRI9SGKD VCKSTHIIGCEIIICV~NNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGEEFEVJVKQF VTGI IDSLTI SPKAARVGLLQYSTQVHTEFTLRNFNSKDMKKAVHMYMGKGSMTGLALKHMFERS FTQGEGARPFSTRVPRAAIVFTDGRAQIDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNyH .LFYAEDFSTMDEISEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTBSEPVTINIQDLLSCSNFAVQ HRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKDQCKCENLMFQNANEEVRKTQRLEEMTQRMEAL ENRLRYR NOV13b, 274051273 ISEQ ID,.NO: 147 1170 8 bp _______ DNA Sequence lRF Start: at 1 IORF Stop: TGTA at 850 GCCCTCGAGGGATTTTCTGAATCGCACCTCGCTCTCCATCTTGCTGTTCCAGGGAGACTTCTG TCACTTrGGTO3TACACACCAGGTTTGTTTCTCTGGCCACAGCCTGTGCCCCAGCTGGTGACACCTGCC AGGTACCAGCc3GTTGTTCTGCTCACAGACAAGAGGCCCCCCGCTGTCTCCCTGGCAGOAGTCTCTGCC CCCACGAAGGTCCCCAGCACACATCATCCTTGGGGTAAGGTAACTGTCATAGACCAAGTAGTCATTGC ATTTCTTGAAGTCGATGAGATTGACCTGCACCTCCCGGAGGAAGGGGGATGTCTTGTCATCTGTCTCC CTGGTCTTGCCAAAGCCTGTGATCCAGCAGGTCTCATTGAGGCTAGGTCTGTCCTGCATGGGGAG GCAAGCAGGGTGGATGTGAGCGGACAGOGTCAGGGGCTTGQACAGCCGCATGAGGGCGATGTCATAGT CGTCCTCCTCATCGGTGTAATTGCTGTTGATGATGATCTCGCA\JTGGAGGCTGCCTOAGGCAACTGG TGCGGTTGCTGGTGCCCGCGTACACCTTCCAGCCCTCCAGGACCTTCTCCCGGGTCACGAAGAAGCA GTGGGCGGCAGTGAGCACCCACTGGGCGTCAATGAGCGTGCCTCCACAGATGTGGGTGTGCCAGT GCAGACTCACTTGCOAAGGCCACTTGCTATCCGAGGCCAGCGCCCCTCCCACGATCCGCCCGGTCATG GCCCTCAGTCCGCAQTGGGAACACTGGA.GGGAGATATACCGCTGGGAAGGGCATTCAGACCTGTGGAG GCTTTCCTGGATGGTGGAGTTGTATCTCA1AGATTGAGAAGCTGTTGGCAAAATCCCTGTGGGCAACCT CGGTTGTCCGGTGAGCACTCTCGAAACCCAkGCTGCTGGCAGGTCTTCTCTGAGTAGGAGTCATTCCAG TTGCTGCTACAGATGGGAAGCCACTGATGGGAGGACCCAGAGTAGATTTTAAGCAGAGACTTGTCCCA GTCAAACCTCACGCAGCCCAGCTCGTCACTCTTCAGCTTGCAGTCCACCACCCCGTCACAGCGAACAG CGTGCTTGGGACAGCTCTCCCTCTGCTCCTTGTACCTGATCCCTGTGTGGCCCTGCCAGACTGGAAG AGGATGATGAGCGAAACCACCAGGGCAATGAGGAGGAGCACGCACCCGATGAGCGGTAGCTGCTTCTG GCCCTCCCGCCAGGTGAACTTGGGAGGCTCGTACCTGGGCTCTQCCTGGTGGCCCTGGTTGCTGGTG CTGACCTGGCAGGAGATGATCGGATGGGTACAGCCCCCACTGGTGTTGCTCTACAAGGTACACTCTG GTTGGGGAGGTTGTCACCGAGGCTGACCTGGCGGATGATGACCTGCCGGATGAGGACCTGGAGTGA TGCCAGAGCCGGAGATGCCCGGGCTGGAGATGCCTGGGCTGGAGATGCCCGGCCTGGAGATGCCCGGC CTGGAGGTGTACCAGCTGGAGATGCCTGGGCTGGAGATGCCCGGCCCGGAGGTGTCCCAGCTGGAGAT GCCTGGGCTGGAGATGCCTGGGCTGGAGATGCCCGGCCTGGAGGTGTCCCAGCTGGAOATGCCTGGGC TGGAGATGCTCCAGCTGAAGGTGTTCTTGCTGGAGATGCATTCCCGTGGCTGTCCCTCTCCATGGTGG ATCCGGTG NOV13b, 274051273 SEQ ID NO: 148:283 aa. MW at 2979.9kD PoenSequence ALEGFSESILALHLAVNPGKNFCH-FGVIiTRFVSLATACAPAGDTCQVPAVVLLTDKRPPAVSLA-GVSA PTVSHPGVVDVIPEDILLPEGLILGAADALEKLMG ASRVDVSGQGQGLGQPIHEGDVIVVLLIGVIAVDDDLGNGGCLRQLVQVAGRVHLPALQDLLPGHEEA VGGSEHPLGVNERASTDVGGAEVQTHLPRPIZ\IRGQRPSHDPPGIHGPQSAVGTLEDIPLGJAFRPVE AFLDGGVVSQD 218 WO 03/093432 PCT/11S03/13690 N OVI13c, 274051251 ISEQIDNO: 149 2893bp DNA Sequence JORF Start: at 2 *ORF Stop: end of sequence CACCAGATCTCCCACCATGGAAAAGATGCTCGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCC TCTCTCGGCAGACCCCTOAGCACCACGAAA~CCGC CACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGA CACCCC.TTA-ACAG TTC AGCAGGTACTGCTTGAA TCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAG TTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTC CACGGGCACCATGACTGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGG CCCGGCCCCTQAGGGAGAATGTGCCACGGGTCATAA TGATCGTGACAGATGGGAGACCTCAGGACTCC GTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCALTTGGTGTGGGCCAGGT AGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATT TCAGCCAGATTGAGACGCTGACCTCCGTGTTCCAG'AGAAGTTGTGCACGGCCCACATGTGCAGCACC CTGGAGCATAACTGTGCCCACTTCTGCATCAALCATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGG CTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACT GTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTOGOCT GAGGATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTG TGTAAATGCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAA CGTGCAC!AAAGATAGACTACTGTGCCTrCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGAT GATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGAT CAACTACTGTc4CACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAALCATGGAGGAGAGCTACTACT GCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAAOCTGCAGCCGAGTGGACCACTGTGOA CAGCAGGACCATGGCTGTGAGCA3CTGTGTCTGAACZAQGGAGGATTCCTTCGTCTGCCAGTGCTCAGA AGGCTTCCTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATG GTTGTGAATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTC CGCAGCGATGGGAAGACGTGTGCA-AAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTC GTGTGTAA\GCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAA AAACCTGCAGAAGGAAAGATGTCTGCCAAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGT GACGACTCATACACTGCGAGTGCTTGGAGGGATTCCGGCTCCTGAGGATGGGAAACGCTGCCGAAG GAAGGATGTCTGCAAATCAACCC-ACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACA TCTGCAALATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGOC CCATTGACCTGGTCTTTGTGATCGATGGATCCAAGGTCTTGGAGAAGAGAATTTTGAGGTCGTGAA GCAGTTTGTCACTGGGATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCC AGTATTCCACACAGGTCCALCACAGAGTTCACTCTGAGAAACTTCAACTCAGCCA-AACATGAAAAA GCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGA GAGAA GTTTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTOT TCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACT ATGTATGCTGTTGGGGTAGGAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAA CAAGCATCTCTTCTATGCCGAAGACTTCAGCACpATGGATGAGATAAGTGAAAAACTCAAGAAAGGCA TCTGTGAAGCTCTAGAALGACTCCGATGGAAG.ACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTC CAACAGCCAACAGAATCTGAGCCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTGC AGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAA CAAAACCTTCAGGAAGCCCTTTGGAAGAAAACACGATCAATGCAAATGTG2AAAACCTTATAATGTTC CAGACCTTGCAACGAGAAGTAAGAAATTAACACAGCGCTTAGAAGAATGACACAGGAA-TGGA AGCCCTGcGAAAATCGCCTGAGATA.CAGAGTCGACGGC INOV13c, 274051251 ISEQ ID NO: 150 1964 aa 1MW at 107650.5kD ~Protein Sequence TRSPTMEKMLAGCFLLILGQIVLLPAEAPERSRGRSISRGRHARTRPQTAuJLESSCENKPRADLVFI ID SSRSVNTHDYAKKEFIVDILQFLDIGPVTRVGLLQYGSTVKNESLKTFRKSEVERAVKRRILS TGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAACARDTGILIFAIGVGQV DFNThKSIGSEPHED~rWFLVANFSQIETLTSVFQKCKLCTAHMCSTLEHNCAHFCINIPGSYVCRCKQG YILNSDQTTCRIQDLCA4EDHNCEQLCVNVPGS FVCQCYSGYALAEDGKRCVAVDYCASENHGCEHEC VNADGSYLCQCHEGFALNPDEKTCTCIDYCASSNHGCQHECVN'TDDSYSCHCLKGFTLNPDKKTCRRI NYCALNKPGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSE GFLINEDLKTCSRVDYCLLSDHGCEYSCNMDRSFACQCPEGHVRSDGKTCAKLDSCALGDHiGCEHIS CVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGEEZFEVVYK 219 WO 03/093432 PCT1US03113690 QFVTGI IDSLTISPKARVGLLQYSTQVHTEFTLRFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFE RSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSEWASKAKAGITMYAVGVGKAIEEELQEIASEPT' KHLFYAEDFSTMDEI SEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFA VQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENIMFQNANEEVRKLTQRLEEMTQRME ALENRLRYRVDG NOV13d, 274051253 ISEQID NO: 151 2893bp JDNA Sequence - ORF Start: at 2 JORF Stop: end of sequence CACCAGATCTCCCACC!ATGGAAAA!GATGCTCGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCC TCCTCCCTGCCGAGGtZCAGGGAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACC CACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGA CAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAAT TCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAG TTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTC CACGGGCACCATGACTGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGG CCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCC GTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGT AGACTTCAACACCTTGAAGTCCA-TTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATT TCAGCCAGAkTTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACOGCCCACATGTGCAGCACC CTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGG CTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACT GTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCT GAGGATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTG TGTAAATGCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAAAA CGTGCACAAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGAT GATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGAT CAACTACTGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACT GCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCA CAGCAGGACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGA AGGCTTCCTCATC~ACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACC-ATG GTTGTGAATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTC CGCAGCGATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTC GTGTGTAAGCAGTGAA! GATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAA1 AACCTGCAGAAGGAAGATGTCTGCCAGCTATAGACCATGGCTGTGAACACATTTGTGTGAACAGT GACGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAG GAAGGATGTCTGCAATCACCCACCATGGCTCGAACACATTTGTGTTAATAATGGGAATTCCTACA TCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGC CCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTTGGAGAAGAGAATTTTGAGGTCGTGA GCAGTTTGTCACTGGGATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCC AGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAA-ACTTCAACTCAGCCA.AAGACATGAAAAAA GCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGA GAGAAGTTTTACCCAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGT TCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAA.GGCCAATGGTATCACT ATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAA CAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATcGATGAGATAAGTGAAAAACTCAAGAAAGGCA TCTGTGAAGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTC CALACAGCCAACAGAATCTGAGCCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTGC AGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAA CAAAACCTTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTC CAGAACCTTGCAACGAAGAAGTAAGAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGA AGCCCTGGAAAATCGCCTGAGATACAGAGTCGACGGC 1 NOV13d, 274051253 SE DN:152 6 aa M t175. PoenSequence _SE-ID-N-:-111264 M at075.k TRSPTMEKD4LAGCFLLILGQIVLLPAEARERSRGRS ISRGRHARTHPQTALLESSCENKP-AnLVFIID SSRSVNTHDYAkKYEFIVDILQFLDGPDVTRVGLLQYGSTVKNFSLKTFKRKSEVERAVJRMRHLS TGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAA@ARDTGILIFAIGVGQV DFNTLKS IGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAHMCSTLEHNCAflFCINIPGSYVCRCKQG 220 WO 03/093432 PCT1US03113690 YILNSDQTTCRIQDLCMEDHNCEQLCVNVPGSFVCQCYSGYAIJ4DGKRCVAVDYCASEIflGCEHEC VNADGSYLCQCHEGFANPDKTCTKIDYCASSNHGCQHECVNTDDSYS CHCLKGFTL NPDKKTCRRI NYCALN'KPGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLN'rEDSFVCQCSE GFLINEDLKTCSRVDYCLLhSDHGCEYSCVNMDRS FACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHS CVS SEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRR KDCSHGEIVNNYCCEPLEDRCKTGILFIGKLENEV QFVTGI IDSLTISPKRVGLLQYSTQVHTFTLRNUSADMKKAVAKYMGGSMTGLALaMFE RSFTQGEGAPLSTRVPRAAIVFTDRAQDDVSEWASCAKANGITMYAVGVGKAIEEELQEIASEPTN KHLFYAEDFSTMDEISEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFA VQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHmQCRCENLIMFQNLANEEVRKLTQRLEEMTQRME ALENRLRYRVDG NOV 13e, 306562753 EIDN:13 286b DNA Sequence __ ~ORF Start: at 2 ~ORF Stop: end of sequence CACCAGATCTCCCACQATGGAAAAGATGCTCGCAGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCC TCCTCCCTGCCGAGGCCAGGGAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCGACACGCTCOACC CACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGA CAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAAT TCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCACACTGTCAAGATGAG TTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAGAGGATGCGGCATCTGTC CACGGGCACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAO3AGGGGG CCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCC GTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTATCTTTGCCATTGGTGTGGGCCAGGT AGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATT TCAGCCAGATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACC CTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAACA(G CTACATTCTCACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACA~CT GTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCT GAGGATGGGAAGAGGTGTGTGGCTGTGGATACTGTGCCTCAGAACCACGGATGTGACATGAGTG TGAAGTAGCCTCTTCATCCTAGATGTTACCGTAAA CGTGCACAAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTACACAGAT GATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAGAAAACCTGCAGAAGGAT CAACTACTGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCACATGGGGAGAGCTACTACT GCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCA CAGCAGGACC7ATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGA AGGCTTCCTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATG GTTGTGAATACTCCTGTGTCAACATGOACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTC CGCAGCGATGGGAAGACGTGTGCAAATTGGACTCTTGTGCTCTGGGGOACCACGGTTGTGAACATTC GTGTGTAAGCAGTGAGATTCGTTTGTTGCCAGTGCTTTGAAGOTTATATACTCCGTGAAGATGGAA AACCTGCAGAGAAGATGTCTGCCAGCTATAGACCATGGCTGTGACACATTTGTGTGMCAGT GACGACTCATACACGTGCGAGTGCTTGAGGGATTCCGGCTCGCTGAGGATGACGCTOCCGAAG GAGAGCGAACACACTGTCGAAATGGTAATGATCTC TCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGGACGGTGCAGATGCACTGAAGGC CCATTGACCTGGTCTTTGTGATCGATGGATCCAGAGTCTTGGAGAGAGAATTTTGAGGTCGTGAA GCGTTTGTCACTGGAATTATAGATTCCTTGACATTTCCCCCAAGCCGCTCGAGTGGGGCTGCTCC AGATCCCGTCCCGGTATTAAATCATACAAAAGAAk GCCGTGGCCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGA GAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAGGGTGCCCAGAGCAGCCATTGTGT TCACCGACGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAAAGCCAAGGCCAATGGTATCACT ATGTATGCTGTTGGGGTAGGAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAA CAAGCATCTCTTCTATGCCGAAOACTTCAGCACA.ZTGGATGAGATAAGTGAAAACTcAAGAAAGGCA TCTGTGAAGCTCTAGAAGACTCCGATGGAGACAGACTCTCCACAGGGACTGCCAAACGGTC CAACAGCCAACAGTGCAACACAGATATCTGTTTGAAGAGACAATCTTTTACGGTCTACACAAAAGCT TTCCCATTCAACAAAACCTTCAOGAAGCCCTTTGGJAGAACACGATCAATGCAAATGTGAAA7ACC TTTAGTCGACTCACAGATAGAATAAACCTGAAAGC CAGAGAATGGAAGCCCTGGAAAATCG3CCTGAGATACAGAGTCGACGGC 221 WO 03/093432 PCTUSO3I1369O NOV13e, 306562753 ]SEQ ID NO: 154 1§45 a MW at 105589.3kD Protein Sequence TRSPTMEICMLAGCFLLLGQIVLLPAEARERSRGRSISRGRHARTHPQTALLE .S .SCENIRADLVFI ID SSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVxE2FSLKTFKRKSEVRAVYJRMRJS TGTMTGLAIQYAI.NIAFSEAEGRPLRENVPRVIMIVTDGRPQDSVAEVAAjADTGILIFAIGVGQV DFNTLKS IGS EPHEDHVFLVANFSQIETLTSVFQKKLCTAHMCSTLEHNCAnFCINIPGSYVCRCKQG YILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVCQCYSGYAJAEDGKRCVAVDYCASENHGCEHEC VNADGSYIJCQCHEGFAIJNPDEKTCTKIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRI NYCALNKPGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSE GFLINEDLKTCSRVDYCLLSDHGCEYSCVNRSFACQCPEGHVLRSDGKTCALDSCALGDHGCEHS CVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDG(RCRR KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGP IDLVFIDGSKSLGEENFEVVK QFVTGIIDLIP RGLYTVTFLNNSKMKVHKMKSTLLHP RS FTQGEOARPLSTRVPRAAIVFTDGRAQDDVSEWASKAKANGITM4YAVGVGKAIEEELQEIASEPTN KHLFYAEDFSTMvDEI SEKLKKGICEALEDSDGRQDSPAGELPKTVQQPTVQIHnYLFEEDNLLRSTQKcL SHSTKPSGSPLEEKHDQCKCENLIMFQNLNERVRKLTQRLEEMTQRMEALENRLRYRVDG 1NOV13f, CG51018-02 SEQ ID NO: 155 12742 b ?DNA Sequence 6iStr:at I IORF Stop: end of sequence~___ AGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGCAGACGGCCCT TCTGGAGAGTTCCTGTGAGAACAAGCGGGCAG.ACCTGGTTTTCATCATTGACAGCTCTCGCAGTGTCA ACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGACATTGGTCCT GAGCCCATGCTCCATTGAGATTAGAGGTTCTAGCT CAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGCACCATGACTG GGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAGCAGAGGGGGCCCGGCCCCTGAGGGAG AATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCGAGGTGGCTGC TAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTAACACTTGA AGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCAGATTGAGACG CTGACCTCCGT3GTTCCAGAAGAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGCATAACTGTGC CCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAACAGGCTACATTCTCAACTCTG ATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACACTGTGAGCAGCTCTGTGTG AATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATGGGAAGAGGTG TGTGGCTGTGGACTACTGTGCCTCAGAXACCACGGATGTGAACATGAGTGTGTAAXJTGCTGATGGCT CCACT*C GCTAGGTTCCTACAAAG.AAGGAAAAAA TACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGATGATTCCTATTCCTGCCA CTTTAAGTTCCGACAAAGAACTCGAGTACATTCCG ACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTGCCACCGTGGC TACACTCTGGACCCCAAT GGCAAAACCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCTGGCTG TGAGCAGCTGTGTCTGACACGGAGGATTCCTTCGTCTGCCAGTGCTAGAAGGCTTCCTCATCAACG AGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGATACTCCTGT GTCAPAATGGACAGATCCTTTGCCTGTAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAGAC GTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGACATTCGTGTGTAGCAGTGAAG ATCTTTTCATCTG7AGTTTATCTACTGAACTCGAGA GAGCGC* TTGCATGTTACCTTTTAAATAGCCTCCT CGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGCGCTGCCGAGGAGGATGTCTGCAT CACCCACCATGGCTGCGACACATTTGTGTTATATGGGATTCCTACATCTGCAAATGCTCAGAG GOATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGATGCACTGAAGGCCCAATTGACCTGGTCTT TGTGATCGATGGATCCAAGAGTCTTGGAGAGAGATTTTGAGGTCGTGAAGCAGTTTGTCACTGGAA TTATAGATTCCTTGACAATTTCCCCCAAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACCAGGTC CAAAATCCCGGACTACCGCAGCTAAAGCTGCACTA ATACATGGGAAGGGCTCTATGACTGGGCTGGCCCTGAACACATCTTTGAGAGA&GTTTTACCCAG GAGAAGGGGCCAGGCCCCTTTCOACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGACGGACGGGCT CAGGATGACGTCTCCAGTGGGCCAGTAGCCAGGCCATTGTATCACTATGTATGCTGTTGGGT AGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACXAACAAGCATCTCTTCTATG CCGAAGACTTCAGCACAATGGATGAGATAJAGTGAAACTCAAGAAGGCATCTGTGAAGCTCTAGAA GACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAACGGTCCAACAGCCAACAGTGCA ACCGTTTTTAGAAATTTACGCAAAAGTTCATACAA CTCGAGCTTGAAAAAGTATCATT.AACTTAGTCGA 222 WO 03/093432 PCTUSO3I1369O CTTGCAACGAAGAGTAAGAAAATTAACACAGCGCTTAGAGAAATGACACAGAGAATGGAAGCCCT GGAA1AATCGCCTGAGATACAGA NOV13f, CG51018-02 ISEQ ID NO: 156 .914,aa jMW at O2314.4kD Protein Sequence 1 RQRSRGRSISRGRH1ARTHPQTALLESSCENKRZADLVFI IDSSRSVNTHDYAKVKEFIVDILQFLDIGP DVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRE NVJPRVIMIVTDGRPQDSVAEVAAKARDTGILIFAIGVGQVDFNTLKS IGSEPHEDHVFLVANFSQIET LTSVFQKKLCTAHMCSTLEHN'CAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMVEDHNCEQLCV NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDKKTCTKID YCASSNBIGCQHECVNTDDSYSCHCLKGFTLlQPDKKACRRINYCALNKPGCEHECVNMEESYYCRCHRO YTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCEYSC VNNDRSIFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCVSSEDSFVCQCFEGYILREDGKTCRRK DVCQAIDHGCEHICVNSDDSYTCECLEGFRLAEDGKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSE GFVILAEDGRRCKKCTEGPIDLVFVIDGSKSLGEENFEVVKQFVTGI IDSLTISPKAARVG 4 IQYSTQV HTEFTLRNFNSAKDMKKAVAHMKYMGKGSMTGLALKIIFERSFTQGEGARPLSTRVPRAAIVFTDGRA QDDVSEWASKAX1ANCITMYAVGVGKAIEELQEIASEPTNKHLFYAEDFSTMDEI SEKLKKGICEALE DSDGRQDSPAGELPKTVQQPTVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQN LAEEVRKLTQRLEEMTQRMEALENRLRYR NOV13g, CG51018-03 ISEQ ID NO: 157 176 bp DNA Sequence jORF Start: ATG at 3 00 RE Stop: TGYA at 2718 TGACCTTGCCCCTCTTGCTCGCCTTGAAATGGAAAAiGATGCTCGCAGGCTGCTTTCTGCTGATCCTC GGACAGATCGTCCTCCTCCCTGCCGAGGCCAGGGAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAG ACACGCTCGGACCCACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAACATGCGGGCAGACCTGG TTTTCATCATTGACAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTG GACATCTTGCAATTCTTGGACATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCC!AATATGGCAGCAC TGTCAAGAATGAGTTCTCCCTCAAGACCTTCAAGAGGAAGTCCGAGGTGGAGCGTGCTGTCAAGAGGA TGCGGCATCTGTCCACGGGCACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCA GAAGCAGAGGGGGCCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAG ACCTCAGGACTCCGTGGCCGAGGTGGCTGCTAAGGCACGGGACACGGGCATCCTAATCTTTGCCATTG GTGTGGGCCAGGTAGACTTCAACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTC CTTGTGGCCAATTTCAGCCAGATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCA CATGTGCAGCACCCTGGAGCATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCA GGTGCAAACAAGGCTACATTCTCA-ACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATG GAGGACCACAACTGTGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGG CTACGCCCTGGCTGAGGATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCATCTAATCACGGAT GTCAGCACGAGTGTGTTAACACAGATGATTCCTATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAAT CCAGATAAGAAACCTGCAGAAGGATCACTACTGTGCACTAACAAACCGGGCTGTGAGCATGAGTG CGTCAACATGGAGGAGAGCTACTACTGCCGCTGCCACCGTGGCTACACTCTGGACCCCAATGGCAAAA CCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAG GATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTCCTCATCAACGAGGACCTCAAGACCTGCTCCCGGGT GGATTACTGCCTGCTGAGTGACCATGGTTGTGAATACTCCTGTGTCAACATGGACAGATCCTTTGCCT GTCAGTGTCCTGAGGGACACGTGCTCCGCAGCGATGGGAAGACOTGTGCAA2 AATTGGACTCTTGTGCT CTGGGGGACCACGGTTGTGAACATTCGTGTGTAAGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGA AGGTTATATACTCCGTGAAGATGGAA-AAACCTGCAGAAGGAAAGATGTCTGCCAAGCTATAGACCATG GCTGTGAACACATTTGTGTGAACAGTGATGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGCTC GCTGAGGATGGGAALACGCTGCCGA7LGGAAGGATGTCTGCAAATCAACCCACCATGGCTGCGAACACAT TTGTGTTAATAATGGGAATTCCTACATCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAA GACGGTGCAAGAAATGCACTG2AAGGCCCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTCTT GGAGAAGAGAATTTTGAGGTCGTG2AAGCAGTTTGTCACTGGAATTATAGATTCCTTGACAATTTCCCC CAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAAACT TCAACTCAGCCAAGACATGAAAAGCCGTGGCCCACATGAATACATGGGAAGGGCTCTATGACT GGGCTGGCCCTGAAACACATGTTTGAGAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCAC AAGGGTGCCCAGAGCAGCCATTGTGTTCACCGACGGACGGGCTCAGGATGACGTCTCCZ4GTGGGCCA GTAAAGCCAAGGCC'ATGGTATCACTATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTA CAAGAGATTGCCTCTGAGCCCACAAACAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATGGATGA GATAALGTGAAAAACTCAAGAAAGGCATCTGTGAALGCTCTArAAGACTCCGATGGAAGACAGGACTCTC 223 WO 031093432 PCTIUS03I1 3690 CAGCAGGGGAACTGCCAAAACGTCCAACAGCCAACAGTGCAACACAGATATCTGTTTGAAGAAGAC AATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACAAAACCTTCAGGAAGCCCTTTGGGAA ACACOATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAACCTTGCAAACGAAGAAGTAAGAAjAT TAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCTGGAAATCGCCTGAGATACAGATGA AGATTAGAAA7 TCGCGACACATTTGTAAAGGGCGAAT NOY13g, CG51018-03 SEQ DNO: 158 896 aa MW at 1OO259.6kD Protein Sequence MEKLAGCFLLIGQIVLLPAEARERSRGRSISGRHARTPQTALLESSCENMRADLVFI IDSSRSV NTHDYAKlCEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFICKSEVERAVKPMRHLSTGTMT GLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAAKARDTGILIFAIGVGQVDFNTL KSIGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNS DQTTCRIQDLCAMEDHNCEQLCVNVPGSFVCQCYSGYALAEDGK.CVAVDYCASSNHGCQHECVNTDD SYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNMEESYYCRCHRGYTLDPNGKTCSRVDHCAQ QDHGCEQLCLNTEDSFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLR SDGKTCARJJDSCALGDHGCEMSCVS SEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSD DSYTCECLEGFRLAEDGKRCPRKDVCKSTHHGCEHICVNNGNSYICKCSEGPVLAEDGRRCKKCTEGP IDLVFVIIDGSKSLGEENFEVVKQFVTGI IDSLTISPKAARVGLLQYSTQVHTEFTLRNFSAKDMKKA VAMKYMGKGSMTGLALKHMFERSFTQGEGAP.PLSTRVPRAAIVFTDGRAQDDVSEWASKAKANGITM YAVGVGKAIEEELQEIASEPTNKELFYAEDFSTMDEISEKLKKGICEALEDSDGRQDSPAGELPKTVQ QPTVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLAEEVRKLTQRLEEMTQ RMEALENRLRYR NOV13h, 13374217 SNP for JSEQ ID NO: 3447 bp SNP: 462 TIC CG5 1018-01 159 DNA Sequence JORE Start: ORE Stop: end of sequence ______________________ATG at 55 GGTAGCCGACGCGCCGGCCGGCGCGTGACCTTGCCCCTCTTGCTCGCCTTGAA-AATGGAAAAGATGCTCGC AGGCTGCTTTCTGCTGATCCTCGGACAGATCGTCCTCCTCCCTGCCGAGGCCAGGCAGCGGTCACGTGGGA GGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGCAGACGGCCCTTCTGGAGAGTTCCTGTGAGAAC AAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCTCGCAGTGTCAACACCCATGACTATGCAAAGGTCAA GGAGTTCATCGTGGACATCTTGCAATTCTTGGACATTGGTCCTGATGTCACCCQAGTGGGCCTGCTCCAAT ATGGCAGCACTGTC7AAGAATGAGTTCTCCCTCAAGACCTTCAAGAGG2AAGTCCGAGGTGGAGCGTGCTGTC AAGAGGATGCGGCATCTGTCCACGGGCACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATT CTCAGAAGCAGAGGGGGCCCGGCCCCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGA GACCTCAGGACTCCGTGGCCGAGGTGGCTGCTATAGGCACGGGACACGGGCATCQTAATCTTTGCCATTGGT GTGGGCCAGGTAGACTTCAACACCTTGAAGTCCATTGGGAQTGAGCCCCATGAOGACCATGTCTTCCTTGT GGCCAATTTCAGCCAGATTGAGACGCTGACCTCCGTCTTCAGA&GA-AGTTGTGCACGGCCCACATGTGCA GCACCCTGGAGCATAACTGTGCCCACTTCTGCATCA.L'CATCCCTGGCTCATACGTCTGCAGGTGCAAACAAL GGCTACATTCTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAJACTG TGAGCAGCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGG ATGGGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAACCACGGATGTGACATGAGTGTGTAT GCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTAACCCAGATGAAAACGTGCACAAA GATAGACTACTGTGCCTCATCTAATCATGGATGTCAGTACGAGTGTGTTAACACAGATGATTCCTATTCCT GCCACTOCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAAACCTGCAGAAGGATCAACTACTGTGCACTG AACAACCGGGCTGTGAGCATGAGTCGTCAACATGAGAGACTACTAC'GCCGCTGCCACCQTGGCTA CACTCTGGACCCCAATGGCAAACCCTGCAGCCGAGTGGACCACTGTGCACAGCAGGACCATGGCTGTGAGC AGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTCCTCATCAACGAGGACCTC AAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGAATACTCCTGTGTCAACATGGA CAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTCTCCGCACGATGGGAAGACGTGTGC.AA3-ATTGG ACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTAAGCAGTGAACATTCGTTTGTGTGCCAG TGCTTTGAAGGTTATATACTCCGTGAAGATGGAAAAACCTGCAGAAGGAA.AGATGTCTGCCAAGCTATAGA CCATGGCTGTGAACACATTTGTGTGAACAGTGACGACTCATACACGTGCGAGTGCTTGGAGGGATTCCGGC TCACTGAGGATGGGAACGCTGCCGAATTTCCTCAGGGAAGGATGTCTGCAAATCAACCCAC!CATGGCTGC GAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAAATGCTCAGAGGGATTTGTTCTAGCTGAGGA CGGAAGACGGTGCAAGAA7ATGCACTGAAGGCCCAATTGACCTGGTCTTTGTGATCGATGGATCCAAGAGTC TTGGAGAAGAGAATTTTGA~GGTCGTAAGCAGTTTGTCACTGGAATTATAGATTCCTTGACAATTTCCCCC AAGCCGCTCGAGTGGGGCTGCTCCAGTATTCCACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAA 224 WO 03/093432 PCT/US03/13690 CTCAGCCAAAGACATGAAAAAAGCCGTGGCCCACATGAAATACATGiGGAAAGGGCTCTATGACTGGGTG CCCTGAAACAC.ATGTTTGAGAGAAGTTTTACCCAAGGAGAAGGGGCCAGGCCCTTTTCCACAAGGGTGCCC AGAGCAGCCATTGTGTTCACCGACGGACGGGCTCAGGATGACGTCTCCAGTGGGCCAGTAAAGCCAAGGC CAATGGTATCACTATGTATGCTGTTGGGGTAGGAAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTG AGCCCACAAACAAGCATCTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAG AAAGGCATCTGTGAAGCTCTAGAAGACTCCGATGGAAGACAGACTCTCCAGCAGGGGAACTGCCAAAAAC GGTCCAACAGCCAACAGAATCTGAGCCAGTCACCATAAATATCCAAGACCTACTTTCCTGTTCTAATTTTG CAGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACA AAACCTTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAAATGTGAAAACCTTATAATGTTCCAGAA CCTTGCAAACGAAGAAGTAAGAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAATGGAAGCCCTGG AAAATCG3CCTGAGATACAGATGAAGATTAGAAATCGCGACACATTTGTAGTCATTGTATCACGGATTACA A TGAACGCAGTGCAGAGCCCCAAA:GCTCAGGCTATTGTTAAATCAATAATGTTGTGAAGTAAAACAATCAGT ACTGAGAAACCTGGTTTGCCACAGAACAAAGACAAGAAGTATACACTAACTTATATA AATTTATrTAGGA n AAAAATCCTTCAGAATTCTAAGATGAATTTACCAGGTGAGAATGAATAAAPTATGAmAGGATTTTGArAm ATACTGTGGACACAACTTGOTTCTGCCTCATCCTGCCTTAGTGTGCAATCTCATTTGACTATACGATAAAG TTTGCACAGTCTTACTTCTGTAGAACACTGGCCATAGGAAATGCTGTTTTTTTGTAPTGGArTTTE PCTTG ATATATGTATATGGATGTATGCATAAAATCATAGGACATATATACTTAT~AAAAGTTGGATTTTTTnAT CAATATTAAAATTCACCACTTCAGAGAAAAGTAAAAAAA NOV1 3h, 13374217 SNP SEQ ID NO: -959 aa SNP: no change in the protein for 160 sequence CG51018-01 Protein Sequence MEKMLAGCPLLILGQIVLLPAEARQRSRGRSISRGRHARTHPQTALLESSCENKRADLVFIIDSSRSVNTH DYAKVKEFIVDILQPLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMRHLSTGTMTGLAIQY ALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHE DHVFLVANFSQIETLTSVFQKKLOTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCA MEDHNCEQLCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD ERTCTKIDYCASSNHGCQYECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNMEESYYC RCHRGYTLDPNGKPCSRVDHCAQQDHGCEQLCLNTED)SFVCQCSEGFLINEDLKTCSRVDYCLLSDHGCEY SCVNMDRSPACQCPEGHVLRSDGRTCARLDSCALGDHGCEHSCVSSEDSFVCQCFEGYILREDGKTCRRKD VCQAIDHGCEHICVNSDDSYTCECLEGFRLTEDGKRCRISSGKDVCKSTHHGCEHICVNNGNSYICKCSEG FVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEF TLRNFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFERSF TQGEGARPFSTRVPRAAIVFTDGRAQDDVSEW ASKAKANGITMYAVOVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDSDGRQDSPA GELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCEN LIMFQNLANEEVRKLTQRLEEMTQRMEALENRLRYR A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 13B. NOV13a ----- MEKMLAGCFLLILGQIVLLPAEARQRSRGRSISRGRHARTHPQTALLESSCENKR NOV13b ------ --------------------------------------- NOV13c TRSPTMEKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKR NOV13d TRSPTMEKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKR NOV13e TRSPTMEKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENKR NOV13f ---------------------------- RQRSRGRSISRGRHARTHPQTALLESSCENKR NOV13g -----MEKMLAGCFLLILGQIVLLPAEARERSRGRSISRGRHARTHPQTALLESSCENMR NOV13a ADLVFIIDSSRSVNTHDYAKVKEF'IVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK NOV13b ----------------------- ----------------------------- NOV13c ADLVFIIDSSRSVNTEDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK NOV13d ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK NOV13e ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK 225 WO 031093432 PCT/US03/13690 NOV13f ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK NOV13g ADLVFIIDSSRSVNTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFK NOV13a RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD NOV13b ---------------------------------------------------------- NOV13c RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD NOV13d RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGR2QD NOV13e RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD NOV13f RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQD NOV13g RKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARPLRENVPRVIMTVTDGRPQD NOV13a SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK NOV13b ----------------------------------------------- NOV13c SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK NOV13d SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK NOV13e SVAEVAAKARDTGILIFATGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK NOV13f SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK NOV13g SVAEVAAKARDTGILIFAIGVGQVDFNTLKSIGSEPHEDHVFLVANFSQIETLTSVFQKK NOV13a LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13b ------------------------------------------------------ NOV13c LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13d LCTAHMCSTLEHrnCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13e LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13f LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13g LCTAHMCSTLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCV NOV13a NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD NOV13b -------------------------------------------------------- NOV13c NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNAUGSYLCQCHEGFALNPD NOV13d NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD NOV13e NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD NOV13f NVPGSFVCQCYSGYALAEDGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPD NOV13g NVPGSFVCQCYSGYALAEDGKRCVAVDYCASS--------------------------- NOV13a EKTCTKIDYCASSNHGCQYECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH NOV13b ------------------------------------------------------- NOV13c EKTCTKIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH NOV13d EKTCTKIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH NOV13e EKTCTKIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH NOV13f KKTCTKIDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKACRRINYCALNKPGCEH NOV13g -------------- NHGCQRECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEH NOV13a ECVNMEESYYCRCHRGYTLDPNGKP-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL NOV13b ALEGFSESHLA-LH--LAVNP-GKNFCHFGVH--TRFVSLATACAPAGD--TCQVPAVVL NOV13c ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL NOV13d ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL NOV13e ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL NOV13f ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL NOV13g ECVNMEESYYCRCHRGYTLDPNGKT-CSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFL NOV13a INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH NOV13b LTDKRP--PAVSLAGVSAP------TKVPSTHH--- PWGKVTVIDQVVIAFLEVDEIDLH NOV13c INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH NOV13d INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH NOV13e INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDB NOV13f INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH 226 WO 031093432 PCT/US03/13690 NOV13g INEDLKTCSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDH NOV13a G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL NOV13b LPEEGGCLVI-------CLPGLA----KACDPAGLIEAKGLS-MHGEASRVD--VSGQG NOV13c G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL NOV13d G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCERICVNSDDSYTCECL NOV13e G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL NOV13f G-CEHSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL NOV13g G-CERSCVSSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECL NOV13a EGFRLTEDGKRCRISSGKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT NOV13b QGLGQPHEG---------DVIVVLLIGVIAVDDDLGNG---GCLRQLVQVA-GAR----V NOV13c EGFRLAEDGKRCRR---KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT NOV13d EGFRLAEDGKRCRR---KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT NOV13e EGFRLAEDGKRCRR---KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT NOV13f EGFRLAEDGKRCRR---KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT NOV13g EGFRLAEDGKRCRR---KDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCT NOV13a EGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL NOV13b HLPA--LQDLLP----GHE--EAVG----GSEHPLGVNERASTDVGGAEV--QTHLPRPL NOV13c EGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL NOV13d EGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL NOV13e EGPIDLVFYIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA~ARVGLLQYSTQVHTEFTL NOV13f EGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLQYSTQVHTEFTL NOV13g EGPTDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTISPKA-ARVGLLYSTQVHTEFTL NOV13a RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFERSFTQGEGARPFSTRVPRAAIVFTDG NOV13b AIRGQRP------SHDP---PG--------HGPQSAVGTLEGDIPLG-RAFRPVEAFLDG NOV13c RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG NOV13d RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG NOV13e RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG NOV13f RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHIFERSFTQGEGARPLSTRVPRAAIVFTDG NOV13g RNFNSAKDMKKAVAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDG NOV13a --RAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS NOV13b GVVSQD----------------------------------------------------- NOV13c --RAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS NOV13d --PAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS NOV13e --RAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS NOV13f --RAQDDVSEWASKAKANCITMYAVGVGKAIEEELEIASEPTNKHLFYAEDFSTMDEIS NOV13g -- RAQDDVSEWASKAKANGITMYAGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEIS NOV13a EKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFE NOV13b ----------------------------------------------------------- NOV13c EKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFE NOV13d EKLKKGICEALEDSDGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFE NOV13e EKLKKGICEALEDSDGRQDSPAGELPKTVQQPT-------------------VQHRYLFE NOV13f EKLKKGICEALEDSDGRQDSPAGELPKTVQQPT--------------------VQHRYLFE NOV13g EKLKKGICEALEDSDGRQDSPAGELPKTVQQPT-------------------VQHRYLFE NOV13a EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMEQNLANEEVRKLTQRLEEMTQRME NOV13b --------------------------------------------------------- NOV13c EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTRME NOV13d EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME NOV13e EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME NOV13f EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME NOV13g EDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRME 227 WO 03/093432 PCT/US03/13690 NOV13a ALENRLRYR-- NOV13b ----------- NOV13c ALENRLRYRVDG NOV13d ALENRLRYRVDG NOV13e ALENRLRYRVDG NOV13f ALENRLRYR-- NOV13g ALENRLRYR-- NOV13a (SEQ ID NO: 146) NOV13b (SEQ ID NO: 148) NOV13c (SEQ ID NO: 150) NOV13d (SEQ ID NO: 152) NOV13e (SEQ ID NO: 154) NOVI3f (SEQ ID NO: 156) NOV13g (SEQ ID NO: 158) Further analysis of the NOV13a protein yielded the following properties shown in Table 13C. 228 WO 03/093432 PCT/US03/13690 Table 13C. Protein Sequence Properties NOV13a SignalP analysis: Cleavage site between residues 24 and 25 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 3; pos.chg 1; neg.chg 1 H-region: length 18; peak value 10.51 PSG score: 6.11 GvR: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -0.88 possible cleavage site: between 23 and 24 >>> Seems to have a cleavable signal peptide (1 to 23) ALOM: Klein et al's method for TM region allocation Init position for calculation: 24 Tentative number of TMS(s) for the threshold 0.5: 0 number of TMS(s) .. fixed PERIPIHERAL Likelihood = 1.27 (at 188) ALOM score: 1.27 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 11 Charge difference: 4.0 C( 5.0) - N( 1.0) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 8.86 Hyd Moment(95): 9.72 G content: 2 D/E content: 2 S/T content: 0 Score: -7.20 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 49 ARTIHP NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 11.4% 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 229 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7 COIL: Lupas's algorithm to detect coiled-coil regions 925 M 0.82 926 F 0.94 927 Q 1.00 928 N 1.00 929 L 1.00 930 A 1.00 931 N 1.00 932 E 1.00 933 E 1.00 934 V 1.00 935 R 1.00 936 K 1.00 937 L 1.00 938 T 1.00 939 Q 1.00 940 R 1.00 941 L 1.00 942 E 1.00 943 E 1.00 944 M 1.00 945 T 1.00 946 Q 1.00 947 R 1.00 948 M 1.00 949 E 1.00 950 A 1.00 951 L 1.00 952 E 1.00 953 N 1.00 230 WO 03/093432 PCT/USO3/13690 954 R 1.00 955 L 1.00 956 R 1.00 957 Y 1.00 958 R 0.99 total: 34 residues Final Results (k = 9/23): 60.9 %: nuclear 17.4 %: mitochondrial 8.7 %: cytoplasmic 8.7 %: extracellular, including cell wall 4.3 %: peroxisomal >> prediction for CG51018-01 is nuc (k=23) A search of the NOV13 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 13D. Table 13D. Geneseq Results for NOV13a NOV13a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region ABJ10549 Human NOV4a protein - Homo 1..959 959/959 (100%) 0.0 sapiens, 977 aa. [WO200246408-A2, 19..977 959/959 (100%) 13-JUN-2002J AAB20159 Human protein SECP5 - Homo 1..959 956/959 (99%) 0.0 sapiens, 959 aa. [WO200105971-A2, 1..959 958/959 (99%) 25-JAN-2001] AAEO3877 Human gene 3 encoded secreted 1..959 929/959 (96%) 0.0 protein fragment, SEQ ID NO:127 - 47..983 931/959 (96%) Homo sapiens, 983 aa. [WO200136440-A1, 25-MAY-2001] ABG64542 Human albumin fusion protein #1217 4..959 926/956 (96%) 0.0 - Homo sapiens, 934 aa. 1..934 928/956 (96%) [WO200177137-A1, 18-OCT-2001] AAE03843 Human gene 3 encoded secreted 4..959 926/956 (96%) 0.0 protein HOGDP46, SEQ ID NO: 89 - 1..934 928/956 (96%) Homo sapiens, 934 aa. [WO200136440-A1, 25-MAY-2001] 231 WO 03/093432 PCT/US03/13690 In a BLAST search of public sequence databases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E. Table 13E. Public BLASTP Results for NOV13a Protein NOV13a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value Residues Portion CAC32426 Sequence 9 from Patent 1..959 956/959 (99%) 0.0 WO0105971 - Homo sapiens 1..959 958/959 (99%) (Human), 959 aa. Q8NDE6 Hypothetical protein - Homo 1..959 950/959 (99%) 0.0 sapiens (Human), 1016 aa 61..1016 952/959 (99%) (fragment). 000339 Matrilin-2 precursor - Homo 1..959 949/959 (98%) 0.0 sapiens (Human), 956 aa. 1..956 952/959 (98%) Q96FT5 Matrilin 2 - Homo sapiens 1..959 931/959 (97%) 0.0 (Human), 937 aa. 1..937 933/959 (97%) Q99K64 Matrilin 2 - Mus musculus 1..959 832/960 (86%) 0.0 (Mouse), 956 aa. 1..956 888/960(91%) PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13F. 232 WO 03/093432 PCT/US03/13690 Table 13F. Domain Analysis.of NOV13a Identities/ Pfam Domain NOV13a Match Region Similarities Expect Value for the Matched Region vwa 57..232 80/197 (41%) 4.3e-64 161/197 (82%) EGF 242..277 13/47 (28%) 1.2e-06 27/47 (57%) EGF 283..318 17/47(36%) 9.1 e-09 30/47 (64%) EGF 324..359 15/47 (32%) 8.8e-08 30/47 (64%) EGF 365..400 15/47 (32%) 7.7e-06 28/47 (60%) EGF 406..441 16/47(34%) 6.2e-06 29/47 (62%) EGF 447..482 11/47 (23%) 1.1e-05 28/47 (60%) EGF 488..523 13/47 (28%) 2.9e-06 26/47 (55%) granulin 488..525 11/44 (25%) 0.82 22/44 (50%) TIL 476..529 15/73 (21%) 0.8 39/73 (53%) EGF 529..564 13/47(28%) 2.1le-06 29/47 (62%) EGF 570..605 16/47 (34%) 2.4e-07 29/47 (62%) EGF 614..649 13/47 (28%) 4.8e-08 29/47 (62%) vwa 658..833 83/197 (42%) 1.6e-63 156/197 (79%) 233 WO 031093432 PCT/US03/13690 Example 14. The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A. Table 14A. NOV14 Sequence Analysis NOV14a, CG51051-07 SEQ ID NO: 161 1495 bp DNA Sequence JORF Start: ATG at 46 ORF Stop: TAG at 1486 TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTC GATTCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATG ATTTGTGTAAGACTCAGATTTACACGGAAGAAGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAA TCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCC TGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGC TGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCC ACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCT AACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCG ATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGAT CCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAAC AGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGAC CTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTT ACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACA CTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATG CCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGAC TGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAA AGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATAT GGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACA GTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCA GAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCG AGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGC TCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCAC MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFPAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELELARYFYAISDIKVRGRCKCNLEATVCVYDNSKLTCECERNTTOPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVC DNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF NOV14b, CG51051-14 SEQ ID NO: 163 169 bp DNA Sequence ORF Start: ATG at 46 ORF Stop: TAG at 1360 TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTC GATTCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATG ATTTGTGTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAA TCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCC TGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGC TGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCC ACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCT AACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCG ATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGAT CCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAAC AGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGAC CTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTT 234 WO 031093432 PCT/US03/13690 ACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGTGAGCTACA CTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATG CCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGAC TGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAA AGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTACGAATGTCTGCGACAACGAGCTCC TGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGC ATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCC CCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCT AGGTGTCAC NOVI4b, CG51051-14 SEQ ID NO: 164438aa _MW at 49339.7kD Protein Sequence MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELARPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDPFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGTNVCDNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCG SDSGQGAPPHGSPALLLLTTLLGTASPLVF NOV14c, 254537195 SEQ IDNO: 165 1398 bp DNA Sequence .. ... ... DNA SequenceORE Start: at 1 IORE Stop: end of sequence AGATCTGTGATGCAGCCCTACCCTTTGGTTTGGGGAATTATGATTTGTGTAAGACTCAGATTTACAC GGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGA AAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAAT CCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTT TGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTC TCCAGGTTAACATCACTCTGTCTTGGACAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTT GAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTA TCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCAC AGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATA ATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTOCTGGACCTCGCCTACGCAATATGGCTTCCCT CTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGC TOTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATC TCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAG CAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATC AGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCC AGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGT TTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACC ACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAAC GTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGG CAGCTGCGGCTCCGACTCTGGCCAGGGOGCGCCCCCGCACGGCTCCCCAGCGCTGOTGCTGCTGACCA CGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCCTCGAG NOV14c, 254537195 SEQ ID NO: 166 466 aa MW at 52338.1kD Protein Sequence RSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPPDITCGDPPETFCAMGN PYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITF ESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFMMDPKSVKDLSQHTVLEIICTEEYSTGYTTNSKI IHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFVDELHLARYFYAI SDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSPGSYLPIPKGTANTCIP SISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDNELLHCQNGGTCHNN VRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVFLE 1 ~4,,254537282 {SEQ ID NO: 1 67 750 bp IDNA Sequence IORF Start: at I ORF Stop: end of sequence AGATCTTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATAT TACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTG 235 WO 031093432 PCT/US03/13690 ATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCC ACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTG GAQCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGA TCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTA GATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTG CACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCACTTTGAAATCAAAGACAGGT TCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAG AAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCGTTGGGGAAAT ATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGACTCG AG NOV14d, 254537282 IEQ IDJ NO: 168%.250 aa 1MW at 28958.6kD Protein Sequence. RSCQPESTDMTKYLKVKLDPPDITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPS TFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCL DAPHMDPKSVKDLSQHTVLEIICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTK KLRDFFTVTDLRIRLLRPAVGEIFVDELHLARYFYAISDIKVRGLE NOV14e, CG51051-09 iSEQ ID NO: 169 140b DNA Sequence ORF Start: ATG at 26 IORF Stop: end of sequence AGGCTCCGCGGCCGCCCCCTTCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTT GAGGTTTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGC AAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACA ACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAG GCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCT GACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTC NOV14e, CG51051-09 1SEQ 1 NO: 170 480 aa1 MW at 53945.OkD Protein Sequence V MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCTQIYTEEGRVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDPEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFEMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLKATVCVYDNSKLTCECEHTTGPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVC DNELLHCQNGGTCMNVRCLCPAAYTGILCERLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF NOV14f, 304965116 SEQ ID NO: 171 1465 bp DNA Sequence ORF Start: at 2.OR Stop: end of sequence CACCAGATCTCCCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGiGTGTCCT CAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAA 236 WO 031093432 PCTIUS03I1 3690 GAAGGG7AAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGT GAAZACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCT ACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGAT TTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCA GGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAAT CTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAG TATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCA TACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCA2CAGGGTATACAACAAATAGCAA-AATAATCC ACTTTGAP.ATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTAC GGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGIATAAGGCTGTT AAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAG AZCATAAAGGTGCGAGGAAGGTGCAAGTGTAJATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAA TTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGG CCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCA2A.GGCACTGCAAATACCTGTATCCCCAGTA TTTCCAGTATTGGTJA 1CCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCT AACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTG4TTCAAGTTGCAAACCACAA GAGAGCGAI4TGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACACAACGTGC GCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTOCGAGGAGGCTGGCAGC TGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCcCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCT GCTGGGAACCGCCAGCCCCCTGG TGTTCCTCGAGGGC NOV14f, 3049651 16 SEQ ID NO: 17 48~MWa 576.k Protein Sequence TRSPTMYLSRFLS IHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVW7DYMACQPESTDNTKYLKV KLDPDITCGDPETFCAMGNPYMCNUNECDASTPELAPPELMDFEGRHPSTFWQSATWKEYPKPLQ VNITLSWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFIIDMPKSVKDLSQH TVLEI ICTEEYSTGYTTNSKI TNFEIKDRFAPFAGPRLRNMASLYGQLDTTKKLRDFPTVTDLRIRLL RPAVGEIFVDEJLHLARYFYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQG RPWSPGSYLPIrPKGTANTCIPSISSIGNPPKFNRIWPNISSLEVSNPKQvAPKLALSTVSVQVAHK RAVCDNEJLHCQNGGrCHNNVRCIJCPAAYTGIIJCEKLRCEEAGSCGSDSGQGAPPHGSPALLLITTI. LGTASPLVFLPG NOV4g, 273711018 ISEQ IDNO: 173 12818 bp DNA Sequence IORE Start: at 2 IORE Stop: end of sequence CACCAGATCTAGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGC AGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCT CGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGCAATTCTTGGA CATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCAATATGGCAGCACTGTCAAGAATGAGTTCTCCC TCPAGACCTTCAAGAGGAALGTCCGAGGTGGAGCGTGCTGTCAAGAGGATGCGGCATCTGTCCACGGGC ACCATGACTGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAGCAGAGGGGGCCCGGcC CCTGAGGGAGAAkTGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCG AGGTGGCTGCTAGGACGGGACACGGGCATCCATCTTTGCCATTGGTGTGGGCCAGGTAGACTTC AACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCA GATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGC ATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAxACAAGGCTACATT CTCAACTCGGATCAGACGACTTGCAGAATCC!AGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCA GCTCTGTGTG2ATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATG GGAAGAGGTGTGTGCTTGGACTACTGTGCCTCAGAACCACGGATGTGAACATGAGTGTGTAAAT GCGTGTCACTGCGGCTAGGTTCCTACAAGA-AGGA AAAGATAGACTACTGTG5CCTCATCTAATCACGGATGTCAGCACGAGTGTGTTAACACAGATGATTCCT ATTCCTGCCACTGCCTGAAAGGCTTTACCCTGAATCCAGATAAGAAACCTGCAGAAGGATCAACTAC TGTGCACTGAACAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGAGAGCTACTACTGCCGCTG CCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGO.AOCACTGTGCACAGCAGG ACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTC CTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGA ATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCG ATGGGAAGACGTGTGCAAAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGAACATTCGTGTGTA AGCAGTGAAGATTCGTTTGTGTGCCAGTGCTTTGAAGGTTATATACTCCGTGAAGATGGAAAAACCTG 237 WO 031093432 PCT/US03/1 3690 CAGAALGAAGATGTCTGCCAAGCTATAGACCATGGCTGTGAACACA'ITTGTG3TGACAGTGACGACT CATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAGGAAGGAT GTTCATALCACGCGGAAATTTTATAGGATCAACGA ATGCTCAGAGGGATTTGTTCTAGCTGAGACGGAGACGGTGCAGATGCACTGAGGCCCAATTG ACCTGGTCTTTGTGATCGATGGATCCAGAGTCTTGGAGAJAGAGAATTTTGAGGTCGTGAAGCAGTTT GTCACTGGAATTATAGATTCCTTOACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTC CACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAGCCGTOG CCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAAACACATGTTTGAGAGA-AGT TTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGA CGGACGGGCTCAGGATGACGTCTCCGAGTGGGCCAGTAJAAGCCAAGGCCAJTGGTATCACTATGTATG CTGTTG(GGGTAGGAAAAG(CCATTGAGGAGGAACTACAAGAGATTGC~CTGAGCCCAcAAACAAGCAT CTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAACTCAGAAACcATCTGTGA AGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCpJACAGC CAACAGAATCTGAGCCAGTCACCATAATATCCAAGACCTACTTTCCTGTTCTAjTTTTGCAGTGC1A CACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCATTCAACAAACC TTCAGGAAGCCCTTTGGAAGAAAAACACGATCAATGCAATGTGAAACCTTATATGTTCCAGAACC TTGCAAACGAA.GAAGTAAG\AAATTAACCAGCGCTTAGAGAJATGACACAGAGAATGGAAGCCCTG GAAAATCGCCTGAGATACAGAGTCGACGGC NOV14g, 273711018 [SEQ ID INO: 174 [93 9 W j at 104995.2kD Protein Sequence TRSRQRSRGRSISRGRHARTHPQTALLESSCENKRADLVFIIJSSRSVNTHDYAKVKEFIVDILQFLD IGPDVTRVGLLQYGS TVKNEFSLKTFKRKSEVERAVKRMRHLSTGTMTGLAIQYALNIAFSEAEGARP LRENVPR VIMI VTDGRPQDS VAEVAAKARDTGILIFAIGVGQVDFNTLKs IGSEPHEDHVFLVA3NFSQ IETLTSVFQKLCTACSTLENCAHFCLNTPGSYVCRCKQGYIJNSDQTTCRIQDLCAMEDHNCEQ LCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENRGCEHECVNADGSYLCQCREGFALTPDEKTCT KIDYCASSNHGCQHECVNTDDSYSCECLKGFTLNPDKTCRRIYCANPGCEHECVMESYYCRC HRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSVCQCSEGFLINEDLKTCSRVDYCLLSDHGCE YSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCVS SEDS FVCQCFEGYILREDGKTC RRKDVCQAID1IGCEHICVNSDDSYTCECLEGFRLADGIRCRKDVCKSTHJHGCEHICVNNGNSYICK CSEGFVLAEDGRRCKKCTEGPIDLVFVIDGSKSLGBENFEVVKQFVTGIIDSLTISPKAARVG.LQYS TQVHTEFTLRNrFNSAKDMKKAVAHMRYMGKGSMTGLALKMFERSFTQGEGARPLSTRVPRAAIVPTD GRAQDDVSEWASKAKANGITMYAVGVGKAIEEELQEIASEPTNKHIJFYAEDFSTMDEISEKJKKGICE ALEDSDGPQDSPAGELP(TVQQPTESEPVTINIQDLLSCSNFAVQIRYLBEEDbTLLRSTQKLSHSTKP SGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQPMEALENRLRYRVDG NOV14h, 273711053 SEQID NO:175 j2347bp DNA Sequence lORF Start: at 2 ORF Stop: end of sequence ____ CACCGATCTAGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAGACACGCTCGGACCCACCCGC AGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGACCTGGTTTTCATCATTGACAGCTCT CGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAGTTCATCGTGGACATCTTGQAATTCTTGGA CATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCATATGGCAGCACTGTCAGAATGAGTTCTCCC TCAGACCTTCAGGGAGTCCGAGGTGGAGCGTGCTGTCAGAGGATGCGGCATCTGTCCACGGGC ACCATGACCGGGCTOGCCATCCAGTATGCCCTGACATCGCATTCTCAGAAGCAGAGGGGCCCGGCC CCTGAGGGAGAATGTGCCACGGGTCATAATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCG AGGTGGCTGCTAALGGCACGGGACACGGGCATCCTAATCTTTGCCATTGGTGTGGGCCAGGTAGACTTC AACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCATTTCAGCCA GATTGAGACGCTGACCTCCGTGTTCCAGAAGAAGTTGTGCACGGCCCACATGTGCAGCACCCTGGAGC ATAACTGTGCCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAAACAAGGC!TACATT CTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCA GCTCTGTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTACGCCCTGGCTGAGGATG GGAAGAGGTGTGTGGCTGTGGACTACTGTGCCTCAGAAAACCACGGATGTGAACATGAGTGTGTAAAT GCTGATGGCTCCTACCTTTGCCAGTGCCATG2-GGATTTGCTCTTAACCCAGATGAAAAJACGTGCAC AAAGATAGACTACTGTGCCTCATCTAATCACGGATGTCAGCACGAGTGTGTTACACAGATGATTCCT ATCTCATCTAAGTTCCGACAAAGAACGAGAGAC7CA TGTGCACTGAALCAAACCGGGCTGTGAGCATGAGTGCGTCAACATGGAGGA3AGCTACTACTGCCGCTG CCACCGTGGCTACACTCTGGACCCCAATGGCAAAACCTGCAGCCGAGTGGACCACTGTGCACAGCAGG AGAGGCTGTGAGCAGCTGTGTCTGAACACGGAGGATTCCTTCGTCTGCCAGTGCTCAGAAGGCTTC,,. 238 WO 03/093432 PCT/US03/13690 CTCATCAACGAGGACCTCAAGACCTGCTCCCGGGTGGATTACTGCCTGCTGAGTGACCATGGTTGEGA ATACTCCTGTGTCAACATGGACAGATCCTTTGCCTGTCAGTGTCCTGAGGGACACGTGCTCCGCAGCG CATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGACGCTGCCGAGGAAGGAT GTTCATAACACTGTCACCTTTTATAGGATCAACGA ATGCTCAGAGGGATTTGTTCTAGCTGAGGACGGAAGACGGTGCAAGAGTATCACTATGTATGCTGTTG GGTAGGAAQ-ACCATTGAGGAGGAACTACAGAGATTGCCTCTGAGCCCACACAGCATCTCTTC TGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAGCTTTCCCATTCAACA CCCTGGAAAATCGCCTGAGATACAGAGTCGACGCC h OV14h, 273711053 SEQ ID NO: 176 782 aa, MWat 87838.8kD Protein Sequence TRSRQRSRGRSISRGRHARTHPQTALLESSCENKRADLVFI IDSSRSVNTHDYAI(VKEFIVD)ILQFLD IGPDVTRVGLLQYGs TVKNEFSLKTFKRKSEVERAVK4MRHLSTGTMTGLAIQYATLTIAPSEAEIARP LRENVPRVIMIVTDGRPQDSVAVAAKARDTGILTFAIGVGQVDFNTLKS IGSEPHEDHVFLVANFSQ HRGYTLDPNGKTCSRDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDKTCSRVYCLLSDHGCE YSCVNDRSACQCPEGHLRSDGKTAJDSCAGD~GCEHSCVSEDSFVCQCFEGYILREDGKTC RRVQIHCHCNDSTELGRADRCRDCSHGEIVNNYC CSEGB'VT-A DGRRCKS ITDYAVGVGKIEEELQEIASEPTNLFYADFSTEISEKLKGICEAL EDSDGRQDSPAGELPKTVQQPTVQHRYLFEEDNLLRSTQKLSHSTKPSGS PLEEKHDQCKCENLIMFQ NLANEEVRKLTQRLEEMTQRMEALENRLRYRVDG NOV14i, 274051275 'ISEQIDN09:177 1276 DNA Sequence jORF Str:at 2 ORF Stop: endf sequence

