Patent Publication Number: US-2003224982-A1

Title: Therapeutic polypeptides, nucleic acids encoding same, and methods of use

Description:
RELATED APPLICATIONS  
     [0001] This application claims priority to provisional patent applications U.S. S. No. 60/303,046, filed Jul. 5, 2001; U.S. S. No. 60/303,828, filed Jul. 9, 2001; U.S. S. No. 60/304,502, filed Jul. 11, 2001; U.S. S. No. 60/305,011, filed Jul. 12, 2001; U.S. S. No. 60/305,262, filed Jul. 13, 2001; U.S. S. No. 60/305,673, filed Jul. 16, 2001; U.S. S. No. 60/306,085, filed Jul. 17, 2001; U.S. S. No. 60/307,536, filed Jul. 24, 2002; U.S. S. No. 60/308,228, filed Jul. 27, 2001; U.S. S. No. 60/308,877, filed Jul. 30, 2001; U.S. S. No. 60/312,203, filed Aug. 14, 2001; U.S. S. No. 60/322,640, filed Sep. 17, 2001; U.S. S. No. 60/323,484, filed Sep. 19, 2001; U.S. S. No. 60/323,821, filed Sep. 21, 2001; U.S. S. No. 60/323,948, filed Sep. 21, 2001; U.S. S. No. 60/324,711, filed Sep. 25, 2001; U.S. S. No. 60/327,893, filed Oct. 9, 2001; U.S. S. No. 60/331,768, filed Nov. 21, 2001; U.S. S. No. 60/359,191, filed Feb. 21, 2002; U.S. S. No. 60/358,939, filed Feb. 22, 2002; U.S. S. No. 60/360,923, filed Feb. 28, 2002; U.S. S. No. 60/360,830, filed Mar. 1, 2002; U.S. S. No. 60/361,178, filed Mar. 1, 2002; U.S. S. No. 60/361,748, filed Mar. 5, 2002; U.S. S. No. 60/363,429, filed Mar. 12, 2002; U.S. S. No. 60/363,683, filed Mar. 12, 2002; U.S. S. No. 60/372,141, filed Apr. 12, 2002; U.S. S. No. 60/372,967, filed Apr. 16, 2002; U.S. S. No. 60/373,051, filed Apr. 16, 2002; U.S. S. No. 60/373,063, filed Apr. 16, 2002; U.S. S. No. 60/373,280, filed Apr. 17, 2002; U.S. S. No. 60/373,287, filed Apr. 17, 2002; U.S. S. No. 60/373,881, filed Apr. 19, 2002; each of which is incorporated herein by reference in its entirety. 
    
    
     
       FIELD OF THE INVENTION  
       [0002] The present invention relates to novel polypeptides, and the nucleic acids encoding them, having properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.  
       BACKGROUND OF THE INVENTION  
       [0003] Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways involve extracellular signaling proteins, cellular receptors that bind the signaling proteins, and signal transducing components located within the cells.  
       [0004] Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding, biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect.  
       [0005] Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.  
       [0006] Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or LIp-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.  
       [0007] 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 cognatc 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.  
       [0008] 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  
       [0009] 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 61. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid or polypeptide sequences.  
       [0010] 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 1 and 61, 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. 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 61. 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 61 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 61, 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.  
       [0011] 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 61. 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 61. The variant polypeptide where any amino acid changed in the chosen sequence is changed to provide a conservative sobstitution.  
       [0012] 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 61 and a pharmaceutically acceptable carrier. In another embodiment, the invention involves a kit, including, in one or more containers, this pharmaceutical composition.  
       [0013] 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 61 wherein said therapeutic is the polypeptide selected from this group.  
       [0014] 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 61 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 bound to the polypeptide, thereby determining the presence or amount of polypeptide in the sample.  
       [0015] 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 61 in a first mammalian subject, the method involving measuring the level of expression of the 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.  
       [0016] 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 61, 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.  
       [0017] 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 61, 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.  
       [0018] 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 61, 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 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 be the native gene promoter of the transgene.  
       [0019] 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 61, 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.  
       [0020] 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 61, 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.  
       [0021] 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 61 or a biologically active fragment thereof.  
       [0022] 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 61; 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 61 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 from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 61; 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 61, 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 61 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.  
       [0023] 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 61, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant.  
       [0024] 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 61 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.  
       [0025] 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 61, 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 61.  
       [0026] 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 61, 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 61; 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 61 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 61; 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 61 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.  
       [0027] 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 61, 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 61, or a complement of the nucleotide sequence.  
       [0028] 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 61, 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.  
       [0029] 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 1 and 61. This vector can have a promoter operably linked to the nucleic acid molecule. This vector can be located within a cell.  
       [0030] 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 amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 61 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.  
       [0031] 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 61 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.  
       [0032] 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 1×10 −9  M. More preferably, the NOVX antibody neutralizes the activity of the NOVX polypeptide.  
       [0033] 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.  
       [0034] 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.  
       [0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting.  
       [0036] Other features and advantages of the invention will be apparent from the following detailed description and claims.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0037] 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 polyiucleotides” 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   SEQ                   ID   ID       NOVX       NO   NO       Assign-   Internal   (nucleic)   (amino       ment   Identification   acid)   acid)   Homology                                          1a   CG103191-02   1   2   chromogranin A-like        1b   CG103191-03   3   4   chromogranin A-like        1c   CG103191-04   5   6   chromogranin A-like        1d   251425133   7   8   chromogranin A-like        1c   251425611   9   10   chromogranin A-like        1f   278460276   11   12   chromogranin A-like        1g   278456175   13   14   chromogranin A-like        2a   CG105757-01   15   16   Kelch and BTB/POZ                       containing membrane                       protein like        3a   CG108175-01   17   18   neurexin III-alpha                       membrane-bound type 1                       precursor like        3b   CG108175-02   19   20   neurexin III-alpha                       membrane-bound type 1                       precursor like        3c   CG108175-03   21   22   neurexin III-alpha                       membrane-bound type 1                       precursor like        3d   CG108175-04   23   24   neurexin III-alpha                       membrane-bound type 1                       precursor like        3e   CG108175-05   25   26   neurexin III-alpha                       membrane-bound type 1                       precursor like        4a   CG108624-01   27   28   protocadherin 68-like        5a   CG108771-01   29   30   Type 1b membrane                       protein like        6a   CG108782-01   31   32   Transmembrane like        6b   CG108782-02   33   34   Transmnembrane like        7a   CG108801-01   35   36   EGF-domain                       Transmembrane Protein                       like        7b   CG108801-02   37   38   EGF-domain                       Transmembrane Protein                       like        8a   CG109717-01   39   40   Single Pass                       Transmembrane-Like        9a   CG110477-01   41   42   Desmoglein 3 variant                       like       10a   CG110540-01   43   44   Pheromone Receptor like       10b   CG110578-02   45   46   Neuralin 2 like       11a   CG110725-01   47   48   Osteopotin like       11b   209934449   119   120   osteopontin-like       12a   CG111683-01   49   50   surfactant protein-C like       12b   CG111683-02   51   52   surfactant protein-C like       12c   CG111683-03   53   54   surfactant protein-C like       13a   CG112655-01   55   56   germ cell-less 1                       protein like       14a   CG112813-01   57   58   NK receptor-like       14b   CG112813-02   S9   60   NK receptor-like       14c   CG112813-04   61   62   NK receptor-like       14d   CG112813-01   63   64   NK receptor-like       14e   CG112813-06   6S   66   NK receptor-like       14f   209886463   67   68   NK receptor-like       14g   277731421   69   70   NK receptor-like       15a   CG112869-01   71   72   Pecanex like       16a   CG113377-01   73   74   G1-related zinc finger                       protein like       17a   CG113730-01   75   76   nodal precursor like       17b   210982580   77   78   nodal precursor like       17c   CG113794-02   79   80   PA domain containing                       protein like       18a   CG115187-01   81   82   transmembrane protein                       like       18b   CG115187-02   83   84   transmembrane protein                       like       18c   CG115187-03   85   86   transmembrane protein                       like       18d   262770580   87   88   transmembrane protein                       like       18e   257788219   121   122   transmembrane-protein                       like       19a   CG115540-01   89   90   Membrane Protein                       containing Collagen                       triple helix repeat like       20a   CG118689-01   91   92   Uroplakin 1b-like       20b   CG118689-02   93   94   Uroplakin 1b-like       21a   CG120748-01   95   96   LMBR1 Long Form like       22a   CG121519-01   97   98   LDL Receptor Domain                       Containing Protein       23a   CG122176-01   99   100   Fibronectin domain                       containing protein like       24a   CG122691-01   101   102   Fn3/TSPN/Collagen/                       vWF domain cotaining                       protein like       25a   CG122863-01   103   104   Membrane Protein like       25b   CG122863-02   105   106   neurotrirnin like       26a   CG50880-04   107   108   Estrogen regulated                       protein like       27a   CG51812-03   109   110   protocadherin like       28a   CG51923-01   111   112   protocadherin like       28b   CG51923-03   113   114   Protocadherin FAT-like       28c   207756525   115   116   protocadherin like       28d   207756686   117   118   protocadherin like                  
 
       [0038] 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.  
       [0039] Pathologies, diseases, disorders and condition and the like that arc associated with NOVX sequences include, but are not limited to: e.g., cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, metabolic disturbances associated with obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, cellular regeneration, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn&#39;s disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders including autoimmune disorders, hematopoietic disorders, and the various dyslipidemias, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation and fertility.  
       [0040] 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.  
       [0041] 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.  
       [0042] 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.  
       [0043] 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, eg. detection of a variety of cancers.  
       [0044] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.  
       [0045] NOVX Clones  
       [0046] 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.  
       [0047] The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, eg., 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.  
       [0048] 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.  
       [0049] 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 61; (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 61, 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 61; (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 61 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).  
       [0050] In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 61; (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 61 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 61; (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 61, 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 61 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.  
       [0051] 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 61; (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 61 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 61; 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 61 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.  
       [0052] NOVX Nucleic Acids and Polypeptides  
       [0053] One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e g., NOVX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.  
       [0054] 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 methioninie residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.  
       [0055] The term “probe”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 100 nt, or as many as approximately, e.g, 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single-stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.  
       [0056] 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.  
       [0057] A nucleic acid molecule of the invention, eg., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, 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 61, as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), M OLECULAR  C LONING : A L ABORATORY  M ANUAL  2 nd  Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; and Ausubel, et al., (eds.), C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, New York, N.Y., 1993.)  
       [0058] 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.  
       [0059] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.  
       [0060] 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 61, 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 61, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, 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 61, thereby forming a stable duplex.  
       [0061] 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.  
       [0062] 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.  
       [0063] 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-flame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 5′ direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 3′ direction of the disclosed sequence.  
       [0064] 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, eg. 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.  
       [0065] Derivatives and analogs may be full length or other than full length. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, New York, N.Y., 1993, and below.  
       [0066] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences include those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for a NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.  
       [0067] A NOVX polypeptide is encoded by the open reading frame (“ORF”) of a NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bona fide cellular protein, a minimum size requirement is often set, eg., a stretch of DNA that would encode a protein of 50 amino acids or more.  
       [0068] 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 61; or an anti-sense strand nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61; or of a naturally occurring mutant of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61.  
       [0069] 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.  
       [0070] “A polypeptide having a biologically-active portion of a NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, 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.  
       [0071] NOVX Nucleic Acid and Polypeptide Variants  
       [0072] 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 61, due to degeneracy of the genetic code and thus encode the same  
       [0073] NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61.  
       [0074] 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 61.  
       [0075] In addition to the human NOVX nucleotide sequences of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding a NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.  
       [0076] 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 a? is an integer between 1 and 61, 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.  
       [0077] 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 61. 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.  
       [0078] 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.  
       [0079] As used herein, the phrase astringent 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 il different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH 1. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60° C. for longer probes, primers and oligonucleotides.  
       [0080] Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.  
       [0081] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6×SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2×SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, 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).  
       [0082] 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 61, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5×Reinhardt&#39;s solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, NY, and Krieger, 1990; G ENE  T RANSFER AND  E XPRESSION , A L ABORATORY  M ANUAL , Stockton Press, NY.  
       [0083] 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 61, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, NY, and Kriegler, 1990, G ENE    TRANSFER AND  E XPRESSION , A L ABORATORY  M ANUAL , Stockton Press, NY; Shilo and Weinberg, 1981.  Proc Natl Acad Sci USA  78: 6789-6792.  
       [0084] Conservative Mutations  
       [0085] 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 61, 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 61. 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-known within the art.  
       [0086] 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 61, 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 61. 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 61; more preferably at least about 70% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 61; still more preferably at least about 80% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 61; even more preferably at least about 90% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 61; and most preferably at least about 95% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 61.  
       [0087] 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 61, 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 61, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.  
       [0088] Mutations can be introduced any one of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, 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, isoleucinie) 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 61, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.  
       [0089] The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved “strong” residues or fully conserved “weak” residues. The “strong” group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the “weak” group of conserved residues may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code.  
       [0090] 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).  
       [0091] 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).  
       [0092] Antisense Nucleic Acids  
       [0093] 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 61, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of a NOVX protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 61, 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 61, are additionally provided.  
       [0094] 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).  
       [0095] Given the coding strand sequences encoding the NOVX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of NOVX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e g, an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used).  
       [0096] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-carboxymethylaminomethyl-2-thiouridine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methlylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 2-methylthio-N-6-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 (ie, 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).  
       [0097] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.  
       [0098] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987.  Nucl. Acids Res.  15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (See, e.g. Inoue, et al. 1987.  Nucl. Acids Res.  15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987.  FEBS Lett.  215: 327-330.  
       [0099] Ribozymes and PNA Moieties  
       [0100] 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.  
       [0101] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988.  Nature  334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a NOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et al. and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al., (1993)  Science  261:1411-1418.  
       [0102] Alternatively, NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g, the NOVX promoter and/or enhancers) to form triple helical structures that prevent transcription of the NOVX gene in target cells. See, e.g., Helene, 1991.  Anticancer Drug Des.  6: 569-84; Helene, et al. 1992.  Ann. N.Y. Acad. Sci.  660: 27-36; Maher, 1992.  Bioassays  14: 807-15.  
       [0103] In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, eg., Hyrup, et al., 1996.  Bioorg Med Chem  4: 5-23. As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O&#39;Keefe, et al., 1996.  Proc. Natl Acad. Sci. USA  93: 14670-14675.  
       [0104] 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, eg., S 1  nucleases (See. Hyrup, et al., 1996, supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O&#39;Keefe, et al., 1996. supra).  
       [0105] In another embodiment, PNAs of NOVX can be modified, e.g, to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e g., RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleotide bases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al., 1996.  Nucl Acids Res  24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5′ end of DNA. See, eg, Mag, et al., 1989.  Nucl Acid Res  17: 5973-5988. PNA monomers arc then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment. See, e.g., Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment. See, e.g., Petersen, et al., 1975.  Bioorg. Med Chem. Lett.  5: 1119-11124.  
       [0106] 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. USA  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, eg, 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.  
       [0107] NOVX Polypeptides  
       [0108] 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 61. 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 61, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.  
       [0109] 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.  
       [0110] One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.  
       [0111] 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.  
       [0112] 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.  
       [0113] 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 61) 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.  
       [0114] 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.  
       [0115] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 61. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 61, and retains the functional activity of the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 61, 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 61, and retains the functional activity of the NOVX proteins of SEQ ID NO: 2n, wherein n is an integer between 1 and 61.  
       [0116] Determining Homology Between Two or More Sequences  
       [0117] 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”).  
       [0118] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970.  J Mol Biol  48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61.  
       [0119] The term “sequence identity” refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term “percentage of sequence identity” is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i.e, the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term “substantial identity” as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.  
       [0120] Chimeric and Fusion Proteins  
       [0121] 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 61, 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, eg., 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.  
       [0122] 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.  
       [0123] In another embodiment, the fusion protein is a NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (eg., mammalian host cells), expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.  
       [0124] In yet another embodiment, the fusion protein is a NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between a NOVX ligand and a NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of a NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e.g. promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with a NOVX ligand.  
       [0125] A NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, eg., Ausubel, et al. (eds.) C URRENT  P ROTOCOLS IN  M OLECULAR  B IOLOGY , John Wiley &amp; Sons, 1992). Moreover, many expression vectors are commercially available that already encode a 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.  
       [0126] NOVX Agonists and Antagonists  
       [0127] 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.  
       [0128] 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. Anna Rev. Biochem. 53: 323; Itakura, et al., 1984.  Science  198: 1056; Ike, et al., 1983.  Nucl. Acids Res.  11: 477.  
       [0129] Polypeptide Libraries  
       [0130] 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.  
       [0131] 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.  
       [0132] Anti-NOVX Antibodies  
       [0133] Included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, F ab , F ab′  and F (ab′)2  fragments, and an F ab  expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG 1 , IgG 2 , and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.  
       [0134] 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 61, 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.  
       [0135] 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, eg, Hopp and Woods, 1981,  Proc Natl. 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.  
       [0136] The term “epitope” includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (K D ) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.  
       [0137] 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.  
       [0138] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.  
       [0139] Polyclonal Antibodies  
       [0140] For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund&#39;s (complete and incomplete), mineral gels (e.g. aluminum hydroxide), surface active substances (e.g, lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and  Corynebacterium parvum , or similar immunostimulatory agents. Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).  
       [0141] The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of the immune serum. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (Apr. 17, 2000), pp. 25-28).  
       [0142] Monoclonal Antibodies  
       [0143] 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.  
       [0144] 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.  
       [0145] 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.  
       [0146] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).  
       [0147] 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.  
       [0148] After the desired hybridoma cells are identified, the clones can bc subcloned by limiting dilution procedures and grown by standard methods (Goding, 1986). Suitable culture media for this purpose include, for example, Dulbeeco&#39;s Modified Eagle&#39;s Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.  
       [0149] 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.  
       [0150] The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.  
       [0151] Humanized Antibodies  
       [0152] The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′) 2  or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Pat. No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986;  Riechmann et al.,  1988; and Presta, Cur. Op. Struct. Biol., 2:593-596 (1992)).  
       [0153] Human Antibodies  
       [0154] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: M ONOCLONAL  A NTIBODIES AND  C ANCER  T HERAPY , Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: M ONOCLONAL  A NTIBODIES AND  C ANCER  T HERAPY , Alan R. Liss, Inc., pp. 77-96).  
       [0155] In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. (Nature 368 856-859 (1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild et al,(Nature Biotechnology 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).  
       [0156] Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal&#39;s endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host&#39;s genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse 1M  as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.  
       [0157] An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Pat. No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rearrangement of the locus and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.  
       [0158] A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Pat. No. 5,916,771. It includes introducing(, an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.  
       [0159] 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.  
       [0160] F ab  Fragments and Single Chain Antibodies  
       [0161] According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Pat. No. 4,946,778). In addition, methods can be adapted for the construction of F ab  expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal F ab  fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F (ab′)2  fragment produced by pepsin digestion of an antibody molecule; (ii) an F ab  fragment generated by reducing the disulfide bridges of an F (ab′)2  fragment; (iii) an F ab  fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) F v  fragments.  
       [0162] Bispecific Antibodies  
       [0163] 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.  
       [0164] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).  
       [0165] Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).  
       [0166] According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.  
       [0167] 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 mercaptoethylaminie 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.  
       [0168] 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.  
       [0169] Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab′ portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The “diabody” technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (V H ) connected to a light-chain variable domain (V L ) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the V H  and V L  domains of one fragment are forced to pair with the complementary V L  and V H  domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).  
       [0170] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).  
       [0171] 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 (eg CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FCγRII (CD32) and FcγRIII (CD16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).  
       [0172] Heteroconjugate Antibodies  
       [0173] Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980), and for 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. Pat. No. 4,676,980.  
       [0174] Effector Function Engineering  
       [0175] 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).  
       [0176] Immunoconjugates  
       [0177] 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).  
       [0178] Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from  Pseudomonas aeruginosa ), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin,  Aleurites fordii  proteins, dianthin proteins,  Phytolaca americana  proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include  212 Bi,  131 In,  131 In,  90 Y, and  186 Re.  
       [0179] Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al.,  Science,  238: 1098 (1987). Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.  
       [0180] 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.  
       [0181] Immunoliposomes  
       [0182] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.  
       [0183] 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: 986-288 (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).  
       [0184] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention  
       [0185] In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme linked immunosorbent assay (ELISA) and other immunologically mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.  
       [0186] 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”).  
       [0187] An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include 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  125 I,  131 I,  35 S or  3 H.  
       [0188] Antibody Therapeutics  
       [0189] Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligated, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible.  
       [0190] 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.  
       [0191] 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.  
       [0192] Pharmaceutical Compositions of Antibodies  
       [0193] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington: The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug, Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.  
       [0194] 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.  
       [0195] 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) albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.  
       [0196] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.  
       [0197] 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™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.  
       [0198] ELISA Assay  
       [0199] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., F ab  or F (ab)2 ) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (ie., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling, of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Thory 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.  
       [0200] NOVX Recombinant Expression Vectors and Host Cells  
       [0201] 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 arc 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.  
       [0202] 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).  
       [0203] The term “regulatory sequence” is intended to includes promoters, enhancers and other expression control elements (e.g, polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).  
       [0204] The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as  Escherichia coli,  insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.  
       [0205] Expression of proteins in prokaryotes is most often carried out in  Escherichia coli  with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: (i) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988.  Gene  67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.  
       [0206] Examples of suitable inducible non-fusion  E. coli  expression vectors include pTrc (Amrann et al., (1988)  Gene  69:301-315) and pET 11d (Studier et al., G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990) 60-89).  
       [0207] One strategy to maximize recombinant protein expression in  E. coli  is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g. Gottesman, G ENE  E XPRESSION  T ECHNOLOGY : M ETHODS IN  E NZYMOLOGY  185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in  E. coli  (see. e.g, Wada, et al., 1992.  Nucl. Acids Res.  20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.  
       [0208] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast  Saccharomyces cerivisae  include pYepSec1 (Baldari, et al., 1987.  EMBO J  6: 229-234), pMFa (Kurjan and Herskowitz, 1982.  Cell  30: 933-943), pJRY88 (Schultz et al., 1987.  Gene  54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (In Vitrogen Corp, San Diego, Calif.).  
       [0209] Alternatively, NOVX can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (eg, 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).  
       [0210] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987.  Nature  329: 840) and pMT2PC (Kaufman, et al., 1987. EMBO J. 6: 187-195). When used in mammalian cells, the expression vector&#39;s control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., M OLECULAR  C LONING : A L ABORATORY  M ANUAL . 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.  
       [0211] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987.  Genes Dev.  1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988.  Adv. Immunol.  43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989.  EMBO J.  8: 729-733) and immunoglobulins (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 α-fetoprotein promoter (Campes and Tilghman, 1989.  Genes Dev.  3: 537-546).  
       [0212] 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.  
       [0213] 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.  
       [0214] 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.  
       [0215] Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (M OLECULAR  C LONING : A L ABORATORY  M ANUAL . 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.  
       [0216] 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 (eg, cells that have incorporated the selectable marker gene will survive, while the other cells die).  
       [0217] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (ie, 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.  
       [0218] Transgenic NOVX Animals  
       [0219] The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NOVX sequences have been altered. Such animals are useful for studying the function and/or activity of NOVX protein and for identifying and/or evaluating modulators of NOVX protein activity. As used herein, a “transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a “homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous NOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g, an embryonic cell of the animal, prior to development of the animal.  
       [0220] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences, i.e., any one of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: M ANIPULATING THE  M OUSE  E MBRYO , Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other transgenes.  
       [0221] 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 61), but more preferably, is a non-human homologue of a human NOVX genie. For example, a mouse homologue of hulllan NOVX gene of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 61, 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).  
       [0222] 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.  
       [0223] The selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras. See, e.g., Bradley, 1987. In: T ERATOCARCINOMAS AND  E MBRYONIC  S TEM  C ELLS : A P RACTICAL  A PPROACH , Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991.  Curr. Opin. Biotechnol.  2: 823-829; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169.  
       [0224] In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, See, e.g, Lakso, et al., 1992.  Proc. Natl. Acad. Sci. USA  89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of  Saccharomyces cerevisiae.  See, O&#39;Gorman, et al., 1991.  Science  251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of “double” transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.  
       [0225] 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, eg, 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.  
       [0226] Pharmaceutical Compositions  
       [0227] 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&#39;s Pharmaceutical Sciences, a standard reference text in the field, which is incorporated herein by reference. Preferred examples of Such carriers or diluents include, but are not limited to, water, saline, finger&#39;s solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.  
       [0228] 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 (eg, inhalation), transdermal (ie. 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.  
       [0229] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.  
       [0230] Sterile injectable solutions can be prepared by incorporating the active compound (eg, 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.  
       [0231] 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.  
       [0232] 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.  
       [0233] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration., detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.  
       [0234] 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.  
       [0235] In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, Such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.  
       [0236] 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.  
       [0237] The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Pat. No. 5,328,470) or by stereotactic injection (see, e.g, Chen, et al., 1994.  Proc. Natl. Acad. Sci. USA  91: 3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system.  
       [0238] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.  
       [0239] Screening and Detection Methods  
       [0240] 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.  
       [0241] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.  
       [0242] Screening Assays  
       [0243] 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.  
       [0244] In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the “one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g., Lam, 1997.  Anticancer Drug Design  12: 145.  
       [0245] 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.  
       [0246] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al., 1993.  Proc. Natl. Acad. Sci. U.S.A.  90: 6909; Erb, et al., 1994.  Proc. Natl Acad. Sci. U.S.A.  91: 11422; Zuckermann, et al., 1994.  J. Med. Chem.  37: 2678; Cho, et al., 1993.  Science  261: 1303; Carrell, et al., 1994.  Angew. Chem. Int. Ed. Engl.  33: 2059; Carell, et al., 1994.  Angew. Chem. Int. Ed. Engl.  33: 2061; and Gallop, et al., 1994.  J. Med. Chem.  37: 1233.  
       [0247] Libraries of compounds may be presented in solution (e.g, Houghten, 1992.  Biotechniques  13: 412-421), or on beads (Lam, 1991.  Nature  354: 82-84), on chips (Fodor, 1993.  Nature  364: 555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992.  Proc. Natl. Acad Sci USA  89: 1865-1869) or on phage (Scott and Smith, 1990.  Science  249: 386-390; Devlin, 1990.  Science  249: 404-406; Cwirla, et al., 1990.  Proc Natl. Acad. Sci. U.S.A.  87: 6378-6382; Felici, 1991.  J. Mol. Biol.  222: 301-310; Ladner, U.S. Pat. No. 5,233,409).  
       [0248] In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to a NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with  125 I,  35 S,  14 C, or  3 H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting. Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.  
       [0249] 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 (eg. 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.  
       [0250] Determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with a NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e. intracellular Ca 2+ , diacylglycerol, IP 3 , etc), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising a NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g, luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.  
       [0251] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof: Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. II 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.  
       [0252] 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.  
       [0253] 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.  
       [0254] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent Such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizinig agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether) n , N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).  
       [0255] In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either NOVX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-NOVX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g, at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra. Alternatively, the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.  
       [0256] 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 (eg, biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.  
       [0257] In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (i.e., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.  
       [0258] 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, eg., U.S. Pat. No. 5,283,317; Zervos, et al., 1993.  Cell  72: 223-232; Madura, et al., 1993.  J. Biol. Chem  268: 12046-12054; Bartel, et al., 1993.  Biotechniques  14: 920-924; Iwabuchi, et al., 1993.  Oncogene  8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) and modulate NOVX activity. Such NOVX-binding proteins are also involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.  
       [0259] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.  
       [0260] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.  
       [0261] Detection Assays  
       [0262] Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.  
       [0263] Chromosome Mapping  
       [0264] 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 61, 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.  
       [0265] 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.  
       [0266] 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.  
       [0267] By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D&#39;Eustachio, et al., 1983.  Science  220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.  
       [0268] 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.  
       [0269] 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 target than 1,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al., H UMAN  C HROMOSOMES : A M ANUAL OF  B ASIC  T ECHNIQUES  (Pergamon Press, New York 1988).  
       [0270] 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.  
       [0271] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, M ENDELIAN  I NHERITANCE IN  M AN , available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, eg., Egeland, et al., 1987.  Nature,  325: 783-787.  
       [0272] 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.  
       [0273] Tissue Typing  
       [0274] The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual&#39;s genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences of the invention are useful as additional DNA markers for RFLP (“restriction fragment length polymorphisms,” described in U.S. Pat. No. 5,272,057).  
       [0275] Furthermore, the sequences of the invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual&#39;s genome. Thus, the NOVX sequences described herein can be used to prepare two PCR primers from the 5′- and 3′-termini of the sequences. These primers can then be used to amplify an individual&#39;s DNA and subsequently sequence it.  
       [0276] Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the invention can be used to obtain such identification sequences from individuals and from tissue. The NOVX sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much of the allelic variation is due to single nucleotide polymorphisms (SNPs), which include restriction fragment length polymorphisms (RFLPs).  
       [0277] 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 61, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.  
       [0278] Predictive Medicine  
       [0279] The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g, blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer&#39;s Disease, Parkinson&#39;s Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.  
       [0280] Another aspect of the invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as “pharmacogenomics”). Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability of the individual to respond to a particular agent.)  
       [0281] 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.  
       [0282] These and other agents are described in further detail in the following sections.  
       [0283] Diagnostic Assays  
       [0284] 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 61, 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.  
       [0285] 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 fiagmllent 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. Examples of indirect antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, 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.  
       [0286] 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.  
       [0287] 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.  
       [0288] 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.  
       [0289] Prognostic Assays  
       [0290] The diagnostic methods described herein can furthermore be utilized to identify 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., mPNA, 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.  
       [0291] 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).  
       [0292] The methods of the invention can also be used to detect genetic lesions in a NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding a NOVX-protein, or the misexpression of the NOVX gene. For example, Such genetic lesions can be detected by ascertaining the existence of at least one of: (i) a deletion of one or more nucleotides from a NOVX gene; (ii) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) aberrant modification of a NOVX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non-wild-type splicing pattern of a messenger RNA transcript of a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in a NOVX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.  
       [0293] In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, eg., 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.  
       [0294] Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al., 1990.  Proc Natl Acad Sci USA  87: 1874-1878), transcriptional amplification system (see, Kwoh, et al., 1989.  Proc. Natl. Acad. Sci. USA  86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988.  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.  
       [0295] In an alternative embodiment, mutations in a NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Pat. No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.  
       [0296] In other embodiments, genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density arrays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al., 1996.  Human Mutation  7: 244-255; Kozal, et al., 1996.  Nat. Med.  2: 753-759. For example, genetic mutations in NOVX can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, et al., supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations. This is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.  
       [0297] In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence of the sample NOVX with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977.  Proc. Natl. Acad. Sci. USA  74: 560 or Sanger, 1977.  Proc. Natl. Acad. Sci USA  74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g. Naeve, et al., 1995.  Biotechniques  19: 448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101; Cohen, et al., 1996.  Adv. Chromatography  36: 127-162; and Griffin, et al., 1993.  Appl. Biochem. Biotechnol.  38: 147-159).  
       [0298] Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al., 1985.  Science  230: 1242. In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex Such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S 1  nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al., 1988.  Proc. Natl. Acad. Sci. USA  85: 4397; Saleeba, et al., 1992.  Methods Enzymol.  217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.  
       [0299] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of  E. coli  cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al., 1994.  Carcinogenesis  15: 1657-1662. According to an exemplary embodiment, a probe based on a NOVX sequence, e.g., a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Pat. No. 5,459,039.  
       [0300] 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.  
       [0301] 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.  
       [0302] 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.  
       [0303] 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.  
       [0304] 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.  
       [0305] 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.  
       [0306] Pharmacogenomics  
       [0307] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. She 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.  
       [0308] In conjunction With such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual&#39;s genotype and that individual&#39;s response to a foreign compound or drug) of the individual may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, the pharmacogenomics of the individual permits the selection of effective agents (e g., drugs) for prophylactic or therapeutic treatments based on a consideration of the individual&#39;s genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual.  
       [0309] Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons.  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.  
       [0310] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.  
       [0311] Thus, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual&#39;s drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with a NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.  
       [0312] Monitoring of Effects During Clinical Trials  
       [0313] 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.  
       [0314] By way of example, and not of limitation, genes, including NOVX, that are modulated in cells by treatment with an agent (eg, compound, drug or small molecule) that modulates NOVX activity (e.g, identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder. The levels of gene expression (ie., 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.  
       [0315] 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.  
       [0316] Methods of Treatment  
       [0317] 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, eg., 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.  
       [0318] These methods of treatment will be discussed more fully, below.  
       [0319] Diseases and Disorders  
       [0320] Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i e., reduce or inhibit) activity. Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to: (i) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof, (ii) antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are “dysfunctional” (i.e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to “knockout” endogenous function of an aforementioned peptide by homologous recombination (see, eg, Capecchi, 1989.  Science  244: 1288-1292); or (v) modulators (i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide of the invention) that alter the interaction between an aforementioned peptide and its binding partner.  
       [0321] 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.  
       [0322] Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity of the expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (eg., Northern assays, dot blots, in situ hybridization, and the like).  
       [0323] Prophylactic Methods  
       [0324] In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by aberrant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the NOVX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX aberrancy, for example, a NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.  
       [0325] Therapeutic Methods  
       [0326] 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.  
       [0327] 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 (eg, cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).  
       [0328] Determination of the Biological Effect of the Therapeutic  
       [0329] 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.  
       [0330] In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient&#39;s disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any of the animal model system known in the art may be used prior to administration to human subjects.  
       [0331] Prophylactic and Therapeutic Uses of the Compositions of the Invention  
       [0332] 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.  
       [0333] 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.  
       [0334] 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.  
       [0335] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. 
     
    
    
     EXAMPLES  
     Example A  
     [0336] Polynucleotide and Polypeptide Sequences, and Homology Data  
     Example 1  
     [0337] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.  
               TABLE IA                       NOV1 Sequence Analysis                                                    SEQ ID NO: 1   960 bp                             NOV 1a,     CTCGCCCGGTGCCTAGGTGCCCGGCCCCACACCGCCAGCTGCTCGGCGCCCGGGTCCG             CG 103191-02     CC   ATG CGCTCCGCCGCTGTCCTGGCTCTTCTGCTCTGCGCCGGGCAAGTCACTGCGCT       DNA Sequence   CCCTGTGAACAGCCCTATGAATAAAGGGGATACCGAGGTGATGAAATGCATCGTTGAG                   GTCATCTCCGACACACTTTCCAAGCCCAGCCCCATGCCTGTCAGCCAGGAATGTTTTG                   AGACACTCCGAGGAGATGAACGGATCCTTTCCATTCTGAGACATCAGAATTTACTGAA                   GGAGCTCCAAGACCTCGCTCTCCAAGGCGCCAAGGAGAGGGCACATCAGCAGAAGAAA                   CACAGCGGTTTTGAAGATGAACTCTCAGAGGTTCTTGAGAACCAGAGCAGCCAGGCCG                   AGCTGAAAGAGGCGGTGGAAGAGCCATCATCCAAGGATGTTATGGAGAAAAGAGAGGA                   TTCCAAGGAGGCAGAGAAAAGTGGTGAAGCCACAGACGGAGCCAGGCCCCAGGCCCTC                   CCGGAGCCCATGCAGGAGTCCAAGGCTGAGGGGAACAATCAGGCCCCTGGGGAGGAAG                   AGGAGGAGGAGGAGGAGGCCACCAACACCCACCCTCCAGCCAGCCTCCCCAGCCAGAA                   ATACCCAGGCCCACAGGCCGAGGGGGACAGTGAGGGCCTCTCTCAGGGTCTGGTGGAC                   AGAGAGAAGGGCCTGAGTGCAGAGCCCGGGTGGCAGGCAAAGAGAGAAGAGGAGGAGG                   AGGAGGAGGAGGCTGAGGCTGGAGAGGAGGCTGTCCCCGAGGAAGAAGGCCCCACTGT                   AGTGCTGAACCCCGAGGAGAAGAAAGAGGAGGAGGGCAGCGCAAACCGCAGACCAGAG                   GACCAGGAGCTGGAGAGCCTGTCGGCCATTGAAGCAGAGCTGGAGAAAGTGGCCCACC                   AGCTGCAGGCACTACGGCGGGGC TGA   GACACC                                           ORF Start: ATG at 61   ORF Stop: TGA at 952                                         SEQ ID NO: 2   297aa   MW at 32591.3 Da                             NOV 1a,   MRSAAVLALLLCAGQVTALPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFE           CG103191-02   TLRGDERILSILRHQNLLKELQDLALQGAKERAHQQKKHSGFEDELSEVLENQSSQAE       Protein Sequence   LKEAVEEPSSKDVMEKREDSKEAEKSGEATDGARPQALPERMQESKAEGNNQAPGEEE                   EEEEEATNTHPPASLPSQKYPGPQAEGDSEGLSQGLVDREKGLSAEPGWQAKREEEEE                   EEEAEAGEEAVPEEEGPTVVLNPEEKKEEEGSANRRPEDQELESLSAIEAELEKVAHQ                   LQALRRG                                         SEQ ID NO 3   837 bp                             NOV 1b,     CCACACCGTCAGCTGCTCGGCGCCCGGGTCCGCC   ATG CGCTCCGCCGCTGTCCTGGCT           CG103191-03   CTTCTGCTCTGCGCCGGGCAAGTCACTGCGCTCCCTGTGAACAGCCCTATGAATAAAG       DNA Sequence   GGGATACCGAGGTGATGAAATGCATCGTTGAGGTCATCTCCGACACACTTTCCAAGCC                   CAGCCCCATGCCTGTCAGCCAGGAATGTTTTGAGACACTCCGAGGAGATGAACGGATC                   CTTTCCATTCTGAGACATCAGAATTTACTGAAGGAGCTCCAAGACCTCGCTCTCCAAG                   GCGCCAAGGAGAGGGCACATCAGCAGAAGAAACACAGCGGTTTTGAAGATGAACTCTC                   AGAGGTTCTTGAGAACCAGAGCAGCCAGGCCGAGCTGAAAGAGGCGGTGGAAGAGCCA                   TCATCCAAGGATGTTATGGAGAAAAGAGAGGATTCCAAGGAGGCAGAGAAAAGTGGTG                   AAGCCACAGACGGAGCCAGGCCCCAGGCCCTCCCGGAGCCCATGCAGGACAACCGGGA                   CAGTTCCATGAAGCTCTCCTTCCGGGCCCGGGCCTACGGCTTCAGGGGCCCTGGGCCG                   CAGCTGCGACGAGGCTGGAGGCCATCCTCCTGGGAGGACAGCCTTGAGGCGGGCCTGC                   CCCTCCAGGTCCGAGGCTACCCCGAGGAGAAGAAAGAGGAGGAGGGCAGCGCAAACCG                   CAGACCAGAGGACCAGGAGCTGGAGAGCCTGTCGGCCATTGAGGCAGAGCTGGAGAAA                   GTGGCCCACCAGCTGCGGGCACTACGGCGGGGC TGA   GACACCGGCTGGCAGGGCTGGC                       CCCAGGGCACCCTGTGGGCCTGGCT                                           ORF Start: ATG at 35   ORF Stop: TGA at 788                                         SEQ ID NO: 4   251 aa   MW at 28029.1 Da                             NOV 1b,   MRSAAVLALLLCAGQVTALPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFE           CG103191-03   TLRGDERILSILRHQNLLKELQDLALQGAKERAHQQKKHSGFEDELSEVLENQSSQAE       Protein Sequence   LKEAVEEPSSKDVMEKREDSKEAEKSGEATDGARPQALPEPMQDNRDSSMKLSFRARA                   YGFRGPGPQLRRGWRPSSWEDSLEAGLPLQVRGYPEEKKEEEGSANRRPEDQELESLS                   AIEAELEKVAHQLRALRRG                                         SEQ ID NO: 5   1002 bp                             NOV 1c,     CCACACCGCCAGCTGCTCGGCGCCCGGGTCCGCC   ATG CGCTCCGCCGCTGTCCTGGCT           CG103191-04   CTTCTGCTCTGCGCCGGGCAAGTCACTGCGCTCCCTGTGAACAGCCCTATGAATAAAG       DNA Sequence   GGGATACCGAGGTGATGAAATGCATCGTTGAGGTCATCTCCGACACACTTTCCAAGCC                   CAGCCCCATGCCTGTCAGCCACGAATGTTTTGAGACACTCCGAGGAGATGAACGGATC                   CTTTCCATTCTGAGACATCAGAATTTACTGAAGGAGCTCCAAGACCTCGCTCTCCAAG                   GCGCCAAGGACAGGGCACATCAGCAGAAGAAACACAGCGGTTTTGAAGATGAACTCTC                   AGAGGTTCTTGAGAACCAGAGCAGCCAGGCCGAGCTGAAAGGTCGGTCGGAGGCTCTG                   GCTGTGGATGGAGCTGGGAAGCCTGGGGCTGAGGAGGCTCAGGACCCCGAAGGGAAGG                   GAGAACAGGAGCACTCCCAGCAGAAAGAGGAGGAGGAGGAGATGGCAGTGGTCCCGCA                   AGGCCTCTTCCGGGGTGGGAAGAGCGGAGAGCTGGAGCAGGAGGAGGAGCGGCTCTCC                   AAGGAGTGGGAGGACTCCAAACGCTGGAGCAAGATGGACCAGCTGGCCAAGGAGCTGA                   CGGCTGAGAAGCCGCTGGAGGGGCAGGAGGAGGAGGAGGACAACCGGGACAGTTCCAT                   CGAGGCTGGAGGCCATCCTCCCGGGAGGACAGCCTTGAGGCGGGCCTGCCCCTCCAGG                   TCCGAGGCTACCCCGAGGAGAAGAAAGAGGAGGAGGGCAGCGCAAACCGCAGACCAGA                   GGACCAGGAGCTGGAGAGCCTGTCGGCCATTGAGGCAGAGCTGGAGAAAGTGGCCCAC                   CAGCTGCAGGCACTACGGCGGGGC TGA   GACACCGGCTGGCAGGGCTGGCCCCAGGGCA                   CCCTGTGGGCCTGGCT                                           ORF Start: ATG at 35   ORF Stop: TGA at 953                                         SEQ ID NO:6   306 aa   MW at 34268.8 Da                             NOV 1c,   MRSAAVLALLLCAGQVTALPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFE           CG103191-04   TLRGDERILSILRHQNLLKELQDLALQGAKERAHQQKKHSGFEDELSEVLENQSSQAE       Protein Sequence   LKGRSEALAVDGAGKPGAEEAQDPEGKGEQEHSQQKEEEEEMAVVPQGLFRGGKSGEL                   EQEEERLSKEWEDSKRWSKMDQLAKELTAEKRLEGQEEEEDNRDSSMKLSFRARAYGF                   RGPGPQLRRGWRPSSREDSLEAGLPLQVRGYPEEKKEEEGSANRRPEDQELESLSAIE                   AELEKVAHQLQALRRG                                         SEQ ID NO: 7   337 bp                             NOV 1d,     C   ACC AGATCTCTCCCTGTGAACAGCCCTATGAATAAAGGGGATACCGAGGTGATGAAA           251425133 DNA   TGCATCGTTGAGGTCATCTCCGACACACTTTCCAAGCCCAGCCCCATGCCTGTCAGCC       Sequence   AGGAATGTTTTGAGACACTCCGAGGAGATGAACGGATCCTTTCCATTCTGAGACATCA                   GAATTTACTGAAGGAGCTCCAAGACCTCGCTCTCCAAGGCGCCAAGGAGAGGGCACAT                   CAGCAGAAGAAACACAGCGGTTTTGAAGATGAACTCTCAGAGGTTCTTGAGAACCAGA                   GCAGCCAGGCCGAGCTGAAAGGTCGGTCGGAGGCTCTGCTCGAGGGC                                         ORF Start: at 2   ORF Stop: end of sequence                                         SEQ ID NO: 8   112 aa   MW at 12528.0 Da               NOV 1d,   TRSLPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFETLRGDERILSILRHQ           251425133 Protein   NLLKELQDLALQGAKERAHQQKKHSGFEDELSEVLENQSSQAELKCRSEALLEG           Sequence                                             SEQ ID NO: 9   595 bp                             NOV 1e,     C   ACC AGATCTGCCGAGCTGAAAGGTCGGTCGGAGGCTCTGGCTGTGGATGGAGCTGGG           251425611 DNA   AAGCCTGGGGCTGAGGAGGCTCAGGACCCCGAAGGGAAGGGAGAACAGGAGCACTCCC       Sequence   AGCAGAAAGAGGAGGAGGAGGAGATGGCAGTGGTCCCGCAAGGCCTCTTCCCGGGTGG                   GAAGAGCGGAGAGCTGGAGCAGGAGGAGGAGCGGCTCTCCAAGGAGTGGGAGGACTCC                   AAACGCTGGAGCAAGATGGACCAGCTGGCCAAGGAGCTGACGGCTGAGAAGCGGCTGG                   AGGGGCAGGAGGAGGAGGAGGACAACCGGGACAGTTCCATGAAGCTCTCCTTCCGGGC                   CCGGGCCTACGGCTTCAGGGGCCCTGGGCCGCAGCTGCGACGAGGCTGGAGGCCATCC                   TCCCGGGAGGACAGCCTTGAGGCGGGCCTGCCCCTCCAGGTCCGAGGCTACCCCGAGG                   AGAAGAAAGAGGAGGAGGGCAGCGCAAACCGCAGACCAGAGGACCAGGAGCTGGAGAG                   CCTGTCGGCCATTGAGGCGGAGCTCCAGAAAGTGGCCCACCAGCTGCAGGCACTACGG                   CGGGGCCTCGAGGGC                                         ORF Start: at 2   ORF Stop: end of sequence                                         SEQ ID NO: 10   198 aa   MW at 22331.2 Da                             NOV 1e,   TRSAELKGRSEALAVDGAGKPGAEEAQDPEGKGEQEHSQQKEEEEEMAVVPQGLFRGG           251425611 Protein   KSGELEQEEERLSKEWEDSKRWSKMDQLAKELTAEKRLEGQEEEEDNRDSSMKLSFRA       Sequence   RAYGFRGPGPQLRRGWRPSSREDSLEAGLPLQVRGYPEEKKEEEGSANRRPEDQELES           LSAIEAELEKVAHQLQALRRGLEG                                         SEQ ID NO: 11   718 bp                             NOV 1f   CACCAGATCTCTCCCTGTGAACAGCCCTATGAATAAAGGGGATACCGAGGTGATGAAA           278460276 DNA   TGCATCGTTGAGGTCATCTCCGACACACTTTCCAAGCCCAGCCCCATGCCTGTCAGCC       Sequence   AGGAATGTTTTGAGACACTCCGAGGAGATGAACGGATCCTTTCCATTCTGAGACATCA                   GAATTTACTGAAGGAGCTCCAAGACCTCGCTCTCCAAGGCGCCAAGGAGAGGGCACAT                   CAGCAGAAGAAACACAGCGGTTTTGAAGATGAACTCTCAGAGGTTCTTGAGAACCAGA                   GCAGCCAGGCCGAGCTGAAAGAGGCGGTGGAAGAGCCATCATCCAAGGATGTTATGGA                   GAAAAGAGAGGATTCCAAGGAGGCAGAGAAAAGTGGTGAAGCCACAGACGGAGCCAGG                   CCCCAGGCCCTCCCGGAGCCCATGCAGGACAACCGGGACAGTTCCATGAAGCTCTCCT                   TCCGGGCCCGGGCCTACGGCTTCAGGGGCCCTGGGCCGCAGCTGCGACGAGGCTGGAG                   GCCATCCTCCTGGGAGGACAGCCTTGAGGCGGGCCTGCCCCTCCAGGTCCGAGGCTAC                   CCCGAGGAGAAGAAAGAGGAGGAGGGCAGCGCAAACCGCAGACCAGAGGACCAGGAGC                   TGGAGAGCCTGTCGGCCATTGAGGCAGAGCTGGAGAAAGTGGCCCACCAGCTGCGGGC                   ACTACGGCGGGGCCTCGAGGGC                                         ORF Start: at 2   ORF Stop: end of sequence                                         SEQ ID NO: 12   239 aa   MW at 26902.7 Da                             NOV 1f   TRSLPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFETLRGDERILSILRHQ           278460276 Protein   NLLKELQDLALQGAKERAHQQKKHSGFEDELSEVLENQSSQAELKEAVEEPSSKDVME       Sequence   KREDSKEAEKSGEATDGARPQALPEPMQDNRDSSMKLSFRARAYGFRGPGPQLRRGWR                   PSSWEDSLEAGLPLQVRGYPEEKKEEEGSANRRPEDQELESLSAIEAELEKVAHQLRA                   LRRGLEG                                         SEQ ID NO: 13   856 bp                             NOV 1g,     C   ACC AGATCTCTCCCTGTGAACAGCCCTATGAATAAAGGGGATACCGAGGTGATGAAA           278456175 DNA   TGCATCGTTGAGGTCATCTCCGACACACTTTCCAAGCCCAGCCCCATGCCTGTCAGCC       Sequence   AGGAATGTTTTGAGACACTCCGAGGAGATGAACGGATCCTTTCCATTCTGAGACATCA                   GAATTTACTGAAGCAGCTCCAAGACCTCGCTCTCCAAGGCGCCAAGGAGACGGCACAT                   CAGCAGAAGAAACACACCGGTTTTGAAGATGAACTCTCAGAGGTTCTTGAGAACCAGA                   GCAGCCAGGCCGAGCTGAAAGAGGCGGTGGAAGAGCCATCATCCAAGGATGTTATGGA                   GAAAAGAGAGGATTCCAAGGAGGCAGAGAAAAGTGGTGAAGCCACACACGGAGCCAGG                   CCCCAGGCCCTCCCGGAGCCCATGCAGGAGTCCAAGGCTGAGGGGAACAATCAGGCCC                   CTGGGGAGGAAGAGGAGGAGGAGGAGGAGGCCACCAACACCCACCCTCCAGCCAGCCT                   CCCCAGCCAGAAATACCCAGGCCCACAGGCCGAGGGGGACAGTGAGGGCCTCTCTCAG                   GGTCTGGTGGACAGAGAGAAGGGCCTGAGTGCAGAGCCCGGGTGGCAGGCAAAGAGAG                   AAGAGGAGGAGGAGGAGGAGGAGGCTGAGGCTGGAGAGGAGGCTGTCCCCGAGGAAGA                   AGGCCCCACTGTAGTGCTGAACCCCGAGGAGAAGAAAGAGGAGGAGGGCAGCGCAAAC                   CGCAGACCAGAGGACCAGGAGCTGGAGAGCCTGTCGGCCATTGAAGCAGAGCTGGAGA                   AAGTGGCCCACCAGCTGCAGGCACTACGGCGGGGCCTCGAGGGC                                         ORF Start: at 2   ORF Stop: end of sequence                                         SEQ ID NO: 14   285 aa   MW at 31464.9 Da                             NOV 1g,   TRSLPVNSPMNKGDTEVMKCIVEVISDTLSKPSPMPVSQECFETLRGDERILSILRHQ           278456175 Protein   NLLKELQDLALQGAKERAHQQKKHSGFEDELSEVLENQSSQAELKEAVEEPSSKDVME       Sequence   KREDSKEAEKSGEATDGARPQALPEPMQESKAEGNNQAPGEEEEEEEEATNTHPPASL                   PSQKYPGPQAEGDSEGLSQGLVDREKGLSAEPGWQAKREEEEEEEEAEAGEEAVPEEE                   GPTVVLNPEEKKEEEGSANRRPEDQELESLSAIEAELEKVAHQLQALRRGLEG                  
 
     [0338] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.  
               TABLE 1B                          Comparison of NOV1a against NOV1b through NOV1g.                                 Protein   NOV1a Residues/   Identities/Similarities for           Sequence   Match Residues   the Matched Region                       NOV1b    1 . . . 297   201/297 (67%)                1 . . . 251   212/297 (70%)           NOV1c    1 . . . 297   172/313 (34%)                1 . . . 306   188/313 (59%)           NOV1d    18 . . . 118   100/101 (99%)                3 . . . 103   101/101 (99%)           NOV1e   192 . . . 297    46/109 (42%)                94 . . . 195    55/109 (50%)           NOV1f    18 . . . 297   183/280 (65%)                3 . . . 236   195/280 (69%)           NOV1g    18 . . . 297   236/280 (84%)                3 . . . 282   237/280 (84%)                      
 
     [0339] Further analysis of the NOV1a protein yielded the following properties shown in  
               TABLE 1C                       Protein Sequence Properties NOV1a                                        PSort   0.7618 probability located in outside; 0.1000 probability       analysis:   located in endoplasmic reticulum (membrane); 0.1000           probability located in endoplasmic reticulum (lumen);           0.1000 probability located in lysosome (lumen)       SignalP   Cleavage site between residues 19 and 20       analysis:                  
 
     [0340] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1D.  
               TABLE 1D                          Geneseq Results for NOV1a                                             Identities/                       Similari-               NOV1a/   ties           Protein/   Residues/   for the       Geneseq   Organism/Length   Match   Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAY53797   Amino acid   19 . . . 255   237/238    e−132           sequence of the   1 . . . 238   (99%)           mature human       237/238           chromogranin A       (99%)           (CgA) protein -             Homo sapiens , 439 aa.           [WO9958980-A1,           18 NOV. 1999]       AAU86000   Modified vasostatin II   19 . . . 131   113/113   2e−58           antibiotic peptide -   1 . . . 113   (100%)           Unidentified,       113/113            113 aa.       (100%)           [WO200210195-           A2, 07 FEB. 2002]       AAY53798   Amino acids 145-234   163 . . . 251   89/90   4c−45           of the mature human   1 . . . 90   (98%)           chromogranin A       89/90           (CgA) protein -  Homo         (98%)             sapiens , 90 aa.           [WO9958980-A1,           18 NOV. 1999]       AAB37069   Recombinant   17 . . . 96   80/80   2e−39           vasostatin I   2 . . . 81   (100%)           peptide -   80/80           Unidentified, 81 aa.       (100%)           [FR2792638-A1,           27 OCT. 2000]       AAB37066   Human vasostatin I   19 . . . 94   76/76   4e−37           peptide -  Homo     1.76   (100%)             sapiens , 76 aa.           [FR2792638-A1,       76/76           27 OCT. 2000]       (100%)                  
 
     [0341] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E.  
               TABLE 1E                          Public BLASTP Results for NOV1a                                             Identities/                       Similari-               NOV1a   ties       Protein       Residues/   for the       Accession       Match   Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               A28468   chromogranin A   1 . . . 255   255/256    e−142           [validated] -   1 . . . 256   (99%)           human, 457 aa.       255/256                   (99%)       P10645   Chromogranin A   1 . . . 255   255/256    e−142           precursor (CGA)   1 . . . 256   (99%)           (Pituitary secretory       255/256           protein I)       (99%)           (SP-1) [Contains:           Vasostatin I;           Vasostatin II;           EA-92; ES-43;           Pancreastatin           SS-18; WA-8; WE-14;           LF-19; AL-11; GV-19;           GR-44; ER;37] -  Homo               sapiens  (Human),           457 aa.       Q96GL7   Similar to chromogranin   54 . . . 255   202/203    e−111           A (Parathyroid secretory   4 . . . 206   (73%)           protein 1)  Homo sapiens         202/203           (Human), 407 aa       (99%)           (fragment).       P05059   Chromogranin A   1 . . . 271   202/276    e−100           precursor (CGA)       (73%)           (Pituitary secretory       215/276           protein 1) (SP-1)       (77%)           [Contains:           Vasostatin-1;           Chromostatin;           Chromacin;           Pancreastatin;           We − 14; Catestatin] -           Bos taurus (Bovine),           449 aa.       A41520   chromogranin A   1 . . . 271   199/276   3e−99           precursor       (72%)           [validated] - bovine,       213/276           449 aa.       (77%)                  
 
     [0342] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1F.  
               TABLE 1F                          Domain Analysis of NOV1a                                     Identities           Pfam   NOV1a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               Granin   1 . . . 297   138/689 (20%)   1.7e−29               291/689 (42%)                  
 