CACCAGATCTAGGCAGCGGTCACGTGGGAGGTCCATCTCTAGGGGCAG.AOACGCTCGGACCCACCCGC

AGACGGCCCTTCTGGAGAGTTCCTGTGAGAACAAGCGGGCAGA.CCTGGTTTTCATCATTGACAGCTCT CGCAGTGTCAACACCCATGACTATGCAAAGGTCAAGGAzGTTCATCGTGGACATCTTGCAATTCTTGGA CATTGGTCCTGATGTCACCCGAGTGGGCCTGCTCCATATGGCAGCACTGTCAGATGAGTTCTCCC TCAGACCTTCAGAGGAGTCCGAGGTGGAGCGTGCTGTCAGAGGATGCGGCATCTGTCCACGGGC ACCATGACCGGGCTGGCCATCCAGTATGCCCTGAACATCGCATTCTCAGAAJGCAGAGGGGCCCGGCC CCTGAGGGAGAATGTGCCACGGGTCAJATGATCGTGACAGATGGGAGACCTCAGGACTCCGTGGCCG AQGTGGCTGCTAGGCACGGGACACGGGCATCCTAATCTTTGCCATI.GGTGTGGGCCAGGTAGACTTC AACACCTTGAAGTCCATTGGGAGTGAGCCCCATGAGGACCATGTCTTCCTTGTGGCCAATTTCAGCCA GATTGAGACGCTGACCTCCGTGTTCCAGAJAGAAGTTOTOCACGGCCCACATGTGCAGCACCCTGGAGC ATACTGTGCCACTTCTGCATCAACATCCCTGGCTCATACGTCTGCAGGTGCAACAJAGGCTACATT *CTCAACTCGGATCAGACGACTTGCAGAATCCAGGATCTGTGTGCCATGGAGGACCACAACTGTGAGCA GCTCTGTGAATGTGCCGGGCTCCTTCGTCTGCCAGTGCTACAGTGGCTAC!GCCCTGGCTGAGGATG GGAAGAGGTGTGTGOCTGTGGACTACTGTGCCTCAGAACCACGGATGTGACATGAtGTGTGTAAA.T GCTGATGGCTCCTACCTTTGCCAGTGCCATGAAGGATTTGCTCTTCCCAGATGAACGTGC AAGATAGACTACTGTGCCTCATCTAA.TCACGGATGTCAGCACGAGTGTGTTAACACAGATGATTCCT ATCTCATCTAAGTTCCGACCGTAAZACTCGAGTACA TGTGCACTGACAAACCGGGCTGTGAGCATGA.GTGCGTCACATGAGGAGAGCTACTACTGCCGCTG CCACCGTGGCTACACTCTGACCCCAATGGCAACCTGCAGCCGAGTGGACCACTGTGCAAGCAGG ACCATGGCTGTGAGCAGCTGTGTCTGAACACGGAGGI TTCCTTCGTCTGCCAGTGCTCAGAGGCTTC CTCATCACGAGGACCTCAGACCTGCTCCCGGTGGATTACTGCCTGCTGAGTGACCATGGTTGTGA ATACTCCTGTGTCACATGGACAGATCCTTTGCCTGTCGTGTCCTGAGGGACACGTGCTCCGCAGCG ATGGGAAGACGTGTGCOAATTGGACTCTTGTGCTCTGGGGGACCACGGTTGTGACATTCGTGTGTA AGATAGTCTTTTCATCTGAGTAAATCTAGTGAACT CAGAAGGAAGATGTCTGCCAAGCTATAGACCATGGCTGTGACACATTTGTGTGAAAGTGACGACT 239 WO 031093432 PCTIUS03I1 3690 CATACACGTGCGAGTGCTTGGAGGGATTCCGGCTCGCTGAGGATGGGAAACGCTGCCGAAGGAAGGAT, GTCTGCAAATCAACCCACCATGGCTGCGAACACATTTGTGTTAATAATGGGAATTCCTACATCTGCAA 7ATCCTC2AGAGGGATTTGTTCTIAGCTGAGGACGGAAGACGGTGCAAGAAATGCACTGAAGGCCCAATTG GTCACTGGATATTATAGATTCCTTGACAATTTCCCCCAAAGCCGCTCGAGTGGGGCTGCTCCAGTATTC CACACAGGTCCACACAGAGTTCACTCTGAGAAACTTCAACTCAGCCAAAGACATGAAAAAAGCCGTCG CCCACATGAAATACATGGGAAAGGGCTCTATGACTGGGCTGGCCCTGAA.ACACATGTTTGAGAGAAGT TTTACCCAAGGAGAAGGGGCCAGGCCCCTTTCCACAAGGGTGCCCAGAGCAGCCATTGTGTTCACCGA CGGACGGGCTCAGGATGACGTrCTCCGAGTGGGCCAGTAAAGCCAAGGCCAAIGGTATCACTATGTATG CTGTTGGGGTAGGAAAGCCATTGAGGAGGAACTACAAGAGATTGCCTCTGAGCCCACAAACAAGCAT CTCTTCTATGCCGAAGACTTCAGCACAATGGATGAGATAAGTGAAAAACTCAAGAAAGGCATCTGTGA AGCTCTAGAAGACTCCGATGGAAGACAGGACTCTCCAGCAGGGGAACTGCCAAAAACGGTCCAACAGC CAACAGTGCAACACAGATATCTGTTTGAAGAAGACAATCTTTTACGGTCTACACAAAAGCTTTCCCAT TCAACAAACCTTCAGGAAGCCCTTTGGAAGAAAACACGATCATGCAAATGTGAAALACCTTATAAT GTTCCAGAACCTTGCAAACGAAGAAGTAA GAAAATTAACACAGCGCTTAGAAGAAATGACACAGAGAA TGGAAGCCCTGGAA2AATCGCCTGAGATACAGAGTCGACGGC NOVL4i, 274051275 SEQ ID NO: 178 920 aa MW at 102933.OkD Protein Sequence T'RSRQRSRGRS ISRGRHPARTHPQTALLES SCENFKRZDLNFI IDS SRSVNTHDYAKVKEF IVDILQFLD IGPDVTRVGLLQYGSTVNFSLKTFKRKSEVERAVRMRHLSTGTMTGLAIQYALNIAFSEEGAPP LRENVPRVIMIVTDGRPQDSVAE-VAAKARDTGILIFAGVGQVDFNTLKS LGSEPHEDIIVFL-VANFSQ IETLTSVFQKKLCTAHiMCSTLEHWCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQ LCVNVPGSFVCQCYSGYALAEDGKRCVAVDYCASENBGCEHECVNADGSYLCQCHEGFALNPDEKTCT KIDYCASSNGCQHECVNTDDSYSCHCLKGFTLNPDXU(TCRRINCALNKPGCEHECVNMEESYYCRC NGYTLDPNGKTCSRVDHCAQQDIGCEQLCLNTEDSP'VCQCSEGFLINFDLKTCSRVDYCLLSDHGCE YSCVNIVDRSFACQCPEGEVLRSDGKTCAKLDSCALGD)HGCEHSCVS SEDSFVCQCFEGYILREDGKTC RRKDVCQAIDHGCEI{ICVNSDDSYTCECLEGFRLAEDGKRCRRKDVCKSTHHGCEHICVNNGNSYI CK CSEGFXLADGRRCKKCTEGPIDLVFVIDGSKSLGEENFEVVKQFVTGIIDSLTI SPKAARVGLLQYS TQVHTEFTLRNFNSAKDMKKAVAIiMRYMGKGSMTGLALKIEMFERS FTQGEGARPLSTRVPRAAIVFTD GRAQDDVSEWASKANMGITMYA-\GVGKAIEEELQEIASEPTNKHLFYAEDFSTMDRISEKLKXGI CE ALEDSDGRQDSPAGELPKTVQQPTVQHRYLFEEDNLLRSTQKLSHSTKPSGSPLEEKHDQCKCENLIM FQNLANEEVRKLTQRLEEMTQRMEALENRLRYRVDG NOV14j CG5105 1-01 ISEQ ID NO: 179 1909 bp DNA Sequence JORF Start: AT6 at 230 ORF Stop: TAG at 1670 GGCTTCCACCAAAG3TCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTOGTTTTGG GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCDJACAT ACATATGTGTATATATATGTAP-ACTAGACAAAGATCGCAGA TCATAAAGCAAGC!TCTGCTTTAGTTTC CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA CGGTGTCCTCAGTGATrGCAGCCCTACCCTTTGGTTTGGGGAz CATTA1'GATTTGTGTAAGACTCAGATT TACACGGAAGAAGGOAAAGTTTGGGATTACATGGCCTGCCA.GCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GQAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACC-CCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAA.ATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAA.ATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAATTGACATGCGATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATOGCCGAATATTTCTTCCCTT GAGGTTTCTAALCCCAAAAQAAGTTGCTCCCAAATTACTTTTCAACAQTTTCTTCTGTTCAAGTTGC AAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACA ,,,, 240 WO 031093432 PCT/US03/13690 ACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAG GCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCT GACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACACCGGACGGGC CTQTGCCGTGGGGAAGCAGACACAACCCAAACATTTGCTACTAACATAGGAAACACACACATACAGAC ACCCCCACTCAGACAGTGTACAAACTAAGAAGGCCTAACTGAACTAAGCCATATTTATCACCCGTGGA CAGCACATCCGAGTCAGGACTGTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTTGATATTATCACT GCAA NOV 14j, CG51051-01 JSEQ ID NO: 180 J480 aa JMW at53945.OkD IProtein Sequence MYLSRFLSIHfALWVTVSSVMQPYPLVWGH-YDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANKRANVC DNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF NOV14k, CG51051-02 SEQ ID NO: 181 1343 bp DNA Sequence ORE Start: ATG at 18 OR Stop: End of Sequence ATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCC TCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGA AGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAG TGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCC TACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGA TTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCC AGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAA TCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCA GTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGC ATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATC CACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTA CGGACAGCTGOATACAACCAAGAAACTCAGGGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGT TAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCA GACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAA ATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTACCAGG GCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCGCTGCAAATACCTGTATCCCCAGT ATTTCCAGTATTGGTAAGTGTTATTGTAACCCTTTGGGCTCAATCCATGATCGTTGTAATGGCTCAGG ATTTTGTGAGTGTAAGACTGGAACAACAGGGCCTAAGTGTGATGAGTGTCTGCCGGGCAATTCCTGGC ACTACGGCTGTCAACCGAATGTCTGCGACAACGAGCTCCTGCCACCATGTATTTGTCAAGATTCCTGT CGATTCTATCTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCTCGAGAAGGG NOV14k, CG51051-02 SEQ ID NO: 182442aa W at 50335.9kD Protein Sequence MYSRFLS IHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDPEGRHPSTPWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELELARYPYAISDIKVRGRCKCNLATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPIPKGAANTCIPS ISSIGKCYCNPLGS IHDRCNGSGFCECKTGTTGPKCDECLPGNSWHYGCQP NVCDNELLPPCICQDSCRFYLWPGRAPARLPREG NO V141, CGS1051-03 SEQ IDNO: 183 1544 bp DNA Sequence ORF Start: ATG at 230 ORF Stop: TAG at 1517 GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTGG GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT ACATATGTGTATATATATGTAAACTAGACAAAGATCGCAGATCATAAAGCAAGCTCTGCTTTAGTTTC CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA 241 WO 031093432 PCTIUS03I1 3690 CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAALTGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAOCTG ATGTTTGATTTTG2AAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAA~ATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACATAGCA AAATAATCCACTTTGAAUATCAAAGACAkGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGCGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AAACATGCTCATTACCAACAAGCAATTGAAGAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAALATACCTCGA ATGTCTGCGA CAA.CGAG3CTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTG TGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCAGGAGCTGGCAGCTGCGGCTC CGACTCTGGTCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAA CCGCCAGCCCCCTGGTGTTTTAGGTGTCACCTCCAGCCACACCGGACG NOV14I, CG51051-03 SQINO1842aaMW at48439.7kD Protein Sequence MYLSRPLS IHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVXLDPP DITCGDPPBTFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SVWSKTIELTDNIVITFESGRPDQMILEKSLaDYGRTWQPYQYYATDCLDAFDPKSVDLSQHTVLI ICTEEYSTGYTTNSKIIFEIKDRFAFFAGPRLRNM1ASLYGQLDTTKLRDPFTVTDLRIRLLRPAVG EIFVDELHLARYFYAtSDIKRGRCKCLATVCVYDNSKLTCECEHNTTGPDCGKCKNYQGRPWSP GSYLPIPKGTANTSNVCDNELLHCQNGGTCNN~VRCLCPAAYTGILCEXLRCEEAGSCGSDSGQGAPP HGSPALLLLTTLLGTASPLVF NOV4m, CG51051-04 ~S QID NO: 185 11771 b DNA Sequence ORF Start: ATG at 230 'ORF Stop: TAG at 1544 GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTGG GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT ACATATGTGTATATATATGTAACTAGACAAAGATCGCAGATCATAAGCAAGCTCTGCTTTAGTTTC CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGACTGACAATA TCTGAAOTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG .ATGTTTGATTTTGAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAGGAGTATCCA GCCTCTCCAGGTTAALCATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGACTGGCAG CCTTATTAGCCGCGTAAGTTCC-GACTATCTAGAT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACATAGCA AAATAATCCACTTTGAAATCAAAGACAOGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGAkCCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGC-ACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGATGTGAGCACACACTACAGGTCCAGACTGTGGGTGCAGAGA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAATACCTGTA TCCCCAGTATTTCCAGTATTGGTACGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGG ACGTGCCAkCAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAGCTGCG GTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGC TGCTGCTGCTGACCZ\CGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACA CCGGACGGG~CTGTGCCGrGGGGAAGCAGACACAACCCAAACATTTGCTACTAACATAGGAAACACAC ACATACAGACACCCCCACTCAGACAGTGTACAAACTAAGAAGGCCTAACTGAACTAAGCCATATTTAT CACCCGTGGACAGCACATCCGAGTCAAGACTOTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTG 242 WO 031093432 PCT/US03/13690 TAT NOV14tn, CG51051-04 SEQ ID NO: 186 438 aa MW at 49339.7kD Protein Sequence MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTRYLKVKLDPP DITCGDPPETFCANGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGTNVCDNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCG SDSGQGAPPHGSPALLLLTTLLGTASPLVF NOV14n, CG51051-05 ISEQ ID NO: 187 -1771 bp DNA Sequence ORF Start: ATG at 230 JORE Stop: TAG at 1544 GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTOGTTTTGG GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT ACATATGTGTATATATATGTAAACTAGACAAAGATCGCAGATCATAAAGCAAGCTCTGCTTTAGTTTC CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTACGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGG ACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCG GTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGC TGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACA CCGGACGGGCCTGTGCCGTGGGGAAGCAGACACAACCCAAACATTTGCTACTAACATAGGAAACACAC ACATACAGACACCCCCACTCAGACAGTGTACAAACTAAGAAGGCCTAACTGAACTAAGCCATATTTAT CACCCGTGGACAGCACATCCGAGTCAAGACTGTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTTGA TAT NOV14n, CG51051-05 SEQ ID NO: 188 438aa MW at 49339.7kD Protein Sequence MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDPEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCRKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGTNVCDNELLrCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCG SDSGQGAPPHGSPALLLLTTLLGTASPLVF NOV14o, CG51051-06 SEQIDNO: 189 1290 bp DNA Sequence ORFStart:ATG at ORF Stop: end ofsequence ATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGCTACGGTGTCCTCAGTGATGCAGCCCTA CCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGG ATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCG GATATTACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGA 243 WO 031093432 PCTIUS03I1 3690 GTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAG3AAGACATC CCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTG TCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCA AGATCCTGGAGAAZGTCTCTCGATTATOGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACT GCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAA-TC ATTTGCACAGAAGAGTACTCAACAGGGTATACAACAATAGCAAAATAATCCACTTTGAAATCAAAGA CAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAA CCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGG GAALATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGG AAGGTGCAAGTGTAA-TCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAATGTG AGCACAACACTACAGGTCCAGACTGTGGGAAATGCAA.GAAGAATTATCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCA3TATTTCCAGTATTGGTAC GAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCC'ACAACAACGTGCGCTGCC TGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGC TCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCTCGAGAAGGGCAATTCCACCACACTGG AC NOV14o, CG51051-06 SEQ ID NO: 19040a MW at 48548.6kD Protein Sequence43aa MYLSRFLSIHLWATVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPY14CNN~ECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHiTVLEI ICTEEYSTGYTTNSKI IHFEIKDRFAFFAGPRLRM~SLYGQLDTTKKLRDBTTVTDIJRIRDLRPAVG EIFVDELHLRYYAISDIhVRRCKCNLHATVCVYDNS(LTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPfPKGTANTCIPSIS SIGTNVCDNELLHCQNGGTCHfNNVRCLCPAAYTGILCEKLRCEEAGSCG SDSGQGAPPHGSLEKGNSTTLD NOV14p, CG51051-08 IjSEQ ID NO: 191" 1837 bp DN eqec _iO1 Start: ATG at 230 , ORF Stop: TAG at 1610 GGCTTCCACCAAAGTCCTCAATATACCTGAATACGCACAATATCTTAACTCTTCATATTTGGTTTTOG GATCTGCTTTGAGGTCCCATCTTCATTTAAAAAAAAATACAGAGACCTACCTACCCGTACGCATACAT ACATATGTGTATATATATGTAAACTAGACAAGATCCAGATCATAAGCAGCTCTGCTTTAGTTTC CAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTA CGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGAC!TCAGATT TACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGACATGACAAA.ATA TCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAACCCTCCTGAGACGTTCTGTGCATGG GCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTG ATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAG3GAGTATCCCAA GCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTA CCTTTGAATCTGGGCGTCCAGACCAI'ATGATCCTGGAGAAGTCTCTCGATTATGACGAACATGGCAG CCCTATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCA CATGGATCCTAAATCCGTGAAGGATTT ATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCA AAATAATCCACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCT TCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGAT AAGGCTGTTAAGACCAGCCGTTGGGGAAATATTTOTAGATOAGCTACACTTGGCACGCTACTTTTACG CGATCTCAGACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAC AACAGCAAATTGACATGCGATGTGAGCACACACTACAGGTCCAGACTGTGGGAAATGCAGAAGAA TTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTA TCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTT GAGGTTTCTAACCCAAAACAAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGAC GTGCCACACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGQCATCCTCTGCGAAAGCTGCGGT GCGAGGAGGCTGGCA\GCTGCGGCTCCGACTCTGCCAGGGCGeGCCCCGCA CGGCTrCCCCAGCGCTG CTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTGTCACCTCCAGCCACACC GGACGGGCCTGTGCCGTGGGGAAGCAGACACAACCCACATTTGCTACTAACATAGGAAACACACAC ATACAGACACCCCCACTCAGACAGTGTACAAkCTAAGAGGCCTAACTGACTAAGCC!ATATTTATC-A CCCGTGGACAGCACATCCGAGTCAAGACTGTTAATTTCTGACTCCAGAGGAGTTGGCAGCTGTTGATA NOV14p, CG5 051-0I SEQ ID NO: 1921460 aa, MW at 51857.6kD PoenSequence 244 WO 031093432 PCTIUS03I1 3690 MYLSRFLS IHALWVTVSSVMQPYPLVWGI.YDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKvK LDPP DITCGDPPETFCAMGNPYMCNNECDASTPELARPPELMFDFEGRPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI I C'EEYSTGYTTNSKI IHFEIXKDRFAFFAGPRLRNASLYGQIDTTKKLRDFFTVTDLR-IRLLRPAVG EIVEHAYYIDKRRKNHVVZ~SLCCHTGDGCKYGPS GSYLPIPKGTANTCIPSISSIGNPPKFIWPNISSLEVSNPKQNVCDNELLCQNGGTCEJNVRCL CPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVF NOV14q, CG51051-10 JSEQID NO: 193 11426 bp DNA Sequence ~ ORIF Start: at 29 jORF Stop: end of sequence GGCTi cGCGGCCGCCCCCTTCACCGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGT GTAAGACTCAGATTTACACGGAAGAAGGGAZ.AGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACG GACATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGAC GTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCAC ACCCCCCTGAGCTGATGTTT&ATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGG AAGGAGTATCCCAAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAA\CCATTGAGCTAACAGA CAACATAGTTATTACCTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATG GACGAACATGGCAGCCCTA.TCAGTATTATGCCACAGr&TGCTTAGATGCTTTTCACATGGATCCTAAAL TCCGTGAGGATTTATCACAGCATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTA TACAACA-ATAGCAAATAATCCACTTTGAAATCAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCC TACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTC ACAGACCTGAGGATAAGGCTGTTAGACCAGCCGTTGGGAAATATTTGTAGATGAGCTACACTTGGC ACGCTACTTTTACGCGTCTC1AGACATAAAGGTGCGAGGAAGGTGCAAGTGTAA TCTCCATGCCACTG .TATGTGTGTATGACAACAGCAAATTGA4CATGCGAATGTGAGCACAACACTACAGGTCCAGACTGTGGG AAATGCAAGAALGAATTATCAGGGCCGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCAC TGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGA ATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCT TCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGG AGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGC TGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCA GCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCAAGGGTGGGCGCGCC NOV14q, CG51051-10 SEQ ID NO: 194.462 aa. MW at 5I852.6kD Protein Sequence VMQPYPLVWGI{YDLCKTQIYTEEGKVWDYMACQPESTDMTRYLKVKLDPPDITCGDPPETFCAMGNPY MCNNECDASTPELAH{PPELMFDFEGRHPSTFWQSATWKEYKPLQVNITLSWSKTIELTDNIVITFES GRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEIICTREYSTGYTTNSKI IH FEIKDRFAFFAGPRLRlMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFVDEIALARYFYAISD IKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKINYQGRPWSPGSYLPIPKGTANTCIPS I SSIGNPPKFNIWPISSLEVSNPKQVAPKLALSTVSSVQVANKRANVCDNELLICQNGGTCHN'WR CLCPAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPLLLLTTLLGTASPLVF NOV4r, CG51051-11 ISEQ ID NO: 195 778 bp _________ D NA Sequence OFStart: at 2 IORF Stop: end of sequence G7GCTCCGCGGCCGCCCCCTTCACCTGCCAGCCGAATCCACGGACATGACAAAATATCTGAAAGTGA AACTCGATCCTCCGcATATTACCTGTGGAGACCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTAC ATGTGCAA.TAATGAGTGTGATGCGAGTACCCCTGAGCTGGCAC!ACCCCCCTGAGCTGATGTTTGATTT TGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGG TTAACATCACTCTGTCTTQGAGCAAAALCCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCT GGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGTA TTATGCCACAGACTGCTTAGATGCTTTTCACA-TGGATCCTAA\ATCCGTGAAGGATTTATCACAGCATA CGGTCTThGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCAC TTTGAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGG AOAGCTGGATACACCAAGAAACTCA4GAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAA GACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGAC ATAAAGGTGCGAGGAAAGGGTGGGCGCGCC NOVl4r, CG51051-1 1 SQID NO: 19 59 aa MW at 29645.3k]) Protein Sequence 1 E 91 245 WO 031093432 PCTIUS03I1 3690 GSAAAPFTCQPESTDMTKYLKVKLDPPDITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDF EGRHPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQY YATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKI IHFEIKDRFAFFAPL1RNMASLYG QLDTTKKLRDFFTVTDLRIRLLRPAVGEJFVDELELARYFYAISDIKVRGKGGRA NOV 14s, CG51051-12 SEQ ID NO: 197 1452 bp ___ DNA Sequence ORE Start: ATGj at7ORF Stop: end of sequence AGATCTATGTATTTGTCAAGATTCCTGTCGATTCATCCCTTTGGG3TTACGGTGTCCTCAGTGATGCA GCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAAGAAGGGAAAG TTTGGGZTTACATGGCCTGeCAGCCGGAATCCACGGCATGACAAATATCTGAAAGTGAAACTCGAT CCTCCGGATATTACCTGTGAACCCTCCTGGACGTTCTGTGCATGGGCAATCCCTACATGTGCAA TAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAA GACATCC2CTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATC ACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAATCTGGGCGTCC AGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACAT15GCAGCCCTATCAGTATTATGCCA CAGACTOCTTAGATGCTTTTCACATGGATCCTAAJCCGTIGAAGOATTTATCACAGCATACGOTCTTA GAA1ATCATTTGCACAGAAGAGTACTCAACAGGTATACAACAAATAGCAAAATAATCCACT'TTGAAAT CAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGG ATACAACCAAGAAACTCAGAGATTTCTTTACAGTCAC!AGACCTGAGGATAAGGCTGTTAAGACCAGCC GTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGT GCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCG AATGTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGAcCTTGG AGTCCAGGCTCCTATCTCCCCATCCCCAAGGCACTCAATCCTGTATCCCCAGTATTTCCAGTAT TGGTA7ATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAAC AAGTTGCTCCCAATTAGCTTTGTCACAGTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAAT GTCTGCCACAACGAGCTCCTGCAOTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTG CCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCG ACTCTGCCAGGGCGCGCCCCCGCACGGCTCCCCACGCTGCTGCTGCTGACCACGCTGCTGGGAACC GCCAGCCCCCTGGTGTTC NOV14s, CG51OS1-1 SEQ ID NO: 19 4OaaMat34.k Protein Sequence MYLSRFLSILVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNNCDASTPELHPPELFDEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKI IHFEIKDRFAFFAGPRLR1N4ASLYGQLflTTKKLRDFFTVTDLRIRLiLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLATVCVYDNSKLTCECEHNTTGDCGKCKNQGRPWSP GSYLPIPKGTANTCIPSISSIGPPKFNRIPNISLVSNPKQVAPKLALSTVSSVQVANHKRANVC DNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF NOV 14t, CG51051-13 JSEQ ID NO: 199 750 b D INA -Sequence OR tr:at 1 IORF Stop: end of sequence TGCCAGCCGGAATCCACCGACATGACAAAATATCTGAAAGTGAAJ\CTCGATCCTCCGGATAT TACCTGTGGAGACCCTCCTGAGACGTTCTGTGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTG ATGCGAGTACCCCTOAGCTGGCACACCCCCCTGAGCTGATGTTTGATTTTGAAGGAAGACATCCCTCC ACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAAGCCTCTCCAGGTTAACATCA-CTCTGTCTTG GAGCAAAACCATTGAGCTAACAGACAACAT-AGTTATTACCTTTGAALTCTGGGCGTCCAGACCAALATGA TCCTGGAGAAGTCTCTCATTATGGACGAACATGGCAGCCCTATCAGTATTATGCCACAGACTGCTTA GATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCATACGGTCTTAGAAATCATTTG CACAGAAGAGTACTCAACAGGGTATACAACAATAGCAAAATAATCCACTTTGATAAGACAGGT TCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGACAGCTGGATACAACCAAG AAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCAGCCGTTGGGGAAAT ATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGTGCGAGGA NOV4t, CG51051-13 SEQ ID NO: 200 246~ Ma at 28473.OkD Protein SequenceI CQESDTKYLKVKLDPPDITCGDPPETFCAMGNPYMCNNECDASTPBELAI{PPELMFDFEGRHPSTF 246 WO 031093432 PCTIUS03I1 3690 WQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRPDQMILEI(SLDYGRTWQPYQYYATDCLDA FHfM1PKSVKDLSQHTVLEI ICTEEYS TGYTT.NSKI IHFEIKDRFAFFAGPRLRflMASLYGQLDTTKKL RDPFTDJRILLRPAVGEIFVDELHLARYFYAISDIKVRG NOVI 4u, CG51051-15 jSEQ ID NO: 20111465 bp _______ DNA Sequence JORF Start: ATO at 17 IORF Stop: end of sequence CACCAGATCTCCCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCCT CAGTGATGCAGCCCTACCCTTTGGTTTLGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAA GAAGGG7AAAGTTTGGGATTACATGGCCTGCCAGCCGG2AATCCACGGACATGACAAAATATCTGAAAGT GAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACG3TTCTGTGCAATGGGCAATCCCT ACATGTGCAATATGAGTGTGATGCGAGTACCCCTGGCTGC\CACCCCCCTGAGCTGATGTTTGAT TTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTG.GAAGGAGTATCCCAAGCCTCTCCA GGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTACCTTTGAAT CTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAG TATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAGCA TACGGTCTTAGAAATCATTTGCACAGAAGAI GTACTCAACAGGGTATACAACAAATAGCAAAAThATCC ACTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCA-TATGGCTTCCCTCTAC GGACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAALGGCTGTT AAGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAG ACATAAAGGTGCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAA TTGACATGCGAATGTGAGCACAACACTACAGGTCCAGACTDGTGGGAAATGCAAGAAGAATTATCAGGG CCGACCTTGGAGTCCAGGCTCCTAXTCTCcCCCATCCCCAAAGGCACTGCAAI\TACCTGTATCCCAGTA TTTCCAGTATTGGTAATCCTCCAZAAGTTTAATAGGAThTGGCCGAATATTTCTTCCCTTGAGGTTTCT ACCCAAAACAAGTTGCTCC!CAAATTAGCTTTGTCACAGTTTCTTCTGTTCAGTTGCAAACCACAA GAGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGC GCTGCCTGTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGC L'GCGGCTCCGACTCTGGCCAGGGOGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCT GCTGGGAACCGCCAGCCCCCTGGTGTTC NOVI14u, CG51051-15 SEQ ID NO: 2021,480 aaMW at 53945.OkD Protein Sequence MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEG(VWDYMACQPESTDMTKYLKVKLDPP DITCGDPPETFCAMGNPYMCNECDASTPELAPPELMFDEGRHPSTFWQSATWKYPKPLQVTETL SWSKTIELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLE I I CTEEYSTGYTTNSKI IEFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISD)IKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKC(KNYQGRPWS P GSYLPIPKGTANTCIPSISS IGNPPKFNRIWPNISSLEVSNTPKQVAPKLALSTVSSVQVANIHKRANVC DNLHQGTHNRLPATICKRCRGCSSQAPGPLLTLGA PLVF NOV14v, CG51051-16 1SEQ ID NO: 203-j467 bp DNA .Seq .uen.e 1R1 Start: ATG at 16 jJ9RF Stop: TAG at 1456 CACCGCGGCCGCACCATGTATTTGTCAAGATTCCTGTCGATTCATGCCCTTTGGGTTACGGTGTCCTC AGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGTGTAAGACTCAGATTTACACGGAAG AAGGGAAGTTTGGGATTACATGCCTOCCAGCCGGATCCACGGACATGACA-AATATCTGAAAGTG AACTCGATCTCCGGATATTACCTGTGG'GACCCTCCTGAGAkCGTTCTGTGCAATGQGCAATCCCTA CATGTGCAALTAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTGAGCTGATGTTTGATT TTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCCAA-GCCTCTCCAG GTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACZAACATAGTTATTACCTTTGAATC TGGGCGTCCAGACCAAAT1GATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCTATCAGT ATTATGCC-ACAGACTGCTTAG2\TGCTTTTCAOATGGATCCTAAATCCGTGAAGGATTTATCACAGCAT ACGC*G TATGAAGAATTACGGAACAAAACAAATC CTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACG GACAGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTA AGACCAGCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACOCGATCTCAGA CATAAGGTGCGAGGAAGGTGCAAGTGTAATC!TCCATGCCACTGTATGTGTGTATGACAAkCAGCAALAT TGACATGCGAATGTGAGCACAP CACTACAGGTCCAGACTGTGGGAAATGCAA-GAAGAATTATCAGGGC CGACCTTGGAGTCCAGGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTAT 247 WO 031093432 PCT/US03/13690 TTCCAGTATTGGTAATCCTCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTA ACCCAAAACAAGTTGCTCCCAAATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAG AGAGCGAATGTCTGCGACAACGAGCTCCTGCACTGCCAGAACOGAGGGACGTGCCACAACAACGTGCG CTGCCTOTGCCCGGCCGCATACACGGGCATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCT GCGGCTCCGACTCTGGCCAGGGCGCGCCCCCGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTG CTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTCGACGGC NOV14v, CGS1OSI-16 SEQ ID NO: 204 480 aa MW at 53945.OkD Protein Sequence MYLSRFLSIKALWVTVSSVMQPYLVWGYDLCKTQIYTEEGKVWDYMACQPESTDMTRYLKVKLDPP DITCGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITL SWSKTIELTDNIVITFESGRPDQMILEKSLDYRTWQPYQYYATDCLDAFHMDPKSVKDLSQHTVLEI ICTEEYSTGYTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVG EIFVDELHLARYFYAISDIKVRGRCKCNLKATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSP GSYLPIPKGTANTCIPSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVC DNELLHCQNGGTCHNNVRCLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTAS PLVF NOV14w, 13380736 SNP for SEQ ID NO: 1495 bp, SNP: 217 A/Q CGS1051-07 205 DNA Sequence ORF Start: ORF Stop: TAG at 1486 ATG at 46 TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATGTATTTGTCAAGATTCCTGTCGAT TCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATGATTTGT GTAAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGAC ATGGCAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTG TGCAATGGGCAATCCCTACATGTGCAATAATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTG AGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCC AAGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTAC CTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCT ATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAG CATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCA CTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGAC AGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCA GCCGTTGGGGAAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGT GCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGACAACAGCAAATTGACATGCGAAT GTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCC TCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCA AATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAG CTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGG CATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCC CGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTOGGAACCGCCAGCCCCCTGGTGTTCTAGGTG TCAC NOV14w, 13380736 SNP for SEQ ID NO: 480 aa SNP: Thr to Ala at position 58 CG51051-07 206 Protein Sequence MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPESTDMAKYLKVKLDPPDIT CGDPPETFCAMGNPYMCNNECDASTPELAHPPELMFDFEGRHPSTFWQSATWKEYPKPLQVNITLSWSKTI ELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLDAFHMDPKSVEDLSQHTVLEIICTEEYSTG YTTNSKIIHFEIKDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFVDELHLARY PYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSPGSYLPIPKGTANTCI PSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDNELLHCQNGGTCHENVR CLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLLTTLLGTASPLVF NOV14x, 13380734 SNP for S I O: 2 1495 bp, SNP: 872 TG 248 WO 031093432 PCTIUS03I1 3690 C51051-07 jORF Start: ATG at 46 OFStop: TAG at 1486 DNA Sequence TCAAGCTCTGCTTTAGTTTCCAAGAAGATTACAA.AGAATTTAGAGATGTTTTGTC'AAOTCCTGTCGAT TCATGCCCTTTGGGTTACGGTGTCCTCAGTGATGCAGCCCTACCCTTTGGTTTGGGGACATTATG TT GTAAGACTCAGATTTAACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCOGAA.TCCACGGAC ATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCe-TGAGACGTTCTG TGCAATGGGCAATCCCTACATGTGCAATAATGA~GTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTG AGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCC AAGCCTCTCCAGGTTAALCATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTAC CTTTGAATCTGGGCGTCCAGACCAAATGATCCTGGAGAAGTCTCTCGATTATGGACGAACATGGCAGCCCT ATCAGTATTATGCCACAGACTGCTTAGATGCTTTTCACATGGATCCTAAATCCGTGAAGGATTTATCACAG CATACGGTCTTAGAAATCATTTGCACAGAAGAQTACTCAACAGGGTATACAACAAATAGCAA-AATAATCCA CTTTGAAATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACGCAATATGGCTTCCCTCTACGGAC AGCTGGATACAACCAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAGGCTGTTAAGACCA GCCGTTGGGGAAATATTTGGAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAALGGT GCGAGGAGGTGCAGTGTAATCTCCATGCCACTGTATGTGTGTATGACACAGCAATTGACATGCGAAT GTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTALTCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCC-AGTATTTCCAGTATTGGTAATCC TCCAAPGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAAGTTGCTCCCA AATTAGCTTTGTCAACAGTTTCTTCTGTTCAAGTTGCAAACCACAAGAGAGCGAATGTCTGCGACAACGAG CTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGG CATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGOCTCCGACTCTGGCCAGGGCGCGCCCC CGCACGGCTCCCCAGCGCTGCTGCTGCTGACCACGCTGCTGGGAACCGCCAGCCCCCTGGTGTTCTAGGTG Protein Sequence MYL-SRFLS IHALW1VTVSSVMQPYPL-VWGHYDLCKTQIYTEEGC-KVWDYMACQPESTDMTKYLI(VKILDPPDIT CGDPPETFCA4GNPYMCNNTECDASTPELAH-PPELMFDFEGRHPSTFWQSATWKBXPI(PLQVNITLSWSKTI ELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYY7ATDCLAFHMflPKSVKDLSQHTVLEIICTEEYSTG YTTNSKIflHFEIKDRFAFFAGPRL.RNMASLYGQLDTTCKLDFFTVTDLRIRLLRPAVGEIFGDELHLARY FYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGCCKKNYQGRPWSPGSYLPIPKGTANTCI PSISS XGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVAKRAVCDNELLICQNGGTCHWVR CLCPAAYTGILCEKRCBAGSCOSDSGQGAPPHGSPM.LLLTTLLGTASPLVV' NOVL4y, 13382329 SNP for SEQ ID NO: 209 1495b SP 1448 T/A ICG51051-07 ORF Start: ATG at 4 R tp A t18 Seqenc 4 I 1 R tp A t18 TiCAAGCCTGCTTTAGTTTCCAAGAAGATTACAAAGAATTTAGAGATG3TATTTG3TCAAGATTCCTGTCGAT TCATGCCCTTTGGGTTACGGTGTCCTCAGTGATIGCAGCCCTACTTTGGTTTGGGGACATTATGATTTGT GTAGACTCAGATTTACACGGAAGAAGGGAAAGTTTGGGATTACATGGCCTGCCAGCCGGAATCCACGGAC ATGACAAAATATCTGAAAGTGAAACTCGATCCTCCGGATATTACCTGTGGAGACCCTCCTGAGACGTTCTG TGCATGGGCAATCCCTACATGTGCAATATGAGTGTGATGCGAGTACCCCTGAGCTGGCACACCCCCCTG AGCTGATGTTTGATTTTGAAGGAAGACATCCCTCCACATTTTGGCAGTCTGCCACTTGGAAGGAGTATCCC AALGCCTCTCCAGGTTAACATCACTCTGTCTTGGAGCAAAACCATTGAGCTAACAGACAACATAGTTATTAC CTTTGAATCTGGGCGTCCAGACCAATGATCCTGGAGAAGTCTCTCGATTATG-ACGACATGGCACCCT ATCAGTATTATGCCAAGACTGCTTAGATGCTTTTCACA.TGGATCCTAALATCCGTGAAGGATTTATCACAG CATACGGTCTTAGAAATCATTTGCACAGAAGAGTACTCAACAGGGTATACAACAAATAGCAAAATAATCCA CTTTGA7AATCAAAGACAGGTTCGCGTTTTTTGCTGGACCTCGCCTACOCAATATGGCTTCCCTCTACGGAC AGCTGGATACAACCAAGAAACTCAGAGATTTCTTTACAGTCACAGACCTGAGGATAAOGCTGTTAAGACCA GCCGTTGGGGAATATTTGTAGATGAGCTACACTTGGCACGCTACTTTTACGCGATCTCAGACATAAAGGT GCGAGGAAGGTGCAAGTGTAATCTCCATGCCACTGTATGTGTGTATGAACAGC-ATTGACATGCGAAT GTGAGCACAACACTACAGGTCCAGACTGTGGGAAATGCAAGAAGAATTATCAGGGCCGACCTTGGAGTCCA GGCTCCTATCTCCCCATCCCCAAAGGCACTGCAAATACCTGTATCCCCAGTATTTCCAGTATTGGTAATCC TCCAAAGTTTAATAGGATATGGCCGAATATTTCTTCCCTTGAGGTTTCTAACCCAAAACAGTTGCTCCCA AATGTTTA*GTCTCGTAG CACAAGAACATTTCAACA CTCCTGCACTGCCAGAACGGAGGGACGTGCCACAACAACGTGCGCTGCCTGTGCCCGGCCGCATACACGGGI 249 WO 03/093432 PCT/USO3/13690 CATCCTCTGCGAGAAGCTGCGGTGCGAGGAGGCTGGCAGCTGCGGCTCCGACTCTGGCCAGGGCGCGCCCC CGCACGGCTCCCCAGCGCTGCTGCTGCAGACCACGCTGCTGGGAACCGCCAGCCCCCTOGTTTCTAGGTG TCAC NOVI4y, 13382329 SNP for SEQ ID NO: 480 aa SNP: Leu to GI at position 468 CG51051-07 210 Protein Sequence MYLSRFLSIHALWVTVSSVMQPYPLVWGKYDLCKTQIYTEEGKVWDYMACQPESTDMTRYLKVKLDPPDIT CGDPPETFCAMGNPYMCNNECDASTPELARPPELMFDFEGRHPSTWQSATWKEYPKPLQVNITLSWSKTI ELTDNIVITFESGRPDQMILEKSLDYGRTWQPYQYYATDCLIDAFHMDPKSVKDLSQHTVLEIICTEEYSTG YTTNSKIIHFEIRDRFAFFAGPRLRNMASLYGQLDTTKKLRDFFTVTDLRIRLLRPAVGEIFVDELHLARY FYAISDIKVRGRCKCNLHATVCVYDNSKLTCECEHNTTGPDCGKCKKNYQGRPWSPGSYLPIPKGTANTCI PSISSIGNPPKFNRIWPNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDNELLECQNGGTCKKEWR CLCPAAYTGILCEKLRCEEAGSCGSDSGQGAPPHGSPALLLQTTLLGTASPLVF A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 14D. Table 14B. Comparison of the NOV14 protein sequences. NOV14a -----MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14b -----MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14c ---------------------- RSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14d ---------------------------------------------------- RSCQPEST NOV14e ----- MYLSRFLSIALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14f TRSPTMYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14g ------TRSRQRS-RGRSISRGRHARTHPQTALLESSCENK-RADLVFIID--SSR--SV NOV14h ------TRSRQRS-RGRSISRGRHARTHPQTALLESSCENK-RADLVFIID--SSR--SV NOV14i ------TRSRQRS-RGRSTSRGRHARTHPQTALLESSCENK-RADLVFIID--SSR--SV NOV14j ----- MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14k ----- MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV141 ----- MYLSRFLSIRALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14m ----- MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14n ----- MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV140 ----- MYLSRFLSIHALWATVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14p ----- MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14q ------------------------ VMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14r ---------------------------------------------- GSAAAPFTCQPEST NOV14s ----- MYLSRFLSIRALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14t ------------------------------------------------------ CQPEST NOV14u ----- MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14v -----MYLSRFLSIHALWVTVSSVMQPYPLVWGHYDLCKTQIYTEEGKVWDYMACQPEST NOV14a DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14b DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14c DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14d DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14e DMTKYLKVKLOPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14f DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14g NTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMR NOV14h NTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMR NOV14i NTHDYAKVKEFIVDILQFLDIGPDVTRVGLLQYGSTVKNEFSLKTFKRKSEVERAVKRMR NOV14j DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14k DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV141 DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR 250 WO 031093432 PCT/US03/1 3690 NOV14m DMTKYLKVKLDPPDITCG-DP-PETFCAM~GNPYMCNNECDASTPELAHPPELMFDFE-GR NOVi 4n DMTKYLEVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14o DMTKYLKVKLDPPDITCG-DP-PETFCAMGN2YM4CNNECDASTPELAHPPELMFDFE.Ga NOVi dp DMTJYLKVKLDPPDITCGDPPETFCMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14q DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14r DMTKYLKVKLDPPDTTCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE.GR NOV14s DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14t DMKLVLPDTGD-EFAGNYCNCATEAPEMDEG NOVi 4u DMTKYLKVKLDPPDITCG-DP-PETFCAMGNPYMCNNECDASTPELAHPPELMFDFE-GR NOV14v DNTKYLB(VKLDPPDITCG-DP-PETFCA4GNPYMCNNFCDASTPELAHPPLMFDFE-GR NOV14a HPSTFWQSATWKEYPKPLQNTLSWSK-TIELTDNI-VITFESGRPD--QMILEKS NOVI4b HPSTFWQSATKEYPKPLQVNTLSWSKTIELTDNIVITFESRP-QMLSS NOV14c HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRPD--MILEKS NOV14d HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRP-D-QMILEKS NOV14e HPTWSTKYKLVILWKTILDI-IFSGPD-MLK NOV14f HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFSGRP-D-QMILEKS NOV14 g RLSTG--TMTG--LAIQYALNIAFSEAEGARPLRENVPRVTMIVTDGRPQDSVAEVAAKA NOVi 4h HLSTG--TMTG--LAIQYALNIAFSEAEGARPLRENVPRVIMIVTDGRPQDSVAEVAAKA NOV14 i HLSTG--TMTG--LAIQYALNIAFSEAEGAaPLRENVPRVIMIVTDGRPQDSVAEVAK NOV14j HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRP-D-QMILEKS NOV14 k HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRP2D-QMILEKS NOV141 HPSTFWQSATWKYPKPLQVNITLSWSKTIELTDNIVITFESR-D-QMILEKS NOV14m HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESOGRP-D-QMILEKS NOV14n HPSTFWQSATWKEYPKPLQVNITLSWSKTELTDN-VITFES-RP.D-QMILEKS NOV14o HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRP-D-QMILEKS NOV14p HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRP-D-QMILEKS NOV14 q HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFES-GRP.D--QMILEKS NOV14r HPSTFWQSATWKEYPKLQVNITLSWSKTIELTDNIVITFESGRP-D-QMILEKS NOV14s HPSTFWQSATWKEYPKPLQVNITLSWSKTIELTDNIVITFESGRP-D-QMILEKS NOV14t HPSTFWQSATWKEYPPLQVNITLSWSKTIELTDNIVITFES-GRPD-QMILEKS NOV14u HPSTFWQSATWKEYPKLQVNITLSWSKTIELTDN-VITFES-RP.D-QMILEKS NOV14v HPSTFWQSATWKEYPKLQVNITLSWSKTIELTDNIVITFESGRPD-QMLEKS NOV14a LDGTQYYAD-LA -- HDPSVDSEVEITESGTN NOV14b LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOV14 c LDYGRTWQPYQYYATDC--LDAF----HMDPKS-VKDLSQHTVLEI ICTEEYSTGYTTNS NOVi 4d LDGTQYYAD-LA -- EDPSVDSHVEITESCTN NOV14e LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOV14f LDGTQYYAD-LA -- HDPSVDSRVEITESGTN NOVi 4g RDTGLFAIGVGQVDFNTLKSIGSEPHEDRVFLVANFSQIETLTSVFQKKLCTAH-MCS .NOvi 4h RDTGILI FAIGVGQVDFNTLKs IGSEPHEDHVFLVANFSQIETLTSVFQKKLCTAH-MCS NOV14i RDTGILIFAIGVcGQVDFNTLKSIGSE2IEDHVFLVANFSQIETLTSVFQKKLCTAH-MCS NOV14j LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOv14k LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOV14 1 LDGTQYYAD-LA -- MPSVDSHLEICTEEYSTGYTTNS NOVl4ra LDGTQYYAD-LA -- HDPSVDSHVEITESGT NOV14n LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOV14o LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOV14p LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOV14q LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOVi 4r LDYGRTWQPYQYYATDC--LDAF --- MDPKS-VKDLSQTVLEIICTEEYSTGYTTNS N0V14s LDGTQYYAD-LA -- HDPSVDSHVEITESGTN NOV14t LDYGRTWQPYQYYATDC--LDAF--HMDPKSVKDLSQHTVLEIICTEEYSTGYTTNS NOV14 u LDGTQYYAD-LA -- EDPSVDSRVEITESGTN NOV14v LDGTQYYAD-LA -- HDPSVDSHVEITESGTN 251 WO 03/093432 PCT/US03/13690 NOV14a KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14b KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14c KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14d KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14e KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14f KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14g TLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVC NOV14h TLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVC NOV14i TLEHNCAHFCINIPGSYVCRCKQGYILNSDQTTCRIQDLCAMEDHNCEQLCVNVPGSFVC NOV14j KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14k KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV141 KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14m KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14n KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14o KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14p KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14q KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14r KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14s KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14t KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOVl4u KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14v KIIHFEIKDRFAFFAGPRLRNMASLYGQLD-TTKKLRDFFTVTDLRIRLLRPAVGEIFVD NOV14a ELHLARYFYAISDIK---VRGRCCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14b ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14c ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14d ELHLARYFYAISDIK---VRGLE ------------------------------------ NOV14e ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14f ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14g QC-YSGYALAE-DGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCTK NOV14h QC-YSGYALAE-DGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCTK NOV14i QC-YSGYALAE-DGKRCVAVDYCASENHGCEHECVNADGSYLCQCHEGFALNPDEKTCTK NOV14j ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14k ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV141 ELHLARYFYAISDIK---ARGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14m ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14n ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14o ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14p ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14q ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14r ELHLARYFYAISDIK---VRGKGGRA--------------------------------- NOV14s ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14t ELHLARYFYAISDIK---VRG--------------------------------------- NOV14u ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14v ELHLARYFYAISDIK---VRGRCKCNLH--ATVCVYDNSKLTCEC-EHNTTGPD---CGK NOV14a ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT---- C--I--PSISSIGNPPKFNRIW NOV14b ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIG-------- NOV14c ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14d ----------------------------------------------------------- NOV14e ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14f ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14g IDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNME NOV14h IDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNME NOV14i IDYCASSNHGCQHECVNTDDSYSCHCLKGFTLNPDKKTCRRINYCALNKPGCEHECVNME NOV14j ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14k ---CKKNYQG-RPW---SPGSY-LPIPKG-AANT----C--I--PSISSIG-------- 252 WO 03/093432 PCT/US03/13690 NOV141 ---CKKNYQG-RPW---SPGSY-LPIPKG-TAN------------------------- NOV14m ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIG-------- NOV14n ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIG-------- NOV14o ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT ---- C--I--PSISSIG-------- NOV14p ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14q ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT ---- C--I--PSISSIGNPPKFNRIW NOV14r ---------------------------------------------------------- NOV14s ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14t ------------------------------------------------------- NOV14u ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14v ---CKKNYQG-RPW---SPGSY-LPIPKG-TANT----C--I--PSISSIGNPPKFNRIW NOV14a PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14b -------------------------------- TNVCDN--ELLHCQNGG--------- T NOV14c PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14d --------------------------------------------------------- NOV14e PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14f PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14g ESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKT NOV14h ESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKT NOV14i. ESYYCRCHRGYTLDPNGKTCSRVDHCAQQDHGCEQLCLNTEDSFVCQCSEGFLINEDLKT NOV14j PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14k ----------------------------------- KCYCN--PLGSIHD ----------- R NOV141 --------------------------------- TSNVCDN--ELLHCQNGG--------- T NOV14m ---------------------------------- TNVCDN--ELLHCQNGG--------- T NOV14n ---------------------------------- TNVCDN--ELLHCQNGG--------- T NOV14o ---------------------------------- TNVCDN--ELLHCQNGG--------- T NOV14p PNISSLEVSNPK-------------------- QANVCDN--ELLHCQNGG--------- T NOV14q PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14r ------------------------------------------------------- NOV14s PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG---------T NOV14t -------------------------------------------------------- NOV14u PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14v PNISSLEVSNPKQVAPKLALSTVSSVQVANHKRANVCDN--ELLHCQNGG--------- T NOV14a CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14b CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14c CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14d ----------------------------------------------------------- NOV14e CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14f CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14g CSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCV NOV14h CSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCV NOV14i CSRVDYCLLSDHGCEYSCVNMDRSFACQCPEGHVLRSDGKTCAKLDSCALGDHGCEHSCV NOV14j CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14k CNGSGFCECKTGTTGPKCD------ECLPGNSWHYGCQP---NVCDNELLPPCICQDSCR NOV141 CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14m CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14n CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD ------- SGQGAPPHGSPALLL NOV14o CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSLEKGN NOV14p CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14q CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14r ---------------------------------------------------------- NOV14s CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14t ---------------------------------------------------------- NOV14u CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL NOV14v CHNNVRCLCPAAYTGILCE------KLRCEEAGSCGSD------- SGQGAPPHGSPALLL 253 WO 03/093432 PCT/US03/13690 NOV14a L---TTLLGTASPLVF-------------------------------- NOV14b L---TTLLGTASPLVF----------------------------

-

NOV14c L---TTLLGTASPLVFLE---------------------- NOV14d ------------------------------------ NOV14e L---TTLLGTASPLVF--------------------------- NOV14f L---TTLLGTASPLVFLEG------------------------ NOV14g SSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAED NOV14h SSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAED NOV14i SSEDSFVCQCFEGYILREDGKTCRRKDVCQAIDHGCEHICVNSDDSYTCECLEGFRLAED NOV14j L---TTLLGTASPLVF------------------------

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NOV14k F---YLWPGRAPARLPREG------------------ NOV141 L---TTLLGTASPLVF-------------------- NOV14m L---TTLLGTASPLVF-------------------- NOV14n L---TTLLGTASPLVF------------------ NOV14o S---TTLD------------------------- NOV14p L---TTLLGTASPLVF----------------- NOV14q L---TTLLGTASPLVF----------------- NOV14r -------------------------------- NOV14s L---TTLLGTASPLVF-------------------- NOV14t --------------------

--------

NOV14u L---TTLLGTASPLVF------------------ NOV14v L---TTLLGTASPLVF--------------- NOV14a

---------------------

NOV14b

-----------------

NOV14c

------------------

NOV14d

------------------

NOV14e

-----------------

NOV14f ---------------- NOV14g GKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVID NOV14h GKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGR-

---

NOV14i GKRCRRKDVCKSTHHGCEHICVNNGNSYICKCSEGFVLAEDGRRCKKCTEGPIDLVFVID NOV14j ------------------------

--

NOV14k ---------------------- NOV141 ------------------------- NOV14m -------------------------- NOV14n --------------------------- NOV14o -------------------------- NOV14p -------------------------- NOV14q -------------------------- NOV14r ----------------------------- NOV14s ------------------------------- NOV14t -------------------------- - --- NOV14u -------------------------------- NOV14v ------------------------------ NOV14a ------------------------------- NOV14b -------------------------------- NOV14c ----------------------------------- NOV14d -------------------------------- NOV14e ------------------------------------ NOV14f -------------------- -- ------ NOV14g GSKSLGEENFEVVKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSAKDMKKA NOV14h --------------------------------------- NOV14i GSKSLGEENFEVVKQFVTGIIDSLTISPKAARVGLLQYSTQVHTEFTLRNFNSAKDMKKA NOV14j --------------------------------------------- 254 WO 03/093432 PCT/US03/13690 NOV14k ----------------------------------------------------------- NOV141 ---------------------------------------------------------- NOV14m ----------------------------------------------------------- NOV14n ----------------------------------------------------------- NOV14o ----------------------------------------------------------- NOV14p ----------------------------------------------------------- NOV14q ----------------------------------------------------------- NOV14r ----------------------------------------------------------- NOV14s ----------------------------------------------------------- NOV14t ----------------------------------------------------------- NOV14u ----------------------------------------------------------- NOV14v ----------------------------------------------------------- NOV14a ----------------------------------------------------------- NOV14b ----------------------------------------------------------- NOV14c ----------------------------------------------------------- NOV14d ----------------------------------------------------------- NOV14e ----------------------------------------------------------- NOV14f ---------------------------------------------------------- NOV14g VAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSEWASK NOV14h ----------------------------------------------------- NOV14i VAHMKYMGKGSMTGLALKHMFERSFTQGEGARPLSTRVPRAAIVFTDGRAQDDVSEWASK NOV14j --------------------------------------------------------- NOV14k ----------------------------------------------------------- NOV141 ----------------------------------------------------------- NOV14m ---------------------------------------------------------- NOV14n -------------------------------------------------------- NOV14o --------------------------------------------------------- NOV14p ---------------------------------------------------- NOV14q ----------------------------------------------------------- NOV14r ----------------------------------------------------------- NOV14s ----------------------------------------------------------- NOV14t ----------------------------------------------------------- NOV14u ----------------------------------------------------------- NOV14v ----------------------------------------------------------- NOV14a ----------------------------------------------------------- NOV14b ----------------------------------------------------------- NOV14c ----------------------------------------------------------- NOV14d ----------------------------------------------------------- NOV14e ----------------------------------------------------------- NOV14f ---------------------------------------------------------- NOV14g AKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDS NOV14h -RCKSITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDS NOV14i AKANGITMYAVGVGKAIEEELQEIASEPTNKHLFYAEDFSTMDEISEKLKKGICEALEDS NOV14j ----------------------------------------------------------- NOV14k ---------------------------------------------------------- NOV141 ----------------------------------------------------------- NOV14m ----------------------------------------------------------- NOV14n ----------------------------------------------------------- NOV14o ----------------------------------------------------------- NOV14p ----------------------------------------------------------- NOV14q ----------------------------------------------------------- NOV14r ----------------------------------------------------------- NOV14s ----------------------------------------------------------- NOV14t ----------------------------------------------------------- NOV14u ----------------------------------------------------------- 255 WO 03/093432 PCT/US03/13690 NOV14v ----------------------------------------------------------- NOV14a --------------------------------------------------------- INOV14b --------------------------------------------------------- NOV14c --------------------------------------------------------- NOV14d ---------------------------------------------------------- NOV14e ---------------------------------------------------------- NOV14f --------------------------------------------------------- NOV14g DGRQDSPAGELPKTVQQPTESEPVTINIQDLLSCSNFAVQHRYLFEEDNLLRSTQKLSHS NOV14h DGRQDSPAGELPKTVQQPT------------------- VQHRYLFEEDNLLRSTQKLSHS NOV14i DGRQDSPAGELPKTVQQPT------------------- VQHRYLFEEDNLLRSTQKLSHS NOV14j ----------------------------------------------------------- NOV14k----------------------------------------------------------- NOV141 ---------------------------------------------------------- NOV14m ----------------------------------------------------------- NOV14n ---------------------------------------------------------- NOV14o ----------------------------------------------------------- NOV14p ----------------------------------------------------------- NOV14q ----------------------------------------------------------- NOV14r ----------------------------------------------------------- NOV14s ----------------------------------------------------------- NOV14t -------------------------------------------------------- NOV14u -------------------------------------------------------- NOV14v --------------------------------------------------------- NOV14a ------------------------------------------------------- NOV14b --------------------------------------------------------- NOV14c --------------------------------------------------------- NOV14d -------------------------------------------------------- NOV14e ------------------------------------------------------ NOV14f -------------------------------------------------------- NOV14g TKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRMEALENRLRYRVDG NOV14h TKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRMEALENRLRYRVDG NOV14i TKPSGSPLEEKHDQCKCENLIMFQNLANEEVRKLTQRLEEMTQRMEALENRLRYRVDG NOV14j --------------------------------------------------------- NOV14k --------------------------------------------------------- NOV141 --------------------------------------------------------- NOV14m---------------------------------------------------------- NOV14n --------------------------------------------------------- NOV14o -------------------------------------------------------- NOV14p -------------------------------------------------------- NOV14q -------------------------------------------------------- NOV14r -------------------------------------------------------- NOV14s -------------------------------------------------------- NOV14t ------------------------------------------------------- NOV14u --------------------------------------------------------- NOV14v ----------------------------------------------------- NOV14a (SEQ ID NO: 162) NOV14b (SEQ ID NO: 164) NOV14c (SEQ ID NO: 166) NOV14d (SEQ ID NO: 168) NOV14e (SEQ ID NO: 170) NOV14f (SEQ ID NO: 172) NOV14g (SEQ ID NO: 174) NOV14h (SEQ ID NO: 176) NOV14i (SEQ ID NO: 178) 256 WO 03/093432 PCT/US03/13690 NOV14j (SEQ ID NO: 180) NOV14k (SEQ ID NO: 182) NOV141 (SEQ ID NO: 184) NOV14m (SEQ ID NO: 186) NOV14n (SEQ ID NO: 188) NOV14o (SEQ ID NO: 190) NOV14p (SEQ ID NO: 192) NOV14q (SEQ ID NO: 194) NOV14r (SEQ ID NO: 196) NOV14s (SEQ ID NO: 198) NOV14t (SEQ ID NO: 200) NOV14u (SEQ ID NO: 204) NOV14v (SEQ ID NO: 206) Further analysis of the NOV14a protein yielded the following properties shown in Table 14C. Table 14C. Protein Sequence Properties NOV14a SignalP analysis: Cleavage site between residues 19 and 20 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 5; pos.chg 1; neg.chg 0 H-region: length 25; peak value 8.10 PSG score: 3.70 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.81 possible cleavage site: between 18 and 19 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 = -2.87 Transmembrane 464 - 480 PERIPHERAL Likelihood = 3.34 (at 3) ALOM score: -2.87 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 471 Charge difference: 0.5 C( 0.0) - N(-0.5) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide >>> Single TMS is located near the C-terminus >>> membrane topology: type Nt (cytoplasmic tail 1 to 463) MITDISC: discrimination of mitochondrial targeting seq R content: 1 Hyd Moment(75): 7.91 Hyd Moment(95): 7.87 G content: 1 257 WO 03/093432 PCT/US03/13690 D/E content: 1 S/T content: 5 Score: -2.60 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 15 SRFILS 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: YLSR 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: too long tail Dileucine motif in the tail: found LL at 266 LL at 412 checking 63 PROSITE DNA binding motifs: none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 70.6 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues 258 WO 03/093432 PCT/US03/13690 Final Results (k = 9/23): 30.4 %: nuclear 21.7 %: cytoplasmic 13.0 %: Golgi 13.0 %: mitochondrial 8.7 %: endoplasmic reticulum 4.3 %: peroxisomal 4.3 %: plasma membrane 4.3 %: vesicles of secretory system >> prediction for CG51051-07 is nuc (k=23) A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14D. 259 WO 03/093432 PCT/US03/13690 Table 14D. Geneseq Results for NOV14a NOV14a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAB49651 Human SEC3 protein sequence SEQ 1..480 480/480 (100%) 0.0 ID 6 - Homo sapiens, 480 aa. 1..480 480/480 (100%) [WO200070046-A2, 23-NOV-2000] ABB05421 Mouse membrane bound type netrin 1..480 461/480 (96%) 0.0 protein SEQ ID NO:14 - Mus 1..480 467/480 (97%) musculus, 480 aa. [JP2001327289 A, 27-NOV-2001] ABB05422 Mouse membrane bound type netrin 1..480 441/480 (91%) 0.0 protein SEQ ID NO:16 - Mus 1..460 447/480 (92%) musculus, 460 aa. [JP2001327289 A, 27-NOV-2001] ABU07468 Protein differentially regulated in 1..363 362/363 (99%) 0.0 prostate cancer #71 - Homo sapiens, 1..363 363/363 (99%) 364 aa. [WO200281638-A2, 17 OCT-2002] ABU07437 Protein differentially regulated in 1..363 362/363 (99%) 0.0 prostate cancer #40 - Homo sapiens, 1..363 363/363 (99%) 364 aa. [WO200281638-A2, 17 OCT-2002] In a BLAST search of public sequence databases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14E. 260 WO 03/093432 PCT/USO3/13690 Table 14E. Public BLASTP Results for NOV14a NOV14a Identities/ Protein Residues/ Similarities for Expect Accession Protein/Organism/Length Match the Matched Value Number Residues Portion CAC21786 Sequence 5 from Patent 1..480 480/480 (100%) 0.0 WO0070046 - Homo sapiens 1..480 480/480 (100%) (Human), 480 aa. Q9ESR6 Netrin-GId - Mus musculus 1..480 461/480 (96%) 0.0 (Mouse), 480 aa. 1..480 467/480 (97%) Q8R4F8 Laminet-ID - Mus musculus 1..480 460/480 (95%) 0.0 domesticus (western European 1..480 466/480 (96%) house mouse), 480 aa. Q9ESR7 Netrin-Gle (Netrin Gl) - Mus 1..480 441/480 (91%) 0.0 musculus (Mouse), 460 aa. 1..460 447/480 (92%) Q8R4F7 Laminet-lE - Mus musculus 1..480 440/480 (91%) 0.0 domesticus (western European 1 ..460 446/480 (92%) house mouse), 460 aa. PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14F. Table 14F. Domain Analysis of NOV14a Identities/ Pfam Domain NOV14a Match Region Similarities Expect Value for the Matched Region laminin Nterm 50..295 73/286 (26%) 1.7e-12 134/286 (47%) laminin EGF 297..341 19/59 (32%) 1.5e-05 30/59 (51%) EGF 408..438 15/47 (32%) 0.55 21/47(45%) 261 WO 03/093432 PCT/US03/13690 Example 15. The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A. Table 15A. NOV15 Sequence Analysis NOVI5a, CG52261-01 ISEQ ID NO: 211 937 bp DNA Sequence JORF Start: ATG at 317 ORF Stop: TAG at 644 TCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCA GTTACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGG CTGGTGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTC AAACTCAGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCT ACTGTGTGTTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTG CCATCCCCAATGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGT CACCAAAAGGATGTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCT TTCTCCTGGTTCTACTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCC AATGGCAGCCCAACGCACAGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTT TCTGGTAACACTTCCCACCTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCC AGCTGAGTCACCTGTCATTTGAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCC ATCCACCATCTCTGTGCCCCGTCCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAA CTAAGTTTGGGATGATGTGTTACACAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGG CTCCCTCTGCCTAAGACATGTGTTTCTGCACATCCATTCACACAGCCAAGAAG NOV15a, CG52261-01 SEQ ID NO: 2121109 aa IMW at 12122.2kD Protein Sequence MLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLVLLEGSPLQKLA SLKPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC NOVI 5b, 268667469 SEQ ID NO: 213 346 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence CACCGGATCCATGCTCTTTTGCAACGTGACCCTGCCATCCCCAATGACAGTGGGAGTCCAATCCTCTC CTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGTCACCAAAAGGATGTGGCAGAAGTGGCACTGTTCA ACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCTTTCTCCTGGTTCTACTAGAAGGCTCCCCCCTACA GAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCCAATGGCAGCCCAACGCACGGGAGAGGCTTGCATG TGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTTTCTGGTAACACTTCCCACCTGTCAGATGTGCCTC GAGGGC NOV15b, 268667469 ISEQ ID NO: 214 115 aa MW at 12567.6kD Protein Sequence TGSMLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLVLLEGSPLQ KLASLKPSSRANGSPTHGRGLHVLQSPAPDEPSFLVTLPTCQMCLEG NOV15c, CG52261-02 SEQ ID NO: 215 937 bp DNA Sequence ORF Start: ATG at 317 IORF Stop: TAG at 644 TCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCA GTTACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGG CTGGTGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTC AAACTCAGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCT ACTGTGTGTTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTG CCATCCCCAATGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGT CACCAAAAGGATGTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCT TTCTCCTGGTTCTACTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCC AATGGCAGCCCAACGCACAGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTT TCTGGTAACACTTCCCACCTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCC AGCTGAGTCACCTGTCATTTGAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCC ATCCACCATCTCTGTGCCCCGTCCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAA 262 WO 03/093432 PCT/USO3/13690 CTAAGTTTGGGATGATGTGTTACACAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGG CTCCCTCTGCCTAAGACATGTGTTTCTGCACATCCATTCACACAGCCAAGAAG NOV15c, CG52261-02 SEQ ID NO: 216 109 aa MW at 12122.2kD Protein Sequence MLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLVLLEGSPLQKLA SLKPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC NOV15d, 13382342 SNP for SEQ ID NO: 217 937 bp SNP: 347 C/T CG52261-01 ORF Start: ATG at ORF Stop: end of sequence DNA Sequence 317 TCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCAGT TACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGGCTGG TGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTCAAACTC AGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCTACTGTGTG TTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTGCCATCCTCAA TGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGTCACCAAAAGGAT GTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCTTTCTCCTGGTTCTA CTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCCAATGGCAGCCCAACGC ACAGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTTTCTGGTAACACTTCCCAC CTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCCAGCTGAGTCACCTGTCATTT GAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCCATCCACCATCTCTGTGCCCCGT CCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAACTAAGTTTGGGATGATGTGTTACA CAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGGCTCCCTCTGCCTAAGACATGTGTTTC TGCACATCCATTCACACAGCCAAGAAG NOV15d, 13382342 SNP for SEQ ID NO: 109 aa SNP: Pro to Ser at position CG52261-01 218 11 Protein Sequence MLFCNVTLPSSMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLVLLEGSPLQKLASL KPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC NOV15e, 13382341 SNP for SEQ ID NO: 219 937 bp SNP: 563 A/G CG52261-01 IORF Start: ATG at ORF Stop: end of sequence DNA Sequence 317 TCAGTCCTGGTCCCTCCCCTTCTTGGGTTCCTCATCCTGCTCTTCTAAATGTCGAGATGCCTGCAGCAGT TACGCTTATCTCTGGCCACTATCTCTGCTTTTATCTCCTTTCTTAAAAGTCTTCAATGTCTCTAGGCTGG TGTGTAAAGTCCTCTATCTTCAGTTACTACACCCTTTTCACCTTCAAAATCCTATGCGCACCTCAAACTC AGCAAGTGTTAACTGAATTAGTCATCTTTGCTGCCATCGGCTGCCAACCTCCACTGTGGCCTACTGTGTG TTTCAAAGATGGCTCCGGAAATTATTCCCGTCCCACATGCTCTTTTGCAACGTGACCCTGCCATCCCCAA TGACAGTGGGAGTCCAATCCTCTCCTCTTGAATCTGGGCTGGCTCTTAGGACTCTTGTCACCAAAAGGAT GTGGCAGAAGTGGCACTGTTCAACTTTTGAGGCTAGGCTGAAAAGACTGTACAGCTTTCTCCTGGTTCTA CTAGAAGGCTCCCCCCTACAGAAGCTCGCCTCTCTCAAACCCAGCAGCCGTGCCAATGGCAGCCCAACGC ACGGGAGAGGCTTGCATGTGCTTCAGTCACCAGCTCCAGATGAGCCCAGTTTTCTGGTAACACTTCCCAC CTGTCAGATGTGCTAGCGAGGGCACCTCCAGATGACTCCAGTCCTCAGCCAGCTGAGTCACCTGTCATTT GAATTCTTCCAGCTGAGGCTCCCAGACATTGTCAGACAGAGACAAGCCATCCACCATCTCTGTGCCCCGT CCAAACTCCTGACCCACGCAGTCCATAAGGAAGAGGTTCTATGCAACTAAGTTTGGGATGATGTGTTACA CAGCAGTACCCACCACACCCAACAAAACCACCAGTGCTTCCTGGCTCCCTCTGCCTAAGACATGTGTTTC TGCACATCCATTCACACAGCCAAGAAG NOV15e, 13382341 SNP for SEQ ID NO: 109 aa SNP: Arg to Gly at position 83 CG52261-01 20 Protein Sequence MLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLVLLEGSPLQKLASL KPSSRANGSPTHGRGLKVLQSPAPDEPSPLVTLPTCQMC 263 WO 03/093432 PCT/US03/13690 A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 15B. 264 WO 03/093432 PCT/US03/13690 Table 15B. Comparison of the NOV15 protein sequences. NOV15a ---MLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLV NOV15b TGSMLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLV NOV15c ---MLFCNVTLPSPMTVGVQSSPLESGLALRTLVTKRMWQKWHCSTFEARLKRLYSFLLV NOV15a LLEGSPLQKLASLKPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC-- NOV15b LLEGSPLQKLASLKPSSRANGSPTHGRGLHVLQSPAPDEPSFLVTLPTCQMCLEG NOV15c LLEGSPLQKLASLKPSSRANGSPTHRRGLHVLQSPAPDEPSFLVTLPTCQMC-- NOV15a (SEQ ID NO: 212) NOV15b (SEQ ID NO: 214) NOV15c (SEQ ID NO: 216) Further analysis of the NOV15a protein yielded the following properties shown in Table 15C. Table 15C. Protein Sequence Properties NOV15a SignalP analysis: Cleavage site between residues 65 and 66 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 21; peak value 7.16 PSG score: 2.76 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.57 possible cleavage site: between 18 and 19 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 = 3.18 (at 54) ALOM score: 3.18 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 6 Charge difference: 1.0 C( 2.0) - N( 1.0) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 5.42 Hyd Moment(95): 2.82 G content: 1 D/E content: 1 S/T content: 5 Score: -4.44 Gavel: prediction of cleavage sites for mitochondrial preseq 265 WO 03/093432 PCT/US03/13690 R-3 motif at 53 KRLYIS NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 11.0% NLS Score: -0.47 KDEL: ER retention motif in the C-terminus: none IER 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 89 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 65.2 %: nuclear 21.7 %: mitochondrial 8.7 %: cytoplasmic 4.3 %: peroxisomal 266 WO 03/093432 PCT/US03/13690 >> prediction for CG52261-01 is nuc (k=23) A search of the NOV 15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15D. Table 15D. Geneseq Results for NOV15a NOV15a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAB85225 Human secreted protein (SECX) 1..109 109/109 (100%) 2e-59 sequence (clone 3277237) - Homo 1..109 109/109 (100%) sapiens, 109 aa. [WO200144287-A2, 21-JUN-2001] AAB14303 Human secreted protein encoded by 1..109 109/109 (100%) 2e-59 cDNA clone 3277237 - Homo 1..109 109/109 (100%) sapiens, 109 aa. [WO200037634-A2, 29-JUN-2000] AAB46696 Fowlpox virus DNA polymerase 2..57 15/56 (26%) 3.9 protein fragment SEQ ID NO 5 - 448..503 34/56 (59%) Fowlpox virus-874 aa. [WO200075335-A2, 14-DEC-2000] AAU41849 Propionibacterium acnes 10..40 14/34 (41%) 3.9 Propionibacterium acnes, 109 aa. [WO200181581-A2, 01-NOV-2001] AAO16328 Human polyamine oxidase (PAO) 52..97 17/50 (34%) 6.7 isoform 4 - Homo sapiens, 532 aa. 429..478 27/50 (54%) [WO2002100884-A2, 19-DEC 2002] In a BLAST search of public sequence databases, the NOV 15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15E. 267 WO 03/093432 PCT/USO3/13690 Table 15E. Public BLASTP Results for NOV15a NOV15a Identities/ Protein Residues/ Similarities for Expect Accession Protein/Organism/Length Match the Matched Value Number Residues Portion CAC50793 Sequence 7 from Patent 1..109 109/109 (100%) 7e-59 WO0144287 - Homo sapiens 1..109 109/109 (100%) (Human), 109 aa. Example 16. The NOV16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A. Table 16A. NOV16 Sequence Analysis NOV1I6a, CG52414-02 SEQIDNO:221 3040 bp DNA Sequence jORF Start: ATG at 338 ORF Stop: TGA at 2819 TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAG GCCAGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGG CAGGTGGAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCAC AGACTGAGGCTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCT TCACAGCAAGACCCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATG GCCTCTGCTGACAAGAATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCC ACCCAACCTCTCCATCACCATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCA TGCTGCCTGAGAGGAAGAACCCAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGG CAGGAGAGTTCAGAGAAGCGCCCTGGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGG CGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCC TGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGC CAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCC GCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCCCACGCCCCGCACCCACCGC TGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGGCTACTCCCACCTGCCACGC CGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCCTCCTCAAGGGGCGCTCGGT GCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTTTGCCTTCCCGAGCTTCCTGGAGG AGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAAGGAAGAAATGAGCTCCATG CCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGGATCCCACACTCAGCCTC CCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCCAGTCCCCGGGCCCC GGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGCGGCACTACGGC CTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTGCAGCGGCA GCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCATCATCA CGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGCTG GTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCC CAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCG AGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCC GGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGA CACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGG ACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGG CCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGG CCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGC ACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTG CTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGC 268 WO 03/093432 PCT/US03/13690 TGGGGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGG CCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATC TTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCGGCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGT GGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTCCTCAACCTCTCGGCCATCG TGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGCCCACATCTTCGGCTTCCTC AGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCACCAGCGACAAGTACCGCAA GCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCCGCCCTCGTGCTGTGGCTGT ACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCCCTTCACCAGCCGCTTCTGC GAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTGCCCCTCAGCCCTGCTG GAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGAGAGCCAGAGACCC AAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGCGTGAGATAGA TGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA OV16a, CG52414-02 ISEQ ID NO: 222 7aa MW at 93378.2kD Protein Sequence MASADKlGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSR WQESSERRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELP SQEAPSPQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLP RRKRMSVAHMSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSS MPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGRIASKVKHFAFDRKKRHY GLGVVGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQ LVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDH SGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGAHIWPDDITK WPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCG LLPFLNPEVPDQFYRLWLSLFLHAGVVHCLVSVVFQMTILRDLEKLAGWHRIAIIFILSGITGNLASA IFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLERPWKAFLNLSAIVLFLFICGLLPWIDNIAHIFGF LSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRF CEKYELDQVLH NOV16b, 305262879 SEQ ID NO: 223 1694 bp DNA Sequence JORF Start: at 2 RFT Stop: end of sequence CACCAGATCTCAGCACGTCACCACCCAGCTGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGT ACATCCAGCAGGAGAACTTCTGGGTTGGCCCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTC TCACCCTGCATCCGGAAGGACGGGCAGATCGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGA CTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGA CTTTGGCCACTTTTOTCAAGTGGCAGGATGACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAG AAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGC CCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACACG GCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAG ATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCA GGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCT ACAGGCTCGAGGGC NOV16b, 305262879 SEQ3 D :224l231aa 1MWat26183.3kD Protein Sequence TRSQHVTTQLVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERD SGCCVQNDHSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA HIWPDDITKWPICTEQARSNHTGFLEMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQ VHCLDKVCGLLPFLNPEVPDQFYRLEG NOV16c, 319073326 SEQ ID NO: 225 12506 bp DNA Sequence lORF Start: at 2 ORF Stop: end of sequence CACCAGATCTCCCACCATGGCCTCTGCTGACAAGAATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCC GCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCACCATCCCGCCACCCGAGAAAGAGACCCAGGCC CCTGGCGAGCAAGACAGCATGCTGCCTGAGAGGAAGAACCCAGCCTACTTGAAGAGCGTCAGCCTCCA GGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCTGGCTTCCGCCGCCAGGCCTCACTGT CCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAG CAGTGGCAGCGCCGCAGCCCGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCG 269 WO 03/093432 PCT/US03/13690 TGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGA TGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCC CACGCCCTGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGG CTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCC TCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGATGGTCAAGCGCAGCTTTGCC TTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAA GGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAG GGATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGA GCCCCAGTCCCCGGGCCCCGGCGCGGTGAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCG GAAGAAGCGGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGTTACCGCCGCAGCATCA GCAGCACTGTGCAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACC TTCGTCCATGTCATCATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCA GCACGTCACCACCCAGCTGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGG AGAACTTCTGGGTTGGCCCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATC CGGAAGGACGGGCAGATCGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTG TGTCCAGAATGACCACTCCGGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTT TTGTCAAGTGGCAGGATGACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCG GGGGCTGTCTGCCACCAGGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCC CGATGACATCACTAAGTGGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACA TGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGG GAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTT GGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGC TGTCTCTCTTCCTACATGCTGGCGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTG AGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGG CAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTGGGCCCGGCCGGCTCACAGTTCGGCC TCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTC CTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGC CCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCA CCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCC GCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACCTCGAGGGC NOV16c, 319073326 JSEQ ID NO: 226 835 aa ]MW at 94253.1kD Protein Sequence TRSPTMASADEGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQ EPRSRWQESSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSPHCSMRYGRLKASCQR DLELPSQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHALHPPLTPGVLSLTSFTSVRSG YSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQRCRMVKRSFAFPSFLEEDVVDGADTFDSSFFSK EEMSSMPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGERIASKVKHFAFDR KKRHYGLGVVGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQ HVTTQLVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCC VQNDHSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGAHIWP DDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCL DKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVVHCLVSVVFQMTILRDLEKLAGWHRIAIIFILSGITG NLASAIFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLERPWKAPLNLSAIVLFLFICGLLPWIDNIA HIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFP FTSRFCEKYELDQVLHLEG NOV16d, CG52414-01 SEQ ID NO: 227 2596 bp DNA Sequence ORF Start: ATG at 289 ORF Stop: TGA at 2413 TCAATTGACTTGATATGATTTATTATTTTTACTACTTATAAGAATGGAAATAAGTTCTCCTTAGTTTT TTTCTTGGAGAAAGTCTGACATGTGAGGCACAGATGAGTTATTAAAGGCAGATGACTTTCCAGCCTTG TCTTAAATGTTCCATTCTTTACCTTAGAAATTATTTAAATTTGTGTCCTGTCCCAGAGCATCCGCAAG GGCGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAG CCTGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCA GCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGATGCCCAAGATTGTGGAT CCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCCCACGCCCTGCACCCACC GCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGGCTACTCCCACCTGCCAC 270 WO 03/093432 PCT/US03/13690 GCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCCTCCTCAAGGGGCGCTCG GTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTTTGCCTTCCCGAGCTTCCTGGA GGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAAGGAAGAAATGAGCTCCA TGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGGATCCCACACTCAGCC TCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCCAGTCCCCGGGCC CCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGCGGCACTACG GCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTGCAGCGG CAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCATCAT CACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGC CCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGAT CGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACT CCGGCTGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGAT GACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCA GGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGT GGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAG GGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCAT GCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGC TGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACAT GCTGGCGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCT GGCCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGGCAACCTCGCCAGTACCA TCTTTCTCCCATACCGGGCAGAGGTGGGCCCGGCCGGCTCACAGTTCGGCCTCCTCGCCTGCCTCTTC GTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTCCTCAACCTCTCGACCAT CGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGCCCACATCTTCGGCTTCC TCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCACCAGCGACAAGTACCGC AAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCCGCCCTCGTGCTGTGGCT GTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCCCTTCACCAGCCGCTTCT GCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTGCCCCTCAGCCCTGC TGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGAGAGCCAGAGAC CCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGCGTGAGATG GTTGGTTAAGGC NOV16d, CG52414-01 SEQ ID NO: 228 708 aa MW at 80098.6kD Protein Sequence MRYGRLKASCQRDLELPSQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHALHPPLTPGV LSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVD GADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKR IASKVKHFAFDRKKRHYGLGVVGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFV-VIITLLVI CTYGIAPVGFAQHVTTQLVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVL RERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTC EEPASSGAHIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVVHCLVSVVFQMTILRDLEKLAGWHR IAIIFILSGITGNLASTIFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLERPWKAFLNLSTIVLFLF ICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPI NWPWIEHLTCFPFTSRFCEKYELDQVLH NOV16e, CG52414-03 SEQ ID NO: 229 2516 bp DNA Sequence ORF Start: ATG at 17 ORF Stop: end of sequence CACCAGATCTCCCACCATGGCCTCTGCTGACAAGAATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCC GCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCACCATCCCGCCACCCGAGAAAGAGACCCAGGCC CCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACCCAGCCTACTTGAAGAGCGTCAGCCTCCA GGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCTGGCTTCCGCCGCCAGGCCTCACTGT CCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGGCGACTGGGAGGGGCAGCGGCAG CAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCCTGAAGGCCTCGTGCCAGCG TGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCCCCAAAGCCCTGCAAGA TGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGAGATGGACAGGCCC CACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTGTCCGTTCTGG CTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCCGCTGCCC 271 WO 03/093432 PCT/US03/13690 TCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTTTGCC TTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTAA GGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAG GGATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGA GCCCCAGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCG GAGAAGCGGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCA GCAGCACTGTGCAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACC TTCGTCCATGTCATCATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCA GCACGTCACCACCCAGCTGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGG AGAACTTCTGGGTTGGCCCCAGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATC CGGAAGGACGGGCAGATCGAGCAGCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTG TGTCCAGAATGACCACTCCGGATGCATCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTT TTGTCAAGTGGCAGGATGACACTGGGCCCCCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCG GGGGCTGTCTGCCACCAGGACCCCAGGACCTGCGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCC CGATGACATCACTAAGTGGCCGATCTGCACAGAGCAGGCCAGGAGCAACCACACAGGCTTCCTGCACA TGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGCACCAAGGGCAGCTGTGAGATCACCACCCGG GAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGCAACACTCTGCTCCCAGGTGCACTGCTT GGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCCCAGATCAGTTCTACAGGCTCTGGC TGTCTCTCTTCCTACATGCTGGCGTGGTGCACTGCCTCGTGTCTGTGGTCTTTCAAATGACCATCCTG AGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCATCCTCAGTGGCATCACAGG CAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTGGGCCCGGCCGGCTCACAGTTCGGCC TCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCCTGGAAGGCCTTC CTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGACAACATCGC CCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCTTCGGCA CCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTCGCC GCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCAC NOV16e, CG52414-03 SEQ ID NO: 230 827 aa MW at 93378.2kD Protein Sequence MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSR WQESSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELP SQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPRAPHPPLTPGVLSLTSFTSVRSGYSHLP RRKRNSVAHMSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSS MPDDVFESPPLSASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHY GLGVVGNWLNRSYRRSISSTVQRQLESFDSHRPYFTYWLTFVKVIITLLVICTYGIAPVGFAQHVTTQ LVLRNKGVYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDH SGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGAHIWPDDITK WPICTEQARSNHTGFLKMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCG LLPFLNPEVPDQFYRLWLSLFLAGVVHCLVSVVFQMTILRDLEKLAGWHRIAIFILSGITGNLASA IPLPYRAEVGPAGSQFGLLACLFVELFQSWPLLERPWKAFLNLSAIVLFLFICGLLPWIDNIAHIFGF LSGLLLAFAFLPYITFGTSDKYRKRALILVSLLAFAGLFAALVLWLYIYPINWPWIERLTCFPFTSRF CEKYELDQVLH NOV16f, 13379509 SNP for SEQ ID NO: 231 _40bpSNP: 873 C/T CG52414-02 ORF Start: ATG at ORF Stop: TGA at 2819 DNA Sequence 338 TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG CTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCTTCACAGCAAGAC CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATGGCCTCTGCTGACAAG AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCT GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC 272 WO 03/093432 PCT/US03/13690 CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCTGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCC AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC AGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG GCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC TGGAAGGCCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT TCGGCACCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA pGAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAA NOV16f, 13379509 SNP for SEQ ID NO: 827 aa SNP: Pro to Leu at position 179 CG52414-02 232 Protein Sequence MASADKNGGSVSSVSS SRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSRWQE SSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLKHCSMRYGRLKASCQRDLELPSQEAPS FQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHALPPLTPGVLSLTSFTSVRSGYSHLPRRKMRSVAH MSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLS ASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGNWENRSYRR SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQKVTTQLVLRNKGVYESVKYIQQE NFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSCCVQNDHSGCIQTQRKDCSETLATFVKW QDDTGPPMDKSDLGQKRTSGAVCQDPRTCEEPASSGAHIWPDDITKWPICTEQARSNHTGFLHMCEIKG RPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVV HCLVSVVFQMTILRDLEKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQSW PLLERPWKAFLNLSAIvLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLL AFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH NOV16g, 13381817 SNP for SEQ ID NO: 233 3040bp SNP: 971 G/A CG52414-02 ORF Start: ATG at 338 ORF Stop: TGA at 2819 DNA Sequence TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG CTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCTTCACAGCAAGAC CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATGGCCTCTGCTGACAAG AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC 273 WO 03/093432 PCT/US03/13690 CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCT GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGACCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCC AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC AGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG GCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC TGGAAGGCCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT TCGGCACCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA GAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA NOV16g,13381817 SNP for SEQ ID NO: 827 aa SNP: Ala to Thr at position CG52414-02 234 212 Protemn Sequence MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSRWQE SSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELPSQEAPS FQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVTH MSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLS ASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGNWENRSYRR SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKGVYESVKYIQQE NFWVGPSSIDLIKLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVKW QDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGAHIWPDDITKWPICTEQARSNHTGFLEMDCEIKG RPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLKAGVV HCLVSVVFQMTILRDLEKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQSW PLLERPWAFLNLSAIVLLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLL AFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH NOV16h, 13382069 SNP for SEQ ID NO: 235 3040bp SNP: 1247C/T CG52414-02ORF Start: ATG at 338 ORF Stop: TAA at 1247 DNA Sequence TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC 274 WO 03/093432 PCT/US03/13690 AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG CTTGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACATGCTCTAAAGCCCTTCACAGCAAGAC CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATGGCCTCTGCTGACAAG AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCT GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGTAAATCCCTCTGAAGGAGTATGGCCGAGCCCC AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC AGCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG GCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC TGGAAGGCCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT TCGGCACCAGCGACAAGTACCGCAAGCGGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA GAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA NOV16h, 13382069 SNP for SEQ ID NO: 827 aa SNP: Gln to STOP at position CG52414-02 236 304 Protein Sequence_ MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPAYLKSVSLQEPRSRWQE SSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELPSQEAPS FQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAR MSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLS ASYFRGIPHSASPVSPDGV* NOV16i, 13381560 SNP for SEQ ID NO: 237 .3040 bp SNP: 2493 C/T CG52414-02 ORF Start: ATGat 338 ORFE Stop: TGA at 2819 DNA Sequence TTTGGGGCCGCAGGGAGGTTCCCAGACCAGAGGACTGTTGTTAGGTGATTGGCTGTGAACGCCCTGAGGCC AGTGCCCCTCGCTGCTTGGCACTCGGAGATGCCTGATTAGCACCTTTAATCCCTTACCAATGAGGCAGGTG GAATTGGCCCCATTTTACAGATGGGGAGACTGAGCCACCTGTCTGTCCAGCCACCCTTCCACAGACTGAGG 275 WO 03/093432 PCT/US03/13690 CGACACCGGAGCATCTGTACAGAGCAAGGAGAAGACAAGAACAGCTCTAAAGCCCTTCACAGCAAGAC CCAGGAAGCCGCGGGCAAACTCAGACTCGAAGCCCTCCCACCTCCTGCCCACAATGGCCTCTGCTGACAAG AATGGCGGGAGCGTGTCCTCTGTGTCCAGCAGCCGCCTGCAGAGCCGGAAGCCACCCAACCTCTCCATCAC CATCCCGCCACCCGAGAAAGAGACCCAGGCCCCTGGCGAGCAGGACAGCATGCTGCCTGAGAGGAAGAACC CAGCCTACTTGAAGAGCGTCAGCCTCCAGGAGCCACGCAGCCGATGGCAGGAGAGTTCAGAGAAGCGCCCT GGCTTCCGCCGCCAGGCCTCACTGTCCCAGAGCATCCGCAAGGGCGCAGCCCAGTGGTTTGGAGTCAGCGG CGACTGGGAGGGGCAGCGGCAGCAGTGGCAGCGCCGCAGCCTGCACCACTGCAGCATGCGCTACGGCCGCC TGAAGGCCTCGTGCCAGCGTGACCTGGAGCTCCCCAGCCAGGAGGCACCGTCCTTCCAGGGCACTGAGTCC CCAAAGCCCTGCAAGATGCCCAAGATTGTGGATCCGCTGGCCCGGGGCCGGGCCTTCCGCCACCCGGAGGA GATGGACAGGCCCCACGCCCCGCACCCACCGCTGACCCCCGGAGTCCTGTCCCTCACCTCCTTCACCAGTG TCCGTTCTGGCTACTCCCACCTGCCACGCCGCAAGAGAATGTCTGTGGCCCACATGAGCTTGCAAGCTGCC GCTGCCCTCCTCAAGGGGCGCTCGGTGCTGGATGCCACCGGACAGCGGTGCCGGGTGGTCAAGCGCAGCTT TGCCTTCCCGAGCTTCCTGGAGGAGGATGTGGTCGATGGGGCAGACACGTTTGACTCCTCCTTTTTTAGTA AGGAAGAAATGAGCTCCATGCCTGATGATGTCTTTGAGTCCCCCCCACTCTCTGCCAGCTACTTCCGAGGG ATCCCACACTCAGCCTCCCCTGTCTCCCCCGATGGGGTGCAAATCCCTCTGAAGGAGTATGGCCGAGCCCC AGTCCCCGGGCCCCGGCGCGGCAAGCGCATCGCCTCCAAGGTGAAGCACTTTGCCTTTGATCGGAAGAAGC GGCACTACGGCCTCGGCGTGGTGGGCAACTGGCTGAACCGCAGCTACCGCCGCAGCATCAGCAGCACTGTG CAGCGGCAGCTGGAGAGCTTCGACAGCCACCGGCCCTACTTCACCTACTGGCTGACCTTCGTCCATGTCAT CATCACGCTGCTGGTGATTTGCACGTATGGCATCGCACCCGTGGGCTTTGCCCAGCACGTCACCACCCAGC TGGTGCTGCGGAACAAAGGTGTGTACGAGAGCGTGAAGTACATCCAGCAGGAGAACTTCTGGGTTGGCCCC GCTCGATTGACCTGATCCACCTGGGGGCCAAGTTCTCACCCTGCATCCGGAAGGACGGGCAGATCGAGCA GCTGGTGCTGCGCGAGCGAGACCTGGAGCGGGACTCAGGCTGCTGTGTCCAGAATGACCACTCCGGATGCA TCCAGACCCAGCGGAAGGACTGCTCGGAGACTTTGGCCACTTTTGTCAAGTGGCAGGATGACACTGGGCCC CCCATGGACAAGTCTGATCTGGGCCAGAAGCGGACTTCGGGGGCTGTCTGCCACCAGGACCCCAGGACCTG CGAGGAGCCAGCCTCCAGCGGTGCCCACATCTGGCCCGATGACATCACTAAGTGGCCGATCTGCACAGAGC AGGCCAGGAGCAACCACACAGGCTTCCTGCACATGGACTGCGAGATCAAGGGCCGCCCCTGCTGCATCGGC ACCAAGGGCAGCTGTGAGATCACCACCCGGGAATACTGTGAGTTCATGCACGGCTATTTCCATGAGGAAGC AACACTCTGCTCCCAGGTGCACTGCTTGGACAAGGTGTGTGGGCTGCTGCCCTTCCTCAACCCTGAGGTCC CAGATCAGTTCTACAGGCTCTGGCTGTCTCTCTTCCTACATGCTGGGGTGGTGCACTGCCTCGTGTCTGTG GTCTTTCAAATGACCATCCTGAGGGACCTGGAGAAGCTGGCCGGCTGGCACCGTATCGCCATCATCTTCAT CCTCAGTGGCATCACAGGCAACCTCGCCAGTGCCATCTTTCTCCCATACCGGGCAGAGGTAGGCCCGGCCG GCTCACAGTTCGGCCTCCTCGCCTGCCTCTTCGTGGAGCTCTTCCAGAGCTGGCCGCTGCTGGAGAGGCCC TGGAAGGTCTTCCTCAACCTCTCGGCCATCGTGCTCTTCCTGTTCATCTGTGGCCTCCTGCCCTGGATCGA CAACATCGCCCACATCTTCGGCTTCCTCAGTGGCCTGCTGCTGGCCTTCGCCTTCCTGCCCTACATCACCT TCGGCACCAGCGACAAGTACCGCAAGCOGGCACTCATCCTGGTGTCACTGCTGGCCTTTGCCGGCCTCTTC GCCGCCCTCGTGCTGTGGCTGTACATCTACCCCATTAACTGGCCCTGGATCGAGCACCTCACCTGCTTCCC CTTCACCAGCCGCTTCTGCGAGAAGTATGAGCTGGACCAGGTGCTGCACTGACCGCTGGGCCACACGGCTG CCCCTCAGCCCTGCTGGAACAGGGTCTGCCTGCGAGGGCTGCCCTCTGCAGAGCGCTCTCTGTGTGCCAGA GAGCCAGAGACCCAAGACAGGGCCCGGGCTCTGGACCTGGGTGCCCCCCTGCCAGGCGAGGCTGACTCCGC GTGAGATAGATGGTTGGTTAAGGCGGGGTTTTTCCGGGCCGCGCCCCCCCCCTCTAAA NOV16i, 13381560 SNP for SEQ ID NO: 827 aa SNP: Ala to Val at position 719 CG52414-02 38 Protein Sequence MASADKNGGSVS SVSSSRLQSRKPPNLSITIPPPEETQAPGEQDSMPERKPAYLKSVSLQEPRSRWQE SSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSLHHCSMRYGRLKASCQRDLELPSQEAPS FQGTESPKPCKMPKIVDPLARGRAFRHPEEMDRPHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAH MSLQAAAALLKGRSVLDATGQRCRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLS ASYFRGIPHSASPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGNWLNRSYRR SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHSTTQLVLRNKGVYESVKYIQQE NFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQNDHSGCIQTQRKDCSETLATFVKW QDDTGPPMDKSDLGQRRTSGAVCHQDPRTCEEPASSGAHIWPDDITKWPICTEQARSNHTGFLHMCEIKG RPCCIGTKGSCEITTREYCEFMHGYFHEEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVV HCLVSVVFQMTILRDLEKLAGWBRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLEVELFQSW PLLERPWKVFLNLSAIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRALILVSLL AVAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH 276 WO 03/093432 PCT/US03/13690 A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 16B. Table 16B1. Comparison of the NOV16 protein sequences. NOV16a ----- MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPA NOV16b ----------------------------------------------------------- NOV16c TRSPTMASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPA NOV16d ----------------------------------------------------------- NOV16e ------ MASADKNGGSVSSVSSSRLQSRKPPNLSITIPPPEKETQAPGEQDSMLPERKNPA NOV16a YLKSVSLQEPRSRWQESSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSL NOV16b ---------------------------------------------------------- NOV16c YLKSVSLQEPRSRWQESSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSP NOV16d -----------------------------------------