     Example 2  
     [0343] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.  
               TABLE 2A                       NOV2 Sequence Analysis                                                    SEQ ID NO: 15   2521 bp                             NOV2a,     ACAGTTGTAAGGGATCTTGTGGCTGTCAGG   ATG GCAGAGGAGCAGGAGTTCACCCAGC           CG105757-01   TCTGCAAGTTGCCTGCACAGCCCTCACACCCACACTGCGTGAACAACACCTACCGCAG       DNA Sequence   CGCACAGCACTCCCAGGCTCTGCTCCGAGGGCTGCTGGCTCTCCGGGACAGCGGAATC                   CTCTTCGATGTTGTGCTGGTGGTGGAGGGCAGACACATCGAGGCCCATCCCATCCTGC                   TGGCTGCGTCCTGCGATTACTTCAGGAGAGGAATGTTTGCTGGGGGATTGAAGGAGAT                   GGAACAGGAAGAGGTCCTGATCCACGGTGTGTCCTACAATGCTATGTGCCAAATCCTA                   CATTTCATATACACCTCCGAGCTGGAGCTCAGCCTGAGCAATGTACAAGAGACACTGG                   TGGCTGCCTGCCAGCTGCAGATCCCAGAAATTATCCATTTCTGCTGTGATTTCCTCAT                   GTCCTGGGTGGACGAAGAGAACATTCTCGATGTCTACCGGCTGGCAGAGCTGTTTGAC                   TTGAGCCGCCTGACTGAGCAACTGGACACCTATATCCTCAAAAACTTTGTGGCCTTCT                   CTCGGACTGACAAGTACCGCCAGCTTCCATTGGAGAAGGTCTACTCCCTCCTCAGCAG                   CAATCGCCTGGAGGTCTCCTGCGAGACCGAGGTATATGAGGGGGCCCTTCTCTACCAT                   TATAGCCTGGAGCAGGTGCAGGCTGACCAGATCTCGCTGCACGAGCCCCCAAAGCTCC                   TTGAGACAGTGCGGTTTCCGCTGATGGAAGCTGAGGTCCTGCAGCGGCTGCATGACAA                   GCTGGACCCCAGCCCTTTGAGGGACACAGTGCCCAGCGCCCTCATGTACCACCGGAAC                   GAGAGCCTACAGCCCAGCCTGCAGAGCCCGCAAACGGAGCTGCGGTCGGACTTCCAGT                   GCGTTGTGGGCTTCGGGGGCATTCACTCCACGCCGTCCACTGTCCTCAGCGACCAGGC                   CAAGTATCTAAACCCCTTACTGGGAGAGTGGAAGCACTTCACTGCCTCCCTGGCCCCC                   CGCATGTCCAACCAGGGCATCGCGGTGCTCAACAACTTCCTATACTTGATTGGAGGGG                   ACAACAATGTCCAAGGATTTCGAGCAGAGTCCCGATGCTGGAGGTATGACCCACCGCA                   CAACCGCTGGTTCCAGATCCAGTCCCTGCAGCAGGAGCACGCCGACCTGTCCGTGTGT                   GTTGTAGGCAGGTACATCTACGCTGTGGCGGGCCGTGACTACCACAATGACCTGAATG                   CTGTGGAGCGCTACGACCCTGCCACCAACTCCTGGGCATACGTGGCCCCACTCAAGAG                   GGAGGTAGTGTATGCCCACGCAGGCGCGACGCTGGAGGGGAAGATGTATATCACCTGC                   GGCCGCAGAGGGGAGGATTACCTGAAAGAGACACACTGCTACGATCCAGGCAGCAACA                   CTTGGCACACACTGGCTGATGGGCCTGTGCGGCGCGCCTGGCACGGCATGGCAACCCT                   CCTCAACAAGCTGTATGTGATCGGGGGCAGCAACAACGATGCCGGATACAGGAGGGAC                   GTGCACCAGCTCCCAGGTGCCCACGTGCTGCGCTGGCTGGAGGCAGCAAGGGGACGAG                   TGTGGGATTGCGGTGTGCGAACGCAACTCCACGTGCTCAGAGAACGAGGTGTGCGTGA                   GGCCTGGCGAGTGCCGCTGCCGCCACGGCTACTTCGGTGCCAACTGCGACACCAGTGT                   GGCCAGTGCAAGGGGCCAGCAGCCGTGCACGGTGGCCGAGGGCCGCTGCTTGACGTGC                   GAGCCCGGCTGGAACGGAACCAAGTGCGACCAGCCTTGCGCCACCGGTTTCTATGCCG                   AGGGCTGCAGCCACCGCTGTCCGCCATGCCGCGACGGGCATGCCTG TAA   CCATGTCAC                       CGGCAAGTGTACGCGCTGCAACGCGGGCTGGATCGGCGACCGGTGCGAGACCAAGTGT                       AGCAATGGCACTTACGGCGAGGACTGCGCCTTCGTGTGCGCCGACTGCGGCAGCGGAC                       ACTGCGACTTCCAGTCGGGGCGCTGCCTGTGCAGCCCTGGCGTCCACGGGCCCCAGTG                       AGTGCCCCGGGACCGGGAGGGGGTTGGGGGCTTGTACCTGCCACAGAGGGGGGTCCAG                       CCGACGAGGTGGCCTCTCCACCCTGAGCTGGGTTATCACCTCAGCCTTGGTCCCTTAC                       CCCAGCTAGGGAGTGACAGTAGGCTCTTTGGGGGCAGTTTCCTGCCTGGATGTCGGGG                       AGCTCACGTTCAGCGCAGGATCTGGTGACCAGTCCAGCCTGTGTCAGTGGGCTCTTAA                       GGTGACCCCGAGTTGGTACAGAAGGACCAGGGACCTCCACTTACAGCCAAGGGTCTGG                       TTCAGCAGCCCCTCTTCCCACCTAGCCGAGTCAGCCCCAGCAGTGGGCGCTGCCGCGC                       GGCCACCACGGGTCCTATCCCCCAGGCCCCCCCACTAGTGTTGTGCAACATTCGTTTC                       CAAAACATCCACTACCCAATATGTGCC                                           ORF Start: ATG at 31   ORF Stop: TAA at 1903                                         SEQ ID NO: 16   624 aa   MW at 71369.7 Da               NOV 2a,   MAEEQEFTQLCKLPAQPSHPHCVNNTYRSAQHSQALLRGLLALRDSGILFDVVLVVEG           CG105757-01   RHIEAHRILLAASCDYFRROMFAGGLKEMEQEEVLIHGVSYNAMCQILHFIYTSELEL           Protein Sequence   SLSNVQETLVAACQLQIPEIIHFCCDFLMSWVDEENILDVYRLAELFDLSRLTEQLDT                           YILKNPVAFSRTDKYRQLPLEKVYSLLSSNRLEVSCETEVYEGALLYHYSLEQVQADQ                           ISLHEPPKLLETVRFPLMEAEVLQRLHDKLDPSPLRDTVASALMYHRNESLQPSLQSP                           QTELRSDFQCVVGFGGIHSTPSTVLSDQAKYLNPLLGEWKHFTASLAPRMSNQGIAVL                           NNFVYLIGGDNNVQGFRAESRCWRYDPRHNRWFQIQSLQQEHADLSVCVVGRYIYAVA                           GRDYHNDLNAVERYDPATNSWAYVAPLKREVVYAHAGATLEGKMYITCGRRGEDYLKE                           THCYDPGSNTWHTLADGPVRRAWHGMATLLNKLYVIGGSNNDAGYRRDVHQLPGAHVL                           RWLEAARGRVWDCGVRRQLHVLRERGVREAWRVPLPPRLLRCQLRHQCGQCKGPAAVH                           GGRGPLLDVRARLERNQVRPALRHRFLWRGLQPPLSAMPRRACL                      
 
     [0344] Further analysis of the NOV2a protein yielded the following properties shown in Table 2B.  
               TABLE 2B                       Protein Sequence Properties NOV2a                                        PSort   0.7900 probability located in plasma membrane; 0.3000       analysis:   probability located in microbody (peroxisome); 0.3000           probability located in Golgi body; 0.2000 probability located           in endoplasmic reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0345] 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 2C.  
               TABLE 2C                          Geneseq Results for NOV2a                                             Identities/                       Similari-               NOV2a/   ties           Protein/   Residues/   for the       Geneseq   Organism/Length   Match   Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAM39985   Human polypeptide    1 . . . 516   512/516   0.0           SEQ ID NO 3130 -    1 . . . 514   (99%)             Homo sapiens , 634 aa.       514/516           [WO200153312-A1,       (99%)           26 JUL. 2001]       AAB92457   Human protein    1 . . . 503   501/503   0.0           sequence    1 . . . 501   (99%)           SEQ ID NO: 10499 -       501/503             Homo sapiens , 525 aa.       (99%)           [EP1074617-A2,           07 FEB. 2001]       AAB60095   Human transport    1 . . . 457   453/457   0.0           protein TPPT-15-    1 . . . 455   (99%)             Homo sapiens , 462 aa.       454/457           [WO200078953-A2,       (99%)           28 DEC. 2000]       AAM41771   Human polypeptide    1 . . . 458   447/458   0.0           SEQ ID NO 6702 -    66 . . . .521   (97%)             Homo sapiens , 524 aa.       451/458           [WO200153312-A1,       (97%)           26 JUL. 2001]       ABG27028   Novel human    78 . . . 372   295/295   e−171           diagnostic protein   127 . . . .421   (100%)           #27019 -       295/295             Homo sapiens , 421 aa.       (100%)           [WO200175067-A2,           11 OCT. 2001]                  
 
     [0346] 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 2D.  
               TABLE 2D                          Public BLASTP Results for NOV2a                                             Identities/                       Similari-               NOV1a   ties       Protein       Residues/   for the       Accession   Protein/   Match   Matched   Expect       Number   Organism/Length   Residues   Portion   Value               Q96B68   Hypothetical 71.7 kDa   1 . . . 516   513/516   0.0           protein -  Homo     1 . . . 514   (99%)             sapiens  (Human),       514/516           634 aa.           (99%)       Q9KC6   CDNA FLJ14360   1 . . . 503   501/503   0.0           fis, clone   1 . . . 501   (99%)           HEMBA 1000488,   501/503           weakly similar to       (99%)           RING CANAL           protein -  Homo               sapiens             (Human), 525 aa.       Q99JN2   Hypothetical 71.7 kDa   1 . . . 516   487/516   0.0           protein -  Mus     1 . . . 514   (99%)             musculus  (Mouse),       502/516           634 aa.       (96%)       Q96Q17   Hypothetical 98.2 kDa   27 . . . 504   170/486   4e−75           protein -  Homo     18 . . . 493   (34%)             sapiens  (Human),       274/486           604 aa.       (55%)       Q9P2N7   Hypothetical protein   27 . . . 504   170/486   4e−75           KIAA1309 -  Homo     53 . . . 528   (34%)             sapiens  (Human),       274/486           639 aa (fragment).       (55%)                  
 
     [0347] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2E.  
               TABLE 2E                          Domain Analysis of NOV2a                                     Identities           Pfam   NOV2a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               BTB    34 . . . 146   37/144 (26%)   1.6e−22               87/144 (60%)       Kelch   339 . . . 387   13/49 (27%)   1.5e−06               37/49 (76%)       Kelch   389 . . . 434   12/47 (26%)     8e−07               35/47 (74%)       Kelch   437 . . . 482   12/47 (26%)   0.0079               31/47 (66%)                  
 