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NOVI16e YLKSVSLQEPRSRWQESSEKRPGFRRQASLSQSIRKGAAQWFGVSGDWEGQRQQWQRRSL NOV16a HHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDR NOV16b ----------------------------------------------------------- NOV16c HHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDR NOV16d ----MRYGRLKASCQRDLELPSQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDR NOV16e HHCSMRYGRLKASCQRDLELPSQEAPSFQGTESPKPCKMPKIVDPLARGRAFRHPEEMDR NOV16a PHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR NOV16b ----------------------------------------------------- NOV16c PHALHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR NOV16d PHALHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR NOV16e PHAPHPPLTPGVLSLTSFTSVRSGYSHLPRRKRMSVAHMSLQAAAALLKGRSVLDATGQR NOV16a CRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA NOV16b ----------------------------------------------------------- NOV16c CRMVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA NOV16d CRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA NOV16e CRVVKRSFAFPSFLEEDVVDGADTFDSSFFSKEEMSSMPDDVFESPPLSASYFRGIPHSA NOV16a SPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGNWLNRSYRR NOV16b ----------------------------------------------------------- NOV16c SPVSPDGVQIPLKEYGRAPVPGPRRGERIASKVKHFAFDRKKRHYGLGVVGNWLNRSYRR NOV16d SPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGNWLNRSYRR NOV16e SPVSPDGVQIPLKEYGRAPVPGPRRGKRIASKVKHFAFDRKKRHYGLGVVGNWLNRSYRR NOV16a SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKG NOV16b ---------------------------------------------- TRSQHVTTQLVLRNKG NOV16c SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKG NOV16d SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKG NOV16e SISSTVQRQLESFDSHRPYFTYWLTFVHVIITLLVICTYGIAPVGFAQHVTTQLVLRNKG NOV16a VYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOV16b VYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOV16c VYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOV16d VYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOV16e VYESVKYIQQENFWVGPSSIDLIHLGAKFSPCIRKDGQIEQLVLRERDLERDSGCCVQND NOV16a HSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA NOV16b HSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA NOV16c HSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA 277 WO 03/093432 PCT/US03/13690 NOV16d HSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA NOV16e HSGCIQTQRKDCSETLATFVKWQDDTGPPMDKSDLGQKRTSGAVCHQDPRTCEEPASSGA NOV16a HIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH NOV16b HIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH NOV16c HIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH NOV16d HIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH NOV16e HIWPDDITKWPICTEQARSNHTGFLHMDCEIKGRPCCIGTKGSCEITTREYCEFMHGYFH NOV16a EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVVHCLVSVVFQMTILRDL NOV16b EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLEG------------------------ NOV16c EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVVHCLVSVVFQMTILRDL NOV16d EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVVHCLVSVVFQMTILRDL NOV16e EEATLCSQVHCLDKVCGLLPFLNPEVPDQFYRLWLSLFLHAGVVHCLVSVVFQMTILRDL NOV16a EKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLER NOV16b ------------------------------------------------------- NOV16c EKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLER NOV16d EKLAGWHRIAIIFILSGITGNLASTIFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLER NOV16e EKLAGWHRIAIIFILSGITGNLASAIFLPYRAEVGPAGSQFGLLACLFVELFQSWPLLER NOV16a PWKAFLNLSAIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL NOV16b --------- --------- ---------- ----------------- NOV16c PWKAFLNLSAIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL NOV16d PWKAFLNLSTIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL NOV16e PWKAFLNLSAIVLFLFICGLLPWIDNIAHIFGFLSGLLLAFAFLPYITFGTSDKYRKRAL NOV16a ILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH-- NOV16b ------------------------------------------------ NOV16c ILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLHLEG NOV16d ILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH-- NOV16e ILVSLLAFAGLFAALVLWLYIYPINWPWIEHLTCFPFTSRFCEKYELDQVLH-- NOVl6a (SEQ ID NO: 222) NOV16b (SEQ ID NO: 224) NOV16c (SEQ ID NO: 226) NOV16d (SEQ ID NO: 228) NOV16e (SEQ ID NO: 230) Further analysis of the NOV 16a protein yielded the following properties shown in Table 16C. Table 16C. Protein Sequence Properties NOV16a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 6; pos.chg 1; neg.chg 1 H-region: length 11; peak value 5.03 PSG score: 0.62 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -7.64 278 WO 03/093432 PCT/US03/13690 possible cleavage site: between 21 and 22 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 7 INTEGRAL Likelihood = -6.42 Transmembrane 381 - 397 INTEGRAL Likelihood = -4.25 Transmembrane 630 - 646 INTEGRAL Likelihood = -3.08 Transmembrane 666 - 682 INTEGRAL Likelihood = 0.37 Transmembrane 697 - 713 INTEGRAL Likelihood = -9.08 Transmembrane 720 - 736 INTEGRAL Likelihood = -4.83 Transmembrane 742 - 758 INTEGRAL Likelihood =-10.83 Transmembrane 775 - 791 PERIPHERAL Likelihood = 5.25 (at 600) ALOM score: -10.83 (number of TMSs: 7) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 388 Charge difference: 0.5 C( 1.5) - N( 1.0) C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide >>> membrane topology: type 3b MITDISC: discrimination of mitochondrial targeting seq R content: 2 Hyd Moment(75): 6.30 Hyd Moment(95): 5.24 G content: 2 D/E content: 2 S/T content: 10 Score: -3.23 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 32 SRKIPP NUCDISC: discrimination of nuclear localization signals pat4: PRRK (4) at 204 pat4: RRKR (5) at 205 pat4: RKKR (5) at 335 pat4: KKRH (3) at 336 pat7: PRRKRMS (5) at 204 pat7: PGPRRGK (3) at 316 pat7: PRRGKRI (5) at 318 bipartite: KRIASKVKHFAFDRKKR at 322 content of basic residues: 11.6% NLS Score: 2.37 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 279 WO 03/093432 PCT/US03/13690 Actinin-type actin-binding motif: type 1: none type 2: none NMYR: N-myristoylation pattern : none Prenylation motif: none minemYQRL: 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's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 70.6 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 55.6 %: endoplasmic reticulum 11.1 %: vacuolar 11.1 %: mitochondrial 11.1 %: vesicles of secretory system 11.1 %: Golgi >> prediction for CG52414-02 is end (k=9) A search of the NOV 16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16D. Table 16D. Geneseq Results for NOV16a NOV16a Identities/ Geneseq Protein/Organism/Length [Patent #, Residues/ Similarities for Expect Identifier Date] Match the Matched Value Residues Region AAB61148 Human NOV17 protein - Homo 120..827 705/708 (99%) 0.0 sapiens, 708 aa. [WO200075321-A2, 1..708 705/708 (99%) 14-DEC-2000] 280 WO 03/093432 PCT/US03/13690 AAB61147 Human NOV16 protein - Homo 120..604 484/485 (99%) 0.0 sapiens, 578 aa. [WO200075321-A2, 1..485 484/485 (99%) 14-DEC-2000] ABG64458 Human albumin fusion protein #1133 498..827 328/330 (99%) 0.0 - Homo sapiens, 349 aa. 20..349 330/330 (99%) [WO200177137-A1, 18-OCT-2001] 1 ...... AAE03323 Human gene 7 encoded secreted 498..827 328/330 (99%) 0.0 protein HCRNC80, SEQ ID NO:97 - 20..349 330/330 (99%) Homo sapiens, 349 aa. [WO200134800-A1, 17-MAY-2001] ABB90342 Human polypeptide SEQ ID NO 2718 505..827 322/323 (99%) 0.0 - Homo sapiens, 323 aa. 1..323 323/323 (99%) S[WO200190304-A2, 29-NOV-2001] ..... In a BLAST search of public sequence databases, the NOV 16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16E. 281 WO 03/093432 PCT/USO3/13690 Table 16E. Public BLASTP Results for NOV16a Protein NOV16a Identities/ Protein /OrganismLength Residues/ Similarities for Expect Accession Protein/Organism/Length Match the Matched Value Number Residues Portion Q8BJ70 Epidermal growth factor receptor- 1..827 759/830 (91%) 0.0 related protein homolog - Mus 1..827 790/830 (94%) musculus (Mouse), 827 aa. CAC22528 Sequence 33 from Patent 120..827 705/708 (99%) 0.0 WO0075321 - Homo sapiens 1..708 705/708 (99%) (Human), 708 aa. Q9H6E9 Hypothetical protein FLJ22341 - 209..827 619/619 (100%) 0.0 Homo sapiens (Human), 619 aa. 1..619 619/619 (100%) BAB84860 FLJ00080 protein - Homo sapiens 80..689 603/613 (98%) 0.0 (Human), 716 aa (fragment). 52..664 605/613 (98%) Q8K217 Similar to hypothetical protein 222..827 564/608 (92%) 0.0 FLJ22341 - Mus musculus 1..607 585/608 (95%) (Mouse), 607 aa (fragment). PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16F. Table 16F. Domain Analysis of NOV16a Identities/ Pfam Domain NOV16a Match Region Similarities Expect Value for the Matched Region Rhomboid 619..763 56/171 (33%) 7.9e-44 127/171 (74%) Example 17. The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A. Table 17A. NOV17 Sequence Analysis NOV17a, CG52643-02 SEQ ID NO: 239 15573 bp DNA Sequence IORF Start: ATG at 408 ORF Stop: TGA at 2934 GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATGCTGGCCTTTGGTTCAGAATGGCACAT CATTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCATAGGG ACATCATACAACAGTCGCCTTTATCTGAGGTTGTGCAAAGAGGGATGGAGGAGAAAACAATGGAGAAT CCCTGGCAGATTTCCCCAGGACGAGAGAAGGATATCCAATTGCTCATCAGGGAAGGTGCTAGGTCTCC 282 WO 03/093432 PCT/11S03/13690 CAGCCAGACGCCCTCAGAGGCCGGTGTCAIAGTCTCCCTCACCTCTGTGATGTGAAGTCAGCTCGTTCA TGACCTGGGCAGGCAGAGGGTCAGAGGGGCAGATGGAGCACTCCTGGCCTGATGAAGACTCATCAAAA TGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGG ATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAG CTTTGAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGT TCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGA4GACAGGGGAGCCCGAATGCCAGTGCCTGGAG GCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAACCACTGTAAGCT CCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAG GTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTG CAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCT GTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGA AGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTAC AACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGC CCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCC ATGGAGACCTGAGGCCACCAA&TCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAA GACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAA TTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGC CAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCAT GCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTC CAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAG GGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAA GACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTT CTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCA AACCCACGGAAAGATTTTCATGAGCTATGAAGAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAG CCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAG CAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGG CTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCC CGACCAAGTCTCCAGGTGATCACAGAAGCCAGC-ACCGGCCAGAGCCAGCACCTCATCCGCACACCCTT TGCAGGAGTGGATGATTTCTTCATTCCCCCAACA-AACCTCATCATCAACCACATCAGGTTTGGCTTCA TCTTCA-ACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATC GGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCAT CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTG TGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGT GCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTA TGACCTGCAATAXACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAAT ACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTG GGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAAT CATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCA ATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTG GGTGAGGTATOAAGGGCCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGC CTCAAGCAGGTACGCTGTACATTTTTACAGACAAAAGCAAAAACCTGTACTCGCTTTGTGGTTCAACA CTGGTCTCCTTGCAAGTTTCCTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGG AAGTATGATTTATGCCTTGAGCTACGATGAGAACATATGCTGCTGTGTAA.AGGGATCATTTCTGTGCC AAGCTGCACACCGAGTGACCTGGGGACATCATGGAACCAAGGGATCCTGCTCTCCAAGCAGACACCTC TGTCAGTTGCCTTCACATAGTCATTGTCCCTTACTGCCAGACCCAGCCAGACTTTGCCCTGACGGAGT GGCCCGGAAGCAGAGGCCGACCAGGAGCAGGGGCCTCCCTCCCGAACTGAAAGCCCATCCGTCCTCGC GTGGGACCGCATCTTCTCCCTCGCAGCTGCTTCTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTG AGGGAGAGCCAACAAGACTTACTGCATCTTGGGGGATGGGGAAATCACTCACTTTATTTTGGAAATTT TTGATTAAAAAAAAATTTTATAATCTCAAATGCTAGTAAGCAGAAAGATGCTCTCCGAGGTCCAA-CTA TATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGGTCACAACCCCACATCCCACAGCCAGAAAGAAC AATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGCCACCCTGCTTCTCCAAGAGCAGAC!CAGGCC ACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAAAAAACCAGAACAAGTTCTGTGTGCCTCC TTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTACCCCAGATTCAGGGCAGACTGGGCTT GCCTGGCAGTTGGTGGCCTCCAGGCTCAATGCAGAAACCCCAAGGACACGAGTGGGGCCAGGTG AGTTCCTGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACCTGTGGCCCATCCACTCCTCTCT GGTACCCACCCCATCAGCACTGCAGAGAGAACACATTTCGGCGAGGGTTTTCTTACCCA.CATTC CCCAATCAATACACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCTGGCACTACTGCATTCTCC TTATGTGTCTCAGGCTGTGGTGACTCTCACATGCATCGAAGAAGTACACCCACATAGCCCTCTGG 283 WO 03/093432 PCT/US03/13690 AGACCGCCTAGATCAGAGACTCAGCAA CAGGCTCGCCTTCCCTCTCCCACATATGAGTGGAACTT ACATGTGTCCTOGTTTGATGATCATTTTGCAAGCCACACGGGTTGGGAGAGGTGGTCTCACCACAGA CGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCATTAAGGAATG AACTCTTTCAAGGAGAGGAAACCCTAGACTCTGTGTCACTCTCACACACACAGCTCCTTTCACTCCT GCCTGACTGCCAAGCCACCTGCATCCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATGTCTCAC GCAACTTGGTCCACCAAACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTCTGTT TTTTATTTTAAAAGATATGCTATGTAGATATAAGTTRAGGAAGCTCACCTCAAAAGCCTAGAATGCAG TTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGA TATGTTATGTTTACTCCCAATCTCCCATTTTTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTT TGGAAAAATTTCCATTGTATCAGCCCCTGACAGAAAAGGATCTCTGAGCCTAAAGGAGGAAAAGTCC CACCAACTACCAGACCAGAACACGAGCCCCTCTGGGCAGCAGGATTCCTAAGTCAAAGACCAGTTTGA CCCAAACTGGCCTTTTAAAATAATCAGGAGTGACAGAGTCAACTTCTGCAGCACCTGCTTCTCCCCCA CTGTCCCTTCCATCTTGGAATGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTT CCTGGAGACGGCAGGCTTAGGTCTCACTGACAGCATGCCAGACACALACTGAATCGAAGCAGGCCTGAA GCCTAGGTCAGGGTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAATGCCT TTTGGCAGGAAAACCAATAGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAGAAGGAGGAAGAGGA GGAAGGCCAGACTGGCCTGCCCTTTCTCCCATACTTCACCCCAGCAGAGGTTCATGGGACACAGTTGG AAGCCACTGGGAGGAAATGCCTCACTACAGGGGGGCCTCCTGTAGCAAGCCCAGCCGGTAATCCTCC TAATGAACCCACAAGGTCAATTCACAACTGATATCTTAGCTATTAALAGAAGTACTGACTTTACCAAAA GAATCATCAAGAAAGC-TATTTATATAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTTACAA OV17a, CG52643-02 SEQ ID NO: 240 842 aa MW at 93094.8kD Protein Sequence * KPGGFWLHLTLLGAS LPAALG WMVDPGTSRGPDVGVGESQAEEPRS FEVTRREGLS SHNELLASCGKK FFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHICKLHRAACLLGKRITVIHSKDCFLK GDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVL KKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAV KGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVP PVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDT GAYTCIAIKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHL KPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLP AKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRPGF IFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQANAHTHLGGYFFIQCRQDSPASAAROLLVDSVTDS VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLEVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQ YNTYAA.LHTEPDLLFLELSTGKVGMLK<NLKEPRAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLI NGRQNTLRCEVSGIKGGTTVVWVGEV NOV1 7b,259341359 ISEQ ID NO: 241 J2538 bp DNA Sequence OR tr:at 1 I0RF Stop: end of sequence TC TGAACAGGGG T 2CGCTTAACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTOCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCAkCGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT 284 WO 03/093432 PCT/US03/13690 CATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAA ACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGG CACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGC AACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAG CACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCT CTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCA CAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCA CACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTT GGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAA GACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACT TCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACA GACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCAT AGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGA CCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGC AATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGG GAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCC ACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTC CTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGT GTGGGTGGGTGAGGTACTCGAG bKIV17b, 259341359 IS1BQIDNO: 242 .846 aa MW'at 93579.4d) Protein Sequence LEMKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCG KKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLRAACLLGKRITVIHSKDCF LKGDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQH VLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTC AVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVN VPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYE DTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQR HLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDP LPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRF GFIFNKSDPAVHKVDLETMMPLKTIGLHHKGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLEVDSVT DSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTES NQYNIYAALHTEPDLLLELSTGKVGMLKLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLF LINGRQNTLRCEVSGIKGGTTVVWVGEVLE NOV17c, 268824728 SEQ IDNO:243 2511 bp DNA Sequence lORF Start: at 1 ORF Stop: end of sequence CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTGCACCATTGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT CATTGAAGACTCAGCTAGAAAGACCCGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACG 285 WO 03/093432 PCT/US03/13690 GTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTC ATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGC AGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACA TCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAG TCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGAT CACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCT TCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCT GCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTG CGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCC CCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGAT GTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTG GCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGG GCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTG CACATGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAA GGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGT TTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTG CGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTACTCGAG NOV170, 268824728 SEQ IlDNO:2 44 837aa MWP at 92565.3kl) Protein Sequence LEMKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCG KKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCF LKGDTCTIAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQH VLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTC AVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTVLQVN VPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYE DTGAYTCIAKNEVGVDEDISSLFIEDSARKTRLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIF MSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDK SHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDP AVHKVDLETMMPLKTIGLHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGD VTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAAL HMEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTL RCEVSGIKGGTTVVWVGEVLE NOV17d, 268825987 ISEQ lDlNO:245 2439bp DNA Sequence ORF Start: at 1 JORF Stop: end of sequence CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCTGGG AAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCT ACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGC AGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGG CAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACT TACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTC CGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGAC CACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCA TCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGAT GATTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCA CGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGA GCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGA ATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAA TGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAA ATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCA AACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTAT CATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGA GCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTC AATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCA 286 WO 03/093432 PCT/US03/13690 AGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCAC ATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACA GAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCAT TCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAG TCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTG CCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGC CTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAA CAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTG CACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCAT CTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACA TGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAG CCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGG ACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGT GTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTACTCGAG NOV17d, 268825987 SEQ ID NO: 246 813 aa MW at 89900.2kD Protein Sequence KKFCSRGSRCVLSRKTGEPECLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQEGDS RQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTL REFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGED DSLYITKTTIMGNYTCASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPR ITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLA NILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPREKNATQPCQWVSAV NVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVIT EASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCV PQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWL KVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLD KE PPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVLE NVl7e, 268825997 JSEQ ID NO: 247 2472 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence CTCGAGTGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGA GCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCG GGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAG TGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCA CTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTT TCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAG ACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGT GGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGC ATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTT GACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCT CAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCT GCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTG GACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCA CATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGA ATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTA AGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAAC TCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATG AAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTC TTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGG AAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGA GGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAAT GCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCC AGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACC CTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTG cACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCG CACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGT 287 WO 03/093432 PCT/US03/13690 TTGGCTTCATCTTCAACAAGTCTGATCCTACAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTC AAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTA CTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCA CAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTC ATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCA GACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAA GCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACG GGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTAC CCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGT TCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTG GTGTGGGTGGGTGAGGTACTCGAG NOV17e, 268825997 SEQ ID NO: 248 824 aa MW at 91376.7kD Protein Sequence LEWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPECQ CLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQ TRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLRF DDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPIIWKRNGLTLNFL DLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASL RCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSL FIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKN ATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSDQVWVLSWGDV HKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPTVHKVDLETMMPL KTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRF IVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELST GKVGMLINLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTV VWVGEVLE NOV17f, 275698334 SEQ ID NO:2 2538 bp DNA Sequence JORF Start: at 1 ORF Stop: end of sequence CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTOCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT CATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAA ACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGG CACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGC AACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAG CACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCT CTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCA CAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCA CACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTT GGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAA 288 WO 03/093432 PCT/US03/13690 GACCATCGGCCTGCACCACCATGGCTGCGTOCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACT TCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACA GACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCAT AGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGA CCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGC AATCAATACAACATCTACGCGGCTCTGCACATGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGG GAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCC ACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTC CTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGT GTGGGTGGGTGAGGTACTCGAG NOVI7f, 275698334 SE DNO6:250 846aa MW at 93609.5kD Protein Sequence LEMKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCG KKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCF LKGDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQH VLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTC AVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVN VPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYE DTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQR HLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDP LPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRF GFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVT DSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTES NQYNIYAALHMEPDLLFLELSTGKVGMLK1LKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLF LINGRQNTLRCEVSGIKGGTTVVWVGEVLE NOV17g, CG52643-04 SEQ ID NO: 251 2538 bp DNA Sequence ORF Start: ATG at 7 JORF Stop: end of sequence CTCGAGATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCT GGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGC CCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGG AAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTG CCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACT GTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTC CTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGAC CCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGG AA.TCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCAT GTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGA CGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCA GCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGC GCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGA CTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACA TGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAAT GTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAG ATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTC AGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAA GACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTT CATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAA ACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGG CACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCT.GTCCTCAAAGAGAAAAAAATGC AACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAG CACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCT CTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCA CAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCA CACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTT GGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAA GACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACT 289 WO 03/093432 PCT/t1S03/13690 TCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACA GACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCAT AGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACGTGCGGGGCGAGATCCAGA CCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAGC AATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGG GAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCC ACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTC CTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAGGGGGGGACCACAGTGGT *GTGGGTGGGTGAGGTA NOVI 7g, CG52643-04 _ISEQ ID NO: 252 ,842aa IMW at 93094.8kD Protein Sequence MKPGGFWL HLTLLGASLPALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSNELLASCGK. FCRSCLRTEEQLARSVVGSGFEHKHACLKIVHKCL GDCMGALNLAQRQLEDS PSKLVSFDDDNHSSSELAQHVL KKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQQLSPEDRVSVTTGLSVTCAV HGDLRPPIIWRGTNLLDNFEDLIKVTHGYCAGELQHLVV PVIRVYPESQAQEPGVAASLRCHEGIPMPRITWLNGVDVSTQMSKQLSLINGSELHISSVYEDT GAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGI IVIHPVDCEIQRHL KPEIMYECQENTPQVANRNYYAPLRLVIAKLSGDL AI(LSYDKSHDQVWVLSWGDVKSRPSLQVITEASTGQSQHLIRTPFAGDDFFIPPTNLI INHIRFGF IFKDAHVLTMLTGHHCPAMHHGYFQRDPSAQLDVD VLGPNGDVTGTPHTSPDGRFIVSAADSPWLHVQEITVRGEIQTLDLQINSGISDAQRSFTESNQ YNIYAALHTEPDLLFLELSTGKVGMLLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLI NGRQNTLRCEVSGIKGGTTVVWVGEV INOV17h,301380586 fSEQIDNO:253 2548bp DNA Sequence ORF Start: at 2 ORF Stop: end ofsqec CACCGGATCCACCATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGG CTGCGCTGGGATGGATGG7ACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCA GAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTC CTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAGACAGGGAGCCCGAAT GCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAA AACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAGAGGATCACCGTCATCCGCAGGA CTGTTTCCTCAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGATGTCCTTCTGGCAC TCCAGACCCGTCTcCAGCCACTCOAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTC CTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGC TCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCC GATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTT CAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCT GACCTGCGCCGTCCATGGAGACCTGAGCCACCAATCATCTGGAGCGCACGGCTCACCCTGAACT TCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACC ATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCA GGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCA GCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAACGGCGTGGATGTC TCAA CTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCG GTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAGATATCTCCT CGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGA.GGCCTCAGC GTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGAT CCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAATCTGTCCTCAGAGA AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCC CAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCADTAGGTGT GGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGG ACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTC ATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACACCTCATATCAACCACAT CAGGTTTGGCTTCATCTTCACAAGTCTGATCCTGCAGTCCACAGGTGGACCTGGAACAATGATGC CCCTCAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCTGCACACACCCACCTGGGC GGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAG 290 WO 03/093432 PCT/US03/13690 TGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGC GCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAG ATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCAC TGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGT CCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGG GGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTC ACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCA CAGTGGTGTGGGTGGGTGAGGTAGAATTCGGC NO 71 7h, 3013 805 86 S1BQDNO:2541 849aa AfWat93774.5ldD Protein Sequence TGSTMKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLAS CGKKFCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKD CFLKGDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELA QHVLKKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVL TCAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQ VNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVR YEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEI QRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGV DPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHI RFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMARTHLGGYFFIQCRQDSPASAARQLLVDS VTDSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFT ESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARES LFLINGRQNTLRCEVSGIKGGTTVVWVGEVEFG NOV17i, 289087852 SEQ ID NO: 255 1842 bp DNA Sequence JORF Start: at1 ORF Stop: end of sequence CTCGAGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAA GCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCC TGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAG CTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGC ACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTT GGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGC GAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGT GGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCC TGTGGCGAGAGGAAGATGCATCCACGTGGCCGGTTTCTTGTGTGTTCAATGCTGCGTGTGACCCTGCC CAGGGGCCGACTGCTTGGAGGGCATGCCCATTCCATTTGCTCCTCCCAGGCCTCAGCGTGGGAAACAT GTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACC TCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACC CAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACT GAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGC CGGCTAAGCTGTCCTATGGCAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAG TCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACC CTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCT TCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACC ATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTT CATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACT CTGTGCTTGGCCCCAATGGCGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTC AGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCT GTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATC AATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAG GTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAG AATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCA TCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGG CTCGAG Sequnce~614aa MW at67956.6kD OV17i, 289087852 SEQ ID NO: 256 1a . 291 WO 03/093432 PCT/US03/13690 LEGLSTVLTCAVHGDEPPITWKRNGL'LNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQ LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGS ELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEDASTWPVSCVFNAACDPA QGPTAWRACPFHLLLPGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNAT QPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYGKSHDQVWVLSWGDVHK SRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKT IGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIV SAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELSTGK VGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVW LE NOV17j, 289081920 SEQ ID NO: 257 1713 bp DNA Sequence ORF Start: at I ORF Stop: end of sequence CTCGAGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAA GCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCC TGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAG CTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGC ACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTT GGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGC GAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGT GGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCGCCTCAGCGTGG GAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATCCAG AGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAAAAAA TGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCAGC CAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGAC CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGT GCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCC GCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCAACAAACCTCATTCAACCACATCAGG TTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCT CAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCT ACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTC ACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTT CATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCC AGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAA AGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCAC GGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTA CCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTG TTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGT GGTGTGGCTCGAG NOV17j, 289081920 SEQ ID NO: 2581571 aa MW at 63363.4kD Protein Sequence LEGLSTVLTCAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQ LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGS ELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTRLSVGNMFYVFSDDGIIVIHPVDCEIQ RHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVD PLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIR FGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSV TDSVLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTE SNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESL FLINGRQNTLRCEVSGIKGGTTVVWLE NOV17k, 289098038 ISEQ ID NO: 259 1740 bp DNA Sequence ORF Start: at 1 ORF Stop: end of sequence CTCGAGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAA GCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCC TGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAG CTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGC 292 WO 03/093432 PCT/US03/13690 ACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTT GGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAACAGCTCTCCCTTTTAGCCAATGGGAGC GAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGT GGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCC TGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTC ATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGA AGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCC GGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAG AAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCA AGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCA GCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCA ACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAA GGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGG CCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCT GCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCAC CCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGC AGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGAC TTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCC GGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCG CAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTAC CTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGT GTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGCTCGAG NOV17k, 289098038 S260 1580 aa W at 64389.6kD Protein Sequence _SQI O M LEGLSTVLTCAVHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCEASGHEQ LFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGS ELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIV IHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQ KVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPP TNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASA ARQLLVDSVTDSVLOPNGDVTGTPHTSPDGRFIVSAAADSPWLKVQEITVRGEIQTLYDLQINSGISD LAFQRSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQY LLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWLE NOVI~ 71 10018 SQI O:21158bp DNA Sequence ORF Start: at 13 JORF Stop: end of sequence GCCAGGTGATGATATCTCAGATTCGCCTTCACCGGATCCTGGATGGACCCAGGAACCAGCAGAGGCCC GGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGC TTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTG CTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGT GTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAA AGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTAC GCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAG ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCA ATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTA CTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCG CGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCA CAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATC TGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGA TTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACG AGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGC CAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAAT CACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATG GGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAAT GAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAA CATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCA TCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGC 293 WO 03/093432 PCT/US03/13690 TATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAA TGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAG CCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACAT GACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGA AGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTC CCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTC CACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCC CCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCT CTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACA GGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCA CGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCT CAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACG GAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCC ACCCGCAGGGCCAGCTCAGCCCCGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGAC AGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGT GAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTAGAATTCGGC NOVI 71, 311060818 SEQ ID NO: 262 832 aa MWat 92208.6kD Protein Sequence YLRFAFTGS 6 6TSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRK TGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLK NVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCS PGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPIIWKRN GLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQE PGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGV DEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEI CPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDRSHDQVW SWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVD LETMMPLKTIGLHHHGCVPQAMATHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPH TSPDGRFIVSAAADSPWLKVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDL LFLELSTGKVGMLKNLKEPPAGPAQPRGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSG IKGGTTVVWVGEVEFG NOVI7m, 311885703 SEQ ID NO: 263 2479 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence CACCGGATCCTGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAG AGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCC TGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATG CCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAA ACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGAC TGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACT CCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCC TGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCT CAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCCG ATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTC AGCTCAGCCTCGCCCCCGAGGACAGGGCCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCTG ACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTOGAAGCGCAACGGGCTCACCCTGAACTT CCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACCA TCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAG GTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAG CCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTCT CAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCGG TATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCTC GCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGCG TGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGATC CAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTOTCCTCAAAGAGAAAA AAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCC AGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTG 294 WO 03/093432 PCT/US03/13690 GACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGA CGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCA TCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCAACAAACCTCATCATCAACCACATC AGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCC CCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCG GCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGT GTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCG CTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGA TCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACT GAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTC CACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGOGGGG GTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCA CTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCAC AGTGGTGTGGGTGGGTGAGGTAGAATTCGGC NOV17m, 311885703 SEQ ID NO: 264 826 aa MW at 91412.7kD Protein Sequence TGSWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPEC CLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIESKDCFLKGDTCTMAGYARLKNVLLAL QTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLR FDDYNSDSSLTLREFYMAFQVVQLSLAPEDRASVTTVTVGLSTVLTCAVHGDLRPPIIWKRNGLTLNF LDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAAS LRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISS LFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREK NATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGD VHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRPGFIFNKSDPAVHKVDLETMMP LKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGR FIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELS TGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTT VVWVGEVEFG NOV17n, CG52643-01 SEQ ID NO: 265 1689 bp DNA Sequence IORF Start: ATG at 199 ORF Stop: TGA at 1147 TAGAATTCAGCGGCCGCTTAATTCTAGAACGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCC TGGGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCC GGCTACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGA CAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAG ATGGCAATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAA GACTTACTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGAC CCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTG TGACCACAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCA ATCATCTGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGA GGATGATTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCG GCCACGAGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCA GAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCC CAGAATCACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAG CCAATGGGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCC AAAAATGAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCT TGCAAACATCCTGTGGCGAGAGGAAGGTACCAAGCTTCATTGTTTTGCGTCATGCCTGTGATCACGTG TGTTTGGTTCTATGATGGGCCGTCTTTCCATGATCTGCCACCAGCTTTCCCACACAAAGCAGCCCTAT GGGAGCAGGAAGTCAATGTCAAATTCAAGTGGCATATGCATTGAATCAAATTTAAAATGTACTCCTGT CTTTAATGAGAAATTTTTAAATGCAAAGCTTTCATTAAAAGTGGCTTGTAACCTCTGCTGAAGCAGAA CAGTTGGTAAGGGTTCCTGGTCAGATCTGGGCCTTAAACTTTTTTCCAGTAGCTGACTGGTGTTGGGT TTAGTGTTTTGCCTATCTTGTGTGGTTTTAAAAAGACAAAACAAGTTGTAGATCTCTACTAGATAGTC ACTGTACCTTAAATATGCTTTGATTGAGGAAAACCCGAGGAAAAAGCTGCCATGATTTCTGCCAATGT ATATTTTTAAATGTATAGATGTTTAGAAACATATTTATCAAGCAAATCTTTAGTAAGTTGAGCCATAT GAAGTTGCCATTTTTGTGCATCAAAGTGGTCTAAGATTGACAATTTCATATGGCTGA 295 WO 03/093432 PCT/US03/13690 NOV17n, CG52643-01 SEQ ID NO: 266 316 aa MW at 35059.2kD Protein Sequence MAGYARLKNVLLAQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDL DEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLR PPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRV YPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTC IARNEVGVDEDISSLFIEDSARKTLANILWREEGTKLHCFASCL NOV17o, CG52643-03 SEQ ID NO: 267 914 bp DNA Sequence ORF Start: at 12 ORF Stop end of sequence TGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGAGGAGTCACAGGCA GAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTC CTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAAT GCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAA AACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCGCCGTCATCCACAGCAAGGA CTGTTTCCTCAAAGGTGACACGTGCACCATGGGCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCAC TCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTC CTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGC TCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCC GATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTT CAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCC GACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACT TCCTGGACTTGGAAGACATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGG GGGACCACAGTGGTGTGGGTGGGTGAGGTA 2 61 6O: 268 301a, R NOV17o, CG52643-03 ISEQ ID NO: 26830aa, MW at 33218.2kD Protein Sequence______ WMDPGTSRGPDVGVEESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPECQCL EACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRIAVIHSKDCFLKGDTCTMGGYARLKNVLLALQTR LQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDEDLLGCSPGDLLRFDD YSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVPTCAVHGDLRPPIIWKRNGLTLNFLDL EDINGRQNTLRCEVSGIKGGTTVVWVGEV NOV17p, CG52643-05 SEQ ID NO: 269 12548 bp DNA Sequence ORF Start: ATG at 14 ORF Stop: end of sequence CACCGGATCCACCATGAAACCAGGAGGCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGG CTGCGCTGGGATGGATGGACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCA GAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTC CTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAAT GCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAA AACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAAAGAGGATCACCGTCATCCACAGCAAGGA CTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTACGCCCGCTTGAAGAATGTCCTTCTGGCAC TCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAGACAAGACCCTGCCTCCCAGAAGCGCCTC CTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAATGGCCACCTCAGCAGCTCCGAACTGGC TCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTGGTTGCTCACCAGGTGACCTCCTCC GATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTTCTACATGGCCTTCCAAGTGGTT CAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACCGTGGGGCTGAGCACAGTGCT GACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCAACGGGCTCACCCTGAACT TCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACATCACCAAGGTGACCACC ATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAGACCCACGTCCTGCA GGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTGGAGTGGCAGCCA GCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAATCACTTGGCTGAAAAACGGCGTGGATGTC TCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGCAGTGTTCG GTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATATCTCCT CGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCTCAGC GTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAGAT CCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAA AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCC 296 WO 03/093432 PCT/US03/13690 CAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGT GGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGG ACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTC ATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCAACAAACCTCATCATCAACCACAT CAGGTTTGGCTTCATCTTCAACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGC CCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGC GGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAG TGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGC GCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAG ATCCAGACCCTGTATGACCTGCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCAC TGAAAGCAATCAATACAACATCTACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGT CCACGGGGAAGGTGGGCATGCTGAAGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGG GGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTC ACTGTTCCTCATCAATGGGAGACAAAACACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCA CAGTGGTGTGGGTGGGTGAGGTA NOV17p, CG52643-05 SEQ ID NO: 270 842 aa MW at 93094.8kD Protein Sequence MKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKK FCSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLK GDTCTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVL KKQDLDEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAV HGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGREQLFQTHVLQVMVP PVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDT GAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHL KPTEKIFMSYEEICPQREKATPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLP AlLSYDKSHDQVWVLSWGDVHKSRPSLQVITASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGF IFNKSDPAVHKVDLETMMPLKTIGLHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQ YNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLI NGRQNTLRCEVSGIKGGTTVVWVGEV NOV17q, CG52643-06 SEQ ID NO: 271 2460 bp DNA Sequence ORF Start: at 1 OIFStop: end of sequence TGGATGGACCCAGGAACCAGCAGAGGCCC GGATGTGGGTOTGGGGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGAAGTCACAAGAAGAGAAGGGC TTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCCGGTGCGTG CTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGTGCCTGT GTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTGGGAA AGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCTAC GCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAG ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCA ATGGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTA CTTGGTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCG CGAGTTCTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCA CAGTGACCGTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATC TGGAAGCGCAACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGA TTCCCTGTACATCACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACG AGCAGCTGTTCCAGACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGC CAGGCACAGGAGCCTGGAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAAT CACTTGGCTGAAAAACGGCGTGGATGTCTCAACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATG GGAGCGAACTCCACATCAGCAGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAAT GAAGTGGGTGTGGATGAAGATATCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAA CATCCTGTGGCGAGAGGAAGGCCTCAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCA TCGTCATCCATCCTGTGGACTGTGAGATCCAGAGGCACCTCAAACCCACGGAAAAGATTTTCATGAGC TATGAAGAAATCTGTCCTCAAAGAGAAAAAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAA TGTCCGGAACCGGTACATCTATGTGGCCCAGCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAG CCCAGAAAGTCCTACAGTCCATAGGTGTGGACCCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACAT 297 WO 03/093432 PCT/t1S03/13690 GACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGCACAAGTCCCGACCAAGTCTCCAGGTGATCA CAGA AGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCACACCCTTTGCAGGAGTGGATGATTTCTTCATTC CCCCAACAAACCTCATCATCAACCACATCAGGTTTGGCTTCATCTTCACAGTCTGATCCTGCAGTC CACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCATCGGCCTGCACCACCATGGCTGCGTGCC CCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCATCCAGTGCCGACAGGACAGCCCCGCCT CTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTGCTTGGCCCCAATGGTGATGTAACA GGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTGCAGCTGACAGCCCCTGGCTGCA CGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCTGCAAATAACTCGGGCATCT CAGACTTGGCCTTCCAGCGCTCCTTCACTGAAAGCAATCAA.TACAACATCTACGCGGCTCTGCACACG GAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGAGCTTAGGAGCC ACCCGCAGGGCCAGCTCAGCCCCGGGGGGGTACCCACAGAATCATGAGGGACAGTGGGCTGTTTGGAC AGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCTGGGAGACAAACACGCTGCGGTGT GAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTA ~NOV17q, CG52643-06 SEQ ID NO: 272 .820 aa MW at 90832.lkD 1 Protein Sequence WMPTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSRGSRCVLSRKTGEPECQCL EARSVVGDRYNCLRALGRIVHKCLGTTAYRKVLLT LQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELQHVL~KKQDLDEDLLGCSPGDLLRFDD YNSDSSLTLREFYMAFQWVQLSLAPEDRVSVTTVTVGLSTVLTCAHGDLRPPI IWKRNGLTLNFLDL EDINDFGEDDSLYITKVTTHMGNYTCHASGHEQLFQTHQVPPVIRVYPESQAQEPGVAASLRC HAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHIS SVRYEDTGAYTCIAKNEVGVDEDISSLFI EDSARKTLANILWREEGLSVGNMFYVFSDDGI IVIHPVDCEIQRI{LKPTEKIFMSYEEICPQREKNAT QPQVANRRIVQASVVDQQKLSGDLALYKHQWLWDH SRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLI INHIRFGFIFNKSDPAVHKVDJETMMPLKT IGLHHmGCVPQAAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPGDVGTPH~TSPDGRFIV SAAJADSPWLHVQITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELSTGK VGMLKNLKEPPAGPAQPRGGTHRIMRDSGLFGQYLLTPRESLFLINGRQTLRCEVSGIKGGTVV VGEV N OVl7r, 13382322S fo SEQ N:273 5573_l SP: 1 G/A CG52643-02 ORF Start: ATG at IORIF Stop: TGA at 2934 DASequence 1408 GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATGCTGGCCTTTGGTTCAGAATGGCACATCA TTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCATAGGGACAT CATACAACAGTCGCCTTTATCTGAGGTTGTGCAAAGAGGGATGGAGGAGACATGGAGAATCCCTGG CAATCCAGCAAAGAACATGCCTAGAGTCAGCCCGCG CGCCCTCAGAGGCCGGTGTCA1AGTCTCCCTCACCTCTGTGATTGAGTCAGCTCGTTCATGACCTGGGC AGCGGGCGGGCGTGGATCGCTAGAATACAAGALCGA GCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGGATGGACCCAGGAAC CAGCAGAGGCCCGGATGTGGGTGTGGAGGAGTCACAGGCAGAGGAGCCCAGAGCTTTGAGTCACAAGA AGAGAAGGGCTTTCCAGCCACACGAGCTGCTGGCCTCCTGCGGGAGAGTTCTGCAGCCGAGGGAGCC GGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTG GGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCT ACCCCT-.GAGCTCGCCCAGCCTTCGCCCAGAGGCGA ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAAT GGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAGAAGCAGGACCTGGATGAAGACTTACTTG GTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTT CTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACC GTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCATCATCTGGAAGCGCA ACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACAT CACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCC-A TGCTTCCGGCCACGAGCAGCTGTTCCAG ACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTG GATGACACTAAGCTCGGGATCCTCCGACCTGTAAAG CGTGGATGTCTCAACTCAGATGTCCAACAGCTCTCCCTTTTAGCCATGGGAGCGACTCCACATCAGC AGGTGTTAGCCGGCTCCTCATCAAAGATGTTGTAGT TCCTGTTCTGAATACAAAACCTCACTCGGCAAGAGC 298 WO 03/093432 PCT/11S03/13690 CAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAG ATCGGCCTAACAGAAGTTCAGGTTAGATTTCCAGGA AAAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCATGTCCGGACCGGTACATCTATGTGGCCCA GCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAGCCCAGAAGTCCTACAGTCCATAGGTGTGGAC CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAGTGTGGGTCCTGAGCTGGGGGGACGTGC ACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCAC ACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCACAAA(CCcATCATCAACCACATCAGGTTTGGC TTACTACATTACTCGCAAGGGACGAAATAGCCCAAC TCGGCCTGCACCACCATGGCTGCGTGCCCCGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCAT CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTG CTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTG CAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCT GCATACCGCTTAATGCTCAGGTCTATAACACAAACT TACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAGGTGGGCATGCTGA AGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGATCATGAGGGACAG TGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTACTGTTCCTCATCATGGGAGACAAC ACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTATGAGGG CCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGT ACATTTTTACAGACAAAAGCAAACCTGTACTCGCTTTGTGGTTCAACACTGGTCTCCTTGCAAGTTTC CTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGGAAGTATGATTTATGCCTTGAGC TACGATGAGAACATATGCTGCTGTGTAAAGGGATCATTTCTGTGCCAGCTGCACACCGAGTGACCTGGG GACATCATGGAACCAAGGGATCCTGCTCTCCAAGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTG TCCCTTACTGCCAGACCCAGCCAGACTTTGCCCTGACGGAGTGGCCCGGAGCAGAGGCCGACCAGGAGC AGGGGCCTCCCTCCCGAACTGAAAGCCCATCCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGC TTCTTGCTTTTCTTTCCATTTGACTTGCTGTAGCCTGAGGGAGAGCCAAGACTTACTGCATCTTGG GGGATGGGG-AATCACTCACTTTATTTTGATTTTTGATTAAATTTTATATCTCAATGCT AGTAAGCAGAAAGATGCTCTCCGAGGTCCACTATATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGG TCACAACCCCACATCCCACAGCCAGAGAALCATGTCTCTGAGATACTGGCCCTGTCGACTATTGC CACCCTGCTTCTCCAAGAGCAGACCAGGCCACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAA ?AAAACCAGAACAAGTTCTGTGTGCCTCCTTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTA CCCCAGATTCAkGGGCAGACTGGGCTTGCCTGGCAGGTATGGGTGGCCTCCAGGCTCATGCAGACCC CAAGGACACGAGTGGGGCCAGGTGAGTTCCTGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACC TGTGGCCCATCCACTCCTCTCTGGTACCCCATCCCCGCATCAGCACTGCAGAGAGAACACATTTCGGCGA GGGTTTTCTTACCCACATTCCCCAATCAATACACACACACTGCAGACCCAGAACAGAGGCCACAGGCT GGCACTACTGCATTCTCCTTATGTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAGGTACAAC CCACATAGCCCTCTGGAGACCGCCTAGATCAGAGACTC'AGC~AAACAGGC!TCGCCTTCCCTCTCCCACA TATGAGTGGAACTTACATGTGTCCTGGTTTG.kATGATCATTTTGCAGCCACACGGGTTGGGAGAGGTGG TCTCACCACAGACGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCA TTAAGGAATGAACTCTTTCAAGGAGAGGOACCCTAGACTCTGTGTCACTCTCAACACACACGCTCCTT TCACTCCTGCCTGACTGCCAAGCCACCTGCATCCCCCGCCCCAGATCTCATGAGATCATCACTTGTATG TCTCACGCAACTTGGTCCACCAAACGCCTGTCCCCTGTACTCCTAGGGGTGCGCCTAGACAGGTACGTC TGTTTTTTATTTTAAAGATATGCTATGTAGATATAGTTGAGGAGCTCACCTCAAGCCTAGAATGC AGTTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGA FAGTTTTCCCACCCTTTCACA-ATTCACTCTACTTTT GAAAATTTCCATTGTATCAGCCCCTGACAGAGGATCTCTGAGCCTAAGAGGAAAGTCCCACC iaCTACCAGACCAGAACACGAGCCCCTCTGGGCAGCAGGATTCCTGTCGACAGTTTGACCCA CTQGCCTTTTAAATAATCAGGAGTGACAGAGTCACTTCTGCAGCACCTGCTTCTCCCCCACTGTCCCT TCCATCTTGGAATGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACG GCAGGCTTAGGTCTCACTGACAGCATGCCAGACACACTGATCOAAGCAGGCCTGAGCCTAGGTCAGG GTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTATGCCTTTTGGCAGGAAC FC5T-AGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAG-GGAGGAAGAGGAGGAAGGCCAGACTGGCI CTGCCCTTTCTCCCATACTTCACCCCAGCAGAGGTTCATGGGACACGTTGGAAGCCACTGGGAGGA. GCCCAAGGGCCTTGAGCAGCGATCCTAGACAAGTA TTAACGTTTACATAGATCGCTACAAGACTAG AACATATTACCCCGCATTAAAATATTAA NOV17r, 13382322 SNP for SEQ ID NO: :842 aa SN:Gly to Glu at position 37 CG52643-02 ~ 274 SP Protein Sequence I 299 WO 03/093432 PCT/t1S03/13690 MKGFLLLGSPAGMPTRPVVESAERFVRELSNLACKF SRSCLRTEEQLARSVVGDRYNCLRALGIVHKCLGT TMAGYARLIVLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDAGNGHLS SSELAQHVLKKQDLaD EDLLGCSPGDLLRFDDYNSDSSLTLREFYAFQQLSLAPEDRVSVTVGLSTVLTCAVHGDLRPPI IWRGTNLLDNFEDLIKTIMGYCAGELQHLVVPIVPS AQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLAGSELHI SSVRYEDTGAYTCIAKNEVG VDDSLIDAKLNLRELVNFVFDGIIPDEQHKTKFSEI PQREKNATQPCQWVSAVRRYIYVAQPALSRVLVVDIQAQKVLQS IGVDPLPAKLSYDKSHDQVWVLS WGVKRSQIESGSHITFGDFFPTLIHRGINSPVKDEM PLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDS PASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRF IVSAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYYAHTPDLLLELSTGK VGMLKTLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLLINGRQNTLRCEVSGIKGGTVWG EV NOV17s, 13382324 SNP for SEQ ID NO: 275 15573 bp SNP: 880 G/A CG52643-02 lORE Start: ATG at lORF Stop: end of sequence DNA Sequence 1408 GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATOCTGCCTTTGGTTCAGAATGGCACATCA TTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCATAGGGACAT CATACAACAGTCGCCTTTATCTGAGGTTGTGCGAGGGATGGAGGAGACATGGAGATCCCTGG CAGATTTCCCCAGGACGAGAGAAGGATATCCATTGCTCATCAGGGAGGTGCTAGGTCTCCCAGCCAGA IGCCCTCAGAGGCCGGTGTCAAGTCTCCCTCACCTCTGTGATGTGAAGTCAGCTCGTTCATGACCTGGGC AGGCAGAGGGTCAGAGGGGCAGATGGAGCACTCCTGGCCTGATGGACTCATCATGACCAGGAG GCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGGATGGACCCAGGAA-C CAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCAGAGCTTTGAAGTCACAGA AGAGAAGGGCTTTCCAGCCACACGAGCTGCTGGCCTCCTGCGGGAAGAGTTCTGCAGCCGAGGGAGCC GGTGCGTGCTCAGCAGGAAGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTG GGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAGGTGACACGTGCACCATGGCCGGCT ACGCCCGCTTGAAGATGTCCTTCTGGCACTCCAGACCCATCTGCAGCCACTCCAGAGGAGACAGCAG ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAAT GGCCTACGTCACGCCGAGGCGAAGAGCTGBTAGCTCT GTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACACAGTGACAGCTCCCTGACCCTCCGCGAGTT CTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACC GTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACATCATCTGGAAGCGCA ACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCATGACTTTGGAGAGGATGATTCCCTGTACAT CACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAG ACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTG GAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGATCACTTGGCTGAAACGG CGTGGATGTCTCAACTCAGATGTCCAACAGCTCTCCCTTTTAGCCAATGGGAGCGACTCCACATCAGC AGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAATGAGTGGGTGTGGATGAAGATA TCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAACCCTTGCAACATCCTGTGGCGAGAGGAAGGCCT CAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAG ATCCAGAGGCACCTCAACCCACGGAAGATTTTCATGAGCTATAATCTGTCCTCAGAGA AAATGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCATGTCCGGACCGGTACATCTATGTGGCCCA GCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAGTCCTACAGTCCATAGGTGTGGAC CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAGTGTGGGTCCTGAGCTGGGGGGACGTGC ACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCC ACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCACAAACCTCATCATCACCACATCAGGTTTGGC TTCATCTTCACAAGTCTGATCCTGCAGTCCACAGGTGGACCTGGACATGATGCCCCTCAAGACCA TCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACCACCCACCTGGGCGGCTACTTCTTCAT CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTG CTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTG CAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCT GCAATAACTCGGCATCTCAGACTTGGCCTTCCAGCGCTCCTTCACTGAGCATCAATACACATC TACGCGGCTCTGCACACGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGA AGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGATCATGAGGGACAG TGGGCTGTTTGGACAGTACCTCCTCACACCAGCCCGAGAGTCACTGTTCCTCATCATGGGAGACAACI 300 WO 03/093432 PCT/US03/13690 ACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTATGAAGGG CCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGT ACATTTTTACAGACAAAAGCAAAAACCTGT ACTCGCTTTGTGGTTCAACACTGGTCTCCTTGCAAGTTTCCTAGTATAAGGTATGCGCTGCTACCAAGAT TGGGGTTTTTTCGTTAGGAAGTATGATTTATGCCTTGAGCTACGATGAGAACATATGCTGCTGTGTAAAG GGATCATTTCTGTGCCAAGCTGCACACCGAGTGACCTGGGGACATCATGGAACCAAGGGATCCTGCTCTC CAAGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTGTCCCTTACTGCCAGACCCAGCCAGACTTTG CCCTGACGGAGTGGCCCGGAAGCAGAGGCCGACCAGGAGCAGGGGCCTCCCTCCCGAACTGAAAGCCCAT CCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGCTTCTTGCTTTTCTTTCCATTTGACTTGCTG TAAGCCTGAGGGAGAGCCAACAAGACTTACTGCATCTTGGGGGATGGGGAAATCACTCACTTTATTTTGG AAATTTTTGATTAAAAAAAAATTTTATAATCTCAAATGCTAGTAAGCAGAAAGATGCTCTCCGAGGTCCA ACTATATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGGTCACAACCCCACATCCCACAGCCAGAAAGA ACAATGGTCATCTGAGAATACTGGCCCTGTCGACTATTGCCACCCTGCTTCTCCAAGAGCAGACCAGGCC ACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAAAAAACCAGAACAAGTTCTGTGTGCCTCCTT TCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTACCCCAGATTCAGGGCAGACTGGGCTTGCCT GGCAAGGTATGGGTGGCCTCCAGGCTCAATGCAGAAACCCCAAGGACACGAGTGGGGCCAGGTGAGTTCC TGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACCTGTGGCCCATCCACTCCTCTCTGGTACCCC ATCCCCGCATCAGCACTGCAGAGAGAACACATTTCGGCGAGGGTTTTCTTACCCACATTCCCCAATCAAT ACACACACACTGCAGAACCCAGAACAGAAGGCCACAGGCTGGCACTACTGCATTCTCCTTATGTGTCTCA GGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAACCCACATAGCCCTCTGGAGACCGCCTAGATC AGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACATATGAGTGGAACTTACATGTGTCCTGGTTT GAATGATCATTTTGCAAGCCACACGGGTTGGGAGAGGTGGTCTCACCACAGACGTCTTTGCTAATTTGGC CACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCATTAAGGAATGAACTCTTTCAAGGAGAGGAA ACCCTAGACTCTGTGTCACTCTCAACACACACAGCTCCTTTCACTCCTGCCTGACTGCCAAGCCACCTGC ATCCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATGTCTCACGCAACTTGGTCCACCAAACGCCTG TCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTCTGTTTTTTATTTTAAAAGATATGCTATGTA GATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGCAGTTTCACAGTAGCTGGGATGCATGGATGA CCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGATATGTTATGTTTACTCCCAATCTCCCATTT TTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTTTGGAAAAATTTCCATTGTATCAGCCCCTGACA GAAAAAGGATCTCTGAGCCTAAAGGAGGAAAAGTCCCACCAACTACCAGACCAGAACACGAGCCCCTCTG GGCAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAACTGGCCTTTTAAAATAATCAGGAGTGACAG AGTCAACTTCTOCAGCACCTGCTTCTCCCCCACTGTCCCTTCCATCTTGGAATGTGTCTAAAAAAGCATA GCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACGGCAGGCTTAGGTCTCACTGACAGCATGCCA GACACAACTGAATCGAAGCAGGCCTGAAGCCTAGGTCAGGGTTTCAGGAGTCCAGCCCCAGGAGGCAAAG TCACCAATGCAGGGAGGTAAATGCCTTTTGGCAGGAAAACCAATAGAGTTGGTTGGGTGGGGAGTCAGGG GTGGGAGGAGAAGGAGGAAGAGGAGGAAGGCCAGACTGGCCTGCCCTTTCTCCCATACTTCACCCCAGCA GAGGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAATGCCTCACTACAGGGGGGCCTCCTGTAGCA AGCCCAGCCGGTAATCCTCCTAATGAACCCACAAGGTCAATTCACAACTGATATCTTAGCTATTAAAGAA GTACTGACTTTACCAAAAGAATCATCAAGAAAGCTATTTATATAAACCCCCTCAGTCATTTTGAAATAAA ATTAATTTTACAA NOV17s, 13382324 SNP for SEQ ID NO: 842 aa SNP: Arg to His at position CG52643-02 276 158 Protein Sequence MKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFC SRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDTC TMAGYARLKNVLLALQTHLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQIVLKKQDLD EDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPPI IWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPESQ AQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVG VDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEIC PQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSEDQVWVLS WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNRSDPAVHKVDLETMM PLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRF IVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLELSTGK VGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVG EV NOV17t, 13381678 SNP for SEQ ID NO 277 5573 bp SNP: 2677 C/T 301 WO 03/093432 PCTUSO3I1369O 1CG52643-02 ORE Start: ATG at JORF Stop: end of sequence ~DNA-Sequence 14.08 GGAGAGGGCTGCATTGCTGTTGCTCACTGACCTTCTTTTATGCTGGCCTTTGGTTCAGAATGGCACATCAi TTCCTCGTTTTTGGCCCTCCAGCTGAACACCTGTTCTCTGTGGCACTGACTCCTCTTTCCNLAGGGACAT CATACAACAGTCGCCTTTATCTGAGGTTGTGCAAAGAGGGATGGAGGAGAAAACAATGGAGAATCCCTGG CAGATTTCCCCAGGACGAGAGAAGGATATCCAALTTGCTCATCAGGGAAGGTGCTAGGTCTCCCAGCCAGA CGCCCTCAGAGGCCGGTGTCAAGTCTCCCTCACCTCTGTGATGTGAAGTCAGCTCGTTCATGACCTGGGC AGGCAGAGGGTCAGAGGGGCAGATGGAGCACTCCTGGCCTGATGAAGACTCATCAAATGAA.ACCAGGAG GCTTTTGGCTGCATCTCACACTGCTCGGAGCCTCCCTGCCGGCTGCGCTGGGATGGATGG ACCCAGGAACCAGCAGAGGCCCGGATGTGGGTGTGGGGGAGTCACAGGCAGAGGAGCCCAGAAGCTTTGA AGTCACAAGA AGAGAAGGGCTTTCCAGCCACAACGAGCTGCTGGCCTCCTGCGGGAAGAAGTTCTGCAGCCGAGGGAGCC GGTGCGTGCTCAGCAGGAALGACAGGGGAGCCCGAATGCCAGTGCCTGGAGGCATGCAGGCCCAGCTACGT GCCTGTGTGCGGCTCTGATGGGAGGTTTTATGAAAACCACTGTAAGCTCCACCGTGCTGCTTGCCTCCTG GGAAAGAGGATCACCGTCATCCACAGCAAGGACTGTTTCCTCAAAGGTGACACGTGCACCATGGCCGGCT ACGCCCGCTTGAAGAATGTCCTTCTGGCACTCCAGACCCGTCTGCAGCCACTCCAAGAAGGAGACAGCAG ACAAGACCCTGCCTCCCAGAAGCGCCTCCTGGTGGAATCTCTGTTCAGGGACTTAGATGCAGATGGCAAT GGCCACCTCAGCAGCTCCGAACTGGCTCAGCATGTGCTGAAGAAGCAGGACCTGGATGAAGACTTACTTG GTTGCTCACCAGGTGACCTCCTCCGATTTGACGATTACAACAGTGACAGCTCCCTGACCCTCCGCGAGTT CTACATGGCCTTCCAAGTGGTTCAGCTCAGCCTCGCCCCCGAGGACAGGGTCAGTGTGACCACAGTGACC GTGGGGCTGAGCACAGTGCTGACCTGCGCCGTCCATGGAGACCTGAGGCCACCAATCATCTGGAAGCGCA ACGGGCTCACCCTGAACTTCCTGGACTTGGAAGACATCAATGACTTTGGAGAGGATGATTCCCTGTACAT. CACCAAGGTGACCACCATCCACATGGGCAATTACACCTGCCATGCTTCCGGCCACGAGCAGCTGTTCCAG ACCCACGTCCTGCAGGTGAATGTGCCGCCAGTCATCCGTGTCTATCCAGAGAGCCAGGCACAGGAGCCTG GAGTGGCAGCCAGCCTAAGATGCCATGCTGAGGGCATTCCCATGCCCAGAA-TCACTTGGCTGAAAAACGG CGTGGATGTCTCALACTCAGATGTCCAAACAGCTCTCCCTTTTAGCCAATGGGAGCGAACTCCACATCAGC AGTGTTCGGTATGAAGACACAGGGGCATACACCTGCATTGCCAAAAATGAAGTGGGTGTGGATGAAGATA TCTCCTCGCTCTTCATTGAAGACTCAGCTAGAAAGACCCTTGCAAACATCCTGTGGCGAGAGGAAGGCCT CAGCGTGGGAAACATGTTCTATGTCTTCTCCGACGACGGTATCATCGTCATCCATCCTGTGGACTGTGAG ATCCAGAGGCACCTCAACCCACGGA4AAGATTTTCATGAGCTATGAAGAAATCTGTCCTCAAAGAGAAA AAAA.TGCAACCCAGCCCTGCCAGTGGGTATCTGCAGTCAATGTCCGGAACCGGTACATCTATGTGGCCCA GCCAGCACTGAGCAGAGTCCTTGTGGTCGACATCCAAGCCCAGAAAGTCCTACAGTCCATAGGTGTGGAC CCTCTGCCGGCTAAGCTGTCCTATGACAAGTCACATGACCAAGTGTGGGTCCTGAGCTGGGGGGACGTGC ACAAGTCCCGACCAAGTCTCCAGGTGATCACAGAAGCCAGCACCGGCCAGAGCCAGCACCTCATCCGCAC ACCCTTTGCAGGAGTGGATGATTTCTTCATTCCCCCACAACCTCATCATCAACCACATCAGGTTTGGC TTCATCTTCACAAGTCTGATCCTGCAGTCCACAAGGTGGACCTGGAAACAATGATGCCCCTCAAGACCA TCGGCCTGCACCACCATGGCTGCGTGCCCCAGGCCATGGCACACACCCACCTGGGCGGCTACTTCTTCAT CCAGTGCCGACAGGACAGCCCCGCCTCTGCTGCCCGACAGCTGCTCGTTGACAGTGTCACAGACTCTGTG CTTGGCCCCAATGGTGATGTAACAGGCACCCCACACACATCCCCCGACGGGCGCTTCATAGTCAGTGCTG CAGCTGACAGCCCCTGGCTGCACGTGCAGGAGATCACAGTGCGGGGCGAGATCCAGACCCTGTATGACCT GCAAATAAACTCGGGCATCTCAGACTTGGCCTTCCGCGCTCCTTCACTGAAAGCAATCAATACAACATC TACGCGGCTCTGCACATGGAGCCGGACCTGCTGTTCCTGGAGCTGTCCACGGGGAAGGTGGGCATGCTGA AGAACTTAAAGGAGCCACCCGCAGGGCCAGCTCAGCCCTGGGGGGGTACCCACAGAATCATGAGGGACAG TGGOCTGTTTGGACAGTACCTCCTCACACCAGCCCGAAGTCACTGTTCCTCATCAATGGAGACAAAAC ACGCTGCGGTGTGAGGTGTCAGGTATAAAGGGGGGGACCACAGTGGTGTGGGTGGGTGAGGTATGAAGGG CCCAGAGCAGAGCCCTGGGCCAAGGAACACCCCCTAGTCCTGACACTGCAGCCTCAAGCAGGTACGCTGT ACATTTTTACAGACAAAAGCAAAAACCTGTACTCGCTTTGTGGTTCAACACTGGTCTCCTTGCAAGTTTC CTAGTATAAGGTATGCGCTGCTACCAAGATTGGGGTTTTTTCGTTAGGAAGTATGATTTATGCCTTGAGC TACGATGAGAACATATGCTGCTGTGTAAAGGGATCATTTCTGTGCCAAGCTGCACACCGAGTGACCTGGG GACATCATGGZAACCAAGGGATCCTGCTCTCCAAGCAGACACCTCTGTCAGTTGCCTTCACATAGTCATTG TCCCTTACTGCCAGACCCAGCCAGACTTTGCCCTGACGGAGTGGCCCGGAAGCAGAGGCCGACCAGGAGC AGGGGCCTCCCTCCCGAACTGAAAGCCCATCCGTCCTCGCGTGGGACCGCATCTTCTCCCTCGCAGCTGC TTCTTGCTTTTCTTTCCATTTGACTTGCTGTAAGCCTGAGGGAGAGCCAACAAGACTTACTGCATCTTGG GGGATGGGGAAATCACTCACTTTATTTTGGAAATTTTTGATTAAAAAAAAATTTTATAATCTCAAATGCT AGTAAGCAGAAAGATGCTCTCCGAGGTCCAACTATATCCTTCCCTGCCTTAGGCCGAGTCTCGGGGGTGGI CACCCTGCTTCTCCAAGAGCAGACCAGGCCACCTCATCCGTAAGGACTCGGTTCTGTGTTGGGACCCCAA AAAACCAGAACAAGTTCTGTGTGCCTCCTTTCAGCACAGAAGGGAGACATCTCATTAGTCAGGTCTGGTA 302 WO 03/093432 PCT/US03/13690 CCCCAGATTCAGGGCAGACTGGGCTTGCCTGGCAAGGTATGGGTGGCCTCCAGGCTCAATGCAGAAACCC CAAGGACACGAGTGGGGCCAGGTGAGTTCCTGAAGCTATACCTTTTCAAAACAGATTTTGTTTTCCTACC TGTGGCCCATCCACTCCTCTCTGGTACCCCATCCCCGCATCAGCACTGCAGAGAGAACACATTTCGGCGA GGGTTTTCTTACCCACATTCCCCAATCAATACACACACACTGCAGAACCCAGAACAGAAGGCCAAGGCT GGCACTACTGCATTCTCCTTATGTGTCTCAGGCTGTGGTGACTCTCACATGGGCATCGAAGAAGTACAAC CCACATAGCCCTCTGGAGACCGCCTAGATCAGAGACTCAGCAAAAACAGGCTCGCCTTCCCTCTCCCACA TATGAGTGGAACTTACATGTGTCCTGGTTTGAATGATCATTTTGCAAGCCACACGGGTTGGGAGAGGTGG TCTCACCACAGACGTCTTTGCTAATTTGGCCACCTTCACCTACTGACATGACCAGGATTTTCCTTTGCCA TTAAGGAATGAACTCTTTCAAGGAGAGGAAACCCTAGACTCTGTGTCACTCTCAACACACACAGCTCCTT TCACTCCTGCCTGACTGCCAAGCCACCTGCATCCCCCGCCCCAGATCTCATGAGATCAATCACTTGTATG TCTCACGCAACTTGGTCCACCAAACGCCTGTCCCCTGTAACTCCTAGGGGTGCGCCTAGACAGGTACGTC TGTTTTTTATTTTAAAAGATATGCTATGTAGATATAAGTTGAGGAAGCTCACCTCAAAAGCCTAGAATGC AGTTTCACAGTAGCTGGGATGCATGGATGACCCATCTCACCCCTTTTTTTTTCCTGCCTCAATATCTTGA TATGTTATGTTTACTCCCAATCTCCCATTTTTACCACTAAAATTCTCCAACTTTCATAAACTTTTTTTTG GAAAAATTTCCATTGTATCAGCCCCTGACAGAAAAAGGATCTCTGAGCCTAAAGGAGGAAAAGTCCCACC AACTACCAGACCAGAACACGAGCCCCTCTGGGCAGCAGGATTCCTAAGTCAAAGACCAGTTTGACCCAAA CTGGCCTTTTAAAATAATCAGGAGTGACAGAGTCAACTTCTGCAGCACCTGCTTCTCCCCCACTGTCCCT TCCATCTTGGAATGTGTCTAAAAAAGCATAGCTGCCCTTTGCTGTCCTCAGAGTGCATTTCCTGGAGACG GCAGGCTTAGGTCTCACTGACAGCATGCCAGACACAACTGAATCGAAGCAGGCCTGAAGCCTAGGTCAGG GTTTCAGGAGTCCAGCCCCAGGAGGCAAAGTCACCAATGCAGGGAGGTAAATGCCTTTTGGCAGGAAAAC CAATAGAGTTGGTTGGGTGGGGAGTCAGGGGTGGGAGGAGAAGGAGGAAGAGGAGGAAGGCCAGACTGGC CTGCCCTTTCTCCCATACTTCACCCCAGCAGAGGTTCATGGGACACAGTTGGAAAGCCACTGGGAGGAAA TGCCTCACTACAGGGGGGCCTCCTGTAGCAAGCCCAGCCGGTAATCCTCCTAATGAACCCACAAGGTCAA TTCACAACTGATATCTTAGCTATTAAAGAAGTACTGACTTTACCAAAAGAATCATCAAGAAAGCTATTTA TATAAACCCCCTCAGTCATTTTGAAATAAAATTAATTTTACAA NOV17t, 13381678 SNP for SEQ ID NO: 842 aa SNP: Thr to Met at position CG52643-02 278 757 Protein Sequence MKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKF CSRGSRCVLSRKTGEPECQCLEACRPSYVPVCGSDGRFYENHCKLHRAACLLGKRITVIHSKDCFLKGDT CTMAGYARLKNVLLALQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDL DEDLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCAVHGDLRPP IIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIRVYPES QAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEV GVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEI CPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSDQVVL SWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRPGFIFNKSDPAVHKVDLETM MPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGR FIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHMEPDLLFLELSTG KVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWV GEV A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 17B. Table 17B. Comparison of the NOV17 protein sequences. NOV17a ----------------------------------------------------------- NOV17b ---------------------------------------------------------- NOV17c ---------------------------------------------------------- NOV17d LEMKPGGFWLHLTLLGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSH NOV17e ----------------------------------------------------------- NOV17f ----------------------------------------------------------- NOV17g ----------------------------------------------------------- NOV17h ----------------------------------------------------------- 303 WO 03/093432 PCT/11S03/13690 N OV 17i - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 17j - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 17k - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 171 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17m - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV17n ------ - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17o -- - - - -- - - - - - - - - - - - - - - - - - - - - - - - NOV 17p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV 17q - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV 17a - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV 17b - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV 17c - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV17d NELLASCGKKFCSRGSRCVLSRKTGEPECLGKRITVIHSKDCFLKGDTCTMAGYARLKNV NOV 17e - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 17 f - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17g - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17h - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17i - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17j - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV 17k - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 171 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV17m - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV17n - - - - - - - - - - - - - - -7 - - - - - - - - - - - - - - N O V 17o - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17q -- - - - - - - - - - - - - - - - - - - - - - - - - - -- - N O V 17a - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 17lb -- - - - - - - - - - - - - - - - -- - - - - - - - - - - - N OV 17c - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV17d LLAIQTRLQPLQEGDSRQDPASQKRLLVESLFRDLDADGNGHLSSSELAQHVLKKQDLDE NOV 17e - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 1 7 -- - - - - - - - - - - - - - -- - - - - - - - - - - - - - N O V 17g - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 17h - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17i - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 17j - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV 17k - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NO V 171 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV 17m - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N OV 17n - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17o - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17p - - - - - - - - - - - - - - - - - - - - - - - - - - - - - N O V 17q - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV17a---------------------------------------------------- MKPGGFWLHLTL NOV17b------------------------------------------------- LEMKPGGFWLHLTL NOV17c------------------------------------------------- LEMKPGGFWLHLTL NOV17 d DLLGCSPGDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVTVGLSTVLTCA NOV17e - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NOV17f------------------------------------------------- LEMKPGGFWLHLTL NOV17g--------------------------------------------------- MKPGGFWLHLTL NOV17h----------------------------------------------- TGSTMKPGGFWLHLTL NOV17i----------------------------------------------------- LEGLSTVLTCA NOV17j----------------------------------------------------- LEGLSTVLTCA NOV17k----------------------------------------------------- LEGLSTVLTCA 304 WO 03/093432 PCT/US03/13690 NOV171 ---------------------------------------------- NOV17m ----------------------------------------------- NOV17n ---------------------------------------------- NOV17o -------------------------------------------- NOV17p -------------------------------------------------- MKPGGFWLHLTL NOV17q --------------------------------------- -- ----- NOV17a LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17b LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17c LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17d VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOV17e --------- LEWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17f LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17g LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17h LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17i VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOV17j VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOV17k VHGDLRPPIIWKRNGLTLNFLDLEDINDFGEDDSLYITKVTTIHMGNYTCHASGHEQLFQ NOV171 -YLRFAFTGSWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17m -------TGSWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17n ----------------------------------------------------------- NOV17o ----------WMDPGTSRGPDVGVEESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17p LGASLPAALGWMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17q ----------WMDPGTSRGPDVGVGESQAEEPRSFEVTRREGLSSHNELLASCGKKFCSR NOV17a ----------GSRCVLSRKTGEP -------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17b ----------GSRCVLSRKTGEP --------ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17c ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17d THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOV17e ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17f ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17g ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17h ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17i THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOV17j THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOV17k THVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSL NOV171 ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17m ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17n -------------------------------------------------------- NOV17o ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17p ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17q ----------GSRCVLSRKTGEP-------- ECQCLEACRPSYVPVCGSDGRFYENHCKL NOV17a HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17b HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17c HRAACLLGKRITVIHSKDCFLKGDTCTIAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17d LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREE---- NOV17e HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17f HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17g HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ ---- EGDSRQ NOV17h HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ--- EGDSRQ NOV17i LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEDASTW NOV17j LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTR------------ NOV17k LANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREE---- NOV171 HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17m HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17n ---------------------------MAGYARLKNVLLALQTRLQPLQ----EGDSRQ 305 WO 03/093432 PCT/US03/13690 NOV17o HRAACLLGKRIAVIHSKDCFLKGDTCTMGGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17p HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17q HRAACLLGKRITVIHSKDCFLKGDTCTMAGYARLKNVLLALQTRLQPLQ----EGDSRQ NOV17a ----------DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17b ----------DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17c ----------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17d ----------------------------- GLSVGNMFYVFSDDGIIVIHPVDCEIQRHLK NOV17e ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17f ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17g ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17h ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17i PVSCVFNAACDPAQGPTAWRACPFHLLLPGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLK NOV17j ----------------------------- LSVGNMFYVFSDDGIIVIHPVDCEIQRHLK NOV17k -----------------------------GLSVGNMFYVFSDDGIIVIHPVDCEIQRHLK NOV171 ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17m ----------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17n ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17o ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17p ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17q ---------- DPASQK---R---------- LLVESLFRDLDAD--GNGHLSSSELAQHVL NOV17a KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17b KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17c KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17d PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQS NOV17e KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17f KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17g KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17h KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17i PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQS NOV17j PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQS NOV17k PTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQS NOV171 KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17m KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRASVTTVT NOV17n KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17o KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17p KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17q KKQDLDEDLLGCSP---GDLLRFDDYNSDSSLTLREFYMAFQVVQLSLAPEDRVSVTTVT NOV17a VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17b VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17c VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17d IGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF NOV17e VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17f VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17g VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17h VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17i IGVDPLPAKLSYGKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF NOV17j IGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF NOV17k IGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFF NOV171 VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGED---------------- NOV17m VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17n VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17o VGLSTVPTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINGR------------------- NOV17p VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT NOV17q VGLSTVLTCAVHGDLRPPIIWKRNGLTLN-FLDLEDINDFGEDDSLYITKVTTIHMGNYT 306 WO 03/093432 PCT/US03/13690 NOV17a CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17b CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17c CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17d IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF NOV17e CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17f CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17g CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17h CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17i IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF NOV17j IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF NOV17k IPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFF NOV171 ----------------------------------------------------------- NOV17m CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17n CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17o ----------------------------------------------------------- NOV17p CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17q CHASGHEQLFQTHVLQVNVPPVIRVYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVD NOV17a VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN NOV17b VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN NOV17c VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTRLS NOV17d IQCRQDSPASAARQLLVDSVTDSVLG--------------------------------- NOV17e VSTQMSKQLSLLANGSE------------------------------------------ NOV17f VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN NOV17g VSTQMSKQLSLLANGSE------------------------------------------ NOV17h VSTQMSKQLSLLANGSE------------------------------------------ NOV17i IQCRQDSPASAARQLLVDSVTDSVLG--------------------------------- NOV17j IQCRQDSPASAARQLLVDSVTDSVLG--------------------------------- NOV17k IQCRQDSPASAARQLLVDSVTDSVLG--------------------------------- NOV171 ----------------------------------------------------------- NOV17m VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN NOV17n VSTQMSKQLSLLANGSE ------------------------------------------ NOV17o ----------------------------------------------------------- NOV17p VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN NOV17q VSTQMSKQLSLLANGSELHISSVRYEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLAN NOV17a ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP NOV17b ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP NOV17c VGNMFYVFS--------- DDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP NOV17d ----------------------------------------------------------- NOV17e ----------------------------------------------------------- NOV17f ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP NOV17g ----------------------------------------------------------- NOV17h ----------------------------------------------------------- NOV17i ----------------------------------------------------------- NOV17j ---------------------------------------------------------- NOV17k ----------------------------------------------------------- NOV171 ----------------------------------------------------------- NOV17m ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP NOV17n ----------------------------------------------------------- NOV17o ----------------------------------------------------------- NOV17p ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP NOV17q ILWREEGLSVGNMFYVFSDDGIIVIHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQP NOV17a CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS NOV17b CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS 307 WO 03/093432 PCT/US03/13690 NOV17c CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS NOV17d ----------------------------------------------- NOV17e ----------------------------------------------- NOV17f CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS NOV17g ------------------------------------------------- NOV17h ------------------------------------------------ NOV17i ---------------------------------------------- NOV17j ------------------------------------------------- NOV17k ------------------------------------------------- NOV171 ------------------------------------------------ NOV17m CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS NOV17n ----------------------------------------------------------- NOV17o ----------------------------------------------- NOV17p CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS NOV17q CQWVSAVNVRNRYIYVAQPALSRVLVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLS NOV17a WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA NOV17b WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA NOV17c WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA NOVI7d --------------------------------------------------------- NOV17e --------------------------------------------------------- NOV17f WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA NOV17g --------------------------------------------- NOV17h -------------------------------------------- NOV17i --------------------------------------------- NOV17j ------------------------------------------- NOV17k -------------------------------------------- NOV171 -------------------------------------------- NOV17m WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA NOV17n ------------------------------------- --- NOV17o ------------------------------------- NOV17p WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA NOV17q WGDVHKSRPSLQVITEASTGQSQHLIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPA NOV17a VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS NOV17b VHIVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS NOV17c VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS NOV17d --------------------------------------------------------- NOV17e ------------------------------------------------- NOV17f VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS NOV17g -------------------------------------------- NOV17h --------------------------------------------- NOV17i --------------------------------------------- NOV17j --------------------------------------------- NOV17k ------------------------------------------------- NOV171 ----------------------------------------------------- NOV17m VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS NOV17n ------------------------------------------------------ NOV17o --------------------------------------------------------- NOV17p VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS NOV17q VHKVDLETMMPLKTIGLHHHGCVPQAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDS NOV17a VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17b VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17c VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17d --- PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17e ------------------------------------------------------- 308 WO 03/093432 PCT/US03/13690 NOV17f VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17g ------------------------------------------------------- NOV17h --------------------------------------------------------- NOV17i ---PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17j ---PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17k ---PNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV171 ----------------------------------------------------------- NOV17m VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17n ----------------------------------------------------------- NOV17o ----------------------------------------------------------- NOV17p VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17q VLGPNGDVTGTPHTSPDGRFIVSAAADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQ NOV17a RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17b RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17c RSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17d RSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17e ----------------------------------------------------LHISSVRY NOV17f RSFTESNQYNIYAALHMEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17g ----------------------------------------------------LHISSVRY NOV17h ----------------------------------------------------LHISSVRY NOV17i RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17j RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17k RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV171 ----------------------------------------------------------- NOV17m RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17n ----------------------------------------------------LHISSVRY NOV17o ----------------------------------------------------------- NOV17p RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGL NOV17q RSFTESNQYNIYAALHTEPDLLFLELSTGKVGMLKNLKEPPAGPAQPRGGTHRIMRDSGL NOV17a FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV----------------- NOV17b FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVLE-------------- NOV17c FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVLE--------------- NOV17d FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVLE--------------- NOV17e EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVI NOV17f FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVLE--------------- NOV17g EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVI NOV17h EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIVI NOV17i FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWLE------------------- NOV17j FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWLE------------------- NOV17k FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWLE------------------- NOV171 -------------------DSLYITKVTTIHMGNYTCHASGHEQLFQTHVLQVNVPPVIR NOV17m FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEVEFG-------------- NOV17n EDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGTKLHCFASCL------- NOV17o ------------------- QNTLRCEVSGIKGGTTVVWVGEV----------------- NOV17p FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV----------------- NOV17q FGQYLLTPARESLFLINGRQNTLRCEVSGIKGGTTVVWVGEV----------------- NOV17a ----------------------------------------------------------- NOV17b ----------------------------------------------------------- NOV17c ----------------------------------------------------------- NOV17d ------------------------------------------------ ----- NOV17e HPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVL NOV17f ---------------------------------------------------------- NOV17g HPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVL NOV17h HPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRVL 309 WO 03/093432 PCT/US03/13690 NOV17i -------------------------------------------------------- NOV17j ------------------------------------------------------- NOV17k ------------------------------------------------------ NOV171 VYPESQAQEPGVAASLRCHAEGIPMPRITWLKNGVDVSTQMSKQLSLLANGSELHISSVR NOV17m ---------------------------------------------------------- NOV17n -------------------------------------------------------- NOV17o ---------------------------------------------------------- NOV17p ----------------------------------------------------------- NOV17q ----------------------------------------------------------- NOV17a ---------------------------------------------------------- NOV17b ----------------------------------------------------------- NOV17c ----------------------------------------------------------- NOV17d ---------------------------------------------------------- NOV17e VVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHL NOV17f ----------------------------------------------------------- NOV17g VVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHL NOV17h VVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQHL NOV17i ----------------------------------------------------------- NOV17j ---------------------------------------------------------- NOV17k ---------------------------------------------------------- NOV171 YEDTGAYTCIAKNEVGVDEDISSLFIEDSARKTLANILWREEGLSVGNMFYVFSDDGIIV NOV17m ------------------------------------------------------- NOV17n ------------------------------------------------------ NOV17o ------------------------------------------------------ NOV17p ----------------------------------------------------- NOV17q ------------------------------------------------------ NOV17a ---------------------------------------------------- NOV17b ----------------------------------------------------- NOV17c ------------------------------------------------------- NOV17d ------------------------------------------------- NOV17e IRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPTVHKVDLETMMPLKTIGLHHHGCVPQ NOV17f ------------------------------------------------------ NOV17g IRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQ NOV17h IRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVPQ NOV17i ----------------------------------------------------------- NOV17j --------------------------------------------------------- NOV17k ------------------------------------------------------- NOV171 IHPVDCEIQRHLKPTEKIFMSYEEICPQREKNATQPCQWVSAVNVRNRYIYVAQPALSRV NOV17m ------------------------------------------------ NOV17n ------------------------------------------------- NOV17o ------------------------------------------------ NOV17p ------------------------------------------------- NOV17q ------------------------------------------------- NOV17a ----------------------------------------------- NOV17b ------------------------------------------------- NOV17c ------------------------------------------- -- NOV17d ------------------------------------------------ NOV17e AMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAA NOV17f ------------------------------------------- ----- NOV17g AMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAA NOV17h AMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSAA NOV17i ---------------------------------------------- NOV17j ------------------------------------------ NOV17k -------------------------------------------- 310 WO 03/093432 PCT/US03/13690 NOV171 LVVDIQAQKVLQSIGVDPLPAKLSYDKSHDQVWVLSWGDVHKSRPSLQVITEASTGQSQH NOV17m ------------------------------------------------------- n NOV17n ---------------------------------------------- o------- NOV17p ------------------------------------------------------ NOV17p --------------------------------------------------------- NOV17q ------------------------------------------------------ NOV17a ------------------------------------------------------ NOV17b ---------------------------------------------------- NOV17c ----------------------------------------------------- NOV17d -------------------------------------------------- NOV17e ADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLE NOV17f ------------------------------------------------- NOV17g ADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLE NOV17h ADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFLE NOV17i ------------------------------------------------------ NOV17j ------------------------------------------------------ NOV17k ----------------------------------------------------- NOV171 LIRTPFAGVDDFFIPPTNLIINHIRFGFIFNKSDPAVHKVDLETMMPLKTIGLHHHGCVP NOV17m ---------------------------------------------------- NOV17n ---------------------------------------------- -- NOV17o ------------------------------------------- - NOV17p --------------------------------------------- -- NOV17q ---------------------------------------------- --- NOV17a ---------------------------------------------------- NOV17b ----------------------------------------------------- NOV17c ----------------------------------------------------- NOV17d ---------------------------------------------------- NOVl7e LSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRC NOV17f --------------------------------------------------- NOV17g LSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRC NOV17h LSTGKVGMLKNLKEPPAGPAQPWGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLRC NOV17i ------------------------------------------------ NOV17j ------------------------------------------------- NOV17k ------------------------------------------------ NOV171 QAMAHTHLGGYFFIQCRQDSPASAARQLLVDSVTDSVLGPNGDVTGTPHTSPDGRFIVSA NOV17m ------------------------------------------ NOV17n ---------------------------------------- NOV17o ----------------------------------------- NOV17p ----------------------------------------- NOV17q ---------------------------------------- NOV17a ---------------------------------------- NOV17b ------------------------------------------------- NOV17c ---------------------------------------------------- NOV17d ------------------------------------------------------ NOV17e EVSGIKGGTTVVWVGEVLE---------------------------------------- NOV17f --------------------------------------------------------- NOV17g EVSGIKGGTTVVWVGEV------------------------------------------ NOV17h EVSGIKGGTTVVWVGEVEFG--------------------------------------- NOV17i --------------------------------------------------------- NOV17j ----------------------------------------------------------- NOV17k ----------------------------------------------------------- NOV171 AADSPWLHVQEITVRGEIQTLYDLQINSGISDLAFQRSFTESNQYNIYAALHTEPDLLFL NOV17m ----------------------------------------------------------- NOV17n ------------------------------------------------------ 311 WO 03/093432 PCT/US03/13690 NOV17o ----------------------------------------------------------- NOV17p ---------------------------------------------------------- NOV17q ---------------------------------------------------------- NOV17a ---------------------------------------------------------- NOV17b ---------------------------------------------------------- NOV17c ---------------------------------------------------------- NOV17d ----------------------------------------------------------- NOV17e ----------------------------------------------------------- NOV17f ----------------------------------------------------------- NOV17g ----------------------------------------------------------- NOV17h ------------------------------------------------------- NOV17i ---------------------------------------------------------- NOV17j ----------------------------------------------------------- NOV17k ----------------------------------------------------------- NOV171 ELSTGKVGMLKNLKEPPAGPAQPRGGTHRIMRDSGLFGQYLLTPARESLFLINGRQNTLR NOV17m ----------------------------------------------------------- NOV17n ----------------------------------------------------------- NOV17o ----------------------------------------------------------- NOV17p ----------------------------------------------------------- NOV17q ----------------------------------------------------------- NOV17a -------------------- NOV17b -------------------- NOV17c -------------------- NOV17d -------------------- NOV17e -------------------- NOV17f -------------------- NOV17g -------------------- NOV17h ------------------- NOV17i -------------------- NOV17j -------------------- NOV17k -------------------- NOV171 CEVSGIKGGTTVVWVGEVEFG NOV17m -------------------- NOV17n -------------------- NOV17o -------------------- NOV17p -------------------- NOV17q -------------------- NOV17a (SEQ ID NO: 240) NOV17b (-SEQ ID NO: 242) NOV17c (SEQ ID NO: 244) NOV17d (SEQ ID NO: 246) NOV17e (SEQ ID NO: 248) NOV17f (SEQ ID NO: 250) NOV17g (SEQ ID NO: 252) NOV17h (SEQ ID NO: 254) NOV17i (SEQ ID NO: 256) NOV17j (SEQ ID NO: 258) NOV17k (SEQ ID NO: 260) NOV171 (SEQ ID NO: 262) NOV17m (SEQ ID NO: 264) NOV17n (SEQ ID NO: 266) NOV17o (SEQ ID NO: 268) NOV17p (SEQ ID NO: 270) NOV17q (SEQ ID NO: 272) 312 WO 03/093432 PCT/US03/13690 Further analysis of the NOVI 7a protein yielded the following properties shown in Table 17C. 313 WO 03/093432 PCT/US03/13690 Table 17C. Protein Sequence Properties NOV17a SignalP analysis: Cleavage site between residues 23 and 24 PSORT II analysis: ,PSG: a new signal peptide prediction method N-region: length 2; pos.chg 1; neg.chg 0 H-region: length 22; peak value 8.15 PSG score: 3.75 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): 2.14 possible cleavage site: between 22 and 23 >>> Seems to have a cleavable signal peptide (1 to 22) ALOM: Klein et al's method for TM region allocation Init position for calculation: 23 Tentative number of TMS(s) for the threshold 0.5: 1 Number of TMS(s) for threshold 0.5: 0 PERIPHERAL Likelihood = 3.39 (at 513) ALOM score: -0.27 (number of TMSs: 0) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 11 Charge difference: -4.5 C(-2.0) - N( 2.5) N >= C: N-terminal side will be inside MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.60 Hyd Moment(95): 5.25 G content: 4 D/E content: 1 S/T content: 2 Score: -6.75 Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 9.1% 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 314 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 76.7 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 33.3 %: extracellular, including cell wall 22.2 %: vacuolar 22.2 %: mitochondrial 22.2 %: endoplasmic reticulum >> prediction for CG52643-02 is exc (k=9) A search of the NOV1 7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D. 315 WO 03/093432 PCT/US03/13690 Table 17D. Geneseq Results for NOV17a NOV17a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAB82300 Human follistatin-related protein 1..842 842/842 (100%) 0.0 zfsta4 - Homo sapiens, 842 aa. 1..842 842/842 (100%) [WO200132871-A2, 10-MAY 2001] AAB19727 Human SECX Clone 4324229-2 1..842 842/842 (100%) 0.0 encoded protein - Homo sapiens, 1..842 842/842 (100%) 842 aa. [WO200061754-A2, 19 OCT-2000] AAM79505 Human protein SEQ ID NO 3151 - 5..842 837/838 (99%) 0.0 Homo sapiens, 838 aa. 1..838 837/838 (99%) [WO200157190-A2, 09-AUG 2001] AAM78521 Human protein SEQ ID NO 1183 - 24..842 819/819 (100%) 0.0 Homo sapiens, 819 aa. 1..819 819/819 (100%) [WO200157190-A2, 09-AUG ... ... . 2 0 0 1] AAU08678 Human FCTR2 polypeptide 54..842 788/789 (99%) 0.0 sequence - Homo sapiens, 815 aa. 27..815 788/789 (99%) [WO200166747-A2, 13-SEP-2001] In a BLAST search of public sequence databases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E. 316 WO 03/093432 PCT/US03/13690 Table 17E. Public BLASTP Results for NOV17a Protein NOV17a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Accession Protein/Organism/Length MacthMthe Vlu Match the Matched Value Residues Portion CAC39534 Sequence 1 from Patent 1..842 842/842 (100%) 0.0 WO0132871 - Homo sapiens 1..842 842/842 (100%) S(Human), 842 aa. CAC88673 Sequence 3 from Patent 54..842 788/789 (99%) 0.0 WO0166747 - Homo sapiens 27..815 788/789 (99%) (Human), 815 aa. Q9UPU1I Hypothetical protein KIAA1061 - 150..842 693/693 (100%) 0.0 Homo sapiens (Human), 693 aa 1..693 693/693 (100%) (fragment). Q8TBU0 Similar to KIAA1 061 protein - 1..603 601/603 (99%) 0.0 Homo sapiens (Human), 605 aa. 1..603 602/603 (99%) Q8N475 Hypothetical protein 42..841 470/806 (58%) 0.0 DKFZp566D234 - Homo sapiens 42..846 617/806 (76%) (Human), 847 aa. PFam analysis predicts that the NOV 17a protein contains the domains shown in the Table 17F. Table 17F. Domain Analysis of NOV17a Identities/ Pfam Domain NOV17a Match Region Similarities Expect Value _for the Matched Region kazal 89.. 133 21/61 (34%) 3.4e-09 30/61 (49%) efhand 178..206 8/29 (28%) 0.065 21/29 (72%) ig 263..323 22/64 (34%) 0.0056 40/64 (62%) ig 355..415 21/64(33%) 2e-08 46/64 (72%) 317 WO 03/093432 PCT/US03/13690 Example 18. The NOV18 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A. Table 18A. NOV18 Sequence Analysis NOV18a, CG53270-01 SEQ ID NO: 279 11140 bp DNA Sequence ORF Start: ATGat 21 ORF Stop: TGA at 1122 CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATA AATTTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGC GATCAAGATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTG AGATTCTGGCCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGC AAGGTCTACATCGTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGC CCTGCATGAGGACGAAGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACC TGGACGTCGTCCACCGGGACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTG TCCGACTTCAGCTTCTCCAAGCGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTT CTGTGGGTCACCAGCGTATGCGGCCCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACG ACATCTGGAGCCTAGGCGTGATCCTCTACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAAC ATCAAGAAGATGCTGCGTATCCAGAAGGAGCACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGG CGAGTGCAAGGACCTCATCTACCACATGCTGCAGCCCGACGTCAACCGGCGGCTCCACATCGACGAGA TCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGGGATCTCCCTCTGTGGCCATCAACAAGGAGGGG GAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAACCTGGCTCTGACAAGAAGTCTGCCACCAA GCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGAGACAAAACCCGAGGGGACAGCAATGC AAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGTCGACTATGGAGACAGAGGAAGGG CCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGCCCAG NOVI8a, CG53270-01 SEQ ID NO: 280 367 aa MW at 41617.4kD Protein Sequence MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLN HCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVERD LKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGV ILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWM QPKARGSPSVAINKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSE ILGFPSKPSTMETEEGPPQQPPETRAQ NOV8b, 274089779 SEQ ID NO: 281 802 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence CACCGGATCCTACCTCCTGGGGATAAATTTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACT CTGAGCGCCTGAAGTTCAATGTGGCGATCAAGATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTG GAGAAATTCCTTCCCCGGGAAATTGAGATTCTGGCCATGTTAAACCACTGCTCCATCATTAAGACCTA CGAGATCTTTGAGACATCACATGGCAAGOTCTACATCGTCATGGAGCTCGCGGTCCAGGGCGACCTCC TCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGAAGCTCGCAAGAAGTTCCACCAGCTTTCC TTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGGACCTCAAGTGTGACAACCTTCTCCT TGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAGCGCTGCCTGCGGGATGACAGTG GTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGCCCCAGAGGTGCTGCAGGGC ATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCTACATCATGGTCTGCGG CTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAGCACCGCGTCAACT TCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCAGCCCGACGTC AACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGGGTACCGGC NOVI 8b, 274089779 'SEQ ID NO: 282 k67 aa MW at Protein Sequence 3674k TGSYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLNHCSIIKTY EIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNLLL DKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCG SMPYDDSNIKKMLRIQKERRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMGTG 318 WO 03/093432 PCT/US03/13690 NOV18c, CG53270-02 SEQ ID NO: 283 1132 bp DNA Sequence ORF Start: ATG at 15 JORF Stop: TGA at 1116 GCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAATTTA GGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTC TGGCCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTC TACATCGTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCA TGAGGACGAAGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACG TCGTCCACCGGGACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGAC TTCAGCTTCTCCAAGCGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGG GTCACCAGCGTATGCGGCCCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCT GGAGCCTAGGCGTGATCCTCTACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAG AAGATGCTGCGTATCCAGAAGGAGCACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTG CAAGGACCTCATCTACCACATGCTGCAGCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCA GCCACTGCTGGATGCAGCCCAAGGCACGGGGATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGT TCCCGGGGAACTGAACCCTTGTGGACCCCCGAACCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGA GCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGAGACAAAACCCGAGGGGACAGCAATGCAAATGT CCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGTCGACTATGGAGACAGAGGAAGGGCCCCCC CAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGCCC NOV18c, CG53270-02 SEQIDNO:284 367aa MW at 41617.4kD Protein Sequence MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLN HCSIIKTYEIFETSHGKVYIVMLAVQGDLLELIKTRGALHEDEARKKFHQLSLAIYCHDLDVVHRD LKCDNLLLDKDFNIKLSDFSPSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGV ILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLKIDEILSHCWM QPKARGSPSVAINKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSE ILGFPSKPSTMETEEGPPQQPPETRAQ NOV18d, 13382344 SNP for SEQ ID NO: 1140 bp SNP: 89 T/C CG53270-01 285 DNA Sequence ORF Start: ORF Stop: end of sequence ATG at 21 CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT TTAGGAGAGGGCTCCTACGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG NOV18d, 13382344 SNP SEQ ID NO: 367 aa SNP: no change in protein for 286 sequence CG53270-01 Protein Sequence MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEFLPREIEILAMLNHCS IIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL 319 WO 03/093432 PCT/US03/13690 LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ NOV18e, 13382345 SNP for SEQ ID NO: 287 1140 bp SNP: 95 A/G CG53270-01 ORF Start: ATG at 21 ORF Stop: TGA at 1122 DNA Sequence CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT TTAGGAGAGGGCTCCTATGCAAAGGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG NOV18e, 13382345 SNP SEQ ID NO: 367 aa SNP: no change in protein for sequence CG53270-01 Protein Sequence MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLNHCS IIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ NOV18f, 13376391 SNP for SEQ ID NO: 289 . 1140 bp SNP: 310 A/G CG53270-01 ORF Start: ATG at 21 ORF Stop: TGA at 1122 DNA Sequence CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT TTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGGCCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG NOV18f, 13376391 SNP for SEO ID NO: 367 aa SNP: Asp to Gly at position 97 320 WO 03/093432 PCT/US03/13690 CG53270-01 1290 Protein Sequence MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLNHCS IIKTYEIFETSHGKVYIVMELAVQGGLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPRVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ NOVI8g, 13376390 SNP for SEQ ID NO: 291 1140 bp SNP: 978 CIT CG53270-01 ORF Start: ATG at 21 lORF Stop: TGA at 1122 DNA Sequence CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT TTAGGAGAGGGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAA GATCATCGACCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGG CCATGTTAAACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATC GTCATGGAGCTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGA AGCTCGCAAGAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGG ACCTCAAGTGTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAG CGCTGCCTGCGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGC CCCAGAGGTGCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCT ACATCATGGTCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAG CACCGCGTCAACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCA GCCCGACGTCAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGG GATCTCCCTCTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAA CCTGGCTCTGACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGTCCCAGGCACAGCCTGA GACAAAACCCGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGT CGACTATGGAGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGC CCAG NOV18g, 13376390 SNP for SEQ ID NO: 367 aa SNP: Pro to Ser at position 320 CG53270-01 292 Protein Sequence MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPREIEILAMLNHCS IIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPXVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQSQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ NOVL8h, 13376389 SNP for SEQ ID NO: 293 1140 bp SNP: 996 A/G CG53270-01 ORF Start: ATG at 21 ORF Stop: TGA at 1122 DNA Sequence CACTGGGCATTCCTGGCACCATGGATGACGCTGCTGTCCTCAAGCGACGAGGCTACCTCCTGGGGATAAAT TTAGGAGAG GGCTCCTATGCAAAAGTAAAATCTGCTTACTCTGAGCGCCTGAAGTTCAATGTGGCGATCAAGATCATCGA CCGCAAGAAGGCCCCCGCAGACTTCTTGGAGAAATTCCTTCCCCGGGAAATTGAGATTCTGGCCATGTTAA ACCACTGCTCCATCATTAAGACCTACGAGATCTTTGAGACATCACATGGCAAGGTCTACATCGTCATGGAG CTCGCGGTCCAGGGCGACCTCCTCGAGTTAATCAAAACCCGGGGAGCCCTGCATGAGGACGAAGCTCGCAA GAAGTTCCACCAGCTTTCCTTGGCCATCAAGTACTGCCACGACCTGGACGTCGTCCACCGGGACCTCAAGT GTGACAACCTTCTCCTTGACAAGGACTTCAACATCAAGCTGTCCGACTTCAGCTTCTCCAAGCGCTGCCTG CGGGATGACAGTGGTCGAATGGCATTAAGCAAGACCTTCTGTGGGTCACCAGCGTATGCGGCCCCAGAGGT GCTGCAGGGCATTCCCTACCAGCCCAAGGTGTACGACATCTGGAGCCTAGGCGTGATCCTCTACATCATGG TCTGCGGCTCCATGCCCTACGACGACTCCAACATCAAGAAGATGCTGCGTATCCAGAAGGAGCACCGCGTC AACTTCCCACGCTCCAAGCACCTGACAGGCGAGTGCAAGGACCTCATCTACCACATGCTGCAGCCCGACGT CAACCGGCGGCTCCACATCGACGAGATCCTCAGCCACTGCTGGATGCAGCCCAAGGCACGGGGATCTCCCT CTGTGGCCATCAACAAGGAGGGGGAGAGTTCCCGGGGAACTGAACCCTTGTGGACCCCCGAACCTGGCTCT GACAAGAAGTCTGCCACCAAGCTGGAGCCTGAGGGAGAGGCACAGCCCCAGGCACAGCCTGAGGCAAAACC 321 WO 03/093432 PCT/US03/13690 CGAGGGGACAGCAATGCAAATGTCCAGGCAGTCGGAGATCCTGGGTTTCCCCAGCAAGCCGTCGACTATGG AGACAGAGGAAGGGCCCCCCCAACAGCCTCCAGAGACGCGGGCCCAGTGAGCTTCTTGCGGCCCAG NOV18h, 13376389 SNP for SEQ ID NO: 1367 aa SNP: Thrto Ala at position 326 CG53270-01 1294 Protein Sequence MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKI IDRKKAPADFLEKFLPREIEILAMLNHCS IIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQLSLAIKYCHDLDVVHRDLKCDNL LLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPAYAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGS MPYDDSNIKKMLRIQKEHRVNFPRSKHLTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAI NKEGESSRGTEPLWTPEPGSDKKSATKLEPEGEAQPQAQPEAKPEGTAMQMSRQSEILGFPSKPSTMETEE GPPQQPPETRAQ A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 18B. Table 18B. Comparison of the NOV18 protein sequences. NOV18a MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPRE NOV18b --------- TGSYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPRE NOV18c MDDAAVLKRRGYLLGINLGEGSYAKVKSAYSERLKFNVAIKIIDRKKAPADFLEKFLPRE NOV18a IEILAMLNHCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQL NOV18b IEILAMLNHCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQL NOV18c IEILAMLNHCSIIKTYEIFETSHGKVYIVMELAVQGDLLELIKTRGALHEDEARKKFHQL NOV18a SLAIKYCHDLDVVHRDLKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPA NOV18b SLAIKYCHDLDVVHRDLKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPA NOV18c SLAIKYCHDLDVVHRDLKCDNLLLDKDFNIKLSDFSFSKRCLRDDSGRMALSKTFCGSPA NOV1Ia YAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKH NOV18b YAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKH NOVI18c YAAPEVLQGIPYQPKVYDIWSLGVILYIMVCGSMPYDDSNIKKMLRIQKEHRVNFPRSKH NOV18a LTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAINKEGESSRGTEPLWTP NOV18b LTGECKDLIYHMLQPDVNRRLHIDEILSHCWMGTG-------------------------- NOV18c LTGECKDLIYHMLQPDVNRRLHIDEILSHCWMQPKARGSPSVAINKEGESSRGTEPLWTP NOV18a EPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEEGPPQQ NOV18b -------------------------------------------- NOV18c EPGSDKKSATKLEPEGEAQPQAQPETKPEGTAMQMSRQSEILGFPSKPSTMETEEGPPQQ NOV18a PPETRAQ NOV18b ------ NOV18c PPETRAQ NOV18a (SEQ ID NO: 280) NOV18b (SEQ ID NO: 282) NOV18c (SEQ ID NO: 284) Further analysis of the NOV18a protein yielded the following properties shown in Table 18C. 322 WO 03/093432 PCT/US03/13690 Table 18C. Protein Sequence Properties NOV18a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 10; pos.chg 3; neg.chg 2 H-region: length 9; peak value 4.19 PSG score: -0.21 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -5.57 possible cleavage site: between 24 and 25 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 = 1.11 (at 86) ALOM score: -1.44 (number of TMSs: 0) MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 8.48 Hyd Moment(95): 7.98 G content: 0 D/E content: 2 S/T content: 0 Score: -6.50 Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 14.2% 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 323 WO 03/093432 PCT/US03/13690 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's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 76.7 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 60.9 %: nuclear 17.4 %: cytoplasmic 13.0 %: peroxisomal 8.7 %: mitochondrial >> prediction for CG53270-01 is nuc (k=23) A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18D. 324 WO 03/093432 PCT/US03/13690 Table 18D. Geneseq Results for NOV18a NOV18a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAM47929 Human htssk-1 SEQ ID NO 2 - 1..367 367/367 (100%) 0.0 Homo sapiens, 367 aa. 1..367 367/367 (100%) [WO200183768-A2, 08-NOV 2001] ABB05005 Human kinase protein SEQ ID 1..367 367/367 (100%) 0.0 NO:2 - Homo sapiens, 367 aa. 1..367 367/367 (100%) [WO200190328-A2, 29-NOV 2001] AAG78493 Human 53070 protein kinase - 1..367 367/367 (100%) 0.0 Homo sapiens, 367 aa. 1..367 367/367 (100%) [WO200196544-A2, 20-DEC-2001] ABP60983 Novel human protein. SEQ ID 70 - 1..367 367/367 (100%) 0.0 Homo sapiens, 367 aa. 1..367 367/367 (100%) [WO200250105-Al, 27-JUN-2002] ABG30415 Human testis specific kinase 1..367 367/367 (100%) 0.0 (TSSK) 1 protein - Homo sapiens, 1..367 367/367 (100%) 367 aa. [WO200238732-A2, 16 MAY-2002] In a BLAST search of public sequence databases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18E. 325 WO 03/093432 PCT/US03/13690 Table 18E. Public BLASTP Results for NOV18a Protein NOV18a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value Residues Portion Q9BXA7 Serine/threonine kinase FKSG81 1.367 367/367 (100%) 0.0 (Testis-specific serine/threonine 1..367 367/367 (100%) kinase 1) - Homo sapiens (Human), 367 aa. Q61241 Serine/threonine kinase - Mus 1..364 307/364 (84%) e-176 musculus (Mouse), 364 aa. 1..362 328/364 (89%) Q81IY55 Hypothetical protein - Homo sapiens 1..352 241/353 (68%) e-136 (Human), 358 aa. 1..334 282/353 (79%) Q96PF2 Testis specific serine/threonine 1..352 241/353 (68%) e-136 kinase 2 - Homo sapiens (Human), 1..334 281/353 (79%) 358 aa. 054863 Protein kinase - Mus musculus 1..340 246/347 (70%) e-136 (Mouse), 357 aa. 1..344 277/347 (78%) PFam analysis predicts that the NOV 18a protein contains the domains shown in the Table 18F. Table 18F. Domain Analysis of NOV18a Identities/ Pfam Domain NOV18a Match Region Similarities Expect Value for the Matched Region pkinase 12..272 94/304 (31%) 5.5e-73 204/304 (67%) 326 WO 03/093432 PCT/US03/13690 Example 19. The NOVI9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19A. Table 19A. NOV19 Sequence Analysis NOV 19a, CG54254-04 SEQ ID NO: 295 2040 bp DNA sequence ORF Start: ATG at 1 jORF Stop: TGA at 2023 ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGT GATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGA CGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAAC GACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAA CCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTAT ACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGAC AACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGA TGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGC TCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGG CTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCT GGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACC TCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTG CAGAAACTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGA GCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGG GGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGG GACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGT CCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCG GCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCC CTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGC CACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCA CGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCC GTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCC CAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACAC CCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAAC GCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTT CCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCT ACAACCGGGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTG GAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGT CCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCA CGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG NOV19a, CG54254-04 SEQ ID NO: 296 674 aa MW at 74087.4kD Protein Sequence MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQD NNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELR LDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL QKLYLQDNAISHIPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLR DWVRARAAVVNVRGLMCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGS LFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPA VGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQN AGPMASLPAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSREKDDYMESGTKKDNSIL EIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT NOV19b, 247846813 SEQ ID NO: 297 1933 bp DNA Sequence - ORF Start: at 2 ORF Stop: end of sequence AGGCTCCGCGGCCGCCCCCTTCACCGGATCCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCG ACAACGGCTTCATCTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCC 327 WO 03/093432 PCT/US03/13690

ACCACCCTCTACCTGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACAAGGT

CAACGTGCAGGTCATCTACCTATACGAGAATGACCTGGATGAGTTCCCCATCACCTGCCCCGCTCCC TCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCG CTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGC CGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGC CGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAG GGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGA CACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCC TCAACCTGCCCAGCGCCCACCTGCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTAC AACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCC CCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTG GCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTC ATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTG TTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCT CTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGAC TCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCT GACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGC TGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAG TACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAA TGCCTACGTAGCTGATGAGACACCTGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCA CCACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGG GCAGTGGCTCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGA GCTGCTGACCCGGGAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGA CCAAGAAGGATAACTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTAC CGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCAC ACACACCATTGGCTATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCT ACACACTCGAGGGCAAGGGTGGGCGCGCC N(W19b,247846813 LSEQIDNOhit98 644aa M at70572.3l) Protein Sequence GSAAAPFTGSIDSTTCPSVCRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKV NVQVIYLYENDLDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFA DSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLEAFKGLNSLRRLVLDGNLLANQRIADD TFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELERLDLSNNNLTTLP RGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMCQGPBKVRGMAIKDITSEMDEC FETGPQGGVAMAAAKTTASNHASATTPQGSLFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIKVKAL TADSIRITWRATLPASSFRLSWLRLGHSPAVGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSN AYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGE LLTRERAYNRGSRKKDDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIPPSNGSSLCKAT HTIGYGTTRGYRDGGIPDIDYSYTLEGKGGRA NOV19c, 247846825 SEQ ID NO: 299 1785bp DNA Sequence ORF Start: at 2 JORF Stop: 784 AGGCTCCGCGGCCGCCCCCTTCACCGGATCCGACGCCACCACCCTCTATCTGCAGAACAACCAGATCA ACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAAT GACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGT GCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACT CCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTG AGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGA CAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGG ACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAG CTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACT CTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGC GGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGCTCGAG GGCAAGGGTGGGCGCGCCGACCCAGCTTTCTTGTACA NOV19c, 247846825 SEQ ID NO: 300 261aa MW at 29146.5kD Protein Sequence 328 WO 03/093432 PCT/US03/13690 GSAAAPFTGSDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQDNNV RTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDD NRISTIPLEAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKL YLQDNAISHIPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGLEGKGGRADPAFLY NOV19d, 247846967 SEQ ID NO:301 1880bp DNA Sequence I JORE Start: at 2 jORF Stop: 1879 ACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAAT GACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGT GCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACT CCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTG AGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGA CAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGG ACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAG CTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAGCT CTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGC GGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTG GCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGT GAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCA TGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCC AATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTAC CCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTG ATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAG GCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTC CATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCA CCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACACCCGTGTGT GCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGCCC CATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTGGTCC TGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCGG GGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCG CGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTA TCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGC TACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACACTCGAGGGCAAGGGTGGGCGCCCCGA CCCAGCTTTCTTGTACACAGCTGGCATTATAAGAAGCCATTGCT NOV19d, 247846967 SEQ ID NO: 302 626 aa MW at 68699.3kD Protein Sequence GSAAAPFTGSDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQDNNV RTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDD NRISTIPLKAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNELAAPPLNLPSAHLQKL YLQDNAISHIPYNTLAKNRELERLDLSNNNLTTLPRGLPDDLGNLAQLLLRNNPWFCGCNLMWLRDWV KARAAVVNVRGLMCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFT LKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGS ITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGP MASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKKDDYMESGTKKDNSILEIR GPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYTLEGKGGRPD PAFLYTAGIIRSHC NOV19e, 283841186 SEQ ID NO: 303 2041 bp DNA Sequence ORF Start: at 2 ORF Stop end of sequence CACCGGATCCATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGG CCACCGTTGTGATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATC GCCTTCCTGACGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCAT CTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTACC TGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTC 329 WO 03/093432 PCT/t1S03/13690 ATCTACCTATACGAGAATGACC!TGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCA CCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAG2 GC TGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAG CTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATcCCCTCGGGGCTGCCGCACACGCTGGA GGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCC TGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGC CTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAG CGCCCACCTGCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAJ.CACGCTGGCCA AGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTC GACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAJACCTCAT GTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCC CTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGG CCGCAGGGCGGCGTGGCCAATGCrGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACnACGCC CCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAJACATTGACT ACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCC ATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCA CAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAG CCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCATGCCTACGTAGCT GATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGC!TATGGCCCTACCACCACACTC~AACCA GGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGG TCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGGCTGCTGACCCGG GAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAA CTCCATCCTGGAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAA~CCCGTACCGCGCCAJGAGG AGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGC TATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACACTCGAGGG C NOV19e, 283841186 'SEQ ID NO: 304 680 aa MW at74631.lkD Protein Sequence TGSMVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFI YCNDRGLTS IP2ADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELH LQDNN~VRTIARDSLARIPLLEKLHLDDNSVSTVS IEEDAFADfSKQLKLLFLSRNHLS SIPSGLPHTLE ELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLA1IQRIADDTFSRLQNLTELSLVFRNSLAAPPLNLPS * LQKLYLQDNAISHIPYNTLAMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCLM WLRDWVKARAAVVNVRGLMCQGPEKVRGMAIDITSEMDECFETGPQGGVA.TTASHSATTP QGSLFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHfl(ALTADS IRITWKATLPASSFRLSWLRLGH SPAVGS ITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQ EQNAGPMASLPLAGI IGGAVALVFLFLVLGAICWYVHQAGELLTRERAY&RGSRKKDDYMESGTKKDN S ILE IRGPGLQMLFINPYRAKEEYVVHTIFPSNGS SLCKATHTIGYGTTRGYRDGGIPD IDYSYTLEG NOV19f, CG54254-01 jSEQ ID NO: 305 12025 bp DNA Sequence IORE Start: ATG at 1 --- ORF Stop: TGA at 2023 ATG;GTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGT GATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGA CGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCACc GACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGAkTGCCACCACCCTCTACCTGCAGACAA CCAGATCAACAACGCCGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCTCTACCTAT ACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGAC AACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGA TGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAGCTGC TCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGG CTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCT GGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACC TC-ACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTG CAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGA GCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACOCTGCCCCGCGGCCTGTTCGACGACCTGG GGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGG G ACTGGGTGAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGT 330 WO 03/093432 PCT/t1S03/13690 CCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCG GCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCC CTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGC CACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCA CGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCC GTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCC CAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACAC CCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAAC GCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTT CCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCT ACAACCGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTG GAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGT CCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTACGGCACC~A CGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGA NOVl9f, CG54254-01 ISEQ ID NO: 306 m MWa 48.k PoenSequence 67aj at48.k MVVAHPTATATTTPTATVTATVVMTTATMVDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTS IPADIPDDATTLYLQNNQINNAGIPQDLKTKVVQVIYLYENDLDEFPINLPRSLRELHLQD NNVRTIARDSLARIPLLEKLHLDDNSVSTVS IEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELR LDDNRI STIPLHAFKGLNSLRRLVIJDGNILLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL QKLYLQDNAISHIPYNTLAKMRELERLDLSNNNLTTLPGLFDDLGNLAQLLLRNNPWFCGCNLMWLR DWVKAAAVVNVRGLMCQGPEKVRGMIKDITSEMDECFETGPQGGVA1NAAAKTTASNHASATTPQGS LFTLKARPGLRLPDSNIDYPMATGDGATLAIHVKALTADSIRITWCATLPAS SFRLS WLRIJGHS PA VGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAETPVCAATASYGPTTTLQEQN AGMSPAIGAAVLLLACYH GLTEANGRKDMSTKNIL EIRGPGLQMLPINPYRAKEEYI\JBTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT NOV19g, CG54254-02 ISEQ ID NO: 307 1199 bp DNA Sequence ., -1,-ORF Start: ATG at I lORF Stop: TGAat19 ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGT GATGACCACGGCCACCATGGACCTGCG3GGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGA CGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAC GACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGATGCCACCACCCTCTACCTGCAGAJACA CCAGATCAACAACGCCGGCATCCCCCAGGACCTCAGACCAAGGTCAACGTGCAGGTCATCTACCTAT ACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGAC AACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGA TGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGAACAGCTCAAGCTGC TCTTCCTGAGCCGGAACCAC!CTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGG CTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCT GGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACC TCACAGAGCTCTCOCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCTACCTGCAGGACAATGCCATC AGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGACTGGACGGCTGGACCTGTCCCA CCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACA ACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTC AACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAG CGAGGTGGAGAGTGTTTTGAGACGGGCGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAJAGACCACGG CCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGG CTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCAT CCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTT TCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACOTTGGTGCAG GGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCAC

CATGGAGACCAGCAATGCCTACGTAGCTGATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACA

GCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCG GGCATCATCGGCGGGGCAGTGGCTCTCGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGT GCACCAGGCTGGCGAGCTGCTGACCCcGGGAGAGGGCCTACAACCGGGGCAGCAGGAAAJ&GGATGACT ATATGGAGTCAGGGACCAAGAGGATAACTCCATCCTGGAATCCGCGGCCCTGGGCTCAGATGCTG CCCATCAACCCGTACCGCGCCAAAGAAGAGTACGTGGTCCACACTATrCTTCCCCTCCAACGGCAGCAG 331 WO 03/093432 PCT/US03/13690 CCTCTGCAAGGCCACACACACCATTGGCTACGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCG ACATAGACTACTCCTACACATGA NOVI 9g, CG54254-02 SEQ ID NO: 308 664 aa JMW at 72982.3kD Protein Sequence MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQD NNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELR LDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLYLQDNAI SHIPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVV NVRGLMCQGPEKVRGMAIKDITSEVESVLRRAPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRPG LRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGSITETLVQ GDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAAETADSYGPTTTLNQEQNAGPMASLPLA GIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKKDDYMESGTKKDNSILEIRGPGLQML PINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT NOV19h, CG54254-03 .SEQ ID NO: 309 1485 bp DNA Sequence lORF Start: at 1 ORF Stop: end of sequence ACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGACTCACATC CATCCCCGCAGATATCCCTGATGATGCCACCACCCTCTACCTGCAGAACAACCAGATCAACAACGCCG GCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGGAT GAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCAT TGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCA CCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAAC CACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCAT CTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACC TGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTG GTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAGCTCTACCTGCA GGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACC TGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTG CTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACG GGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCA AGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCT GCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGC CAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCA AGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTC CCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGA GACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCA TCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGACACCCGTGTGTGCCAAGGCA GAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGC NOV19h, CG54254-03 ISEQ ID NO: 310 495aa MW at 54572.3kD Protein Sequence TTCPSVCRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLD EFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRN HLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRREVLDGNLLANQRIADDTFSRLQNLTELSL VRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQL LLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMCQGPEKVRGMAIKDITSEMDECFETPQGGVANAA AKTTASNHASATTPQGSLFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATL PASSFRLSWLRLGHSPAVGSITETLVQGDKTEYLLTALEPKSTYI ICMVTMETSNAYVADETPVCAKA ETADSYGPTTTLNQEQNAG NOV19i, CG54254-05 ISEQ ID NO: 311 '2041 bp DNA Sequence ORF Start: ATG at 11 ORF Stop: end of sequence CACCGGATCCATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGG CCACCGTTGTGATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATC GCCTTCCTGACGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACOGCTTCAT CTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTACC 332 WO 03/093432 PCT/US03/13690 TGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTC ATCTACCTATACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCA CCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGC TGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAG CTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGA GGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCC TGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGC CTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAG CGCCCACCTOCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCA AGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTC GACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCAT GTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCC CTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGG CCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACCACGCC CCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACT ACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCC ATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCA CAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAG CCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCT GATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCA GGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGG TCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGG GAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAA CTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGG AGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGC TATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACA C NOV19i, CG54254-05 SEQ ID NO: 312 674 aa MW at 74086.5kD Protein Sequence MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQD NNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELR LDDNRISTIPLEAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLMLPSAHL QKLYLQDNAISHIPYNTLAKMRELERLDLSNKRLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLR DWVKARAAVVNVRGLMCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNKSATTPQGS LFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPA VGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQN AGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKKDDYMESGTKKDNSIL EIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT NOV19), CG54254-06 ISEQ ID NO: l3 12039 bp DNA Sequence (RFStat:at1 jORF Stop: TAG at 2020 ACCGCCACTGCCACCACTACGCCCACTGCCACTGTCACGGCCACCGTTGTGATGACCACGGCCACCAT GGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGGTCATCGACAGCA CCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGACTCACATCC ATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTACCTGCAGAACAACCAGATCAACAACGCCGG CATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGGATG AGTTCCCCATCAACCTGCCCCGCCCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCAC CGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACC ACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATC TCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCT GCTGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGG TGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAGCTCTACCTGCAG GACAATGCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCT GTCCAACAACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGC TGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGG 333 WO 03/093432 PCT/US03/13690 GCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAA GGACATTACCAGCGAGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTG CCAAGACCACGGCCAGCAACCACGCCACTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCC AAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAA GACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCC CCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAG ACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCAT CTGCATGGTCACCATGGAGACCAGCAATGCCTATGTAGCTGATGAGACACCCGTGTGTGCCAAGGCAG AGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGC CTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCAT CTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCGGGGCAGCAGGA AAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCGCGGCCCTGGG CTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTCCCCTC CAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTACGGCACCACGCGGGGCTACCGCCACT GCCACCACCTCCCCGACATAGACTACTCCTACACACGATCCCCGACATAGACTACTCCTACACATGA NOVI 9j, CG54254-06 SEQ ID NO: 314 673 aa MW at 74202.6kD Protein Sequence TATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDRGLTS IPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRPLRELHLQDNNVRTI ARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRI STIPLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQ DNAISHIPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKAR AAVVNVRGLMCQGPEKVRGMA1KDITSEMDECFETGPQGGVANAAAKTTASNHATATTPQGSLFTLKA KRPGLRLPDSNIDYPMATGDGARTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGSITE TLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMAS LPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTREPAYNRGSRKKDDYMESGTKKDNSILEIRGPG LQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRHCHHLPDIDYSYTRSPT NOVI 9k, CG54254-07 SEQIDNO:315 2049bp DNA Sequence ORF Start: ATGat-16 ORE Stop: TAG at 2038 CACCGCGGCCGCACCATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGT CACGGCCACCGTTGTGATGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGC TCATCGCCTTCCTGACGGAGGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGC TTCATCTACTGCAACGACCGGGGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCT CTACCTGCAGAACAACCAGATCAACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGC AGGTCATCTACCTATACGAGAATGACCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAG CTGCACCTGCAGGACAACAATGTGCGCACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGA GAAGCTGCACCTGGATGACAACTCCGTGTCCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCA AACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACG CTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAA CAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCAGCGCATCGCCGACGACACCTTCA GCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGGCCGCGCCACCCCTCAACCTG CCCAGCGCCCACCTGCAGAAGCTCTACCTGCAGGACAATGCCATCAGCCACATCCCCTACAACACGCT GGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCACGCTGCCCCGCGGCC TGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTTGTGGCTGCAAC CTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTCATGTGCCA GGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTTTGAGA CGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCACC ACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACAT TGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAG ACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTG GGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCT GACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACG TAGCTGATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTC AACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGC TCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGA CCCGGGAGAGGGCCTACAACCGGGGCAGCAGGAAAAAGGATGACTATATGGAGTCAGGGACCAAGAAG 334 WO 03/093432 PCT/US03/13690 GATAACTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAA AGAGGAGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACCA TTGGCTATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATAG GTCGACGGC NOV19k, CG54254-07 SEQ ID NO: 316 674 aa MW at 74086.5kD Protein Sequence MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCN DRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQD NNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELR LDDNRISTIPLHAFKGLNSLRRLVLDGNLLANORIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHL QKLYLQDNAISHIPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLR DWVKARAAVVNVRGLMCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAARTTASNHASATTPQGS LFTLKAKRPGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPA VGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQN AGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKKDDYMESGTKKDNSIL EIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT NOV191, 13375078 SNP for SEQ ID NO: 2040 bp SNP: 34 A/G CG54254-04 17 DNA Sequence ORF Start: ORF Stop: TGA at 2023 ATG at 1 ATGGTGGTGGCACACCCCACCGCCACTGCCACCGCCACGCCCACTGCCACTGTCACGGCCACCGTTGTGA TGACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGA GGTCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGG GGACTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCA ACAACGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGA CCTGGATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGC ACCATTGCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGT CCACCGTCAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAA CCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATC TCCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGC TGGCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCG CAATTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAAT GCCATCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACA ACAACCTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAA CAACCCTTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTC AACGTGCGGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCG AGATGGACGAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAG CAACCACGCCTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGC CTCCCCGACTCCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGA AGGCCCTGACGGCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAG TTGGCTGCGCCTGGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACA GAGTACCTGCTGACAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCA ATGCCTACGTAGCTGATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCAC CACACTCAACCAGGAGCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCA GTGGCTCTGGTCTTCCTCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGC TGACCCGGGAGAGGGCCTACAACCGGGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAA GGATAACTCCATCCTGGAAATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAA GAGGAGTACGTGGTCCACACTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTG GCTATGGCACCACGCGGGGCTACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCC GCCCACCCGG NOV191, 13375078 SNP for SEQ ID NO: 674 aa SNP: Thr to Ala at position 12 CG54254-04 318 Protein Sequence MVVAHPTATATATPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDR GLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQDNNVR 335 WO 03/093432 PCT/US03/13690 TIARDSLARIPLLELHLDDNSVSTVSIEEDAFADSKQLRLLFLSRNHLSSIPSGLPHTLEELRLDDNRI STIPLHAFKGLNSLRRLVLDGNLLANQRIADDTPSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDN AISHIPYNTLAKMRELERLDLSNNNLTTLPRGLDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVV NVRGLMCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRPGLR LPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGSITETLVQGDKT EYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGA VALVFLFLVLGAICWYVHQAGELLTRERAYNRGSREKDDYMESGTKKDNSILEIRGPGLQMLPINPYRAK EEYVVHTIFPSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT NOV19m, 13376406 SNP for ISEQ ID NO: 319 2040 bp SNP: 47 C/T CG54254-04 ORF Start: ATG at1 ORF Stop: TGA at 2023 ]DNA Sequence ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGTCACTGTCACGGCCACCGTTGTGAT GACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGG TCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGA CTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCAACAA CGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGG ATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGT CAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAA CCACCTGAGCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCT CCACCATCCCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTG GCCAACCAGCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAA TTCGCTGGCCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAATGCCA TCAGCCACATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAAC CTGACCACGCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTOCTCAGGAACAACCC TTGGTTTTGTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGC GGGGCCTCATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGAC GAGTGTTTTGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGC CTCTGCCACCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACT CCAACATTGACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACG GCAGACTCCATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCT GGGCCACAGCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGA CAGCCCTGGAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCT GATGAGACACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGA GCAGAACGCTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCC TCTTCCTGGTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCC TACAACCGGGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGA AATCCGCGGCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACA CTATCTTCCCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGC TACCGGGACGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG NOV19m, 13376406 SNP for SEQ ID NO: 674 aa SNP: Ala to Val at position 16 CG54254-04 320 Protein Sequence MVVAHPTATATTTPTVTVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDRG LTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQDNNVRTI ARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTI PLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISH IPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGL MCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRPGLRLPDSNI DYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGSITETLVQGDKTEYLLTAL EPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGAVALVFLFL VLGAICWYVHQAGELLTRERAYNROSREKDDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIF PSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT fNOV19n, 13375079 SNP for SEQ ID NO. 321 bp SNP: 106 T/C CG54254-04 JORE Start: ATG at 1 ORF Stop: TGA at 2023 DNA Sequence 336 WO 03/093432 PCT/US03/13690 ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGTGAT GACCACGGCCACCATGGACCTGCGGGACTGGCTGCTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGG TCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGA CTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCAACAA CGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGAGAATGACCTGG ATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGT CAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGA GCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATC CCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCA GCGCATCGCCGACGACACCTTCAGCCGCCTACAGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGG CCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAATGCCATCAGCCAC ATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCAC GCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTT GTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTC ATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTT TGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCA CCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATT GACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTC CATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACA GCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTG GAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGAC ACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACG CTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTG GTCCTGGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCG GGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCGCG GCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTC CCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGCTACCGGGA CGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG NOV19n, 13375079 SNP for SEQ ID NO: 674 aa SNP: Phe to Leu at position 36 CG54254-04 322 Protein Sequence MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLLLCYGLTAFLTEVIDSTTCPSVCRCDNGFIYCNDRG LTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYENDLDEFPINLPRSLRELHLQDNNVRTI ARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTI PLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISH IPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGL MCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRPGLRLPDSNI DYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGSITETLVQGDKTEYLLTAL EPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGAVALVFLFL VLGAICWYVHQAGELLTRERAYNRGSREKDDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIF PSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT NOV19o, 13376405 SNP for SEQ ID NO: 323 2040 bp SNP: 344 A/T CG54254-04 ORF Start: ATG at 1 ORF Stop: TGA at 2023 DNA Sequence ATGGTGGTGGCACACCCCACCGCCACTGCCACCACCACGCCCACTGCCACTGTCACGGCCACCGTTGTGAT GACCACGGCCACCATGGACCTGCGGGACTGGCTGTTCCTCTGCTACGGGCTCATCGCCTTCCTGACGGAGG TCATCGACAGCACCACCTGCCCCTCGGTGTGCCGCTGCGACAACGGCTTCATCTACTGCAACGACCGGGGA CTCACATCCATCCCCGCAGATATCCCTGATGACGCCACCACCCTCTATCTGCAGAACAACCAGATCAACAA CGCTGGCATCCCCCAGGACCTCAAGACCAAGGTCAACGTGCAGGTCATCTACCTATACGTGAATGACCTGG ATGAGTTCCCCATCAACCTGCCCCGCTCCCTCCGGGAGCTGCACCTGCAGGACAACAATGTGCGCACCATT GCCAGGGACTCGCTGGCCCGCATCCCGCTGCTGGAGAAGCTGCACCTGGATGACAACTCCGTGTCCACCGT CAGCATTGAGGAGGACGCCTTCGCCGACAGCAAACAGCTCAAGCTGCTCTTCCTGAGCCGGAACCACCTGA GCAGCATCCCCTCGGGGCTGCCGCACACGCTGGAGGAGCTGCGGCTGGATGACAACCGCATCTCCACCATC CCGCTGCATGCCTTCAAGGGCCTCAACAGCCTGCGGCGCCTGGTGCTGGACGGTAACCTGCTGGCCAACCA GCGCATCGCCGACGACACCTTCAGCCGCCTA-AGAACCTCACAGAGCTCTCGCTGGTGCGCAATTCGCTGG 337 WO 03/093432 PCT/US03/13690 CCGCGCCACCCCTCAACCTGCCCAGCGCCCACCTGCAGAAACTCTACCTGCAGGACAATGCCATCAGCCAC ATCCCCTACAACACGCTGGCCAAGATGCGTGAGCTGGAGCGGCTGGACCTGTCCAACAACAACCTGACCAC GCTGCCCCGCGGCCTGTTCGACGACCTGGGGAACCTGGCCCAGCTGCTGCTCAGGAACAACCCTTGGTTTT GTGGCTGCAACCTCATGTGGCTGCGGGACTGGGTGAAGGCACGGGCGGCCGTGGTCAACGTGCGGGGCCTC ATGTGCCAGGGCCCTGAGAAGGTCCGGGGCATGGCCATCAAGGACATTACCAGCGAGATGGACGAGTGTTT TGAGACGGGGCCGCAGGGCGGCGTGGCCAATGCGGCTGCCAAGACCACGGCCAGCAACCACGCCTCTGCCA CCACGCCCCAGGGTTCCCTGTTTACCCTCAAGGCCAAAAGGCCAGGGCTGCGCCTCCCCGACTCCAACATT GACTACCCCATGGCCACGGGTGATGGCGCCAAGACCCTGGCCATCCACGTGAAGGCCCTGACGGCAGACTC CATCCGCATCACGTGGAAGGCCACGCTCCCCGCCTCCTCTTTCCGGCTCAGTTGGCTGCGCCTGGGCCACA GCCCAGCCGTGGGCTCCATCACGGAGACCTTGGTGCAGGGGGACAAGACAGAGTACCTGCTGACAGCCCTG GAGCCCAAGTCCACCTACATCATCTGCATGGTCACCATGGAGACCAGCAATGCCTACGTAGCTGATGAGAC ACCCGTGTGTGCCAAGGCAGAGACAGCCGACAGCTATGGCCCTACCACCACACTCAACCAGGAGCAGAACG CTGGCCCCATGGCGAGCCTGCCCCTGGCGGGCATCATCGGCGGGGCAGTGGCTCTGGTCTTCCTCTTCCTG GTCCTOGGGGCCATCTGCTGGTACGTGCACCAGGCTGGCGAGCTGCTGACCCGGGAGAGGGCCTACAACCG GGGCAGCAGGGAAAAGGATGACTATATGGAGTCAGGGACCAAGAAGGATAACTCCATCCTGGAAATCCGCG GCCCTGGGCTGCAGATGCTGCCCATCAACCCGTACCGCGCCAAAGAGGAGTACGTGGTCCACACTATCTTC CCCTCCAACGGCAGCAGCCTCTGCAAGGCCACACACACCATTGGCTATGGCACCACGCGGGGCTACCGGGA CGGCGGCATCCCCGACATAGACTACTCCTACACATGATGCCCGCCCACCCGG NOV19o, 13376405 SNP for SEQ ID NO: 674 aa SNP: Glu to Val at position 115 CG54254-04 324 Protein Sequence MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSVCRCDNGFIYCNDRG LTSIPADIPDDATTLYLQNNQINAGIPQDLKTKVNVQVIYLYVNDLDEFPINLPRSLRELHLQDNNVRTI ARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSKQLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTI PLHAFKGLNSLRRLVLDGNLLANQRIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISH IPYNTLAKMRELERLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGL MCQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAARTTASNHASATTPQGSLFTLKAKRPGLRLPDSNI DYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAVGSITETLVQGDKTEYLLTAL EPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTTTLNQEQNAGPMASLPLAGIIGGAVALVFLFL VLGAICWYVHQAGELLTRERAYNRGSREKDDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIF PSNGSSLCKATHTIGYGTTRGYRDGGIPDIDYSYT A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 19B. Table 19B. Comparison of the NOV19 protein sequences. NOV19a --- MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSV NOV19b ----------------------------------------- GSAAAPFTGSIDSTTCPSV NOV19c ----------------------------------------------------------- NOV19d ----------------------------------------------------------- NOV19e TGSMVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLTAFLTEVIDSTTCPSV NOV19f --- MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSV NOV19g --- MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSV NOV19h ------------------------------------------------------ TTCPSV NOV19i ---MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSV NOV19j ---------- TATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSV NOV19k ---MVVAHPTATATTTPTATVTATVVMTTATMDLRDWLFLCYGLIAFLTEVIDSTTCPSV NOV19a CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19b CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19c --------------GSAAAPFTGSDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19d --------------GSAAAPFTGSDATTLYLQNNQINNAGTPQDLKTKVNVQVIYLYEND NOV19e CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19f CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND 338 WO 03/093432 PCT/US03/13690 NOV19g CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19h CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19i CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVTYLYEND NOV19j CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19k CRCDNGFIYCNDRGLTSIPADIPDDATTLYLQNNQINNAGIPQDLKTKVNVQVIYLYEND NOV19a LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19b LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19c LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19d LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19e LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19f LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19g LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19h LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19i LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSTEEDAFADSK NOV19j LDEFPINLPRPLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19k LDEFPINLPRSLRELHLQDNNVRTIARDSLARIPLLEKLHLDDNSVSTVSIEEDAFADSK NOV19a QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19b QLKLLFLSRNELSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV190 QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19d QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19e QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NQV19f QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19g QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19h QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19i QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19j QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19k QLKLLFLSRNHLSSIPSGLPHTLEELRLDDNRISTIPLHAFKGLNSLRRLVLDGNLLANQ NOV19a RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19b RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19c RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19d RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19e RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19f RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19g RIADDTFSRLQNLTELSLVRNSLAAPPL----------YLQDNAISHIPYNTLAKMRELE NOV19h RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19i RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19j RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19k RIADDTFSRLQNLTELSLVRNSLAAPPLNLPSAHLQKLYLQDNAISHIPYNTLAKMRELE NOV19a RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVARAAVVNVRGLMC NOV19b RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOV19c RLDLSNNNLTTLPRGLFDDLG-LEGKGGRADPAFLY----------------------- NOV19d RLDLSNNNLTTLPRGLFDDLG-NLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLM NOV19e RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOVl9f RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOV19g RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOV19h RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOV19i RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOV19j RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOV19k RLDLSNNNLTTLPRGLFDDLGNLAQLLLRNNPWFCGCNLMWLRDWVKARAAVVNVRGLMC NOV19a QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19b QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19c ---------------------------------------------------------- 339 WO 03/093432 PCT/US03/13690 NOV19d CQGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKR NOV19e QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19f QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19g QGPEKVRGMAIKDITSEVESVLRRAPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19h QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19i QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19j QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHATATTPQGSLFTLKAKRP NOV19k QGPEKVRGMAIKDITSEMDECFETGPQGGVANAAAKTTASNHASATTPQGSLFTLKAKRP NOV19a GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19b GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19c ----------------------------------------------------------- NOV19d PGLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPA NOV19e GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19f GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19g GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19h GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19i GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19j GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19k GLRLPDSNIDYPMATGDGAKTLAIHVKALTADSIRITWKATLPASSFRLSWLRLGHSPAV NOV19a GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19b GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19c ----------------------------------------------------------- NOV19d VGSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPT NOV19e GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19f GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19g GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19h GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19i GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19j GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19k GSITETLVQGDKTEYLLTALEPKSTYIICMVTMETSNAYVADETPVCAKAETADSYGPTT NOV19a TLNQEQNAGPMASLPLAGTIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSREK NOV19b TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKK NOV19c ---------------------------------------------------------- NOV19d TTLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRK NOV19e TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKK NOV19f TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKK NOV19g TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTREPAYNRGSRKK NOV19h TLNQEQNAG-------------------------------------------------- NOV19i TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKK NOV19j TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKK NOV19k TLNQEQNAGPMASLPLAGIIGGAVALVFLFLVLGAICWYVHQAGELLTRERAYNRGSRKK NOV19a DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT NOV19b DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT NOV19c --------------------------------------------------------- NOV19d KDDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYG NOV19e DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT NOV19f DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT NOV19g DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT NOV19h ----------------------------------------------------------- NOV19i DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT NOV19j DDYMESGTKKDNSILEIRGPGLQMLPINPYRAKEEYVVHTIFPSNGSSLCKATHTIGYGT NOV19k DDYMESGTKKDNSILEIRGPGLQMLPINPYAKEEYVVHTIFPSNGSSLCKATHTIGYGT 340 WO 03/093432 PCT/US03/13690 NOVl9a TRGYRD-GGIPDIDYSYT- ---------------------- NOV19b TRGYRD-GGIPDIDYSYTLEGKGGRA-------------- NOV19c ---------------------------------------- NOV19d TTRGYRDGGIPDIDYSYTLEGKGGRPDPAFLYTAGIIRSHC NOV19e TRGYRD-GGIPDIDYSYTLEG------------------- NOV19f TRGYRD-GGIPDIDYSYT---------------------- NOV19g TRGYRD-GGIPDIDYSYT----------------------- NOV19h ---------------------------------------- NOV19i TRGYRD-GGIPDIDYSYT---------------------- NOV19j TRGYRHCHHLPDIDYSYTRSPT ------------------ NOV19k TRGYRD-GGIPDIDYSYT- ---------------------- NOV19a (SEQ ID NO: 296) NOV19b (SEQ ID NO: 298) NOV19c (SEQ ID NO: 300) NOV19d (SEQ ID NO: 302) NOV19e (SEQ ID NO: 304) NOV19f (SEQ ID NO: 306) NOV19g (SEQ ID NO: 308) NOV19h (SEQ ID NO: 310) NOV19i (SEQ ID NO: 312) NOV19j (SEQ ID NO: 314) NOV19k (SEQ ID NO: 316) Further analysis of the NOV19a protein yielded the following properties shown in Table 19C. Table 19C. Protein Sequence Properties NOV19a SignalP analysis: Cleavage site between residues 52 and 53 PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 0; pos.chg 0; neg.chg 0 H-region: length 29; peak value 8.99 PSG score: 4.59 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -3.42 possible cleavage site: between 53 and 54 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al's method for TM region allocation Init position for calculation: 1 Tentative number of TMS(s) for the threshold 0.5: 2 Number of TMS(s) for threshold 0.5: 1 INTEGRAL Likelihood =-10.46 Transmembrane 553 - 569 PERIPHERAL Likelihood = 4.93 (at 493) ALOM score: -10.46 (number of TMSs: 1) MTOP: Prediction of membrane topology (Hartmann et al.) Center position for calculation: 560 Charge difference: 4.5 C( 1.5) - N(-3.0) 341 WO 03/093432 PCT/US03/13690 C > N: C-terminal side will be inside >>>Caution: Inconsistent mtop result with signal peptide >>> Single TMS is located near the C-terminus >>> membrane topology: type Nt (cytoplasmic tail 1 to 552) MITDISC: discrimination of mitochondrial targeting seq R content: 0 Hyd Moment(75): 3.83 Hyd Moment(95): 1.63 G content: 0 D/E content: 1 S/T content: 12 Score: -2.21 Gavel: prediction of cleavage sites for mitochondrial preseq cleavage site motif not found NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 9.2% 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: too long tail Dileucine motif in the tail: found LL at 152 LL at 181 LL at 233 LL at 323 LL at 324 checking 63 PROSITE DNA binding motifs: Leucine zipper pattern (PS00029): *** found *** LFLSRNHLSSIPSGLPHTLEEL at 182 342 WO 03/093432 PCT/US03/13690 LDLSNNNLTTLPRGLFDDLGNL at 299 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: nuclear Reliability: 55.5 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 30.4 %: nuclear 26.1%: cytoplasmic 13.0 %: Golgi 13.0 %: mitochondrial 8.7 %: endoplasmic reticulum 4.3 %: vesicles of secretory system 4.3 %: peroxisomal >> prediction for CG54254-04 is nuc (k=23) A search of the NOV19a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 19D. 343 WO 03/093432 PCT/USO3/13690 Table 19D. Geneseq Results for NOV19a NOV19a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAE23800 Proteoglycan-like (NOV3) protein - 1..674 673/674 (99%) 0.0 Unidentified, 674 aa. 1..674 674/674 (99%) [WO200230979-A2, 18-APR-2002] AAU00692 Proteoglycan-like protein - Homo 1..674 673/674 (99%) 0.0 sapiens, 674 aa. [WO200129217- 1..674 674/674 (99%) _ _ A2, 26-APR-2001] AAU12189 Human PRO1483 polypeptide 1..674 673/674 (99%) 0.0 sequence - Homo sapiens, 674 aa. 1..674 674/674 (99%) [WO200140466-A2, 07-JUN-2001] AAM40226 Human polypeptide SEQ ID NO 1..674 673/674 (99%) 0.0 3371 - Homo sapiens, 674 aa. 1..674 674/674 (99%) [W0200153312-Al, 26-JUL-2001] AAE23802 Fibromodulin-like (NOV5) protein - 1..674 655/674 (97%) 0.0 Unidentified, 664 aa. 1..664 658/674 (97%) ... ..... [W 0200230979-A2, 18-APR-2002]......... ..... ____ In a BLAST search of public sequence databases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19E. 344 WO 03/093432 PCT/USO3/13690 Table 19E. Public BLASTP Results for NOV19a Protein NOV19a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value Residues Portion Q8WVA2 Hypothetical protein - Homo sapiens 1..674 673/674 (99%) 0.0 (Human), 674 aa. 1..674 674/674 (99%) Q9NZUI Leucine-rich repeat transmembrane 29..674 646/646 (100%) 0.0 protein FLRT1 precursor 1..646 646/646 (100%) (Fibronectin-like domain-containing leucine-rich transmembrane protein 1) - Homo sapiens (Human), 646 aa. Q9NZU0 Leucine-rich repeat transmembrane 53..674 377/627 (60%) 0.0 protein FLRT3 precursor 30..649 465/627 (74%) (Fibronectin-like domain-containing leucine-rich transmembrane protein 3) - Homo sapiens (Human), 649 aa. CAC33411 Sequence 5 from Patent WO0 110902 53..674 377/627 (60%) 0.0 - Homo sapiens (Human), 649 aa. 30..649 464/627 (73%) Q8BGT1 Fibronectin leucine rich 53..674 375/627 (59%) 0.0 transmembrane protein 3 homolog - 30..649 462/627 (72%) Mus musculus (Mouse), 649 aa. PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19F. Table 19F. Domain Analysis of NOV19a Identities/ Pfam Domain NOV19a Match Region Similarities Expect Value for the Matched Region LRRNT 53..80 12/35 (34%) 1.le-05 19/35 (54%) LRR 128..151 8/25 (32%) 0.11 21/25(84%) LRR 178..197 10/25 (40%) 0.38 18/25 (72%) LRR 199..222 10/25(40%) 0.0026 23/25(92%) LRR 271..294 5/25 (20%) 0.056 22/25(88%) 345 WO 03/093432 PCT/US03/13690 LRR 295..318 13/25 (52%) 0.00046 21/25 (84%) LRRCT 328..379 15/54 (28%) 8.2e-13 43/54 (80%) fn3 435..513 16/88(18%) 0.12 54/88 (61%) Example 20. The NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A. Table 20A. NOV20 Sequence Analysis NOV20a, CG96778-02 SEQ ID NO: 325 1365 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 1363 ATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGATCACA GCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAGCAGA AAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATATGAT AAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACACAT TCCAGAGAACTGTGACTACAGTGTTTGCCCACTTTTGGAAGCTTGCACTCTATACCTAGATGCGTTTT TCCTTCTTCTAACTGGTTCCAACCTTAACTTGCACCTAAACCTTGGAGGTCTTGGACTTGGAACTTTT GATGCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAA TTCTTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAA TGACTGAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGT ATAAAGACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAA CGGAGGAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATA AAGCCTTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTAAAC ATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGT TTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAG CTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAA ACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGT TGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAATACCTATT ATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATA CTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCA GATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAA ATTAA NOV20a, CG96778-02 SEQ ID NO: 326 454aa MWat 50270.lkD Protein Sequence MAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYD KTGEYPVPLIRRAWELGLMNTHIPENCDYSVCPLLEACTLYLDAFFLLLTGSNLNLHLNLGGLGLGTF DACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAG IKTKAEKKGDEYIINGQKMWITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELN MGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERK TFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQI LGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN NOV20b, CG96778-01 SEQ ID NO: 327 3387 bp DNA Sequence ORF Start: ATG at 1387 ORF Stop: TAA at 2650 CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACAT GTTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAG GCATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGG 346 WO 03/093432 PCT/11S03/13690 ACAIXAGGAGACATGAATAGACAATTCCTAIXTCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACA CCACCACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTT CCTGGTACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGkCTAACACACTA TAATTCCCAGAAGACAAAGTAGGGGAATACATAACAGGATATAGATTTTAACAGCTATTAGAT GAATTTATGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTAC CACTCAAAACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCA CTTCCATCATTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAOGACACCA CACGGAAGCTACGCTGATAGGAAGCATTCTACATA TTCTCTTTTAAATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGCATTTGAGAGCAJATG TACTAATACTTTGAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAGGTGAA GGCTGACCACGGGGCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCAC CGCGCCGCA-AGTCCCCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCG CCCTGGCTCTCTTTCCGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAJACGCAG AAAACCAAACCAGGACTATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGAC GGCGCACGCAAGGGTCACGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAG CGCAGCGCCCCGTCCTTCCGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTC CAGTGGGCGGGACCAGAGGAGTCCCGCGTTCGGGGAGTATGTCAALGGCCGTGACCCGTGTATTATTGT CCGAGTGGCCGGAACGGAGAGCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGT ATTTCTCGTTTTCATTGGAGATCACAGCATACAAAAGCCJXATCGACAACGTGAACCAGGATTAGGATT TATTGGTACACGAAAATTAGTCGTGA.TTCAAAGA TCATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTG GACTGTATACCCCTCAAAATTGGTTGATGACTTAG TTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGTTCAGACTGCTATTGAGGATTCTT GAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAGCTCCTGCTJATAGCC TTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGGGATTACATGGG CCGGTTCGTCAAGATTTCGAAGGAGGCAAAATTTA TTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAACCAGACCTGTAGTAGCTGCT GGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAALCTTT CGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGTGGCTGAGTTGAAC TAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCT TCTATTGCAAJAGGCATTTGCTGGAGATATTGCAAA)TCAGTTAGCTACTGATGCTGTG3CAGATACTTGG AGGCAATGGATTTAATACAGAATATCCTGTAGAAACTATGAGGGATGCCAXJXATCTATCAGATTT GGCTTTAACGTTTTTTCCAGTGAACAATCCTCTTATATTATCTAGCACTGCTTATTATAGT AGTTTATACTTTTGCTTACTCTGTTATGTCTCTTAGCAGGTTTGGTTTTTATTAATGATGTGTT TTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAACTACATAGGTTATTTTGATCTCTTAA GATTAATGTAGCAGAATTTCTTGGAATTTTATTTTTGTATGACAGAAGTGGGCTTAGAAGTAT TCAAGATGTTACAAATTTACATTTAGAATATTGTAGTATTTGATACTGTCAACTTGACAGTAAC TTTGTAGACTTAATGGTATTATTAGTTCTTTTTATTGCAGTTTGGAAGCATTTGTGACTTTCT GTTTGGCACAGAAACAGTCAAATTTTGACATTCATATTCTCCTATTTTACAGCTACAAGACTTTCT TGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTATATCATAAGCTTGC CTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCTATTGTACACAATCTCATTTC ATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTATTATCAT MAAGFGRCCRVLRS ISRFHWRSQHTKAflRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEY KTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPI IIA GNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKGDEYIINGQKaMWITNrGGFcN FLL AP.SDPDPKAPAKFTGIVEATPGIQIGRKELNGQRCSDTRGIVFEDVxVPKNVLIGDGAGFKV AMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRA AWEVDSGRPNTYYAS IAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQP. ILIVAREH -IDKYKN SID NO: 329 18bp 347 WO 03/093432 PCT/US03/13690 NOV20c, 276657466 SEQ ID NO: 329 bp DNA Sequence TTGGCAG CGTT ~AT CACAGCATACAAAAGCCAATCGACAAC TGAACCAGGATTAGGATTTAGTTTTGAG UGGGAGAGGAAANFGAC-TACGGWT-CAA- T-TGGG-AGAGAGGAAAT-GAUGGG-CAG-T GGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTT TAATGAACACACACATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATT AGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAAT GCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTOGGGAGAATGACTGAGGAGCCAT TGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCA GAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAA TTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAA4GCTCCTGCTAATAAAGCCTTTACTGGAT TCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAAAGGAATTAAACATGGGCCAGCGATGT TCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGG AGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTG GATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTA CTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAAT GAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAA AGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGA TTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTAC TTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAAATGTCGACGGC NOV20c, 276657466 SEQ ID NO: 330 429 aa MW at 47401.7kD Protein Sequence TRSPTMAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPV AAEYDKTGEYPVPLIRPAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQM PIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKAN WYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVRVPKENVLIGDG AGPKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARM SYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGT SQIQRLIVAREHIDKYXNVDG SEQ ID NO: 331 1387 bp OqRF Start: at 2 IORF Stop: end of sequence CACCAGATCTCCCAkCCATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTT TTCATTGGAGATCACAkGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAG TTCACCGAACAGCAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGT GGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTOGGAACTTGGTT TAATGAACACACACATTCCAGAGAACTGTGACTACAGTGTTTGCCCACTTTTGGAAGCTTGCACTCTA TACCTAGATGCGTTTTTCCTTCTTCTAACTGGTTCCAACCTTAACTTGCACCTAAACCTTGGAGGTCT TGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGA CTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAG AAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGG CTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGA AGATGTGGATAACCAACGGAG3GAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCT AAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGG GAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAG TGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAA ACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTA TGCCCTGGAAAGGAAAACTTTCGGAA.AGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTG AAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGT CGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTAC TGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAACTAATGAGGG ATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACAC ATTGACAAGTACAAAAATGTCGACGGC NOV20d, 276657530 SEQ ID NO: 3321462 aa JMW at 51083.9kD Protein Sequence 348 WO 03/093432 PCT/US03/13690 TRSPTMAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPV AAEYDKTGEYPVPLIRRAWELGLMNTHIPENCDYSVCPLLEACTLYLDAFFLLLTGSNLNLHLNLGGL GLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAG SDVAGIKTKAEKKGDEYIINGQKWITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIG RKELNMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKY ALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLAT DAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG NOV20e, 276657538 SEQ ID NO: 333 1300bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence CACCAGATCTCCCACCATGGCAGCGGGGTTCGGGCGATGCTGCAGGTGTTCTTTACAGGTCCTGAGAA GTATTTCTCGTTTTCATTGGAGATCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGA TTTAGTTTTGAGTTCACCGAACAGCAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGA AATCATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCT GGGAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGAT GCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTC TTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGA CTGAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATA AAGACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGG AGGAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAG CCTTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAAAAAGGAATTAAACATG GGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTT AATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGCTG CTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACT TTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGA ACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATG CTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTT GGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCAGAT TTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAAATG TCGACGGC NOV20e, 276657538 SEQ ID NO: 334 433 aa 47805.2kD Protein Sequence TRSPTMAAGFGRCCRCSLQVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREE IIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGOTGVQTAIEGNS LGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNG GKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGKKELNMGQRCSDTRGIVFEDVKVPKENVL IGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVE LARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQI YEGTSQIQRLIVAREHIDKYKNVDG NOV20f, 276657616 SEQ ID NO: 335 $1147 bp DNA Sequence ORF Start: at 2 ORF Stop: end of sequence CACC6AGATCTTTCACCGAACAGCAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAA TCATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGG GAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGC TTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTT TGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACT GAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAA GACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAG GAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCC TTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGG CCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAA TTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCT GGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTT CGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGAAC 349 WO 03/093432 PCT/US03/13690 TAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCT TCTATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTTGG AGGCAATGGATTTAATACAGAATATCCTGT.AGAAAAACTAATGAGGGATGCCAAAATCTATCAGATTT ATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGTCGACGGC NOV20f, 276657616 SEQ ID NO: 336 382 aa MW at 41891.5kD Protein Sequence TRSFTEQQKEFQATARKFAREIIPVAAYDKTGEYPVLTRRAWFLG LMTHTPENCGGLGL:GTFDA CLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIK TKAEKRGDEYIINGQKMWITNGGKANWYPLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMG QRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTF GKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAPAGDIANQLATDAVQILG GNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIVDG JNOV20g, CG96778-03 SEQ ID NO: 337 1278 bp DNA Sequence ORF Start: ATG at 1 ORF Stop: TAA at 1276 ATGGCAGCGGGGTTCGGGCGATGCTGCAGGTGTTCTTTACAGGTCCTGAGAAGTATTTCTCGTTTTCA TTGGAGATCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCA GACACACACATTCCAGAGACTGTGGAGGTCTTGGACTTGGACTTTTGATGCTTGTTTATAT AAGAATTGGCTTATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCT AkTTATTATTGCTGGA-AATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGAT GTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAA AGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGG TATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCAT TGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAAAAAGGAATTAAACATGGGCCAGCGATGTTCAG ATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTOGTGACGGAGCT GGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATT AGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTG TAGAGCACCAAGCAATATCATTTATGCTGGCTGAATGGCAATGAAAGTTGAACTAGCTAGAATGAGT TACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGC ATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTA ATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCA CAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAAAATTAA NOV20g, CG96778-03 SEQ ID NO: 338 425 aa MWat 46991.4kD Protein Sequence MAAGFGRCCRCSLQVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVA AEYDKTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMP IIIAGNDQQKKKYLGRMTEEPLMAYCTEPGAGSDVAGIKTAKKGDEYI INGQKMWITNGGAN YFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGKKELNMGQRCSDTRGIVFEDVKVPKENVLIGDGA OGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMS YQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTS QIQRLIVAREHIDKYKN OV2Oh, 13382351 SNP for SEQ ID NO: 339 3387 bp SNP: 1673 G/T CG96778-01 ORF Start: ATG at ORF Stop: TAA at 2650 DNA Sequence 1387 CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTA T TTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTTACAGTAAGAAGGGGTTACAATAGGCAT ATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAACAAA GGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCACCACT TTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGGTACTT TCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAAATTCCCAGA AGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTATGGGTGA CCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAAACTCAGGG TCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCATT 350 WO 031093432 PCT/US03/13690 CCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGACAAGTCATAA ACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAAATTTTAAGGAA ACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTTGAATCCGCCAAG CAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGGGCCGCTCTCCCTC CAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCCCCCCACCGTTCAGC GCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTCCGCGCTGCGTCAGCC TCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGACTATCAGAGATTGCCCG GAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCACGGAGCATGCGTTGGCT ATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTCCGCAGCCCAACCGCCTCT TCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGGAGTCCCGCGTTCGGGGAGT ATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGAGCCAACATGGCAGCGGGGTT CGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGATCACAGCATACAAAAGCCAAT CGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAGCAGAAAGAATTTCAAGCTACTG CTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGT CCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGTAGGTCTT GGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAGACTG CTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAACAAAAGAAGAAGTA TTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGTGTAACAGAACCTGGAGCAGGCTCTGAT GTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAGTATATTATTAATGGTCAGAAGATGTGGA TAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGC TAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTA AACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAAAATG TTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACCAGACCTGTAGTAGC TGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACCAAGTATGCCCTGGAAAGGAAAACT TTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCATTTATGCTGGCTGAAATGGCAATGAAAGTTGAAC TAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCTTC TATTGCAAAGGCATTTGCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGC AATGGATTTAATACAGAATATCCTGTAGAAAALACTAATGAGGGATGCCAAAATCTATCAGATTTATGAAG GTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAATTAAAAAAATTA CTGTAGAAATATTGAATAACTAGAACACAAGCCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACG TTTTTTCCAGTGAAAACAAATCCTCTTATATTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTT TGCTTAACTCTGTTATGTCTCTTAAGCAGGTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCAC TTTACTTGAATTACATTAACCTAGAAAACTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAA ATTTCTTGGAATTTTATTTTTGTAATGACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATT TACATTTAGAAAATATTGTAGTATTTGAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATT ATTAAAGTTCTTTTTATTGCAGTTTGGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAA ATTTTGACATTCATATTCTCCTATTTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGC CCATATTTCACTTACCTTATTTAAAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTG GTCTCTAGGTAGCCTTTGGTCTATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTA ATAAAATTGTTCAGTGCTTATTATCAT NOV20h, 13382351 SNP for SEQ ID NO: 421 aa SNP: Gly to Val at position 96 CG96778-01 340 Protein Sequence MAAGFGRCCRVLRS ISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYDKT GEYPVPLIRRAWELGLMNTHIPENCVGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGNDQ QKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKANWYFLLARSDPD PKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKT RPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRN TYYASIAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYK N NOV20i, 13382352 SNP for SEQ ID NO: 341 3387 bp SNP: 1717 CG96778-01 G/C DNA Sequence ORF Start: ATG at ORF Stop: TAA at 1387 12650 CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC 351 WO 03/093432 PCT/11S03/13690 A TATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAATGTTCAGAATAAGAATTGGAAC AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAA.GAGTCCGCTTTGTGTTTTCATTACACACCAC CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG TACTTTCACTTTGA2ATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATATT CCCAGAAGACAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA TGGGTGACCTTTATTGGGCAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCAkTCA TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA CAAGTCATAACAGCCTTGGGATACGCGGALGGTCAATTTACCTAACAATTA4\ATTCTCTTTTAA ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTT GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAGGCTrGACCACcG GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCALGTCC CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC TATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA CGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG AGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAG CAGAAAGAATTTCAAGCTACTGCTCOTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATA2AAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAACAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAGACCAAAGCAGAAGAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAAC.GGAGGAAAAGCTAATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAkGTTGCAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGAAATGGCAJ\TGAJAAGTTGAACTACTAGATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCmGGCATTTGCTGGAGATATTGCAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC CGTGAACACATTGACAAGTACAAAAATTAAAAAAATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAGAAGGGCTTTAACGTTTTTTCCAGTGAAA-ACAAALTCCTCTTATA TTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG GTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAA CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG ACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT GAATACTGTCAACTTGACAGTAACTTTGTAGACTTA1ATGGTATTATTAAAGTTCTTTTTATTGCAGTTT GGAAGCATTTGTGAAACTTTCTGTTTGGCACAGA\CAGTCAAAATTTTGACATTCATATTCTCCTAT TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTA AAATAALATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT ATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAALAGAACTTAATAAAATTGTTCAGTGCTTAT TATCAT MAAGFGRCCRVLRS ISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEI IPVAAEYDK TGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEQLAYGCTGVQTAIEGNSLGQMPII TAGN DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYI INGQKMWITNOGKA1NWYFLLARS DPDPKAPANAFTGFIVEADTPGIQIGRCELNNGQRCSDTRGIFEDVKVPKENVLIGDGAGFKvAMGA FDKTRPVVAAGAVGLAQALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQ.AAWEVD SGRRNTYYAS IAKAFAGDIANQATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVE 352 WO 03/093432 PCT/US03/13690 HIDKYKN NOV20j, 13382353 SNP for SEQ ID NO: 343 3387 bp SNP: 2204 C/T CG96778-01 ORF Start: ATG at 1387 ORF Stop: TAA at 2650 DNA Sequence CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC ATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAAC AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCAC CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG TACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAAATT CCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA TGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCA TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA CAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAA ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTT GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGG GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCC CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC TATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA CGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG AGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAG CAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGTAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC CGTGAACACATTGACAAGTACAAAAATTAAAAAAATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATA TTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG GTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAA CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG ACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT GAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTT GGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAAATTTTGACATTCATATTCTCCTAT TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTA AAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT ATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTAT TATCAT NOV20j, 13382353 SNP for SEQ ID NO: 344 421 aa SNP: Ala to Val at 273 CG96778-01 Protein Sequence 353 WO 03/093432 PCT1US03113690 MAAGFGRCCRVLRS ISRFHWRSQHTKA1NRQREPGIJGFSFEFTEQQKEFQATARKFAREEI IPVAAEYDK TGEYPVPLIRRAWELGLMNTHIPENCGGL.GLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPII IAGW DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKANWYFLLARS DPDPKAPANKAFTGFIVEADTPGIQIGRKELJMGQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVVMGA FDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVD SGRRNTYYAS IAKAFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAJKIYQIYEGTSQIQRLIVARE IIIDKYKN NOV2Ok, 13382354 SNP for ~SEQ ID NO: 345 ~3387 bp SNP: 2547 M/G CG96778-01c ORF Start: ATG at 1387 OR tp TAA at 2650 CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC ATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAAC AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCAC CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG TACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAA.ATT CCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA TGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCA TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA CAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAA ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTA&TACTTT GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGG GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCC CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC TATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA CGOAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG AGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGACAG CAGAAAGAATTTCAAGCTACTGCTCGTA.AATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATAA1AACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTAkTTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAALAAGCTZXATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAAGTATGCCCTGGAAALGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGZAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTGGAAAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC CGTGAACACATTGACAAGTACAAAAATTAA-ATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATA TTAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG GTTTGGTTTTTATTAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAG2AA CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG ACAGAAAAGTGGGCTTAGAA\AGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT GAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTT GGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAAATTTTGACATTCATATTCTCCTAT TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCAC!TTACCTTATTTA 354 WO 03/093432 PCT/US03/13690 AAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT ATTGTACACAATCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTAT TATCAT NOV20k, 13382354 SNP SEQ ID NO: 421 aa SNP: no change in the protein for 346 sequence CG96778-01 Protein Sequence MAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYDK TGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKANWYFLLARS DPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVPENVLIGDGAGFVAMGA FDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVD SGRRNTYYASIAK(AFAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVARE HIDKYKN NOV201, 12252113 SNP for SEQ ID NO: 347 3387 bp SNP: 3324 CG96778-01 DNA Sequence ORF Start: ATG at lORF Stop: TAA at 1387 ]2650 CTGCAGGACAGACAAACAAGGGGGTAGCTTGCTTGGGTGAATGGTGGCAGGAACTACCGACTAGACATG TTTAAGATGAGGGCTCCATCTTCGCTTCTCTGCCAGCCACGTGTACAGTAAGAAGGGGTTACAATAGGC ATATGGGTGATTTTGTGCTTTTCGTTCATCTTTTCTGTGTTTAAAATGTTCAGAATAAGAAATTGGAAC AAAGGAGACATGAATAGACAATTCCTAATCATCTTTAAGAGTCCGCTTTGTGTTTTCATTACACACCAC CACTTTGAAGGCTTTCTTGCCTATACCAGGACAAACTCAGCTCTTTATCCCTTTTCCGAATTTTCCTGG TACTTTCACTTTGAATATAGCGCTTAATTAACATTCTGCCTTGTACCTAGGACTAACACACTATAAATT CCCAGAAGACAAAGTAGGGGAATACAATAACAGGATATAGAATTTTAACAGCTAAATTAGATGAATTTA TGGGTGACCTTTATTGGGCAAAAGAAAATGTTAAGTTAGTATAAGATTTAGTATAAGCTACCACTCAAA ACTCAGGGTCTCACTGGAAGAGAAAGTGACTCCAGGTAGAATTCCTCAGGGAGACATTCACTTCCATCA TTCGCTGAACCAGGAGCTTTGGACAGCCTCGGATTGCACCCGCATATCCAAGGACACCACATCAGCGGA CAAGTCATAAACAGCCTTGGGAATACGCGGAAAGGTCAAATTTACCTAAACAATTAAATTCTCTTTTAA ATTTTAAGGAAACACAAGTATGCTTTCGCTTTAGGTAGGGCATTTGAGAGCAAAATGTACTAATACTTT GAATCCGCCAAGCAGACACGATCTGGGTTTGACCTTTCTCTCCGGGTAAAGGTGAAGGCTGACCACGGG GCCGCTCTCCCTCCAGCCCCAGCCACGCCCTCTAACCCAGGTTCCCGTCCTGCACCGCGCCGCAAGTCC CCCCACCGTTCAGCGCAACCGGCCCTCCCAGCCCCGCCGCCGTCCCCCTCCCCGCCCTGGCTCTCTTTC CGCGCTGCGTCAGCCTCGGCGTCCCACAGAGAGGGCCAGAGGTGGAAACGCAGAAAACCAAACCAGGAC TATCAGAGATTGCCCGGAGAGGGGATGCGACCCCTCCCCAGGTCGCAGCGACGGCGCACGCAAGGGTCA CGGAGCATGCGTTGGCTATCCGGCGCCGGGGACCGCTGCCACCCCGCCTAGCGCAGCGCCCCGTCCTTC CGCAGCCCAACCGCCTCTTCCCGCCCCGCCCCATCCCGCCCCACGGGCTCCAGTGGGCGGGACCAGAGG AGTCCCGCGTTCGGGGAGTATGTCAAGGCCGTGACCCGTGTATTATTGTCCGAGTGGCCGGAACGGAGA GCCAACATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGGAGA TCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAGTTCACCGAACAG CAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATCATCCCAGTGGCTGCAGAATAT GATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGAGCCTGGGAACTTGGTTTAATGAACACACAC ATTCCAGAGAACTGTGGAGGTCTTGGACTTGGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCT TATGGATGTACAGGGGTTCAGACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCT GGAAATGATCAACAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGT GTAACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGAGATGAG TATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGGTATTTTTTATTGGCA CGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACTGGATTCATTGTGGAAGCAGATACC CCAGGAATTCAGATTGGGAGAAAGGAATTAAACATGGGCCAGCGATGTTCAGATACTAGAGGAATTGTC TTCGAAGATGTGAAAGTGCCTAAAGAAAATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATG GGAGCTTTTGATAAAACCAGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGAT GAAGCTACCAAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA TTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCAGCTTGGGAG GTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTTGCTGGAGATATTGCAAAT CAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGATTTAATACAGAATATCCTGTAGAAAAA CTAATGAGGGATGCCAAAATCTATCAGATTTATGAAGGTACTTCACAAATTCAAAGACTTATTGTAGCC 355 WO 03/093432 PCT/US03/13690 CGTGAACACATTGACAAGTACAAAAATTAAAAAAATTACTGTAGAAATATTGAATAACTAGAACACAAG CCACTGTTTCAGCTCCAGAAAAAAGAAAGGGCTTTAACGTTTTTTCCAGTGAAAACAAATCCTCTTATA TTAAATCTAAGCAACTGCTTATTATAGTAGTTTATACTTTTGCTTAACTCTGTTATGTCTCTTAAGCAG GTTTGGTTTTTATTAAAATGATGTGTTTTCTTTAGTACCACTTTACTTGAATTACATTAACCTAGAAAA CTACATAGGTTATTTTGATCTCTTAAGATTAATGTAGCAGAAATTTCTTGGAATTTTATTTTTGTAATG ACAGAAAAGTGGGCTTAGAAAGTATTCAAGATGTTACAAAATTTACATTTAGAAAATATTGTAGTATTT GAATACTGTCAACTTGACAGTAACTTTGTAGACTTAATGGTATTATTAAAGTTCTTTTTATTGCAGTTT GGAAAGCATTTGTGAAACTTTCTGTTTGGCACAGAAACAGTCAAAATTTTGACATTCATATTCTCCTAT TTTACAGCTACAAGAACTTTCTTGAAAATCTTATTTAATTCTGAGCCCATATTTCACTTACCTTATTTA AAATAAATCAATAAAGCTTGCCTTAAATTATTTTTATATGACTGTTGGTCTCTAGGTAGCCTTTGGTCT ATTGTACACAACCTCATTTCATATGTTTGCATTTTGGCAAAGAACTTAATAAAATTGTTCAGTGCTTAT TATCAT NOV201, 12252113 SNP for SEQ ID NO: 421 aa SNP is in the non coding CG96778-01 348 region Protein Sequence MAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEIIPVAAEYDK TGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKANWYFLLARS DPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVVPKENVLIGDGAGFKVAMGA FDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVD SGRRNTYYASIAKAAGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVARE IHIDKYKN A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 20B. 356 WO 03/093432 PCT/US03/13690 Table 20B. Comparison of the NOV20 protein sequences. NOV20a ----- MAAGFGRCCR ---- VLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQAT NOV20b ----- MAAGFGRCCR----VLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQAT NOV20c TRSPTMAAGFGRCCR----VLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQAT NOV20d TRSPTMAAGFGRCCR----VLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQAT NOV20e TRSPTMAAGFGRCCRCSLQVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQAT NOV20f ----------------------------------------------TRSFTEQQKEFQAT NOV20g -----MAAGFGRCCRCSLQVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQAT NOV20a ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCDYSVCPLLEACTLYLD NOV20b ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPEN-----C---------- NOV20c ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCG--------------- NOV20d ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCDYSVCPLLEACTLYLD NOV20e ARKFAREETIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCG--------------- NOV20f ARKFAREETIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCG--------------- NOV20g ARKFAREEIIPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCG--------------- NOV20a AFFLLLTGSNLNLHLNLGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN NOV20b G-----------------GLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN NOV20c G------------------LGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN NOV20d AFFLLLTGSNLNLHLNLGGLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN NOV20e G------------------LGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN NOV20f ------------------GLGLGTFDACLISEELAYGCTGVQTAIEGNSLGQMPIIIAGN NOV20g G------------------LGLGTFDACLISEELAYGCTGVQTATEGNSLGQMPIIIAGN NOV20a DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA NOV20b DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA NOV20c DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA NOV20d DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA NOV20e DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA NOV20f DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYIINGQKMWITNGGKA NOV20g DQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKGDEYTINGQKMWITNGGKA NOV20a NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP NOV20b NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP NOV20c NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP NOV20d NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP NOV20e NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGKKELNMGQRCSDTRGIVFEDVKVP NOV20f NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNMGQRCSDTRGIVFEDVKVP NOV20g NWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGKKELNMGQRCSDTRGIVFEDVKVP NOV20a KENVLTGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA NOV20b KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA NOV20c KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA NOV20d KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA NOV20e KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA NOV20f KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA NOV20g KENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEATKYALERKTFGKLLVEHQA NOV20a ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20b ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20c ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20d ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20e ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG 357 WO 03/093432 PCT/US03/13690 NOV20f ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20g ISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAFAGDIANQLATDAVQILGG NOV20a NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN-- NOV20b NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN-- NOV20c NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG NOV20d NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG NOV20e NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKNVDG NOV20f NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIVDG---- NOV20g NGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYKN-- NOV20a (SEQ ID NO: 326) NOV20b (SEQ ID NO: 328) NOV20c (SEQ ID NO: 330) NOV20d (SEQ ID NO: 332) NOV20e (SEQ ID NO: 334) NOV20f (SEQ ID NO: 336) NOV20g (SEQ ID NO: 338) Further analysis of the NOV20a protein yielded the following properties shown in Table 20C. Table 20C. Protein Sequence Properties NOV20a SignalP analysis: No Known Signal Sequence Predicted PSORT II analysis: PSG: a new signal peptide prediction method N-region: length 10; pos.chg 2; neg.chg 0 H-region: length 2; peak value -5.86 PSG score: -10.26 GvH: von Heijne's method for signal seq. recognition GvH score (threshold: -2.1): -9.99 possible cleavage site: between 14 and 15 >>> Seems to have no N-terminal signal peptide ALOM: Klein et al'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 = 3.39 (at 126) ALOM score: -0.90 (number of TMSs: 0) MITDISC: discrimination of mitochondrial targeting seq R content: 7 Hyd Moment(75): 6.98 Hyd Moment(95): 9.53 G content: 2 D/E content: 1 S/T content: 4 Score: 2.17 Gavel: prediction of cleavage sites for mitochondrial preseq R-2 motif at 39 NRQIRE 358 WO 03/093432 PCT/US03/13690 NUCDISC: discrimination of nuclear localization signals pat4: none pat7: none bipartite: none content of basic residues: 12.1% NLS Score: -0.47 KDEL: ER retention motif in the C-terminus: none ER Membrane Retention Signals: KKXX-like motif in the C-terminus: DKYK 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: Leucine zipper pattern (PS00029): *** found *** LEACTLYLDAFFLLLTGSNLNL at 103 none checking 71 PROSITE ribosomal protein motifs: none checking 33 PROSITE prokaryotic DNA binding motifs: none NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination Prediction: cytoplasmic Reliability: 94.1 COIL: Lupas's algorithm to detect coiled-coil regions total: 0 residues Final Results (k = 9/23): 91.3 %: mitochondrial 4.3 %: nuclear 4.3 %: peroxisomal 359 WO 03/093432 PCT/US03/13690 >> prediction for CG96778-02 is mit (k=23) A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20D. Table 20D. Geneseq Results for NOV20a NOV20a Identities/ Geneseq Protein/Organism/Length [Patent Residues/ Similarities for Expect Identifier #, Date] Match the Matched Value Residues Region AAG66900 Human medium chain acyl-CoA 1..454 414/454 (91%) 0.0 dehydrogenase (ACADM) - Homo 1..421 417/454 (91%) sapiens, 421 aa. [WO200177336-A2, 18-OCT-2001] ABB61315 Drosophila melanogaster polypeptide 10..453 286/444 (64%) e-164 SEQ IDNO 10737 - Drosophila 13..416 338/444 (75%) melanogaster, 419 aa. [WO200171042-A2, 27-SEP-2001] AAU44325 Propionibacterium acnes 34..447 153/417 (36%) le-69 immunogenic protein #5221 - 2..380 227/417 (53%) Propionibacterium acnes, 386 aa. [WO200181581-A2, 01-NOV-2001 ] ABB60897 Drosophila melanogaster polypeptide 42..452 147/412 (35%) 8e-62 SEQ ID NO 9483 - Drosophila 28..403 214/412 (51%) melanogaster, 405 aa. [WO200171042-A2, 27-SEP-2001] ABP10124 Human ORFX protein sequence SEQ 324..443 109/120 (90%) 3e-56 ID NO:20230 - Homo sapiens, 120 1..120 115/120 (95%) aa. [WO200192523-A2, 06-DEC 2001] In a BLAST search of public sequence databases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20E. 360 WO 03/093432 PCT/USO3/13690 Table 20E. Public BLASTP Results for NOV20a Protein NOV20a Identities/ Accession Protein/Organism/Length Residues/ Similarities for Expect Number Match the Matched Value _ _ _ _Residues Portion P11310 Acyl-CoA dehydrogenase, medium- 1..454 421/454 (92%) 0.0 chain specific, mitochondrial 1..421 421/454 (92%) precursor (EC 1.3.99.3) (MCAD) Homo sapiens (Human), 421 aa. Q8HXY8 Medium-chain acyl-CoA 1..454 405/454 (89%) 0.0 dehydrogenase - Macaca fascicularis 1..421 415/454 (91%) (Crab eating macaque) (Cynomolgus monkey), 421 aa. P45952 Acyl-CoA dehydrogenase, medium- 1..454 370/454 (81%) 0.0 chain specific, mitochondrial 1..421 399/454 (87%) precursor (EC 1.3.99.3) (MCAD) Mus musculus (Mouse), 421 aa. Q91WS8 Acetyl-coenzyme A dehydrogenase, 1..454 369/454 (81%) 0.0 medium chain - Mus musculus 1..421 398/454 (87%) (Mouse), 421 aa. P08503 Acyl-CoA dehydrogenase, medium- 1..454 364/454 (80%) 0.0 chain specific, mitochondrial 1..421 396/454 (87%) precursor (EC 1.3.99.3) (MCAD) Rattus norvegicus (Rat), 421 aa. PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20F. Table 20F. Domain Analysis of NOV20a Identities/ Pfam Domain NOV20a Match Region Similarities Expect Value for the Matched Region Acyl-CoA dh N 41..190 51/165 (31%) 1.8e-45 130/165 (79%) Acyl-CoA dh M 192..296 64/106 (60%) 8e-69 104/106 (98%) Acyl-CoA dh 300..449 78/162 (48%) 7.3e-68 126/162 (78%) HpaB 148..454 63/399 (16%) 0.023 203/399 (51%) 361 WO 03/093432 PCT/US03/13690 Example B: Sequencing Methodology and Identification of NOVX Clones 1. GeneCalling m 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 eDNA 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 eDNA 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. 2. SeqCalling TM 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's proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. eDNA 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'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 362 WO 03/093432 PCT/US03/13690 portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations. 3. PathCallingT m Technology: The NOVX nucleic acid sequences are derived by laboratory screening of eDNA 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's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof. The laboratory screening was performed using the methods summarized below: 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 (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, CA) were then transferred from E.coli into a CuraGen Corporation proprietary yeast strain (disclosed in U. S. Patents 6,057,101 and 6,083,693, incorporated herein by reference in their entireties). Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion eDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-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'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. 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) 363 WO 03/093432 PCT/US03/13690 used to make the eDNA 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. Patents 6,057,101 and 6,083,693). 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of eDNA ends (RACE), were used to isolate or complete the predicted sequence of the eDNA 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. 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 predicted 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'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 364 WO 03/093432 PCT/US03/13690 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. 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. 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 The quantitative expression of various NOV genes 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) performed on an Applied Biosystems (Foster City, CA) ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. RNA integrity of all samples was determined 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 (degradation products). Control samples to detect genomic DNA contamination included 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. RNA samples were normalized in reference to nucleic acids encoding constitutively expressed genes (i.e., 13-actin and GAPDH). Alternatively, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Corporation, Carlsbad, CA, Catalog No. 18064-147) and random hexamers according to the manufacturer's instructions. Reactions containing up to 10 gg of total RNA in a volume of 20 ld or were scaled up to contain 50 [Lg of total RNA in a volume of 100 1 and were 365 WO 03/093432 PCT/US03/13690 incubated for 60 minutes at 42 0 C. sscDNA samples were then normalized in reference to nucleic acids as described above. Probes and primers were designed according to Applied Biosystems Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default reaction condition settings and the following parameters were set before selecting primers: 250 nM primer concentration; 58o 600 C primer melting temperature (Tm) range; 590 C primer optimal Tm; 20 C maximum primer difference (if probe does not have 5' G, probe Tm must be 100 C greater than primer Tm; and 75 bp to 100 bp amplicon size. The selected probes and primers were synthesized by Synthegen (Houston, TX). 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: 900 nM forward and reverse primers, and 200nM probe. Normalized RNA was spotted in individual wells of a 96 or 384-well PCR plate (Applied Biosystems, Foster City, CA). PCR cocktails included a single gene-specific probe and primers set or two multiplexed probe and primers sets. PCR reactions were done using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803) following manufacturer's instructions. Reverse transcription was performed at 48o C for 30 minutes followed by amplification/PCR cycles: 95o C 10 min, then 40 cycles at 950 C for 15 seconds, followed by 600 C for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) and plotted 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 was the reciprocal of the RNA difference multiplied by 100. CT values below 28 indicate high expression, between 28 and 32 indicate moderate expression, between 32 and 35 indicate low expression and above 35 reflect levels of expression that were too low to be measured reliably. Normalized sscDNA was analyzed by RTQ-PCR using IX TaqMan@ Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions. PCR amplification and analysis were done as described above. 366 WO 03/093432 PCT/US03/13690 Panels 1, 1.1, 1.2, and 1.3D Panels 1, 1.1, 1.2 and 1.3D included 2 control wells (genomic DNA control and chemistry control) and 94 wells of cDNA samples from cultured cell lines and primary normal tissues. Cell lines were derived from carcinomas (ca) including: lung, small cell (s cell var), non small cell (non-s or non-sm); breast; melanoma; colon; prostate; glioma (glio), astrocytoma (astro) and neuroblastoma (neuro); squamous cell (squam); ovarian; liver; renal; gastric and pancreatic from the American Type Culture Collection (ATCC, Bethesda, MD). Normal tissues were obtained from individual adults or fetuses and included: adult and fetal skeletal muscle, adult and fetal heart, adult and fetal kidney, adult and fetal liver, adult and fetal lung, brain, 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. The following abbreviations are used in reporting the results: metastasis (met); pleural effusion (pl. eff or pl effusion) and * indicates established from metastasis. GENERAL_SCREENING_PANELV1.4, V1.5, V1.6 AND 1.7 Panels 1.4, 1.5, 1.6 and 1.7 were as described for Panels 1, 1.1, 1.2 and 1.3D, above except that normal tissue samples were pooled from 2 to 5 different adults or fetuses. Panels 2D, 2.2, 2.3, and 2.4 Panels 2D, 2.2, 2.3 and 2.4 included 2 control wells and 94 wells containing RNA or cDNA from human surgical specimens procured through the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI), Ardais (Lexington, MA) or Clinomics BioSciences (Frederick, MD). Tissues included human malignancies and in some cases matched adjacent normal tissue (NAT). Information regarding histopathological assessment of tumor differentiation grade as well as the clinical stage of the patient from which samples were obtained was generally available. Normal tissue RNA and cDNA samples were purchased from various commercial sources such as Clontech (Palo Alto, CA), Research Genetics and Invitrogen (Carlsbad, CA). HASS PANEL V1.O The HASS Panel vl.0 included 93 cDNA samples and two controls including: 81 samples of cultured human cancer cell lines subjected to serum starvation, acidosis and anoxia according to established procedures for various lengths of time; 3 human primary 367 WO 03/093432 PCT/US03/13690 cells; 9 malignant brain cancers (4 medulloblastomas and 5 glioblastomas); and 2 controls. Cancer cell lines (ATCC) were cultured using recommended conditions and included: breast, prostate, bladder, pancreatic and CNS. Primary human cells were obtained from Clonetics (Walkersville, MD). Malignant brain samples were gifts from the Henry Ford Cancer Center. ARDAIS PANEL V1.0 The ARDAIS Panel vl.0 included 2 controls and 22 test samples including: human lung adenocarcinomas, lung squamous cell carcinomas, and in some cases matched adjacent normal tissues (NAT) obtained from Ardais. Unmatched malignant and non-malignant RNA samples from lungs with gross histopathological assessment of tumor differentiation grade and stage and clinical state of the patient were obtained from Ardais. ARDAIS PROSTATE V1.0 ARDAIS Prostate v1.0 panel included 2 controls and 68 test samples of human prostate malignancies and in some cases matched adjacent normal tissues (NAT) obtained from Ardais. RNA from unmatched malignant and non-malignant prostate samples with gross histopathological assessment of tumor differentiation grade and stage and clinical state of the patient were also obtained from Ardais. ARDAIS KIDNEY V1.0 ARDAIS Kidney vl.0 panel included 2 control wells and 44 test samples of human renal cell carcinoma and in some cases matched adjacent normal tissue (NAT) obtained from Ardais. RNA from unmatched renal cell carcinoma and normal tissue with gross histopathological assessment of tumor differentiation grade and stage and clinical state of the patient were also obtained from Ardais. PANELS 3D, 3.1 AND 3.2 Panels 3D, 3.1, and 3.2 included two controls, 92 cDNA samples of cultured human cancer cell lines and 2 samples of human primary cerebellum. Cell lines (ATCC, National Cancer Institute (NCI), German tumor cell bank) were cultured as recommended and were derived from: squamous cell carcinoma of the tongue, melanoma, sarcoma, leukemia, lymphoma, and epidermoid, bladder, pancreas, kidney, breast, prostate, ovary, uterus, cervix, stomach, colon, lung and CNS carcinomas. 368 WO 03/093432 PCT/US03/13690 Panels 4D, 4R, and 4.1D Panels 4D, 4R, and 4.1D included 2 control wells and 94 test samples of RNA (Panel 4R) or eDNA (Panels 4D and 4.1D) from human cell lines or tissues related to inflammatory conditions. Controls included total RNA from normal tissues such as colon, lung (Stratagene, La Jolla, CA), thymus and kidney (Clontech, Palo Alto, CA). Total RNA from cirrhotic and lupus kidney was obtained from BioChain Institute, Inc., (Hayward, CA). Crohn's intestinal and ulcerative colitis samples were obtained from the National Disease Research Interchange (NDRI, Philadelphia, PA). Cells purchased from Clonetics (Walkersville, MD) included: 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, and human umbilical vein endothelial. These primary cell types were activated by incubating with various cytokines (IL-1 beta ~1-5 ng/ml, TNF alpha -5-10 ng/ml, IFN gamma -20-50 ng/ml, IL-4 -5-10 ng/ml, IL-9 -5-10 ng/ml, IL-13 5-10 ng/ml) or combinations of cytokines as indicated. Starved endothelial cells were cultured in the basal media (Clonetics, Walkersville, MD) with 0.1% serum. Mononuclear cells were prepared from blood donations using Ficoll. LAK cells were cultured in culture media [DMEM, 5% FCS (Hyclone, Logan, UT), 100 [tM non essential amino acids (Gibco/Life Technologies, Rockville, MD), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5 x 10 -5 M (Gibco), and 10 mM Hepes (Gibco)] and interleukin 2 for 4-6 days. Cells were activated with 10-20 ng/ml PMA and 1-2 .g/ml ionomycin, 5-10 ng/ml IL 12, 20-50 ng/ml IFN gamma or 5-10 ng/ml IL-18 for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in culture media with -5 ptg/ml PHA (phytohemagglutinin) or PWM (pokeweed mitogen; Sigma-Aldrich Corp., St. Louis, MO). 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 them 1:1 at a final concentration of -2x106 cells/ml in culture media. The MLR samples were taken at various time points from 1- 7 days for RNA preparation. Monocytes were isolated from mononuclear cells using CD 14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet (Miltenyi Biotec, Auburn, CA) according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culturing in culture media with 50 ng/ml GMCSF and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culturing monocytes for 5-7 days in culture media with -50 ng/rnl 10% type AB 369 WO 03/093432 PCT/US03/13690 Human Serum (Life technologies, Rockville, MD) or MCSF (Macrophage colony stimulating factor; R&D, Minneapolis, MN). Monocytes, macrophages and dendritic cells were stimulated for 6 or 12-14 hours with 100 ng/mnl lipopolysaccharide (LPS). Dendritic cells were also stimulated with 10 pg/ml anti-CD40 monoclonal antibody (Pharmingen, San Diego, CA) for 6 or 12-14 hours. 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 (Miltenyi Biotec, Auburn, CA) according to the manufacturer's instructions. CD45+RA and CD45+RO CD4+ lymphocytes were isolated by depleting mononuclear cells of CD8+, CD56+, CD14+ and CD 19+ cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO Miltenyi beads were then used to separate the CD45+RO CD4+ lymphocytes from CD45+RA CD4+ lymphocytes. CD45+RA CD4+, CD45+RO CD4 +and CD8+ lymphocytes were cultured in culture media at 106 cells/ml in culture plates precoated overnight with 0.5 ptg/ml anti-CD28 (Pharmingen, San Diego, CA) and 3 O g/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, isolated CD8+ lymphocytes were activated for 4 days on anti-CD28, anti-CD3 coated plates and then harvested and expanded in culture media with IL-2 (1 ng/ml). These CD8+ cells were activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as described above. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. Isolated NK cells were cultured in culture media with 1 ng/ml IL-2 for 4-6 days before RNA was prepared. B cells were prepared from minced and sieved tonsil tissue (NDRI). Tonsil cells were pelleted and resupended at 106 cells/ml in culture media. Cells were activated using 5 tig/ml PWM (Sigma-Aldrich Corp., St. Louis, MO) or -10 [ig/ml anti-CD40 (Pharmingen, San Diego, CA) and 5-10 ng/ml IL-4. Cells were harvested for RNA preparation after 24, 48 and 72 hours. To prepare primary and secondary Thl/Th2 and Trl cells, umbilical cord blood CD4+ lymrnphocytes (Poietic Systems, German Town, MD) were cultured at 10 5 -10 6 cells/ml in culture media with IL-2 (4 ng/ml) in 6-well Falcon plates (precoated overnight with 10 pg/ml anti-CD28 (Pharmingen) and 2 pg/ml anti-CD3 (OKT3; ATCC) then washed twice with PBS). To stimulate Thl phenotype differentiation, IL-12 (5 ng/ml) and anti-IL4 (1 tg/ml) were used; for Th2 phenotype differentiation, IL-4 (5 ng/ml) and anti-IFN gamma (1 pLg/ml) 370 WO 03/093432 PCT/US03/13690 were used; and for Trl phenotype differentiation, IL-10 (5 ng/ml) was used. After 4-5 days, the activated Thl, Th2 and Trl lymphocytes were washed once with DMEM and expanded for 4-7 days in culture media with IL-2 (1 ng/ml). Activated Thl, Th2 and Trl lymphocytes were re-stimulated for 5 days with anti-CD28/CD3 and cytokines as described above with the addition of anti-CD95L (1 ptg/ml) to prevent apoptosis. After 4-5 days, the Thl, Th2 and Trl lymphocytes were washed and expanded in culture media with IL-2 for 4-7 days. Activated Thl and Th2 lymphocytes were maintained for a maximum of three cycles. RNA was prepared from primary and secondary Thl, Th2 and Trl 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. Leukocyte cells lines Ramos, EOL-1, KU-812 were obtained from the ATCC. EOL-1 cells were further differentiated by culturing in culture media at 5 x10 5 cells/ml with 0.1 mM dbcAMP for 8 days, changing the media every 3 days and adjusting the cell concentration to 5 x105 cells/ml. RNA was prepared from resting cells or cells activated with PMA (10 ng/ml) and ionomycin (1 pg/ml) for 6 and 14 hours. RNA was prepared from resting CCD 1106 keratinocyte cell line (ATCC) or from cells activated with -5 ng/ml TNF alpha and 1 ng/ml IL-1 beta. RNA was prepared from resting NCI-H292, airway epithelial tumor cell line (ATCC) or from cells activated for 6 and 14 hours in culture media with 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13, and 25 ng/ml IFN gamma. RNA was prepared by lysing approximately 10' cells/ml using Trizol (Gibco BRL) then adding 1/10 volume of bromochloropropane (Molecular Research Corporation, Cincinnati, OH), vortexing, incubating for 10 minutes at room temperature and then spinning at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was placed in a 15 ml Falcon Tube and an equal volume of isopropanol was added and left at -200 C overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min and washed in 70% ethanol. The pellet was redissolved in 300 1 d of RNAse-free water with 35 pl buffer (Promega, Madison, WI) 5 LI DTT, 7 pl RNAsin and 8 pl DNAse and incubated at 370 C for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with 1/10 volume of 3 M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down, placed in RNAse free water and stored at -800 C. 371 WO 03/093432 PCT/US03/13690 AI comprehensive panel vl.0 Autoimmunity (AI) comprehensive panel v1.0 included two controls and 89 cDNA test samples isolated from male (M) and female (F) surgical and postmortem human tissues that were obtained from the Backus Hospital and Clinomics (Frederick, MD). Tissue samples included : normal, adjacent (Adj); matched normal adjacent (match control); joint tissues (synovial (Syn) fluid, synovium, bone and cartilage, osteoarthritis (OA), rheumatoid arthritis (RA)); psoriatic; ulcerative colitis colon; Crohns disease colon; and emphysmatic, asthmatic, allergic and chronic obstructive pulmonary disease (COPD) lung. AI.05 chondrosarcoma AI.05 chondrosarcoma plates included SW1353 cells (ATCC) subjected to serum starvation and treated for 6 and 18 h with cytokines that are known to induce MMP (1, 3 and 13) synthesis (e.g. ILlbeta). These treatments included: IL-103 (10 ng/ml), IL-103 + TNF-a (50 ng/ml), IL- 10 + Oncostatin (50 ng/ml) and PMA (100 ng/ml). Supernatants were collected and analyzed for MMP 1, 3 and 13 production. RNA was prepared from these samples using standard procedures. Panels 5D and 51 Panel 5D and 51 included two controls and eDNAs isolated from human tissues, human pancreatic islets cells, cell lines, metabolic tissues obtained from patients enrolled in the Gestational Diabetes study (described below), and cells from different stages of adipocyte differentiation, including differentiated (AD), midway differentiated (AM), and undifferentiated (U; human mesenchymal stem cells). Gestational Diabetes study subjects were young (18 - 40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. Uterine wall smooth muscle (UT), visceral (Vis) adipose, skeletal muscle (SK), placenta (P1) greater omentum adipose (GO Adipose) and subcutaneous (SubQ) adipose samples (<1 cc) were collected, rinsed in sterile saline, blotted and flash frozen in liquid nitrogen. Patients included: Patient 2, an overweight diabetic Hispanic not on insulin; Patient 7-9, obese non-diabetic Caucasians with body mass index (BMI) greater than 30; Patient 10, an overweight diabetic Hispanic, on insulin; Patient 11, an overweight nondiabetic African American; and Patient 12, a diabetic Hispanic on insulin. 372 WO 03/093432 PCT/US03/13690 Differentiated adipocytes were obtained from induced donor progenitor cells (Clonetics, Walkersville, MD). Differentiated human mesenchymal stem cells (HuMSCs) were prepared as described in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr 2 1999: 143-147. mRNA was isolated and sscDNA was produced from Trizol lysates or frozen pellets. Human cell lines (ATCC, NCI or German tumor cell bank) included: kidney proximal convoluted tubule, uterine smooth muscle cells, small intestine, liver HepG2 cancer cells, heart primary stromal cells and adrenal cortical adenoma cells. Cells were cultured, RNA extracted and sscDNA was produced using standard procedures Panel SI also contains pancreatic islets (Diabetes Research Institute at the University of Miami School of Medicine). Human Metabolic RTQ-PCR Panel Human Metabolic RTQ-PCR Panel included two controls (genomic DNA control and chemistry control) and 211 cDNAs isolated from human tissues and cell lines relevant to metabolic diseases. This panel identifies genes that play a role in the etiology and pathogenesis of obesity and/or diabetes. Metabolic tissues including placenta (P1), uterine wall smooth muscle (Ut), visceral adipose, skeletal muscle (Sk) and subcutaneous (SubQ) adipose were obtained from the Gestational Diabetes study (described above). Included in the panel are: Patients 7 and 8, obese non-diabetic Caucasians; Patient 12 a diabetic Caucasian with unknown BMI, on insulin (treated); Patient 13, an overweight diabetic Caucasian, not on insulin (untreated); Patient 15, an obese, untreated, diabetic Caucasian; Patient 17 and 25, untreated diabetic Caucasians of normal weight; Patient 18, an obese, untreated, diabetic Hispanic; Patient 19, a non-diabetic Caucasian of normal weight; Patient 20, an overweight, treated diabetic Caucasian; Patient 21 and 23, overweight non-diabetic Caucasians; Patient 22, a treated diabetic Caucasian of normal weight; Patient 23, an overweight non-diabetic Caucasian; and Patients 26 and 27, obese, treated, diabetic Caucasians. Total RNA was isolated from metabolic tissues including: hypothalamus, liver, pancreas, pancreatic islets, small intestine, psoas muscle, diaphragm muscle, visceral (Vis) adipose, subcutaneous (SubQ) adipose and greater omentum (Go) from 12 Type II diabetic (Diab) patients and 12 non diabetic (Norm) at autopsy. Control diabetic and non-diabetic subjects were matched where possible for: age; sex, male (M); female (F); ethnicity, Caucasian (CC); Hispanic (HI); African American (AA); Asian (AS); and BMI, 20-25 (Low BM), 26-30 (Med BM) or overweight (Overwt), BMI greater than 30 (Hi BMI) (obese). 373 WO 03/093432 PCT/US03/13690 RNA was extracted and ss eDNA was produced from cell lines (ATCC) by standard methods. CNS Panels CNS Panels CNSD.01, CNS Neurodegeneration V1.0 and CNS Neurodegeneration V2.0 included two controls and 46 to 94 test cDNA samples isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital). Brains were removed from calvaria of donors between 4 and 24 hours after death, and frozen at -80 0 C in liquid nitrogen vapor. Panel CNSD.01 Panel CNSD.01 included two specimens each from: Alzheimer's disease, Parkinson's disease, Huntington's disease, Progressive Supernuclear Palsy (PSP), Depression, and normal controls. Collected tissues included: cingulate gyrus (Cing Gyr), temporal pole (Temp Pole), globus palladus (Glob palladus), substantia nigra (Sub Nigra), primary motor strip (Brodman Area 4), parietal cortex (Brodman Area 7), prefrontal cortex (Brodman Area 9), and occipital cortex (Brodman area 17). Not all brain regions are represented in all cases. Panel CNS Neurodegeneration V1.0 The CNS Neurodegeneration V1.0 panel included: six Alzheimner's disease (AD) brains and eight normals which included no dementia and no Alzheimer's like pathology (control) or no dementia but evidence of severe Alzheimer's like pathology (Control Path), 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. Tissues collected included: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), occipital cortex (Brodman area 17) superior temporal cortex (Sup Temporal Ctx) and inferior temporal cortex (Inf Temproal Ctx). Gene expression was analyzed after normalization using a scaling factor calculated by subtracting the Well mean (CT average for the specific tissue) from the Grand mean (average CT value for all wells across all runs). The scaled CT value is the result of the raw CT value plus the scaling factor. Panel CNS Neurodegeneration V2.0 The CNS Neurodegeneration V2.0 panel included sixteen cases of Alzheimer's disease (AD) and twenty-nine normal controls (no evidence of dementia prior to death) including fourteen controls (Control) with no dementia and no Alzheimer's like pathology 374 WO 03/093432 PCT/US03/13690 and fifteen controls with no dementia but evidence of severe Alzheimer's like pathology (AH3), 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. Tissues from the temporal cortex (Brodman Area 21) included the inferior and superior temporal cortex that was pooled from a given individual (Inf & Sup Temp Ctx Pool). A. CG103910-02: BMP7. Expression of gene CG103910-02 was assessed using the primer-probe set Ag7249, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB and AC. Table AA. Probe Name Ag7249 Start SEQ ID Primers Sequences Length Start SEQ ID ..... Position No Forward 5'-aacgtggcaggtccactt-3' 18 949 349 Probe TET-5'-atcaacccggaaacggtgcccaa-3'- 23 968 350 ~Probe j AP 23 968 350 TAMRA Reverse 5'-catcgaagtagaggacggagat-3' 22 1022 351 Table AB. General_screening_panelv1.7 Column A - Rel. Exp.(o) Ag7249, Run 318008815 Tissue Name A Tissue Name A Adipose 0.2 Gastricca. (liver met.) NCI-N87 1.5 HUVEC 0.0 Stomach 0.0 Melanoma* Hs688(A).T 0.0 Colon ca. SW-948 6.2 Melanoma* Hs688(B).T 10.7Colon ca. SW480 0.9 Melanoma (met) SK-MEL- 5 Colon ca. (SW480 met) SW620 61 Testis 0.7 Colon ca. HT29 0.0 Prostate ca. (bone met) PC-3 0.0 Colon ca. HCT-116 10.3 Prostate ca. DU145 0.0 Colon cancer tissue 0.9 Prostate pool 0.0 Colon ca. SW1116 6.2 Uterus pool 0.0 Colon ca. Colo-205 19.6 Ovarian ca. OVCAR-3 12.1 Colon ca. SW-48 1.2 Ovarian ca. (ascites) SK-OV-3 I0. Colon 0.0 Ovarian ca. OVCAR-4 62.0 Small Intestine 0.0 Ovarian ca. OVCAR-5 0.0 Fetal Heart 4.3 Ovarian ca. IGROV-1 1 H00. eart 0.0 Ovarian ca. OVCAR-8 0.0 Lymph Node pool 1 0.0 Ovary 0.0 Lymph Node pool2 0.3 Breast ca. MCF-7 32.8 Fetal Skeletal Muscle 1.1 Breast ca. MDA-MB-231 Skeletal Muscle pool Breast ca. BT-549 0.0 Skeletal Muscle 0.0 375 WO 03/093432 PCT/US03/13690 Breast ca. T47D .0.0 Spleen 0.3 Breast pool 0.0 Thymus 0.0 Trachea 3.1 CNS cancer (glio/astro) SF-268 0.0 Lung 0.8 CNS cancer (glio/astro) T98G 8.5 Fetal Lung 2.6 CNS cancer (neuro;met) SK-N-AS 0.0 Lung ca. NCI-N417 0.0 CNS cancer (astro) SF-539 0.2 Lung ca. LX-1 10.2 CNS cancer (astro) SNB-75 3.9 Lung ca. NCI-H146 0.0 CNS cancer (glio) SNB-19 0.2 Lung ca. SHP-77 0.0 CNS cancer (glio) SF-295 8.4 Lung ca. NCI-H23 15.5 Brain (Amygdala) 2.5 Lung ca. NCI-H460 0.3 Brain (Cerebellum) 3.3 Lung ca. HOP-62 0.0 Brain (Fetal) 6.3 Lung ca. NCI-H522 19.2 Brain (Hippocampus) 2.3 Lung ca. DMS-l 14 3.0 Cerebral Cortex pool 1.4 Liver 0.0 Brain (Substantia nigra) 0.0 Fetal Liver 0.0 Brain (Thalamus) 1.9 Kidney pool 1.4 Brain (Whole) 7.0 Fetal Kidney 4.7 Spinal Cord 1.4 Renal ca. 786-0 0.0 Adrenal Gland 0.3 Renal ca. A498 0.0 Pituitary Gland 0.0 Renal ca. ACHN 0.0 Salivary Gland 0.3 Renal ca. UO-31 0.0 Thyroid 6.9 Renal ca. TK- 10 0.0 Pancreatic ca. PANC-1 2.4 Bladder 1.2 Pancreas pool 0.2 Table AC. Panel 4.1D Column A - Rel. Exp.(%) Ag7249, Run 296433954 Tissue Name A Tissue Name A Secondary Thl act 0.0 HUVEC IL-lbeta 0.0 Secondary Th2 act 0.0 HUVEC LEN gamma 0.0 Secondary Trl act 0.0 LUVEC TNF alpha + IFN gamma 0.0 Secondary Thl rest O.0 1.IHUVEC TNF alpha + IL4 0.0 Secondary Th2 rest 0.0 HUVEC IL-11 10.0 Secondary Trl rest 0.0 Lung Microvascular EC none 0.0 Primary Thl act 0.0 Lung Microvascular EC TNFalpha + IL-1beta 0.0 Primary Th2 act 0.0 Microvascular Dermal EC none 0.0 Microsvasular Dermal EC TNFalpha + IL Primary Trl act 0.0 beta 0.0 Primary Thl rest 0.0 Bronchial epithelium TNFalpha + ILIbeta 0.0 Primary Th2 rest 0.0 Small airway epithelium none 0.0 Primary Trl rest .0 jSmall airway epithelium TNFalpha + IL-1beta 0.0 376 WO 03/093432 PCT/US03/13690 CD45RA CD4 lymphocyte act 0.0 Coronery artery SMC rest 0.0 CD45RO CD4 lymphocyte act 0.0 Coronery artery SMC TNFalpha + IL-lbeta 0.0 CJD8 lymphocyte act 0.0 Astrocytes rest 0.0 Secondary CD8 lymphocyte rest 0.0 Astrocytes TNFalpha + IL- I beta 0.0 Secondary CD8 lymphocyte act 0.0 KU-812 (Basophil) rest 0.0 CD4 lymphocyte none 0.0 KU-812 (Basophil) PMA/ionomycin 0.0 2ry Thl/Th2/Trl anti-CD95 0.0 CCD 106 (Keratinocytes) none 0.0 H11- 0.0CCD 1106 (Keratinocytes) none CHI1I LAKCCD1106 (Keratinocytes) TNFalpha + IL- 0.0 LAK cells rest 0. beta l beta 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 gamma 0.0 NCI-H292 IL-4 0.0 LAK cells IL-2+ IL-18 0.0 NCI-H292 IL-9 0.0 LAK cells PMA/ionomycin 0.0 NCI-H292 IL-130.0 NK Cells IL-2 rest 0.0 NCI-H292 IFN gamma 0.0 Two Way MLR 3 day 0.0 HPAECnone 00 Two Way MLR 5 day 0.0 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 + IL-1 beta 0.0 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 49.3 Lung fibroblast IL-130.0 Ramos (B cell) ionomycin 100.0 Lung fibroblast IFN gamma 0.0 B lymphocytes PWM 0.0 Dermal fibroblast CCD1070 rest 0.0 B lymphocytes CD40L and IL-4 0.0 Dermal fibroblast CCD1070 TNFalpha 0.0 EOL-1 dbcAMP 0.0 Dermal fibroblast CCD1070 IL-1 beta 0.0 EOL-1 dbcAMP PMA/ionomycin 0.0 Dermal fibroblast IFN gamma j. Dendritic cells none 0.0 Dermal fibroblast IL-4 0.0 Dendritic cells LPS 0.0 Dermal Fibroblasts rest 0.0 Dendritic cells anti-CD40 0.0 Neutrophils TNFa+LPS 0.0 Monocytes rest j0.0 Neutrophils rest Monocytes LPS 0.0 Colon 0.0 Macrophages rest .. 0.0 ]Lung 0.0 Macrophages LPS 0.0 Thymus 0.0 HUVEC none . 0.0 Kidney 10.0 HUVEC starved 0.0! General_screeningpanel_v1.7 Summary: Ag7249 Highest expression of this gene was detected in ovarian cancer cell line IGROV-1 (CT=28.8) and moderate expression was detected in cancer cell lines derived from melanoma, ovarian, lung, breast, colon and brain 377 WO 03/093432 PCT/US03/13690 cancers. CG103910-02 gene expression is a marker of cancer vs normal tissue and is useful to detect cancers. Therapeutic modulation of this gene, expressed protein and/or the use of antibodies or small molecule drugs targeting this gene or gene product are useful in the treatment of melanoma, ovarian, lung, breast, colon and brain cancers. Gene expression was detected at low levels in certain regions of the central nervous system examined including: amygdala, hippocampus, thalamus, cerebellum, cerebral cortex, and spinal cord. Therapeutic modulation of this gene product is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.Gene expression was detected at low levels in thyroid, fetal heart, kidney, and trachea. Panel 4.1D Summary: Ag7249 Low expression of this gene was detected in activated Ramos B cells (CT=34.4). Lower but significant gene expression was detected in untreated Ramos B cells. B cells contribute to the immune response through various functional roles, including antibody production and are implicated in the production of auto-antibodies against self-antigens in autoimmune disorders. Therapeutic modulation of this gene, encoded protein and/or antibodies or small molecule drugs that antagonize its function reduce or eliminate the symptoms of patients suffering from asthma, allergies, chronic obstructive pulmonary disease, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, osteoarthritis, systemic lupus erythematosus and other autoinimune disorders. B. CG103910-03: BMP7. Expression of gene CG103910-03 was assessed using the primer-probe set Ag7250, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC and BD. Table BA. Probe Name Ag7250 Start SEQ ID Primers Sequences _ _ _ _ _ __ Length Position No Forward 5'-acgtggcaggactggatc-3' 18 950 352 Probe TET-5'-cctgaaggctacgccgcctactactg-3'- 26 974 353 TAMRA Reverse 5'-gagttcagagggaaggcaca-3' 20 1010 354 378 WO 03/093432 PCT/US03/13690 Table BB. AI.05 chondrosarcoma Column A - Rel. Exp.(%) Ag7250, Run 312643038 Tissue Name A Tissue Name A 138353_ PMA(18hrs) 11.1 138346 IL-beta + Oncostatin M (6hrs) 14.6 138352 IL-1beta + Oncostatin M (18hrs) 11.7 138345 IL-lbeta+TNFa(6hrs) 15.5 138351 IL-lbeta+TNFa (18hrs) :100.0 138344 IL-lbeta (6hrs) 4.7 .138350 IL- .. beta (8hrs) 2.5 138348 Untreated-complete medium . - (6hrs) 13854 Untreeadcompetemedium ... .... .. .. 138354- Untreated-complete medi 0.7 138349 Untreated-serum starved (6hrs) 10.7 (1 8hrs) 1138347_PMA (6hrs) 122.41 Table BC. General_screening_panel_vl.7 Column A - Rel. Exp.(%) Ag7250, Run 318008817 Tissue Name A Tissue Name A Adipose 1.8 lGastric ca. (liver met.) NCI-N87 0.8 HlVEC 0.0 Stomach 0.1 Melanoma* Hs688(A).T 0.0 Colon ca. SW-948 26.1 Melanoma* Hs688(B).T 9.1 Colon ca. SW480 1.0 Melanoma (met) SK-MEL-5 1.5 Colon ca. (SW480 met) SW620 38.7 Testis 1.2 lColon ca. HT29 0.0 Prostate ca. (bone met) PC-3 0.0 ]Colon ca. HCT- 116 8.4 Prostate ca. DU145 0.1 Colon cancer tissue 2.4 Prostate pool 1.0 Colon ca.SW116 1 7.7 Uterus pool 0.2 Colon ca. Colo-205 110.3 Ovarian ca. OVCAR-3 42.6 Colon ca. SW-48 3.3 Ovarian ca. (ascites) SK-OV-3 0.0 Colon 0.8 Ovarian ca. OVCAR-4 100.0 Small Intestine 0.2 * *' -a ' : -- ................................ " -: -9-p 'N a - 0 i ................... ..... ...-....... .

Ovarian ca. OVCAR-5 0.1 1Fetal Heart 4.1 Ovarian ca. IGROV-1 38.4 Hat0.5 Ovarian ca. OVCAR-8 0.0 Lymph Node pool 1 0.7 Ovary 0.3 Lymph Node pool 2 0.9 Breast ca. MCF-7 45.1 Fetal Skeletal Muscle 0.9 Breast ca. MDA-MB-231 0.0 Skeletal Muscle pool 0.0 Breast ca. BT-549 1.2 Skeletal Muscle 0.2 Breast ca. T47D 0.1 Spleen 0.4_ Breast pool 0.1 Thymus 1.0 Trachea 5.4 ... CNS cancer (glio/astro) SF-268 0.0 Lung 1.4 CNS cancer (glio/astro) T98G 4.9 Fetal Lung 8.5 CNS cancer (neuro;met) SK-N-AS 0.1 Lung ca. NCI-N417 .. 0 NS cancer (astro) SF-539 0.0 379 WO 03/093432 PCT/US03/13690 Lung ca. LX-I 7.2 CNS cancer (astro) SNB-75 ._6 Lung ca. NCI-H146 0.0 CNS cancer (glio) SNB-19 0.2 Lung ca. SHP-77 0.0 CNS cancer (glio) SF-295 7.9 Lung ca. NCI-H23 10.0 Brain (Amygdala) 6.9 Lung ca. NCI-H460 0.1 Brain (Cerebellum) 6.4 Lung ca. HOP-62 0.0 Brain (Fetal) 9.0 Lung ca. NCI-H522 . 11.4 Brain (Hippocampus) 11.1 Lung ca. DMS-114 1.2 Cerebral Cortex pool 5.4 Liver 0.0 Brain (Substantia nigra) 2.6 Fetal Liver 0.1 Brain (Thalamus) 7.6 Kidney pool 5.5 Brain (Whole) 19.3 Fetal Kidney 13.0 Spinal Cord 6.2 Renal ca. 786-0 0.0 Adrenal Gland 2.1 Renal ca. A498 0.0 Pituitary Gland 0.7 Renal ca. ACHN 0.0 Salivary Gland 0.2 Renal ca. UO-31 0.0 Thyroid 60.3 Renal ca. TK-10 0.0 Pancreatic ca. PANC-1 2.4 Bladder 2.4 Pancreas pool 0.5 Table BD. Panel 4.1D Column A - Rel. Exp.(%) Ag7250, Run 296422907 Tissue Name A Tissue Name A Secondary Thi act 0.1 HUVEC IL-lbeta 0.0 Secondary Th2 act 0.1 JHUVEC IFN gamma 0.0 Secondary Trl act 0.0 HUVEC TNF alpha + IFN gamma .. 01 Secondary Th1 rest 0.0 HUVEC TNF alpha + IL4 0.0 Secondary Th2 rest 10.0 HUVEC IL-11 0.0 Secondary Trl rest 0.0 Lung Microvascular EC none 0.0 Primary Thl act 0.1 Lung Microvascular EC TNFalpha + IL-lbeta 0.0 Primary Th2 act 0.1 Microvascular Dermal EC none . 0.0 Primary Tn- act 1 0.0 Microsvasular Dermal EC TNFalpha + IL P _..... ... .. _ "' lbeta ' Primary Th1 rest 0.0 Bronchial epithelium TNFalpha + IL1beta .0.1 Primary Th2 rest 0.0 Small airway epithelium none 0.01 Prim ary Trl rest 0.0 Small airway epithelium TNFalpha+ IL-ibeta 0.3 CD45RA CD4 lymphocyte act 0.0 Coronery artery SMC rest 0.0 CD45RO CD4 lymphocyte act 0.2 Coronery artery SMC TNFalpha + IL-1beta 0.0 CD8 lymphocyte act 0.0 Astrocytes rest 0.3 Secondary CD8 lymphocyte rest 0.0 Astrocytes TNFalpha +IL-1 beta . .0.0 Secondary CD8 lymphocyte act 0.0 KU-812 (Basophil) rest 0.0 CD4 lymphocyte none .0.0 ... JKU-812 (Basophil) PMA/ionomycin 0.0 380 WO 03/093432 PCT/US03/13690 2ry Thl/Th2/Trl anti-CD95 CyHI r- 0.0 CCD1106 (Keratinocytes) none 0.1 CHI I LAK cells rest 0 0.0 CCD 1106 (Keratinocytes) TNFalpha + IL- 0.0 LAK cells rest 0.0_lbta__ 0.0 l beta LAK cells IL-2 0.0 Liver cirrhosis 0.2 LAK cells IL-2+IL-12 _ _0.0 NCI-H292 none 0.5 LAK cells IL-2+

I

FN gamma 0.1 NCI-H292 IL-4 0.0 LAK cells IL-2+ IL- 18 .0.0 NCI-H292 IL-9 0.4 LAK cells PMA/ionomycin 0.0 NCI-H292 IL-13 0.2 NK Cells IL-2 rest 0.0 NCI-H292 IFN gamma 0.3 Two Way MLR 3 day 0.0 HPAEC none 0.0 Two Way MLR 5 day . . 0.0 HPAEC TNF alpha + IL- beta 0.0 Two Way MLR 7 day 0.0 Lung fibroblast none 0.0 PBMC rest 0.0 Lung fibroblast TNF alpha + IL-I beta 0.0 PBMC PWM 0.0 Lung fibroblast IL-4 o.0 PBMC PHA-L 0.0 'Lung fibroblast IL-9 .0.0 Ramos (B cell) none 38.4 Lung fibroblast IL-13 0.0 Ramos (B cell) ionomycin 100.OLung fibroblast IFN gamma 0.1 B lymphocytes PWM 0.1 Dennrmal fibroblast CCD1070 rest '0.0 B lymphocytes CD40L and IL-4 1.5 Dermal fibroblast CCD1070 TNF alpha 0.0 EOL-1 dbcAMP 0.0 Dermal fibroblast CCD1070 IL-1 beta 0.0 EOL-1 dbcAMP PMA/ionomycin 0.0 Dermal fibroblast IFN gamma 0.1 Dendritic cells none 0.0 Dermal fibroblast IL-4 0.0 Dendritilc cells LPS 0.0 iDermal Fibroblasts rest 0.9 Dendritic cells anti-CD40 0.0 Neutrophils TNFa+LPS 0.0 Monocytes rest 0.0 Neutrophils rest 0. Monocytes LPS .0 .0 C.oon 0.2 Macrophages rest 0..1 Lung 0.1 Macrophages LPS 0.0 Thymus. HUVEC none 0.0 Kidney HUVEC starved 0.0.. AI.05 chondrosarcoma Summary: Ag7250 Highest CG103910-03 gene expression was detected in activated chondrosarcoma cell line (CT=28.4). Gene expression was upregulated upon IL-1 treatment, a potent activator of pro-inflammatory cytokines and matrix metalloproteinases which participate in the destruction of cartilage observed in Osteoarthritis (OA). Modulation of gene expression or its encoded protein and/or the use of antibodies, small molecules or antisense targeting the gene or the encoded protein are important for preventing the degeneration of cartilage observed in OA. General_screeningpanel_vl.7 Summary: Ag7250 Highest gene expression was detected in ovarian cancer OVCAR cell line (CT=22.6). High gene expression was detected in cancer 381 WO 03/093432 PCT/US03/13690 cell lines derived from melanoma, ovarian, lung, breast, colon and brain cancers. CG103910 03 gene expression is a marker useful to differentiate these cancers and to detect their presence in vitro and in vivo. Therapeutic modulation of this gene or encoded protein and/or use of antibodies or small molecule drug targeting the gene or the encoded protein is useful in the treatment of melanoma, ovarian, lung, breast, colon and brain cancers. Gene expression was high in all the regions of the central nervous system examined including: amygdala, hippocampus, thalamus, cerebellum, substantia nigra, cerebral cortex, and spinal cord. Therapeutic modulation of this gene or the encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Among tissues with metabolic or endocrine function, gene expression was moderate in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Panel 4.1D Summary: Ag7250 Highest gene expression was detected in activated Ramos B cells (CT=28.4) with significant expression also detected in untreated Ramos B cells. B cells contribute to the immune response through various functional roles, including antibody production and are implicated in the production of auto-antibodies against self-antigens in autoimmune disorders. Therapeutic modulation of this gene, encoded protein and/or antibodies or small molecule drugs that antagonize its function reduce or eliminate the symptoms of patients suffering from asthma, allergies, chronic obstructive pulmonary disease, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, osteoarthritis, systemic lupus erythematosus and other autoimmune disorders. C. CG183860-01: Novel Membrane Protein. Expression of gene CG183860-01 was assessed using the primer-probe set Ag6837, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB, CC and CD. Table CA. Probe Name Ag6837 Start SEQ ID Primers Sequences SLength Seu e Position No Forward 5'-ggctgagccaggtggat-3' 17 1168 355 Probe TET-5' -cgccatacaccaccagccactca-3'- 2 1 TAMRA 23 1185 356 Reverse 5'-catccgcaggttctcctt-3' 18 ... 1249 357 ... 382 WO 03/093432 PCT/USO3/13690 Table CB. CNS_neurodegeneration__v1.0 Column A - Rel. Exp.(%) Ag6837, Run 279057825 fTissue Name A Tissue Name A AD 1 Hippo 0.2 Control (Path) 3 Temporal Ctx 12.4 AD 2 Hippo 3.3 Control (Path) 4 Temporal Ctx 12.2 AD 3 Hippo 12.7 AD 1 Occipital Ctx 15.6 AD 4 Hippo 3.7 AD 2 Occipital Ctx (Missing) 0.0 AD 5 hippo __6.9 AD 3 Occipital Ctx 19.1 AD 6 Hippo 100.0 AD 4 Occipital Ctx 13.3 Control 2 Hippo 5.2 AD 5 Occipital Ctx 15.8 Control 2 Hippo ......... ............. 8 Control 4 Hippo .1.8 AD 6 Occipital Ctx 0.0 Control (Path) 3 Hippo 4.7- Control 1 Occipital Ctx 11 AD 1 Temporal Ctx 6.4 Control 2 Occipital Ctx 9.3 AD 2 Temporal Ctx 108 Control 3 Occipital Ctx 7... 7....... AD 3 Temporal Ctx 2.1 Control 4 Occipital Ctx 5.4 AD 4 Temporal Ctx 9.9 Control (Path) 1 Occipital Ctx 19.9 AD 5 InfTemporal Ctx 9.5 Control (Path) 2 Occipital Ctx 5.4 AD 5 SupTemporal Ctx 25.3 Control (Path) 3 Occipital Ctx 8.2 AD 6 Inf Temporal Ctx 92.7 Control (Path) 4 Occipital Ctx 21.6 AD 6Sup Temporal Ctx 81.2 Control 1 Parietal Ctx 7.6 ... r o i T.m oI.i I.. tL .--........... ...... ........ . .. ... Control 1 Temporal Ctx 7.2 control 2 Parietal Ctx 33.9 Control 2 Temporal Ctx 9.7 iControl 3 Parietal Ctx 6.1 Control 3 Temporal Ctx 9.3 Control (Path) 1 Parietal Ctx 10.8 Control 4 Temporal Ctx 5.1 jControl (Path) 2 Parietal Ctx 4.0 [Corol T 5.0 Control (Path) 3 Parietal Ctx 13.2 Control (Path) 2 Temporal Ctx 1. Control (Path) 4 Parietal Ctx 9.9 Table CC. Generalscreeningpanel vl.6 Column A - Rel. Exp.(%) Ag6837, Run 278368620 [Tissue Name A Tissue Name A 0Adipose 0 Renal ca. TK-10 0.0 Melanoma* Hs688(A).T 0.0 Bladder 0.1 MelanomaHs688(B).T_ 0.0 Gastric ca. (liver met.) NCI-N87 0.1 Melanoma* M14 ......... 7 Gastric ca. KATO III 0.0 Melanoma* LOXIMVI 0 Colon ca. SW-948 0.0 Melanoma* SK-MEL-5 0.0 Colon ca. SW480 0.0 Squamous cell carcinoma SCC-4 0 Colon ca.* (SW480 met)SW620 0.0 Testis Pool J 0.7 IColon ca. HT29 0.0 Prostate ca.* (bone met) PC-3 100.0 Colon ca. HCT- 16 0.0 Prostate Pool .o. 2 lCon ca. CaCo-2 0.0 Placenta .0.0 Colon cancer tissue 0.1 383 WO 03/093432 PCT/USO3/13690 Uterus Pool 0.1 Colon ca. SW1116 0.0 Ovarian ca. OVCAR-3 0. Colon ca. Colo-205 0.0 Ovarian ca. SK-OV-3 0.2 Colon ca. SW-48 0.0 Ovarian ca. OVCAR-4 0.0 Colon Pool 0.1 Ovarian ca. OVCAR-5 0.4 Small Intestine Pool 1.7 Ovarian ca. IGROV-1 11.2 Stomach Pool0.3 Ovarian ca. OVCAR-8 0.0 Bone Marrow Pool 0.1 Ovary 0.0 Fetal Heart 0.9 Breast ca. MCF-7 0.0 Heart Pool 0.5 Breast ca. MDA-MB-231 0.3 Lymph Node Pool 0.2 Breast ca. BT 549 0.1 Fetal Skeletal Muscle 0.6 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N 0.0 Spleen Pool 0.1 Breast Pool 0.1 Thymus Pool 0.4 Trachea 1.1 CNS cancer (glio/astro) U87-MG 0.0 Lung 0.4 CNS cancer (glio/astro) U- I 18-MG 0.0 Fetal Lung 4.6 CNS cancer (neuro;met) SK-N-AS 1.4 Lung ca. NCI-N417 0.0 CNS cancer (astro) SF-539 0.0 Lung ca. LX-1 0.0 CNS cancer (astro) SNB-75 0.1 Lung ca. NCI-H146 0.0 CNS cancer (glio) SNB-19 10.4 Lung ca. SHP-77 0.0 CNS cancer (glio) SF-295 0.5 Lung ca. A549 0.0 Brain (Amygdala) Pool 0.1 Lung ca. NCI-H526 0.0 Brain (cerebellum) 0.1 Lung ca. NCI-H23 0.2 Brain (fetal) 0.1 Lung ca. NCI-H460 0.4 Brain (Hippocampus) Pool 0.1 Lung ca. HOP-62 0.2 Cerebral Cortex Pool 0.0 Lung ca. NCI-H522 0.0 Brain (Substantia nigra) Pool 0.0 Liver 0.1 Brain (Thalamus) Pool 0.1 Fetal Liver 0.3 Brain (whole) 0.1 Liver ca. HepG2 0. Spinal Cord Pool 0.1 Kidney Pool 0.2 Adrenal Gland 0.6 Fetal Kidney 16.6 Pituitary gland Pool 0.1 Renal ca. 786-0 0.0 Salivary Gland 0.1 Renal ca. A498 0.1 Thyroid (female) 0.2 Renal ca. ACHN 0.0 Pancreatic ca. CAPAN2 0.1 Renal ca. UO-31 0.1 Pancreas Pool 0.0 384 WO 03/093432 PCT/USO3/13690 Table CD. Panel 4.1D Column A - Rel. Exp.(%) Ag6837, Run 279029111 Tissue Name A Tissue Name A Secondary Thl act 0.0 HUVEC IL-Ibeta 33.7 Secondary Th2 act 1.1 HUVEC IFN gamma 28.9 Secondary Tr act 0.0 HUVEC TNF alpha + IFN gamma 2 Secondary Thl rest 0.0 HUVEC TNF alpha + IL4 16.0 Secondary Th2 rest 0.0 HUVEC IL-1 1 25.9 Secondary Trl rest 0.10 Lung Microvascular EC none .1 Primary Thl act 10.0 Lung Microvascular EC TNFalpha + IL-Ibeta 1.7 Primary Th2 act 1.8 Microvascular Dermal EC none 5.6 .rm r ....... ... ............................................... . .. c.. ... u Primary T act 0.0 Microsvasular Dermal EC TNFalpha + IL- 0.0 Primary Trl act 0.0 e0. 1betaI Primary Thl rest 10.0 Bronchial epithelium TNFalpha + ILIbeta 0.0 Primary Th2 rest 0.0 Small airway epithelium none 0.0 Primary Trl rest 0.0 Small airway epithelium TNFalpha + IL-Ibeta 0.0 CD45RA CD4 lymphocyte act 0.0 Coronery artery SMC rest 3.4 CD45RO CD4 lymphocyte act 0.0 Coronery artery SMC TNFalpha + IL-lbeta 2.7 CD8 lymphocyte act i0.0 Astrocytes rest 0.0 Secondary CD8 lymphocyte rest 0.0 Astrocytes TNFalpha + IL-lbeta 0. Secondary CD8 lymphocyte act 1.7 KU-812 (Basophil) rest 0.0 CD4 lymphocyte none 00I KU-812 (Basophil) PMA/ionomycin 0.0 2ry Thl/Th2/Trl anti-CD95 2ry Th/Th2/Tlanti-CD95 0.0 CCD 1106 (Keratinocytes) none 0.0 CHIl LAK cells rest 1.4 CCD 1106 (Keratinocytes) TNFalpha + IL LAK cells rest 1 0.0ta beta LAK cells IL-2 1.6 Liver cirrhosis 6.9 LAK cells IL-2+IL-12 0.0 NCI-H292 none 0.0 LAK cells IL-2+IFN gamma 0.0 NCI-H292 IL-4 0.0 LAK cells IL-2+ IL-18 0.0 NCI-H292 IL-9 0.0 LAK cells PMA/ionomycin 0.0 NCI-H292 IL-13 0.0 NK Cells IL-2 rest 0.0 NCI-H292 IFN gamma 0.0 Two Way MLR 3 day 0.0 HPAEC none 49.3 Two Way MLR 5 day 0.0 HPAEC TNF alpha + IL-1 beta 13.4 Two Way MLR 7 day 0.0 Lung fibroblast none 3.0 PBMC rest 0.0 Lung fibroblast TNF alpha + IL-1 beta 0.0 PBMC PWM 0.0 Lung fibroblast IL-4 1.2 PBMC PHA-L 00.0 Lung fibroblast IL-9 0.0 Ramos (B cell) none 0.0 Lung fibroblast IL-132.0 Ramos (B cell) ionomycin 0.0 Lung fibroblast IFN gamma 0.0 B lymphocytes PWM 0.0 Dermal fibroblast CCD1070 rest 0.0 JBlymphocytes CD40L andIL-4 2.1 Dermal fibroblast CCD1070 TNF alpha 0.0 385 WO 03/093432 PCT/US03/13690 EOL-1 dbcAMP 0.0 Dermal fibroblast CCD1070 IL-I beta 0.0 EOL-1 dbcAMP PMA/ionomycin 0.0 Dermal fibroblast IFN gamma 0.0 Dendritic cells none 0.0 Dermal fibroblast IL-4 2.2 Dendritic cells LPS 0.0 Dermal Fibroblasts rest 0.0 Dendritic cells anti-CD40 0.0 Neutrophils TNFa+LPS 0.0 Monocytes rest 0.0 Neutrophils rest 0.0 Monocytes LPS 0.0 Colon 2.8 Macrophages rest 0.0 Lung 3.7 Macrophages LPS 0.0 Thymus 0.0 HUVEC none 57.0 Kidney 100.0 HUVEC starved 42.9 CNS_neurodegeneration_vl.0 Summary: Ag6837 Highest CG183860 gene expression was detected in the hippocampus of an Alzheimer's patient (CT=31) and was also determined to be upregulated in the temporal cortex of Alzheimer's disease patients. Therapeutic modulation of the expression or function of this gene, encoded protein and/or use of antibodies or small molecule drug targeting the encoded protein to decrease neuronal cell death is useful in the treatment of this disease. General_screening_panelvl.6 Summary: Ag6837 Highest gene expression was detected in a prostate cancer cell line (CT=24.5) and high levels of expression were also seen in ovarian and brain cancer cell lines. CGl 83860 gene expression is a marker for differentiating cancerous from normal tissues and to detect the presence of these cancers. Therapeutic modulation of the expression or function of this gene, encoded protein and/or use of antibodies or small molecule drug targeting the encoded protein are effective in the treatment of cancer. Gene expression was also detected at higher levels in fetal kidney and lung (CTs=27-29) relative to expression in the corresponding adult tissues (CTs=32-33). The relative over expression of this gene in these fetal tissues suggests that the protein product may enhance lung and kidney growth or development in the fetus and are useful in a regenerative capacity in the adult. Panel 4.1D Summary: Ag6837 Highest expression was seen in kidney (CT=32.7). Low but significant gene expression was detected in samples derived from human endothelium cells from umbilical vein and pulmonary artery (HUVEC and HPAEC). Therapeutic modulation of this gene, encoded protein and/or antibodies, small molecule drug targeting the encoded protein will reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases that involve endothelial cells, such as lupus erythematosus, asthma, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, osteoarthritis, and psoriasis. 386 WO 03/093432 PCT/US03/13690 D. CG110590-02: SIMILAR TO CHORDIN-LIKE. Expression of gene CG1 10590-02 was assessed using the primer-probe set Ag7182, described in Table DA. Results of the RTQ-PCR runs are shown in Table DB. Table DA. Probe Name Ag7182 .1 ~Start SEQ ID Primers Sequences Length Start SEQ ID Position No Forward 5'-gaccacctcaggoattcto-3' 19 1220 358 Probe TET-5 r -ctcctcaaacatcctcttggagatcttct-3 TAMRA 29 1255 359 Reverse 5'-ctcagggttgttctggtcac-3' 20 ... 1302 360 Table DB. General_screening_panel_vl.7 Column A - Rel. Exp.(%) Ag7182, Run 318350049 Tissue Name A Tissue Name A Adipose 100.0 Gastric ca. (liver met.) NCI-N87 0.0 HUVEC 0.0 Stomach 0.7 Melanoma* Hs688(A).T 0.0 Colon ca. SW-948 0.0 Melanoma* Hs688(B).T 0.0 Colon ca. SW480 0.0 Melanoma (met) SK-MEL-5 0.0 Colon ca. (SW480 met) SW620 0.0 Testis 6.2 Colon ca. HT29 0.0 Prostate ca. (bone met) PC-3 0.0 Colon ca. HCT-1 16 40.0 Prostate ca. DU145 0.0 Colon cancer tissue j 0.0 Prostate pool 11.0 Colon ca. SW1116 0.0 Uterus pool 3.4 Colon ca. Colo-205 0.0 Ovarian ca. OVCAR-3 0.9 Colon ca. SW-48 0.0 Ovarian ca. (ascites) SK-OV-3 1.5 Colon Ovarian ca. OVCAR-4 0.0 Small Intestine 13.4 Ovarian ca. OVCAR-5 2.1 Fetal Heart 10.0 Ovarian ca. IGROV-1 0.0 Heart 15.9 Ovarian ca. OVCAR-8 14.7 JLymph Node pool 1 0.0 Ovary 35.1 Lymph Node pool 17.7 Breast ca. MCF-7 0.0 Fetal Skeletal Muscle 1.0 Breast ca. MDA-MB-231 40.4 Skeletal Muscle pool 0.8 Breast ca. BT-549 3.6 Skeletal Muscle 1.4 Breast ca. T47D 0.0 Spleen 3.6 Breast pool 0.0 Thymus 1.6 Trachea 15.3 CNS cancer (glio/astro) SF-268 1.0 Lung 54.3 CNS cancer (gioastro) T98G 0.0 Fetal Lung 12.2 CNS cancer (neuro;met) SK-N-AS 0.0 Lung ca. NCI-N 4 1 7 0.0 CNS cancer (astro) SF-539 1.7 Lng ca.NCI-N47 .