     Example 3  
     [0348] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.  
               TABLE 3A                       NOV3 Sequence Analysis                                                    SEQ ID NO: 17   5369 bp                             NOV 3a,     ATCCTCTCCGGGCTGTTCCCTGGCCTGTCTGCTCCTCCGGGCTCTGTCCCAGCAGCGA             CG108175-01     CA   ATG AGCTCCACACTCCACTCGGTTTTCTTCACCCTGAAGGTCAGCATCCTGCTGGG       DNA Sequence   GTCCCTGCTGGGGCTCTGCCTGGGCCTTGAGTTCATGGGCCTCCCCAACCAGTGGGCC                   CGCTACCTCCGCTGGGATGCCAGCACACGCAGTGACCTGAGTTTCCAGTTCAAGACCA                   ACGTCTCTACGGGGCTGCTCCTCTACCTGGATGATGGCGGCGTCTGCGACTTCCTATG                   CCTCTCCCTGGTGGATGGCCGCGTTCAGCTCCGCTTCAGCATGGACTGTGCCGAGACT                   GCCGTGCTGTCCAACAAGCAGGTGAATGACAGCAGCTGGCACTTCCTCATGGTGAGCC                   GTGACCGCCTGCGCACGGTGCTGATGCTTGATGGCGAGGGCCAGTCTGGGGAGCTGCA                   GCCCCAGCGGCCCTACATGGATGTGGTCAGTGACTTGTTCCTTGGTGGAGTCCCTACT                   GACATACGACCTTCTGCCCTGACCCTTGATGGAGTTCAGGCCATGCCCGGCTTCAAGG                   GGTTAATTCTGGATCTCAAGTATGGAAACTCGGAGCCTCGGCTTCTGGGGAGCCGGGG                   TGTCCAGATGGATGCCGAGGGACCCTGTGGTGAGCGTCCCTGTGAAAATGGTGGGATC                   TGCTTTCTCCTGGACGGCCACCCCACCTGTGACTGTTCTACCACTGGCTATGGTGGCA                   AGCTCTGCTCAGAAGGCCTCTCCCACCTCATGATGAGTGAACAAGCTCGAGAGGAGAA                   TGTGGCCACTTTCCGAGGCTCAGAGTATCTGTGCTACGACCTGTCTCAGAACCCGATC                   CAGAGCAGCAGTGATGAAATCACCCTCTCCTTTAAGACCTGGCAGCGTAACGGCCTCA                   TCCTGCACACGGGCAAGTCGGCTGACTATGTCAACCTGGCTCTGAAGGATGGTGCGGT                   CTCCTTGGTCATTAACCTGGGGTCCGGGGCCTTTGAGGCCATTGTGGAGCCAGTGAAT                   GGAAAATTCAACGACAACGCCTGGCATGATGTCAAAGTGACACGCAACCTCCGGCAGG                   TGACAATCTCTGTGGATGGCATTCTTACCACGACGGGCTACACTCAAGAGGACTATAC                   CATGCTGGGCTCGGACGACTTCTTCTATGTAGGAGGAAGCCCAAGTACCGCTGACTTG                   CCTGGCTCCCCTGTCAGCAACAACTTCATGGGCTGCCTTAAAGAGGTTGTTTATAAGA                   ATAATGACATCCGTCTGGAGCTGTCTCGCCTGGCCCGGATTGCGGACACCAAGATGAA                   AATCTATGGCGAAGTTGTGTTTAAGTGTGAGAATGTGGCCACACTGGACCCCATCAAC                   TTTGAGACCCCAGAGGCTTACATCAGCTTGCCCAAGTGGAACACTAAACGTATGGGCT                   CCATCTCCTTTGACTTCCGCACCACAGAGCCCAATGGCCTGATCCTCTTCACTCATGG                   AAAGCCCCAAGAGAGGAAGGATGCTCGGAGCCAGAAGAATACAAAAGTAGACTTCTTT                   GCCGTGGAACTCCTCGATGGCAACCTGTACTTGCTGCTTGACATGGGCTCTGGCACCA                   TCAAAGTGAAAGCCACTCAGAAGAAAGCCAATGATGGGGAATGGTACCATGTGGACAT                   TCAGCGAGATGGCAGATCAGGTACTATATCAGTGAACAGCAGGCGCACGCCATTCACC                   CCCAGTGGGGAGAGCGAGATCCTGGACCTGGAAGGAGACATGTACCTGGGAGGGCTGC                   CGGAGAACCGTGCTGGCCTTATTCTCCCCACCGAGCTGTGGACTGCCATGCTCAACTA                   TGGCTACGTGGGCTGCATCCGCGACCTATTCATTGATGGGCGCAGCAAGAACATTCGA                   CAGCTGGCAGAGATGCAGAATGCTGCGGGTGTCAAGTCCTCCTGTTCACGGATGAGTG                   CCAAGCAGTGTGACAGCTACCCCTGCAAGAATAATGCTGTGTGCAAGGACGGCTGGAA                   CCGCTTCATCTGCGACTGCACCGGCACCGGATACTGGGGAAGAACCTGCGAAAGGGAG                   GCATCCATCCTGAGCTATGATGGTAGCATGTACATGAAGATCATCATGCCCATGGTCA                   TGCATACTGAGGCAGAGGATGTGTCCTTCCGCTTCATGTCCCAGCGAGCTTATGGGCT                   GCTGGTGGCTACGACCTCCAGGGACTCTGCCGACACCCTGCGTCTGGAGCTGGATGGG                   GGGCGTGTCAAGCTCATGGTTAACTTAGACTGTATCAGGATAAACTGTAACTCCAGCA                   AAGGACCAGAGACCTTGTATGCAGGGCAGAAGCTCAATGACAACGAGTGGCACACCGT                   TCGGGTGGTGCGGAGAGGAAAAAGCCTTAAGTTAACCGTGGATGATGATGTGGCTGAG                   GGTACAATGGTGGGAGACCATACCCGTTTGGAGTTCCACAACATTGAAACGGGAATCA                   TGACTGAGAAACGCTACATCTCCGTTGTCCCCTCCAGCTTTATTGGCCATCTGCAGAG                   CCTCATGTTTAATGGCCTTCTCTACATTGACTTGTGCAAAAATGGTGACATTGATTAT                   TGTGAGCTGAAGGCTCGTTTTGGACTGAGGAACATCATCGCTGACCCTGTCACCTTTA                   AGACCAAGAGCAGCTACCTGAGCCTTGCCACTCTTCAGGCTTACACCTCCATGCACCT                   CTTCTTCCAGTTCAAGACCACCTCACCAGATGGCTTCATTCTCTTCAATAGTGGTGAT                   GGCAATGACTTCATTGCAGTCGAGCTTGTCAAGGGGTATATACACTACGTTTTTGACC                   TCGGAAACGGTCCCAATGTGATCAAAGGCAACAGTGACCGCCCCCTGAATGACAACCA                   GTGGCACAATGTCGTCATCACTCGGGACAATAGTAACACTCATAGCCTGAAAGTGGAC                   ACCAAAGTGGTCACTCAGGTTATCAATGGTGCCAAAAATCTGGATTTGAAAGGTGATC                   TCTATATGGCTGGTCTGGCCCAAGGCATGTACAGCAACCTCCCAAAGCTCGTGGCCTC                   TCGAGATGCCTTTCAGGGCTGTCTAGCATCAGTGGACTTGAATGGACGCCTGCCAGAC                   CTCATCAATGATGCTCTTCATCGGAGCGGACAGATCGAGCGTGGCTGTGAAGGTACAA                   CCTTACTAGGACCCAGTACCACCTGCCAGGAAGATTCATGTGCCAACCAGGGGGTCTG                   CATGCAACAATGGGAGGGCTTCACCTGTGATTGTTCTATGACCTCTTATTCTGGAAAC                   CAGTGCAATGATCCTGGCGCTACGTACATCTTTGGGAAAAGTGGTGGGCTTATCCTCT                   ACACCTGGCCAGCCAATGACAGGCCCAGCACGCGGTCTGACCGCCTTGCCGTGGGCTT                   CAGCACCACTGTGAAGGATGGCATCTTGGTCCGCATCGACAGTGCTCCAGGACTTGGT                   GACTTCCTCCAGCTTCACATAGAACAGGGGAAAATTGGAGTTGTCTTCAACATTGGCA                   CAGTTGACATCTCCATCAAAGAGGAGAGAACCCCTGTAAATGACGGCAAATACCATGT                   GGTACGCTTCACCAGGAACGGCGGCAACGCCACCCTGCAGGTGGACAACTGGCCAGTG                   AATGAACATTATCCTACAGGCAACACTGATAATGAACGCTTCCAAATGGTAAAACAGA                   AAATCCCCTTCAAATATAATCGGCCTGTAGAGGAGTGGCTGCAGGAAAAAGGCCGGCA                   GTTAACCATCTTCAACACTCAGGCGCAAATAGCCATTGGTGGAAAGGACAAAGGACGC                   CTCTTCCAAGGCCAACTCTCTGGGCTCTATTATGATGGTTTGAAAGTACTGAACATGG                   CGGCTGAGAACAACCCCAATATTAAAATCAATGGAAGTGTTCGGCTGGTTGGAGAAGT                   CCCATCAATTTTGGGAACAACACAGACGACCTCCATGCCACCAGAAATGTCTACTACT                   GTCATGGAAACCACTACTACAATGGCGACTACCACAACCCGTAAGAATCGCTCTACAG                   CCAGCATTCAGCCAACATCAGATGATCTTGTTTCATCTGCTGAATGTTCAAGTGATGA                   TGAAGACTTTGTTGAATGTGAGCCGAGTACAGGAGGTGAATTAGTTATCCCTCTTCTT                   GTAGAAGACCCTTTAGCTACCCCTCCTATTGCTACTCGTGCACCTTCCATTACACTCC                   CCCCTACCTTTCGCCCCCTCCTCACCATTATTGAGACCACCAAAGATTCCCTGTCCAT                   GACCTCTGAGGCGGGGTTACCTTGCTTGTCGGACCAAGGCAGCGATGGTTGTGATGAT                   GATGGCTTGGTGATATCTGGGTATGGCTCAGGGGAAACCTTTGACTCTAACCTGCCCC                   CTACTGATGATGAAGATTTTTACACCACCTTCTCCTTGGTAACAGATAAGAGTCTTTC                   CACTTCAATCTTCGAAGGTGGCTACAAAGCACATGCGCCCAAGTGGGAATCCAAGGAC                   TTTAGACCTAACAAAGTCTCCGAAACTAGTAGGACTACTACCACATCTTTATCCCCTG                   AGCTGATCCGCTTCACAGCTTCCTCCTCGTCTGGGATGGTGCCCAAATTGCCAGCTGG                   CAAAATGAATAACCGTGATCTCAAACCCCAGCCTGATATAGTCTTGCTTCCGTTGCCC                   ACTGCCTATGAGCTAGACAGCACCAAACTGAAGAGCCCACTAATTACTTCCCCCATGT                   TCCCTAATGTGCCCACAGCAAACCCCACGGAGCCGGGAATCAGACGGGTTCCGGGGGC                   CTCAGAGGTGATCCGGGAGTCGAGCAGCACAACAGGGATGGTCGTCGGCATTGTGGCT                   GCTGCCGCCCTCTGCATCTTGATCCTCCTGTACGCCATGTACAAGTACAGGAACAGGG                   ACGAGGGGTCCTATCAAGTGGACGAGACGCGGAACTACATCAGCAACTCCGCCCAGAG                   CAACGGCACGCTCATGAAGGAGAAGCAGCAGAGCTCGAAGAGCGGCCACAAGAAACAG                   AAAAACAAGGACAGGGAGTATTACGTG TAA   ACATGCGAACACTGCTCACACGCGAGTT                       TTCACAGTTATTTCTATCCACGCCTATGAATCTTTGGACGGTGAGATCTCACAGATGT                       CAGAACTGCTGGAACTATGAAATGGGGTATATAACCACGACTCTGGTGGGGAAAACCG                       TTTTTTAAAGGACACACACACACACACAGCGATGCATCTCTCTCTAAAGCTCAGCCAC                       GGCTGCGGCAAGGTCCCAGCGGTCGCTGGGAGACAGAAGGTTTTGTGCCCTGCTGTAT                       CATAAAGCACACACTTAGCGCTCTGGAGCCGGA                                           ORF Start: ATG at 61   ORF Stop: TAA at 5074                                         SEQ ID NO: 18   1671 aa   MW at 184075.2 Da                             NOV 3a,   MSSTLHSVFFTLKVSILLGSLLGLCLGLEFMGLPNQWARYLRWDASTRSDLSFQFKTN           CG108175-01   VSTGLLLYLDDGGVCDFLCLSLVDGRVQLRFSMDCAETAVLSNKQVNDSSWHFLMVSR       Protein Sequence   DRLRTVLMLDGEGQSGELQPQRPYMDVVSDLFLGGVPTDIRPSALTLDGVQAMPGFKG                   LILDLKYGNSEPRLLGSRGVQMDAEGPCGERPCENGGICFLLDGHPTCDCSTTGYGGK                   LCSEGLSHLMMSEQAREENVATFRGSEYLCYDLSQNPIQSSSDEITLSFKTWQRNGLI                   LHTGKSADYVNLALKDGAVSLVINLGSGAFEAIVEPVNGKFNDNAWHDVKVTRNLRQV                   TISVDGILTTTGYTQEDYTMLGSDDFFYVGGSPSTADLPGSPVSNNFMGCLKEVVYKN                   NDIRLELSRLARIADTKMKIYGEVVFKCENVATLDPINFETPEAYISLPKWNTKRMGS                   ISFDFRTTEPNGLILFTHGKPQERKDARSQKNTKVDFFAVELLDGNLYLLLDMGSGTI                   KVKATQKKANDGEWYHVDIQRDGRSGTISVNSRRTPFTASGESEILDLEGDMYLGGLP                   ENRAGLILPTELWTAMLNYGYVGCIRDLFIDGRSKNIRQLAEMQNAAGVKSSCSRMSA                   KQCDSYPCKNNAVCKDGWNRFICDCTGTGYWGRTCEREASILSYDGSMYMKIIMPMVM                   HTEAEDVSFRFMSQRAYGLLVATTSRDSADTLRLELDGGRVKLMVNLDCIRINCNSSK                   GPETLYAGQKLNDNEWHTVRVVRRGKSLKLTVDDDVAEGTMVGDHTRLEFHNIETGIM                   TEKRYISVVPSSFIGHLQSLMFNGLLYIDLCKNGDIDYCELKARFGLRNIIADPVTFK                   TKSSYLSLATLQAYTSMHLFFQFKTTSPDGFILFNSGDGNDFIAVELVKGYIHYVFDL                   GNGPNVIKGNSDRPLNDNQWHNVVITRDNSNTHSLKVDTKVVTQVINGAKNLDLKGDL                   YMAGLAQGMYSNLPKLVASRDGFQGCLASVDLNGRLPDLINDALHRSGQIERGCEGTT                   LLGPSTTCQEDSCANQGVCMQQWEGFTCDCSMTSYSGNQCNDPGATYIFGKSGGLILY                   TWPANDRPSTRSDRLAVGFSTTVKDGILVRIDSAPGLGDFLQLHIEQGKIGVVFNIGT                   VDISIKEERTPVNDGKYHVVRFTRNGGNATLQVDNWPVNEHYPTGNTDNERFQMVKQK                   IPFKYNRPVEEWLQEKGRQLTIFNTQAQIAIGGKDKGRLFQGQLSGLYYDGLKVLNMA                   AENNPNIKINGSVRLVGEVPSILGTTQTTSMPPEMSTTVMETTTTMATTTTRKNRSTA                   SIQPTSDDLVSSAECSSDDEDFVECEPSTGGELVIPLLVEDPLATPPIATRAPSITLP                   PTFRPLLTIIETTKDSLSMTSEAGLPCLSDQGSDGCDDDGLVISGYGSGETFDSNLPP                   TDDEDFYTTFSLVTDKSLSTSIFEGGYKAHAPKWESKDFRPNKVSETSRTTTTSLSPE                   LIRFTASSSSGMVPKLPAGKMNNRDLKPQPDIVLLPLPTAYELDSTKLKSPLITSPMF                   RNVPTANPTEPGIRRVPGASEVIRESSSTTGMVVGIVAAAALCILILLYAMYKYRNRD                   EGSYQVDETRNYISNSAQSNGTLMKEKQQSSKSGHKKQKNKDREYYV                                         SEQ ID NO: 19   5335 bp                             NOV 3b,     CATACAGACAGATCCCAAATCTTCTGTTCAACTGGAAAGGTCTTTTCTCTGGAGTCCT             CG108175-02     GGGAGGCAAGTTATGGGCAGCACTGCTTCTGGCCGCACCATGAAGCCTGAGTCTGCTT         DNA Sequence     GCGCTCTGCCCAGGGCCCTGCTCTGTCTGAGCATTGGGCTTCTAGCTGCCCCCCTCCC                       CACAGCCTGCCGCTGCTAGGAGGTAGAACTTTAGGAGTGGTCCTTGGCCTGTTTCTAC                       CTGTCACCTGGCTCACCTCACCACTCACTCCTCCTCCATCACAGCACCCCGGCCCTCC                       CTGTCCCTGGCCTCCCTGGCTGGGGCATTTGGGGGTCCGCTGGGAGGAGTGCATCGCT                       GAAGGCTTCTTCCTACTCTCCTGCACCTTCTCCTCCTTGAGTCAAGGCCTCCGGATCC                       ACATGGATAGCTGAGATCTTTTCTTGGAGAAAGACGCTTTCCTCTTTACTCCAGTCCC                       TCACTTCCCCACCTGATTTTCCTCCTCTTCTGCTGGTCCTGTCTTTTTCTACTGCCTC                       TTTATTCAATTTCTTGCTTGTGTGCCCCTCTGGGACTCTCTTGTACACTTTCCTCCAT                       CTCCACTATCTCAGGATCTGTGTGTGTGCTGCCTTCCTCCTGTGTGCTTTCTGTCCCC                       CCATCTCTGTCTTGTCTTTCCCACTTCTATTGCCAAAGGGAGAGATCCTCTCCGGGCT                       GTTCCCTGGCCTGTCTGCTCCTCCGGGCTCTGTCCCAGCAGCGACA   ATG AGCTCCACA                   CTCCACTCGGTTTTCTTCACCCTGAAGGTCAGCATCCTGCTGGGGTCCCTGCTGGGGC                   TCTGCCTGGGCCTTGAGTTCATGGGCCTCCCCAACCAGTGGGCCCGCTACCTCCGCTG                   GGATGCCAGCACACGCAGTGACCTGAGTTTCCAGTTCAAGACCAACGTCTCTACGGGG                   CTGCTCCTCTACCTGGATGATGGCGGCGTCTGCGACTTCCTATGCCTCTCCCTGGTGG                   ATGGCCGCGTTCAGCTCCGCTTCAGCATGGACTGTGCCGAGACTGCCGTGCTGTCCAA                   CAAGCAGGTGAATCACAGCAGCTGGCACTTCCTCATGGTGAGCCGTGACCGCCTGCGC                   ACGGTGCTGATGCTTGATGGCCAGGGCCAGTCTGGGGAGCTGCAGCCCCAGCGGCCCT                   ACATGGATGTGGTCAGTGACTTGTTCCTTGGTGGAGTCCCTACTGACATACGACCTTC                   TGCCCTGACCCTTGATGGAGTTCAGGCCATGCCCGGCTTCAAGGGGTTAATTCTGGAT                   CTCAAGTATGGAAACTCGGAGCCTCGGCTTCTGGGGAGCCGGGGTGTCCAGATGGATG                   CCGAGGGACCCTGTGGTGAGCGTCCCTGTGAAAATGGTGGGATCTGCTTTCTCCTGGA                   CGGCCACCCCACCTGTGACTGTTCTACCACTGGCTATGGTGGCAAGCTCTGCTCAGAA                   GATGTCAGTCAAGATCCAGGCCTCTCCCACCTCATGATGAGTGAACAAGGTAGGTGCT                   TTGCTCGAGAGGAGAATCTGGCCACTTTCCGAGGCTCAGAGTATCTGTGCTACGACCT                   GTCTCAGAACCCGATCCAGAGCAGCAGTGATGAAATCACCCTCTCCTTTAAGACCTGG                   CAGCGTAACGGCCTCATCCTGCACACGGGCAAGTCGGCTGACTATGTCAACCTGGCTC                   TGAAGGATGGTGCGGTCTCCTTGGTCATTAACCTGGGGTCCGGGGCCTTTGAGGCCAT                   TGTGGAGCCAGTGAATGGAAAATTCAACGACAACGCCTGGCATGATGTCAAAGTGACA                   CGCAACCTCCGGCAGGTGACAATCTCTGTGGATGGCATTCTTACCACGACGGGCTACA                   CTCAAGAGGACTATACCATGCTGGGCTCGGACGACTTCTTCTATGTAGGAGGAAGCCC                   AAGTACCGCTGACTTGCCTGGCTCCCCTGTCAGCAACAACTTCATGGGCTGCCTTAAA                   GAGGTTGTTTATAAGAATAATGACATCCGTCTGGAGCTGTCTCGCCTGGCCCGGATTG                   CGGACACCAAGATGAAAATCTATGGCGAAGTTGTGTTTAAGTGTGAGAATGTGGCCAC                   ACTGGACCCCATCAACTTTGAGACCCCAGAGGCTTACATCAGCTTGCCCAAGTGGAAC                   ACTAAACGTATGGGCTCCATCTCCTTTGACTTCCGCACCACAGAGCCCAATGGCCTGA                   TCCTCTTCACTCATGGAAAGCCCCAAGAGAGGAAGGATGCTCGGAGCCAGAAGAATAC                   AAAAGTAGACTTCTTTGCCGTGGAACTCCTCGATGGCAACCTGTACTTGCTGCTTGAC                   ATGGGCTCTGGCACCATCAAAGTGAAAGCCACTCAGAAGAAAGCCAATGATGGGGAAT                   GGTACCATGTGGACATTCAGCGAGATGGCAGATCAGGTACTATATCAGTGAACAGCAG                   GCGCACGCCATTCACCGCCAGTGGGGAGAGCGAGATCCTGGACCTGGAAGGAGACATG                   TACCTGGGAGGGCTGCCGGAGAACCGTGCTGGCCTTATTCTCCCCACCGAGCTGTGGA                   CTGCCATGCTCAACTATGGCTACGTGGGCTGCATCCGCGACCTATTCATTGATGGGCG                   CAGCAAGAACATTCGACAGCTGGCAGAGATGCAGAATGCTGCGGGTGTCAAGTCCTCC                   TGTTCACGGATGAGTGCCAAGCAGTGTGACAGCTACCCCTGCAAGAATAATGCTGTGT                   GCAAGGACGGCTGGAACCGCTTCATCTGCGACTGCACCGGCACCGGATACTGGGGAAG                   AACCTGCGAAAGGGAGGCATCCATCCTGAGCTATGATGGTAGCATGTACATGAAGATC                   ATCATGCCCATGGTCATGCATACTGAGGCAGAGGATGTGTCCTTCCGCTTCATGTCCC                   AGCGAGCTTATGGGCTGCTGGTGGCTACGACCTCCAGGGACTCTGCCGACACCCTGCG                   TCTGGAGCTGGATGGGGGGCGTGTCAAGCTCATGGTTAACTTAGACTGTATCAGGATA                   AACTGTAACTCCAGCAAAGGACCAGAGACCTTGTATCCAGGGCAGAAGCTCAATGACA                   ACGAGTGGCACACCGTTCGGGTGGTGCGGAGAGGAAAAAGCCTTAAGTTAACCCTGGA                   TGATGATGTGGCTGAGGGTACAATGGTGGGAGACCATACCCGTTTGGAGTTCCACAAC                   ATTGAAACGGGAATCATGACTGAGAAACGCTACATCTCCGTTGTCCCCTCCAGCTTTA                   TTGGCCATCTGCAGAGCCTCATGTTTAATGGCCTTCTCTACATTGACTTGTGCAAAAA                   TGGTGACATTGATTATTGTGAGCTGAAGGCTCGTTTTGGACTGAGGAACATCATCGCT                   GACCCTGTCACCTTTAAGACCAAGAGCAGCTACCTGAGCCTTGCCACTCTTCAGGCTT                   ACACCTCCATGCACCTCTTCTTCCAGTTCAAGACCACCTCACCAGATGGCTTCATTCT                   CTTCAATAGTGGTGATGGCAATGACTTCATTGCAGTCGAGCTTGTCAAGGGGTATATA                   CACTACGTTTTTGACCTCGGAAACGGTCCCAATGTGATCAAAGGCAACAGTGACCGCC                   CCCTGAATGACAACCAGTGGCACAATGTCGTCATCACTCGGGACAATAGTAACACTCA                   TAGCCTGAAAGTGGACACCAAAGTGGTCACTCAGGTTATCAATGGTGCCAAAAATCTG                   GATTTGAAAGGTGATCTCTATATGGCTGGTCTGGCCCAAGGCATGTACAGCAACCTCC                   CAAAGCTCGTGGCCTCTCGAGATGGCTTTCAGGGCTGTCTAGCATCAGTGGACTTGAA                   TGGACGCCTGCCAGACCTCATCAATGATGCTCTTCATCGGAGCGGACAGATCGAGCGT                   GGCTGTGAAGGACCCAGTACCACCTGCCAGGAAGATTCATGTGCCAACCACGGGGTCT                   GCATGCAACAATGGGAGGGCTTCACCTGTGATTGTTCTATGACCTCTTATTCTGGAAA                   CCAGTGCAATGATCCTGGCGCTACGTACATCTTTGGGAAAAGTGGTGGGCTTATCCTC                   TACACCTGGCCAGCCAATGACAGGCCCAGCACGCGGTCTGACCGCCTTGCCGTGGGCT                   TCAGCACCACTGTGAAGGATGGCATCTTGGTCCGCATCGACAGTGCTCCAGGACTTGG                   TGACTTCCTCCAGCTTCACATAGAACAGGGGAAAATTGGAGTTGTCTTCAACATTGGC                   ACAGTTGACATCTCCATCAAAGAGGAGAGAACCCCTGTAAATGACGGCAAATACCATG                   TGGTACGCTTCACCAGGAACGGCGGCAACGCCACCCTGCAGGTGGACAACTGGCCAGT                   GAATGAACATTATCCTACAGGCAACACTGATAATGAACGCTTCCAAATGGTAAAACAG                   AAAATCCCCTTCAAATATAATCGGCCTGTAGAGGAGTGGCTGCAGGAAAAAGGCCGGC                   AGTTAACCATCTTCAACACTCAGGCGCAAATAGCCATTGGTGGAAAGGACAAAGGACG                   CCTCTTCCAAGGCCAACTCTCTGGGCTCTATTATGATGGTTTGAAGTACTGAAACATG                   GCGGCTGAGAACAACCCCAATATTAAAATCAATGGAAGTGTTCGGCTGGTTGGAGAAG                   TCCCATCAATTTTGGGAACAACACAGACGACCTCCATGCCACCAGAAATGTCTACTAC                   TGTCATGGAAACCACTACTACAATGGCGACTACCACAACCCGTAAGAATCGCTCTACA                   GCCAGCATTCAGCCAACATCAGATGATCTTGTTTCATCTGCTGAATGTTCAAGTGATG                   ATGAAGACTTTGTTGAATGTGAGCCGAGTACAGGTAGGTCAGCAAACCCCACGGAGCC                   GGGAATCAGACGGGTTCCGGGGGCCTCAGAGGTGATCCGGGAGTCGAGCAGCACAACA                   GGGATGGTCGTCGGCATTGTGGCTGCTGCCGCCCTCTGCATCTTGATCCTCCTGTACG                   CCATGTACAAGTACAGGAACAGGGACGAGGGGTCCTATCAAGTGGACGAGACGCGGAA                   CTACATCAGCAACTCCGCCCAGAGCAACGGCACGCTCATGAAGGAGAAGCAGCAGAGC                   TCGAAGAGCGGCCACAAGAAACAGAAAAACAAGGACAGGGAGTATTACGTG TAA   ACAT                       GCGAACACTGCTCACACGCGAGTTTTCACAGTTATTTCTATCCACGCCTATGAATCTT                       TGGACGGTGAGATCTCACAGATGTCAGAACTGCTGGAACTATGAAATGGGGTATATAA                       CCACGACTCTGGTGGGGAAAACCGTTTTTAAAGGACACACACACACACACAGCGATG                                           ORF Start: ATG at 743   ORF Stop: TAA at 5156                                         SEQ ID NO: 20   1471 aa   MW at 162660.3 Da                             NOV 3b,   MSSTLHSVFFTLKVSILLGSLLGLCLGLEFMGLPNQWARYLRWDASTRSDLSFQFKTN           CG108175-02   VSTGLLLYLDDGGVCDFLCLSLVDGRVQLRFSMDCAETAVLSNKQVNDSSWHFLMVSR       Protein Sequence   DRLRTVLMLDGEGQSGELQPQRPYMDVVSDLFLGGVPTDIRPSALTLDGVQAMPGFKG                   LILDLKYGNSEPRLLGSRGVQMDAEGPCGERPCENGGICFLLDGHPTCDCSTTGYGGK                   LCSEDVSQDPGLSHLMMSEQGRCFAREENVATFRGSEYLCYDLSQNPIQSSSDEITLS                   FKTWQRNGLILHTGKSADYVNLALKDGAVSLVINLGSGAFEAIVEPVNGKFNDNAWHD                   VKVTRNLRQVTISVDGILTTTGYTQEDYTMLGSDDFFYVGGSPSTADLRGSPVSNNFM                   GCLKEVVYKNNDIRLELSRLARIADTKMKIYGEVVFKCENVATLDPINFETPEAYISL                   PKWNTKRMGSISFDFRTTEPNGLILFTHGKPQERKDARSQKNTKVDFFAVELLDGNLY                   LLLDMGSGTIKVKATQKKANDGEWYHVDIQRDGRSGTISVNSRRTPFTASGESEILDL                   EGDMYLGGLPENRAGLILPTELWTAMLNYGYVGCIRDLFIDGRSKNIRQLAEMQNAAG                   VKSSCSRMSAKQCDSYPCKNNAVCKDGWNRFICDCTGTGYWGRTCEREASILSYDGSM                   YMKIIMPMVMHTEAEDVSFRFMSQRAYGLLVATTSRDSADTLRLELDGGRVKLMVNLD                   CIRINCNSSKGPETLYAGQKLNDNEWHTVRVVRRGKSLKLTVDDDVAEGTMVGDHTRL                   EFHNIETGIMTEKRYISVVPSSFIGHLQSLMFNGLLYIDLCKNGDIDYCELKARFGLR                   NIIADPVTFKTKSSYLSLATLQAYTSMHLFFQFKTTSPDGFILFNSGDGNDFIAVELV                   KGYIHYVFDLGNGPNVIKGNSDRPLNDNQWHNVVITRDNSNTHSLKVDTKVVTQVING                   AKNLDLKGDLYMAGLAQGMYSNLPKLVASRDGFQGCLASVDLNGRLPDLINDALHRSG                   QIERGCEGPSTTCQEDSCANQGVCMQQWEGFTCDCSMTSYSGNQCNDPGATYIFGKSG                   GLILYTWPANDRPSTRSDRLAVGFSTTVKDGILVRIDSAPGLGDFLQLHIEQGKIGVV                   FNIGTVDISIKEERTPVNDGKYHVVRFTRNGGNATLQVDNWPVNEHYPTGNTDNERFQ                   MVKQKIPFKYNRPVEEWLQEKGRQLTIFNTQAQIAIGGKDKGRLFQGQLSGLYYDGLK                   VLNMAAENNPNIKINGSVRLVGEVPSILGTTQTTSMPPEMSTTVMETTTTMATTTTRK                   NRSTASIQPTSDDLVSSAECSSDDEDFVECEPSTGRSANPTEPGIRRVPGASEVIRES                   SSTTGMVVGIVAAAALCILILLYAMYKYRNRDEGSYQVDETRNYISNSAQSNGTLMKE                   KQQSSKSGHKKQKNKDREYYV                                         SEQ ID NO: 21   5116 bp                             NOV 3c,     CATACAGACAGATCCCAAATCTTCTGTTCAACTGGAAAGGTCTTTTCTCTGCAGTCCT             CG108175-03     GGGAGGCAAGTTATGGGCAGCACTGCTTCTGGCCGCACCATGAAGCCTGAGTCTGCTT         DNA Sequence     GCGCTCTGCCCAGGGCCCTGCTCTGTCTGAGCATTGGGCTTCTAGCTGCCCCCCTCCC                       CACAGCCTGCCGCTGCTAGGAGGTAGAACTTTAGGAGTGGTCCTTGGCCTGTTTCTAC                       CTGTCACCTGGCTCACCTCACCACTCACTCCTCCTCCATCACAGCACCCCGGCCCTCC                       CTGTCCCTGGCCTCCCTGGCTGGGGCATTTGGGGGTCCCCTGGGAGGAGTGCATCGCT                       GAAGGCTTCTTCCTACTCTCCTGCACCTTCTCCTCCTTGAGTCAAGGCCTCCGGATCC                       ACATGGATAGCTGAGATCTTTTCTTGGAGAAAGACGCTTTCCTCTTTACTCCAGTCCC                       TCACTTCCCCACCTGATTTTCCTCCTCTTCTGCTGGTCCTGTCTTTTTCTACTGCCTC                       TTTATTCAATTTCTTGCTTGTGTGCCCCTCTGGGACTCTCTTGTACACTTTCCTCCAT                       CTCCACTATCTCAGGATCTGTGTGTGTGCTGCCTTCCTCCTGTGTGCTTTCTGTCCCC                       CCATCTCTGTCTTGTCTTTCCCACTTCTATTGCCAAAGGGAGAGATCCTCTCCGGGCT                       GTTCCCTGGCCTGTCTGCTCCTCCGGGCTCTGTCCCAGCAGCGACA   ATG AGCTCCACA                   CTCCACTCGGTTTTCTTCACCCTGAAGGTCAGCATCCTGCTGGGGTCCCTGCTGGGGC                   TCTGCCTGGGCCTTGAGTTCATGGGCCTCCCCAACCAGTGGGCCCGCTACCTCCGCTG                   GGATGCCAGCACACGCAGTGACCTGAGTTTCCAGTTCAAGACCAACGTCTCTACGGGG                   CTGCTCCTCTACCTGGATGATGGCGGCGTCTGCGACTTCCTATGCCTCTCCCTGGTGG                   ATGGCCGCGTTCAGCTCCGCTTCAGCATGGACTGTGCCGAGACTGCCGTGCTGTCCAA                   CAAGCAGGTGAATGACAGCAGCTGGCACTTCCTCATGGTGAGCCGTGACCGCCTGCGC                   ACGGTGCTGATCCTTGATGGCGAGGGCCAGTCTGGGGAGCTGCAGCCCCAGCGGCCCT                   ACATGGATGTGGTCAGTGACTTGTTCCTTGGTGGAGTCCCTACTGACATACGACCTTC                   TGCCCTGACCCTTGATGGAGTTCAGGCCATGCCCGGCTTCAAGGGGTTAATTCTGGAT                   CTCAAGTATGGAAACTCGGAGCCTCGGCTTCTGGGGAGCCGGGGTGTCCAGATGGATG                   CCGAGGGACCCTGTGGTGAGCGTCCCTGTGAAAATGGTGGGATCTGCTTTCTCCTGGA                   CGGCCACCCCACCTGTGACTGTTCTACCACTGGCTATGGTGGCAAGCTCTGCTCAGAA                   GATGTCAGTCAAGATCCAGGCCTCTCCCACCTCATGATGAGTGAACAAGGTAGGTGCT                   TTGCTCGAGAGGAGAATGTGGCCACTTTCCGAGGCTCAGAGTATCTGTGCTACGACCT                   GTCTCAGAACCCGATCCAGAGCAGCAGTGATGAAATCACCCTCTCCTTTAAGACCTGG                   CAGCGTAACGGCCTCATCCTGCACACGGGCAAGTCGGCTGACTATGTCAACCTGGCTC                   TGAAGGATGGTGCGGTCTCCTTGGTCATTAACCTGGGGTCCGGGGCCTTTGAGGCCAT                   TGTGGAGCCAGTGAATGGAAAATTCAACGACAACGCCTGGCATGATGTCAAAGTGACA                   CGCAACCTCCGGCAGGTGACAATCTCTGTGGATGGCATTCTTACCACGACGGGCTACA                   CTCAAGAGGACTATACCATGCTGGGCTCGGACGACTTCTTCTATGTAGGAGGAAGCCC                   AAGTACCGCTGACTTGCCTGGCTCCCCTGTCAGCAACAACTTCATGGGCTGCCTTAAA                   GAGGTTGTTTATAAGAATAATGACATCCGTCTGGAGCTGTCTCGCCTGGCCCGGATTG                   CGGACACCAAGATGAAAATCTATGGCGAAGTTGTGTTTAAGTGTGAGAATGTGGCCAC                   ACTGGACCCCATCAACTTTGAGACCCCAGAGGCTTACATCAGCTTGCCCAAGTGGAAC                   ACTAAACGTATGGGCTCCATCTCCTTTGACTTCCGCACCACAGAGCCCAATGGCCTGA                   TCCTCTTCACTCATGGAAAGCCCCAAGAGAGGAAGGATGCTCGGAGCCAGAAGAATAC                   AAAAGTAGACTTCTTTGCCGTGGAACTCCTCGATGGCAACCTGTACTTGCTGCTTGAC                   ATGGGCTCTGGCACCATCAAAGTGAAAGCCACTCAGAAGAAAGCCAATGATGGGGAAT                   GGTACCATGTGGACATTCAGCGAGATGGCAGATCAGGTACTATATCAGTGAACAGCAG                   GCGCACGCCATTCACCGCCAGTGGGGAGAGCGAGATCCTGGACCTGGAAGGAGACATG                   TACCTGGGAGGGCTGCCGGAGAACCGTGCTGGCCTTATTCTCCCCACCGAGCTGTGGA                   CTGCCATGCTCAACTATGGCTACGTGGGCTGCATCCGCGACCTATTCATTGATGGGCG                   CAGCAAGAACATTCGACAGCTGGCAGAGATGCAGAATGCTGCGGGTGTCAAGTCCTCC                   TGTTCACGGATGAGTGCCAAGCAGTGTGACAGCTACCCCTGCAAGAATAATGCTGTGT                   GCAAGGACGGCTGGAACCGCTTCATCTGCGACTGCACCGGCACCGGATACTGGGGAAG                   AACCTGCGAAAGGGAGGCATCCATCCTGAGCTATGATGGTAGCATGTACATGAAGATC                   ATCATGCCCATGGTCATGCATACTGAGGCAGAGGATGTGTCCTTCCGCTTCATGTCCC                   AGCGAGCTTATGGGCTGCTGGTGGCTACGACCTCCAGGGACTCTGCCGACACCCTGCG                   TCTGGAGCTGGATGGGGGGCGTGTCAAGCTCATGGTTAACTTAGACTGTATCAGGATA                   AACTGTAACTCCAGCAAAGGACCAGAGACCTTGTATGCAGGGCAGAAGCTCAATGACA                   ACGAGTGGCACACCGTTCGGCTGGTGCGGAGAGGAAAAAGCCTTAAGTTAACCGTGGA                   TGATGATGTGGCTGAGGGTACAATGGTGGGAGACCATACCCGTTTGGAGTTCCACAAC                   ATTGAAACGGGAATCATGACTGAGAAACGCTACATCTCCGTTGTCCCCTCCAGCTTTA                   TTGGCCATCTGCAGAGCCTCATGTTTAATGGCCTTCTCTACATTGACTTGTGCAAAAA                   TGGTGACATTGATTATTGTGAGCTGAAGGCTCGTTTTGGACTGAGGAACATCATCGCT                   GACCCTGTCACCTTTAAGACCAAGAGCAGCTACCTGAGCCTTGCCACTCTTCAGGCTT                   ACACCTCCATGCACCTCTTCTTCCAGTTCAAGACCACCTCACCAGATGGCTTCATTCT                   CTTCAATAGTGGTGATGGCAATGACTTCATTGCAGTCGAGCTTGTCAAGGGGTATATA                   CACTACGTTTTTGACCTCGGAAACGGTCCCAATGTGATCAAAGGCAACAGTGACCGCC                   CCCTGAATGACAACCAGTGGCACAATGTCGTCATCACTCGGGACAATAGTAACACTCA                   TAGCCTGAAAGTGGACACCAAAGTGGTCACTCAGGTTATCAATGGTGCCAAAAATCTG                   GATTTGAAAGGTGATCTCTATATGGCTGGTCTGGCCCAAGGCATGTACAGCAACCTCC                   CAAAGCTCGTGGGCTCTCGAGATGGCTTTCAGGGCTGTCTAGCATCAGTGGACTTGAA                   TGGACGCCTGCCAGACCTCATCAATGATGCTCTTCATCGGAGCGGACAGATCGAGCGT                   GGCTGTGAAGGACCCAGTACCACCTGCCAGGAAGATTCATGTGCCAACCAGGGGGTCT                   GCATGCAACAATGGGAGGGCTTCACCTGTGATTGTTCTATGACCTCTTATTCTGGAAA                   CCAGTGCAATGATCCTGGCGCTACGTACATCTTTGGGAAAAGTGGTGGGCTTATCCTC                   TACACCTGGCCAGCCAATGACAGGCCCAGCACGCGGTCTGACCGCCTTGCCGTGGGCT                   TCAGCACCACTGTGAAGGATGGCATCTTGGTCCGCATCGACAGTGCTCCAGGACTTGG                   TGACTTCCTCCAGCTTCACATAGAACAGGGGAAAATTGGAGTTGTCTTCAACATTGGC                   ACAGTTGACATCTCCATCAAAGAGGAGAGAACCCCTGTAAATGACGGCAAATACCATG                   TGGTACGCTTCACCAGGAACGGCGGCAACGCCACCCTGCAGGTGGACAACTGGCCAGT                   GAATGAACATTATCCTACAGGCAACACTGATAATGAACGCTTCCAAATGGTAAAACAG                   AAAATCCCCTTCAAATATAATCGGCCTGTAGAGGAGTGGCTGCAGGAAAAAGGCCGGC                   AGTTAACCATCTTCAACACTCAGGCGCAAATAGCCATTGGTGGAAAGGACAAAGGACG                   CCTCTTCCAAGGCCAACTCTCTGGGCTCTATTATGATGGTTTGAAAGTACTGAACATG                   GCGGCTGAGAACAACCCCAATATTAAAATCAATGGAAGTGTTCGGCTGGTTGGAGAAG                   TCCCATCAATTTTGGGAACAACACAGACGACCTCCATGCCACCAGAAATGTCTACTAC                   TGTCATGGAAACCACTACTACAATGGCGACTACCACAACCCGTAAGAATCGCTCTACA                   GCCAGCATTCAGCCAACATCAGATGATCTTGTTTCATCTGCTGAATGTTCAAGTGATG                   ATGAAGACTTTGTTGAATGTGAGCCGAGTACAGGTAGGTCAGCCAGAAGCTCTAATGC                   AGCTAGAATCACTCCGTGCCGCCCTTACATGGACATGGCGACTCACTTACACATTTAC                   TCCTATCATCTTCATCTCCTGTGTAGTTCACTCATAGATATGACCCTCCCCTTCCTGC                   ATCTTTCCTTCCCCATTCTCCCCCTTTCTTTAGCATTGTTAAAATTTATGTGCTGTCA                   TCCATCTCCC TAA   ATTAAAGAAAGCCTAAAATTTGTCAAAAAGACAAAAAAATATATA                       TATCTGAAAACT                                           ORF Start: ATG at 743   ORF Stop: TAA at 5057                                         SEQ ID NO: 22   1143 aa   MW at 159120.8 Da                             NOV3c,   MSSTLHSVFFTLKVSILLGSLLGLCLGLEFMGLPNQWARYLRWDASTRSDLSFQFKTN           CG108175-03   VSTGLLLYLDDGGVCDFLCLSLVDGRVQLRFSMDCAETAVLSNKQVNDSSWHFLMVSR       Protein Sequence   DRLRTVLMLDGEGQSGELQPQRPYMDVVSDLFLGGVPTDIRPSALTLDGVQAMPGFKG                   LILDLKYGNSEPRLLGSRGVQMDAEGPCGERPCENGGICFLLDGHPTCDCSTTGYGGK                   LCSEDVSQDPGLSHLMMSEQGRCFAREENVATFRGSEYLCYDLSQNPIQSSSDEITLS                   FKTWQRNGLILHTGKSADYVNLALKDGAVSLVINLGSGAFEAIVEPVNGKFNDNAWHD                   VKVTRNLRQVTISVDGILTTTGYTQEDYTMLGSDDFFYVGGSPSTADLPGSPVSNNFM                   GCLKEVVYKNNDIRLELSRLARIADTKMKIYGEVVFKCENVATLDPINFETPEAYISL                   PKWNTKRMGSISFDFRTTEPNGLILFTHGKPQERKDARSQKNTKVDFFAVELLDGNLY                   LLLDMGSGTIKVKATQKKANDGEWYHVDIQRDGRSGTISVNSRRTPFTASGESEILDL                   EGDMYLGGLPENRAGLILPTELWTAMLNYGYVGCIRDLFIDGRSKNIRQLAEMQNAAG                   VKSSCSRMSAKQCDSYPCKNNAVCKDGWNRFICDCTGTGYWGRTCEREASILSYDGSM                   YMKIIMPMVMHTEAEDVSFRFMSQRAYGLLVATTSRDSADTLRLELDGGRVKLMVNLD                   CIRINCNSSKGPETLYAGQKLNDNEWHTVRVVRRGKSLKLTVDDDVAEGTMVGDHTRL                   EFHNIETGIMTEKRYISVVPSSFIGHLQSLMFNGLLYIDLCKNGDIDYCELKARFGLR                   NIIADPVTFKTKSSYLSLATLQAYTSMHLFFQFKTTSPDGFILFNSGDGNDFIAVELV                   KGYIHYVFDLGNGPNVIKGNSDRPLNDNQWHNVVITRDNSNTHSLKVDTKVVTQVING                   AKNLDLKGDLYMAGLAQGMYSNLPKLVASRDGFQGCLASVDLNGRLPDLINDALHRSG                   QIERGCEGPSTTCQEDSCANQGVCMQQWEGFTCDCSMTSYSGNQCNDPGATYIFGKSG                   GLILYTWPANDRPSTRSDRLAVGFSTTVKDGILVRIDSAPGLGDFLQLHIEQGKIGVV                   FNIGTVDISIKEERTPVNDGKYHVVRFTRNGGNATLQVDNWPVNEHYPTGNTDNERFQ                   MVKQKIPFKYNRPVEEWLQEKGRQLTIFNTQAQIAIGGKDKGRLFQGQLSGLYYDGLK                   VLNMAAENNPNIKINGSVRLVGEVPSILGTTQTTSMPPEMSTTVMETTTTMATTTTRK                   NRSTASIQPTSDDLVSSAECSSDDEDFVECEPSTGRSARSSNAARITPCRPYMDMATH                   LHIYSYHLHLLCSSLIDMTLPFLHLSFPILPLSLALLKFMCCHPSP                                         SEQ ID NO: 23   5656 bp                             NOV3d,     CATACAGACAGATCCCAAATCTTCTGTTCAACTGGAAAGGTCTTTTCTCTGGAGTCCT             CG108175-04     GGGAGGCAAGTTATGGGCAGCACTGCTTCTGGCCGCACCATGAAGCCTGAGTCTGCTT         DNA Sequence     GCGCTCTGCCCAGGGCCCTGCTCTGTCTGAGCATTGGGCTTCTAGCTGCCCCCCTCCC                       CACAGCCTGCCGCTGCTAGGAGGTAGAACTTTAGGAGTGGTCCTTGGCCTGTTTCTAC                       CTGTCACCTGGCTCACCTCACCACTCACTCCTCCTCCATCACAGCACCCCGGCCCTCC                       CTGTCCCTGGCCTCCCTGGCTGGGGCATTTGGGGGTCCGCTGGGAGGAGTGCATCGCT                       GAACGCTTCTTCCTACTCTCCTGCACCTTCTCCTCCTTGAGTCAAGGCCTCCGGATCC                       ACATGGATAGCTGAGATCTTTTCTTGGAGAAAGACGCTTTCCTCTTTACTCCAGTCCC                       TCACTTCCCCACCTGATTTTCCTCCTCTTCTGCTGGTCCTGTCTTTTTCTACTGCCTC                       TTTATTCAATTTCTTGCTTGTGTGCCCCTCTGGGACTCTCTTGTACACTTTCCTCCAT                       CTCCACTATCTCAGGATCTGTGTGTGTGCTGCCTTCCTCCTGTGTGCTTTCTGTCCCC                       CCATCTCTGTCTTGTCTTTCCCACTTCTATTGCCAAAGGGAGAGATCCTCTCCGGGCT                       GTTCCCTGGCCTGTCTGCTCCTCCGGGCTCTGTCCCAGCAGCGACA   ATG AGCTCCACA                   CTCCACTCGGTTTTCTTCACCCTGAAGGTCAGCATCCTGCTGGGGTCCCTGCTGGGGC                   TCTGCCTGGGCCTTGAGTTCATGGGCCTCCCCAACCAGTGGGCCCGCTACCTCCGCTG                   GGATGCCAGCACACGCAGTGACCTGAGTTTCCAGTTCAAGACCAACGTCTCTACGGGG                   CTGCTCCTCTACCTGGATGATGGCGGCGTCTGCGACTTCCTATGCCTCTCCCTGGTGG                   ATGGCCGCGTTCAGCTCCGCTTCAGCATGGACTGTGCCGAGACTGCCGTGCTGTCCAA                   CAAGCAGGTGAATGACAGCAGCTGGCACTTCCTCATGGTGAGCCGTGACCGCCTGCGC                   ACGGTGCTGATGCTTGATGGCGAGGGCCAGTCTGGGGAGCTGCAGCCCCAGCGGCCCT                   ACATGGATGTGGTCAGTGACTTGTTCCTTGGTGGAGTCCCTACTGACATACGACCTTC                   TGCCCTGACCCTTGATGGAGTTCAGGCCATGCCCGGCTTCAAGGGGTTAATTCTGGAT                   CTCAAGTATGGAAACTCGGAGCCTCGGCTTCTGGGGAGCCGGGGTGTCCAGATGGATG                   CCGAGGGACCCTGTGGTGAGCGTCCCTGTGAAAATGGTGGGATCTGCTTTCTCCTGGA                   CGGCCACCCCACCTGTGACTGTTCTACCACTGGCTATGGTGGCAAGCTCTGCTCAGAA                   GATGTCAGTCAAGATCCAGGCCTCTCCCACCTCATGATGAGTGAACAAGGTAGGTGCT                   TTGCTCGAGAGGAGAATGTGGCCACTTTCCGAGGCTCAGAGTATCTGTGCTACGACCT                   GTCTCAGAACCCGATCCAGAGCAGCAGTGATGAAATCACCCTCTCCTTTAAGACCTGG                   CAGCGTAACGGCCTCATCCTGCACACGGGCAAGTCGGCTGACTATGTCAACCTGGCTC                   TGAAGGATGGTGCGGTCTCCTTGGTCATTAACCTGGGGTCCGGGGCCTTTGAGGCCAT                   TGTGGAGCCAGTGAATGGAAAATTCAACGACAACGCCTGGCATGATGTCAAAGTGACA                   CGCAACCTCCGGCAGGTGACAATCTCTGTGGATGGCATTCTTACCACGACGGGCTACA                   CTCAAGAGGACTATACCATGCTGGGCTCGGACGACTTCTTCTATGTAGGAGGAAGCCC                   AAGTACCGCTGACTTGCCTGGCTCCCCTGTCAGCAACAACTTCATGGGCTGCCTTAAA                   GAGGTTGTTTATAAGAATAATGACATCCGTCTGGAGCTGTCTCGCCTGGCCCGGATTG                   CGGACACCAAGATGAAAATCTATGGCGAAGTTGTGTTTAAGTGTGAGAATGTGGCCAC                   ACTGGACCCCATCAACTTTGAGACCCCAGAGGCTTACATCAGCTTGCCCAAGTGGAAC                   ACTAAACGTATGGGCTCCATCTCCTTTGACTTCCGCACCACAGAGCCCAATGGCCTGA                   TCCTCTTCACTCATGGAAAGCCCCAAGAGAGGAAGGATGCTCGGAGCCAGAAGAATAC                   AAAAGTAGACTTCTTTGCCGTGGAACTCCTCGATGGCAACCTGTACTTGCTGCTTGAC                   ATGGGCTCTGGCACCATCAAAGTGAAAGCCACTCAGAAGAAAGCCAATGATGGGGAAT                   GGTACCATGTGGACATTCAGCGAGATGGCAGATCAGGTACTATATCAGTGAACAGCAG                   GCGCACGCCATTCACCGCCAGTGGGGAGAGCCAGATCCTGGACCTGGAAGGAGACATG                   TACCTGGGAGGGCTGCCGGAGAACCGTGCTGGCCTTATTCTCCCCACCGAGCTGTGGA                   CTGCCATGCTCAACTATGGCTACGTGGGCTGCATCCGCGACCTATTCATTGATGGGCG                   CAGCAAGAACATTCGACAGCTGGCAGAGATGCAGAATGCTGCGGGTGTCAAGTCCTCC                   TGTTCACGGATGAGTGCCAAGCAGTGTGACAGCTACCCCTGCAAGAATAATGCTGTGT                   GCAAGGACGGCTGGAACCGCTTCATCTGCGACTGCACCGGCACCGGATACTGGGGAAG                   AACCTGCGAAAGGGAGGCATCCATCCTGAGCTATGATGGTAGCATGTACATGAAGATC                   ATCATGCCCATGGTCATGCATACTGAGGCAGAGGATGTGTCCTTCCGCTTCATGTCCC                   AGCGAGCTTATGGGCTGCTGGTGGCTACGACCTCCAGGGACTCTGCCGACACCCTGCG                   TCTGGAGCTGGATGGGGGGCGTGTCAAGCTCATGGTTAACTTAGACTGTATCAGGATA                   AACTGTAACTCCAGCAAAGGACCAGAGACCTTGTATGCAGGGCAGAACCTCAATGACA                   ACGAGTGGCACACCGTTCGGGTGGTGCGGAGAGGAAAAAGCCTTAAGTTAACCGTGGA                   TGATGATGTGGCTCAGGGTACAATGGTGGGAGACCATACCCGTTTGGAGTTCCACAAC                   ATTGAAACGGGAATCATGACTGAGAAACGCTACATCTCCGTTGTCCCCTCCAGCTTTA                   TTGGCCATCTGCAGAGCCTCATGTTTAATGCCCTTCTCTACATTGACTTGTGCAAAAA                   TGGTGACATTGATTATTGTGAGCTGAAGGCTCGTTTTGGACTGAGGAACATCATCGCT                   GACCCTGTCACCTTTAAGACCAAGAGCAGCTACCTGAGCCTTGCCACTCTTCAGGCTT                   ACACCTCCATGCACCTCTTCTTCCAGTTCAAGACCACCTCACCAGATGCCTTCATTCT                   CTTCAATAGTGGTGATGGCAATGACTTCATTGCAGTCGAGCTTGTCAAGGGGTATATA                   CACTACGTTTTTGACCTCGGAAACGGTCCCAATGTGATCAAAGGCAACAGTGACCGCC                   CCCTGAATGACAACCACTGGCACAATGTCGTCATCACTCGGGACAATAGTAACACTCA                   TAGCCTGAAAGTGGACACCAAAGTGGTCACTCAGGTTATCAATGGTGCCAAAAATCTG                   GATTTGAAAGGTGATCTCTATATGGCTGGTCTGGCCCAAGGCATGTACAGCAACCTCC                   CAAAGCTCGTGGCCTCTCGAGATGGCTTTCAGGGCTGTCTAGCATCAGTGGACTTGAA                   TGGACGCCTGCCAGACCTCATCAATGATGCTCTTCATCGGAGCGGACAGATCGAGCGT                   GGCTGTGAAGGACCCAGTACCACCTGCCAGGAAGATTCATGTGCCAACCAGGGGGTCT                   GCATGCAACAATGGGAGGGCTTCACCTGTGATTGTTCTATGACCTCTTATTCTGGAAA                   CCAGTGCAATGATCCTGGCGCTACGTACATCTTTGGGAAAAGTGGTGGGCTTATCCTC                   TACACCTGGCCAGCCAATGACAGGCCCAGCACGCGGTCTGACCGCCTTGCCGTGGGCT                   TCAGCACCACTGTGAAGGATGGCATCTTGGTCCGCATCGACAGTGCTCCAGGACTTGG                   TGACTTCCTCCAGCTTCACATAGAACAGGGGAAAATTGGAGTTGTCTTCAACATTGGC                   ACAGTTGACATCTCCATCAAAGAGGAGAGAACCCCTGTAAATGACGGCAAATACCATG                   TGGTACGCTTCACCAGGAACGGCGGCAACGCCACCCTGCAGGTGGACAACTGGCCAGT                   GAATGAACATTATCCTACAGGCAACACTGATAATGAACGCTTCCAAATGGTAAAACAG                   AAAATCCCCTTCAAATATAATCGGCCTGTAGAGGAGTGGCTGCAGGAAAAAGGCCGGC                   AGTTAACCATCTTCAACACTCAGGCGCAAATAGCCATTGGTGGAAAGGACAAAGGACG                   CCTCTTCCAAGGCCAACTCTCTGGGCTCTATTATGATGGTTTGAAAGTACTGAACATG                   GCGGCTGAGAACAACCCCAATATTAAAATCAATGGAAGTGTTCGGCTGGTTGGAGAAG                   TCCCATCAATTTTGGGAACAACACAGACGACCTCCATGCCACCAGAAATGTCTACTAC                   TGTCATGGAAACCACTACTACAATGGCGACTACCACAACCCGTAAGAATCGCTCTACA                   GCCAGCATTCAGCCAACATCAGATGATCTTGTTTCATCTGCTGAATGTTCAAGTGATG                   ATGAAGACTTTGTTGAATGTGAGCCGAGTACAGGTAGGTCAGATAAGAGTCTTTCCAC                   TTCAATCTTCGAAGGTGGCTACAAAGCACATGCGCCCAAGTGGGAATCCAAGGACTTT                   AGACCTAACAAAGTCTCCGAAACTAGTAGGACTACTACCACATCTTTATCCCCTGAGC                   TGATCCGCTTCACAGCTTCCTCCTCGTCTGGGATGGTGCCCAAATTGCCAGCTGGCAA                   AATGAATAACCGTGATCTCAAACCCCAGCCTGATATAGTCTTGCTTCCGTTGCCCACT                   GCCTATGAGCTAGACAGCACCAAACTGAAGAGCCCACTAATTACTTCCCCCATGTTCC                   GTAATGTGCCCACAGCAAACCCCACGGAGCCGGGAATCAGACGGGTTCCGGGGGCCTC                   AGAGGTGATCCGGGAGTCGAGCAGCACAACAGGGATGGTCGTCGGCATTGTGGCTGCT                   GCCGCCCTCTGCATCTTGATCCTCCTGTACGCCATGTACAAGTACAGGAACAGGGACG                   AGGGGTCCTATCAAGTGGACGAGACGCGGAACTACATCAGCAACTCCGCCCAGAGCAA                   CGGCACGCTCATGAAGGAGAAGCAGCAGAGCTCGAAGAGCGGCCACAAGAAACAGAAA                   AACAAGGACAGGGACTATTACGTG TAA   ACATGCGAACACTGCTCACACGCGAGTTTTC                       ACAGTTATTTCTATCCACGCCTATGAATCTTTGGACCGTGAGATCTCACAGATGTCAG                       AACTGCTGGAACTATGAAATGGGGTATATAACCACGACTCTGGTGGGGAAAACCGTTT                       TTAAAGGACACACACACACACACAGCGATG                                           ORF Start: ATG at 743   ORF Stop: TAA at 5477                                         SEQ ID NO: 24   1578 aa   MW at 174421.6 Da                             NOV3d,   MSSTLHSVFFTLKVSILLGSLLGLCLGLEFMGLPNQWARYLRWDASTRSDLSFQFKTN           CG108175-04   VSTGLLLYLDDGGVCDFLCLSLVDGRVQLRFSMDCAETAVLSNKQVNDSSWHFLMVSR       Protein Sequence   DRLRTVLMLDGEGQSGELQPQRPYMDVVSDLFLGGVPTDIRPSALTLDGVQAMPGFKG                   LILDLKYGNSEPRLLGSRGVQMDAEGPCGERPCENGGICFLLDGHPTCDCSTTGYGGK                   LCSEDVSQDPGLSHLMMSEQGRCFAREENVATFRGSEYLCYDLSQNPIQSSSDEITLS                   FKTWQRNGLILHTGKSADYVNLALKDGAVSLVINLGSGAFEAIVEPVNGKFNDNAWHD                   VKVTRNLRQVTISVDGILTTTGYTQEDYTMLGSDDFFYVGGSPSTADLPGSPVSNNFM                   GCLKEVVYKNNDIRLELSRLARIADTKMKIYGEVVFKCENVATLDPINFETPEAYISL                   PKWNTKRMGSISFDFRTTEPNGLILFTHGKPQERKDARSQKNTKVDFFAVELLDGNLY                   LLLDMGSGTIKVKATQKKANDGEWYHVDIQRDGRSGTISVNSRRTPFTASGESEILDL                   EGDMYLGGLPENRAGLILPTELWTAMLNYGYVGCIRDLFIDGRSKNIRQLAEMQNAAG                   VKSSCSRMSAKQCDSYPCKNNAVCKDGWNRFICDCTGTGYWGRTCEREASILSYDGSM                   YMKIIMPMVMHTEAEDVSFRFMSQRAYGLLVATTSRDSADTLRLELDGGRVKLMVNLD                   CIRINCNSSKGPETLYAGQKLNDNEWHTVRVVRRGKSLKLTVDDDVAEGTMVGDHTRL                   EFHNIETGIMTEKRYISVVPSSFIGHLQSLMFNGLLYIDLCKNGDIDYCELKARFGLR                   NIIADPVTFKTKSSYLSLATLQAYTSMHLFFQFKTTSPDGFILFNSGDGNDFIAVELV                   KGYIHYVFDLGNGPNVIKGNSDRPLNDNQWHNVVITRDNSNTHSLKVDTKVVTQVING                   AKNLDLKGDLYMAGLAQGMYSNLPKLVASRDGFQGCLASVDLNGRLPDLINDALHRSG                   QIERGCEGPSTTCQEDSCANQGVCMQQWEGFTCDCSMTSYSGNQCNDPGATYIFGKSG                   GLILYTWPANDRPSTRSDRLAVGFSTTVKDGILVRIDSAPGLGDFLQLHIEQGKIGVV                   FNIGIVDISIKEERTPVNDGKYHVVRFTRNGGNATLQVDNWPVNEHYPTGNTDNERFQ                   MVKQKIPFKYNRPVEEWLQEKGRQLTIFNTQAQIAIGGKDKGRLFQGQLSGLYYDGLK                   VLNMAAENNPNIKINGSVRLVGEVPSILGTTQTTSMPPEMSTTVMETTTTMATTTTRK                   NRSTASIQPTSDDLVSSAECSSDDEDFVECEPSTGRSDKSLSTSIFEGGYKAHAPKWE                   SKDFRPNKVSETSRTTTTSLSPELIRFTASSSSGMVPKLPAGKMNNRDLKPQPDIVLL                   PLPTAYELDSTKLKSPLITSPMFRNVPTANPTEPGIRRVPGASEVIRESSSTTGMVVG                   IVAAAALCILILLYAMYKYRNRDEGSYQVDETRNYISNSAQSNGTLMKEKQQSSKSGH                   KKQKNKDREYYV                                         SEQ ID NO: 25   4999 bp                             NOV3e,     CATACAGACAGATCCCAAATCTTCTGTTCAACTGGAAAGGTCTTTTCTCTGGAGTCCT             CG108175-05     GGGAGGCAAGTTATGGGCAGCACTGCTTCTGGCCGCACCATGAAGCCTGAGTCTGCTT         DNA Sequence     GCGCTCTGCCCAGGGCCCTGCTCTGTCTGAGCATTGGGCTTCTAGCTGCCCCCCTCCC                       CACAGCCTGCCGCTGCTAGGAGGTAGAACTTTAGGAGTGGTCCTTGGCCTGTTTCTAC                       CTGTCACCTGGCTCACCTCACCACTCACTCCTCCTCCATCACAGCACCCCGGCCCTCC                       CTGTCCCTGGCCTCCCTGGCTGGGGCATTTGGGGGTCCGCTGGGAGGAGTGCATCGCT                       GAAGGCTTCTTCCTACTCTCCTGCACCTTCTCCTCCTTGAGTCAAGGCCTCCGGATCC                       ACATGGATAGCTGAGATCTTTTCTTGGAGAAAGACGCTTTCCTCTTTACTCCAGTCCC                       TCACTTCCCCACCTGATTTTCCTCCTCTTCTGCTGGTCCTGTCTTTTTCTACTGCCTC                       TTTATTCAATTTCTTGCTTGTGTGCCCCTCTGGGACTCTCTTGTACACTTTCCTCCAT                       CTCCACTATCTCAGGATCTGTGTGTGTGCTGCCTTCCTCCTGTGTGCTTTCTGTCCCC                       CCATCTCTGTCTTGTCTTTCCCACTTCTATTGCCAAAGGGAGAGATCCTCTCCGGGCT                       GTTCCCTGGCCTGTCTGCTCCTCCGGGCTCTGTCCCAGCAGCGACA   ATG AGCTCCACA                   CTCCACTCGGTTTTCTTCACCCTGAAGGTCAGCATCCTGCTGGGGTCCCTGCTGGGGC                   TCTGCCTGGGCCTTGAGTTCATGGGCCTCCCCAACCAGTGGGCCCGCTACCTCCGCTG                   GGATGCCAGCACACGCAGTGACCTGAGTTTCCAGTTCAAGACCAACGTCTCTACGGGG                   CTGCTCCTCTACCTGGATGATGGCGGCGTCTGCGACTTCCTATGCCTCTCCCTGGTGG                   ATGGCCGCGTTCAGCTCCGCTTCAGCATGGACTGTGCCGAGACTGCCGTGCTGTCCAA                   CAAGCAGGTGAATGACAGCAGCTGGCACTTCCTCATGGTGAGCCGTGACCGCCTGCGC                   ACGGTGCTGATGCTTGATGGCGAGCGCCAGTCTGGGGAGCTGCAGCCCCAGCGGCCCT                   ACATGGATGTGGTCAGTGACTTGTTCCTTGGTGGAGTCCCTACTGACATACGACCTTC                   TGCCCTGACCCTTGATGGAGTTCAGGCCATGCCCGGCTTCAAGGGGTTAATTCTGGAT                   CTCAAGTATGGAAACTCGGAGCCTCGGCTTCTGGGGAGCCGGGGTGTCCAGATCGATG                   CCGAGGGACCCTGTGGTGAGCGTCCCTGTGAAAATGGTGGGATCTGCTTTCTCCTGGA                   CGGCCACCCCACCTGTGACTGTTCTACCACTGGCTATGGTGGCAAGCTCTGCTCAGAA                   GATGTCAGTCAAGATCCAGGCCTCTCCCACCTCATGATGAGTGAACAAGGTAGGTGCT                   TTGCTCGAGAGGAGAATGTGGCCACTTTCCGAGGCTCACAGTATCTGTGCTACGACCT                   GTCTCAGAACCCGATCCAGAGCAGCAGTGATGAAATCACCCTCTCCTTTAAGACCTGG                   CAGCGTAACGGCCTCATCCTGCACACGGGCAAGTCGGCTGACTATGTCAACCTGGCTC                   TGAAGGATGGTGCGGTCTCCTTGGTCATTAACCTGGGGTCCGGGGCCTTTGAGGCCAT                   TGTGGAGCCAGTGAATGGAAAATTCAACGACAACGCCTGGCATGATGTCAAAGTGACA                   CGCAACCTCCGGCAGGTGACAATCTCTGTGGATGGCATTCTTACCACGACGGGCTACA                   CTCAAGAGGACTATACCATGCTGGGCTCGGACGACTTCTTCTATGTAGGAGGAAGCCC                   AAGTACCGCTGACTTGCCTGGCTCCCCTGTCAGCAACAACTTCATGGGCTGCCTTAAA                   GAGGTTGTTTATAAGAATAATGACATCCGTCTGGAGCTGTCTCGCCTGGCCCGGATTG                   CGGACACCAAGATGAAAATCTATGGCGAAGTTGTGTTTAAGTGTGAGAATGTGGCCAC                   ACTGGACCCCATCAACTTTGAGACCCCACAGGCTTACATCAGCTTGCCCAAGTGGAAC                   ACTAAACGTATGGGCTCCATCTCCTTTGACTTCCGCACCACACAGCCCAATGGCCTGA                   TCCTCTTCACTCATGGAAAGCCCCAAGAGAGGAAGGATGCTCGGAGCCAGAAGAATAC                   AAAAGTAGACTTCTTTGCCGTGGAACTCCTCGATGGCAACCTGTACTTGCTGCTTGAC                   ATGGGCTCTGGCACCATCAAAGTGAAAGCCACTCAGAAGAAAGCCAATGATGGGGAAT                   GGTACCATGTGGACATTCAGCGAGATGGCAGATCAGGTACTATATCAGTGAACAGCAG                   GCGCACGCCATTCACCGCCAGTGGGGAGAGCGAGATCCTGGACCTGGAAGGAGACATG                   TACCTGGGAGGGCTGCCGGAGAACCGTGCTGGCCTTATTCTCCCCACCGAGCTGTGGA                   CTGCCATGCTCAACTATGGCTACGTGGGCTGCATCCGCGACCTATTCATTGATGGGCG                   CAGCAAGAACATTCGACAGCTGGCAGAGATGCAGAATGCTGCGGGTGTCAAGTCCTCC                   TGTTCACGGATGAGTGCCAAGCAGTGTGACAGCTACCCCTGCAAGAATAATGCTGTGT                   GCAAGGACGGCTGGAACCGCTTCATCTGCGACTGCACCGGCACCGGATACTGGGGAAG                   AACCTGCGAAAGCGAGGCATCCATCCTGAGCTATGATGGTAGCATGTACATGAAGATC                   ATCATGCCCATGGTCATGCATACTGAGGCAGAGGATGTGTCCTTCCGCTTCATGTCCC                   AGCGAGCTTATGGGCTGCTGGTGGCTACGACCTCCAGGGACTCTGCCGACACCCTGCG                   TCTGGAGCTGGATGGGGGGCGTCTCAAGCTCATGGTTAACTTAGACTGTATCAGGATA                   AACTGTAACTCCAGCAAAGGACCAGAGACCTTGTATGCAGGGCAGAAGCTCAATGACA                   ACGAGTGGCACACCGTTCGGGTGGTGCGGAGAGGAAAAAGCCTTAAGTTAACCGTGGA                   TGATGATGTGGCTGAGGGTACAATGGTGGGAGACCATACCCGTTTGGAGTTCCACAAC                   ATTGAAACGGGAATCATGACTGAGAAACGCTACATCTCCGTTGTCCCCTCCAGCTTTA                   TTGGCCATCTGCAGAGCCTCATGTTTAATGGCCTTCTCTACATTGACTTGTGCAAAAA                   TGGTGACATTGATTATTGTGAGCTGAAGGCTCGTTTTGGACTGAGGAACATCATCGCT                   GACCCTGTCACCTTTAAGACCAAGAGCAGCTACCTGAGCCTTGCCACTCTTCAGGCTT                   ACACCTCCATGCACCTCTTCTTCCAGTTCAAGACCACCTCACCAGATGGCTTCATTCT                   CTTCAATAGTGGTGATGGCAATGACTTCATTGCAGTCGAGCTTGTCAAGGGGTATATA                   CACTACGTTTTTGACCTCGGAAACGGTCCCAATGTGATCAAAGGCAACAGTGACCGCC                   CCCTGAATGACAACCAGTGGCACAATGTCGTCATCACTCGGGACAATAGTAACACTCA                   TAGCCTGAAAGTGGACACCAAAGTGGTCACTCAGGTTATCAATGGTGCCAAAAATCTG                   GATTTGAAAGGTGATCTCTATATGGCTGGTCTGGCCCAAGGCATGTACAGCAACCTCC                   CAAAGCTCGTGGCCTCTCGAGATGGCTTTCAGGGCTGTCTAGCATCAGTGGACTTGAA                   TGGACGCCTGCCAGACCTCATCAATGATGCTCTTCATCGGAGCGGACAGATCGAGCGT                   GGCTGTGAAGGACCCAGTACCACCTGCCAGGAAGATTCATGTGCCAACCAGGGGGTCT                   GCATGCAACAATGGGAGGGCTTCACCTGTGATTGTTCTATGACCTCTTATTCTGGAAA                   CCAGTGCAATGATCCTGCCGCTACGTACATCTTTGGGAAAAGTGGTGGGCTTATCCTC                   TACACCTGGCCAGCCAATCACAGGCCCAGCACGCGGTCTGACCGCCTTGCCGTGGGCT                   TCAGCACCACTGTGAAGGATGGCATCTTGGTCCGCATCGACAGTGCTCCAGGACTTGG                   TGACTTCCTCCAGCTTCACATAGAACAGGGGAAAATTGGAGTTGTCTTCAACATTGGC                   ACAGTTGACATCTCCATCAAAGAGGAGAGAACCCCTGTAAATGACGGCAAATACCATG                   TGGTACGCTTCACCAGGAACGGCGGCAACGCCACCCTGCAGGTGGACAACTGGCCAGT                   GAATGAACATTATCCTACAGGCAACACTGATAATGAACGCTTCCAAATGGTAAAACAG                   AAAATCCCCTTCAAATATAATCGGCCTGTAGAGGAGTGGCTGCAGGAAAAAGGCCGGC                   AGTTAACCATCTTCAACACTCAGGCGCAAATAGCCATTGGTGGAAAGGACAAAGGACG                   CCTCTTCCAAGGCCAACTCTCTGGGCTCTATTATGATGGTTTGAAAGTACTGAACATG                   GCGGCTGAGAACAACCCCAATATTAAAATCAATGGAAGTGTTCGGCTGGTTGGAGAAG                   TCCCATCAATTTTGGGAACAACACAGACGACCTCCATGCCACCAGAAATGTCTACTAC                   TGTCATGGAAACCACTACTACAATGGCGACTACCACAACCCGTAAGAATCGCTCTACA                   GCCAGCATTCAGCCAACATCAGATGATCTTGTTTCATCTGCTGAATGTTCAAGTGATG                   ATGAAGACTTTGTTGAATGTGAGCCGAGTACAGGTAGGTCAGTAAGAAATGACAACAA                   AAAAAGCAAGTTACAAGAATGTGGCAATTCTATTTGTCCAAGAGCATTCTTACACAAC                   TTTCTTTTG TAA   ATTTTTCTTTCATGCCAAAAAACATGCGGGCAATTTGTTGATGTAA                       GTTGACTATAA                                           ORF Start: ATG at 743   ORF Stop: TAA at 4940                                         SEQ ID NO: 26   1399 aa   MW at 154757.5 Da                             NOV3e,   MSSTLHSVFFTLKVSILLGSLLGLCLGLEFMGLPNQWARYLRWDASTRSDLSFQFKTN           CG108175-05   VSTGLLLYLDDGGVCDFLCLSLVDGRVQLRFSMDCAETAVLSNKQVNDSSWHFLMVSR       Protein Sequence   DRLRTVLMLDGEGQSGELQPQRPYMDVVSDLFLGGVPTDIRPSALTLDGVQAMPGFKG                   LILDLKYGNSEPRLLCSRGVQMDAEGPCGERPCENGGICFLLDGHPTCDCSTTGYGGK                   LCSEDVSQDPGLSHLMMSEQGRCFAREENVATFRGSEYLCYDLSQNPIQSSSDEITLS                   FKTWQRNGLILHTGKSADYVNLALKDGAVSLVINLGSGAFEAIVEPVNGKENDNAWHD                   VKVTRNLRQVTISVDGILTTTGYTQEDYTMLGSDDFFYVGGSPSTADLPGSPVSNNFM                   GCLKEVVYKNNDIRLELSRLARIADTKMKIYGEVVFKCENVATLDPINFETPEAYISL                   PKWNTKRMGSISFDFRTTEPNGLILFTHGKPQERKDARSQKNTKVDFFAVELLDGNLY                   LLLDMGSGTIKVKATQKKANDGEWYHVDIQRDGRSGTISVNSRRTPFTASGESEILDL                   EGDMYLGGLPENRAGLILPTELWTAMLNYGYVGCIRDLFIDGRSKJIRQLAEMQNAAG                   VKSSCSRMSAKQCDSYPCKNNAVCKDGWNRFICDCTGTGYWGRTCEREASILSYDGSM                   YMKIIMPMVMHTEAEDVSFRFMSQRAYGLLVATTSRDSADTLRLELDGGRVKLMVNLD                   CIRINCNSSKGPETLYAGQKLNDNEWHTVRVVRRGKSLKLTVDDDVAEGTMVGDHTRL                   EFHNIETGIMTEKRYISVVPSSFIGHLQSLMFNGLLYIDLCKNGDIDYCELKARFGLR                   NIIADPVTFKTKSSYLSLATLQAYTSMHLFFQFKTTSPDGFILFNSGDGNDFIAVELV                   KGYIHYVFDLGNGPNVIKGNSDRPLNDNQWHNVVTTRDNSNTHSLKVDTKVVTQVING                   AKNLDLKGDLYMAGLAQGMYSNLPKLVASRDGFQGCLASVDLNGRLPDLINDALHRSG                   QIERGCEGPSTTCQEDSCANQGVCMQQWEGFTCDCSMTSYSGNQCNDPGATYIFGKSG                   GLILYTWPANDRPSTRSDRLAVGFSTTVKDGILVRIDSAPGLGDFLQLHIEQGKIGVV                   FNIGTVDISIKEERTPVNDGKYHVVRFTRNGGNATLQVDNWPVNEHYPTGNTDNERFQ                   MVKQKIPFKYNRPVEEWLQEKGRQLTIFNTQAQIAIGGKDKGRLFQGQLSGLYYDGLK                   VLNMAAENNPNIKINGSVRLVGEVPSILGTTQTTSMPPEMSTTVMETTTTMATTTTRK                   NRSTASIQPTSDDLVSSAECSSDDEDFVECEPSTGRSVRNDNKKSKLQECGNSICPRA                   FLHNFLL                  
 