13871 387 WO 03/093432 PCT/US03/13690 Lung ca. LX-1 0.0 CNS cancer (astro) SNB-75 4 Lung ca. NCI-HI46 0.0 CNS cancer (glio) SNB-19 0. Lung ca. SHP-77 0.4 CNS cancer (glio) SF-295 0.0 Lung ca. NCI-H23 0.4 Brain (Amygdala) 4.0 Lung ca. NCI-H460 0.0 Brain (Cerebellum) 6.7 Lung ca. HOP-62 0.0 Brain (Fetal) 19.3 Lung ca. NCI-H522 0.0 Brain (Hippocampus) 6.9 Lung ca. DMS-114 0.0 Cerebral Cortex pool 8.2 Liver 0.0 Brain (Substantia nigra) 3.0 Fetal Liver 0.0 Brain (Thalamus) 5.3 Kidney pool 7.9 Brain (Whole) 33.4 Fetal Kidney 0.9 Spinal Cord 0.0 Renal ca. 786-0 0.0 Adrenal Gland 2.9 Renal ca. A498 0.0 Pituitary Gland 4.0 Renal ca. ACHN 7.2 Salivary Gland1.8 Renal ca. UO-31 0.0 Thyroid 14.5 Renal ca. TK-10 J0.0 Pancreatic ca. PANC-i1 0.0 Bladder . 9.4 ;Pancreas pool 0.4 General screeningpanelvl.7 Summary: Ag7182 Highest CGI 10590 gene expression was seen in adipose (CT=31.9). Therapeutic modulation of this gene and encoded protein is useful in the treatment of adipose related diseases such as obesity and diabetes. Low gene expression was seen in fetal and adult brain. Therapeutic modulation of this gene and/or encoded protein is useful in the treatment of neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. E. CG184416-01: metalloprotease mmp21/22C. Expression of gene CG184416-01 was assessed using the primer-probe set Ag7014, described in Table EA. Results of the RTQ-PCR runs are shown in Table EB. Table EA. Probe Name Ag7014 Primersl Sequences Length Start Position SEQ ID No Forward 5'-cgctcccgataggatgc-3' .17 862 361 Probe TET-5'-acgcgcacacgaacagcctgtc-3'-TAMRA 22 882 362. Reverse s'-ggcagagcctcttcatgag-3' 19 942 363 388 WO 03/093432 PCT/US03/13690 Table EB. General_ screening_panelvi.6 Column A - Rel. Exp.(%) Ag7014, Run 279032748 Tisue Name A Tissue Name A Adipose TsuN. i0.3 jRenal ca. TK-10 1.3 Melanoma* Hs688(A).T 0.0 Bladder .5 Melanoma* Hs688(B).T 1.5 Gastric ca. (liver met.) NCI-N87 0.0 Melanoma* M14 i 0.0 Gastric ca. KATO III 1.6 Melanoma* LOXIMVI 0.0 Colon ca. SW-948 0.0 Melanoma* SK-MEL-5 15. Colon ca. SW480 Squamous cell carcinoma SCC-4 1.6 Colon ca.* (SW480 met) SW620 0.9 Testis Pool 0.0 Colon ca. HT29 1 Prostate ca.* (bone met) PC-3 9.5 Colon ca. HCT-116 1.4 Prostate Pool 0.0 Colon ca. CaCo-2 0.0 Placenta ......... 0.8. Colon cancer tissue 2.0 Uterus Pool ... 1.9 Colon ca. SW1116 4.9 Ovarian ca. OVCAR-3 0.0 Colon ca. Colo-205 0.0 Ovarian ca. SK-OV-3 0.9 Colon ca. SW-48 1.2 Ovarian ca. OVCAR-4 0.3 Colon Pool . 1.1 Ovarian ca. OVCAR-5 2.7 Small Intestine Pool 0.2 Ovarian ca. IGROV-1 0.0 Stomach Pool 0.6 Ovarian ca. OVCAR-8 100.0 Bone Marrow Pool . 1 Ovary 0.0 Fetal Heart2.8 Breast ca. MCF-7 1.3 Heart Pool2.6 Breast ca. MDA-MB-231 1.2 Lymph Node Pool 6.1 Breast ca. BT 549 3.3 Fetal Skeletal Muscle . 0 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.8 Breast ca. MDA-N 0.6 Spleen Pool 0.2 Breast Pool 4.7 Thymus Pool 0.1 Trachea 1.2 CNS cancer (glio/astro) U87-MG 0.0 Lung 0.0 CNS cancer (glio/astro) U-I 18-MG0 Fetal Lung 4.7 CNS cancer (neuro;met) SK-N-AS 0.0 Lung ca. NCI-N417 1.8 CNS cancer (astro) SF-539 0.5 Lung ca. LX-1 0.7 CNS cancer (astro) SNB-75 5.1 Lung ca. NCI-H146 0.5 CNS cancer (glio) SNB-19 2.2 Lung ca. SHP-77 1.1 CNS cancer (glio) SF-295 1.1 Lung ca. A549 0.0 Brain (Amygdala) Pool 0.0 Lung ca. NCI-H526 0.0 Brain (cerebellum) 1.0 Lung ca. NCI-H23 0.0 Brain (fetal) 0.0 g ca. NCI-H460 0.0. Brain (Hippocampus) Pool 1.1 ung ca. HOP-62 2.3 Cerebral Cortex Pool 0.0 389 WO 03/093432 PCT/USO3/13690 Lung ca. NCI-H522 0.0 Brain (Substantia nigra) Pool 0.0 Liver 0.0 Brain (Thalamus) Pool 0.0 Fetal Liver 1.0 Brain (whole) 0.0 Liver ca. HepG2 0.0 , Spinal Cord Pool 0.0 Kidney Pool 7.1 Adrenal Gland 0.0 Fetal Kidney 0.0 Pituitary gland Pool 2.0 Renal ca. 786-0 1.6 Salivary Gland 0.0 Renal ca. A498 0.0 Thyroid (female) 0.0 Renal ca. ACHN 0.0 Pancreatic ca. CAPAN2 0.1 Renal ca. UO-31 0.0 ancreas Pool 1.5 Generalscreening_panel_vl.6 Summary: Ag7014 Highest gene expression was detected in an ovarian cancer cell line (CT=29.8), with low but significant expression in a prostate cancer cell line. Gene expression level is a marker of ovarian and prostate cancer tissue and for detecting the presence of these cancers in vitro or in vivo. F. CG50513-01: Tumor-related protein (PDRC1). Expression of gene CG50513-01 was assessed using the primer-probe sets Ag2752 and Ag5, described in Tables FA and FB. Results of the RTQ-PCR runs are shown in Tables FC, FD, FE and FF. Table FA. Probe Name Ag2752 Start SEQ ID Primers Sequences Length Position No i .................. P osition N o Forward 5'-gaagacagctggagagagtttg-3' 22 1387 364 Probe TET-5'-cttgtcctgcatggccaatccagt-3'- 24 1410 365 r TAMRA Reverse 5'-agctgcataatgaagagctgat- 3 ' .22 1450 366 Table FB. Probe Name Ag5 Start SEQ ID Primers Sequences Length Position No For d s'-gtgatcctcaggctggacca-3' 20 1219 367 Probe TET-5'-ccagtgtttcctcagcacagggcc-3'- 24 1253 368 Reverse 5 '-ttctgactggctgcatcc-3' 19 1278 369 390 WO 03/093432 PCT/USO3/13690 Table FC. Panel 1 _ _Column A - Rel. Exp.(%) Ag5, Run 87354971 Tissue Name A Tissue Name AI Endothelial cells 0.0 Renal ca. 786-0 0.0 Endothelial cells (treated) 0.0 Renal ca. A498 j0.1 Pancreas 0.0Renalca.RXF 393 0.0 Pancreatic ca. CAPAN 2 0.0 Renal ca. ACHN 0.0 Adrenal gland 0.2 Renal ca. UO-31 0.2 Thyroid 3.5 Renal ca. TK-10 0.1 Salivary gland 3 3.7 Liver0.0 Pituitary gland 1.6 Liver (fetal) 0.0 Brain (fetal) 0.0 Liver ca. (hepatoblast) HepG2 0.0 Brain (whole) 0.0 Lung 0.0 Brain (amygdala) 0.0 Lung (fetal) 0.0 Brain (cerebellum) 0.2 Lung ca. (small cell) LX-1 0.0 Brain (hippocampus) 0.1 Lung ca. (small cell) NCI-H69 0.6 Brain (substantia nigra) 0.0 Lung ca. (s.cell var.) SHP-77 0.0 Brain (thalamus) 0.0 Lung ca. (large cell)NCI-H460 0.0 Brain (hypothalamus) 0.0 Lung ca. (non-sm. cell) A549 0.1 Spinal cord 1.7 Lung ca. (non-s.cell) NCI-H23 0.1 Sp n lc r . u g ca. ( -..... .......... ..... glio/astro U87-MG 0.0 Lung ca. (non-s.cell) HOP-62 0.0 glio/astro U-118-MG 0.0 Lung ca. (non-s.cl) NCI-H522 0.0 astrocytoma SW1783 0.0 Lung ca. (squam.) SW 900 0.2 neuro*; met SK-N-AS 0.2 Lung ca. (squam.) NCI-H596 0.3 astrocytoma SF-539 0.0 Mammary gland 0.0 astrocytoma SNB-75 0.0 Breast ca.* (pl.ef) MCF-7 0.0 glioma SNB-19 0.2 Breast ca.* (pl.ef) MDA-MB-231 0.2 glioma U251 0.1 Breast ca.* (pl. ef) T47D 0.9 glioma SF-295 0.0 Breast ca. BT-549 0.0 Heart 0.1 Breast ca. MDA-N 0.0 Skeletal muscle 0.2 Ovary 0.0 Bone marrow 0.0 Ovarian ca. OVCAR-3 0.1 Thymus 0.7 Ovarian ca. OVCAR-4 0.0 Spleen .... 0.0 Ovarian ca. OVCAR-5 0.6 Lymph node 7 0.1 Ovarianca. OVCAR-8 0.0 Colon (ascending) 1.3 Ovarian ca. IGROV-1 0.0 Stomach 0.0 Ovarian ca. (ascites) SK-OV-3 0.0 Small intestine 0.0 ~Uterus 0.0 Colon ca. SW480 0.1 Placenta 0.0 Colon ca.* SW620 (SW480 met) 0.0 Prostate0.0 Colon ca. HT29 0.0 Prostate ca.* (bone met) PC-3 0.0 391 WO 03/093432 PCT/US03/13690 Colon ca. HCT-116 0.0 Testis 3.6 Colon ca. CaCo-2 0.0 Melanoma Hs688(A).T 0.0 Colon ca. HCT-15 0.2 Melanoma* (met) Hs688(B).T 10.0 Colon ca. HCC-2998 0.0 Melanoma UACC-62 0.0.. Gastric ca. * (liver met) NCI-N87 0.0 Melanoma M14 0.2 Bladder 0.1 Melanoma LOX IMVI .0.1 Trachea 100.0 Melanoma* (met) SK-MEL-5 0.0 Kidney 0.0 Melanoma SK-MEL-28 0.0 IKidney (fetal) 0.0 Table FD. Panel 1.3D Column A - Rel. Exp.(%) Ag2752, Run 165527213 Tissue Name A Tissue Name A ILiver adenocarcinoma 0.0 Kidney (fetal) 0.3 Pancreas 0.0 Renal ca. 786-0 0.0 Pancreatic ca. CAPAN 2 0.0 Renal ca. A498 0.2 Adrenal gland 0.0 Renal ca. RXF 393 0.0 Thyroid 2.1 Renal ca. ACHN 0.0 Salivary gland 12.9 Renal ca. UO-31 0.0 Pituitary gland 0.0 Renal ca. TK-10 0 Brain (fetal) 0.0 Liver 0. Brain (whole) 0.8 Liver (fetal) 0.0 Brain (amygdala) 0.5 Liver ca. (hepatoblast) HepG2 0.0 Brain (cerebellum) 0.0 Lung 0.3 Brain (hippocampus) 0.5 Lung (fetal) 0.0 Brain (substantia nigra) 0.0 Lung ca. (small cell) LX-10.0 Brain (thalamus) 0.0 Lung ca. (small cell) NCI-H69 0.0 Cerebral Cortex 0.0 Lung ca. (s.cell var.) SHP-77 0.0 Spinal cord 100.0 Lung ca. (large cell)NCI-H460 0.4 glio/astro U87-MG 0.0 Lung ca. (non-sm. cell) A549 0.0 glio/astro U-11 8-MG 0.0 Lung ca. (non-s.cell) NCI-H23 0.0 astrocytoma SW1783 0.0 Lung ca. (non-s.cell) HOP-62 0.0 neuro*; met SK-N-AS 0.0 Lung ca. (non-s.cl) NCI-H522 0.0 astrocytoma SF-539 .0.0 Lung ca. (squam.) SW 900 . astrocytoma SNB-75 0.0 Lung ca. (squam.) NCI-H596 0.0 glioma SNB-19 .0.4 Mammary gland 146.7 glioma U251 .40.4 Breast ca.* (pl.ef) MCF-7 0.0 glioma SF-295 .0.0 Breast ca.* (pl.ef) MDA-MB-231 0.0 Heart (fetal) .0.0 Breast ca.* (pl.ef) T47D Heart -0.0 jBreast ca. BT-549 - 0.0 Skeletal muscle (fetal) . 0'[ Breast ca. MDA-N 0.0 392 WO 03/093432 PCT/US03/13690 Skeletal muscle 0.0 Ovary 0.0 Bone marrow 0.0 Ovarian ca. OVCAR-3 O. Thymus 8.9 Ovarian ca. OVCAR-4 0.0 Spleen 0.6 Ovarian ca. OVCAR-5 Lymph node 2.7 Ovarian ca. OVCAR-8 0.0 Colorectal 0.2 Ovarian ca. IGROV-1 0.0 Stomach 44.8 !Ovarian ca.* (ascites) SK-OV-3 0.6 Small intestine 0.0 Uterus 2.1 Colon ca. SW480 0.3 Placenta 0.0 Colon ca.* SW620(SW480 met) 0.0 Prostate 2.4 Colon ca. HT29 0.0Prostate ca.* (bone met)PC-3 0.0 Colon ca. HCT- 116 0.0 Testis 1.4 Colon ca. CaCo-2 0.0 Melanoma Hs688(A).T 0.0 Colon ca. tissue(ODO3866) 0.0 Melanoma* (met) Hs688(B).T 0.0 Colon ca. HCC-2998 0.0 Melanoma UACC-62 0.0 Gastric ca.* (liver met) NCI-N87 0.0 Melanoma M14 0.0 Bladder 0.0 Melanoma LOX IMVI 05 Trachea 19.5 Melanoma* (met) SK-MEL-5 0.0 Kidney 0.0 Adipose 0.0 Table FE. Panel 2D Column A - Rel. Exp.(%) Ag2752, Run 162555825 ............................ ............ ......... T ~ s u e a m e ........ ... ................................ .. .. .. .. .. .. .. .. .. ..... ..... . . . ........ ... ....... . .T.s N a m .... ...... .. ... .. .A.. Tissue Name A Tissue Name A Normal Colon 3.6 Kidney Margin 8120608 0.0 CC Well to Mod Diff(ODO3866) 0.0 Kidney Cancer 8120613 0.0 CC Margin (ODO3866) 3.0 Kidney Margin 8120614 0.0 CC Gr.2 rectosigmoid (ODO3868) 0.9 Kidney Cancer 9010320 1.4 CC Margin (ODO3868) 0.0 Kidney Margin 9010321 3.9 CC Mod Diff (ODO3920) 0.0 Normal Uterus 0.0 CC Margin (ODO3920) 0.0 Uterus Cancer 064011 0.0 CC Gr.2 ascend colon (OD03921) 0.0 Normal Thyroid CC Margin (ODO3921) 0.0 Thyroid Cancer 064010 0.0 CC from Partial Hepatectomy (ODO4309) Cne 04 0.0 Thyroid Cancer A302152 2.1 Mets . o ancer Liver Margin (ODO4309) 0.0 Thyroid Margin A302153 6.6 Colon mets to lung (OD04451-01) 0.0 jNormal Breast 0.0 Lung Margin (OD04451-02) 0.0 Breast Cancer (OD04566) 0.0 ,Normal Prostate 6546-1 100.0 Breast Cancer (OD04590-01) 0.0 Prostate Cancer (OD04410) 0.0 Breast Cancer Mets (OD04590-03) 0.0 Prostate Margin (OD0441 0) 35 Breast Cancer Metastasis (OD04655 39305) 393 WO 03/093432 PCT/US03/13690 Prostate Cancer (OD04720-01) 0.0 Breast Cancer 064006 0.0 Prostate Margin (OD04720-02) 0.0 Breast Cancer 1024 0.0 Normal Lung 061010 0.0 Breast Cancer 9100266 0.0 Lung Met to Muscle (ODO4286) 1.0 Breast Margin 9100265 0.0 Muscle Margin (ODO4286) 0.0 Breast Cancer A209073 0.0 Lung Malignant Cancer (OD03126) 0.0 Breast Margin A209073 0. Lung Margin (OD03126) 0.0 Normal Liver 10.0 Lung Cancer (OD04404) 24.5 Liver Cancer 064003 5.0 Lung Margin (OD04404) 0.0 Liver Cancer 1025 0.0 Lung Cancer (OD04565) 0.0 Liver Cancer 1026 0.0 Lung Margin (OD04565) 0.0 Liver Cancer 6004-T 0.0 Lung Cancer (OD04237-01) 0.0 Liver Tissue 6004-N 0.0 Lung Margin (OD04237-02) 0.0 Liver Cancer 6005-T 0.0 Ocular Mel Met to Liver (ODO4310) 0.0 Liver Tissue 6005-N 0.0 Liver Margin (ODO4310) 0.0 Normal Bladder 3.3 Melanoma Mets to Lung (OD04321) 2.7 Bladder Cancer 1023 0.0 Lung Margin (OD04321) 0.0 Bladder Cancer A302173 3.3 Normal Kidney 3. Bladder Cancer (OD04718-01) 0.0 Bladder Normal Adjacent Kidney Ca, Nuclear grade 2 (OD04338) 1.2 A n 2.6 (ODO4718-03) Kidney Margin (OD04338) 2.1 Normal Ovary 0.0 Kidney Ca Nuclear grade 1/2 (OD04339) 0.0 Ovarian Cancer 064008 0.0 Kidney Margin (OD04339) 0.8 Ovarian Cancer (OD04768-07) 0.0 Kidney Ca, Clear cell type (OD04340) 0.0 Ovary Margin (OD04768-08) 0.0 Kidney Margin (OD04340) 1.2 Normal Stomach 0.8 Kidney Ca, Nuclear grade 3 (OD04348) 0.0 Gastric Cancer 9060358 0.0 Kidney Margin (OD04348) 2.0 Stomach Margin 9060359 0.0 Kidney Cancer (OD04622-01) 0.0 iGastric Cancer 9060395 0.0 Kidney Margin (OD04622-03) 0.0 Stomach Margin 9060394 0.0 Kidney Cancer (OD04450-01) 0.9 Gastric Cancer 9060397 0.0 Kidney Margin (OD04450-03) 0-.0 Stomach Margin 9060396 0.0 Kidney Cancer 8120607 . 0.0 Gastric Cancer 064005 0.0 Table FF. Panel 4D Column A - Rel. Exp.(%) Ag2752, Run 162015236 Tissue Name A Tissue Name A Secondary Thl act 0.0 1HUVEC IL-lbeta 0.0 Secondary Th2 act 0.01 HUVEC IFN gamma 0.0 Secondary Trl act 0.0 HUVEC TNF alpha + IFN gamma 0.0 Secondary Thl rest 0.0 HUVEC TNF alpha + IL4 0.0 Secondary Th2 rest 0.0 HUVEC IL-11 0.0 394 WO 03/093432 PCT/USO3/13690 Secondary Trl rest 0.0 Lung Microvascular EC none 1.9 Primary Thl act 0.0 Lung Microvascular EC TNFalpha + IL-lbeta 0.0 Primary Th2 act 0.0 Microvascular Dermal EC none 0.0 0 Microsvasular Dermal EC TNFalpha + IL- 0 Primary Trl act 10.01 0beta Ilbeta Primary Thl rest 0.0]Bronchial epithelium TNFalpha + ILlbeta 0. Primary Th2 rest L.O Small airway epithelium none . Primary Tr rest 0.0 Small airway epithelium TNFalpha + IL-1 beta 80.7 CD45RA CD4 lymphocyte act O.0Coronery artery SMC rest 1.7 CD45RO CD4 lymphocyte act 0.0 Coronery artery SMC TNFalpha + IL-I beta 0.0 CD8 lymphocyte act 0.0 Astrocytes rest 0.0 Secondary CD8 lymphocyte rest 0.0 Astrocytes TNFalpha+ IL-lbeta 0.0 Secondary CD8 lymphocyte act 0.0 KU-812 (Basophil) rest 0.0 CD4 lymphocyte none 0.0 KU-812 (Basophil) PMA/ionomycin 0.0 2ry Thl/Th2/Trl anti-CD95 CH1- C0.CCD1106 (Keratinocytes) none 0.0 CH1I LAK cells rest 0.0 CCD1106 (Keratinocytes) TNFalpha + IL- 0 l beta LAK cells IL-2 0.0 Liver cirrhosis 8.1 LAK cells IL-2+IL-12 0.0 Lupus kidney 0.0 LAK cells IL-2+IFN gamma 0.0 NCI-H292 none 0.0 LAK cells IL-2+ IL-18 0.NCI-H292 IL-4 0.0 LAK cells PMA/ionomycin 0.0 NCI-H292 IL-9 0.0 NK Cells IL-2 rest 0.0 NCI-H292 IL-13 3.2 Two Way MLR 3 day . 0.0 NCI-H292 IFN gamma 0.0 Two Way MLR 5 day 00HPAEC none 0.0 Two Way MLR 7 day 0.0 HPAEC TNF alpha + IL- 1 beta 0.0 PBMC rest 0.0 Lung fibroblast none 0.0 PBMC PWM 0.0 Lung fibroblast TNF alpha + IL-1 beta 0.0 PBMC PHA-L 0.0 Lung fibroblast IL-4 0.0 Ramos (B cell) none 0.01Lung fibroblast IL-9 0.0 Ramos (B cell) ionomycin 0.0 Lung fibroblast IL-13 0.0 B lymphocytes PWM 0.0' Lung fibroblast IFN gamma 0.0 B lymphocytes CD40L and IL-4 2.6jDermal fibroblast CCD1070 rest 0.0 EOL-1 dbcAMP 0.0 Dermal fibroblast CCD1070 TNF alpha 0.3 EOL-1 dbcAMP PMA/ionomycin 0.0 Dermal fibroblast CCD1070 IL-1 beta 0.0 Dendritic cells none 0.0 Dermal fibroblast IFN gamma 0.0 Dendritic cells LPS 0.0 Dermal fibroblast IL-4 Dendritic cells anti-CD40 0.0 IBD Colitis 2 0.01 Monocytes rest 0.0 IBD Crohn's 0.0 Monocytes rest p6 Monocytes LPS 0.,O Colon .0.0 Macrophages rest 0.0 Lung 4.7 395 WO 03/093432 PCT/USO3/13690 Macrophages LPS 0.0 Th y m us 0.0 HUVEC none 0.0 Kidney 3.6 HUVEC starved 0.0 Panel 1 Summary: Ag5 Highest CG50513-01 gene expression was seen in trachea (CT=25.2) with low to moderate expression detected in normal tissues including: testis, colon, thymus, skeletal muscle, spinal cord, pituitary gland, salivary gland, thyroid, and adrenal gland. Therefore, therapeutic modulation of this gene, encoded protein and/or antibodies, small molecule drug targeting the protein are useful in the treatment of the diseases associated with these tissues including obesity, diabetes, fertility and hypogonadism. Low gene expression was also seen in breast, lung and brain cancer cell lines. Gene expression level is a marker of these cancer tissues and for detecting the presence of these cancers in vitro or in vivo. Therapeutic modulation of this gene gene, encoded protein and/or antibodies, small molecule drug targeting the protein is useful in the treatment of these cancers. Panel 2D Summary: Ag2752 Highest gene expression was seen in normal prostate (CT=31.4) and significant expression was also seen in normal prostate and thyroid compared to cancer samples. Therapeutic modulation of this gene and/or encoded protein that increases the activity of this gene and the encoded protein are useful in the treatment of prostate and thyroid cancers. Low gene expression was also detected in lung cancer which was higher than expression in normal lung. Therefore, expression level of this gene will be useful as marker to detect the presence of lung cancer and therapeutic modulation of this gene, encoded protein is useful in the treatment of lung cancer. Panel 4D Summary: Ag2752 Significant gene expression was detected in resting and activated small airway epithelium (CTs=31.5) and modulation of the expression or activity of this gene and/or the protein encoded by it is useful in the treatment of asthma, COPD, and emphysema. G. CG50949-03: MEMBRANE-TYPE MOSAIC SERINE PROTEASE. Expression of gene CG50949-03 was assessed using the primer-probe sets Ag020b, Ag20 and Ag5238, described in Tables GA, GB and GC. Results of the RTQ-PCR runs are shown in Tables GD, GE and GF. 396 WO 03/093432 PCT/USO3/13690 Table GA. Probe Name Ag020b Start ISEQ ID Primers; Sequences Lengt Position No Forward '-gtgggaacactggagggagat-3' 21 1039 370 TET-5 -aggtctgaatgcccttcccagcg-3 '- 23 1012 371 TAMRA Reverse 5'-caactccaccatccaggaaag-3' 21 984 372 Table GB. Probe Name Ag20 Primers Sequences Length Start SEQ D Position No Forward 5' -gtgggaacactggagggagat-3' 21 1039 373 Probe TET-5 '-aggtctgaatgcccttcccagcg-3'- 23 1012 374 Reverse 5-caactccaccatccaggaaag-3' 21 984 375 Table GC. Probe Name Ag5238 Primers Sequences Length Start Position SEQ ID No Forward 5'-ggaggtaagatccctgcaqc-3' 20 1785 376 Probe TET-5'-acttcctcaggtggggaccct-3'-TAMRA 21 1831 377 Reverse 1 ' -tgaggggacctctgcctaca-3' 2 . 1868 38 Table GD. Generalscreeningpanelvl.5 Column A - Rel. Exp.(%) Ag5238, Run 229665050 Tissue Name A Tissue Name A Adipose 1.9 Renal ca. TK-10 0.0 Melanoma* Hs688(A).T 0.0 Bladder 16.0 Melanoma* Hs688(B).T 0.0 Gastric ca. (liver met.) NCI-N87 55.9 Melanoma* M14 61.6 Gastric ca. KATO III 0.0 Melanoma* LOXIMVI 0.0 Colon ca. SW-948 1.2 Melanoma* SK-MEL-5 0.0 Colon ca. SW480 0.0 Squamous cell carcinoma SCC-4 0.0 Colon ca.* (SW480 met) SW620 1.5 Testis Pool 1.3 Colon ca. HT29 2.0 Prostate ca.* (bone met) PC-3 0.0 Colon ca. HCT-116 2.1 Prostate Pool 7.3 Colon ca. CaCo-2 19.3 Placenta 28.7 Colon cancer tissue 7.9 Uterus Pool 0.0 Colon ca. SW1116 0.0 Ovarian ca. OVCAR-3 5.8 Colon ca. Colo-205 3.7 Ovarian ca. SK-OV-3 0.0 Colon ca. SW-48 00 Ovarian ca. OVCAR-4 3.0 Colon Pool Ovarian ca. OVCAR-5 10.3 Small Intestine Pool 36 397 WO 03/093432 PCT/US03/13690 Ovarian ca. IGROV-1 0.0 Stomach Pool 4.7 Ovarian ca. OVCAR-8 0.0 Bone Marrow Pool 1.8 Ovary 2.8 Fetal Heart 6.3 Breast ca. MCF-7 63.3 Heart Pool 1.6 Breast ca. MDA-MB-231 0.0 Lymph Node Pool 4.2 Breast ca. BT 549 4.7 Fetal Skeletal Muscle 0.0 Breast ca. T47D 100.0 ISkeletal Muscle Pool 0.0 Breast ca. MDA-N 0.0 Spleen Pool 0.0 Breast Pool 0.0 Thymus Pool 0.0 Trachea 9.0 CNS cancer (glio/astro) U87-MG 0.0 Lung 0.0 CNS cancer (glio/astro) U-118-MG 0.0 Fetal Lung 4.7 CNS cancer (neuro;met) SK-N-AS 0.0 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 4.0 CNS cancer (glio) SNB-19 0.0 Lung ca. SHP-77 0.0 CNS cancer (glio) SF-295 0.0 Lung ca. A549 0.0 Brain (Amygdala) Pool 0.0 Lung ca. NCI-H526 1.9 Brain (cerebellum) 0.0 Lung ca. NCI-H23 3.3 Brain (fetal) 2.9 Lung ca. NCI-H460 87.1 Brain (Hippocampus) Pool 2.3 Lung ca. HOP-62 0.0 Cerebral Cortex Pool 0.0 Lung ca. NCI-H522 0.0 Brain (Substantia nigra) Pool 2.6 Liver 0.0 Brain (Thalamus) Pool 0.0 Fetal Liver 6.3 Brain (whole) 0.0 Liver ca. HepG2 0.0 Spinal Cord Pool 0.0 Kidney Pool 1.5 Adrenal Gland 2.4 Fetal Kidney 2.5 Pituitary gland Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland6.1 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 7.0 Table GE. General_screening_panelvl.6 Column A - Rel. Exp.(%) Ag20, Run 277226634 . Tissue Name A Tissue Name A Adipose ."2 Renal ca. TK-10 0.1 0.0 IBladder39 jMelanoma* Hs688(A).T ____________________3.9___ Melanoma* Hs688(B).T .0.0 Gast ric ca. (liver met.) NCI-N87 -42.3 eanma* M 4 . . . . 9.4 G astric ca. KATO III 1.5 Melanoma* LOXIM 30.4 Colon ca. SW-948 0.5 Melanoma* SK-MEL-5 1 0.8 jColon ca. SW480 0.6 398 WO 03/093432 PCT/US03/13690 Squamous cell carcinoma SCC-4 1.8 Colon ca.* (SW480 met) SW620 0.3 Testis Pool 0.3 Colon ca. HT296.8 Prostate ca.* (bone met) PC-3 0.3 Colon ca. HCT-116 2.0 Prostate Pool 0.9Colon ca. CaCo-2 92.7 Placenta 30.1 Colon cancer tissue 23.3 Uterus Pool 0.8 Colon ca. SW 116 0.2 Ovarian ca. OVCAR-3 9.5 Colon ca. Colo-205 8.2 Ovarian ca. SK-OV-3 01Colon ca. SW-48 1.8 Ovarian ca. OVCAR-4 1.6 Colon Pool 0.7 Ovarian ca. OVCAR-5 35.6 Small Intestine Pool 1.7 Ovarian ca. IGROV-1 0.2 Stomach Pool 1.0 Ovarian ca. OVCAR-8 0.0 Bone Marrow Pool 1.3 Ovary .... 0.2 Fjetal Heart 0.1 Breast ca. MCF-7 77.9 Heart Pool 0.0 Breast ca. MDA-MB-231 0.2 Lymph Node Pool 0.7 Breast ca. BT 549 0.4 Fetal Skeletal Muscle 0.1 Breast ca. T47D 100.0 Skeletal Muscle Pool 0.2 Breast ca. MDA-N 0.3 Spleen Pool 1.0 Breast Pool 0.5 Thymus Pool 1.2 Trachea 6.9 CNS cancer (glio/astro) U87-MG 0.1 Lung 0.1 CNS cancer (glio/astro) U-118-MG 0.3 Fetal Lung 9.0 CNS cancer (neuro;met) SK-N-AS 0.0 Lung ca. NCI-N417 0.0 CNS cancer (astro) SF-539 0.6 Lung ca. LX-1 2.3 CNS cancer (astro) SNB-75 0.0 Lung ca. NCI-HI146 0.4 CNS cancer (glio) SNB-19 10.4 Lung ca. SHP-77 0.2 CNS cancer (glio) SF-295 0.7 Lung ca. A549 0.5 Brain (Amygdala) Pool 0.2 0 Brain (cerebellum)_ Lung ca. NCI-H526 Brain (cerebellum) 0.3 Lung ca. NCI-H23 0.8 Brain (fetal) 1.5 Lung ca. NCI-H460 0.4 Brain (Hippocampus) Pool 1.4 Lung ca. HOP-62 0.2 Cerebral Cortex Pool 0.2 Lung ca. NCI-H522 0.3 Brain (Substantia nigra) Pool 0.2 Liver 0.2 Brain (Thalamus) Pool 0.4 Fetal Liver 2.3 Brain (whole) 0.1 Liver ca. HepG2 0.0 Spinal Cord Pool 0.2 Kidney Pool 0.3 Adrenal Gland 0.2 Fetal Kidney 0.8 Pituitary gland Pool 0.2 Renal ca. 786-0 0.2 alivary Gland 8.8 Renal ca. A498 0.2 Thyroid (female) 6.0 Renal ca. ACHN 1.1 Pancreatic ca. CAPAN2 1.9 Renal ca. UO-31 0.8 Pancreas Pool 3.0 399 WO 03/093432 PCT/US03/13690 Table GF. Panel 4.1D Column A - Rel. Exp.(%) Ag20, Run 268789078 Column B - Rel. Exp.(%) Ag5238, Run 229819576 Tissue Name Tissue Name A B Secondary Thl act 2.3 1.9 H-UVEC IL-lbeta 1 0.0 Secondary Th2 act 12.0 1.8 HUVEC IFN gamma 1.2 0.0 Secondary Trl act 7.7 10.9 HUVEC TNF alpha+ IFN gamma 2.1 23.3 Secondary Thl rest 2.4 2.0 HUVEC TNF alpha + IL4 1.4 0.0 Secondary Th2 rest 4.2 0.0 HUVEC IL-11 2.8 0.0 Secondary Trl rest 3.7 0.0 Lung Microvascular EC none 3.7 0.0 Primary Thl act Lung Microvascular EC TNFalpha+ Primary Th1 act 4. 4.7 be 10.02.1 IL- I beta Primary Th2 act 7.4 2.4 Microvascular Dermal EC none 0.6 0.0 Primary T act Microsvasular Dermal EC TNFalpha + Primary Trl act 6.1 0.0 4.4 2.1 IL- 1beta . Bronchial epithelium TNFalpha + Primary Thl rest 1.4 0.0 IL1beta0.0 0.0 Primary Th2 rest 2.8 0.0 Small airway epithelium none 34.2 0.0 Primary T rest 1.7 0.0Small airway epithelium TNFalpha + 25.9 Primary Trl rest 17002. . IL-lbeta CD45RA CD4 lymphocyte act 6.1 0.0 Coronery artery SMC rest 4.8 0.0 CD45RO CD4 lymphocyte act 6.7 34 Coronery artery SMC TNFalpha + IL- 0.0 0.0 beta CD8 lymphocyte act 8.4 0.0 Astrocytes rest 0.7 0.0 Secondary CD8 lymphocyte I__ Secondary CD8 lymphocyt 7.0 2.5 Astrocytes TNFalpha + IL-lbeta 1.5 1.5 rest Secondary CD8 lymphocyte act 1.2 0.0 KU-812 (Basophil) rest 5.0 .5 CD4 lymphocyte none 6.8 0.0 KU-812 (Basophil) PMA/ionomycin .8 0.0 2ry Thl/Th2/Trl anti-CD95 CH11 6.6 0.0 CCD1106 (Keratinocytes) none 5.1 27.9 LAK cells rest CCD 1106 (Keratinocytes) TNFalpha + LAK cells rest 2.6 8.7 1Llea0.0 3.9 IL-1beta LAK cells IL-2 3.20.0 Liver cirrhosis 6.7 3.4 LAK cells IL-2+IL-12 2.2 11.0 NCI-H1292 none 100.0 0.0 LAK cells IL-2+IFN gamma 2.5 0.0 NCI-H292 IL-4 40.1 0.0 LAK cells IL-2+ IL-18 0.9 2.0 NCI-H4292 IL-9 98.6 19.9 LAK cells PMA/ionomycin 2.3 1.8 NCI-H292 IL-13 73.7 0.0 NK Cells IL-2 rest 12.5 1.6 NCI-H292 IFN gamma 49.0 0.0 Two Way MLR 3 day 6.3 4.5 HPAEC none 8.5 0.0 Two Way MLR 5 day 1.8 0.0 HPAEC TNF alpha + IL-1 beta 4.7 0.0 Two Way MLR 7 day 4.1 16.7 Lung fibroblast none 2.8 0.0 PBMC rest 2.0 Lung fibroblast TNF alpha + IL-1 beta 3.7 4.7 400 WO 03/093432 PCT/USO3/13690 PBMC PWM 0.0 9.7 Lung fibroblast IL-4 2.5 0.0 PBMC PHA-L 5.8 0.0 Lung fibroblast IL-9 4.1 1.9 Ramos (B cell) none 1.5 0.0 Lungfibroblast IL-13 0.0 0.0 .. . . .. .. .. ............................ I..................... ...... .. .. Ramnos (B cell) ionomycin 7.8 0.0 Lung fibroblast IFN gamma .1.4 0.0 B lymphocytes PWM 1.3 1.7 Dermal fibroblast CCD1070 rest 1.3 2.7 B lymphocytes CD40L and1 m ocytes 0.0 Dermal fibroblast CCD1070 TNF alpha 9.1 0.0 IL-4 3 EOL-1 dbcAMP 5.4 0.0 Dermal fibroblast CCD1070 IL-1 beta 2.8 0.0 EOL-1 dbcAMP. I31 1 Mao cA 0.0 1 2.5 Dermal fibroblast IFN gamma 3.1 0.0 PMA/ionomycin H V EC.. non ........ ............. id e .. 9 .... Dendritic cells none J6.2 0.0 Dermal fibroblast IL-4 2.7 J0.0 .E ..... ......... I ..... ... . .. . I -1. . . .... .. . .. I... . ..... . . .

Dendritic cells LPS 10.7 3.0 Dermal Fibroblasts rest e0.3 0.0 Dendritic cells anti-CD40 3.0 0.0 Neutrophils TNFa+LPS 1.7 0.0 Monocytes rest 1.2 40.6 Neutrophils rest 6.6 0.0 Monocytes LPS 27.9 0.0 lColon 3.1 0.0 Macrophages rest 3.2 0.0 Lung 3.1 .133.9 Macrophages LPS 10.4 100.0 Thymus 0.0o0. HUJVEC none 0.4 3.1 Kidney..5 5.9 HUVEC starved 2.8 3.5 Generalscreeningpanelvl.5 Summary: Ag5238 Highest gene expression was detected in T47D breast cancer cell line (CT=32.7) and low expression was also seen in melanoma, lung, gastric, and breast cancers cell lines. Expression level is a useful marker to differentiate these cancers from normal tissues and to detect the presence of these cancers in vitro or in vivo. Generalscreeningpanelv1l.6 Summary: Ag2O Highest gene expression was detected in T47D breast cancer cell line (CT=26). Moderate to low expression was also seen in melanoma, lung, colon, renal, pancreatic, renal, brain, gastric, and breast cancers cell lines. Expression is a useful marker to differentiate these cancers from normal tissues and to detect the presence of these cancers in vitro or in vivo. Among tissues with metabolic or endocrine function, this gene was expressed at moderate to low levels in pancreas, adipose, thyroid, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene was expressed at low levels in most regions of the central nervous system examined including: amygdala, hippocampus, thalamus, cerebellum, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of central nervous 401 WO 03/093432 PCT/US03/13690 system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Panel 4.1D Summary: Ag20 Highest expression of this gene was seen in resting NCI-H292 cells (CT=30) with significant expression also detected in activated NCI-H292 cells, small airway epithelium, activated monocytes and macrophages, dendritic cells, and resting IL2 treated NK cells. Therefore, modulation of this gene and/or expressed protein with a functional therapeutic will alter the functions associated with these cell types and will relieve the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.Ag5238 Highest expression using this probe-primer set was detected in activated macrophages (CT=33). Low gene expression was also seen in resting monocytes, keratinocytes and lung. Therefore, therapeutics modulation of this gene and/or expressed protein is important for the treatment of asthma, emphysema, inflammatory bowel disease, arthritis and psoriasis. H. CG50949-05 and CG50949-06: MOSAIC SERINE PROTEASE. Expression of gene CG50949-05 and CG50949-06 was assessed using the primer probe sets Ag020b, Ag20 and Ag5241, described in Tables HA, HB and HC. Results of the RTQ-PCR runs are shown in Tables HD, HE and HF. Table HA. Probe Name Ag020b Start SEQ ID Primers Sequences Length Position No reward 5'-gtgggaacactggagggagat-3' 21 925 379 Probe TET-5 '-aggtctgaatgcccttcccagcg-3'- 23 898 380 TAMRA Reverse j5'-caactccaccatccaggaaag-3' 1 870 381 Table HB. Probe Name Ag20 Start SEQ ID Primers Sequences Length Start SEQ ID Position No Forward 5 ' -gtgggaacactggagggagat-3' 21 925 382 Probe TET-5'aggtctgaatgcccttcccagcg-3'- 23 898 383 TAMRA Reverse 5'-caactccaccatccaggaaag-3' 21 870 384 402 WO 03/093432 PCT/USO3/13690 Table HC. Probe Name Ag5241 Start SEQ ID Primers Sequences Length Positin No Position No Forward 5'-gagagcccagtccagttctgg-3' 21 544 385 Probe TET-5'-atcaggtacaaggagcagagggaga-3'- 25 580 386 TAMRA Reverse. 5'-caccccgtcacagcgaaca-3' 19 621 387 Table HD. Generalscreeningpanelvl.5 Column A - Rel. Exp.(%) Ag5241, Run 229665051 Tissue Name A Tissue Name A Adipose 0.3 Renal ca. TK-10 0.0 Melanoma* Hs688(A).T 0.0 Bladder 11.2 Melanoma* Hs688(B).T 0.0 Gastric ca. (liver met.) NCI-N87 36.1 Melanoma* M14 38.2 Gastric ca. KATO III 0.5 Melanoma* LOXIMVI 0.8 Colon ca. SW-948 0.0 Melanoma* SK-MEL-5 2.1 Colon ca. SW480 1.2 Squamous cell carcinoma SCC-4 1.9 Colon ca.* (SW480 met) SW620 0.0 Testis Pool 0.4 Colon ca. HT29 6.3 Prostate ca.* (bone met) PC-3 0.0 Colon ca. HCT-116 1.1 Prostate Pool 4.2 Colon ca. CaCo-2 Placenta 19.8 Colon cancer tissue 16.6 Uterus Pool 0.8 Colon ca. SW1116 0.0 Ovarian ca. OVCAR-3 9.3 Colon ca. Colo-205 9.2 Ovarian ca. SK-OV-3 0.2 Colon ca. SW-48 0.6 Ovarian ca. OVCAR-4 1.2 Colon Pool 2.9 Ovarian ca. OVCAR-5 41.5 Small Intestine Pool 1.1 Ovarian ca. IGROV-1 0.4 Stomach Pool 1.1 Ovarian ca. OVCAR-8 0.0 Bone Marrow Pool 0.6 Ovary 1. Fetal Heart 0.7 Breast ca. MCF-7 72.7 Heart Pool 0.0 Breast ca. MDA-MB-231 0.0 Lymph Node Pool 0.7 Breast ca. BT 549 0.0 Fetal Skeletal Muscle 1.1 Breast ca. T47D 100.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N 0.7 Spleen Pool 5.9 Breast Pool 1.8Thymus Pool 2.9 Trachea 10.7 CNS cancer (glio/astro) U87-MG 0.0 Lung 0.0 CNS cancer (glio/astro) U-118-MG 0.0 Fetal Lung 28.9 CNS cancer (neuro;met) SK-N-AS 0.0 Lung ca. NCI-N417 0.0 CNS cancer (astro) SF-539 0.0 Lung ca. LX-1 0.9 CNS cancer (astro) SNB-75 0.0 Lung ca. NCI-H146 3.0 CNS cancer (glio) SNB-19 2.4 403 WO 03/093432 PCT/US03/13690 Lung ca. SHP-77 0.0 CNS cancer (glio) SF-295 0.9 Lung ca. A549 0.8 Brain (Amygdala) Pool 0.0 Lung ca. NCI-H526 0.0 Brain (cerebellum) 1.4 Lung ca. NCI-H23 1.7 Brain (fetal) 16.3 Lung ca. NCI-H460 7.3 Brain (Hippocampus) Pool 3.0 Lung ca. HOP-62 0.0 Cerebral Cortex Pool 0.4 ung ca.NCI-1522 0.3 Brain (Substantia nigra) Pool 1.1 Liver 0.0Brain (Thalamus) Pool 3.3 Fetal Liver 0.0 Brain (whole) 4.0 Liver ca. HepG2 0.0 Spinal Cord Pool 1.5 Kidney Pool . . ... . . 4.0 . ............ ... Adrenal GlPand 0.9 Fetal Kidney 2.0 Pituitary gland Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 5.7 Renal ca. A498 0.0 Thyroid (female) 8.8 Renal ca. ACHN a 3. Panreati ca. CAPAN2 1.1 Renal ca. UO-3 10.4 Pancreas Pool 6.5 Table HE. General_screening_panel_v1.6 [ Column A - Rel. Exp.(%) Ag20, Run 277226634 Tissue Name A Tissue Name A Adipose 0.2 Renal ca. TK-10 0.1 Melanoma* Hs688(A).T 0.0 Bladder 3.9 Melanoma* Hs688(B).T 0.0 Gastric ca. (liver met.) NCI-N87 42.3 Melanoma* M14 9.4 Gastric ca. KATO III 1.5 Melanoma* LOXIMVI 0.4 Colon ca. SW-948 0.5 Melanoma* SK-MEL-5 0.8 Colon ca. SW480 0.6 Squamous cell carcinoma SCC-4 1.8 Colon ca.* (SW480 met) SW620 0.3 Testis Pool 0.3 Colon ca. HT29 6.8 Prostate ca.* (bone met) PC-3 F0.3 Colon ca. HCT-116 2.0 Prostate Pool 0.9 Colon ca. CaCo-2 92.7 Placenta 30.1 Colon cancer tissue 23.3 Uterus Pool 0.8 Colon ca. SW1116 0.2 Ovarian ca. OVCAR-3 9.5 Colon ca. Colo-205 8.2 Ovarian ca. SK-OV-3 f0.1 Colon ca. SW-48 1.8 Ovarian ca. OVCAR-4 1.6 Colon Pool 0.7 Ovarian ca. OVCAR-5 [35.6 Small Intestine Pool 1.7 Ovarian ca. IGROV-1 0.2 Stomach Pool 1.0 Ovarian ca. OVCAR-8 0.0 Bone Marrow Pool 1.3 Ovary 0.2 Fetal Heart 0.1 Breast ca. MCF-7 77.9 Heart Pool Breast ca. MDA-MB-231 0.2 Lymph Node Pool 0.7 404 WO 03/093432 PCT/US03/13690 Breast ca. BT 549 0.4 Fetal Skeletal Muscle 0.1 Breast ca. T47D 100.0 Skeletal Muscle Pool 0.2 Breast ca. MDA-N 0.3 Spleen Pool . Breast Pool 0.5 Thymus Pool 1.2 Trachea 6..................9 CNS cancer (gliolastro) U87-MG 0.1 Lung 0.1 CNS cancer (glio/astro) U-1 18-MG 0.3 Fetal Lung 9.0 CNS cancer (neuro;met) SK-N- AS 0.0 [Lung ca. NCI-N417 0.0 [CNS cancer (astro) SF-539 [0.6 Lung Ca. LX-1 2.3 CNS cancer (astro) SNB-75 0.0 Lung ca. NCI-H146 0.4 CNS cancer (glio) SNB-19 0.4 Lung ca. SHP-77 0.2 CNS cancer (glio) SF-295 0.7 Lung ca. A549 0.5 Brain (Amygdala) Pool 0.2 L .g..ca, A 549

"

~~ ~~~~ .................................................. ........ .5 _ in. ( a a P.o ................... .............................. Lung ca. NCI-H526 0.4 Brain (cerebellum) 0.3 Lung ca. NCI-H23 0.8 Brain (fetal) 1.5 Lung ca. NCI-11460 0.4 :Brain (Hippocampus) Pool 1.4 Lung ca. HOP-62 0.2 Cerebral Cortex Pool 0.2 Lung ca. NCI-H522 0.3 Brain (Substantia nigra) Pool 0.2 Liver 0.2 Brain (Thalamus) Pool 0.4 Fetal Liver 2.3 Brain (whole) 0.1 Liver ca. HepG2 0.0 Spinal Cord Pool 0.2 Kidney Pool 0.3 Adrenal Gland 0.2 Fetal Kidney 0.8 Pituitary gland Pool 0.2 Renal ca. 786-0 0.2 Salivary Gland 8.8 Renal ca. A498 0.2 Thyroid (female) 6.0 Renal ca. ACHN 1.1 Pancreatic ca. CAPAN2 1.9 Renal ca. UO-31 0.8 Pancreas Pool3.0 Table HF. Panel 4.1D Column A - Rel. Exp.(%) Ag20, Run 268789078 Column B - Rel. Exp.(%) Ag5241, Run 229851725 Tissue Name A B B Tissue Name A B Secondary Thl act 2.3 6.1 HUVEC IL-1beta 1.1 0.0 Secondary Th2 act 12..... 2.0 22.8 [HUVEC IFNgamma 1.2 10.0 Secondary Trl act 7.7j 6.0 HUVEC TNF alpha +IFN gamma 2.1 0.0 Secondary Thl rest 2.4 0.0 HUVEC TNF alpha + IL4 1.4 0.0 Secondary Th2 rest 4.2 13.3 H JVEC IL- 11 2.8 3.6 Secondary Trl rest 3.7 21.3 Lung Microvascular EC none 3.7 0.0 Primary Th act 4.5 0.0 Lung Microvascular EC TNFalpha+ IL- beta Primary Th2 act f7.4 8.8 Microvascular Dermal EC none .6 0.0 o. Microsvasular Dermal EC TNFalpha+ Primary Trl act 6.1 0.0 I... Da4beta 4.4 0.0 405 WO 03/093432 PCT/US03/13690 primary Th rest Bronchial epithelium TNFalpha + ± Primary Th1 rest 1.4 1.7 0.0 0.0 i [ILlbeta Primary Th2 res__ t 2.8 6.6 Small airway epithelium none 34.2 0.0 ________________tSmall airway epithelium TNFalpha + Primary Trl rest 1.7 4.4 25.9 9.6 [~~~L- 1beta..... CD45RA CD4 lymphocyte act 6.1 10.2 Coronery artery SMC rest 4.8 0.0 CD45RO CD4 lymphocyte act 6. 24.7 Coronery artery SMC TNFalpha + IL- 0.0 l beta CD8 lymphocyte act 8.4 0.0 Astrocytes rest . Secondary CD8 lymphocyte rest 7.0 5.2 Astrocytes TNFalpha + IL-1beta 1.5 0 rest ......... Secondary CD8 lymphocyte act 1.2 9.9 KU-812 (Basophil) rest 5.0 3.3 act CD4 lymphocyte none 6.8 1.1 KU-812 (Basophil) PMA/ionomycin 0.8 0.0 2ty Thl/Th2/Trl anti-CD95 Santi-CD95 6.6 4.9 CCD 1106 (Keratinocytes) none 5.1 6.8 CH 1 1 ..... L LAK cells rest 2.6 12.3 CCD 1106 (Keratinocytes) TNFalpha + 1 0 0 LAK cells rest 2.6 I2.3 10.0.6. IL-1beta LAK cells IL-2 3.2 9.8 Liver cirrhosis 67 3.2 LAK cells IL-2+IL- 12 2.2 0.0 jNCI-H292 none 100.0 15.3 LAK cells IL-2+IFN gamma 2.5 0.0 NCI-H292 IL-4 40.1 22.8 LAK cells IL-2+ IL-18 10.9 5.8 NCI-H1292 IL-9 98.6 49.3 LAK cells PMA/ionomycin 2.3 8.8 NCI-H292 IL-13 73.7 29.3 NK Cells IL-2 rest 12.5 25.5 NCI-H1292 IFN gamma 49.0 15.9 Two Way MLR 3 day 6.325.9 HPAEC none 8.5 0.0 Two Way MLR 5 day 1.8 5.0 HPAEC TNF alpha + IL-1 beta 4.7 0.0 Two Way MLR 7 day 4.1 7.2 Lung fibroblast none2.8 0.0 PBMC rest 5.9 6.3 Lung fibroblast TNF alpha + IL-1 beta 3.7 0.0 PBMC PWM 0.0 0.0 Lung fibroblast IL-4 2.5 0.0 PBMC PHA-L 5.8 13.3 Lung fibroblast IL-9 4.1 0.0 Ramos (B cell) none 1.5 1.8 Lung fibroblast IL-13 0.0 0.0 Ramos (B cell) ionomycin 7.8 3.3 Lung fibroblast IFN gamma 1.4 0.0 B lymphocytes PWM 1.3 6.4 Dermal fibroblast CCD1070 rest 1.3 0.0 B lymphocytes CD40L and IL-4 0.4 Dermal fibroblast CCD 1070 TNF alpha 9.1 21.5 EOL-1 dbcAMP 5.4 3.0 Dermal fibroblast CCD 1070 IL-1 beta 2.8 EOL-1 dbcAMP 0.0 0.0 PMA/ionomyc Dermal fibroblast IFN gamma 3.1 PMA/ionomycin0. Dendritic cells none . 6.2 8.6 Dermal fibroblast IL-4 2.7 0.0 Dendritic cells LPS 10.7 19.8Dl s . . Dendritic cells anti-CD40 13.0 12.7 Neutrophils TNFa+LPS 1.7 12.8 Monocytes rest 1.2 6.6 Neutrophils rest 6.6 0.0 Monocytes LPS 210.Colon 3.1 0.0 406 WO 03/093432 PCT/USO3/13690 Macrophages rest 3.2 0.0 Lung 3.1 0.0 Macrophages LPS 10.4 28.1 'Thymus 0.0 0.0 HUVEC none 0.4 0.0 Kidney 4. 3.4 HUVEC starved 1.8 .0.0..... 1 General-screening_panelvl.5 Summary: Ag5241 Highest gene expression was detected in T47D breast cancer cell line (CT=30.6) and moderate to low gene expression was detected in melanoma, colon, gastric, gastric, ovarian and breast cancer cell lines. CG50959 gene expression level is a useful marker to differentiate these cancers from normal tissues and to detect the presence of these cancers in vitro or in vivo. Furthermore, therapeutic modulation of this gene is useful in the treatment of these cancers. Low gene expression was detected in fetal lung and brain. The relative over expression in fetal tissue indicates that the expressed protein enhances lung and brain growth or development and acts in a regenerative capacity in the adult.. General_screening_panelvl.6 Summary: Ag20 Highest expression of this gene was detected in T47D breast cancer cell line (CT=26) and moderate to low gene expression was also detected in melanoma, lung, colon, renal, pancreatic, renal, brain, gastric, and breast cancer cell lines. Expression level is a useful marker for differentiating these cancers from normal tissues and to detect the presence of these cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate to low levels in pancreas, adipose, thyroid, fetal liver and gastrointestinal tract. Therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Low gene expression levels was detected in the central nervous system including: amygdala, hippocampus, thalamus, cerebellum, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the diagnosis and/or treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Panel 4.1D Summary: Ag20 Highest gene expression was seen in resting NCI-H292 (CT=30) and significant expression was detected in activated NCI-H292 cells, small airway epithelium, activated monocytes and macrophages, dendritic cells, and resting IL2 treated NK cells. Ag5241 Highest gene expression using this probe-primer set was detected in LPS activated monocytes (CT=33). Upon activation with pathogens such as LPS, monocytes contribute to innate and specific immunity by migrating to the site of tissue injury and releasing inflammatory cytokines. Modulation of gene expression and/or encoded protein prevents the recruitment of monocytes and the initiation of the inflammatory process, and 407 WO 03/093432 PCT/US03/13690 relieves the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, or osteoarthritis. I. CG51018-01: Matrilin-2 precursor. Expression of gene CG51018-01 was assessed using the primer-probe set Ag2764, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB, IC, ID and IE. Table IA. Probe Name Ag2764 Start SEQ ID Primers Sequences Length Start SEQ ID Length Position No Forward 5 '-tttgcagtgcaacacagatatc-3' 22 2695 388 Probe TET-5 ' -ttacggtctacacaaaagctttccca-3' - 26 2737 389 Poe26 2737 389 Reverse 5'-gcttcctgaaggttttgttga-3' 21 2764 390 Table IB. CNSneurodegenerationvl.0 Column A - Rel. Exp.(%) Ag2764, Run 208698723 Tissue Name A Tissue Name A AD 1 Hippo 13.6 Control (Path) 3 Temporal Ctx 3.8 AD 2 Hippo 40.1 Control (Path) 4 Temporal Ctx 18.4 AD 3 Hippo 9.6 AD 1 Occipital Ctx 10.4 AD 4 Hippo 18.3 AD 2 Occipital Ctx (Missing) 0.0 AD 5 hippo 30.1 AD 3 Occipital Ctx 6.9 AD 6 Hippo -- 100.0 AD 4 Occipital Ctx 14.7 Control 2 Hippo 24.3 AD 5 Occipital Ctx 18.3 Control 4 Hippo 39.5 AD 6 Occipital Ctx 17.2 Control (Path) 3 Hippo 8.3 Control 1 Occipital Ctx 2.1 AD 1 Temporal Ctx 21.5 Control 2 Occipital Ctx 17.7 AD 2 Temporal Ctx 19.1 Control 3 Occipital Ctx 6.3 AD 3 Temporal Ctx 7.5 Control 4 Occipital Ctx 15.3 AD 4 Temporal Ctx -22.1 Control (Path) 1 Occipital Ctx 48.0 AD 5 Inf Temporal Ctx 43.2 Control (Path) 2 Occipital Ctx 9.2 AD 5 SupTemporal Ctx 51.8 Control (Path) 3 Occipital Ctx 1.0 AD 6 InfTemporal Ctx 51.8Control (Path) 4 Occipital Ctx 9.2 AD 6 SUp T pora x 61.6 Control 1 Parietal Ctx 5.2 Control 1 Temporal Ctx 4.2 Control 2 Parietal Ctx 32.5 Control 2 Temporal Ctx 11.3 Control 3 Parietal Ctx .9 Control 3 Temporal Ctx 9 Control (Path) 1 Parietal Ctx 18.8 Control 4 Temporal Ctx 11.3 Control (Path) 2 Parietal Ctx 25.7 Control (Path) 1 Temporal Ctx 33.7 Control (Path) 3 Parietal Ctx 1.9 408 WO 03/093432 PCT/USO3/13690 Control (Path) 2 Temporal Ctx 18.4 Control (Path) 4 Parietal Ctx 17.1 Table IC. Panel 1.3D Column A - Rel. Exp.(%) Ag2764, Run 164024018 Tissue Name A Tissue Name A Liver adenocarcinoma 4.9 Kidney (fetal) 54.3 Pancreas 1.6 Renal ca. 786-0 1.6 Pancreatic ca. CAPAN 2 0.5 Renal ca. A498 6.3 Adrenal gland 6.7 Renal ca. RXF 393 14.0 Thyroid I 00 Rena ca.( ACpN Salivary gland R6.4 ienal ca. UO-31 13.8 Pituitary gland 3.8 Renal ca. TK-10 5.4 Brain (fetal) 0.7 'Liver 3.2 Brain (whole) 3.7 Liver (fetal) 4.6 _ _ _ _ _....................._ _ _ ..... _ _ _ _ __.._ _ __--_ __-_ _ _ _ I ..... Brain (amygdala) 8.2 Liver ca. (hepatoblast) HepG2 Brain (cerebellum) 5.3 Lung 4.8 Brain (hippocampus) 7.4 Lung (fetal) 8.2 Brain (substantia nigra) 2.5 Lung ca. (small cell) LX-1 0.0 Brain (thalamus) 5.4 Lung ca. (small cell) NCI-H69 7.7 Cerebral Cortex 8.1 Lung ca. (s.cell var.) SHP-77 4.8 Spinal cord 37.1 Lung ca. (large cell)NCI-H460 0.0 glio/astro U87-MG 5.4 Lung ca. (non-sm. cell) A549 1.4 glio/astro U-1 18-MG 24.5 Lung ca. (non-s.cell) NCI-H23 3.4 astrocytoma SW1783 ......133.7 Lung ca. (non-s.cell) HOP-62 0.9 neuro*; met SK-N-AS 0.1 Lung ca. (non-s.cl) NCI-H522 0.5 astrocytoma SF-539 13.0 Lung ca. (squam.) SW 900 0.4 astrocytoma SNB-75 7.0 Lung ca. (squam.) NCI-H596 3.3 glioma SNB-19 0.7 Mammary gland29.7 glioma U251 5.6 Breast ca.* (pl.ef) MCF-7 6.0 glioma SF-295 1.0 Breast ca.* (pl.ef) MDA-MB-231 6.3 Heart (fetal) : 8.8 Breast ca.* (pl.ef) T47D 1.8 Heart 20.0 Breast ca. BT-549 7.4 Skeletal muscle (fetal) 54.0 Breast ca. MDA-N 0.0 Skeletal muscle 6.9 Ovary 65.5 Bone marrow 0.9 Ovarian ca. OVCAR-3 0.9 Thymus 7.2 Ovarian ca. OVCAR-4 0.1 Spleen 2.3 Ovarian ca. OVCAR-5 2.0 Lymph node 5.1 Ovarian ca. OVCAR-8 16.3 Colorectal 6.7 Ovarian ca. IGROV-1 0.6 Stomach 7.4 Ovarian ca.* (ascites) SK-OV-3 1. Small intestine 34.6 Uterus 409 WO 03/093432 PCT/US03/13690 SColon ca. SW480 0.7 Placenta 14.8 Colon ca.* SW620(SW480 met) 0. 1 Prostate 20.3 Colon ca. HT29 0.7 Prostate ca.* (bone met)PC-3 5.5 Colon ca. HCT-l 16 0.4 Testis 13.2 Colon ca. CaCo-2 1.5 IMelanoma Hs688(A).T 0.9 Colon ca. tissue(ODO3866) 0.9 Melanoma* (met) Hs688(B).T 0.8 Colon ca. HCC-2998 1.0 Melanoma UACC-62 0.1 Gastric ca.* (liver met) NCI-N87 10.0 Melanoma M14 0.6 Bladder 10.0 'Melanoma LOX IMVI 0.1 Trachea 26.1 Melanoma* (met) SK-MEL-5 0.8 Kidney 12.3 Adipose 13.2 Table ID. Panel 2D Column A- Rel. Exp.(%) Ag2764, Run 162556852 Tissue Name A Tissue Name A Normal Colon 21.2.Kidney Margin 8120608 1.3 CC Well to Mod Diff (ODO3866) 0.3 1Kidney Cancer 8120613 0.2 CC Margin (ODO3866) 4.1 Kidney Margin 8120614 1.0 CC Gr.2 rectosigmoid (ODO3868) 0.5 Kidney Cancer 9010320 0:9 CC Margin (ODO3868) 2.2 Kidney Margin 9010321 1.2 CC Mod Diff (OD03920) 1.0 Normal Uterus 12.2 N o~~~~~~~~~~........ .. u.............................................. CC Margin (ODO3920) . 5.7 ,Uterus Cancer 064011 17.4 CC Gr.2 ascend colon (ODO3921) 4.3 Normal Thyroid 100.0 CC Margin (ODO3921) 14.4 Thyroid Cancer 064010 . {.8 CC from Partial Hepatectomy (ODO4309) C Mets .0jThyroid Cancer A302152 3.6 ,M) -- t.. .... .T h .o....; A ; .... .-........................................... .... . . . ....... Liver Margin (ODO4309) .. ........ 3.8 ]Thyroid Margin A302153 39.8 Colon mets to lung (OD04451-01) 0.4 Normal Breast 9.1 Lung Margin (OD04451-02) . Breast Cancer (OD04566) 2.1 uNormal Prostate 6546-1 .77.4 Breast Cancer (OD04590-01) 2.0 Prostate Cancer (OD04410) 15.1 Breast Cancer Mets (OD04590-03) 4.4 Prostate Margin (D4410) 21.3 Breast Cancer Metastasis (OD04655- 2.0 Prostate Margin (OD044 10) 21. 2.0{0, 05) Prostate Cancer (OD04720-01) 18.3 Breast Cancer 064006 1.5 Prostate Margin (OD04720-02) 23.8 Breast Cancer 1024 3.6 Normal Lung 061010 5.0 Breast Cancer 9100266 2.1 Lung Met to Muscle (ODO4286) 0.4 Breast Margin 9100265 4.9 Muscle Margin (ODO4286) 10.6 Breast Cancer A209073 6.3 Lung Malignant Cancer (OD03126) 1. 1 Breast Margin A209073 8.5 Lung Margin (OD03126) 1.6 INormal Liver 3.5 Lung Cancer (0D04404) 2.2 Liver Cancer 064003 0.8 410 WO 03/093432 PCT/USO3/13690 Lung Margin (.D04404) 2.1 Liver Cancer 1025 1.4 Lung Cancer (OD04565) 3.1 Liver Cancer 1026 0.4 Lung Margin (OD04565) 0.8 Liver Cancer 6004-T 1.2 Lung Cancer (OD04237-01) 1.0 Liver Tissue 6004-N 0.2 Lung Margin (OD04237-02) 2.4 Liver Cancer 6005-T 0.6 Ocular Mel Met to Liver (ODO43 10) 9.7 Liver Tissue 6005-N 0.3 Liver Margin (ODO4310) 3.6 Normal Bladder 4.3 Melanoma Mets to Lung (OD04321) 2.2 Bladder Cancer 1023 0.5 Lung Margin (OD04321) 1.5 Bladder Cancer A302173 1.9 Normal Kidney 16.7 Bladder Cancer (OD04718-01) 6.7 Kidney Ca, Nuclear grade 2 (OD04338) 2.7 Bladder Normal Adjacent Kidney. C,.N.c.er.g.ade2............7(OD04718-03) 8.2 Kidney Margin (OD04338) 9.2 Normal Ovary 6.4 Kidney Ca Nuclear grade 1/2 (0D04339) 0.6 Ovarian Cancer 064008 7.2 Kidney Margin (OD04339) 17.5 Ovarian Cancer (OD04768-07) 4.4 Kidney Ca, Clear cell type (OD04340) 9.3 Ovary Margin (OD04768-08) 3.9 Kidney Margin (OD04340) 8.5 Normal Stomach 6.7 Kidney Ca, Nuclear grade 3 (OD04348) 0.8 Gastric Cancer 9060358 17 Kidney Margin (OD04348) 5.8 Stomach Margin 9060359 2.1 Kidney Cancer (OD04622-01) 0.6 Gastric Cancer 9060395 7.2 Kidney Margin (OD4622-03) 1.0 Stomach Margin 9060394 3.3 Kidney Cancer (OD04450-01) 6.9 Gastric Cancer 90603971.6 Kidney Margin (OD04450-03) 8.2 Stomach Margin 9060396 0.4 Kidney Cancer 8120607 11.9 Gastric Cancer 064005 .6 Table IE. Panel 5 Islet Column A - Rel. Exp.(%) Ag2764, Run 254275033 Tissue Name _A Tissue Name A 97457 Patient-02go adipose .17.6 94709 Donor 2 AM - A adipose 1.4 97476 Patient-07sk skeletal muscle 19.2 94710_Donor 2 AM- B adipose 0.4 97477_ Patient-07ututerus 145.4 19471 1 Donor 2 AM - C adipose 07 97478 Patient-07plplacenta 15.5 194712 Donor 2 AD - A adipose 6.0 99167 Bayer Patient 1 1...0 .. 94713 Donor 2 AD -B adipose 8.1 97482 Patient-08ut uterus 21.5 ]94714 Donor 2 AD - C adipose 12.4 97483 Patient-08pl placenta 16.3 94742 Donor 3 U - A Mesenchymal Stem 1.4 Cells 97486 Patient-09sk skeletal muscle 2.2 94743 Donor 3 U - B Mesenchymal Stem3.0 97487 Patient-09ut uterus 92.7 94730 Donor 3AM - A adipose .8 97488 Patinpt-9placenta 12.0 94731 Donor 3 AM -B adipose 1.1 97492 Patient-10ut uterus 50.3 94732 Donor 3 AM -C adipose 1.2 197493 Patient-Opl placenta 21.5 94733_Donor 3 AD - A adipose 2.8 411 WO 03/093432 PCT/US03/13690 97495 Patient-1 goadipose 12.2 94734 Donor 3 AD - B adipose 2.6 97496 Patient-1 lsk skeletal muscle .2.9 94735 Donor 3 AD - C adipose 4.7 ............. . ....... ... -4 3 _ o o - A D 1 1 1 -- - C:a d4 .7 97497 Patient-1 lut uterus 100.0 77138 Liver HepG2untreated 0.5 97498 Patient-1 Iplplacenta 6.1 73556_HeartCardiac stromal cells '....9Patient-il. p.acnt.(primary) e e 97500 Patient-12go adipose 15.2 81735Small Intest .6 970_atient-i2kseetlmsl g Intesuie 2.6 _ ~72409 KidneyProximal Convoluted 97501 Patient-12sk skeletal muscle 9.2 72409KidneyProximal Convoluted 1.2 Tubule 97502 Patient-12ut uterus 70.2 82685 Small intestine Duodenum 11.3 97503 Patient-12pl placenta 5.3 90650 Adrenal Adrenocortical adenoma 2.0 94721_Donor 2 U - AMesenchymal Stem Cells -3.5 7240 Kidney RCE 0.6 94722 Donor 2 U - B Mesenchymal Stem Cells 2.5 72411 Kidney HRE 0.9 94723_Donor 2 U - CMesenchymal 2.5 73139_Uterus Uterine smooth muscle 8 Stem Cells .. cells -2.8 CNS_ neurodegeneration vl.0 Summary: Ag2764 This gene, a homolog of matrilin-2, is an intercellular matrix protein. The results of this panel shows expression in the brain. Glial scarring is a major inhibitor of CNS repair/regeneration involving intra and extra-cellular proteins. Reduction of expression levels of this gene or protein encoded by this gene decreases glial scarring in response to CNS injury, and promotes healing in spinal cord and/or brain trauma. Panel 1.3D Summary: Ag2764 High gene expressed was detected in the thyroid gland (CT = 26.2), fetal kidney and fetal skeletal muscle (CTs = 27.1) and shows an association with normal tissue when compared to cancer cell lines. This gene was moderately expressed in pancreas, adrenal and pituitary glands, adipose, fetal and adult heart, fetal and adult liver, and adult skeletal muscle. The relative over expression of this gene in fetal skeletal muscle relative to adult skeletal muscle indicates that the protein product enhances muscular growth or development and acts in a regenerative capacity in the adult. Modulation of gene expression is useful in treatment of muscle related diseases treatment of weak or dystrophic muscle with the encoded protein restores muscle mass or function. This gene is expressed in many tissues of the central nervous system including: amygdala, cerebellum, hippocampus, substantia nigra, thalamus, cerebral cortex, spinal cord, and the developing brain. Panel 2D Summary: Ag2764 Highest gene expression was detected in normal thyroid tissue (CT = 24.7) and there was a strong association of gene expression in normal prostate tissue (CT = 25). This gene was overexpressed in normal thyroid tissue relative to samples derived 412 WO 03/093432 PCT/US03/13690 from matched thyroid cancer tissue. Thus, therapeutic modulation of the activity or expression of this gene, encoded protein, and/or antibodies, small molecule drugs targeting the encoded protein is an effective treatment of thyroid and prostate cancers. Panel 5 Islet Summary: Ag2764 Highest expression of this gene was seen in uterus of a non-diabetic but overweight patient (CT=25.9). High gene expression was seen in uterus, adipose, skeletal muscle, placenta, kidney and small intestine and moderate expression was seen in islet cells. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of metabolic/endocrine diseases including obesity and diabetes. J. CG51051-07 and CG51051-09: Netrin G1D like. Expression of gene CG51051-07 and CG51051-09 was assessed using the primer probe sets Ag290 and Ag040, described in Tables JA and JB. Results of the RTQ-PCR runs are shown in Tables JC and JD. Table JA. Probe Name Ag290 Primers Sequences Length Start SEQ ID Position No Forward j5'-ggcacgtcatccgttct-3' 18 1292 391 ro TET-5 -ctgcgacaacgagctcctgcactg-3'- 24 1266 392 .TMRA__ __ _ Reverse 5'-ctgttcaagttgcaaaccacaag-3' ] 23 1232 393 Table JB. Probe Name Ag040 riders Sequences Length Start SEQ ID Primers Sequences eng Position No Forward 5'-ggcacgtccctccgttct-3' 18 1292 394 robe TET-5'-ctgcgacaacgagctcctgcactg-3'- 1266 395 Reverse 5 '-ctgttcaagttgcaaaccacaag-3' 23 1 1232 396 Table JC. CNSneurodegenerationvl.0 Column A - Rel. Exp.(%) Ag040, Run 206975031 Column B - Rel. Exp.(%) Ag040, Run 269217520 Tissue Name A B Tissue Name A B AD 1 Hippo _2.3 -4.2 Control (Path) 3 Temporal Ctx 2.2 5.3 AD 2 Hippo 18.6 38.7 Control (Path) 4 Temporal Ctx 116.3 23.2 AD 3 Hippo 1.4 4.0 AD 1 Occipital Ctx 8.5 19.6 AD 4 Hippo _5.7 8.3 AD 2 Occipital Ctx (Missing) 0.0 j0.0 AD 5 hippo 100.0 100.0 IAD 3 Occipital Ctx 2.7 3.2 AD 6 Hippo 4.9 , 14.2 JAD 4 Occipital Ctx 6.9 14.9 413 WO 03/093432 PCT/US03/13690 Control 2 Hippo ]11.4 23.0 AD 5 Occipital Ctx 6.6 39.8 Control 4 Hippo 2.5 2.7 AD 6 Occipital Ctx 45.1 13.6 Control (Path) 3 Hippo 0.7 2.8 Control 1 Occipital Ctx 3.0 1.6 AD 1 Temporal Ctx 1.2 3.8 Control 2 Occipital Ctx 30.4 74.2 AD 2 Temporal Ctx 7.8 14.5 Control 3 Occipital Ctx 9.9 24.0 AD 3 Temporal Ctx 0.4 4.4 Control 4 Occipital Ctx 2.8 8.4 AD 4 Temporal Ctx 4.6 , 5.8 -Control (Path) 1 Occipital Ctx 39.8 90.1 AD 5 Inf Temporal Ctx . 31.2 44.4 Control (Path) 2 Occipital Ctx 10.4 21.6 AD 5 SupTemporal Ctx 20.0 18.0 ,Control (Path) 3 Occipital Ctx 1.2 7.9 AD 6 Inf Temporal Ctx 6.3 16.4 Control (Path) 4 Occipital Ctx 11.0 29.3 AD 6 Sup Temporal Ctx 9.5 24.7 Control 1 Parietal Ctx 1.7 6.9 Control 1 Temporal Ctx 2.4 3.8 Control 2 Parietal Ctx 11.9 22.7 Control 2 Temporal Ctx 14.1 20.2 Control 3 Parietal Ctx 7.2 9.7 Control 3 Temporal Ctx 4.2 6.6 Control (Path) 1 Parietal Ctx 18.9 62.0 Control 4 Temporal Ctx 0.7 5.4 Control (Path) 2 Parietal Ctx 6.4 14.1 Control (Path) 1 Temporal Ctx 23.0 50.3 Control (Path) 3 Parietal Ctx 0.5 1.6 Control (Path) 2 Temporal Ctx 14.3 42.0 Control (Path) 4 Parietal Ctx 15.7 52.5 Table JD. Panel 1 Column A - Rel. Exp.(%) Ag290, Run 87988084 Tissue Name A Tissue Name A Endothelial cells 0.0 Renal ca. 786-0 .0 Endothelial cells (treated) 0.0 Renal ca. A498 0.0 Pancreas 12.2 Renal ca. RXF 393 0.0 Pancreatic ca. CAPAN 2 1.7 Renal ca. ACHN Adrenal gland 0.2 Renal ca. UO-31 0.0 Thyroid 0. 0 Renal ca. TK-10 1.1 Salivary gland 0.1 Liver 5 Pituitary gland 0.0 Liver (fetal) 0.1 Brain (fetal) 0.0 Liver ca. (hepatoblast) HepG2 0.0 Brain (whole) 8.0 Lung 0.1 Brain (amygdala) 0.0 Lung (fetal) 0.0 Brain (cerebellum) 49.3 Lung ca. (small cell) LX-1 0.0 Brain (hippocampus) 0.0 Lung ca. (small cell) NCI-H69 0.0 Brain (substantia nigra) 0.0 Lung ca. (s.cell var.) SHP-77 0.0 Brain (thalamus) 0.0 Lung ca. (large cell)NCI-H460 0.0 Brain (hypothalamus) 0.0 Lung ca. (non-sm. cell) A549 0.0 Spinal cord 0.0 Lung ca. (non-s.cell) NCI-H23 0.0 glio/astro U87-MG 0.0 Lung ca. (non-s.cell) HOP-62 0.0 glio/astro U-1 18-MG 0.0 Lung ca (non-s.l) NCI-H522 0.0 astrocytoma SW1783 0.9 Lung ca. (squam.) SW 900 0.0 414 WO 03/093432 PCT/USO3/13690 neuro*; met SK-N-AS 0.0 Lung ca. (squam.) NCI-H596 1.6 astrocytoma SF-539 0.0 Mammary gland 95.3 astrocytoma SNB-75 0.0 Breast ca.* (pl.ef) MCF-7 17.1 glioma SNB-19 0.5 Breast ca.* (p.ef) MDA-MB-231 0.0 glioma U251 0.0 Breast ca.* (pl. ef) T47D 0.0 glioma SF-295 3.2 Breast ca. BT-549 0.0 Heart 0.0 Breast ca. MDA-N 0.0 Skeletal muscle 0.0 Ovary 0.0 Bone marrow 8.0 Ovarian ca. OVCAR-3 0.0 Thymus 100.0 Ovarian ca. OVCAR-4 0.0 Spleen 3.3 Ovarian ca. OVCAR-5 1.3 Lymph node 7.3 Ovarian ca. OVCAR-8 0.0 Colon (ascending) 10.7 Ovarian ca. IGROV-1 0.0 Stomach 58.6 Ovarian ca. (ascites) SK-OV-3 0.0 Small intestine 0.8 Uterus 0.3 Colon ca. SW480 0.0 Placenta 9.9 Colon ca.* SW620 (SW480 met) 0.0 Prostate 12.2 Colon ca. HT29 0.0 Prostate ca.* (bone met) PC-3 0.0 Colon ca. HCT-116 0.1 Testis 90.8 Colon ca. CaCo-2 0.9 Melanoma Hs688(A).T 0.0 Colon ca. HCT-15 0.0 Melanoma* (met) Hs688(B).T0.0 Colon ca. HCC-2998 0.0 Melanoma UACC-62 0.0 Gastric ca. * (liver met) NCI-N87 3.7 Melanoma M14 0.0 Bladder 0.0 Melanoma LOX IMVI 0.0 Trachea 28.1 Melanoma* (met) SK-MEL-5 0.0 Kidney 0.1 Melanoma SK-MEL-28 00 Kidney (fetal)- 3.0 . CNS_neurodegenerationvl.0 Summary: Ag040 This gene was downregulated in the temporal cortex of Alzheimer's diseased brain as analyzed by ANCOVA, with RNA quality as a covariate. This gene codes for Netrin like protein. Netrins are secreted proteins which have both neurotrophic and neuroprotective functions. They are believed to play a role in neurodevelopment, both in neuron survival and in axon guidance (Manitt C, Kennedy TE., 2002,Where the rubber meets the road: netrin expression and function in developing and adult nervous systems. Prog Brain Res. 137:425-42;PMID: 12440385). Therefore, up regulation of this gene or its protein product, is useful preventing, treating or ameliorating symptoms associated with this disease. Panel 1 Summary: Ag290 Highest gene expression was seen in thymus (CT=26). Indicating that this gene plays a role in T cell development. Targeting the encoded protein is useful for 415 WO 03/093432 PCT/US03/13690 modulating immune function (T cell development) and is important for organ transplantation, AIDS treatment or post chemotherapy immune reconstitiution. Significant gene expression was seen in tissues with metabolic/endocrine function including pancreas, liver and gastrointestinal tract. Therapeutic gene and/or encoded protein modulation is useful in the treatment of metabolic/endocrine diseases including diabetes and obesity. High gene expression was detected in whole brain and cerebellum. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of neurological disorders such as ataxia, and autism. K. CG51051-14: Netrin G1D like. Expression of gene CG51051-14 was assessed using the primer-probe set Ag6679, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB, KC and KD. Table KA. Probe Name Ag6679 Primersi ... . Sequences Length Start Position SEQ ID No Forward 5'-ccagtattggtacgaatgtctg-3' 22 228 397 Probe TET-5'-ctcctgcactgccagaacggag-3' -TAMRA 22 196 398 Reverse 5 '-acaggcagcgcacgt-3' 15 166 1399 Table KB. CNSneurodegeneration vl.0 Column A - Rel. Exp.(%) Ag6679, Run 275777964 Tissue Name A Tissue Name A AD 1 Hippo 4.5 Control (Path) 3 Temporal Ctx 1.3 AD 2 Hippo 26.4 Control (Path) 4 Temporal Ctx 17.0 AD 3 Hippo 7.1 AD 1 Occipital Ctx 17.0 AD 4 Hippo 8.1 AD 2 Occipital Ctx (Missing) 0.0 AD 5 hippo 67.4 AD 3 Occipital Ctx 2.9 AD 6 Hippo 34.2 AD 4 Occipital Ctx 7.3 Control 2 Hippo 22.4 AD 5 Occipital Ctx20.3 Control 4 Hippo 9.0AD 6 Occipital Ctx 35.1 Control (Path) 3 Hippo 2.3 Control 1 Occipital Ctx 2.0 AD I Temporal Ctx 17.2 Control 2 Occipital Ctx 71.7 AD 2 Temporal Ctx 13.6 Control 3 Occipital Ctx 17.4 AD 3 Temporal Ctx 0.0 Control 4 Occipital Ctx 1.8 AD 4 Temporal Ctx 8.3 Control (Path) 1 Occipital Ctx 100.0 AD 5 Inf Temporal Ctx 24.0 Control (Path) 2 Occipital Ctx 4.5 AD 5 SupTemporal Ctx 27.9 Control (Path) 3 Occipital Ctx 0.9 AD 6 InfTemporal Ctx 11.3 Control (Path) 4 Occipital Ctx 15.3 AD 6 Sup Temporal Ctx 31.0 Control 1 Parietal Ctx 5. 416 WO 03/093432 PCT/USO3/13690 Control 1 Temporal Ctx 1.4 Control 2 Parietal Ctx_ 11.5 Control 2 Temporal Ctx 31.9 Control 3 Parietal Ctx 8.6 Control 3 Temporal Ctx 6.4 Control (Path) 1 Parietal Ctx 34.6 Control 4 Temporal Ctx 1.4 ]Control (Path) 2 Parietal Ctx 12.8 Control (Path) 1 Temporal Ctx 36.1 Control (Path) 3 Parietal Ctx 2.3 Control (Path) 2 Temporal Ctx 38.4 Control (Path) 4 Parietal Ctx 33.0 Table KC. Generalscreeningpanelv1.6 Column A - Rel. Exp.(%) Ag6679, Run 277244468 Tissue Name A Tissue Name A Adipose 3.0 Renal ca. TK-10 4.0 Melanoma* Hs688(A).T 2.7 Bladder 0.4 Melanoma* Hs688(B).T 1.3 Gastric ca. (liver met.) NCI-N87 0.0 Melanoma* M14 0.0 Gastric ca. KATO III 0.0 Melanoma* LOXIMVI 15.0 Colon ca. SW-948 0.0 Melanoma* SK-MEL-5 0.0 Colon ca. SW480 0.0 Squamous cell carcinoma SCC-4 1.3 Colon ca.* (SW480 met) SW620 0.0 Testis Pool 0.2 Colon ca. HT29 0.0 Prostate ca.* (bone met) PC-3 1.2 Colon ca. HCT-116 0.0 Prostate Pool 2.7 Colon ca. CaCo-2 0.1 Placenta 0.3 Colon cancer tissue 0.4 Uterus Pool 0.8 Colon ca. SW11160.0 Ovarian ca. OVCAR-3 3.3 Colon ca. Colo-205 0.0 Ovarian ca. SK-OV-3 66.9 Colon ca. SW-48 0.0 Ovarian ca. OVCAR-4 0.3 Colon Pool 0.1 Ovarian ca. OVCAR-5 0.0 Small Intestine Pool 1.4 Ovarian ca. IGROV-1 0.0 Stomach Pool 0.7 Ovarian ca. OVCAR-8 8.2 Bone Marrow Pool 1.2 Ovary 0.0 Fetal Heart 0.8 Breast ca. MCF-7 0.0 Heart Pool 0.2 Breast ca. MDA-MB-231 0.0 Lymph Node Pool 1.0 Breast ca. BT 549 10.6 Fetal Skeletal Muscle 2.3 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N 0.0 Spleen Pool 0.0 Breast Pool 11.0 Thymus Pool 0.6 Trachea J0.5 ICNS cancer (gliolastro) U87-MG 15.2 Lung 0.0 CNS cancer (glio/astro) U-i 18-MG j100.0 Fetal Lung 35.1 CNS cancer (neuro;met) SK-N-AS 1.3 Lung ca. NCI-N417 110.7 CNS cancer (astro) SF-539 1.1 Lung ca. LX-1 0.0 CNS cancer (astro) SNB-75 27 Lung ca. NCI-H146 27.2 CNS cancer (glio) SNB-19 0.0 417 WO 03/093432 PCT/US03/13690 Lung ca. SHP-77 4.6 CNS cancer (glio) SF-295 . Lung ca. A5490.0 Brain (Amygdala) Pool 7.8 Lung ca. NCI-H526 0.0 Brain (cerebellum) 5.7 Lung ca. NCI-H23 0.0 Brain (fetal) 3.7 Lung ca. NCI-H460 0.2 Brain (Hippocampus) Pool 3.5 Lung ca. HOP-62 0.3 Cerebral Cortex Pool 5.0 Lung ca. NCI-H522 0.0 Brain (Substantia nigra) Pool1.5 Liver ...