     [0349] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 3B.  
               TABLE 3B                          Comparison of NOV3a against NOV3b through NOV3e.                                         Identities/               NOV3a Residues/   Similarities for           Protein Sequence   Match Residues   the Matched Region                       NOV3b   1 . . . 1364   1315/1374 (95%)               1 . . . 1369   1315/1374 (95%)           NOV3c   1 . . . 1364   1315/1374 (95%)               1 . . . 1369   1315/1374 (95%)           NOV3d   1 . . . 1364   1315/1374 (95%)               1 . . . 1369   1315/1374 (95%)           NOV3e   1 . . . 1364   1315/1374 (95%)               1 . . . 1369   1315/1374 (95%)                      
 
     [0350] Further analysis of the NOV3a protein yielded the following properties shown in Table 3C.  
               TABLE 3C                       Protein Sequence Properties NOV3a                                        PSort   0.4600 probability located in plasma membrane;       analysis:   0.1000 probability located in endoplasmic reticulum           (membrane); 0.1000 probability located in endoplasmic           reticulum (lumen); 0.1000 probability located in outside       SignalP   Cleavage site between residues 28 and 29       analysis:                  
 
     [0351] 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                       Residues   Identities/       Geneseq   Protein/Organism/Length   Match   Similarities for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value               AAE17600   Human extracellular messenger    1 . . . 1363   1328/1373 (96%)   0.0           (XMES)-2 protein -  Homo sapiens,      1 . . . 1338   1328/1373 (96%)           1438 aa. [WO200194587-A2,           13 DEC. 2001]       AAU28190   Novel human secretory protein, Seq ID    16 . . . 1671   1093/1724 (63%)   0.0           No 359-  Homo sapiens , 1712 aa.    17 . . . 1712   1324/1724 (76%)           [WO200166689A-), 13 SEP. 2001]       AAU14241   Human novel protein #112 -  Homo     368 . . . 1363    990/996 (99%)   0.0           sapiens, 1091 aa. [WO200155437-A2,    1 . . . 991    990/996 (99%)           02 AUG. 2001]       AAU14240   Human novel protein #111 -  Homo     368 . . . 1363    960/996 (96%)   0.0             sapiens , 1061 aa. [WO200155437-A2,    1 . . . 961    960/996 (96%)           02 AUG. 2001]       AAM79855   Human protein SEQ ID NO 3501 -    16 . . . 1365    952/1392 (68%)   0.0             Homo sapiens , 1522 aa.    65 . . . 1419   1108/1392 (79%)           [WO200157190-A2, 09 AUG. 2001]                  
 
     [0352] 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                                         NOV3a               Protein       Residues/   Identities/       Accession       Match   Similarities for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               A48216   neurexin III-alpha secreted type 1   1 . . . 1364   1333/1374 (97%)   0.0           precursor - rat, 1438 aa.   1 . . . 1369   1346/1374 (97%)       B48218   neurexin III-alpha membrane-bound   1 . . . 1364   1333/1374 (97%)   0.0           type 3 precursor - rat, 1471 aa.   1 . . . 1369   1346/1374 (97%)       I48216   neurexin III-alpha membrane-bound   1 . . . 1364   1333/1374 (97%)   0.0           type I precursor - rat, 1578 aa.   1 . . . 1369   1346/1374 (97%)       Q9Y4C0   Neurexin 3-alpha precursor   1 . . . 1367   1328/1373 (96%)   0.0           (Neurexin III-alpha) -  Homo sapiens     1 . . . 1338   1329/1373 (96%)           (Human), 1541 aa.       Q07310   Neurexin 3-alpha precursor   1 . . . 1364   1318/1374 (95%)   0.0           (Neurexin III-alpha) -  Rattus     1 . . . 1369   1334/1374 (96%)             norvegicus  (Rat), 1578 aa.                  
 
     [0353] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3F.  
               TABLE 3F                          Domain Analysis of NOV3a                                     Identities/           Pfam   NOV3a   Similarities   Expect       Domain   Match Region   for the Matched Region   Value               laminin_G     55 . . . 174    37/132 (24%)   1.5e−11                80/152 (53%)       EGF    202 . . . 234    15/47 (32%)   0.0033                22/47 (47%)       laminin_G    281 . . . 410    41/161 (25%)   2.5e−22                92/161 (57%)       laminin_G    469 . . . 616    53/169 (31%)   2.5e−30               112/169 (66%)       EGF    641 . . . 673    10/47 (21%)   0.016                26/47 (55%)       laminin_G    730 . . . 840    31/137 (23%)   2.1e−05                86/137 (63%)       laminin_G    893 . . . 1024    49/164 (30%)   1.2e−18               104/164 (63%)       EGF   1052 . . . 1084    13/47 (28%)   0.0034                25/47 (53%)       laminin_G   1121 . . . 1196    26/89 (29%)     1e−06                52/89 (58%)                  
 
     Example 4  
     [0354] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.  
               TABLE 4A                       NOV4 Sequence Analysis                                                    SEQ ID NO: 27   2681 bp                             NOV4a,     CTGGG   ATG TACCTTTCCATCTGTTGCTGCTTTCTTCTATGGGCCCCTGCCCTCACTCT           CG108624-01   CAAGAACCTCAACTACTCCGTGCCGGAGGAGCAAGGGGCCGGCACGGTGATCGGGAAC       DNA Sequence   ATCGGCAGGGATGCTCGACTGCAGCCTGGGCTTCCGCCTGCAGAGCGCGGCGCCGGAG                   GGCGCAGCAAGTCGGGTAGCTACCGGGTGCTGGAGAACTCCGCACCGCACCTGCTGGA                   CGTGGACGCAGACAGCGGGCTCCTCTACACCAAGCAGCGCATCGACCGCGAGTCCCTG                   TGCCGCCACAATGCCAAGTGCCAGCTGTCCCTCGAGGTGTTCGCCAACGACAAGGAGA                   TCTGCATGATCAAGGTAGAGATCCAGGACATCAACGACAACGCGCCCTCCTTCTCCTC                   GGACCAGATCGAAATGGACATCTCGGAGAACGCTGCTCCGGGCACCCGCTTCCCCCTC                   ACCAGCGCACATGACCCCGACGCCGGCGAGAATGGGCTCCGCACCTACCTGCTCACGC                   GCGACGATCACGGCCTCTTTGGACTGGACGTTAAGTCCCGCGGCGACGGCACCAAGTT                   CCCAGAACTGGTCATCCAGAAGGCTCTGGACCGCGAGCAACAGAATCACCATACGCTC                   GTGCTGACTGCCCTGGACGGTGGCGAGCCTCCACGTTCCGCCACCGTACAGATCAACG                   TGAAGGTGATTGACTCCAACGACAACAGCCCGGTCTTCGAGGCGCCATCCTACTTGGT                   GGAACTGCCCGAGAACGCTCCGCTGGGTACAGTGGTCATCGATCTGAACGCCACCGAC                   GCCGATGAAGGTCCCAATGGTGAAGTGCTCTACTCTTTCAGCAGCTACGTGCCTGACC                   GCGTGCGGGAGCTCTTCTCCATCGACCCCAAGACCGGCCTAATCCGTGTGAAGGGCAA                   TCTGGACTATGAGGAAAACGGGATGCTGGAGATTGACGTGCAGGCCCGAGACCTGGGG                   CCTAACCCTATCCCAGCCCACTGCAAAGTCACGGTCAAGCTCATCGACCGCAACGACA                   ATGCGCCGTCCATCGGTTTCGTCTCCGTGCGCCAGGGGGCGCTGAGCGAGGCCGCCCC                   TCCCGGCACCGTCATCGCCCTGGTGCGGGTCACTGACCGGGACTCTGGCAAGAACGGA                   CAGCTGCAGTGTCGGGTCCTAGGCGGAGGAGGGACGGGCGGCGGCGGGGGCCTGGGCG                   GGCCCGGGGGTTCCGTCCCCTTCAAGCTTGAGGAGAACTACGACAACTTCTACACGGT                   GGTGACTGACCGCCCGCTGGACCGCGAGACACAAGACGAGTACAACGTGACCATCGTG                   GCGCGGGACGGGGGCTCTCCTCCCCTCAACTCCACCAAGTCGTTCGCGATCAAGATTC                   TAGACGAGAACGACAACCCGCCTCGGTTCACCAAAGGGCTCTACGTGCTTCAGGTGCA                   CGAGAACAACATCCCGGGAGAGTACCTGGGCTCTGTGCTCGCCCAGGATCCCGACCTG                   GGCCAGAACGGCACCGTATCCTACTCTATCCTGCCCTCGCACATCGGCGACGTGTCTA                   TCTACACCTATGTGTCTGTGAATCCCACGAACGGGGCCATCTACGCCCTGCGCTCCTT                   TAACTTCGAGCAGACCAAGGCTTTTGAGTTCAAGGTGCTTGCTAAGGACTCGGGGGCG                   CCCGCGCACTTGGAGAGCAACGCCACGGTGAGGGTGACAGTGCTAGACGTGAATGACA                   ACGCGCCAGTGATCGTGCTCCCCACGCTGCAGAACGACACCGCGGAGCTGCAGGTGCC                   GCGCAACGCTGGCCTGGGCTATCTGGTGAGCACTGTGCGCGCCCTAGACAGCGACTTC                   GGCGAGAGCGGGCGTCTCACCTACGAGATCGTGGACGGCAACGACGACCACCTGTTTG                   AGATCGACCCGTCCAGCGGCGAGATCCGCACGCTGCACCCTTTCTGGGAGGACGTGAC                   GCCCGTGGTGGAGCTGGTGGTGAAGGTGACCGACCACGGCAAGCCTACCCTGTCCGCA                   GTGGCCAAGCTCATCATCCGCTCGGTGAGCGGATCCCTTCCCGAGGGGGTACCACGGG                   TGAATGGCGAGCAGCACCACTGGGACATGTCGCTGCCGCTCATCGTGACTCTGAGCAC                   TATCTCCATCATCCTCCTAGCGGCCATGATCACCATCGCCGTCAAGTGCAAGCGCGAG                   AACAAGGAGATCCGCACTTACAACTGCCGCATCGCCGAGTACAGCCACCCGCAGCTGG                   GTGGGGGCAAGGGCAAGAAGAAGAAGATCAACAAAAATGATATCATGCTGGTGCAGAG                   CGAAGTGGAGGAGAGGAACGCCATGAACGTCATGAACGTGGTGAGCAGCCCCTCCCTG                   GCCACCTCCCCCATGTACTTCGACTACCAGACCCGCCTGCCCCTCAGCTCGCCCCGGT                   CGGAGGTGATGTATCTCAAACCGGCCTCCAACAACCTGACTGTCCCTCAGGGGCACGC                   GGGCTGCCACACCAGCTTCACCGGACAAGGGACTAATGCAAGCGAGACCCCTGCCACT                   CGGATGTCCATAATTCAGACAGACAATTTTCCCGCAGAGCCCAATTACATGGGCAGCA                   GGCAGCAGTTTGTTCAATGTATTTCAGTAGCTCCACGTTTAAGGACCCAGAAAGAGCC                   AGCC TGA   GAGACA                                           ORF Start: ATG at 6   ORF Stop: TGA at 2673                                         SEQ ID NO: 28   889 aa   MW at 96584.6 Da                             NOV4a,   MYLSICCCFLLWAPALTLKNLNYSVPEEQGAGTVIGNIGRDARLQPGLPPAERGGGGR           CG108624-01   SKSGSYRVLENSAPHLLDVDADSGLLYTKQRIDRESLCRHNAKCQLSLEVFANDKEIC       Protein sequence   MIKVEIQDINDNAPSFSSDQIEMDISENAAPGTRFPLTSAHDPDAGENGLRTYLLTRD                   DHGLFGLDVKSRGDGTKFPELVIQKALDREQQNHHTLVLTALDGGEPPRSATVQINVK                   VIDSNDNSPVFEAPSYLVELPENAPLGTVVIDLNATDADEGPNGEVLYSFSSYVPDRV                   RELFSIDPKTGLIRVKGNLDYEENGMLEIDVQARDLGPNPIPAHCKVTVKLIDRNDNA                   PSIGFVSVRQGALSEAAPPGTVIALVRVTDRDSGKNGQLQCRVLGGGGTGGGGGLGGP                   GGSVPFKLEENYDNFYTVVTDRPLDRETQDEYNVTIVARDGGSPPLNSTKSFAIKILD                   ENDNPPRFTKGLYVLQVHENNIPGEYLGSVLAQDPDLGQNGTVSYSILPSHIGDVSIY                   TYVSVNPTNGAIYALRSFNFEQTKAFEFKVLAKDSGAPAHLESNATVRVTVLDVNDNA                   PVIVLPTLQNDTAELQVPRNAGLGYLVSTVRALDSDFGESGRLTYEIVDCNDDHLFEI                   DPSSGEIRTLHPFWEDVTPVVELVVKVTDHGKPTLSAVAKLIIRSVSGSLPEGVPRVN                   GEQHHWDMSLPLIVTLSTISIILLAAMITIAVKCKRENKEIRTYNCRIAEYSHPQLGG                   GKGKKKKINKNDIMLVQSEVEERNAMNVMNVVSSPSLATSPMYFDYQTRLPLSSPRSE                   VMYLKPASNNLTVPQGHAGCHTSFTGQGTNASETPATRMSIIQTDNFPAEPNYMGSRQ                   QFVQCISVAPRLRTQKEPA                  
 
     [0355] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.  
               TABLE 4B                       Protein Sequence Properties NOV4a                                        PSort   0.4600 probability located in plasma membrane;       analysis:   0.1000 probability located in endoplasmic reticulum           (membrane); 0.1000 probability located in endoplasmic           reticulum (lumen); 0.1000 probability located in outside       SignalP   Cleavage site between residues 18 and 19       analysis:                  
 
     [0356] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4C.  
               TABLE 4C                          Geneseq Results for NOV4a                                                                 NOV4a   Identities/               Residues   Similarities       Geneseq   Protein/Organism/Length   Match   for the   Expect       Identifier   [Patent #, Date]   Residues   Matched Region   Value               AAY21687   Cadherin-like polypeptide, ontherin -    1 . . . 889   880/889 (98%)   0.0           Vertebrata, 889 aa. [WO9929853-A1,    1 . . . 889   885/889 (98%)           17 JUN. 1999]       AAY24913   Human ontherin -  Homo sapiens , 889 aa.    10 . . . 889   880/889 (98%)   0.0           [WO9929860-A1, 17 JUN. 1999]    1 . . . 889   885/889 (98%)       AAE17313   Human protocadherin protein,    10 . . . 874   466/869 (53%)   0.0           sbg419582PROTOCADHERIN #2 -  Homo      14 . . . 844   600/869 (68%)             sapiens , 855 aa. [WO200198342-A1,           27 DEC. 2001]       AAE17312   Human protocadherin protein,    10 . . . 840   460/882 (52%)   0.0           sbg419582PROTOCADHERIN #1 -  Homo      14 . . . 857   584/882 (66%)           sapiens, 888 aa. [WO200198342-A1,           27 DEC. 2001]       AAU19545   Human diagnostic and therapeutic   499 . . . 889   370/392 (94%)   0.0           polypeptide (DITHP) #131 -  Homo      36 . . . 427   373/392 (94%)           sapiens, 427 aa. [WO200162927-A2,           30 AUG 2001]                  
 
     [0357] In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4D.  
               TABLE 4D                          Public BLASTP Results for NOV4a                                         NOV4a               Protein       Residues/   Identities/       Accession       Match   Similarities for the   Expect       Number   Protein/Organism/Length   Residues   Matched Portion   Value               Q14917   protocadherin 68 -  Homo sapiens      1 . . . 889   880/889 (98%)   0.0           (Human), 889 aa.    1 . . . 889   883/889 (98%)       Q8TAB3   BA99E24.1.1 (Protocadherin 19   10 . . . 877   467/872 (53%)   0.0           (KIAA1313) protein) -  Homo sapiens      7 . . . 840   601/872 (68%)           (Human), 1094 aa (fragment).       Q9P2E7   KIAA1400 protein -  Homo sapiens     10 . . . 873   394/918 (42%)   0.0           (Human), 1093 aa (fragment).   62 . . . 948   558/918 (59%)       Q96SF0   Protocadherin 10 -  Homo sapiens     10 . . . 838   385/881 (43%)   0.0           (Human), 896 aa.    9 . . . 859   541/881 (60%)       Q92518   OL-protocadherin isoform -  Mus     10 . . . 873   393/918 (42%)   0.0             musculus  (Mouse), 1040 aa.    9 . . . 895   553/918 (59%)                  
 
     [0358] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4E.  
               TABLE 4E                          Domain Analysis of NOV4a                                     Identities/           Pfam   NOV4a   Similarities   Expect       Domain   Match Region   for the Matched Region   Value               cadherin   137 . . . 234   30/111 (27%)   2.3e−17               74/111 (67%)       cadherin   248 . . . 342   41/110 (37%)   5.4e−22       cadherin   357 . . . 463   37/119 (31%)   1.3e−16               86/119 (72%)       cadherin   477 . . . 574   1.2e−13               33/112 (29%)               71/112 (63%)       cadherin   593 . . . 685   38/108 (35%)   1.3e−10               64/108 (59%)                  
 
     Example 5  
     [0359] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences arc shown in Table 5A.  
               TABLE 5A                       NOV5 Sequence Analysis                                                    SEQ ID NO: 29   718 bp                             NOV5a,     AAAAACTAAGCCTGCTTCCAGTCCCCNCGGGAGTCGTAGGAACCCGTTCCTGGACGCT             CG108771-01     GACGTCGGCTTTCAGGGATCCCTCGCCGGACGCCGCGGAGGGACAGAGCCTGGGAAGC         DNA Sequence     CGTCGCCCCGCCCCGTCCCCGCCCCCGCGCGCAGCGGGCCCGGGGCGCTGAGACCCGC                       GTAGAGCAAAGCGCAAGGTCCCAGCGCCCCTTGGATCCTCGGTGGCAGGGTCCGGGCA                       AGTGTCATTGCGAGGGTTCAGGAAGCCCCGGCCTGTGATCGTGAGCGGAAACCCCTCC                       TGGAGTTTCCCCAAAGCC   ATG GACAGCCCTAGTCTTCGTGAGCTTCAACAGCCTCTGC                   TGGAGGGCACAGAATGTGAGACCCCTGCCCAGAAGCCTGGCAGGCATGACCTGGGGTC                   CCCCTTAAGAGAGATAGCCTTTGCCGAGTCCCTGAGGGGTTTGCAGTTCCTCTCACCG                   CCTCTTCCCTCCGTGAGCGCTGGCCTGGGGGAACCAAGGCCCCCTGATGTTGAGGACA                   TGTCATCCAGTGACAGTGACTCGGACTGGGATGGAGGCAGCCGTCTTTCACCATTTCT                   ACCCCACGACCACCTCGGCTTGGCTGTCTTCTCCATGCTGTGTTGTTTCTGGCCCGTT                   GGCATCGCTGCCTTCTGTCTAGCCCAGAAGGTCAGTCTGTGTGTGGGACTTGGAGGGG                   ACTGGAAGCAGGCT TAG   TTTTT                                           ORF Start: ATG at 309   ORF Stop: TAG at 711                                         SEQ ID NO: 30   134 aa   MW at 14376.1 Da                             NOV5a,   MDSPSLRELQQPLLEGTECETPAQKPGRHELGSPLREIAFAESLRGLQFLSPPLPSVS           CG108771-01   AGLGEPRPPDVEDMSSSDSDSDWDGGSRLSPFLPHDHLGLAVFSMLCCFWPVGIAAFC       Protein Sequence   LAQKVSLCVGLGGDWKQA                  
 
     [0360] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.  
               TABLE 5B                       Protein Sequence Properties NOV5a                                        PSort   0.7000 probability located in plasma membrane;       analysis:   0.4412 probability located in microbody (perxisome):           0.2000 probability located in endoplasmic reticulum           (membrane); 0.1000 probability located in mitochondrial inner           membrane       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0361] A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5C.  
               TABLE 5C                          Geneseq Results for NOV5a                                         NOV5a   Identities/                   Residues/   Similiarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABB90246   Human polypeptide SEQ ID NO 2622 -    1 . . . 122   120/122 (98%)   1e−67             Homo sapiens , 172 aa. [WO200190304-    1 . . . 122   121/122 (98%)           A2, 29 NOV. 2001]       AAB25755   Human secreted protein sequence encoded    1 . . . 122   120/122 (98%)   1e−67           by gene 33 SEQ ID NO: 144 -  Homo      1 . . . 122   121/122 (98%)             sapiens , 172 aa. [WO200043495-A2,           27 JUL. 2000]       AAB25754   Human secreted protein sequence encoded   15 . . . 71    57/57 (100%)   2e−27           by gene 33 SEQ ID NO: 143 -  Homo      1 . . . 57    57/57 (100%)             sapiens , 57 aa. [WO200043495-A2,           27 JUL. 2000]       AAB25697   Human secreted protein sequence encoded   72 . . . 122    49/51 (96%)   3e−24           by gene 33 SEQ ID NO: 86 -  Homo      1 . . . 51    50/51 (97%)             sapiens , 101 aa. [WO200043495-A2,           27 JUL. 2000]       AAB43155   Human ORFX ORF2919 polypeptide   86 . . . 122    35/37 (94%)   2e−15           sequence SEQ ID NO: 5838 -  Homo      2 . . . 38    36/37 (96%)             sapiens , 88 aa. [WO200058473-A2,           05 OCT. 2000]                  
 
     [0362] In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.  
               TABLE 5D                          Public BLASTP Results for NOV5a                                             Identities/           Protein       NOV5a   Similiarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9H7V2   CDNA FLJ14220 fis, clone    75 . . . 128   28/54 (51%)   7e−09           NT2RP3003828 -  Homo sapiens  (Human),   161 . . . 214   34/54 (62%)           258 aa.       Q9H514   BA526K17.1 (Novel protein) -  Homo      75 . . . 120   26/46 (56%)   5e−08             sapiens  (Human), 206 aa (fragment)   161 . . . 206   31/46 (66%)       O35449   Hypothetical 31.4 kDa protein -  Mus      92 . . . 128   16/37 (43%)   0.005             musculus  (Mouse), 306 aa.   220 . . . 256   23/37 (61%)       Q96NQ8   CDNA FLJ30323 fis, clone    92 . . . 128   16/37 (43%)   0.005           BRACE2007109, highly similar to   220 . . . 256   23/37 (61%)           extensin-like protein NG5 -  Homo sapiens             (Human), 306 aa.       Q96DW3   Similar to chromosome 6 open reading    92 . . . 128   16/37 (43%)   0.005           frame 31 -  Homo sapiens  (Human), 225 aa.   139 . . . 175   23/37 (61%)                  
 
     [0363] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.  
               TABLE 5E                          Domain Analysis of NOV5a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV5a Match Region   for the Matched Region   Value                         No Significant Known Matches Found                  
 