0..0 Brain (Thalamus) Pool 21.5 Fetal Liver 0.2 Brain (whole) 10.2 Liver ca. HepG2 0.0 Spinal Cord Pool 4.2 Kidney Pool 0.0Adrenal Gland 1.6 Fetal Kidney 6 Pituitary gland Pool 1.3 Renal ca. 786-0 8.1 Salivary Gland 0.1 Renal ca. A498 5.5 Thyroid (female) 0.2 Renal ca. ACHN 3.0 Pancreatic ca. CAPAN2 0.0 Renal ca. UO-31 9 Pancreas Pool 03 Table KD. Panel 4.1D Column A - Rel. Exp.(%) Ag6679, Run 275769774 Tissue Name A Tissue Name A Secondary Thl act 0.0 HUVEC IL-lbeta 0.0 Secondary Th2 act 0.0 HUVEC IFN gamma 0.0 Secondary TrI act 0.0 RUVEC TNF alpha + IFN gamma 0.0 Secondary Thl rest 0.0 HUVEC TNF alpha + IL4 00 Secondary Th2 rest 0.0 HUVEC IL-I1 0.0 Secondary Trl rest 0.0 Lung Micerovascular EC none 7.4 Primary Th act 0.0 Lung Microvascular EC TNFalpha + IL-1 beta 0.0 Primary Th2 act 0.0 Microvascular Dermal EC none 0.0 Primary Trl act 0.0 Microsvasular Dermal EC TNFalpha + IL- 0.0 1 beta Primary Thl1 rest 0.0 Bronchial epithelium TNFalpha + ILlbeta 10.7 Primary Th2 rest 0.0 Small airway epithelium none 8.7 Primary Tr I rest 0.0 Small airway epithelium TNFalpha + IL-lbeta 0.0 CD45RA CD4 lymphocyte act 17.1 Coronery artery SMC rest 0.0 CD45RO CD4 lymphocyte act 0.0 Coronery artery SMC TNFalpha + IL-lbeta 0.0 CD8 lymphocyte act 0.0 Astrocytes rest Secondary CD8 lymphocyte rest 0.0 Astrocytes TNFalpha + IL-lbeta 4.2 Secondary CD8 lymphocyte act 0.0 KU-812 (Basophil) rest 0.0 CD4 lymphocyte none 0.0 KU-812 (Basophil) PMA/ionomycin 0.0 2ry Thl/Th2/Trl anti-CD95 2ryCH11 /Th2Trlanti-CD95 0.0 CCD 1106 (Keratinocytes) none 12.2 418 WO 03/093432 PCT/USO3/13690 LAK cells rest 0. CCDl 106 (Keratinocytes) 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 gamna 0.0 NCI-H292 IL-4 0.0 LAK cells IL-2+ IL-18 0.0 NCI-H292 IL-9 0.0 LAK cells PMA/ionomycin 5.5 NCI-H292 IL-13 0.0 NK Cells IL-2 rest !4.5 NCI-H292 IFN gamma . Two Way MLR 3 day 0.0 HPAEC none 8.8 Two Way MLR 5 day 0.0 HPAEC TNF alpha + IL-1 beta .0.0 Two Way MLR 7 day 0.0 Lung fibroblast none PBMC rest 10.0 Lung fibroblast TNF alpha + IL-1 beta 00 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) ionomycin 0.0 Lung fibroblast IFN gamma 0.0 B lymphocytes PWM 0.0 Dermal fibroblast CCD1070 rest 56.3 B lymphocytes CD40L and IL-4 4.8 Dermal fibroblast CCD1070 TNF alpha 40.6 EOL-1 dbcAMP 0.0 Dermal fibroblast CCD1070 IL-1 beta 65.1 EOL-1 dbcAMP PMA/ionomycin 0.0 Dermal fibroblast IFN gamma 24.5 Dendritic cells none 0.0 Dermal fibroblast IL-4 15.3 Dendritic cells LPS . Dermal Fibroblasts rest56.6 Dendritic cells anti-CD40 0.0 Neutrophils TNFa+LPS 00 Monocytes rest 10.0 Neutrophils rest 0.0 Monocytes LPS 0.0 Colon 0.0 Macrophages rest 0.0 Lung 7.0 Macrophages LPS 0.0 Thymus 0.0 HUVEC none 0.0 Kidney 100.0 HUVEC starved 0.0 CNSneurodegenerationvl.0 Summary: Ag6679 This gene was downregulated in the temporal cortex of Alzheimer's diseased brain as analyzed by ANCOVA, with RNA quality as a covariate. This gene codes for Netrin like protein. Netrins are secreted proteins which have both neurotrophic and neuroprotective functions. They are believed to play a role in neurodevelopment, both in neuron survival and in axon guidance (Manitt C, Kennedy TE., 2002,Where the rubber meets the road: netrin expression and function in developing and adult nervous systems. Prog Brain Res. 137:425-42;PMID: 12440385). Therefore, up regulation of this gene or its protein product, is useful preventing, treating or ameliorating symptoms associated with this disease. 419 WO 03/093432 PCT/US03/13690 Generalscreeningpanel vl.6 Summary: Ag6679 Highest CG51051-14 gene expression was seen in U-118-MG brain cancer cell line (CT=28.1) and moderate to low gene expression was detected in melanoma, ovarian, breast, lung, renal and brain cancer cell lines. Gene expression is a marker of melanoma, ovarian, breast, and lung cancer useful in differentiating these tissues from normal tissues and detection of these cancers in vitro or in vivo. Therapeutic modulation of this gene, expressed protein is useful in the treatment of melanoma, ovarian, breast, lung, renal and brain cancers. Moderate to low gene expression was detected in tissues with metabolic or endocrine function such as: adipose, adrenal gland, pituitary gland, and fetal skeletal muscle. Modulation of gene activity is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Significant gene expression was detected in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Panel 4.1D Summary: Ag6679 Highest gene expression was seen in kidney (CT=32.6). and low gene expression was seen in resting and activated dermal fibroblasts. Therefore, therapeutic modulation of this gene, its encoded protein is useful in the treatment of kidney and skin-related disorders such as lupus, glomerulonephritis and psoriasis. L. CG52261-01: 3277237. Expression of gene CG52261-01 was assessed using the primer-probe sets Ag2653 and Ag044, described in Tables LA and LB. Results of the RTQ-PCR runs are shown in Tables LC, LD, LE, LF and LG. Table LA. Probe Name Ag2653 Start SEQ ID Primers Sequences Length Start SEQ ID . .. ....... Position No Forward '-aaagatggctccggaaattat-3' 21 285...... 400 Probe TET-5 ' -acatgCtcttttgcaacgtgaccct-3 ' - 315 5 401 Reverse 5'-gattcaagaggagaggattgga-3' 22 363 402 Table LB. Probe Name Ag044 Primers Sequences Length Start SEQID Position No Forward5 '-tcccaaacttagttgcatagaacct-3' 25 804 403 420 WO 03/093432 PCT/US03/13690 Probe TET-5'-tcctgacccacgcagtccataagga-3'- 25 777 404 Reverse i5'-tctgtgccccgtccaaa-3' 17 759 405 Pr~be!TAMA 1 { 777 4045 Table LC. Panel 1 Column A - Rel. Exp.(%) Ag044, Run 87361687 Tissue Name A Tissue Name A Endothelial cells 0.8 Renal ca. 786-0 0.0 Endothelial cells (treated) 0.0 Renal ca. A498 _0.0 Pancreas 0.0 Renal ca. RXF 393 0.0...... Pancreatic ca. CAPAN 2 0.0 Renal ca. ACHN 00 Adrenal gland 0.0 Renal ca. UO-31 0.3 Thyroid 0.0 Renal ca. TK-10 k 0.0 Salivary gland ]0.0 Liver 0.0 Pituitary gland 0.0 Liver (fetal) 0.0 Brain (fetal) 40.6 Liver ca. (hepatoblast) HepG2 0.0 Brain (whole) 54.7 Lung 0.0 Brain (amygdala) 11.0 Lung (fetal) 2.3 Brain (cerebellum) 100.0 Lung ca. (small cell) LX- 1 0.0 Brain (hippocampus) 33.2 -Lung ca. (small cell) NCI-H69 0.0 Brain (substantia nigra) 3.3 Lung ca. (s.cell var.) SHP-77 0.0 Brain (thalamus) _5.9 Lung ca. (large cell)NCI-H460 0.0 Brain (hypothalamus) ,6.3 Lung ca. (non-sm. cell) A549 0.0 Spinal cord 0.4 Lung ca. (non-s.cell) NCI-H23 0.0 glio/astro U87-MG 0.0 Lung ca. (non-s.cell) HOP-62 f 0.0 glio/astro U-118-MG 0.0 Lung ca. (non-s.cl) NCI-H522 .11.6 astrocytoma SW1783 0.0 Lung ca. (squam.) SW 900 1.2 neuro*; met SK-N-AS 0.0 Lung ca. (squam.)NCI-H596 0.0 astrocytoma SF-539 0.0 Mammary gland 0.9 astrocytoma SNB-75 0.0 -Breast ca.* (pl.ef) MCF-7 0.0 glioma SNB-19 0.0 Breast ca.* (pl.ef) MDA-MB-231 0.0 glioma U251 0.2 IBreast ca.* (pl. ef) T47D -0.0 glioma SF-295 . .0.0 Breast ca. BT-549 .0.0 Heart 10.3 Breast ca. MDA-N 0.0 Skeletal muscle 0.2 Ovary 0.0 Bone marrow 0.0 Ovarian ca. OVCAR-3 0.0 Thymus 17.2 Ovarian ca. OVCAR-4 10.0 Spleen 0.0 iOvarian ca. OVCAR-5 0.0 Lymph node 0.0 Ovarian ca. OVCAR-8 0.8 Colon (ascending) 2.0 Ovarian ca. IGROV-1 0. Stomach 0.2 Ovarian ca. (ascites) SK-OV-3 0.0 Small intestine 0.5 Uterus 0.0 421 WO 03/093432 PCT/US03/13690 Colon ca. SW480 0.0 Placenta 0. Colon ca.* SW620 (SW480 met) 0.0 Prostate 11.2 Colon ca. HT29 0.0 Prostate ca.* (bone met) PC-3 0.0 Colon ca. HCT- 116 0.0 TIestis 9.3 Colon ca. CaCo-2 0.0 Melanoma Hs688(A).T I0.0 Colon ca. HCT-15 0.0 Melanoma* (met) Hs688(B).T 0.0 Colon ca. HCC-2998 0.0 Melanoma UACC-62 0.0 Gastric ca. (liver met) NCI-N87 0.0 Melanoma M14 0.0 Bladder 0.6 Melanoma LOX IMVI 0.0 Trachea .. 0.4 Melanoma* (met) SK-MEL-5 0.0 Kidney 0.2 Melanoma SK-MEL-28 0.0 Kidney (fetal) 1.4 Table LD. Panel 1.3D Column A - Rel. Exp.(%) Ag2653, Run 165720855 Tissue Name A Tissue Name A Liver adenocarcinoma 3.9 Kidney (fetal) 0.0 Pancreas .... 1.3 Renal ca. 786-0 00...... Pancreatic ca. CAPAN 2 0.0 Renal ca. A498 0.0 Adrenal gland 1.3 Renal ca. RXF 393 1.3 Thyroid 0.6 Renal ca. ACHN 0.0 Salivary gland 0.3 Renal ca. UO-31 2.5 Pituitary gland 3.7 Renal ca. TK- 10 0.0 Brain (fetal) 100.0 Liver 0.9 Brain (whole) 40.9 Liver (fetal) 0.0 Brain (amygdala) 35.6 Liver ca. (hepatoblast) HepG2 0.0 Brain (cerebellum) 39.2 Lung 5.3 Brain (hippocampus) 38.7 Lung (fetal) 11.1 Brain (substantia nigra) 8.2 Lung ca. (small cell) LX-1 0.0 Brain (thalamus) 17.8 Lung ca. (small cell) NCI-H69 0.0 Cerebral Cortex 19.6 Lung ca. (s.cell var.) SHP-77 0.0 Spinal cord 8.8 Lung ca. (large cell)NCI-H460 0.0 glio/astro U87-MG 0.0 Lmung ca. (non-sm. cell) A549 0.0 glio/astro U-118-MG 0.0 Lung ca. (non-s.cell) NCI-H23 2.1 astrocytoma SW1783 0.0 Lung ca. (non-s.cell) HOP-62 0.7 neuro*; met SK-N-AS 0.0 Lung ca. (non-s.cl) NCI-H522 8.2 astrocytoma SF-539 0.0 Lung ca. (squam.) SW 900 0.4 astrocytoma SNB-75 5.4 Lung ca. (squam.) NCI-H596 0.0 glioma SNB-19 0.0 Mammary gland 8.4 glioma U251 4.1 Breast ca.* (pl.ef) MCF-7 0.0 glioma SF-295 0.0 Breast ca.* (pl.ef) MDA-MB-231 5.4 422 WO 03/093432 PCT/US03/13690 Heart (fetal) 0.0 Breast ca.* (pl.ef) T47D .0 Heart 14.5 Breast ca. BT-549 0.0 Skeletal muscle (fetal) 7.3 .Breast ca. MDA.N 0.0 Skeletal muscle 5.9 Ovary 1.4 Bone marrow 0.0 iOvarian ca. OVCAR-3 0.0 Thymus 0.7 Ovarian ca. OVCAR-4 0.0 Spleen 0.0 Ovarian ca. OVCAR-5 0.0 Lymph node 2.5 Ovarian ca. OVCAR-8 2.6 Colorectal 3.9 Ovarian ca. IGROV- 1 2.3 Stomach 2.9 Ovarian ca.* (ascites) SK-OV-3 0.0 Small intestine 6.4 Uterus 7.5 Colon ca. SW480 0.0 Placenta 0.0 Colon ca.* SW620(SW480 met) 0.0 Prostate 1.9 Colon ca. HT29 0.0 Prostate ca.* (bone met)PC-3 0.0 Colon ca. HCT-116 0.0 Testis 0.6 Colon ca. CaCo-2 0.0 Melanoma Hs688(A).T 0.0 Colon ca. tissue(ODO3866) 3.5 Melanoma* (met) Hs688(B).T 0.0 Colon ca. HCC-2998 0.0 Melanoma UACC-62. 1.5 Gastric ca.* (liver met) NCI-N87 0.0 Melanoma M14 0.0 Bladder .8 Melanoma LOX IMVI 0.0 Trachea 0.7 Melanoma* (met) SK-MEL-5 0.0 Kidney 1.6 Adipose 19.2 Table LE. Panel 2.2 Column A - Rel. Exp.(%) Ag2653, Run 175142263 Tissue Name A Tissue Name A Normal Colon 6.8 Kidney Margin (OD04348) 12.7 Colon cancer (OD06064) 0.0 Kidney malignant cancer (OD06204B) 00. ,Colon Margin (ODO6064) 2.7 Kidney normal adjacent tissue 0.0 Colon Margin ,, o) 2.7 (OD06204E) Colon cancer (OD06159) 0.0 Kidney Cancer (OD04450-01) 16.7 Colon Margin (OD06159) 10.3 Kidney Margin (OD04450-03) 1.7 Colon cancer (OD06297-04) 1....1.7 Kidney Cancer 8120613 0.0 Colon Margin (0D06297-05) 25.O- Kidney Margin 8120614 0.0 CC Gr.2 ascend colon (ODO3921) 1.4 Kidney Cancer 9010320 0.0 CC Margin (OD03921) 4.8 K idney Margin 9010321 0.0 Colon cancer metastasis (OD06104) 2.9 Kidney Cancer 8120607 0.0 Lung Margin (OD06104) .0 Kidney Margin 8120608 1.5 Colon mets to lung (OD04451-01) 14.9 Normal Uterus 19.8 Lung Margin (OD04451-02) 127.2 Uterine Cancer 064011 2.2 Normal Prostate 11.2 JNormal Thyroid 0. 423 WO 03/093432 PCT/USO3/13690 Prostate Cancer (OD04410) 0.0 Thyroid Cancer 064010 0.0 Prostate Margin (OD04410) 1.4 Thyroid Cancer A302152 7.4 Normal Ovary 1.6 Thyroid Margin A302153 0.5 Ovarian cancer (OD06283-03) 0.9 Normal Breast 37.6 Ovarian Margin (OD06283-07) 13.8 Breast Cancer (OD04566) 0.0 Ovarian Cancer 064008 17.2 Breast Cancer 1024 5.3 Ovarian cancer (OD06145) 0.0 Breast Cancer (OD04590-01) 1.1 Ovarian Margin (OD06145) 1.7 Breast Cancer Mets (OD04590-03) 14.7 Ovarian cancer OD06455-03 . Breast Cancer Metastasis (OD04655- 1.2 Ovarian cancer (ODO6455-03) 0005)12 Ovarian Margin (OD06455-07) 13.2 Breast Cancer 064006 7.0 Normal Lung 25.9 Breast Cancer 9100266 0.0 Invasive poor diff. lung adeno (D4945-010.0 Breast Margin 9100265 0.6 (ODO4945-01 Lung Margin (ODO4945-03) 100.0 Breast Cancer A209073 0.0 Lung Malignant Cancer (OD03126) 7.3 Breast Margin A2090734 4.4 Lung Margin (OD03126) 37.9 Breast cancer (OD06083) 3.3 Breast cancer node metastasis Lung Cancer (OD05014A) 3.1 (OD06083) 4.1 Lung Margin (OD05014B) 62.9 Normal Liver 0.0 Lung cancer (OD06081) 0.9 Liver Cancer 1026 00 Lung Margin (OD06081) 54.7 Liver Cancer 1025 8 Lung Cancer (OD04237-01) 0.0 Liver Cancer 6004-T 0.0 Lung Margin (OD04237-02) 47.0 Liver Tissue 6004-N 1.2 Ocular Melanoma Metastasis 0.0 Liver Cancer 6005-T 0 Ocular Melanoma Margin (Liver) 1.2 Liver Tissue 6005-N 0 Melanoma Metastasis 2.7 Liver Cancer 064003 2.5 Melanoma Margin (Lung) 28.3 Normal Bladder 1.4 Normal Kidney 0.0 Bladder Cancer 1023 3.1 Kidney Ca, Nuclear grade 2 (OD04338) 6.2 Bladder Cancer A302173 0.0 Kidney Margin (OD04338) 1.1 Normal Stomach 19.1 Kidney Ca Nuclear grade 1/2 (OD04339) 8.9 Gastric Cancer 9060397 0.0 Kidney Margin (OD04339) 1.5 Stomach Margin 9060396 0.0 Kidney Ca, Clear cell type (OD04340) 0.0 Gastric Cancer 9060395 2. Kidney Margin (OD04340) 4.0 Stomach Margin 9060394 1.6 Kidney Ca, Nuclear grade 3 (OD04348) 1.3 Gastric Cancer 064005 3.5 Table LF. Panel 4D Column A - Rel. Exp.(%) Ag2653, Run 158944046 Tissue Name A Tissue Name A Secondary Th1 act 12.8 HUVEC IL-lbeta 6.1 Secondary Th2 act-, - 0.4 I-IJVEC IFN gamma 7.0 424 WO 03/093432 PCT/US03/13690 Secondary Tr act 1 .7 HUVEC TNF alpha + IFN gamma 13.8 Secondary ThI rest 2.9 HUVEC TNF alpha + IL4 8.6 Secondary Th2 rest 0.8 HUVEC IL-11 6.8 Secondary Trl rest 0.6 Lung Microvascular EC none 7.2 Primary Thl act 15.1 Lung Microvascular EC TNFalpha + IL-Ibeta 6.0 Primary Th2 act 5.3 Microvascular Dermal EC none 21.2 Primary Trl act Microsvasular Dermal EC TNFalpha + IL- 1.7 ... ...... .. ..... . . ... bt.. .. Primary Th1 rest 8.0 Bronchial epithelium TNFalpha + ILlbeta Primary Th2 rest 1.3 Small airway epithelium none 2.0 Primary Trl rest 3.4 Small airway epithelium TNFalpha + IL- 1 beta 36.3 CD45RA CD4 lymphocyte act 1.5 Coronery artery SMC rest 19.3 CD45RO CD4 lymphocyte act 3. Coronery artery SMC TNFalpha + IIL-ibeta 4.4 CD8 lymphocyte act 0.0 Astrocytes rest 9.3 Secondary CD8 lymphocyte rest 2.4 Astrocytes TNFalpha + IL-lbeta 3.5 Secondary CD8 lymphocyte act 0.0 KU-812 (Basophil) rest 0.0 CD4 lymphocyte none 0.0 KU-812 (Basophil) PMAJionomycin 0.0 2ry Thl/Th2/Trl anti-CD95 CCD eranocytes) none CH11 1.2 CCD1106 (Keratinocytes) none 0.3 LAK cells rest 0.0 CCD 1106 (Keratinocytes) TNFalpha + IL- 0 l beta LAK cells IL-2 7.1 Liver cirrhosis 1.8 LAK cells IL-2+IL-12 33,Lupus kidney 1.9 LAK cells IL-2+IFN gamma 0.0 NCI-H292 none 9.4 LAK cells IL-2+ IL-18 .1 NCI-H292 IL-4 8.1 LAK cells PMA/ionomycin 0.7 NCI-H292 IL-9 4.2 NK Cells IL-2 rest NCI-H292 IL-13 7.1 Two Way MLR 3 day 1.1 NCI-H292 IFN gamma 4.5 Two Way MLR 5 day 0.0 HPAEC none 10.8 Two Way MLR 7 day 0.0 HPAEC TNF alpha + IL-1 beta 9.0 PBMC rest 0.0 Lung fibroblast none 3.8 PBMC PWM 4.6 Lung fibroblast TNF alpha + IL-1 beta 0.0 PBMC PHA-L 12.2 Lung fibroblast IL-41 Ramos (B cell) none 0.0 Lung fibroblast IL-9 2.1 Ramos (B cell) ionomycin 0.0 Lung fibroblast IL-13 0.7 B lymphocytes PWM 14.0 Lung fibroblast IFN gamma 0.7 B lymphocytes CD40L and IL-4 7.9 Dermal fibroblast CCD1070 rest 0.0 EOL-1 dbcAMP 0.0 Dermal fibroblast CCD1070 TNF alpha 2.4 EOL-1 dbcAMP PMA/ionomycin 0.0 Dermal fibroblast CCD1070 IL-1 beta 0.0 Dendritic cells none 0.4 Dermal fibroblast IFN gamma 2. Dendritic cells LPS 0.0 Dermal fibroblast IL-4 32.1 Dendritic cells anti-CD40 0.0 IBD Colitis 2 2.2 425 WO 03/093432 PCT/US03/13690 Monocytes rest 0.0 IBD Crohn's 3.6 Monocytes LPS 0.0 Colon 17.6 Macrophages rest 0.0 Lung 23.0 Macrophages LPS 0.0 Thymus 6.9 HUVEC none 13.5 Kidney 10.0 HUVEC starved 41.2 Table LG. Panel 5 Islet Column A - Rel. Exp.(%) Ag2653, Run 253239425 Tissue Name A Tissue Name A 97457 Patient-02go adipose 100.0 94709 Donor 2 AM - A adipose 0.0 97476 Patient-07sk skeletal muscle 14.7 94710 Donor 2 AM- B adipose 0.0 97477 Patient-07ut uterus 12.2 94711 Donor 2 AM - Cadipose 00 97478 Patient-07pl placenta 0.0 94712 Donor 2 AD - A adipose 0.0 99167 Bayer Patient 1 0.0 94713 Donor 2 AD - B adipose 0.0 97482 Patient-08ut uterus 3.0 94714 Donor 2 AD - C adipose 0.0 .............. ................ ........ ........ .41 _ o o ... ... C a i o s . 97483 Patient-08plplacenta 0.0 94742_Donor 3 U - A Mesenchymal Stem 1.2 p 0 Cells 97486 Patient-09sk skeletal muscle 17.094743 Donor 3 U - B Mesenchymal Stem 0.0 - t .Cells 97487_Patient-09ut uterus 18.6 94730_Donor 3 AM- Aadipose 0.0 97488_Patient-09plplacenta 6.4 94731 Donor 3 AM - B adipose 0.0 97492 Paient-10ut uterus 8.7 94732 Donor 3 AM - C adipose 0.0 97493 Patient-10plpet a 4. p. 97493_Patient-10plplacenta 4.7 94733 Donor 3 AD- Aadipose 5.6 97495 Patient-11go adipose 57.8 94734 Donor 3 AD - B adipose 0.0 97496 Patient-1i lsk skeletal muscle 38.7 94735 Donor 3 AD - C adipose 0.0 97497 Patient-1lut uterus 19.2 77138 Liver HepG2untreated 13.6 97498_Patient-plplacenta 0.0 73556 Heart Cardiac stromal cells 12.1 (primary) 97500 Patient-12go adipose 87.7 81 7 35 Small Intestine 39.8 97501 Patient-12sk skeletal muscle 37.1 72409 Kidney Proximal Convoluted 10.1 Tubule 97502 Patient-12ut uterus 18.4 82685 Small intestine Duodenum 16.8 97503 Patient- 12pl_placenta 0.0 90650 Adrenal Adrenocortical adenoma 0.0 94721 Donor 2 U - AMesenchymal 2 1 __2 Stem Cells - 2.1 72410_Kidney HRCE 94722 Donor 2 U - B Mesenchymal 0.0 7241Kidney Stem Cells - 7241 Kidney HRE 94723 Donor 2. U - C_Mesenchymal 0. 73139_UterusUterine smooth muscle 0. Stem Cells 1 el0.0 cell 426 WO 03/093432 PCT/US03/13690 Panel 1 Summary: Ag044 Highest CG52261 gene expression was seen in cerebellum (CT=28) and moderate expression was detected in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Modulation of this gene and expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Signigficant gene expression was also seen in fetal lung and two lung cancer cell lines indicating that gene expression level is useful as a marker to differentiate and detect the presence of lung cancer. Furthermore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of the lung cancer. Low expression of this gene was also seen in testis, thymus and heart. Panel 1.3D Summary: Ag2653 Highest CG52261 gene expression was detected in fetal brain (CT=28.8) and moderate gene expression was seen in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Significant gene expression was also seen in brain, lung, colon and breast cancer cell lines. Expression levels of this gene are useful markers to detect the presence of these cancers. Modulation of this gene and/or encoded protein is useful in the treatment of the brain, lung, colon and breast cancers. This gene is expressed at moderate levels in tissues with metabolic or endocrine function including: adipose, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Panel 2.2 Summary: Ag2653 Highest CG52261 gene expression was detected in normal lung (CT=30) and significant expression of this gene was seen in normal lung, colon, breast, ovary, kidney, uterus and stomach tissues collected from tumor margins compared to low gene expression detected in breast, thyroid, kidney, lung, ovary and colon cancer samples. Therefore, modulation of this gene, encoded protein and/or use of agonist targeting the encoded protein is useful in the treatment of these lung, colon, breast, ovary, kidney, uterus and stomach cancers. Panel 4D Summary: Ag2653 Highest expression of this gene was seen in kidney (CT=28.6) and moderate to low expression was detected in activated and resting primary Thl, Trl, Th2 and secondary Thl cells, activated LAK cells, activated PBMC cells, activated B lymphocytes, endothelial cells, activated small airway epithelium, coronery artery SMC cells, 427 WO 03/093432 PCT/US03/13690 astrocytes, NCI-H292 cells, activated lung, dermal fibroblasts, IBD colitis and Crohn's samples. Significant expression was seen in normal colon, thymus and lung tissues. Modulation of this gene, expressed protein and/or use of antibodies, small molecule drug targeting the encoded protein alter functions associated with these cell types and relief of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythernatosus, psoriasis, rheumatoid arthritis, and osteoarthritis. Panel 5 Islet Summary: Ag2653 Highest expression of this gene was seen in adipose tissue from a diabetic patient (CT=32.6). Significant gene expression was seen in adipose, and skeletal muscle from either diabetic or non-diabetic but overweight patients. Low expression was seen in small intestine. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in treatment of metabolic diseases such as obesity and diabetes. M. CG52414-02: Rhomboid. Expression of gene CG52414-02 was assessed using the primer-probe sets Ag2648, Ag2786 and Ag7066, described in Tables MA, MB and MC. Results of the RTQ-PCR runs are shown in Tables MD, ME, MF, MG and MH. Table MA. Probe Name Ag2648 Start SEQ ID Position No iPrimersj Sequences ............. i..io....N. Forward 5 '-ggtggatcaggtcaatcga-3' J19 1637 406 Probe TET-5'-caacccagaagttctcctgctggatg-3'- I 1603 Prrobe T26 1603 407 TAMRA Reverse 5'-gtgtgtacgagagcgtgaagta-3' 122 1581 408 Table MB. Probe Name Ag2786 Sequeces {_Start SEQ ID Primers Sequences Length position No ] -1Position No Forward 5'-tggctgtacatctaccccatta-3' 22 2714 409 TET-5'-ctggatcgagcacctcacctgctt-3'- 24 274 41 Probe TAMRA24 _ 2743 410 Reverse 5'-acctggtccagctcatacttct3; 22 2790 411. Table MC. Probe Name Ag7066 Start SEQ ID Primers Sequences Length Position No Forwward5 '-gttcagagaagcgccctg-3' 8 552 42 428 WO 03/093432 PCT/UtS03/13690 Probe TET-5 ' -aggcctcactgtcccagagcatc-3'- 23 582 413 TAMRA Reverse 5'-tccaaaccactgggctg-3' 17 615 414 Table MD. General screeningpanelvl.7 Column A - Rel. Exp.(%) Ag7066, Run 318350037 Tissue Name A Tissue Name A Adipose 9.2 "Gastric ca. (liver met.) NCI-N87 0.7 HUVEC 16.7 "Stomach .3 Melanoma* Hs688(A).T 0.0 Colon ca. SW-948 5.8 Melanoma* Hs688(B).T 59.5 jColon ca. SW480 0.2 Melanoma (met) SK-MEL-5 31.2 Colon ca. (SW480 met) SW620 47. Testis 1.0 Colon ca. HT29 23.0 Prostate ca. (bone met) PC-3 0.3 Colon ca. HCT-116 13.0 Prostate ca. DU145 29.1 'Colon cancer tissue 2.6 Prostate pool 0.7 .Colonca. SW116 . 13.8 Uterus pool 1.5 Colon ca. Colo-205 21.3 Ovarian ca. OVCAR-3 9.2 Colon ca. SW-48 29.9 Ovarian ca. (ascites) SK-OV-3 2.0 Colon 2.5 Ovarian ca. OVCAR-4 100.0 Small Intestine - 0.4 Ovarian ca. OVCAR-5 59.9 Fetal Heart 2.5 Ovarian ca. IGROV-1 40.9 Heart 1.9 Ovarian ca. OVCAR-8 13.8 LymphNode pool 1 I1.0 Ovary 2.4 Lymph Node pool 2 34.9 Breast ca. MCF-7 11.4 Fetal Skeletal Muscle 1.0 B i ? 2 ;,. D ; B 2 ~~ii~ ......... .. ........ ---- 1.2 ..... e.a M us .o. .......... . Breast ca. MDA-MB-231 71.2 Skeletal Muscle pool 1.2 Breast ca. BT-549 13.1 Skeletal Muscle . Breast ca. T47D 15.7 Spleen 9.9 Breast pool .. _ 2.4 Thymus 2.5 Trachea 7.3 CNS cancer (gliolastro) SF-268 5.1 Lung 11.1 CNS cancer (glio/astro) T98G 9.9 Fetal Lung 7.1 CNS cancer (neuro;met) SK-N-AS 3.3 Lung ca. NCI-N417 4.8 CNS cancer (astro) SF-539 10.5 Lung ca. LX-1 .34.9 CNS cancer (astro) SNB-75 ......... 6.4 Lung ca. NCI-H146 1.9 CNS cancer (glio) SNB-19 9.3 Lung ca. SHP-77 0.9 CNS cancer (glio) SF-295 ............ 29.1 Lung ca. NCI-H23 59.5 Brain (Amygdala) 4.2 Lung ca. NCI-H460 33.2 Brain (Cerebellum) 2.6 Lung ca. HOP-62 42.3 Brain (Fetal) 2.0 Lung ca. NCI-H522 .28.7 Brain (Hippocampus) 5.0 Lung ca. DMS- 114 13.1 Cerebral Cortex pool 3.1 Liver 2.2 Brain (Substantia nigra) 2.0 429 WO 03/093432 PCT/US03/13690 Fetal Liver .2.3 Brain (Thalamus) 3.8 Kidney pool 6.7 Brain (Whole) 5.7 Fetal Kidney 2.9 Spinal Cord 5.0 Renal ca. 786-0 13.9 Adrenal Gland 6.6 Renal ca. A498 63.7 Pituitary Gland 2.0 Renal ca. ACHN 37.9 Salivary Gland 1.8 Renal ca. UO-31 50.0 Thyroid 3.9 Renal ca. TK-10 54.0 Pancreatic ca. PANC-1 40.9 Bladder 3.0 Pancreas pool 3.3 Table ME. Oncology cell linescreening_panel v3.2 Column A - Rel. Exp.(%) Ag2648, Run 268695314 Tissue Name A Tissue Name A 94954_Ca Ski_CerviCal 94905 Daoy Medulloblastoma/Cereb 94954Ca Ski Cervical ellum sscDNA 5.8 epidermoid carcinoma 20.4 e -u scNA. (metastasis) _sscDNA 94906 TE671_Medulloblastom/Cereb 94955 ES-2 Ovarian clear cell 14.5 11.3 ellum sscDNA carcinoma sscDNA 94907_D283 94957 Ramos/6h stim MedMedulloblastoma/Cerebellumss 21.2 Stimulated with 13.8 ceDNA PMA/ionomycin 6h sscDNA 94908_PFSK-1_Primitive 94958 Ramos/14h stim uroectodermal/Cerebellum sscDN 3.8 Stimulated with 24.3 A PMA/ionomycin 14h sscDNA 94962 MEG-01 Chronic 94909_XF-498_CNSsscDNA 2.3 myelogenous leukemia 12.2 (megokaryoblast) ascDNA 94910_SNB- 94963 RajiBurkitt's 0.0 -_aj - Brits14.9 78 CNS/glioma sscDNA lymphoma sscDNA 94911 SF- 94964 Daudi Burkitt's 9.4 - -36.9 268 CNS/glioblastoma sscDNA lymphoma sscDNA 6 94965 U266 B-cell 94912_T98G_Glioblastoma_sscDNA 29.7 plasmacytoma/myeloma sscD 49.3 NA 96776_SK-N-SHNeuroblastoma 23 94968 CA46 Burkitt's 20.6 23.7 20.6 (metastasis) sscDNA lymphoma sscDNA 94913_ SF- 45.4 94970 RL non-Hodgkin's

B

295 _CNS/glioblastoma sscDNA . cell lymphoma sscDNA 18.0 132565 NT2 pool sscDNA 12.0 94972 JM1_pre-B-cell 45.7 lymphoma/leukemia sscDNA 94914 Cerebellum sscDNA 5.3 94973 JurkatT cell 8.0 -_ _ -_leukemia sscDNA 96777_Cerebellum sscDNA 2.5 94974_TF- 7.5 ______________-____ 51 Erythroleukemia sscDNA 7 430 WO 03/093432 PCT/US03/13690 94916 NCI-H292 Mucoepidermoid 94975 HUT 78 T-cell 4 7. 3 -- 32.3 lung carcinoma sscDNA lymphoma sscDNA 94917 DMS- 14 Small cell lung 194977 U937 Histiocytic _______14 ___6_ ______f19.5 cancer sscDNA lymphomasscDNA 94918_DMS-79_Small cell lung 94980 KU-812_Myelogenous7 142.9 1Meono 7.0 $cancer/neuroendocrine sscDNA leukemia sscDNA 94919 NCI-H146 Small cell lung 2.9 94981 769-P Clear cell renal -- 67.9 cancer/neuroendocrine sscDNA carcinoma sscDNA 94920 NCI-H526 Small cell lung 94983 Caki-2 Clear cell renal 58.6 11.1 58.6 cancer/neuroendorinesscDNA carcinoma sscDNA 94921 NCI-N417_Small cell lung 1 94984_SW 839_Clear cell 97.9 cancer/neuroendocrine_sscDNA renal carcinoma sscDNA 94923 NCI-H82_Small cell lung 94986_G401 Wilms' 17.3 1 - 12.3 cancer/neuroendocrinesscDNA tumor sscDNA 12.3 94924 NCI-H157_Squamous cell ln 94924NCI-H157Squamus cell lung 34.2 126768 293 cellssscDNA 19.5 c a n c e r ( m e t a s t a s i s ) _ s s c D N A . .... ... . .., , . .. ... ., . .. . . . ..-.... .... . .. ... . .. .. 94925 NCI-H1155Large cell lung i94987 Hs766T Pancreatic 94925_NCI-H1155_Large cell lung 14.6 carcinoma (LN 17.1 cancer/neuroendocrinesscDNA metastasis) sscDNA 94926 NCI-H299 Large cell lung 94988 CAPAN-1 Pancreatic canc94926e/NCI-H1299Laeuroendocrge cell lung 34.6 adenocarcinoma (liver 60.3 cancerneuroendocrnesscDNA metastasis) sscDNA 94927 NCI-H1727 Lung 94989 SU86.86_Pancreatic arcinoidsscDNA 19.6 carcinoma (liver 100.0 carinoid-sscDNA metastasis) sscDNA 94928 NCI-UMC-1 1Lung 1 94990_BxPC-3 _Pancreatic carcinoid sscDNA adenocarcinoma sscDNA 21.9 94929 LX-1 Small cell lung 7 94991_- HPACPancreatic cancer sscDNA adenocarcinoma sscDNA 94930_Colo-205_Colon 42.9 94992 MIA PaCa-2 Pancreatic 11.6 cancer sscDNA carcinoma sscDNA 94993 CFPAC-1 Pancreatic 9493 I_KMI2_Colon cancer_sscDNA 23.7 ductal 65.1 adenocarcinoma sscDNA 94932 KM20L2 Colon 94994_PANC-1_Pancreatic cancersscDNA 11.7 epithelioid ductal 87.7 ............... _-_......carcinom asscD N A 94933_ NCI-H716 Colon 23 94996 T24 Bladder carcinma 16 cancer sscDNA -(transitional cell) sscDNA 94935 SW-48 Colon 94997 5637 Bladder 50.3 - -74.2 adenocarcinoma sscDNA carcinoma sscDNA 7 94936_SW1116 Colon 94998_HT-1197 Bladder 21.0 adenocarcinoma sscDNA 14.9 carcinoma sscDNA 21.0 94937_LS 174TColon 94999 _UM-UC-3 _Bladder adenocarcinoma sscDNA 54.0 carcinma (transitional 4.9 ____________-_ ___ cell) sscDNA 431 WO 03/093432 PCT/US03/13690 94938 SW-948 Colon 2.95000 A204 Rhabdomyosarco 2 6 adenocarcinoma sscDNA 2 ma sscDNA 26.8 94939 SW-480 Colon 29.3 95001 HT- 55.1 adenocarcinomasscDNA .3 1080 Fibrosarcoma sscDNA 55.1 94940 NCI-SNU-5 Gastric 95002 MG-63 Osteosarcoma117.6 caciom scDA30.4 17.6 jrcioma sscDNA (bone) sscDNA 95003 SK-LMS 112197 KATO IIIStomach sscDNA 19.6 1_Leiomyosarcoma 24.3 .1297.AT.. t95003_SK-LMS 124.3o~o _ ](vulva)sscDNA 94943 NCI-SNU-16_Gastric 95004 SJRH30 Rhabdomyosa carcinoma sscDNA 9.4 rcoma (met to bone 6.7 marrow) sscDNA 94944 NCI-SNU-1 Gastric 95005_A43 Epidermoid 2 95005 A43 1_Epidermoid - - 32.1 , • - -24.7 carcinoma sscDNA carcinoma sscDNA .. 94946 RF-1 Gastric 95007 WM266 adenocarcinoma sscDNA 16.7 4-Melanoma sscDNA 11.7 94947 RF-48 Gastric 112195 DU adenocarcinoma_ sscDNA 12.2 145_Prostate sscDNA 50.0 96778_MKN-45Gastric 95012_MDA-MB-468 Breast carcinoma sscDNA 3. *_ adenocarcinoma sscDNA 22.2 94949_NCI-N87 Gastric 112196 SSC carcinoma sscDNA 43.5 4Tongue sscDNA 20.7 94951 OVCAR-5 Ovarian 112194 SSC ___________25.9____ j84.7. .. carcinoma sscDNA 25.9 9 Tongue sscDNA 84.7 94952 RL95-2 Uterine 112191 SSC __ __ __ __ __ _13.9___ _ - 83.5 carcinoma sscDNA 15 TonguesscDNA3.5 94953 HelaS3Cervical 14.3 95017_CAL 27 Squamous cell 14.3 5. adenocarcinoma sscDNcarcinoma of tongue sscDNA Table MF. Panel 1.3D Column A - Rel. Exp.(%) Ag2648, Run 156606391 Column B - ReL Exp.(%) Ag2786, Run 165527181 Tissue Name A B Tissue Name A B Liver adenocarcinoma 120.9 16.5 Kidney (fetal) 17.1 17.7 Pancreas 10.3 13.0 Renal ca. 786-0 11.3 119.3 Pancreatic ca. CAPAN 2 19.1 13.0 Renal ca. A498 . 100.0 100.0 Adrenal gland 14.5 18.2 Renal ca. RXF 393 18.7 73.2 Thyroid 15.2 13.8IRenal ca. ACHN 17.7 7.5 Salivary gland .6.2 7.9 Renal ca. UO-31 63.3 34.9 Pituitary gland 3.1 4.4 Renal ca. TK-10 49.3 24.7 Brain (fetal) 2.9 6.6 Liver 2.4 4.5 Brain (whole) T4.7 18.6 Liver (fetal) 7.9107 Brain (amygdala) 17.3 32.1 ILiver ca. (hepatoblast) HepG2 35.4 20.9 Brain (cerebellum) 32.19 i Lung 3 0.3 432 WO 03/093432 PCT/USO3/13690 Brain (hippocampus) 50.3 29.5 Lung (fetal) 10.2 9.1 Brain (substantia nigra) 5.4 34.6 ILung ca. (small cell) LX-1 46.0: 42.3 Brain (thalamus) 12.2 29.9 Lung ca. (small cell) NCI-H69 6.6 0.1 Cerebral Cortex 1.9 5.0 Lung ca. (s.cell var.) SHP-77 3.0 2.0 ISpinal cord 111.6 50.0 Lung ca. (large cell)NCI-H460 2.8 11.7 glio/astro U87-MG 20.2 10.2 Lung ca. (non-sm. cell) A549 11.7 7.1 glio/astro U-11 8-MG 7.1 6.3 Lung ca. (non-s.cell) NCI-H23 10.41 11.5 astrocytoma SW1783 19.6 22.7 Lung ca. (non-s.cell) HOP-62 47.0 53.2 neuro*; met SK-N-AS 33.2 16.7 Lung ca. (non-s.cl) NCI-H522 20.6 2.4 astrocytoma SF-539 2.6 7.0 Lung ca. (squam.) SW 900 12.0 9.0 astrocytoma SNB-75 10.9 15.0 Lung ca. (squam.) NCI-H596 0.2 1.0 glioma SNB-19 0.5 6.6 Mammary gland 9.5 23.5 . . .. .. ................ . . :, . . .. .. .... .. .. .. ... .... ... ... ..... .... . ......... ....... .... ............. . ..... .. .. ..... ... .... .... . glioma U251 2.5 17.1 Breast ca.* (pl.ef) MCF-7 11.0 8.1 glioma SF-295 89.5 29.3 Breast ca.* (pl.ef) MDA-MB-231 60.7 43.5 Heart (fetal) 10.3 3.4 Breast ca.* (pl.ef) T47D 7.8 11.2 Heart 2.6 6.5 Breast ca. BT-549 9.4 6.4 Skeletal muscle (fetal) 78.5 8.2 Breast ca. MDA-N 5.0 3.3 Skeletal muscle 2.0 13.3 Ovary 21.9 1.7 Bone marrow 16.6 20.9, Ovarian ca. OVCAR-3 11.5 12.8 Thymus 14.1 12.2 Ovarian ca. OVCAR-4 6.9 15.5 Spleen 55.5 52.9Ovarian ca. OVCAR-5 69.7 44.8 Lymph node 19.8 88.3 .varian ca. OVCAR-8 13.3 2.5 Colorectal 10.4 4.9 !Ovarian ca. IGROV-1 5.4 1.7 Stomach 12.6 24.7 jOvarian ca.* (ascites) SK-OV-3 2.8 6.7 Small intestine 24.8 37.9 Uterus 2.3 23.7 Colon ca. SW480 31.9 15.

7 Placenta 24.0 19.2 Colon ca.* SW620(SW480 met) 37.9 10.2 Prostate 4.2 11.8 Colon ca. HT29 14.0 0.9 Prostate ca.* (bone met)PC-3 21.8 13.2 Colonca. HCT-116 17.1 11.2 Testis 13.2 14.9 Colon ca. CaCo-2 14.6 10.4 Melanoma Hs688(A).T 1.2 2.2 Colon ca. tissue(ODO3866) 31.0 18.3 Melanoma* (met) Hs688(B).T 0.7 3.9 Colon ca. HCC-2998 21.5 11.0 Melanoma UACC-62 3.0 10.8 Gastric ca.* (liver met) NCI-N87 44.4 46.7 Melanoma M14 11.1 47.6 Bladder 12.7 8.1 Melanoma LOX IMVI 7.7 2.6 Trachea 42016.7 Melanoma* (met) SK-MEL-5 12.3 5.8 Kidney 13.7 7.3 Adipose 11.210.3 Table MG. Panel 2D Column A - Rel. Exp.(%) Ag2648, Run 156606695 Column B - Rel. Exp.(%) Ag2786, Run 162570060 Tissue Name B Tissue Name A B 433 WO 03/093432 PCT/US03/13690 Normal Colon 21.9 25.7 Kidney Margin 8120608 10.4 7.1 CC Well to Mod Diff(ODO3866) 26.4 30.6 Kidney Cancer 8120613 29.9 33.7 C Margin (ODO3866) 7.6 6.6 Kidney Margin 8120614 0.0 4.9 CC Gr.2 rectosigmoid (ODO3868) 11.7 10.1Kidney Cancer 9010320 77.9 47.6 CC Margin (ODO3868) 2.3 1.6 Kidney Margin 9010321 27.0 26.1 CC Mod Diff (ODO3920) 23.21 26.1 Normal Uterus 2.8 2.0 CC Margin (ODO3920) 11.3 71 Uterus Cancer 064011 12.9 15.2 CC Gr.2 ascend colon (ODO03921) 54.7 62.4 Normal Thyroid 15.2 9.9 CC Margin (ODO3921) 10.7 8.7 Thyroid Cancer 064010 13.2 10.4 CC from Partial Hepatectomy 441 Thd C A302152 19.2 16.0 (ODO4309) Mets 5 4 1 Thyroid Cancer A302152 Liver Margin (ODO4309) 11.3 9.9 Thyroid Margin A302153 17.2 16.4 Colon mets to lung (OD04451-01) 49.7 41.2 Normal Breast .2 18.8 Lung Margin (OD04451-02) 20.9 8.3 Breast Cancer (OD04566) 37.6 25.2 Normal Prostate 6546-1 8.3 37.4Breast Cancer (OD04590-01) 31.0 34.4 Prostate Cancer (OD04410)16.4 Breast Cancer Mets (OD4590- 56.3 57.0 03) Prostate Margin (OD04410) 15.3 11.3 Breast Cancer Metastasis 28.3 25.7 (OD04655-05) Prostate Cancer (OD04720-01) 11.6 Breast Cancer 064006 23.7 18.9 Prostate Margin (OD04720-02) 19.6 21.2 Breast Cancer 1024 16.6 17.9 Normal Lung 061010 42.3 39.2 Breast Cancer 9100266 33.7 37.1 Lung Met to Muscle (ODO4286) 33.9 37.1 Breast Margin 9100265 9.9 13.0 Muscle Margin (ODO4286) 17.0 17.4 Breast Cancer A209073 42.9 35.4 Lung Malignant Cancer (OD03126) 45.4 47.0 jBreast Margin A209073 16.8 16.8 Lung Margin (OD03126) 44.1 29.9 Normal Liver 4.5 7.0 Lung Cancer (OD04404) 52.5 33.9 Liver Cancer 064003 :6.5 4.8 Lung Margin (OD04404) 24.1 17.7 Liver Cancer 1025 9.3 4.5 Lung Cancer (OD04565) 42.3 31.4 Liver Cancer 1026 25.0 19.6 Lung Margin (OD04565) 28.3 14.0 Liver Cancer 6004-T 10.4 8.0 Lung Cancer (OD04237-01) 36.3 35.1 Liver Tissue 6004-N 28.1 15.5 Lung Margin (OD04237-02) 25.5 31.6 Liver Cancer 6005-T 18.3 16.2 Ocular Mel Met to Liver (ODO4310) 22.1 25.0 Liver Tissue 6005-N 6.0 7.0 Liver Margin (ODO43 10) 10.3 7.1 Normal Bladder 51.4 66.9 Melanoma Mets to Lung (OD04321) 21.3 18.0 Bladder Cancer 1023 31.0 17.4 Lung Margin ( O D 04321) 39.2 34.2 Bladder Cancer A302173 27.4 16.2 Normal Kidney 17.1 16.8 Bladder Cancer (OD04718-01) 100.094.6 Kidney Ca, Nuclear grade 2 Bladder Normal Adjacent [ (OD04338) I8 7. 1 (OD04718-03) 24.0 22.1 Kidney Margin (OD04338) 26.4 18.6 Normal Ovary 8.8 8.3 Kidney Ca Nuclear grade 1/2 (OD04339) 56.6 46.7 jOvarian Cancer 064008 74.7 76.8 Kidney Margin (OD04339) J8.8 10.1 Ovarian Cancer (OD04768-07) 82.4 72.2 434 WO 03/093432 PCT/US03/13690 Kidney Ca, Clear cell type] ] (ODO4340) Clear cell type 97.9 100.0 Ovary Margin (OD04768-08) 19.9 12.9 Kidney Margin (OD04340) 31.2 29.9 Normal Stomach 11.8 9.5 Kidney Ca, Nuclear grade 3 (OD04348) Nuclear grade 3 47.6 40.9 Gastric Cancer 9060358 8.2 1.8 Kidney Margin (0D04348) 21.6 25.2 Stomach Margin 9060359 18.4116.6 Kidney Cancer (OD04622-01) 60.13 42.6 Gastric Cancer 9060395 121.6 18.6 Kidney Margin (OD04622-03) 5.7 4.9 StomachMargin 9060394 23.5 17.7 Kidney Cancer (OD04450-01) 27.9 32.3 Gastric Cancer 9060397 62.0 63.7 Kidney Margin (OD04450-03) -J6.8 6.1 Stomach Margin 9060396 10.29.9 Kidney Cancer 8120607 37.6 29.3 Gastric Cancer 064005 24.1 26.2 Table MH. Panel 4D Column A - Rel. Exp.(%) Ag2648, Run 156607036 Column B - Rel. Exp.(%) Ag2786, Run 162188411 STissue Name .A B Tissue Name ... A B Secondary Thi act 18.4 11.2 HUVEC IL-1lbeta 10.2 4.6 Secondary Th2 act 24.8 17.6 IJHUVEC IFN gamma 33.2]21.9 Secondary Tr act 20.6 10.4 HUVEC TNF alpha + IFN gamma 76.3159.0 Secondary Thl rest 9.6 _ 8.6 HUVEC TNF alpha + IL4 134.6129.9 Secondary Th2 rest 8.2 7.2 iHUVEC IL-11 7.46.3 Secondary Trl rest j9.3 6.7 Lung Microvascular EC none 36.140.6 12 Lung Microvascular EC TNFalpha + 57 57 Primary Thl act 1 9.8 5iL.bet a " .8 IL-1beta Primary Th2 act 11.0 5.3 Microvascular Dermal EC none 34.6 26.2 Primary T act 15.2 5. Microsvasular Dermal EC TNFalpha + 72.775.8 Primary TrKI act 1.2 5.7 JIL-1Ibet a Primary Th1 rest 28.3 15.1 Bronchial epithelium TNFalpha+ 7.4 88.3 ______________________ J 15.1ILl beta Primary Th2 rest 13.6 9.3 Small airway epithelium none 9.9 11.6 Primary T rest 10.4 45Small airway epithelium TNFalpha + 7236 Primar.Tr...est .. .. 4. 5 IL-1beta 1-ronery35 CD45RA CD4 lymphocyte act 22.8 9.9 Coronery artery SMC rest 20.717.4 CD45RO CD4 lymphocyte act 16.5 7.2

C

ronery artery SMC TNFalpha + IL 20.2 9.6 " l b et a "1o. CD8 lymphocyte act 8 12.1 Astrocytes rest 8.3 .8 _et___._ 181. Secondary CD8 lymphocyte rest 15.7 17 .4 Astrocytes TNFalpha + IL-1 beta 18.2j15.8 Secondary CD8 lymphocyte . 8 1KU 12 B act 8.5T5.1 KU-812 (Basophil) rest 2.3 1.9 CD4 lymphocyte none 7.1 5.6 KU-812 (Basophil) PMA/ionomycin 3.4 1.9 2ry Thl/Th2/Trl anti-CD95 2yT-iT9.tiCD5 0 8.2 CCD1106 (Keratinocytes) none 19.5 18 435 WO 03/093432 PCT/USO3/13690 LAK cells rest 83. 5 CCD 1106 (Keratinocytes) TNFalpha+ LA cel et8.5 58.6 1 1~bt . 112.7180.7 IL--1beta LAK cells IL-2 19.3 11.6 Liver cirrhosis . 4.7 4.6 LAK cells IL-2+1L-12 16.0 15.8 JLupus kidney 4.2 2.3 LAK cells IL-2IFN gamma 28.5 17.3 NCI-H292 none 20.0 12.1 LAK cells IL-2+ IL-18 27.4 21.8 NCI-H292 IL-4 23.5 13.5 LAK cells PMA/ionomycin 84.1 60.3 NCI-H292 IL-9 23.3 18.7 NK Cells IL-2 rest ]31.9 26.6 NCI-H292 IL-13 23.715.9 Two Way MLR 3 day 90.1 73.2 NCI-H292 IFN gamma 58.6 38.2 Two Way MLR 5 day 33.9 35.6 HPAEC none 13.8 9.2 Two Way MLR 7 day 13. 12.4 HPAEC TNF alpha + IL-1 beta 89.5 71.7 PBMC rest 12.4 15.3 Lung fibroblast none 3.1 3.2 PBMC PWM 38.2 27.2 Lung fibroblast TNF alpha + IL-1 beta 20.015.6 PBMC PHA-L 25.3 23.2 Lung fibroblast IL-4 4.4 2.5 Ramos (B cell) none 22.7 24.1 ung fibroblast IL-9 4.313.1 Ramos (B cell) ionomycin 49.7 11.3 Lung fibroblast IL-13 1.6 2.9 B lymphocytes PWM 22.8 17.0 Lung fibroblast IFN gamma 27.920.3 B lymphocytes CD40L and Bymphocytes CD4L and 26.6 16.2 Dermal fibroblast CCD 1070 rest 9.6 7.6 IL-4 EOL-1 dbcAMP 2.8 1.6 Dermal fibroblast CCD1070 TNF alpha26.6117.8 EOL-1 dbcAMP PMAionomycin 33.0 25.5 Dermal fibroblast CCD 1070 IL- 1 beta 8.4 6.9 PMAlionomycin. ........ Dendritic cells none 48.3 42.3 Dermal fibroblast IFN gamma 20.212.5 Dendritic cells LPS 83.5 68.3 Dermal fibroblast IL-4 6.0 Dendritic cells anti-CD40 29.3 29.9 IBDColitis2 0.9 1.1 Monocytes rest 42.9 57.0 IBD Crohn's 2.4 0.3 Monocytes LPS 80.7 100.0 Colon 13.7 9.8 Macrophages rest 94.6 82.9 Lung 17.910.8 Macrophages LPS 100.0 94.0 Thymus 5.8 1.5 HUVEC none 11.3 8.7 Kidney 11.3 11.0 HUVEC starved 19.6 10.6 Generalscreeningjpanel vl.7 Summary: Ag7066 Highest CG52414 gene expression was seen in OVCAR-4 ovarian cancer cell line (CT=25.6) and high expression was detected in pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancer cell lines. Expression of this gene is a useful marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene is effective in the treatment of pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, melanoma and brain cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, 436 WO 03/093432 PCT/US03/13690 skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene is moderately expressed in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Oncology celllinescreeningpanelv3.2 Summary: Ag2648 Highest expression of this gene was detected in SU86.86 pancreatic cancer cell line (CT=30) and moderate gene expression was seen in lung, bone marrow, epidermoid, vulva, bone, bladder, pancreatic, renal, B cells and T cells, leukemia, lymphoma, cervical, gastric, colon, lung and brain cancer cell lines. Panel 1.3D Summary: Ag2648/Ag2786 Highest expression of this gene was detected in renal cancer A498 cell line (CTs=28-28.9 and moderate gene expression was seen in pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, melanoma and brain cancer cell lines. Thus, expression of this gene is a useful marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene is effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Among tissues with metabolic or endocrine function, moderate gene expression was detected in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene showed moderate to low levels of expression in central nervous system tissues including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Modulation of this gene and/or encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Panel 2D Summary: Ag2648/Ag2786 Highest expression of this gene was detected in bladder and kidney cancers (CTs=26.4-28) and high to moderate gene expression was detected in cancer and normal samples derived from colon, prostate, liver, lung, kidney, breast, thyroid, ovary and stomach. Expression of this gene was higher in cancer samples especially gastric, bladder, breast, kidney and colon cancer compared to adjacent normal 437 WO 03/093432 PCT/US03/13690 tissues. Expression of this gene is a useful marker to differentiate cancerous from normal adjacent tissues and to detect the presence of these cancers in vitro or in vivo. This gene codes for a protease belonging to Rhomboid family known to activate growth factors ligands (Urban et al. Cell 2001 Oct 19; 107(2):173-82). Therefore this gene likely plays a role in tumor cell proliferation and invasion, by activating growth factors like TGFalpha and EGF that mediates cell growth and invasion. Targeting CG52414-02 protein with a human monoclonal antibody to inhibit the activity of this protein has therapeutic effect on tumors, particularly colon, gastric, kidney, ovarian and bladder tumors. Panel 4D Summary: Ag2648/Ag2786 Highest expression of this gene was detected in LPS activated macrophages and monocytes (CTs=27-28.5) and high to moderate expression levels were detected in cell types significant in the immune response. These cells include: T-cell, B cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal colon, lung, thymus and kidney tissues. Expression of this gene is stimulated in activated endothelial cells, small airway epithelium and fibroblasts. The ubiquitous pattern of expression indicates that this gene product is involved in homeostatic processes. Modulation of the gene, expressed protein and/or antibodies, small molecule drug targeting the encoded protein alters the functions of these cell types and leads 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. N. CG52643-02: 4324229RS. Expression of gene CG52643-02 was assessed using the primer-probe sets Ag2812, Ag2822, Ag861, Agl0, Ag010b and Ag550, described in Tables NA, NB, NC, ND, NE and NF. Results of the RTQ-PCR runs are shown in Tables NG, NH and NI. Table NA. Probe Name Ag2812 1 Lth Start SEQ ID Primers Sequences Length Start SEQID Position No Forward 5'-ctgtactcgctttgtggttca-3' 21 3037 415 Probe T-5-cactggtctccttgcaagtttcctag-3' - 26 3059 416 Reverse 5'-aatcttggtagcagcgcatac-3' 21 3091 417 Table NB. Probe Name Ag2822 438 WO 03/093432 PCT/US03/13690 Primers Sequences Length Start SEQ ID Position No Forward: s'-tcttcatccaggtcctgctt-3' 20 1023 418 Probe TET-5' -cttcagcacatgctgagccagttcg-3'- 25 998 419 Reverse 5'-ttcagggacttagatgcagatg-3' 22 954 420 Table NC. Probe Name Ag861 Primers Sequences Length Start SEQ ID Primer Su e Lg .... Position No Forward 5'-gatgggaggttttatgaaaacc-3' 22 7i7 421 Probe TT-5'-actgtaagctccaccgtgctgcttq-3' - 25 739 422 Reverse 5 '-ggatgacggtgatcctcttt-3' 0 773 423 Table ND. Probe Name Ag 10 Primers Sequences Length Start Position SEQ ID No Forward 5'-gcctggctctctggatagaca-3' 21 1439 424 Probe TET-5'-tggcggcacattcacctgcag-3'-TAMRA 21 1410 425 Reverse 5'-cacgagcagctgttccagac-3' 20 1383 426 Table NE. Probe Name Ag 010b Primers Sequences Length Start SEQ ID Position No Forward 5'-tgagacatccacgccgttt-3' 19 1535 427 Probe TET-5 '-ttcccatgcccagaatcacttggct-3 '- 25 1507 428 Reverse 5 '-agccagcctaagatgccatg-3 ' 20 1478 429 Table NF. Probe Name Ag550 Prime Squenes Leng Start SEQ ID Prim.Sequences Lengthj Position No Forward 5' -ccgccccagatctcatga-3 '8 4516 430 Probe TET-5'-acttgtatgtctcacgcaacttggtecacc-3'- 30 4542 431 Probe 1TET-5' 30 4542 431 Reverse 5'-ggcgcaaccctaggagttac -3' 20 4587 432 439 WO 03/093432 PCT/US03/13690 Table NG. Panel 1 Column A - Rel. Exp.(%) Ag010b, Run 97807632 Column B - Rel. Exp.(%) Agl0, Run 87352582 Column C - Rel. Exp.(%) Ag10, Run 91677212 Tissue Name A B Tissue Name A B C Endothelial cells 0.O 0.0 0.0 Renal ca. 786-0 0.0 0.0 0.0 Endothelial cells (treated) 0.0 0.0 0.0 Renal ca. A498 0.2 0.0 0.1 Pancreas 0.6 2.2 1.5 Renal ca. RXF 393 0.0 0.0 0.0 Pancreatic ca. CAPAN 2 10. 0.0 0.0 Renal ca. ACHN 0.0 0.0 0.1 Adrenal gland 1.3 5.8 4.8 Renal ca. UO-31 0.0 0.0 Thyroid 0.0 0.0 0.1 Renal ca. TK-10 0.0 0.00.0 Salivary gland 0.1 0.3 0.3 Liver 0.0 0.0 0.1 Pituitary gland 0.01 0.0 0.0 Liver (fetal) 0.0 0.0 0.1 Brain (fetal) 03 91.3 Liver ca. (hepatoblast) 6.0 8.2 6.9 HepG2 Brain (whole) 2.7 78.5 24.7 Lung 0.1 2.3 0.3 Brain (amygdala) 2.7113.2 6.9 Lung (fetal) 0.0 0.0 0.2 Brain (cerebellum) 3.8 100.0 5.5 Lung ca. (small cell) LX-1 2.2 3.9 3.4 ____________________ 52.l8.3Lung ca. (small cell) NCI Brain (hippocampus) 1.6 52.1 ung ca. (small cell) NCI-10.4 ............. ..... ..... ..... H 6 9 Brain substantiala nigra) 1.5 7.3 4.2 Lung ca. (s.cell var.) SHP-77 0.9 0.0 9.2 24.5uLung ca. (large cell)NCI Brain (thalamus) 8.2.48.3 24.5 g a lrecl)C- 100.0: 0.0:100.0 ............................ H460 Brain (hypothalamus) 1.6 15.2 8.0 Lung ca. (non-sm. cell) A549 6.9 46.3 14.8 Spinal cord Lung ca. (non-s.cell) NCI H23 glio/ast___o U87-MG 0.6 1.5 1.6 Lung ca. (non-s.cell) HOP-62 0.0 0.0 0.0 t Lung ca. (non-s.cl) NCI gliolastro U-118-MG 0.0 1 0.0 H ca. (nons.cl) NC0.0 0.0 0.0 H522 astrocytoma SW1783 0.0 0.0 0.0 Lung ca. (squam.) SW 900 0.6 3.3 2.6 neuro*; met SK-N-AS 0.0 0.0 0.3 Lung ca. (squam.) NCI-H596 9.0 4.8 22.1 astrocytoma SF-539 0.0 0.0 0.0 Mammary gland 0.3 1.1 j0.4 astrocytoma SNB-75 0.0 0.0 0.0 Breast ca.* (pl.ef) MCF-7 2.2 17.7 9.9 glioma SNB-19 0.00.0 0.0 Breast ca.* (pl.ef) MDA-MB- 0.0 0.0 0.0 glioa SN-19231 glioma U251 0.0 0.0 Breast ca.* (pl. ef) T47D 0.1 0.0 0.1 glioma SF-295 0.0 0.0 0.0 Breast ca. BT-549 0.0 0.0 Heart 0.0 0.0 0.1 Breast ca MDA-N 0.1 0.0 0.3 Skeletal muscle 0.0 0.0 0.1 Ovary 0.2 0.0 0.4 Bone marrow 0.0 0.0 0.1 Ovarian ca. OVCAR-3 0.0 0.0 0.0 Thymus 0.2 1.3 1.3 Ovarian ca. OVCAR-4 0.0 0.5 0.2 Spleen 0.0 0.0 0.0 Ovarian ca. OVCAR-5 .5 12.4 9.0 Lymph node 0.0 0.1 Ovarian ca. OVCAR-8 0.0 0.0 0.0 440 WO 03/093432 PCT/USO3/13690 Colon (ascending) 0.4 0.0 j0.1 Ovarian ca. IGROV-1 1.3 3.0 1.7 tomOvarian ca. (ascites) SK-OV-1 StColon ca. HT29 10.11 0.0 0.0 Prostate ca.* (bone me 0.0 0.0 0.0 CoSm all intestine 0.0 0.2 0.5 Uterus .4 19.3 7.011.8 Colon ca. CaCo-2 0. 0.3 Placenta 140(A . 0.0 0.3 Colon ca.* SW620 (SW480 33 .7Pote 1.m.337trstt 0.7 5.2: 2.1 Colon ca. HT29 0.1 0.0 0.0 prostate ca.* (bone met) PC 0.0 . . . ...... IP0.0 Colon ca. HCT-1 16 0.2100 0. 1 Testis 1.4 14.1 11.81 Colon ca. CaCo-2 0.2 0.3 0.3 Melanoma Hs688(A).T 0.0 0.0 0.3 Colon ca. HCT- 15 0.0.0 . Melanoma* (met)0. 0000 0. 0.00 0. . Hs688(B).T Colon ca. HCC-2998 0.00. 0.1 Melanoma UACC-62 0.1 0.0 0.1 Gastric ca. * (liver met) NCI- 0.0 0.0 0.0 MeanomaM14 0.0 0.0 0.0 Melanoma M14 0.0 0.0 0.1 N87 Bladder 0.3 5.9 1.3 Melanoma LOX IMVI 0.0 0.0 0.0 Trachea 0.1 0.1 0.5 Melanoma* (met)SK-MEL-5 0.5 0.7 1.3 Kidney _ 3.1 10.5 3.6 Melanoma SK-MEL-28 1. 6 0.2 Kidney (fetal) .4 1.7 0.9 . . . . . Table NH. Panel 2D Column A - Rel. Exp.(%) Ag2812, Run 157457938 Column B - Rel. Exp.(%) Ag2822, Run 163578435 Tissue Name IA B Tissue Name TA B Normal Colon 4.6 3.2 Kidney Margin 8120608 5.6 4.1 CC Well to Mod Diff (ODO3866) jo0.0 0.0 Kidney Cancer 8120613 0.4 0.7 CC Margin (ODO3866) .A 4 0.0 Kidney Margin 8120614 23.7 16.6 CC Gr.2 rectosigmoid (ODO3868) 0.8 0.0 .Kidney Cancer 9010320 1.5 12 CC Margin (ODO3868) 0.8 0.0 Kidney Margin 9010321 25.9 25.5 CC Mod Diff (ODO3920) 0.4 0.0 Normal Uterus 0.0 0.0 CC Margin (ODO3920) 0.4 0.8 Uterus Cancer 064011 1:41.4. .3 CC Gr.2 ascend colon (ODO3921) 0.0 0.5 Normal Thyroid 0. 0.3 CC Margin (ODO3921) 0.3 0.7 Thyroid Cancer 064010 0.7 0.0 CC from Partial Hepatectomy CC from Partial Hepatectomy 3.1 0.0 Thyroid Cancer A302152 2.6 0. 7 (ODO4309) Mets ..... ____ ___"_....... Liver Margin (OD04309) I0.4 0.0 Thyroid Margin A302153 0.8 0.8 Colon mets to lung (OD04451-01) 1.5 1.4jNormal Breast 1.8 2.8 Lung Margin (OD04451-02) 2.6 4.6 Breast Cancer (OD04566) 6.6 7.4 Normal Prostate 6546-1 4.0 54.0 Breast Cancer(0 4590-01) 10.711.3 Breast Cancer Mets (ODO4590 Prostate Cancer (OD04410) 1.91 3

.