     Example 6  
     [0364] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.  
               TABLE 6A                       NOV6 Sequence Analysis                                                    SEQ ID NO: 31   1174 bp                             NOV6a,     ACGCGTGGGCGGACGCGTGGTTGGACTCCGCCCGTGGAGCCCTGGGCCTGTTGACCCA             CG108782-01     CCAGCTTAGGAGCACCCACCAAGCTCTGGGTCAACGTGGAGGTACCAGGCCACC   ATG C       DNA Sequence   TCAGTCTCAAGCTGCCCCAACTTCTTCAAGTCCACCAGGTCCCCCGGGTGTTCTGGGA                   AGATGGCATCATCTCTGGCTACCGCCGCCCCACCAGCTCGGCTTTGGACTGTGTCCTC                   AGCTCCTTCCAGATGACCAACGAGACGGTCAACATCTGGACTCACTTCCTGCCCACCT                   GGTACTTCCTGTGGCGGCTCCTGGCGCTGGCGGGCGGCCCCGGCTTCCGTGCGGAGCC                   GTACCACTGGCCGCTGCTGGTCTTCCTGCTGCCCGCCTGCCTCTACCCCTTCGCGTCG                   TGCTGCGCGCACACCTTCAGCTCCATGTCGCCCCGCATGCGCCACATCTGCTACTTCC                   TCGACTACGGCGCGCTCAGCCTCTACAGTCTGGGCTGCGCCTTCCCCTATGCCGCCTA                   CTCCATGCCGGCCTCCTGGCTGCACGGCCACCTGCACCAGTTCTTTGTGCCTGCCGCC                   GCACTCAACTCCTTCCTGTGCACCGGCCTCTCCTGCTACTCCCGGTTCCTGGAGCTGG                   AAACCCCTGGGCTCAGTAAGGTCCTCCGCACAGGAGCCTTCGCCTATCCATTCCTGTT                   CGACAACCTCCCACTCTTTTATCGGCTCGGGCTGTGCTGGGGCAGGGGCCACGGCTGT                   GGGCAGGAGGCCCTGAGCACCAGCCATGGCTACCATCTCTTCTGCGCGCTGCTCACTG                   GCTTCCTCTTCGCCTCCCACCTGCCTGAAAGGCTGGCACCAGGACGCTTTGATTACAT                   CGGTCACAGCCACCAGTTATTCCACATCTGTGCAGTGCTGGGCACCCACTTCCAGCTG                   GAGGCAGTGCTGGCTGATATGGGATCACGCAGAGCCTGGCTGGCCACACAGGAACCTG                   CCCTGGGCCTGGCAGGCACAGTGGCCACACTGGTCTTGGCTGCAGCTGGGAACCTACT                   CATTATTGCTGCTTTCACAGCCACCCTGCTTCGGGCCCCCAGTACATGCCCTCTGCTG                   CAGGGTGGCCCACTGGAGGGGGGTACCCAGGCCAAACAACAG TGA   GGCCCCATCCCTG                       ACCCTGTCCTGGAG                                           ORF Start: ATG at 113   ORF Stop: TGA at 1145                                         SEQ ID NO: 32   344 aa   MW at 37988.7 Da                             NOV6a,   MLSLKLPQLLQVHQVPRVFWEDGIMSGYRRPTSSALDCVLSSFQMTNETVNIWTHFLP           CC108782-01   TWYFLWRLLALAGGPGFRAEPYHWPLLVFLLPACLYPFASCCAHTFSSMSPRMRHICY       Protein Sequence   FLDYGALSLYSLGCAFPYAAYSMPASWLHGHLHQFFVPAAALNSFLCTGLSCYSRFLE                   LESPGLSKVLRTGAFAYPFLFDNLPLFYRLGLCWGRGHGCGQEALSTSHGYHLFCALL                   TGFLFASHLPERLAPGRFDYIGHSHQLFHICAVLGTHFQLEAVLADMGSRRAWLATQE                   PALGLAGTVATLVLAAAGNLLIIAAFTATLLRAPSTCPLLQGGPLEGGTQAKQQ                                         SEQ ID NO: 33   1081 bp                             NOV6b,     CAAGCTCTGGGTCAACGTGGAGGTACCAGGCCACCATGCTCAGTCTCAAGCTGCCCCA             CG108782-02   ACTTCTTCAAGTCCACCAGGTCCCCCGGGTGTTCTGGGAAGATGGCATCATGTCTGGC       DNA Sequence   TACCGCCGCCCCACCAGCTCGGCTTTGGACTGTGTCCTCAGCTCCTTCCAGATGACCA                   ACGAGACGGTCAACATCTGGACTCACTTCCTGCCCACCTGGTACTTCCTGTGGCCGCT                   TCTGGCGCTGGCGGGCGGCCCCGGCTTCCGTGCGGAGCCGTACCACTGGCCGCTGCTG                   GTCTTCCTGCTGCCCGCCTGCCTCTACCCCTTCGCGTCGTGCTGCGCGCACACCTTCA                   GCTCCATGTCGCCCCGCATGCGCCACATCTGCTACTTCCTCGACTACGGCGCGCTCAG                   CCTCTACAGTCTGGGCTGCGCCTTCCCCTATGCCGCCTACTCCATGCCGGCCTCCTGG                   CTGCACGGCCACCTGCACCAGTTCTTTGTGCCTGCCGCCGCACTCAACTCCTTCCTGT                   GCACCGGCCTCTCCTGCTACTCCCGTTTCCTCGAGCTGGAAAGCCCTGGGCTCAGTAA                   GGTCCTCCGCACAGGAGCCTTCGCCTATCCATTCCTGTTCGACAACCTCCCACTCTTT                   TATCGGCTCGGGCTGTGCTGGGGCAGGGGCCACGGCTGTGGGCAGGAGGCCCTGAGCA                   CCAGCCATGGCTACCATCTCTTCTGCGCGCTGCTCACTGGCTTCCTCTTCGCCTCCCA                   CCTGCCTGAAAGGCTGGCACCAGGACGCTTTGATTACATCGGCCACAGCCACCAGTTA                   TTCCACATCTGTGCAGTGCTGGGCACCCACTTCCAGCTGGAGGCAGTGCTGGCTGATA                   TGGGATCACGCAGAGCCTGGCTGGCCACACAGGAACCTGCCCTGGGCCTGGCAGGCAC                   AGTGGCCACACTGGTCTTGGCTGCAGCTGGGAACCTACTCATTATTGCTGCTTTCACA                   GCCACCCTGCTTCGGGCCCCCGGTACATGCCCTCTGCTGCAGGGTGGCCCACTGGAGG                   GGGGTACCCAGCCCAAACAACAG TGA   GCCCCCATCCC                                           ORF Start: ATG at 36   ORF Stop: TGA at 1068                                         SEQ ID NO: 34   344 aa   MW at 37958.7 Da                             NOV6b,   MLSLKLPQLLQVHQVPRVFWEDGIMSGYRRPTSSALDCVLSSFQMTNETVNIWTHFLP           CG108782-02   TWYFLWRLLALAGGPGFRAEPYHWPLLVFLLPACLYPFASCCAHTFSSMSPRMRHICY       Protein Sequence   FLDYGALSLYSLGCAFPYAAYSMPASWLHGHLHQFFVPAAALNSFLCTGLSCYSRFLE                   LESPGLSKVLRTGAFAYPFLFDNLPLFYRLGLCWGRGHGCGQEALSTSHGYHLFCALL                   TGFLFASHLPERLAPGRFDYIGHSHQLFHICAVLGTHFQLEAVLADMGSRRAWLATQE                   PALGLAGTVATLVLAAAGNLLIIAAFTATLLRAPGTCPLLQGGPLEGGTQAKQQ                  
 
     [0365] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 6B.  
               TABLE 6B                          Comparison of NOV6a against NOV6b.                         Protein   NOV6a Residues/           Sequence   Match Residues   Similarities for the Matched Region                                 NOV6b   1 . . . 344   311/344 (90%)           1 . . . 344   311/344 (90%)                  
 
     [0366] Further analysis of the NOV6a protein yielded the following properties shown in Table 6C.  
               TABLE 6C                       Protein Sequence Properties NOV6a                                        PSort   0.6000 probability located in plasma membrane;       analysis:   0.4000 probability located in Golgi body; 0.3000 probability           located in endoplasmic reticulum (membrane); 0.3000           probability located in microbody (peroxisome)       SignalP   Cleavage site between residues 21 and 22       analysis:                  
 
     [0367] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6D.  
               TABLE 6D                          Geneseq Results for NOV6a                                         NOV6a   Identities/                   Residues/   Similiarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABB11063   Human secreted protein homologue, SEQ   176 . . . 271    96/96 (100%)   2e−54           ID NO: 1433 -  Homo sapiens , 96 aa.    1 . . . 96    96/96 (100%)           [WO200157188-A2, 09 AUG. 2001]       ABB89827   Human polypeptide SEQ ID NO 2203 -    57 . . . 243   102/190 (53%)   2e−41             Homo sapiens , 284 aa. [WO200190304-    36 . . . 179   105/190 (54%)           A2, 29 NOV. 2001]       AAG01602   Human secreted protein, SEQ ID NO:    1 . . . 61    59/61 (96%)   2e−28           5683 -  Homo sapiens , 87 aa.    1 . . . 61    60/61 (97%)           [EP1033401-A2, 06 SEP. 2000]       AAG01600   Human secreted protein, SEQ ID NO    1 . . . 61    59/61 (96%)   2e−28           5681 -  Homo sapiens , 87 aa.    1 . . . 61    60/61 (97%)           [EP1033401-A2, 06 SEP. 2000]       AAY35973   Extended human secreted protein    14 . . . 283    82/271 (30%)   5e−28           sequence, SEQ ID NO. 222 -  Homo      37 . . . 301   126/271 (46%)           sapiens, 346 aa. [WO9931236-A2,           24 JUN. 1999]                  
 
     [0368] In a BLAST search of public sequence databases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6E.  
               TABLE 6E                          Public BLASTP Results for NOV6a                                             Identities/           Protein       NOV6a   Similiarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9BGW7   Hypothetical 25.8 kDa protein -  Macaca     107 . . . 344   229/238 (96%)    e−135             fascicularis  (Crab eating macaque)    1 . . . 238   230/238 (96%)           (Cynomolgus monkey), 238 aa.       Q9H621   CDNA: FLJ22672 fis, clone HS109265 -   139 . . . 344   205/206 (99%)    e−119             Homo sapiens  (Human), 206 aa.    1 . . . 206   205/206 (99%)       Q9NXK6   CDNA FLJ20190 fis, clone COLF0714 -    1 . . . 324   166/324 (51%)   1e−96             Homo sapiens  (Human), 330 aa.    1 . . . 321   215/324 (66%)       Q9DCU0   0610010115Rik protein -  Mus musculus      1 . . . 324   171/324 (52%)   2e−96           (Mouse), 330 aa.    1 . . . 321   217/324 (66%)       Q9DA71   1700019B16Rik protein -  Mus musculus      5 . . . 322   104/321 (32%)   7e−34           (Mouse), 354 aa.    32 . . . 342   151/321 (46%)                  
 
     [0369] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6F.  
               TABLE 6F                          Domain Analysis of NOV6a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV6a Match Region   for the Matched Region   Value               UPF0073   33 . . . 276    70/292 (24%)   1.5e−09               152/292 (52%)                  
 
     Example 7  
     [0370] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.  
               TABLE 7A                          NOV7 Sequence Analysis                                                 SEQ ID NO: 35   1441 bp                             NOV7a,     GGCAGCCGCTTCGGCGCCCGGCCCCGCGGCCAGCTAGGGGCGGCCCCGCGCTCCCTCA             CG108801-01     CGGCCCCTCGGCGGCGCCCGTCGGATCCGGCCTCTCTCTGCGCCCCGGGGCGCGCCAC         DNA Sequence     CTCCCCGCCGGAGGTGTCCACGCGTCCGGCCGTCCATCCGTCCGTCCCTCCTGGGGCC                       GGCGCTGACC   ATG CCCAGCGGCTGCCGCTGCCTGCATCTCGTGTGCCTGTTGTGCATT                   CTGGGGGCTCCCGGTCAGCCTGTCCGAGCCGATGACTGCAGCTCCCACTGTGACCTGG                   CCCACGGCTGCTGTGCACCTGACGGCTCCTGCAGGTGTGACCCGGGCTGGGAGGGGCT                   GCACTGTGAGCGCTGTGTGAGGATGCCTGGCTGCCAGCACGGTACCTGCCACCAGCCA                   TGGCAGTGCATCTGCCACAGTGGCTGGGCAGGCAAGTTCTGTGACAAAGATGAACATA                   TCTGTACCACGCAGTCCCCCTGCCAGAATGGAGGCCAGTGCATGTATGACGGGGGCGG                   TGAGTACCATTGTGTGTGCTTACCAGGCTTCCATGGGCGTGACTGCGAGCGCAAGCCT                   GGACCCTGTGAACAGGCAGGCTCCCCATGCCGCAATGGCGGGCAGTGCCAGGACGACC                   AGGGCTTTGCTCTCAACTTCACGTGCCGCTGCTTGGTGGGCTCTGTGGGTGCCCGCTG                   TGAGGTAAATGTGGATGACTGCCTGATGCGGCCTTGTGCTAACGGTGCCACCTGCCTT                   GACGGCATAAACCGCTTCTCCTGCCTCTGTCCTGAGGGCTTTGCTGGACGCTTCTGCA                   CCATCAACCTGGATGACTGTGCCAGCCGCCCATGCCAGAGAGGGGCCCGCTGTCGGGA                   CCGTGTCCACGACTTCGACTGCCTCTGCCCCAGTGGCTATGGTGGCAAGACCTGTGAG                   CTTGTCTTACCTGTCCCAGACCCCCCAACCACAGTCGACACCCCTCTAGGGCCCACCT                   CAGCTGTAGTGGTACCTGCCACGGGGCCAGCCCCCCACAGCGCAGGGGCTGGTCTGCT                   GCGGATCTCAGTGAAGGAGGTGGTGCGGAGGCAAGAGGCTGGGCTAGGTGAGCCTAGC                   TTGGTGGCCCTGGTGGTGTTTGGGGCCCTCACTCCTGCCCTGGTTCTGGCTACTGTGT                   TGCTGACCCTGAGGGCCTGGCGCCGGGGTGTCTGCCCTCCTGGACCCTGTTGCTACCC                   TGCCCCACACTATGCTCCAGCGTGCCAGGACCAGGAGTGTCAGGTTAGCATGCTGCCA                   GCAGGGCTCCCCCTGCCACGTGACTTGCCCCCTGAGCCTGGAAAGACCACAGCACTG T                       GA   TGGAGGTGGGGGCTTTCTGGCCCCCTTCCTCACCTCTTCCACCCCTCAGACTGGAG                       TGGTCCGTTCTCACCACCCTTCAGCTTGGGTACACACACAGAAGGGCGA                                           ORF Start: ATG at 185   ORF Stop: TGA at 1334                                         SEQ ID NO: 36   383 aa   MW at 40487.0 Da                             NOV7a,   MPSGCRCLHLVCLLCILGAPGQPVRADDCSSHCDLAHGCCAPDGSCRCDPGWEGLHCE           CG108801-01   RCVRMPGCQHGTCHQPWQCICHSGWAGKPCDKDEHICTTQSPCQNGGQCMYDGGGEYH       Protein Sequence   CVCLPGFHGRDCERKAGPCEQAGSPCRNGGQCQDDQGFALNFTCRCLVGSVGARCEVN                   VDDCLMRPCANGATCLDGINRFSCLCPEGFAGRFCTINLDDCASRPCQRGARCRDRVH                   DFDCLCPSGYGGKTCELVLPVPDPPTTVDTPLGPTSAVVVPATGPAPHSAGAGLLRIS                   VKEVVRRQEAGLGEPSLVALVVFGALTAALVLATVLLTLRAWRRGVCPPGPCCYPAPH                   YAPACQDQECQVSMLPAGLPLPRDLPPEPGKTTAL                                         SEQ ID NO: 37   1348 bp                             NOV7b,     GGCAGCCGCTTCGGCGCCCGGCCCCGCGGCCAGCTAGGGGCGGCCCCGCGCTCCCTCA             CG108801-02     CGGCCCCTCGGCGCCGCCCGTCGGATCCGGCCTCTCTCTGCGCCCCGGGGCGCGCCAC         DNA Sequence     CTCCCCGCCGGAGGTGTCCACGCGTCCGCCCGTCCATCCGTCCGTCCCTCCTGGGGCC                       GGCGCTGACC   ATG CCCAGCGGCTGCCGCTGCCTGCATCTCGTGTGCCTGTTGTGCATT                   CTGGGGGCTCCCGGTCAGCCTGTCCGAGCCGATGACTGCAGCTCCCACTGTGACCTGG                   CCCACGGCTGCTGTGCACCTCACGGCTCCTGCAGGTGTGACCCGGGCTGGGAGGGGCT                   GCACTGTGAGCGCTGTGTGAGGATGCCTGGCTGCCAGCACGGTACCTGCCACCAGCCA                   TGGCAGTGCATCTGCCACAGTGGCTGGGCAGGCAAGTTCTGTGACAAAGGCTTCCATG                   GGCGTGACTGCGAGCGCAAGGCTGGACCCTGTGAACACGCAGGCTCCCCATGCCGCAA                   TGGCGGGCAGTGCCAGGACGACCAGGGCTTTGCTCTCAACTTCACGTGCCGCTGCTTG                   GTGGGCTCTGTGGGTGCCCGCTGTGAGGTAAATGTGGATGACTGCCTGATGCGGCCTT                   GTGCTAACGGTGCCACCTGCCTTGACGGCATAAACCGCTTCTCCTGCCTCTGTCCTGA                   GGGCTTTGCTGGACGCTTCTGCACCATCAACCTGGATGACTGTGCCAGCCGCCCATGC                   CAGAGAGGGGCCCGCTGTCGGGACCGTGTCCACGACTTCGACTGCCTCTGCCCCAGTG                   GCTATGGTGGCAAGACCTGTGAGCTTGTCTTACCTGTCCCAGACCCCCCAACCACAGT                   GGACACCCCTCTAGGGCCCACCTCAGCTGTAGTGGTACCTGCCACGGGGCCAGCCCCC                   CACAGCGCAGGGGCTGGTCTGCTGCGGATCTCAGTGAAGGAGGTGGTGCGGAGGCAAG                   AGGCTGGGCTAGGTGAGCCTAGCTTGGTGGCCCTGGTGGTGTTTGGGGCCCTCACTGC                   TGCCCTGGTTCTGGCTACTGTGTTGCTGACCCTGAGGGCCTGGCGCCGGGGTGTCTGC                   CCTCCTGGACCCTGTTGCTACCCTGCCCCACACTATGCTCCAGCGTGCCAGGACCAGG                   AGTGTCAGGTTAGCATGCTGCCAGCAGGGCTCCCCCTGCCACGTGACTTGCCCCCTGA                   GCCTGGAAAGACCACAGCACTG TGA   TGGAGGTCGGGGCTTTCTGGCCCCCTTCCTCAC                       CTCTTCCACCCCTCAGACTGGAGTGGTCCGTTCTCACCACCCTTCAGCTTGGGTACAC                       ACACAGAAGGGCGA                                           ORF Start: ATG at 185   ORF Stop: TGA at 1241                                         SEQ ID NO: 38   352 aa   MW at 37158.3 Da                             NOV7b,   MPSGCRCLHLVCLLCILGAPGQPVRADDCSSHCDLAHGCCAPDGSCRCDPGWEGLHCE           CG108801-02   RCVRMPGCQHGTCHQPWQCICHSGWAGKFCDKGFHGRDCERKAGPCEQAGSPCRNGGQ       Protein Sequence   CQDDQGFALNFTCRCLVGSVGARCEVNVDDCLMRPCANGATCLDGINRFSCLCPEGFA                   GRFCTINLDDCASRPCQRGARCRDRVHDFDCLCPSGYGGKTCELVLPVPDPPTTVDTP                   LGPTSAVVVPATGPAPHSAGAGLLRISVKEVVRRQEAGLGEPSLVALVVFGALTAALV                   LATVLLTLRAWRRGVCPPGPCCYPAPHYAPACQDQECQVSMLPAGLPLPRDLPPEPGK                   TTAL                  
 
     [0371] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 7B.  
               TABLE 7B                          Comparison of NOV7a against NOV7b.                         Protein   NOV7a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV7b   1 . . . 383   296/383 (77%)           1 . . . 352   296/383 (77%)                  
 
     [0372] Further analysis of the NOV7a protein yielded the following properties shown in Table 7C.  
               TABLE 7C                       Protein Sequence Properties NOV7a                                        PSort   0.4600 probability located in plasma membrane;       analysis:   0.1000 probability located in endoplasmic reticulum           (membrane); 0.1000 probability located in endoplasmic           reticulum (lumen); 0.1000 probability located in outside       SignalP   Cleavage site between residues 27 and 28       analysis:                  
 
     [0373] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7D.  
               TABLE 7D                          Geneseq Results for NOV7a                                         NOV7a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAG67516   Amino acid sequence of a human    1 . . . 383   382/383 (99%)   0.0           secreted polypeptide -  Homo sapiens ,    1 . . . 383   382/383 (99%)           383 aa. [WO200166690-A2,           13 SEP. 2001]       AAE01167   Human gene 4 encoded secreted protein    1 . . . 383   382/383 (99%)   0.0           HKAAV61, SEQ ID NO: 68 -  Homo      1 . . . 383   382/383 (99%)             sapiens , 383 aa. [WO200134768-A2,           17 MAY 2001]       AAE13632   Human preadipocyte factor-1-like    1 . . . 383   381/383 (99%)   0.0           protein -  Homo sapiens , 383 aa.    1 . . . 383   381/383 (99%)           [WO200157233-A2, 09 AUG. 2001]       AAE13639   Human preadipocyte factor-1-like   27 . . . 383   356/357 (99%)   0.0           protein fragment #1 -  Homo sapiens ,    1 . . . 357   356/357 (99%)           357 aa. [WO200157233-A2,           09 AUG. 2001]       AAE13641   Wheat germ agglutinin #1 found in   57 . . . 233   176/177 999%)   e−116           human Pref-1-like protein -  Triticum      1 . . . 177   176/177 (99%)             aestivum , 177 aa. [WO200157233-A2,           09 AUG. 2001]                  
 
     [0374] 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 in Table 7E.  
               TABLE 7E                          Public BLASTP Results for NOV7a                                         NOV7a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9BQ54   Hypothetical 21.3 kDa protein (Unknown)   180 . . . 383   204/204 (100%)    e−122           (Protein for MGC: 2487) -  Homo sapiens      1 . . . 204   204/204 (100%)           (Human), 204 aa.       O70534   ZOG protein -  Rattus norvegicus  (Rat),    10 . . . 327   127/325 (39%)   2e−67           383 aa.    7 . . . 324   171/325 (52%)       Q62779   Preadipocyte factor 1 -  Rattus norvegicus      10 . . . 325   127/323 (39%)   9e−67           (Rat), 383 aa.    7 . . . 322   169/323 (52%)       Q925U3   Dlk (Delta like) (Delta-like) -  Mus      10 . . . 327   126/327 (38%)   1e−64             musculus  (Mouse), 385 aa.    7 . . . 326   170/327 (51%)       Q09163   Delta-like protein precursor (DLK)    10 . . . 327   126/327 (38%)   1e−64           (Preadipocyte factor 1) (Pref-1)    7 . . . 326   170/327 (51%)           (Adipocyte differentiation inhibitor           protein) [Contains: Fetal antigen 1 (FA1)]-             Mus musculus  (Mouse), 385 aa.                  
 
     [0375] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7F.  
               TABLE 7F                          Domain Analysis of NOV7a                                     Identities           Pfam   NOV7a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               EGF   60 . . . 88   11/47 (23%)   0.0016               23/47 (49%)       EGF   95 . . . 128   16/47 (34%)     8e−08               30/47 (64%)       EGF   135 . . . 171   15/47 (32%)   0.0003               23/47 (49%)       EGF   178 . . . 209   13/47 (28%)    61e−09               26/47 (55%)       EGF   216 . . . 247   14/47 (30%)   5.2e−06               24/47 (51%)                  
 
     Example 8  
     [0376] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.  
               TABLE 8A                       NOV8 Sequence Analysis                                                    SEQ ID NO: 39   2484 bp                             NOV8a,     GGATCTCAGCACTCTGACCCAAGGGGAAGC   ATG TCGAAGAAAGGCCGGAGCAAGGGCG           CG109717-01   AGAAGCCCGAGATGGAGACGGACGCGGTGCAGATGGCCAACGAGGAGCTGCCGGCCAA       DNA Sequence   GCTGACCAGCATTCAGATCGAGTTCCAGCAGGAAAAAAGCAAGGTGGGCAAACTGCGC                   GAGCGGCTGCAGGAGGCGAAGCTGGAGCGCGAGCAGGAGCAGCGACGGCACACGGCCT                   ACATTTCGGAGCTCAAGGCCAAGCTGCATGAGGAGAAGACCAAGGAGCTGCAGGCGCT                   GCGCGAGGGGCTCATCCGGCAGCACGAGCAGGAGGCGCCGCGCACCGCCAAGATCAAG                   GAGGGCGAGCTGCAGCGGCTGCAGGCCACGCTGAACGTGCTGCGCGACGGCGCGGCCG                   ACAAGGTCAAGACGGCGCTGCTGACCGAGGCGCGCGAGGAGGCGCGCAGGGCCTTCGA                   GCAGAGGAGGCGCTCAGTAACTGCATGCAGGCTGACAAGACCAAGGCAGCCGACCTGC                   GTGCCGCCTACCAGGCGCACCAAGACGAGGTGCACCGCATCAAGCGCGAGTGCGAGCG                   CGACATCCGCAGGCTGATGGATGAGATCAAAGGCAAAGACCGTGTGATTCTGGCCTTG                   GAGAAGGAACTTGGCGTGCAGGCTGGGCAGACCCAGAAGCTGCTTCTGCAGAAAGAGG                   CTTTGGATGAGCAGCTGGTTCAGGTCAAGGAGGCCGAGCGGCACCACAGTAGTCCAAA                   GAGAGAGCTCCCGCCCGGGATCGGGGACATGGTGGAGCTCATGGGCGTCCAGGATCAA                   CATATGGACGAGCGAGATGTGAGGCGATTTCAACTAAAAATTGCTGAACTGAATTCAG                   TGATACGGAAGCTGGAAGACAGAAATACGCTGTTGGCAGATGAGAGGAATGAACTGCT                   GAAACGCTCACGAGAGACCGAGGTTCAGCTGAAGCCCCTGGTGGAGAAGAACAAGCGG                   ATGAACAAGAAGAATGAGGATCTGTTGCAGAGTATCCAGAGGATGGAGGAGAAAATCA                   AGAACCTCACGCGGGAAAACGTGGAAATGCTGTCAGCGCAGGCGTCTCTGAAGCGGCA                   TACCTCCTTGAATGACCTCAGCCTGACGAGGGATGAGCAGGAGATCGAGTTCCTGAGG                   CTGCAGGTGCTGGAGCAGCAGCACGTCATTGACGACCTCTCACTGGAGAGAGAACGGC                   TGTTGCGCTCCAAAAGGCATCGAGGGAAAAGTCTGAAACCGCCCAAGAAGCATGTTGT                   GGAGACATTTTTTGGATTTGATCAGGAGTCTGTGGACTCAGAAACGTTGTCCGAAACA                   TCCTACAACACAGACAGGACAGACAGGACCCCAGCCACGCCCGAAGAAGACTTGGACG                   ATAAGGCCACAGCCCGAGAGGAGGCTGACCTGCGCTTCTGCCAGCTGACCCGGGAGTA                   CCAGGCCCTGCAACGCGCCTACGCCCTGCTCCAGGAGCAGGTGGGAGGCACGCTGGAC                   GCTGAGAGGGAGGCCCGGACTCGGGAGCAGCTACAAGCTGATCTGCTGAGGTGTCAGG                   CCAAAATCGAAGATTTGGAGAAGTTACTGGTTGAGAAGGGACAGGTGAGCAGGAGTGA                   TATGGAAGAGAACCAGCTGAAGAATGAAATGCAAGACGCCAAGGATCAGAACGAGCTG                   TTAGAATTCAGAGTGCTAGAACTCGAAGAGAGAGAGAGGAGGTCGCCAGCATTTAACC                   TCCAAATCACCACCTTCCCCGAGAACCACAGCAGCGCTCTCCAGCTGTTCTGTCACCA                   GGAAGGAGTTAAGGATGTGAATGTTTCTGAACTTATGAAGAAATTAGATATCCTTGGC                   GATAACGGGAATTTGAGAAATGAAGAACAGGTTGCAATAATCCAAGCTGGAACTGTGC                   TTGCCCTGTGTGAAAAGTGGCTGAAGCAAATAGAGGGGACCGAGGCCGCCCTGACCCA                   GAAGATGCTGGACCTGGAGAAGGAGCAGGACCTGTTCAGCAGGCAGAAGGGCTACCTG                   GAAGAGGAGCTCGACTACCGGAAGCAAGCCCTTGACCAGGCTTACCTGAAAATCCAAG                   ACCTGGAGGCCACACTGTACACAGCGCTGCAGCAGGAGCCGGGGCGGAGGGCCGGTGA                   GGCGCTGAGCGAGGGCCAGCGGGACGACCTGCAGGCTGCTGTGGAAAAGGTGCGCAGG                   CAGATCCTCAGGCAGAGCCGCGAGTTCGACAGCCAGATCCTGCGGGAGCGCATGGAGC                   TGCTGCAGCAGGCCCAGCAGAGAATCCGAGAACTGGAGGACAAACTGGAGTTTCAGAA                   GCGGCACCTGAAAGAACTGGAGGAAAAGTTTTTGTTCCTTTTTTTGTTTTTCTCACTA                   GCATTCATTCTGTGGCCT TGA   TGACTTCAGTGAGCCAAGAACTCGGGT                                           ORF Start: ATG at 31   ORF Stop: TGA at 2455                                         SEQ ID NO: 40   808 aa   MW at 94479.1 Da                             NOV8a,   MSKKGRSKGEKPEMETDAVQMANEELRAKLTSIQIEFQQEKSKVGKLRERLQEAKLER           CG109717-01   EQEQRRHTAYISELKAKLHEEKTKELQALREGLIRQHEQEAARTAKIKEGELQRLQAT       Protein Sequence   LNVLRDGAADKVKTALLTEAREEARRAFDGERLRLQQEILELKAARKQAEEALSNCMQ                   ADKTKAADLRAAYQAHQDEVHRIKRECERDIRRLMDEIKGKDRVILALEKELGVQAGQ                   TQKLLLQKEALDEQLVQVKEAERHHSSPKRELPPGIGDMVELMGVQDQHMDERDVRRF                   QLKIAELNSVIRKLEDRNTLLADERNELLKRSRETEVQLKPLVEKNKRMNKKNEDLLQ                   SIQRMEEKIKNLTRENVEMLSAQASLKRHTSLNDLSLTRDEQEIEFLRLQVLEQQHVI                   DDLSLERERLLRSKRHRGKSLKPPKKHVVETFFGFDEESVDSETLSETSYNTDRTDRT                   PATPEEDLDDKATAREEADLRFCQLTREYQALQRAYALLQEQVGGTLDAEREARTREQ                   LQADLLRCQAKIEDLEKLLVEKGQVSRSDMEENQLKNEMQDAKDQNELLEPRVLELEE                   RERRSPAFNLQITTFPENHSSALQLFCHQEGVKDVNVSELMKKLDILGDNGNLRNEEQ                   VAIIQAGTVLALCEKWLKQIEGTEAALTQKMLDLEKEQDLFSRQKGYLEEELDYRKQA                   LDQAYLKIQDLEATLYTALQQEPGRRAGEALSEGQREDLQAAVEKVRRQILRQSREFD                   SQILRERMELLQQAQQRIRELEDKLEFQKRHLKELEEKFLFLFLFFSLAFILWP                  
 
     [0377] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.  
               TABLE 8B                       Protein Sequence Properties NOV8a                                        PSort   0 8500 probability located in endoplasmic reticulum       analysis:   (membrane); 0.4400 probability located in plasma           membrane; 0.3000 probability located in microbody           (peroxisome); 0.1000 probability located in mitochondrial           inner membrane       SignalP   No Known Signal Sequence Predicted       analysis;                  
 
     [0378] 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 8C.  
               TABLE 8C                          Geneseq Results for NOV8a                                         NOV8a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABB04608   Human xylose isomerase 43 protein   173 . . . 582   323/431 (74%)    e−162           SEQ ID NO: 2 -  Homo sapiens , 387 aa.    1 . . . 366   332/431 (76%)           [CN1307130-A, 08 AUG. 2001]       AAB42436   Human ORFX ORF2200 polypeptide   194 . . . 431   238/241 (98%)    e−128           sequence SEQ ID NO: 4400 -  Homo      1 . . . 241   238/241 (98%)             sapiens , 241 aa. [WO200058473-A2,           05 OCT. 2000]       AAAM85650   Human immune/haematopoietic antigen   445 . . . 808   238/390 (61%)    e−124           SEQ ID NO: 13243 -  Homo sapiens , 388    4 . . . 388   298/390 (76%)           aa. [WO200157182-A2, 09 AUG. 2001]       ABB61173   Drosophila melanogaster polypeptide    6 . . . 788   179/877 (20%)   4e−24           SEQ ID NO 10311 -  Drosophila     423 . . . 1263   360/877 (40%)             melanogaster , 1690 aa. [WO200171042-A2,           27 SEP. 2001]       AAY30795   A human trichohyalin (TRHY) protein-   24 . . . 794   171/792 (21%)   5e−24             Homo sapiens , 1898 aa. [U.S. Pat. No.   258 . . . 991   345/792 (42%)           5958752-A, 28 SEP. 1999]                  
 
     [0379] 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.  
               TABLE 8D                          Public BLASTP Results for NOV8a                                         NOV8a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Identifier   Protein/Organism/Length   Residues   Portion   Value                                         Q96N16   CDNA FLJ31564 fis, clone    1 . . . 582   575/606 (94%)   0.0           NT2R12001450, weakly similar to    1 . . . 605   578/606 (94%)           trichohyalin -  Homo sapiens  (Human),           626 aa.       T00331   hypothetical protein KIAA0555 -    1 . . . 808   530/812 (65%)   0.0           human, 799 aa.    1 . . . 799   656/812 (80%)       Q96AA8   Hypothetical protein KIAA0555 -  Homo      1 . . . 792   513/817 (62%)   0.0             sapiens  (Human), 810 aa.    1 . . . 804   641/817 (77%)       Q9CU41   6330417G02Rik protein -  Mus musculus      1 . . . 418   262/436 (60%)    e−139           (Mouse), 437 aa (fragment).    1 . . . 435   333/436 (76%)       Q9BGP2   Hypothetical 23.9 kDa protein -  Macaca     609 . . . 808   148/200 (74%)   1e−79             fascicularis  (Crab eating macaque)    2 . . . 201   177/200 (88%)           (Cynomolgus monkey), 201 aa.                  
 