7 1.ast arMe-(D4591 3 3.1 Breast Cancer Metastasis .5 Prostate Margin (OD04410) 1. (D04655-05) 330

(

4 655 41 05) 441 WO 03/093432 PCT/USO3/13690 Prostate Cancer (OD04720-01) 113.1.14.4 Breast Cancer 064006 9.9 5.8 Prostate Margin (OD04720-02) 13.1 10.7 Breast Cancer 1024 100.O 100.0 Normal Lung 061010 14.3 19.2 Breast Cancer 9100266 8.0 6.8 Lung Met to Muscle (0D04286) 1.3 0.0 Breast Margin 9100265 1.4 1.0 Muscle Margin (ODO4286) 27.5 27.0 Breast Cancer A209073 16.2 8.1 Lung Malignant Cancer (OD03126) '50.3 82.4 Breast Margin A209073 2.9 1.9 Lung Margin (OD03126) 18.7 14.2 Normal Liver 0.4 10.0 Lung Cancer (OD04404) 113.1 6.2 Liver Cancer 064003 1.0 0.5 Lung Margin (OD04404) 4.3 4.3 Liver Cancer 1025 0.0 10.0 Lung Cancer (OD04565) 3.2 2.8 Liver Cancer 1026 2.2 2.4 Lung Margin (OD04565) 6.26.7 Liver Cancer 6004-T 1.1 0.0 Lung Cancer (OD04237-01) 7.0 9.1 Liver Tissue 6004-N 2.4 7.0 Lung Margin (OD04237-02) 3.2 4.0 Liver Cancer 6005-T 3.3 2.4 Ocular Mel Met to Liver (ODO43 10) 3.4 0.0 Liver Tissue 6005-N 0.0 0.0 Liver Margin (ODO4310) 0.4 0.0 Normal Bladder 5.7 4.5 Melanoma Mets to Lung (OD04321) 8.5 0.0 Bladder Cancer 1023 0.0 0.0 Lung Margin (OD04321) 9.5 7.5 Bladder Cancer A302173 32.8 20.2 Normal Kidney 23.2 33.0 Bladder Cancer (OD04718-01) 1.4 3.0 Kidney Ca, Nuclear grade 2 20 1.3 Bladder Normal Adjacent 0.0 J0.0 (OD04338) (OD04718-03) Kidney Margin (OD04338) 21.5 13.1 Normal Ovary 0.9 0.7 Kidney Ca Nuclear grade 1/2 1 9 (OD04339) 424.3 varian Cancer 064008 11 Kidney Margin (OD04339) 28.9115.5 Ovarian Cancer (OD04768-07) 0.6 0.0 Kidney Ca, Clear cell type (0D04340) 4.2 4.7 Ovary Margin (OD04768-08) 0.0 0.0 Kidney Margin (OD04340) 24.7 16.4 Normal Stomach 0.5 1.0 Kidney Ca, Nuclear grade 3 (OD0434) .. 0.4 0.0 Gastric Cancer 9060358 0.0 0.0 (ODO4348)_______ ____ Kidney Margin (OD04348) 12.6 13.7 Stomach Margin 9060359 1.4 0.7 Kidney Cancer (OD04622-01) 1.4 0.0 Gastric Cancer 9060395 0.0 0.0 Kidney Margin (OD04622-03) 4.1 5.6 Stomach Margin 9060394 0.8 0.0 Kidney Cancer (0D04450-01) 0.0 0.0 Gastric Cancer 9060397 0.8 0.0 Kidney Margin (OD04450-03) 15.4 18i4 Stomach Margin 9060396 1L6 0.0 Kidney Cancer 8120607 . 0.0 0.0 Gastric Cancer 064005 0.0 10.0 Table NI. Panel 4D Column A - Rel. Exp.(%) Agl0, Run 146090888 Column B - Rel. Exp.(%) Ag2812, Run 157457426 Column C - Rel. Exp.(%) Ag2822, Run 164320847 Tissue Name A B C Tissue Name A f C Secondary Thi act 0.0 0.0 0.0 HUVEC ILibeta 0.9 0.0- 0.0 442 WO 03/093432 PCT/US03/13690 Secondary Th2 act 0.0 0.0 2.9: HUVEC IFN gamma _0.,0 0. 0 . HUTVEC TNF alpha + IFN Secondary Trl act 0.7 0.7 0.0 TNF alpha + IFN 0.0 0.0 gamma Secondary ThI rest 0.0 0.0 1.6 HUVEC TNF alpha + IL4 0.0 0.0 0.0 Secondary Th2 rest 0.0 0.8 1.6 HUVECIL-11 0.7 2.3 0.0 Secondary Trl rest 0.0 0.0 0.0 Lung Microvascular EC none 1.4 1.0 0.0 Primary Th1 act 1.4 2.0 11 6 Lung Microvascular EC 0. 0.0 Primary T ctj.4 .016TNFalpha + IL- 1 beta 0 Primary Th2 act 22.1 16.6 39.5 Microvascular Dermal EC none 2.0 2.0 00 MicrsvaslarDermal EC Primary Trl act 2.6 2 .5 5.0 osasiljDrmal EC 0.0 0.0 0.0 TNFalpha + IL-1beta Primary Th1 rest 0.0 1.0 0.0 Bronchial epithelium TNFalpha 2.1 1.0 2.1 .0 0.0 + ILl beta Primary Th2 rest 1.9 2.6 4.4 Small airway epithelium none 0.9 0.0 0.0 Primary Trl rest 0.0 0.8 0.0 Small airway epithelium 2.5 3.1 2.2 TNFalpha + IL-lbet a CD45RA CD4 lymphocyteact .. 0.8 0.0 0.0 Coronery artery SMC rest 0.0 0.4 0.0 ~lymphocyte act___________________ CD45RO CD4 Coronery artery SMC 0.0 0.0 0.0 0.0 0.0 i0.0 lymphocyte act TNFalpha + IL-Ibeta 00 00 CD8 lymphocyte act 0.0 0.0 0.0 Astrocytes rest 0.0 0.0 0.0 Secondary CD8 00 0.0 00 Astrocytes TNFalpha + IL lymphocyte rest 1 ___jbeta . . . SecondaryCD8 0 Secpocyte act 0.0 0.0 0.0 KU-812 (Basophil) rest 0.7 1.6 0.0 lymphocyte act KU-812 (Basophil) CD4 lymphocyte none 0.0 0.8 0 0 MA/ionomycin 2ry Thl/Th2/Trl anti CD95 CHI 1 0.0 0.2 0.0 CCD 1106 (Keratinocytes) none 1.3 0.0 1.9 LAK c .lls rest 0. 0 0.0 CCD1106 (Keratinocytes) 0.0 0.0 0.0 LA........ ce; rTNFalpha + IL-lbeta LAK cells IL-2 0.4 0.9 3.1 Liver cirrhosis 0.0 2.2 0.0 LAK cells IL-2+IL-12 0.0 0.0 6.3 Lupus kidney 1.1 1.0 3.4 LAK cells IL-2+IFN 0.8 0.6 3.0 NCI-H292 none 1.5 2.4 3.2 gamma LAK cells IL-2+ IL-18 0.8 0.0 0.0 NCI-H292 IL-4 2.7 47.2 LAK cells ____cells_ 0.0 0.0 0.0 NCI-H292 IL-9 2.8 1.7 1.2 PMA/ionomycin K Cells IL-2 rest 0.0 0.0 0.0 NCI-H292 IL-13 2.3 5.1 Two Way MLR 3 day 0.0 00.0 . NCI-H292IFN gamma 0.6 0.6 0.0 Two Way MLR 5 day 0.0 0.6 0.0 HPAEC none 1.4 0.7 0.0 TwoWay MLR 7 day 0.0 0.0 0.0 HPAEC TNF alpha + IL-1 beta 0.0 2.0 PBMC rest 0.9 1.8 0.0 Lung fibroblast none0.0 3.7 0.0 PBMC PWM 0.0 j0.9 0.0 3Lung fibroblast TNF alpha + 0.0 2.0 0.0 443 WO 03/093432 PCT/US03/13690 IL-1 beta PBMC PHA-L 0.0 1.0 0.0 Lung fibroblast IL-4 0.0 2.6 0.0 amos (B cell) none 25.7125.5 0.0 Lung fibroblast IL-9 0.0 5.3 0.0 Ramos (B cell) ionomycin 100.0 68.0Lung fibroblast IL-13 0.0 4.1 0 B lymphocytes PWM 3.5 2.6 0.0 Lung fibroblast IFN gamma 0.0 6.7 0.0 B lymphocytes CD40L .0 1 Dermal fibroblast CCD 1070.0 0 0.0 an L40.0 1.0 1.4 res 0.0 0.0 0.0 and IL-4 ___~ IrestI__ Dermal fibroblast CCD107 0 EOL-1 dbcAMP 0.0 0.0 0.0 Deafiboblast CCD070 .0 0.0 0.0 JTNF alpha EOL-1 dbcAMP Dermal fibroblast CCD1O70 IL-0 PMA/ionomycin 0 00 .0 beta 0 Dendritic cells none 5.3 5.4 14.7 Dermal fibroblast IFN gamma 0.0 0.0 0.0 Dendritic cells LPS 0.8 10.0 0. Dermal fibroblast IL-4 0.0 0.0 Dendritic cells anti-CD40 0.0 0.0 1.8 IBD Colitis 2 0.0 4.2 0.0 Monocytes rest 0.0 0.0 0.0 IBD Crohn's 0.0 0.0 3.8 Mon0ocytes_0. 0.0 00Colon 5.1 8.2 2.0 Macrophages rest 0.0 1.9 0.0 Lung 19.1 j1.0 5.4 arophages LPS 0.0 .00.0 Thymus 95.3,100.0100.0 HUVEC none 0.9 1.0 0.0 Kidney 1 5.7 16.0 23.0 HUVEC starved ._12..00 I Panel 1 Summary: Agl0/Ag010b Highest expression of this gene was seen in NCI-H460 lung cancer cell line and cerebellum (CTs 22-24). High expression of this gene was also seen in melanoma, ovarian, lung, colon and liver cancer cell lines. Expression level of this gene is useful as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of melanoma, ovarian, lung, colon and liver cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate levels in pancreas, adrenal gland, skeletal muscle, and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene was expressed at moderate to high 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 and/or expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Panel 2D Summary: Ag2812/Ag2822 Highest expression of this gene was seen in breast cancer sample (CTs=28-30). Moderate to low expression of this gene was also seen in normal 444 WO 03/093432 PCT/US03/13690 and cancer samples from lung, ovary, bladder, breast, kidney, and prostate. Expression of this gene was higher in bladder and breast cancer samples. Therefore, expression level of this gene is useful as a marker to detect the presence of cancer, especially bladder and breast cancer. Furthermore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of lung, ovary, bladder, breast, kidney, and prostate cancers. Higher expression of this gene was seen in kidney cancer relative to the corresponding normal sample. Thus, modulation of the expression of this gene and/or encoded protein is useful in the treatment of kidney cancer. Panel 4D Summary: AglO/Ag2812/Ag2822 Highest expression of this gene was seen in thymus and activated Ramos B cells (CTs=30-32). Significant expression of this gene was also seen in resting Ramos B cells, activated primary Th2 cells and kidney. Therefore, therapeutic modulation of this gene, encoded protein leads 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. O. CG53270-01 and CG53270-02:. Expression of gene CG53270-01 and CG53270-02 was assessed using the primer probe sets Ag1536 and Ag1589, described in Tables OA and OB. Results of the RTQ-PCR runs are shown in Tables OC, OD, OE and DF. CG53270-02 represents the full length physical clone for CG53270-01. Table OA. Probe Name Ag1536 Start SEQ ID Primers Sequences Length_ . Position No Forward 5'-tcttaatgatggagcagtggtt-3' 22 222 433 obe TET-5 '-aacatggccagaatctcaatttcccg-3 '- 26 195 434 Probe TAMRA 2 19 .434 everse5'-gcagacttcttggagaaattcc-3' 22 168 435 Table OB. Probe Name Agl589 Primers Sequences Length Start SEQ ID Position No Forward 5 ' -aagaagtctgccaccaagct-3' 20 936 436 Probe TET-5'-cacagcctgagacaaaacccgagg-3'- 24 985 437 TAMRA 2 985 43 FReverse s '-cctggacatttgcattgct-3' 1 19 1013 438 445 WO 03/093432 PCT/US03/13690 Table OC. Al comprehensive panel_vi.0 Column A - Rel. Exp.(%) Ag1589, Run 278182088 Tissue Name ]A- Tissue Name A 110967 COPD-F 21.3 112427 Match Control Psoriasis-F 33.4 110980 COPD-F 5.8 112418 Psoriasis-M 24.1 110968 COPD-M 25.0 112723 Match Control Psoriasis-M 43.2 110977 COPD-M 17.7 112419 Psoriasis-M 18.0 110989 Emphysema-F 39.8 112424 Match Control Psoriasis-M 2.0 110992 Emphysema-F 24.3 112420 Psoriasis-M 41.2 110993 Emphysema-F 22.4 112425 Match Control Psoriasis-M 67 110994 Emphysema-F 13.2 1104689 (MF) OA Bone-Backus 20.4 110995 Emphysema-F 29.9 1104690 (MF) Adj "Normal" Bone-Backus 5.2 110996 Emphysema-F 13.8 104691 (MF) OA Synovium-Backus 4.7 110997 Asthma-M 9.0 104692 (BA) OA Catilage-Backus 12.8 111001 Asthma-F _ 31.0 104694 (BA) OA Bone-Backus 46.3 111002 Asthma-F 100.0 104695 (BA) Adj "Normal" Bone-Backus 14.1 111003 Atopic Asthma-F 46.3 104696 (BA) OA Synovium-Backus 15.2 111004 Atopic Asthma-F 91.4 104700 (SS) OA Bone-Backus 6.3 111005 Atopic Asthma-F 41.2 104701 (SS) Adj "Normal" Bone-Backus 12.4 111006 Atopic Asthma-F 9.9 104702 (SS) OA Synovium-Backus 12.0 111417 Allergy-M 68.8 117093 OA Cartilage Rep7 58.2 112347 Allergy-M 0.1 112672 OA Bone 50.7 112349 Normal Lung-F 0.0 112673 OA Synovium 5 17.9 112357 Normal Lung-F .46.0 112674OA Synovial Fluid cells 11.6 112354 Normal Lung-M 8.8 117100 OA Cartilage Repl4 2.5 112374 Crohns-F 30.1 112756 OA Bone9 2.8 112389 Match Control Crohns-F 17.2 112757 OA Synovium9 16.0 112375 Crohns-F 22.7 112758 OA Synovial Fluid Cells9 I8.2 112732 Match Control Crohns-F 22.8 117125 RA Cartilage Rep2 56.3 112725 Crohns-M 4.0 113492 Bone2 RA 6.8 112387 Match Control Crohns-M 9.4 113493 Synovium2 RA 2.8 112378 Crohns-M 0.8 113494 Syn Fluid Cells RA 3.7 112390 Match Control Crohns-M 98.6 113499 Cartilage4 RA 2.1 112726 Crohns-M 47.3 113500 Bone4 RA 3.1 112731 Match Control Crohns-M 34.9 113501 Synovium4 RA 1.6 112380 Ulcer Col-F 73.7 113502 SynFluid Cells4RA 0.1 112734 Match Control Ulcer Col-F 32.1 113495 Cartilage3 RA 1.5 112384 Ulcer Col-F 23.2 113496 Bone3 RA 2.5 112737 Match Control Ulcer Col-F 12.0 113497 Synovium3 RA 0.6 112386 Ulcer Col-F 9.4 ,113498 Syn Fluid Cells3 RA 0.4 112738 Match Control Ulcer Col-F 1.5 117106 Normal Cartilage Rep20 55 446 WO 03/093432 PCT/US03/13690 112381 Ulcer Col-M 0.0 113663 Bone3 Normal 0.0 1112735 Match Control Ulcer Col-M J 1.2 1113664 Synovium3 Normal .0 112382 Ulcer Col-M 38.4 113665 Syn Fluid Cells3 Normal 0.0 112394 Match Control Ulcer Col-M 5.5 117107 Normal Cartilage Rep22 5.2 112383 Ulcer Col-M 38.7 113667 Bone4 Normal 19.3 112736 Match Control Ulcer Col-M }21.8 113668 Synovium4 Normal 11.3 112423 Psoriasis-F 22.2 113669 Syn Fluid Cells4 Normal 23.5 Table OD. Panel 1.2 Column A - Rel. Exp.(%) Ag1536, Run 142232138 Tissue Name A Tissue Name A Endothelial cells 1.9 Renal ca. 786-0 3.1 Heart (Fetal) 0.6 Renal ca. A498 7.8 Pancreas 2.0 iRenal ca. RXF 393 0.0 Pancreatic ca. CAPAN 2 0.5 Renal ca. ACHN 1.4 Adrenal Gland 2.0 Renal ca. UO-31 6.6 Thyroid 0.0 Renal ca. TK-10 3.8 Salivary gland 6.7 Liver 0.5 Pituitary gland 0. 1 Liver (fetal) 0.2 Brain (fetal) 0. 1 Liver ca. (hepatoblast) HepG2 5.2 Brain (whole) 0.4 Lung 0.0 Brain (amygdala) 0.4 jLung (fetal) 0.0 Brain (cerebellum) 0.4 Lung ca. (small cell) LX-1 0.1 Brain (hippocampus) 11.3 ILung ca. (small cell) NCI-H69 3.5 Brain (thalamus) 0.3 JLung ca. (s.cell var.) SHP-77 13 Cerebral Cortex 4.2 jLung ca. (large cell)NCI-H460 4.5 Spinal cord 0.2 Lung ca. (non-sm. cell) A549 1.0 glio/astro U87-MG 0.2 Lung ca. (non-s.cell) NCI-H23 1.0 glio/astro U- 118-MG 2.7 Lung ca. (non-s.cell) HOP-624.2 astrocytoma SW1783 1..8 Lung ca. (non-s.cl) NCI-H522 32.3 neuro*; met SK-N-AS ,6.0 Lung ca. (squam.) SW 900 4.6 astrocytoma SF-539 10.9 Lung ca. (squam.) NCI-H596 1.9 astrocytoma SNB-75 0.7 Mammary gland 2.0 glioma SNB-19 2.7 jBreast ca.* (pl.ef) MCF-7 .3.7 glioma U251 1.7 Breast ca.* (pl.ef) MDA-MB-231 0.1 glioma SF-295 .1.7 Breast ca.* (pl. ef) T47D 8.1 Heart 4.0 Breast ca. BT-549 0.2 Skeletal Muscle 0.7 Breast ca. MDA-N 0.3 Bonemarrow 0.1 Ovar .

1.8 Thymus 0.0 Ovarian ca. OVCAR-3 1.6 Spleen .. 0.0 ]Ovarian ca. OVCAR-4 1.9 447 WO 03/093432 PCT/US03/13690 Lynph node 0.0 Ovarian ca. OVCAR-5 9.3 Colorectal Tissue 0.4 Ovarian ca. OVCAR-8 1.0 Stomach 0.4 Ovarian ca. IGROV-1 0.6 Colon ca. SW480 0.2 Uterus 0.5 Colon ca.* SW620 (SW480 met) 0.0 Placenta 0.1 Colon ca. HT29 0.5 Prostate 8.7 Colon ca. HCT- 16 2.0 Prostate ca.* (bone met) PC-3 0.2 Colon ca. CaCo-2 0.0 Testis 100.0 Colon ca. Tissue (ODO3866) 0.8 Melanoma Hs688(A).T 0.6 Colon ca. HCC-2998 6.0 Melanoma* (met) Hs688(B).T 1.4 Gastric ca.* (liver met) NCI-N87 4.5 Melanoma UACC-62 1.7 Bladder 3.9 Melanoma M14 2.1 Trachea 0.2 Melanoma LOX IMVI 0.0 Kidney 1.3 Melanoma* (met) SK-MEL-5 0.1 Kidney (fetal) 2.3 Table OE. Panel 2D Column A - Rel. Exp.(%) Ag1536, Run 145177050 Column B - Rel. Exp.(%) Ag1536, Run 147091203 Column C - Rel. Exp.(%) Ag1536, Run 147758040 Column D - Rel. Exp.(%) Ag1589, Run 155518625 Tissue Name A B C D Normal Colon 5.2 15.2 17.7 3.8 CC Well to Mod Diff(ODO3866) 2.2 7.1 3.4 4.2 CC Margin (ODO3866) 3.8 2.8 2.3 0.0 CC Gr.2 rectosigmoid (ODO3868) 11.2 8.5 14.4 3.7 CC Margin (ODO3868) 2.4 1.8 0.0 0.0 CC Mod Diff (ODO3920) 1.1 2.6 4.7 0.0 CC Margin (ODO3920) 1.7 3.0 5.3 2.3 CC Gr.2 ascend colon (ODO3921) 0.0 1.8 3.6 3.7 CC Margin (ODO3921) 1.9 1.3 1.9 0.3 CC from Partial Hepatectomy (ODO4309) Mets 0.0 2.2 1.0 Liver Margin (ODO4309) 0.0 1.2 3.5 3.8 Colon mets to lung (OD04451-01) 2.0 -3.0 4.9- 0.0 Lung Margin (OD04451-02) 2.4 2.0 1.6 0.0 Normal Prostate 6546-1 71.2 28.7 17.7 25.5 Prostate Cancer (OD04410) 57.0 27.9 35.6 34.6 Prostate Margin (OD04410) 39.2 32.1 72.2 31.0 Prostate Cancer (OD94720-01) 54.7 74.2 85.3 30.4 Prostate Margin (OD04720-02) 72.7 85.9 100.0 100.0 Normal Lung 061010 8.8 1.5 3.5 28.7 448 WO 03/093432 PCT/USO3/13690 Lung Met to Muscle (ODO4286) 0.0 4.2 8.4 6.4 Muscle Margin (ODO4286) .4 3.4 3.0 0.0 Lung Malignant Cancer (OD03126) 0.0 1.6 3.4 22 Lung Margin (OD03126) 0.0 . ... 1.2 1.9 4.5 Lung Cancer (OD04404) 11.1 10.2 20.6 2.9 ,un C nc r O D 0 56 ) ...................... 1 3 9.................... . 14,91 ........ ... 9,..2..... 2 2 Lung Margin (OD04404) 8.7 10.7 5.6 4.8 Lung Cancer (OD04565) 13.9 14.9 19.2 25.7 Lung Margin (0D04565) 2.3 3.6 3.5 0.0 Lung Cancer (OD04237-01) 11.3 0.0 1.4 0.0 Lung Margin (OD04237-02) 1.1 1.0 1.9 6.6 Ocular Mel Met to Liver (ODO4310) 0.0 0.0 0.0 0.0 Liver Margin (ODO4310) 1.9 0.0 0.0 0.0 Melanoma Mets to Lung (OD04321) 1.8 2.4 1.5 0,3 Lung Margin (OD04321) 0.0 0.0 0.0 0.5 Normal Kidney 4.3 3.6 5.3 8.7 Kidney Ca, Nuclear grade 2 (OD04338) 7.1 8.8 4.5 2.3 Kidney Margin (D04338).7 Kidney CaNuclear grade 1/2 (OD04339) 10.2 10.5 10.8 24.1 Kidney Margin (OD04339) 0.0 4.7 0.9 0.0 Kidney Ca, Clear cell type (OD04340) 0.0 0.0 0.0 2.6 Kidney Margin (OD04340) 0.0- 0.0 1.9 2.0 Kidney Ca, Nuclear grade 3 (ODO4348 ) 1.9 1.5 0.0 0.0 Kidney Margin (OD04348) 2.3 2.6 1.2 Kidney Cancer (OD04622-01) 14.5 12.7 4.7 13.7 Kidney Margin (OD04622-03) 3.3 0.0 0.0 0.0 Kidney Cancer (OD04450-01) 0.0 0.0 0.0 0.0 Kidney Margin (OD04450-03) 4.2 0.0 3.5 0.0 Kidney Cancer 8120607 0.0 0.0 0.0 2.9 Kidney Margin 8120608 1.2 2.6 0.0 0.0 Kidney Cancer 8120613 0.0 0.0 1.6 0.0 Kidney Margin 8120614 0.0 6.0 0.0 0.0 Kidney Cancer 9010320 37 11.0 1.7 8.4 Kidney Margin 9010321 0.0 1.4 0.0 0.0 Normal Uterus-, 11.1 5.2 1 4.7 0.0 Uterus Cancer 064011 8.5 8.4 8.7 3.9 Normal Thyroid 2.2 0.0 3.5 0.0 Thyroid Cancer 064010 9.5 3.7 5.2 0.0 Thyroid Cancer A302152 .1.6 4.5 13.01 7.5 Thyroid Margin A302153 0.0 0.0 0.0 0.0 Normal Breast 19.3 35.8 12.0 17.2 Breast Cancer (OD04566) 16.8 20.0 5.4 5.0 tCancer (OD04590-01) 100.0 1. 7. 449 WO 03/093432 PCT/US03/13690 Breast Cancer Mets (OD04590-03) 71.2 45.1 65.5 50.0 Breast Cancer Metastasis (OD04655-05) 53.2 50.3 81.2 67.8 Breast Cancer 064006 15.8 26.1 21.0 17.7 Breast Cancer 1024 49.3 23.5 Breast Cancer 9100266 10.9 10.1 7.3 6.9 Breast Margin 9100265 9.3 16.6 16.5 15.2 Breast Cancer A209073 10.8 12.6 10.1 16.8 Breast Margin A209073 36.1 4.2 511 43.5 Normal Liver 0.0 2.2 1.2 2.5 Liver Cancer 064003 2.7 2.3 4.0 Liver Cancer 1025 4.0 0.0 3.3 0.0 Liver Cancer 1026 0.0 0.0 0.0 0.0 Liver Cancer 6004-T .6 1.3 2.0 1.8 Liver Tissue 6004-N 2.2 1.5 1.4 2.2 Liver Cancer 6005-T 0.0 0.0 2.2 3.0 Liver Tissue 6005-N 0.0 0.0 0.0 0.0 Normal Bladder 3.3 5.4 7.3 3.7 Bladder Cancer 1023 4.8 0.0 1.6 14.9 Bladder Cancer A302173 241 17.8 13. 12.0 Bladder Cancer (OD04718-01) 2.6 5.7 1.2 0.0 Bladder Normal Adjacent (OD04718-03) 4.9 1.2 3.9 1.3 Normal Ovary .1 2.9 6.6 8.3 Ovarian Cancer 064008 21.5 12.1 12.7 5.9 Ovarian Cancer (OD04768-07) 0.0 1.9 0.0 6.8 Ovary Margin (OD04768-08) 0.0 0.0 2.0 3.1 Normal Stomach 0.0 2.7 2.6 4.3 Gastric Cancer 9060358 0.0 0.0 0.0 2.2 Stomach Margin 9060359 0.0 1.5 0.0 0.0 Gastric Cancer 9060395 3.8 5.7 1.6 5.2 Stomach Margin 9060394 0.0 1.8 2.1 5.5 Gastric Cancer 9060397 0.0 4. 4.4 13.9 Stomach Margin 9060396 0.0 2.5 0.0 0.0 Gastric Cancer 064005 2.4 4.9 8.9 17.9 Table OF. Panel 4D Column A - Rel. Exp.(%) Ag1536, Run 147091255 Column B - Rel. Exp.(%) Ag1536, Run 147758086 Column C - Rel. Exp.(%) Ag1589, Run 146791435 Tissue Name A B3 C Tissue Name _ A B C Secondary Th1 act 000.0 0.0 HUVECIL-1beta 0.0 0.0 0.0 Secondary Th2 act 0.0 0.0 0.0 HUVEC IFN gamma 3.9 5.6 0.0 450 WO 03/093432 PCT/US03/13690 Secondary T actHUVEC TNF alpha + IFN Secondary Trl act 1.5.1.6; 0.0 0.0 0.0 0.0 gamma Secondary Thl rest 0.0 0.O 0.0 HUVEC TNF alpha + IL4 0.0 0.0 0.0 Secondary Th2 rest 0.00. 0.0 HUVEC IL-11 2.0 2.6 6.5 Secondary Trl rest 0.0 0.0 0.0 Lung Microvascular EC none 0.0 8.0 0.0 Primary Th act Lung Microvascular EC ... Primary T.hI act 0.0.0..0.0. TNFalpha + IL- I beta 0 Primary Th2 act 1.60.0 0.0 Microvascular Dermal EC none 2.0 3.6 0.0 Primary TrI act j 3 0 0 .00Microsvasular Dermal EC 0 TNFalpha + IL- 1 beta Bronchial epithelium TNFalpha + Primary Thl rest 0.0 0.0 b 21.3 21.9 20.2 ILlbeta Primary Th2 rest 0.0 0.0 0.0 Small airway epithelium none 12.0 18.0 0.0 Sm airway epithelium ne0.0 Primary Trl rest 0.0 2.0 0.0 Small airway epithelium 100.0 52.1 TNFalpha + IL- 1 beta CD45RA CD4 lymphocyte act 3.20.0 5.0 Coronery artery SMC rest 2.9 4.4 0.0 CD45RO CD4 lymphocyte 0 0 0 .Coronery artery SMC TNFalpha 139 4.2 0.0 act + IL-lbeta CD8 lymphocyte act 0.00.0 0.0 Astrocytes rest 30.4 15.2 11.4 Secondary CD8 lymphocyte rest 0.0 0.0 Astrocytes TNFalpha + IL- 1 beta 3.8 8.5 3.9 Secondary CD8 0.0 00 0.0 KU-812 (Basophil) rest 0.0 0.0 0.0 lymphocyte act (Basophil) CD4 lymphocyte none 0.0 0.0 0.0 KU-812 (Basophi 0.0 0.0 PMA/ionomycmn 2ry Thl/Th2/Trlanti CD95 CH11 3.8 1.6 0.0 CCD1106 (Keratinocytes) none 43.8 28.5 26.6 CCD 1106 (Keratinocytes) LAK cells rest 1 .9 0.0 0.0CCD- eta 1.7 0.0 4.5 TNFalpha + IL-1beta LAK cells IL-2 0.010.0 0.0 Liver cirrhosis 14.2 5.7 37.9 LAK cells IL-2+IL-12 0.00.0 0.0 Lupus kidney 0.0 1.5 0.0 LAK cells IL-2+IFN gamma1.7 0.0 0.0 NCI-H292 none 57.8 53.6 27.4 gamma l I LAK cells IL-2+ IL-18 0.010.0 0.0 NCI-H292 IL-4 77.9 63.7 100.0 LAK cells PMA/ionomycin 0.01. 0.0 NCI-H292 IL-9 64.2 81.2 43. NK Cells IL-2 rest 0.00.0 0.0 NCI-H292 IL-13 52.5 28.5 56.6 Two Way MLR 3 day 0.0 0.0 0.0 NCI-H292 IFN gamma 41.8 22.1 25.0 Two Way MLR 5 day 0.00.0 0.0 HPAEC none 9.2 19.3 17.6 Two Way MLR 7 day 0.00. 0.0 HPAEC TNF alpha + IL-1 beta 6.9 4.5 9.1 PBMC rest 0. 0 0.0 Lung fibroblast none 16.2 16.3 15.1 PBMC PWM 0 .7 3.3 Lung fibroblast TNF alpha + IL- 8.2 1 3.5 3.4 beta PBMC PHA-L 3.1 0.0 0.0 Lung fibroblast IL-4 26.4 31.9 0.0 451 WO 03/093432 PCT/US03/13690 Ramos (B cell) none 0.0 0.0 0.0 Lung fibroblast IL-9 6.2 1.9 43 Ramos (B cell) ionomycin 0.00.0 0.0 Lung fibroblast IL-13 33.7 23.2 18.3 B lymphocytes PWM 0.0 0.0 0.0 Lung fibroblast IFN gamma 16.6 16.8 0.0 B lymphocytes CD40L and IL-4 1.9 1.2 5.1 Dermal fibroblast CCD1070 rest 10.9 6.7 0.0 EOL-1 dbcAMP 0.0 0.0: 0.0 Dermal fibroblast CCD 1070 TNF 1.8 9.7 10.0 alpha EOL-1 dbcAMP 0.. 0 0.0 Dermal fibroblast CCD1070 IL-1 53 0.8 0.0 PMA/ionomycin 0. 0 0 beta 5 0 0.0 Dendritic cells none 0. 0.0 0.0 Dermal fibroblast IFN gamma 2.2 3.3 4.6 Dendritic cells LPS 0.0 0.0 0.0 Dermal fibroblast IL-4 21.0 11.0 9.2 ........ ~~~ ~~ .6- 7 .g a .~g g .g ~ ................ .... . .Ia .... Dendritic cells anti-CD40 0.0 0.0 0.0 IBD Colitis 2 6.1 1.3 0.0 Monocytes rest 0.0 0.0 0.0 IBD Crohn's 1.6 0.0 10.0 Monocytes LPS 0.0 0.0 0.0 Colon 1.7 12.5 0.0 Macrophages rest 0.0_1.7_0.0_Lung_15.5 18.4 16.8 Macrophages LPS 0.0 0.0 2.0 Thymus 1.7 0.9 11.6 HUVEC none 4.9 0.0 0.4 Kidney _ _______2.6 12.6 0.0 HUVEC starved 6.9 7.2 0.0 AI comprehensive panel vl.0 Summary: Ag 1589 Highest expression of this gene was seen in an asthma sample (CT=30). Moderate levels of expression of this gene were detected in samples derived from normal and orthoarthitis bone and adjacent bone, cartilage, synovium and synovial fluid samples, rheumatoid arthritis bone and cartilage, normal lung, COPD lung, emphysema, atopic asthma, asthma, Crohn's disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene and/or expressed protein ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis. Panel 1.2 Summary: Ag1536 Highest expression of this gene was detected in testis (CT=26.4). Therefore, antibody or small molecule therapies targeting encoded protein modulates testis function and is important in the treatment of diseases that affect the testis, including fertility and hypogonadism. Moderate to low expression of this gene was also detected in melanoma, pancreatic, brain, lung, breast, ovarian, renal, liver and colon cancer cell lines. Modulation of this gene and/or encoded protein is useful in the treatment of melanoma, pancreatic, brain, lung, breast, ovarian, renal, liver and colon cancers. Among tissues with metabolic or endocrine function, this gene was expressed at low levels in pancreas, adrenal gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, 452 WO 03/093432 PCT/US03/13690 therapeutic modulation of the activity of this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. This gene was expressed at low levels in regions of the central nervous system including: amygdala, hippocampus, thalamus, cerebellum, and cerebral cortex. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Panel2D Summary: Ag1536/Agl589 Highest expression of this gene was detected in breast cancer and normal prostate samples (CTs=30-32). Significant expression of this gene was seen in normal and cancer samples from prostate, lung, kidney, breast, bladder. Therefore, therapeutic modulations of this gene and/or encoded protein is useful in the treatment of prostate, lung, kidney, breast, bladder cancers. Panel 4D Summary: Ag 1536/Agl589 Highest expression of this gene was detected in activated small airway epithelium and IL-4 activated NCI-H292 (CTs=31-32). Moderate expression of this gene was also seen in resting keratinocytes, activated bronchial epithelium, resting and activated mucoepidermoid NCI-H292 cells, activated lung fibroblasts and liver cirrhosis sample. Therefore, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of liver cirrhosis and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema. P. CG54254-04: LEUCINE-RICH REPEAT TRANSMEMBRANE PROTEIN. Expression of gene CG54254-04 was assessed using the primer-probe sets Ag148 and Ag201, described in Tables PA and PB. Results of the RTQ-PCR runs are shown in Tables PC, PD, PE, PF and PG. Table PA. Probe Name Ag148 Primers Sequences Length Start SEQ ID P___ osition No Forward 5-cagccctga cccaag-3' 17 1484 439 I..................................................... .

1 .. I. ... ..

8 I.............. TET-5 ' -ccacctacatcatctgcatggtcaccat-3

'

Probe TAMRA 28 1502 440 Reverse 5'-gggttctcateagctacgt-3' 21 1547 Table PB. Probe Name Ag201 Primers Sequences ILn Start SEQID 453Position No 453 WO 03/093432 PCT/US03/13690 Forward '-cagccctggagcccaag-3' 17 1484 442 P TET-5'-ccacctacatcatctgcatggtcacca-3'- - 443 Probe 1Tz 27 1502 ]443 TAMRA Reverse 5'-cgggtgtctcatcagctacgta-3' 22 1546 444 Table PC. CNS_neurodegeneration_vl.0 Column A - Rel. Exp.(%) Ag148, Run 206989705 Column B - Rel. Exp.(%) Ag148, Run 219923397 Column C - Rel. Exp.(%) Ag201, Run 206975347 Tissue Name A B C Tissue Name A B Control (Path) 3 Temporal AD 1 Hippo Ctx24.1 15.70.0 C 6.3 7.9 6.0 ~Control (Path) 4 Temporal AD 2 Hippo 39.221.8 34 .6Ctro (Path) 4 Temporal 29.7 24.0 29.7 AD 3 Hippo 20.0 9.9 9.5 AD 1 Occipital Ctx 20.2 7.1 15.2 AD 2 Occipital Ctx AD 4 Hippo 25.5 15.2c30.6z 0.0 0.0 0.0 (Missing) AD 5 Hippo 63.7 85.347.0 AD 3 Occipital Ctx 13.4 4.7 11.9 AD 6 Hipp 50.7 29.9 26.4 AD 4 Occipital Ctx 28.9 16.7 28.9 Control 2 Hippo 51.8 272 38.2 AD 5 Occipital Ctx 59.5 6.8 13.1 Control 4 Hippo 21.8 17.0 30. AD 6 Occipital Ctx 12.0 100.0 53.6 Control (Path) 3 Hippo 103 5.0 9.3 Control 1 Occipital Ctx 10.7 4.9 10.4 AD 1 Temporal Ctx 21.6 18.4 25.9 Control 2 Occipital Ctx 48.6 28.9 48.0 AD 2 Temporal Ctx 24.7 15.8 24.8 Control 3 Occipital Ctx 26.1 15.6 21.8 AD 3 Te p ra. . . .. 1 15 ..... .4.... AD 3 Temporal Ctx 8.7 7.2 10.4 Control 4 Occipital Ctx 20.3 13.1 15.4 Control (Path) 1 Occipital AD 4 Temporal Ctx Ctx97.3 47.0 100.0 Control (Path) 2 Occipital AD 5 Inf Temporal Ctx 62.4 603 50.3 Ct 21.3 12.2 250 Ctx Control (Path) 3 Occipital AD 5 Sup Temporal Ctx 47.3 66.0 32.3 tx9.0 4.0 4.1 Control (Path) 4 Occipital AD 6 Inf Temporal Ctx 47.3 2 9

.

9 2 6 .8 Ct 24.3 10.727.0 AD 6 Sup Temporal Ctx 24.3 26.6Control 1 Parietal Ctx 19.2 10.0 15.4 Control 1 Temporal Ctx 17.2 15.7 21.6 Control 2 Parietal Ctx 57.8 75.8 35.6 Control 2 Temporal Ctx 61.123.8 44.4 Control 3 Parietal Ctx 26.6 17.8 28.7 Control 3 Temporal Ctx 35.4 17.6 21.9 Control (Path) 1 Parietal Ctx 100.0 50.7 85.9 Control 3 Temporal Ctx 20.0 13.9 19.3 Control (Path) 2 Parietal Cx42.6 21.6 36.6 Control (Path) 1 Temporal 89.5 46.3 81.8 Control (Path) 3 Parietal Ctx10.7 7.3 9.1 Ctx Control (Path) 2 Temporal 52.9 25.7 40.1 Control (Path) 4 Parietal Ctx 55.9 35.8 49.3 Ctx Table PD. Panel 1 454 WO 03/093432 PCT/US03/13690 Column A - Rel. Exp.(%) Ag148, Run 87589460 Tissue Name A Tissue Name A Endothelial cells 2.6 Renal ca. 786-0 1.3 Endothelial cells (treated) 0.1 Renal ca. A498 2.8 Pancreas 9.7 Renal ca. RXF 393 0.9 Pancreatic ca. CAPAN 2 2.6 Renal ca. ACHN 1.5 Adrenal gland 6.8 Renal ca. UO-31 0.9 Thyroid 14.4 Renal ca. TK-10 5.6 Salivary gland 6.0 Liver 2.7 Pituitary gland 1.8 Liver (fetal) 1.7 Brain (fetal) 11.9 Liver ca. (hepatoblast) HepG2 2.3 Brain (whole) 61.6 Lung 0.8 Brain (amygdala) 28.1 Lung (fetal) 2.7 Brain (cerebellum) 100.0Lung ca. (small cell) LX-1 4.2 Brain (hippocampus) 18.0 Lung ca. (small cell) NCI-H69 Brain (substantia nigra) 167 Lung ca. (s.cell var.) SHP-77 0.0 Brain (thalamus) 19.5 Lung ca. (large cell)NCI-H460 0.0 Brain (hypothalamus) 2.9 Lung ca. (non-sm. cell) A549 3.9 Spinal cord 8.4 Lung ca. (non-s.cell) NCI-H23 3.8 glio/astro U87-MG 1.8 Lung ca. (non-s.cell) HOP-62 1.5 glio/astro U-118-MG 2.0 Lung ca. (non-s.cl) NCI-H522 5.8 astrocytoma SW1783 0.5 Lung ca. (squam.) SW 900 6.7 neuro*; met SK-N-AS 1.9 Lung ca. (squam.) NCI-H596 7.9 astrocytoma SF-539 2.1 Mammary gland 16.4 astrocytoma SNB-75 12.4 Breast ca.* (pl.ef) MCF-7 17.7 glioma SNB-19 7.6 Breast ca.* (pl.ef) MDA-MB-231 4.4 glioma U251 1.6 Breast ca.* (pl. ef) T47D 16.7 glioma SF-295 1.5 Breast ca. BT-549 0.0 Heart 3.2 Breast ca. MDA-N 17.1 Skeletal muscle 3.

8 Ovary 2.3 Bone marrow 2.0 Ovarian ca. OVCAR-3 5.9 Thymus 5.8 Ovarian ca. OVCAR-4 1.5 Spleen 1.3 Ovarian ca. OVCAR-5 8.7 Lymph node 3.5 Ovarian ca. OVCAR-8 4.3 Colon (ascending) 4.9 Ovarian ca. IGROV- 1 1.1 Stomach 12.9 Ovarian ca. (ascites) SK-OV-3 1.6 Small intestine 5.3 Uterus 31.4 Colon ca. SW480 2.8 Placenta 4.5 Colon ca.* SW620 (SW480 met) 3.9 Prostate 9.0 Colon ca. HT29 6.4 Prostate ca.* (bone met) PC-3 0.0 Colon ca. HCT-116 0.0 Testis 16.5 Colon ca. CaCo-2 4.1 Melanoma Hs688(A).T 0.7 455 WO 03/093432 PCT/US03/13690 Colon ca. HCT-15 5.3 Melanoma* (met) Hs688(B).T 1.3 Colon ca. HCC-2998 4.9 Melanoma UACC-62 1.3 Gastric ca. * (liver met) NCI-N87 13.4 Melanoma M14 3.3 Bladder 3.4 Melanoma LOX IMVI 13.1 Trachea 10.7 Melanoma* (met) SK-MEL-5 1.3 Kidney 15.4 Melanoma SK-MEL-28 .0.6 ............. .2 7 .ii ' l . . Z . ,iii .i 2 .iii .ii .1 .l .l .i +2 . .2Z i ....... . .+ ............ 1. Kidney (fetal) 12.1] Table PE. Panel 1.3D Column A - Rel. Exp.(%) Ag148, Run 150018164 Column B - Rel. Exp.(%) Ag201, Run 152827283 Tissue Name A B Tissue Name AI B Liver adenocarcinoma 3.7 3.1 Kidney (feta l) 4.6 6.4 Pancreas 2.4 4.6 Renal ca. 786-0 1.5 0.8 Pancreatic ca. CAPAN 2 4.7 1.7 Renal ca. A498 7.3 8.2 Adrenal gland 4.8 4.5 Renal ca. RXF 393 0.4f0.0 Thyroid .... 20.6 23.8 Renal ca. ACHN .9 1.2 Salivary gland 1.0 2.8 Renal ca..... UO-31 .... 2.0.. 1.1 Pituitary gland 4.5 2.0 Renal ca. TK-10 3.3 6.7 Brain (fetal) 8.4 11.3 Liver 10.90.0 Brain (whole) 28.5 140.1 Liver (fetal) 0.7 2.1 Brain (amygdala) 48.3 50.0 Liver ca. (hepatoblast) HepG2 4.0J 2.2 Brain (cerebellum) 7.5 7.3 Lung 0.6 1.3 Brain (hippocampus) 97.9 94.6 Lung (fetal) 0712.4 Brain (substantia nigra) 5.8 8.0 Lung ca. (small cell) LX-1 4.5 4.5 Brain (thalamus) 30.4 28.1 Lung ca. (small cell) NCI-H69 I9.1ii 88 Cerebral Cortex 33.4 36.9 Lung ca. (s.cell var.) SHP-77 3.0 4.1 Spinal cord 6.4 10.2 Lung ca. (large cell)NCI-H460 13.6 14.9 gliolastro U87-MG 0.9 1.7 Lung ca. (non-sm. cell) A549 1.7 3.2 ili~ -; 8 ia" i02 .i~l~'i: i Xg'i Xl ia ;; i ;ifXS+i ;ii.. .......... .. ~)ff ,i glio/astro U-118-MG 1.5 3.2 Lung ca. (non-s.cell) NCI-H23 .6.7 8.0 astrocytoma SW1783 .1.0 1.4 1Lung ca. (non-s.cell) HOP-62 5.4 1.8 neuro*; met SK-N-AS 4.9 6.0 Lung ca. (non-s.cl) NCI-H522 4.8 4.8 astrocytoma SF-539 3.4 2.0 'Lung ca. (squam.) SW 900 1.0 1.2 astrocytoma SNB-75 5.8 10.6 ALung ca. (squam.) NCI-H596 4.6 3.4 glioma SNB-19 3.4 4.0 Mammary gland glioma U251 3.3 3.6 Breast ca.* (pl.ef) MCF-7 1 3.3 glioma SF-295 9.3 -10.7 Breast ca.* (pl.ef) MDA-MB-231 1.8 2.4 Heart (fetal) 2.5 1.7 Breast ca.* (pl.ef) T47D 1.6 5.2 Heart 0.8 0.4 Breastca BT-549 . 1.2 Skeletal muscle (fetal) 1j00.0 100.0 Breast ca. MDA-N 4.4 7.5 skeletal muscle 0.3 0.3 Ovary 2.8 2.0 456 WO 03/093432 PCT/US03/13690 Bone marrow 1.2 1.1 Ovarian ca. OVCAR-3 0.7 13.3 Thymus 3.9 2.1 Ovarian ca. OVCAR-4 10.3 10.6 Spleen 0.9 2.3 Ovarian ca. OVCAR-5 4.1 3.9 I; i X h ii ........... ....................... .. ............... ....... ... , != ........... ......... .. 4 0 . 3 -3 ...... ...... Lymph node 1.5 1.1 Ovarian ca. OVCAR-8 14.0 3.3 Colorectal 4.8 5.0 Ovarian ca. IGROV-1 0.6 0.5 Stomach 4.7 9.0 Ovarian ca.* (ascites) SK-OV-3 1.6 0.3 Small intestine 5.8 6.9 Uterus 4.2 4.4 Colon ca. SW480 .7.7 7.0 Placenta 3.5 3.1 Colon ca.* SW620(SW480 met) 3.3 3.0 Prostate 4.7 5.1 Colon ca. HT29 0.6 2.5 Prostate ca.* (bone met)PC-3 . 29 Colon ca. HCT-116 2.7 4.0 Testis 1.8 2.8 Colon ca. CaCo-2 3.2 5.8 Melanoma Hs688(A).T 1.5. 2.6 Colon ca. tissue(ODO3866) 0.5 1.0 Melanoma* (met) Hs688(B).T 4.9 5.6 Colon ca. HCC-2998 2.4 3.4 Melanoma UACC-62 1.4 0.0 Gastric ca.* (liver met) NCI-N87 3.4 6.8 Melanoma M14 0.4 0.9 Bladder 1.8 3.4 MelanomaLOX IMVI 1.4.1.3 Trachea 1.4 8.9 Melanoma* (met) SK-MEL-5 .8 1.2 Kidney 2.8 6.6 jAdipose 0.0 0.6 Table PF. Panel 2D Column A - Rel. Exp.(%) Ag148, Run 147664547 Column B - Rel. Exp.(%) Ag148, Run 150018225 Column C - Rel. Exp.(%) Ag2Ol, Run 152827305 Tissue Name A B C Tissue Name A B C Normal Colon 40.1.59.9 51.8 Kidney Margin 8120608 123.8 25.2 28.9 CC Well to Mod Diff OCWellt od.D.16.2 11.6; 6.6 Kidney Cancer 8120613 7.0 25.9 25.3 (OD03866) CC Margin (ODO3866) 14.825.912.0 Kidney Margin 8120614 12.4 39.0 23.3 CC Gr.2 rectosigmoid CC Gr.2 rectosigmoid 2.3 6.4 4.3 Kidney Cancer 9010320 2.0 4.4 1.0 (ODO3868) 2.3 CC Margin (ODO3868) 14.3116.8 13.2 Kidney Margin 9010321 126.4 26.1 25.9 CC Mod Diff (ODO3920) 11.5 42.0 26.8 Normal Uterus 3.0 7.7 2.5 CC Margin (0D03920) 13.3 25.5 21.5 lUterus Cancer o0640 11 . 8.3 16.3 14.3 . ........ ... .................. .6 .... ...... .. ... / o l s CC Gr.2 ascend colon (ODO3921) 6.7 130.6 14.9 Nonal Thyroid 6. 0614.9 1NoraThod 68.3 100.0 55.9 (ODO3921) CC Margin (ODO3921) 7.6 17.4 15.0 Thyroid Cancer 064010 1.4 8.8 5.8 CC from Partial Hepatectomy (D4309) Mets 2.4 15.8 11.7 Thyroid Cancer A302152 6.0 7.4 2.5 (ODO4309) Mets Liver Margin (0DO4309) 0.3 2.0 3.1 Thyroid Margin A302153 15.2136.6 39.8 Colon mets to lung (OD04451 2.0 0.0 7.6 Normal Breast 8.3 23.7 26.2 01 ) Lung Margin (D04451-02) 1.0, 3.7 0. 1Breast Cancer (OD04566) 14.11 5.6 13.6 457 WO 03/093432 PCT/US03/13690 Breast Cancer (OD04590 Normal Prostate6546-1 20.344.1 21.8 17.2 13.6 23.7 0 1) Breast Cancer Mets Prostate Cancer (OD04410) 18.7k47.6 41.5 920.0 26.8 25.7 (ODO.4590-03) tar.in ( 9. 2.117 Breast Cancer Metastasis 7 Prostate Margin (ODO44 10) 9.8 25.2 17.7 18.91 7.7 7.6 (OD04655-05) Prostate Cancer (ODO4720-01)21.0 35.6 17.1 Breast Cancer 064006 8.1 14.7 20.9 Prostate Margin (OD04720-02) 10.4.23.0 14.3 Breast Cancer 1024 100.0100.0 59.5 Normal Lung 061010 9.6 27.2 14.1 Breast Cancer 9100266 8.7 1 7.9 17.2 Lung Met to Muscle ung Met t(ODO4286) M14.017.6 13.0 Breast Margin 9100265 4.3 16.0 7.1 426)__DO___________ Muscle. Margin (ODO4286) 9.5 21.2 37.1 Breast Cancer A209073 4.0 20.2 17.2 Lung Malignant Cancer 0.3 5.8 10.6 Breast Margin A209073 8.0 18.8 (OD03126) ... ......... Lung Margin (OD03126) 1.216.3 2.3 jNormal Liver 4.4 110.3 6.5 Lung Cancer (OD04404) 1.2 1.5 0.0 Liver Cancer 064003 3.9 1.6 0.0 Lung Margin (OD04404) 4.55.5 3.9 Liver Cancer 1025 5.1 10.6 6.7 Lung Cancer (OD04565) 1.6 3.0 0.9 Liver Cancer 1026 0.0 0.3 6.5 Lung Margin (OD04565) 1.9 2.9 1.1 Liver Cancer 6004-T 4.9 11.0 13.5 Lung Cancer (OD0423 7-01) 5.6 16.6 3.1 Liver Tissue 6004-N 24.5 26.4 29.3 ................................ Lung Margin (OD04237-02) 0.8 3.1 0.9 Liver Cancer 6005-T 2.9 3.1 1.9 Ocular Mel Met to Liver 8.20 Oca 1) M t8.0 7.1 7.8 Liver Tissue 6005-N 0.0 2.0 0.0 (ODO43 10) Liver Margin (ODO4310) 12.6 3.1 0.4 Normal Bladder 4 .7 19.1 14A Melanoma Mets to Lung 1 10.0D04321) 18.6 21.0 Bladder Cancer 1023 1.9 9.1 11.2 (ODO4321) Lung Margin (OD04321) 1 Bladder Cancer A302173 . Bladder Cancer Normal Kidney 29.31 75.3 100.0 Dd C .2.7 6.3 4.1 ........... I(OD04718-01) _ . Kidney Ca, Nuclear grade 2 27 70 1 Bladder Normal Adjacent .. 2.7 7.0 13.5 1.7 5.9 4.5 (OD04338) (OD04718-03) Kidney Margin (OD04338) 39.0 44.4 65.1 Normal Ovary 4.3 9.3 12.0 Kidney Ca Nuclear grade 1/2 6 90 vi cer 06400 (D04339)6.3 9.2 9.0 Ovarian Cancer 064008 4.3 12.2 14.5 .9 Ovarian Cancer Kidney Margin (OD04339) 1 429 11.0 11.2 1 3

.

2 (OD04768-07) Kidney Ca, Clear cell type Ovary Margin (OD04768 11.4 9.2: 5.7 1.1 3.6 0.8 (OD04340) 08) Kidney Margin (OD04340) 901 95.9 Normal Stomach 33.0163 15.2 [Kidney Ca, Nuclear grade 3 . [(OD04 Nuclear 33.7 4.3 3.8 Gastric Cancer 9060358 5.1 1.0 2.8 (ODO4348) Kidney Margin (OD04348) 25.563.7 58.6 Stomach Margin 9060359 2.5 5.8 6.3 Kidney Cancer (OD04622-01) 0.5 3.0.3 Gastric Cancer 9060395 7.8 11.9 Kidney Margin (OD04622-03) 19.2 21.0 9.7 Stomach Margin 9060394 3.4 7.3 458 WO 03/093432 PCT/US03/13690 Kidney Cancer (OD04450-01) 1.8 3.3 0.8 Gastric Cancer9060397 18.3 28.1 9.8 Kidney Margin (OD04450-03) 134.6146.71 53.2 Stomach Margin 9060396 1.5 3.0 4.1 Kidney Cancer 8120607 0.8 2.6 3.4 Gastric Cancer 064005 2.1 11.7 8.6 Table PG. Panel 4D Column A - Rel. Exp.(%) Ag148, Run 150048886 Column B - Rel. Exp.(%) Ag148, Run 152784557 Column C - Rel. Exp.(%) Ag201, Run 152827367 Column D - Rel. Exp.(%) Ag201, Run 157871331 Tissue Name A B C D Secondary Thl act 9.3 20.2 15.9 25.0 Secondary Th2 act 12.5 12.2 14.8 20.2 Secondary Trl act 16.7 11.4 19.8 25.2 Secondary Thl rest 8.9 3.5 0.0 1.3 Secondary Th2 rest 6.7 3.5 7.1 3.2 Secondary Trl rest 110.5 6.6 12.8 1.5 Primary Thl act 26.8 11.7 13.1 14.4 Primary Th2 act 17.2 5.6 24.1 6.8 Primary Trl act 32.8 7.6 22.7 7.0 Primary Thl rest 17.7 5.8 26.6 14.8 Primary Th2 rest 8.8 1.8 13.0 0.6 Primary Trl rest 22.8 5.6 1 7.1 1.1 CD45RA CD4 lymphocyte act 7.915.81 10.7 28.1 CD45RO CD4 lymphocyte act 15.5 24.3 22.8 24.7 CD8 lymphocyte act 22.5 9.1 19.8 10.7 Secondary CD8 lymphocyte rest 8.7 16.0 13.7 16.0 Secondary CD8 lymphocyte act 4.9 1.6 9.4 4.7 CD4 lymphocyte none 3.7 0.0 0.0 3.6 CD 4 ) +yn a p h o +e, U e n o n ................................................................................................................. ............ ,].+,.).7 ....... 0 :.....................0 ..... .... 3.6..... 2ry Thl/Th2/Trl anti-CD95 CH11 3.3 2.7 2.7 0.3 LAK cells rest 9.0 4.9 4.5 3.0 LAK cells IL-2 8.4 2.4 1.3 3.0 LAK cells IL-2+IL-12 10.0 6.3 5.1 6.5 LAK cells IL-2+IFN gamma 6.3 7.0 12.6 0.0 LAK cells IL-2+ IL- 8 11.3 10.3 9.4 4.4 LAK cells PMA/ionomycin 0.0 7.7 4 2 3.8 NK Cells IL-2 rest 2.0 2.1 3.0 6.9 Two Way MLR 3 day 12.4 17.3 5.5 15.0 Two Way MLR 5 day 2.0 7.6 3.0 5.3 Two Way MLR 7 day 1.8 1.5 3.7 10.6 PBMC rest 1.8 1.3 1.8 0.0 IPBMC PWM 32.3 12.6 22.7 13.8 PBMC PHA-L 8.2 1.6 1 6.7 2.5 459 WO 03/093432 PCT/US03/13690 Ramos (B cell) none 12.6 10.8 1K2 2.6 Ramos (B cell) ionomycin 59.0 13.7 47.0 21.3 B lymphocytes PWM 18.2 5.6 19.8 13.7 B lymphocytes CD40L and IL-4 11.5 6.2 10.2 1.5 EOL-1 dbcAMP 46.3 58.6 26.8 39.8 EOL- 1 dbcAMP PMA/ionomycin 5.6 14.7 16.7 21.3 Dendritic cells none 2.0 4.0 6.6 6.5 Dendritic cells LPS 0.0 5.4 1.0 0.0 Dendritic cells anti-CD40 1.5 7.1 2.2 6.4 Monocytes rest 0.0 0.0 1.1 0.0 Monocytes LPS 0.0 3.2 0.0 0.0 Macrophages rest 7.2 1.8 5.7 4.7 Macrophages LPS 0.0 4.5 2.3 0.0 HUVEC none 18.2 17.3 5.3 3.5 HUVEC starved 17.4 0.4 12.6 8.7 HUVEC IL-Ibeta 7.2 1.3 9.4 13.2 HUVEC IFN gamma 7.7 9.1 4.9 7.2 HUVEC TNF alpha + IFN gamma 5.3 2.8 5.8 2.4 HUVEC TNF alpha + IL4 15.0 14.2 11.3 12.6 HUVEC IL-11 5.6 7.1 4.0 1.8 Lung Microvascular EC none 16.0 11.3 24.0 15.5 Lung Microvascular EC TNFalpha + IL-lbeta 12.9 9.8 15.6 6.9 Microvascular Dermal EC none 7.0 5.8 6.1 7 Microsvasular Dermal EC TNFalpha + IL- beta 1.0 8.8 6.7 7.6 Bronchial epithelium TNFalpha + IL 1beta 10.3 0.2 0.0 1.8 Small airway epithelium none 4.6 3.8 0.0 3.3 Small airway epithelium TNFalpha + IL- 1 beta 8.1 4.2 5.3 0.3 Coronery artery SMC rest 0.0 1.1 4.4 2.2 Coronery artery SMC TNFalpha + IL- 1 beta 2.3 1.4 4.6 6.7 Astrocytes rest 7.6 7.3 7.0 11.0 Astrocytes TNFalpha + IL-Ibeta 4.0 13.2 0.8 7.3 KU-812 (Basophil) rest 68.8 63.7 54.7 60.7 KU-812 (Basophil) PMA/ionomycin 47.6 55.1 47.6 21.3 CCD1106 (Keratinocytes) none 16.2 11.3 22.8 17.7 CCD1106 (Keratinocytes) TNFalpha + IL- Ibeta 3.4 0.0 1.5 4.1 Liver cirrhosis 4.3 9.5 13.9 13.1 Lupus kidney 11.3 1.6 3.1 10.4 NCI-H292 none 43.8 16.0 36.6 5.6 NCI-H292 IL-4 95.3 28.5 70.7 39.5 NCI-H292 IL-9 95.9 23.2 65.1 50.7 NCI-H292 IL-13 1.8 100.0 100.0 INCI-H292 IFTN gamma 52. 39.0 95.3 460 WO 03/093432 PCT/US03/13690 HPAEC none . .... 9.5 8.9 7.6 15.1 HPAEC TNF alpha + IL-1 beta 12.0 12.9 5.0 11.1 Lung fibroblast none 40 8.9 7.3 9.1 Lung fibroblast TNF alpha + IL-1 beta 1.7 1.0 3.3 1.4 Lung fibroblast IL-4 4 .0 5.

2 4

.

7 6.7 Lung fibroblast IL-9 12.6 7.9 3.6 6.1 Lung fibroblast IL-13 4.3 5.3 3.2 6.0 Lung fibroblast I

F

N gamma .8.2 4.0 1.1 1.8 Dermal fibroblast CCD 1070 rest 25.0 7.5 21.8 14.3 Dermal fibroblast CCD1070 TNF alpha 44.4 2.5 19.6 9.3 Dermal fibroblast CCD1070 IL-1 beta 5.8 20.6 11.2 6.2 Dermal fibroblast IFN gamma 11.3 10.2 1.3 8.9 Dermal fibroblast IL-4 5.7 6.7 8.7 18.3 IBD Colitis 2 0.0 1.3 1.3 1.7 IBD Crolhn's 1.9 0.0 0.0 5.5 Colon 40.6 26.2 42.3 52.5 Lung 9.0 9.1 27.7 16.7 Thymus 100.0 55.9 100.0 57.4 Kidney .9. 8.7 6.7 14.4 CNS_neurodegeneration_vl.0 Summary: Ag148/Ag201 This gene was down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene, expressed protein, and/or treatment with specific agonists targeting encoded protein is useful in reversing the dementia/memory loss associated with this disease and neuronal death. Panel 1 Summary: Ag148 Highest expression of this gene was detected in cerebellum (CT=24.5) and this gene was expressed at high 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 and/or expressed protein is useful in the diagnosis and treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Moderate gene expression levels was also seen in pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, melanoma and brain cancer cell lines. Thus, expression level of this gene is a useful marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene is an effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, melanoma and brain cancers. Among tissues with metabolic or endocrine function, this gene was expressed at moderate to low levels in pancreas, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of 461 WO 03/093432 PCT/USO3/13690 this gene is useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Panel 1.3D Summary: Agl48/Ag201 Highest expression of this gene was seen in fetal skeletal muscle (CTs=30). Expression of this gene was higher in fetal compared adult skeletal muscle (CTs=38). The relative overexpression of this gene in fetal skeletal muscle indicates that the protein product enhances muscular growth or development and has regenerative capacity in the adult. Therefore, therapeutic modulation of this gene, expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in treatment of muscle related diseases. More specifically, treatment of weak or dystrophic muscle with the protein encoded by this gene restores muscle mass or function. Moderate expression of this gene was seen in all the regions of the brain examined including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Modulation of this gene, the expressed protein and/or use of antibodies or small molecule drugs targeting the gene or gene product are useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Panel 2D Summary: Ag148/Ag201 Highest expression of this gene was seen in breast cancer and normal kidney samples (CTs=30-31). Moderate to low expression of this gene was also seen in normal and cancer samples from stomach, ovary, liver, breast, kidney, metastatic melanoma, lung, prostate and colon. Expression of this gene is consistently higher in normal kidney compared to the corresponding cancer samples. This gene codes for fibronectin leucine repeat transmembrane protein 1 (FLRT1) acts as a matrix adhesion molecule or cell-cell adhesion molecule. This gene or encoded FLRT1 protein inhibits the growth of kidney cancer cells. Panel 4D Summary: Ag148/Ag201 Highest expression of this gene was detected in ILl3 activated NCI-NCI-H292 cells and thymus (CTs=31). This gene showed low wide spread expression in this panel with higher expression in resting and activated mucoepidermoid NCI-NCI-H292 cells, activated dermal fibroblasts, resting and activated basophils, eosinophils, PBMC cells, activated B lymphocytes and normal colon. Therefore, modulation of the gene and/or encoded protein alters functions associated with these cell types and leads to improvement of the symptoms of patients suffering from autoimnimune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis. 462 WO 03/093432 PCT/US03/13690 Q. CG96778-01: Human medium-chain acyl-CoA dehydrogenase. Expression of gene CG96778-01 was assessed using the primer-probe set Ag4326, described in Table QA. Results of the RTQ-PCR runs are shown in Table QB. Table QA. Probe Name Ag4326 Primers Sequences Length Start SEQ ID Position No Forward 5' -catatgggtgattttgtgcttt-3' 22 ] 138 445 .TT- c cttcatttttctgtgtttaaaatgttca-3'- 3 6 4 Prob 30 161 446 Reverse S'-ttcatgtctcctttgttccaat-3' 2 200 447 Table QB. Generalscreening_panel_ v1.4 Column A - Rel. Exp.(%) Ag4326, Run 222377145 Tissue Name A Tissue Name A Adipose 0.0 Renal ca. TK-10 20.7 Melanoma* Hs688(A).T 2.2 Bladder 6.0 Melanoma* Hs688(B).T 5.3 Gastric ca. (liver met.) NCI-N87 100.0 Melanoma* M14 26.8 Gastric ca. KATO III 0.0 Melanoma* LOXIMVI 27.0 Colon ca. SW-948 8.8 Melanoma* SK-MEL-5 16.2 Colon ca. SW480 45.4 Squamous cell carcinoma SCC-4 41.8 Colon ca.* (SW480 met) SW620 39.5 Testis Pool 21.6 Colon ca. HT29 17.0 Prostate ca.* (bone met) PC-3 4.5 Colon ca. HCT-116 304 Prostate Pool 2.0 Colon ca. CaCo-2 7.1 Placenta 3.4 Colon cancer tissue 0.0 Uterus Pool 0.0 Colon ca. SW1 116 2.2 Ovarian ca. OVCAR-3 44.8 Colon ca. Colo-205 3.4 Ovarian ca. SK-OV-3 8.4 Colon ca. SW-48 13.3 Ovarian ca. OVCAR-4 11.6 Colon Pool 0.0 Ovarian ca. OVCAR-5 33.0 Small Intestine Pool 2.7 Ovarian ca. IGROV-1 13.0 Stomach Pool 0.0 Ovarian ca. OVCAR-8 5.8 Bone Marrow Pool0.0 Ovary 4.7 Fetal Heart 0.0 Breast ca. MCF-7 8.7 Heart Pool 0.0 Breast ca. MDA-MB-231 64.6 Lymph Node Pool 0.0 Breast ca. BT 549 22.5 Fetal Skeletal Muscle 0.0 Breast ca. T47D 86.5 Skeletal Muscle Pool 3.8 Breast ca. MDA-N 4.4 Spleen Pool 5.9 Breast Pool 0.0 Thymus Pool 6.2 Trachea 4.6 CNS cancer (gliolastro) U87-MG 18.3 463 WO 03/093432 PCT/US03/13690 Lung 0.0 CNS cancer (glio/astro) U-118-MG 71.7 Fetal Lung 0.0 CNS cancer (neuro;met) SK-N-AS 24.8 Lung ca. NCI-N417 2.5 CNS cancer (astro) SF-539 12.8 Lung ca. LX-1 47.6 CNS cancer (astro) SNB-75 50.0 ILung ca. NCI-Hi 46 13.8 CNS cancer (glio) SNB-19 16.6 Lung ca. SHP-77 11.1 CNS cancer (glio) SF-295 10.4 Lung ca. A549 6.2 Brain (Amygdala) Pool 4.2 Lung ca. NCI-H526 3.1 Brain (cerebellum) 21.6 Lung ca. NCI-H23 37.1 Brain (fetal) 6.1 Lung ca. NCI-H460 4.7 Brain (Hippocampus) Pool 15.3 Lung ca. HOP-62 5.8 Cerebral Cortex Pool 9.4 Lung ca. NCI-H522 40.9 Brain (Substantia nigra) Pool 6.6 Liver 0.0 Brain (Thalamus) Pool 9.5 Fetal Liver 4.5 Brain (whole) 3.3 Liver ca. HepG2 25.2 Spinal Cord Pool 7.7 Kidney Pool 5.0 Adrenal Gland 13.6 Fetal Kidney 4.1 Pituitary gland Pool 10.7 Renal ca. 786-0 32.3 Salivary Gland 0.0 Renal ca. A498 7.7 Thyroid (female) 2.2 Renal ca. ACHN 0.0 Pancreatic ca. CAPAN2 34.9 Renal ca. UO-31 13.6 Pancreas Pool 5.3 General screeningpanel_v1.4 Summary: Ag4326 Highest expression of this gene was mainly seen in NCI-N87 gastric cancer cell line (CT=34.1). Low expression of this gene was also seen in brain and breast cancer cell lines. Therefore, expression level of this gene is a usedful marker to detect the presence of gastric, brain and breast cancers. In addition, therapeutic modulation of this gene and/or encoded protein is useful in the treatment of these cancers. R. CG96778-02: Medium-chain acyl-CoA dehydrogenase. Expression of gene CG96778-02 was assessed using the primer-probe set Ag6978, described in Table RA. Results of the RTQ-PCR runs are shown in Table RB. This sequence represents a physical full length clone. Table RA. Probe Name Ag6978 i I Start SEQ ID Primers Sequences Length PoStn SEQ ID rimerj _Position No Forward 5'-acttggtttaatgaacacicacatt-3' 25 249 448 Probe ET-

S

'-ccagagaactgtgactacagtgtttgccc-3 1- 29 274 449 464 WO 03/093432 PCT/US03/13690 Reverse 5'-gtatagagtgcaagcttccaaaagt-3' 25 303 450 Table RB. Generalscreening_panelvl.6 Column A - Rel. Exp.(%) Ag6978, Run 279065832 Tissue Name IA Tissue Name A Adipose 0.0 Renal ca. TK-10 0.0 Melanoma* Hs688(A).T 0.0 Bladder 0.0 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 0.1 Squamous cell carcinoma SCC-4 0.0 Colon ca.* (SW480 met) SW620 0.6 Testis Pool 0.61 Colon ca. HT29 0.0 Prostate ca.* (bone met) PC-3 0.0 Colon ca. HCT-116 0.0 Prostate Pool 0.0 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 0.0 Colon ca. SW-48 0. Ovarian ca. OVCAR-4 0.0 Colon Pool 0.0 Ovarian ca. OVCAR-5 0.0 Small Intestine Pool 0.0 Ovarian ca. IGROV-1 0.0 Stomach Pool 0.0 Ovarian ca. OVCAR-8 f0.0 Bone Marrow Pool 0.0 Ovary 0.0 Fetal Heart 4.2 Breast ca. MCF-7 0.0 IHeart Pool 5.6 Breast ca. MDA-MB-231 0.6 Lymph Node Pool 0.6 Breast ca. BT 549 0.0 Fetal Skeletal Muscle 3.0 Breast ca. T47D 0.0 Skeletal Muscle Pool 0.0 Breast ca. MDA-N 0.0 Spleen Pool0.0 Breast Pool 0.4 Thymus Pool 0.0 Trachea 0.0 CNS cancer (glio/astro) U87-MG 0.0 Lung 0.5 CNS cancer (glio/astro) U-118-MG 0.0 Fetal Lung 0.0 ICNS cancer (neuro;met) SK-N-AS 0.6 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 0.7 CNS cancer (glio) SNB-19 0.0 ung ca. SHP-77 0.8 CNS cancer (glio) SF-295 0.0 Lung ca. A549 .0.0 Brain (Amygdala) Pool 4.5 Lung ca. NCI-H526 0.0 Brain (cerebellum) 100.0 Lung ca. NCI-H23 10.2 Brain (fetal) 12.2 Lung ca. NCI-H460 0.0 Brain (Hippocampus) Pool ]3.8 465 WO 03/093432 PCT/US03/13690 Lung ca. HOP-62 0.0 Cerebral Cortex Pool 5.7 Lung ca. NCI-H522 0.0 Brain (Substantia nigra) Pool 8.8 Liver 0.0 Brain (Thalamus) Pool 9.3 Fetal Liver 0.0 Brain (whole) .11.9 Liver ca. HepG2 A0.4 Spinal Cord Pool 3.0 Kidney Pool 0.4 Adrenal Gland 0.0 Fetal Kidney 0.5 Pituitary gland Pool 0.0 Renal ca. 786-0 0.0 Salivary Gland 0.0 R ena -ca~ a9-g............................................................... i 0-: "]T h roa ~ ale.......................) ...... Renal ca. A498 0.0 Thyroid (female) 0.4 Renal ca. ACHN 0.0 Pancreatic ca.CAPAN2 0.0 Renal ca. UO-31 0.5 Pancreas Pool 0.0 Generalscreeningpanel_v1.6 Summary: Ag6978 Highest expression of this gene was seen in cerebellum (CT=29.6). Moderate to low expression of this gene was seen in all the regions of central nervous system examined including: amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene and/or expressed protein is useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Low expression of this gene was also seen in fetal and adult heart. Therefore, modulation of this gene and/or encoded protein will be useful in the treatment of heart related diseases. Example D: Expression Data Example D1: Expression of CG50949-07 in stable CHO-K1 cells A 2548 bp long BamHI-XhoI fragment containing the CG52643-05 sequence was subcloned into BamHI-XhoI digested pEEl14.4/Sec to generate plasmid 2134. The resulting plasmid 2134 was transfected into CHO-K1 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Invitrogen/Gibco Stable clones were selected based on resistance against methionine sulfoximine. The expression and secretion levels of the selected clones were assessed by Western blot analysis using HRP conjugated V5 antibody. (The V5 epitope is fused to the gene of interest at the Cter, in the pEE14.4Sec vector.) The CG50949-07 protein is secreted as a 55 kDa protein. Example D2: Expression of CG52643-05 using Baculovirus expression system. A 2.5 kb BamHI-EcoRI fragment containing the CG52643-05 sequence was subcloned into BamHI-EcoRI digested pBlueBac4.5/V5-His (CuraGen Corporation) insect 466 WO 03/093432 PCT/USO3/13690 expression vector to generate plasmid 2599. Following standard procedures (Invitrogen pBlueBac protocol), recombinant baculovirus was generated and plaque-purified. Fresh Sf9 cells in adherent culture were infected with the recombinant baculovirus. The culture media were harvested 5 days post-infection and assayed for CG52643-05 protein expression by Western blot under reducing conditions using an anti-V5 antibody. CG52643-05 is expressed as 111 kDa protein. Example D3: Expression of CG51051-06 in human embryonic kidney 293 cells. A 1.29 kb BamHI-XhoI fragment containing the CG51051-06 sequence was subcloned into BamHI-XhoI digested pCEP4/Sec vector to generate plasmid 209. The resulting plasmid 209 was transfected into 293 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Gibco/BRL). The cell pellet and supernatant were harvested 72h post transfection and examined for CG51051-06 expression by Western blot (reducing conditions) using an anti-V5 antibody. CG51051-06 is expressed as a 60 kDa protein secreted by 293 cells. Example D4: Epithelial Cell survival assay (PE51al) Netrins are a family of guidance molecules that act to both attract and repel the growing axons of a broad range of neuronal cell types during development and are also involved in controling neuronal cell migration. Netrin signaling occurs through specific receptor complexes containing either the colorectal cancer (DCC) or neogenin protein (attractive receptor), or the UNC-5-related proteins (repellent receptor). Netrin-DCC signaling has also been shown to regulate cell death in epithelial cells in vitro, raising the interesting possibility that netrins may also regulate cell death in the developing nervous system (Livesey et al., Cell. Mol. Life Sci. 1999 Oct 1;56(1-2):62-8). CG51051-06 is related to the netrin family of neuronal guidance molecules related to neuronal spreading, migration, development and survival. CG51051-06 may act as a chemotrophic/survival potentiating factor in neuronal repair or regeneration. BrdU Incorporation. Proliferative activity is measured by treatment of serum-starved cultured cells with a given agent and measurement of BRDU incorporation during DNA synthesis. 789-0 and 769-P kidney epithelial cells were cultured in DMEM supplemented with 10% fetal bovine serum or 10% calf serum respectively. Cells were grown to confluence at 37 0 C in 10% C0 2 /air. Cells were then starved in DMEM for 24- 72 h. pCEP4sec or pCEP4sec/CG51051-06 enriched conditioned medium was added (10 pL/100 467 WO 03/093432 PCT/USO3/13690 jtL of culture ) for 18 h. BrdU (10 tM final concentration) was then added and incubated with the cells for 5 h. BrdU incorporation was assayed according to the manufacturer's specifications (Boehringer Mannheim, Indianapolis, IN). CG51051-06 has shown BrdU incorporation activity on 786-0 and 769-P kidney epithelial cells. As shown in Figure 1, CG51051-06 promotes growth and survival of epithelial cells demonstrating that the molecule is functional and may act as a chemotrophic/survival potentiating factor in neuronal repair or regeneration. Example D5: Expression of CG51051-07 in human embryonic kidney 293 cells. A 1.5 kb fragment containing the CG51051-07 sequence was subcloned into pCEP4 Sec-GATEWAY vector to generate plasmid 1729. The resulting plasmid 1729 was transfected into 293 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Gibco/BRL). The cell pellet and supernatant were harvested 72h post transfection and examined for CG51051-07 expression by Western blot (reducing conditions) using an anti-V5 antibody. CG51051-07 is expressed as a 67 kDa protein secreted by 293 cells. Example D6: Expression of CG52643-05 in stable CHO-K1 cells A 2548 bp long BamHI-EcoRI fragment containing the CG52643-05 sequence was subcloned into BamHI-EcoRI digested pEE14.4FL2_MSA to generate plasmid 2809. The resulting plasmid 2809 was transfected into CHO-K1 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Invitrogen/Gibco Stable clones were selected based on resistance against methionine sulfoximine. The expression and secretion levels of the selected clones were assessed by Western blot analysis using HRP conjugated V5 antibody. (The V5 epitope is fused to the gene of interest at the Cter, in the pEE14.4Sec vector.) The CG52643-05 protein is secreted as a 178.4 kDa protein. Example D7: Expression of CG52643-05 using Baculovirus expression system. A 2.5 kb BamHI-EcoRI fragment containing the CG52643-05 sequence was subcloned into BamnHI-EcoRI digested pBlueBac4.5/V5-His (CuraGen Corporation) insect expression vector to generate plasmid 2599. Following standard procedures (Invitrogen pBlueBac protocol), recombinant baculovirus was generated and plaque-purified. Fresh Sf9 cells in adherent culture were infected with the recombinant baculovirus. The culture media were harvested 5 days post-infection and assayed for CG52643-05 protein expression by 468 WO 03/093432 PCT/US03/13690 Western blot under reducing conditions using an anti-V5 antibody. CG52643-05 is expressed as 111 kDa protein. OTHER EMBODIMENTS Although particular embodiments are disclosed herein in detail, this is 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 will 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. 469

Claims (5)

1. An isolated polypeptide comprising the mature form of an amino acid sequenced selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between I and 174.

2. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174.

3. An isolated polypeptide comprising an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174.

4. An isolated polypeptide, wherein the polypeptide comprises an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and

174. 5. The polypeptide of claim 1 wherein said polypeptide is naturally occurring. 6. A composition comprising the polypeptide of claim I and a carrier. 7. A kit comprising, in one or more containers, the composition of claim 6. 8. The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a pathology associated with the polypeptide of claim 1, wherein the therapeutic comprises the polypeptide of claim 1. 9. A method for determining the presence or amount of the polypeptide of claim 1 in a sample, the method comprising: (a) providing said sample; 470 WO 03/093432 PCT/US03/13690 (b) introducing said sample to an antibody that binds immunospecitically to the polypeptide; and (c) determining the presence or amount of antibody bound to said polypeptide, thereby determining the presence or amount of polypeptide in said sample. 10. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the polypeptide of claim 1 in a first mammalian subject, the method comprising: a) measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and b) comparing the expression of said polypeptide in the sample of step (a) to the expression of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, said disease, wherein an alteration in the level of expression of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease. 11. A method of identifying an agent that binds to the polypeptide of claim 1, the method comprising: (a) introducing said polypeptide to said agent; and (b) determining whether said agent binds to said polypeptide. 12. The method of claim 11 wherein the agent is a cellular receptor or a downstream effector. 13. 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 the polypeptide of claim 1, the method comprising: (a) providing a cell expressing the polypeptide of claim 1 and having a property or function ascribable to the polypeptide; (b) contacting the cell with a composition comprising a candidate substance; and (c) determining whether the substance alters the property or function ascribable to the polypeptide; 471 WO 03/093432 PCT/USO3/13690 whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition in the absence of the substance, the substance is identified as a potential therapeutic agent. 14. A method for screening for a modulator of activity of or of latency or predisposition to a pathology associated with the polypeptide of claim 1, said method comprising: (a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses the polypeptide of claim 1; (b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and (c) comparing the activity of said polypeptide in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator activity of or latency or predisposition to, a pathology associated with the polypeptide of claim 1. 15. The method of claim 14, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene. 16. A method for modulating the activity of the polypeptide of claim 1, the method comprising contacting a cell sample expressing the polypeptide of claim 1 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide. 17. A method of treating or preventing a pathology associated with the polypeptide of claim 1, the method comprising administering the polypeptide of claim 1 to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject. 472 WO 03/093432 PCT/USO3/13690 18. The method of claim 17, wherein the subject is a human. 19. A method of treating a pathological state in a mammal, the method comprising administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to 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 174 or a biologically active fragment thereof. 20. An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174. 21. The nucleic acid molecule of claim 20, wherein the nucleic acid molecule is naturally occurring. 22. A nucleic acid molecule, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 174. 23. An isolated nucleic acid molecule encoding the mature form of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 174. 24. An isolated nucleic acid molecule comprising a nucleic acid selected from the group consisting of 2n-1, wherein n is an integer between 1 and 174. 25. The nucleic acid molecule of claim 20, wherein said 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 174, or a complement of said nucleotide sequence. 26. A vector comprising the nucleic acid molecule of claim 20. 473 WO 03/093432 PCT/US03/13690 27. The vector of claim 26, further comprising a promoter operably linked to said nucleic acid molecule. 28. A cell comprising the vector of claim 26. 29. An antibody that immunospecifically binds to the polypeptide of claim 1. 30. The antibody of claim 29, wherein the antibody is a monoclonal antibody. 31. The antibody of claim 29, wherein the antibody is a humanized antibody. 32. A method for determining the presence or amount of the nucleic acid molecule of claim 20 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to a probe that binds to said nucleic acid molecule; and (c) determining the presence or amount of said probe bound to said nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in said sample. 33. The method of claim 32 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type. 34. The method of claim 33 wherein the cell or tissue type is cancerous. 35. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the nucleic acid molecule of claim 20 in a first mammalian subject, the method comprising: a) measuring the level of expression of the nucleic acid in a sample from the first mammalian subject; and b) comparing the level of expression of said nucleic acid in the sample of step (a) to the level of expression of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; 474 WO 03/093432 PCT/USO3/13690 wherein an alteration in the level of expression of the nucleic acid in the tirst subject as compared to the control sample indicates the presence of or predisposition to the disease. 36. A method of producing the polypeptide of claim 1, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174. 37. The method of claim 36 wherein the cell is a bacterial cell. 38. The method of claim 36 wherein the cell is an insect cell. 39. The method of claim 36 wherein the cell is a yeast cell. 40. The method of claim 36 wherein the cell is a mammalian cell. 41. A method of producing the polypeptide of claim 2, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 174. 42. The method of claim 41 wherein the cell is a bacterial cell. 43. The method of claim 41 wherein the cell is an insect cell. 44. The method of claim 41 wherein the cell is a yeast cell. 45. The method of claim 41 wherein the cell is a mammalian cell. 475