     [0380] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.  
               TABLE 8E                          Domain Analysis of NOV8a                                     Identities           Pfam   NOV8a   Similarities       Domain   Match Region   for the Matched Region   Expect Value                         No significant Known Matches Found                  
 
     Example 9  
     [0381] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.  
               TABLE 9A                       NOV9 Sequence Analysis                                                    SEQ ID NO: 41   3040 bp                             NOV9a,     ACA   AT GATGGGGCTCTTCCCCAGAACTACAGGGGCTCTGGCCATCTTCGTGGTAGTCA           CG10477-01   TATTGGTTCATGGAGAATTGCGAATAGAGACTAAAGGTCAATATGATGAAGAAGAGAT       DNA Sequence   GACTATGCAACAAGCTAAAAGAAGGCAAAAACGTGAATGGGTGAAATTTGCCAAACCC                   TGCAGAGAAGGAGAAGATAACTCAAAAAGAAACCCAATTGCCAAGATTACTTCAGATT                   ACCAAGCAACCCAGAAAATCACCTACCGAATCTCTGGAGTGGGAATCGATCAGCCGCC                   TTTTGGAATCTTTGTTGTTGACAAAAACACTGGAGATATTAACATAACAGCTATAGTC                   GACCGGGAGGAAACTCCAAGCTTCCTGATCACATGTCGGGCTCTAAATGCCCAAGGAC                   TAGATGTAGAGAAACCACTTATACTAACGGTTAAAATTTTGGATATTAATGATAATCC                   TCCAGTATTTTCACAACAAATTTTCATGGGTGAAATTGAAGAAAATAGTGCCTCAGAC                   TCACTGGTGATGATACTAAATGCCACAGATGCAGATGAACCAAACCACTTGAATTCTA                   AAATTGCCTTCAAAATTGTCTCTCAGGAACCAGCAGGCACACCCATGTTCCTCCTAAG                   CAGAAACACTGGGGAAGTCCGTACTTTGACCAATTCTCTTGACCGAGAGCAAGCTAGC                   AGCTATCGTCTGGTTGTGAGTGGTGCAGACAAAGATGGAGAAGGACTATCAACTCAAT                   GTGAATGTAATATTAAAGTGAAAGATGTCAACGATAACTTCCCAATGTTTAGAGACTC                   TCAGTATTCAGCACGTATTGAAGAAAATATTTTAAGTTCTGAATTACTTCGATTTCAA                   GTAACAGATTTGGATGAAGAGTACACAGATAATTGGCTTGCAGTATATTTCTTTACCT                   CTGGGAATGAAGGAAATTGGTTTGAAATACAAACTGATCCTAGAACTAATGAAGGCAT                   CCTGAAAGTGGTGAAGGCTCTAGATTATGAACAACTACAAAGCGTGAAACTTAGTATT                   GCTGTCAAAAACAAAGCTGAATTTCACCAATCAGTTATCTCTCGATACCGAGTTCAGT                   CAACCCCAGTCACAATTCAGGTAATAAATGTAAGAGAAGGAATTGCATTCCGTCCTGC                   TTCCAAGACATTTACTGTGCAAAAAGGCATAAGTAGCAAAAAATTGGTGGATTATATC                   CTGGGAACATATCAAGCCATCGATGAGGACACTAACAAAGCTGCCTCAAATGTCAAGT                   ATGTCATGGGACGTAACGATGGTGGATACCTAATGATTGATTCAAAAACTGCTGAAAT                   CAAATTTGTCAAAAATATGAACCGAGATTCTACTTTCATAGTTAACAAAACAATCACA                   GCTGAGGTTCTGGCCATAGATGAATACACGGGTAAAACTTCTACAGGCACGGTATATG                   TTAGAGTACCCGATTTCAATGACAATTGTCCAACAGCTGTCCTCGAAAAAGATGCAGT                   TTGCAGTTCTTCACCTTCCGTGGTTGTCTCCGCTAGAACACTGAATAATAGATACACT                   GGCCCCTATACATTTGCACTGGAAGATCAACCTGTAAAGTTGCCTGCCGTATGGAGTA                   TCACAACCCTCAATGCTACCTCGGCCCTCCTCAGAGCCCAGGAACAGATACCTCCTGG                   AGTATACCACATCTCCCTGGTACTTACAGACAGTCAGAACAATCGGTGTGAGATGCCA                   CGCAGCTTGACACTGGAAGTCTGTCAGTGTGACAACAGGGGCATCTGTGGAACTTCTT                   ACCCAACCACAAGCCCTGGGACCAGGTATGGCAGGCCGCACTCAGGGAGGCTGGGGCC                   TGCCGCCATCGGCCTGCTGCTCCTTGGTCTCCTGCTGCTGCTGGTGGCCCCCCTTCTG                   CTGTTGACCTGTGACTGTGGGGCAGGTTCTACTGGGGGAGTGACAGGTGGTTTTATCC                   CAGTTCCTGATGGCTCAGAAGGAACAATTCATCAGTGGGGAATTGAAGGAGCCCATCC                   TGAAGACAAGGAAATCACAAATATTTGTGTGCCTCCTGTAACAGCCAATGGAGCCGAT                   TTCATGGAAAGTTCTGAAGTTTGTACAAATACGTATGCCAGAGGCACAGCGGTGGAAG                   GCACTTCAGGAATGGAAATGACCACTAAGCTTGGAGCAGCCACTGAATCTGGAGGTGC                   TGCAGGCTTTGCAACAGGGACAGTGTCAGGAGCTGCTTCAGGATTCGGAGCAGCCACT                   GGAGTTGGCATCTGTTCCTCAGGGCAGTCTGGAACCATGAGAACAAGGCATTCCACTG                   GAGGAACCAATAAGGACTACGCTGATGGGGCGATAAGCATGAATTTTCTGGACTCCTA                   CTTTTCTCAGAAAGCATTTGCCTGTGCGGAGGAAGACGATGGCCAGGAAGCAAATGAC                   TGCTTGTTGATCTATGATAATGAAGGCGCAGATGCCACTGGTTCTCCTGTGGGCTCCG                   TGGGTTGTTGCAGTTTTATTGCTGATGACCTGGATGACAGCTTCTTGGACTCACTTGG                   ACCCAAATTTAAAAAACTTGCAGAGATAAGCCTTGGTGTTGATGGTGAAGGCAAAGAA                   GTTCAGCCACCCTCTAAAGACAGCGGTTATGGGATTGAATCCTGTGGCCATCCCATAG                   AAGTCCAGCAGACAGGATTTGTTAAGTGCCAGACTTTGTCAGGAAGTCAAGGAGCTTC                   TGCTTTGTCCACCTCTGGGTCTGTCCAGCCAGCTGTTTCCATCCCTGACCCTCTGCAG                   CATGGTAACTATTTAGTAACGGAGACTTACTCGGCTTCTGGTTCCCTCGTGCAACCTT                   CCACTGCAGGCTTTGATCCACTTCTCACACAAAATGTGATAGTGACAGAAAGGGTGAT                   CTGTCCCATTTCCAGTGTTCCTGGCAACCTAGCTGGCCCAACGCAGCTACGAGGGTCA                   CATACTATGCTCTGTACAGAGGATCCTTGCTCCCGTCTAATA TGA   CCAGAATGAGCTG                       GAATACCACACTGACCAAATCTGG                                           ORF Start: ATG at 4   ORF Stop: TGA at 3001                                         SEQ ID NO: 42   999aa   MW at 107518.8 Da                             NOV9a,   MMGLFPRTTGALAIFVVVILVHGELRIETKGQYDEEEMTMQQAKRRQKREWVKFAKPC           CG110477-01   REGEDNSKRNPIAKITSDYQATQKITYRISGVGIDQPPFGIFVVDKNTGDINITAIVD       Protein Sequence   REETPSFLITCRALNAQGLDVEKPLILTVKILDINDNPPVFSQQIFMGEIEENSASDS                   LVMILNATDADEPNHLNSKIAFKIVSQEPAGTPMFLLSRNTGEVRTLTNSLDREQASS                   YRLVVSGADKDGEGLSTQCECNIKVKDVNDNFPMFRDSQYSARIEENILSSELLRFQV                   TDLDEEYTDNWLAVYFFTSGNEGNWFEIQTDPRTNEGILKVVKALDYEQLQSVKLSIA                   VKNKAEFHQSVISRYRVQSTPVTIQVINVREGIAFRPASKTFTVQKGISSKKLVDYIL                   EVLAIDEYTGKTSTGTVYVRVPDFNDNCPTAVLEKDAVCSSSPSVVVSARTLNNRYTG                   PYTFALEDQPVKLPAVWSITTLNATSALLRAQEQIPPGVYHISLVLTDSQNNRCEMPR                   SLTLEVCQCDNRGICGTSYPTTSPGTRYGRPHSGRLGPAAIGLLLLGLLLLLVAPLLL                   LTCDCGAGSTGGVTGGFIPVPDGSEGTIHQWGIEGAHPEDKEITNICVPPVTANGADF                   MESSEVCTNTYARGTAVEGTSGMEMTTKLGAATESGGAAGFATGTVSGAASGFGAATG                   VGICSSGQSGTMRTRHSTGGTNKDYADGAISMNFLDSYFSQKAFACAEEDDGQEANDC                   LLIYDNEGADATGSPVGSVGCCSFIADDLDDSFLDSLGPKFKKLAEISLGVDGEGKEV                   QPPSKDSGYGIESCGHPIEVQQTGFVKCQTLSGSQGASALSTSGSVQPAVSIPDPLQH                   GNYLVTETYSASGSLVQPSTAGFDPLLTQNVIVTERVICPISSVPGNLAGPTQLRGSH                   TMLCTEDPCSRLI                  
 
     [0382] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.  
               TABLE 9B                       Protein Sequence Properties NOV9a                                        PSort   0.4600 probability located in plasma membrane;       analysis:   0.1000 probability located in endoplasmic reticulum           (membrane); 0.1000 probability located in endoplasmic           reticulum (lumen); 0.1000 probability located in outside       SignalP   Cleavage site between residues 24 and 25           analysis.                  
 
     [0383] 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/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU78054   Human desmoglein 3  (pemphigus      1 . . . 999   996/999 (99%)   0.0             vulgaris  antigen) protein sequence -    1 . . . 999   998/999 (99%)             Homo sapiens , 999 aa. [WO200210767-A2,           07 FEB. 2002]       ABG12435   Novel human diagnostic protein #12426 -    1 . . . 999   996/999 (99%)   0.0             Homo sapiens , 1014 aa. [WO200175067-A2,   16 . . . 1014   998/999 (99%)           11 OCT. 2001]       ABG12435   Novel human diagnostic protein #12426 -    1 . . . 999   996/999 (99%)   0.0             Homo sapiens , 1014 aa. [WO200175067-A2,   16 . . . 1014   998/999 (99%)           11 OCT. 2001]       AAR30742   Human  pemphigus vulgaris  130kD    1 . . . 999   996/999 (99%)   0.0           antigen -  Homo sapiens , 999 aa.    1 . . . 999   998/999 (99%)           [USN7798918-N, 15 DEC. 1992]       AAW07908     Pemphigus vulgaris  antigen protein    2 . . . 615   610/614 (99%)   0.0           extracellular region -  Homo sapiens , 614    1 . . . 614   612/614 (99%)           aa. [JP08188540-A, 23 JUL. 1996]                  
 
     [0384] 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.  
               TABLE 9D                          Public BLASTP Results for NOV9a                                         NOV9a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               P32926   Desmoglein 3 precursor (130 kDa   1 . . . 999   996/999 (99%)   0.0             pemphigus vulgaris  antigen) (PVA) -    1 . . . 999   998/999 (99%)             Homo sapiens  (Human), 999 aa.       O35902   Desmoglein 3 precursor (130 kDa   1 . . . 998   729/1018 (71%)   0.0             pemphigus vulgaris  antigen homolog) -   1 . . . 993   832/1018 (81%)             Mus musculus  (Mouse), 993 aa           (fragment).       Q02413   Desmoglein 1 precursor (Desmosomal   5 . . . 992   429/1003 (42%)   0.0           glycoprotein 1) (DG1) (DG1) ( Pemphigus     5 . . . 896   581/1003 (57%)             foliaceus  antigen) -  Homo sapiens             (Human), 1049aa.       Q8R517   Desmoglein 2 -  Mus musculus  (Mouse),   46 . . . 972   393/960 (40%)   0.0           1122 aa.   51 . . . 977   559/960 (57%)       Q14126   Desmoglein 2 precursor (HDGC) -  Homo     46 . . . 972   376/963 (39%)   e−177             sapiens  (Human), 1117 aa.   45 . . . 973   558/963 (57%)                  
 
     [0385] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.  
               TABLE 9E                          Domain Analysis of NOV9a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV9a Match Region   for the Matched Region   Value               cadherin    54 . . . 148   23/111 (21%)   6.5e−06               68/111 (61%)       cadherin   162 . . . 258   30/110 (27%)     4e−21               75/110 (68%)       cadherin   272 . . . 375   33/107 (31%)   1.6e−30               88/107 (82%)       cadherin   388 . . . 486   24/113 (21%)   0.00099               68/113 (60%)                  
 
     Example 10  
     [0386] The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.  
               TABLE 10A                       NOV10 Sequence Analysis                                                    SEQ ID NO: 43   898 bp                             NOV 10a,     TAAG AT GAATAAAAACAACAAACCTTCCAGTTTCATAGCCATAAGAAATGCTGCTTTC             CG110540-01   TCTGAAGTCGGCATTGGGATCTCTGCCAATGCCATGCTCCTTCTCTTCCACATCCTCA       DNA Sequence   CGTGCCTTCTCAAGCACAGGACCAAGCCCGCTGACCTGATCGTTTGTCATGTGGCTCT                   AATCCATATCATATTGCTGCTACCCACAGAGTTCATAGCTACAGATATTTTTGGGTCT                   CAGGATTCAGAGGATGACATCAAACATAAGTCAGTTATCTACAGGTACAGGTTGATGA                   GAGGCCTCTCCATTTCCACCACCTGCCTGCTGAGTATCCTCCCGGCCATCACCTGCAG                   CCCCAGAAGCTCCTGTTTGGCAGTGTTCAAAAGATTCTCACATCACCAACCACGTTGC                   TTTCTCTTCCTATGGGTCTTCCACATATCCATTAGTGACAGCTTCTTAGTCTCCACTC                   TTCCCATCAAAAATCTGGCCTCAAATAGCCTTACATTTGTCACTCAATCCTGCTCTGC                   TGGGATCCTGAGTTGCTTCCTTGAGCAGACAATTTTCACACTGATGACATTTCAGGAT                   GTCTCCCTTGCAGGGCTCACGGCCCCCTCCAGTGGATACATGGTGATTCTCTTGTCCA                   GGCGTAACAGGCAGTCCCAGCATTTTCACAGCACCAACCTTTCTCCAAAAGCACCCCC                   AGAAAAAATGGCCACGCAGACCATTCTTCTGCTCGTGAGTTGCTTTGTGATTGTGTAT                   GTTTTGGACTGTGTTGTCGCCTCCTGCTCAGGACTGGTGTGGAACAGTGATCCAGTCC                   GTCATCGAGTCCAGATGCTGGTGGACAATGGCTATGCCACCATCAGTCCTTCAGTGCT                   AGTCAGTACTGAAAAA TGA   ATGATCAAA                                           ORF Start: ATG at 5   ORF Stop: TGA at 887                                         SEQ ID NO: 44   294 aa   MW at 32551.7 Da                             NOV10a,   MNKNNKPSSFIAIRNAAFSEVGIGISANAMLLLFHILTCLLKHRTKPADLIVCHVALI           CG110540-01   HIILLLPTEFIATDIFGSQDSEDDIKHKSVIYRYRLMRGLSISTTCLLSILPAITCSP       Protein Sequence   RSSCLAVFKRFSHHQPRCFLFLWVFHISISDSFLVSTLPIKNLASNSLTFVTQSCSAG                   ILSCFLEQTIFTLMTFQDVSLAGLTAPSSGYMVILLSRRNRQSQHFHSTNLSPKAPPE                   KMATQTILLLVSCFVIVYVLDCVVASCSGLVWNSDPVRHRVQMLVDNGYATISPSVLV                   STEK                                         SEQ ID NO: 45   1420 bp                             NOV10b,     TGTGGGTCGCTGCTTCCTGGCCCTTCTCCGACCCCGCTCTAGCAGCAGACCTCCTGGG             CG110578-02     GTCTGTGGGTTGATCTGTGGCCCCTGTGCCTCCGTGTCCTTTTCGTCTCCCTTCCTCC         DNA Sequence     CGACTCCGCTCCCGGACCAGCGGCCTGACCCTGGGGAAAGG   ATG GTTCCCGAGGTGAG                   GGTCCTCTCCTCCTTGCTGGGACTCGCGCTGCTCTGGTTCCCCCTGGACTCCCACGCT                   CGAGCCCGCCCAGACATGTTCTGCCTTTTCCATGGGAAGAGATACTCCCCCGGCGAGA                   GCTGGCACCCCTACTTGGAGCCACAAGGCCTGATGTACTGCCTGCGCTGTACCTGCTC                   AGAGGGCGCCCATGTGAGTTGTTACCGCCTCCACTGTCCGCCTGTCCACTGCCCCCAG                   CCTGTGACGGAGCCACAGCAATGCTGTCCCAAGTGTGTGGAACCTCACACTCCCTCTG                   GACTCCGGGCCCCACCAAAGTCCTGCCAGCACAACGGGACCATGTACCAACACGGAGA                   GATCTTCAGTGCCCATGAGCTGTTCCCCTCCCGCCTGCCCAACCAGTGTGTCCTCTGC                   AGCTGCACAGAGGGCCAGATCTACTGCGGCCTCACAACCTGCCCCGAACCAGGCTGCC                   CAGCACCCCTCCCGCTGCCAGACTCCTGCTGCCAGGCCTGCAAAGATGAGGCAAGTGA                   GCAATCGGATGAAGAGGACAGTGTGCAGTCGCTCCATGGGGTGAGACATCCTCAGGAT                   CCATGTTCCAGTGATGCTGGGAGAAAGAGAGGCCCGGGCACCCCAGCCCCCACTGGCC                   TCAGCGCCCCTCTGAGCTTCATCCCTCGCCACTTCAGACCCAAGGGAGCAGGCAGCAC                   AACTGTCAAGATCGTCCTGAAGGAGAAACATAAGAAAGCCTGTGTGCATGGCGGGAAG                   ACGTACTCCCACGGGGAGGTGTGGCACCCGGCCTTCCGTGCCTTCGGCCCCTTGCCCT                   GCATCCTATGCACCTGTGAGGATGGCCGCCAGGACTGCCAGCGTGTGACCTGTCCCAC                   CGAGTACCCCTGCCGTCACCCCGAGAAAGTGGCTGGGAAGTGCTGCAAGATTTGCCCA                   GAGGACAAAGCAGACCCTGGCCACAGTGAGATCAGTTCTACCAGGTGTCCCAAGGCAC                   CGGGCCGGGTCCTCGTCCACACATCGGTATCCCCAAGCCCAGACAACCTGCGTCGCTT                   TGCCCTGGAACACGAGGCCTCGGACTTGGTGGAGATCTACCTCTGGAAGCTGGTAAAA                   GGAATCTTCCACTTGACTCAGATCAAGAAAGTCAGGAAGCAAGACTTCCAGAAACACA                   TACGCCTCTTCCCTCTTCTGCCCTCCTCCATGCAGGTCACTGGAACGTCTTCC TAG   cc                       CAGATCCTGGAGCTGAAGGTCACGGCCA                                           ORF Start: ATG at 158   ORF Stop: TAG at 1388                                         SEQ ID NO: 46   410 aa   MW at 45294.6 Da                             NOV10b,   MVPEVRVLSSLLGLALLWFPLDSHARARPDMFCLFHGKRYSPGESWHPYLEPQGLMYC           CG110578-02   LRCTCSEGAHVSCYRLHCPPVHCPQPVTEPQQCCPKCVEPHTPSGLRAPPKSCQHNGT       Protein Sequence   MYQHGEIFSAHELFPSRLPNQCVLCSCTEGQIYCGLTTCPEPGCPAPLPLPDSCCQAC                   KDEASEQSDEEDSVQSLHGVRHPQDPCSSDAGRKRGPGTPAPTGLSAPLSFIPRHFRP                   KGAGSTTVKIVLKEKHKKACVHGGKTYSHGEVWHPAFRAFGPLPCILCTCEDGRQDCQ                   RVTCPTEYPCRHPEKVAGKCCKICPEDKADPGHSEISSTRCPKAPGRVLVHTSVSPSP                   DNLRRFALEHEASDLVEIYLWKLVKGIFHLTQIKKVRKQDFQKHIRLFPLLPSSMQVT                   GTSS                  
 
     [0387] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 10B.  
               TABLE 10B                          Comparison of NOV10a against NOV 10b.                         Protein   NOV10a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV 10b   254 . . . 260   4/7 (57%)           138 . . . 144   6/7 (85%)                  
 
     [0388] Further analysis of the NOV10a protein yielded the following properties shown in Table 10C.  
               TABLE 10C                       Protein Sequence Properties NOV10a                                        PSort   0.6000 probability located in plasma membrane;       analysis:   0.4000 probability located in Golgi body; 0.3331 probability           located in mitochondrial inner membrane; 0.3000 probability           located in endoplasmic reticulum (membrane)       SignalP   Cleavage site between residues 46 and 47       analysis:                  
 
     [0389] A search of the NOV10a 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.  
               TABLE 10D                          Geneseq Results for NOV10a                                         NOV10a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAE18646   Human G-protein coupled receptor    1 . . . 294   258/294 (87%)    e−138           (GCREC-7) -  Homo sapiens , 271 aa.    1 . . . 27   258/294 (87%)           [WO200210387-A2, 07 FEB. 2002]       AAW19107   Rat pheromone receptor VN6 -  Rattus     18 . . . 293   140/277 (50%)   7e−67             sp , 310 aa. [WO9714790-A1,   18 . . . 293   181/277 (64%)           24 APR. 1997]       AAM48284   Pheromone receptor protein VN1-18-    1 . . . 125   125/125 (100%)   6e−66           Unidentified, 165 aa. [WO200206333-   17 . . . 141   125/125 (100%)           A1, 24 JAN. 2002]       AAW19104   Rat pheromone receptor VN3 -  Rattus      1 . . . 294   135/295 (45%)   8e−62             sp , 311 aa. [WO9714790-A1,    2 . . . 295   185/295 (61%)           24 APR. 1997]       AAW19103   Rat pheromone receptor VN1 -  Rattus      1 . . . 294   133/295 (45%)   7e−61             sp , 315 aa. [WO9714790-A1,    2 . . . 295   190/295 (64%)           24 APR. 1997]                  
 
     [0390] 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.  
               TABLE 10E                          Public BLASTP Results for NOV10a                                         NOV10a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q8WNV6   Putative pheromone receptor gVIR1 -    3 . . . 294   172/293 (58%   6e−84             Capra hircus  (Goat), 308 aa.    2 . . . 294   205/293 (69%)       Q62855   Pheromone receptor VN6 -  Rattus     18 . . . 293   140/277 (50%)   2e−66             norvegicus  (Rat), 310 aa.   18 . . . 293   181/277 (64%)       Q9EPA4   VN12 (VOMERONASAL receptor    1 . . . 294   136/295 (46%)   7e−64           VIRA1) -  Mus musculus  (Mouse),    1 . . . 294   193/295 (65%)           303 aa.       Q8VIC6   Vomeronasal receptor 1 A8 -  Mus      1 . . . 294   136/295 (46%)   7e−64             musculus  (Mouse), 329 aa.   27 . . . 320   193/295 (65%)       Q9Z195   Pheromone receptor 1 -  Mus      1 . . . 294   136/295 (46%)   7e−64             musculus  (Mouse), 305 aa.    3 . . . 296   193/295 (65%)                  
 
     [0391] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10F.  
               TABLE 10F                          Domain Analysis of NOV10a                                     Identities/           Pfam   NOV10a   Similarities   Expect       Domain   NOV10a Match Region   for the Matched Region   Value                         No Significant Known Matches Found                  
 
     Example 11  
     [0392] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A.  
               TABLE 11A !NOV11 Sequence Analysis                          SEQ ID NO: 47   1024 bp                             NOV11a,     GACTCGTCTCAGGCCAGTTGCAGCCTTCTCAGCCAAACGCCGACCAAGGAAAACTCAC             CG110725-     TACC   ATG AGAATTGCAGTGATTTGCTTTTGCCTCCTAGGCATCACCTGTGCCATACCA       01 DNA   GTTAAACAGGCTGATTCTGGAAGTTCTGAGGAAAAGCAGCTTTACAACAAATACCCAG       Sequence   ATGCTGTGGCCACATGGCTAAACCCTGACCCATCTCAGAAGCAGAATCTCCTAGCCCC                   ACAGAATGCTGTGTCCTCTGAAGAAACCAATGACTTTAAACAAGAGACCCTTCCAAGT                   AAGTCCAACGAAAGCCATGACCACATGGATGATATGGATGATGAAGATGATGATGACC                   ATGTGGACAGCCAGGACTCCATTGACTCGAACGACTCTGATGATGTAGATGACACTGA                   TGATTCTCACCAGTCTGATGAGTCTCACCATTCTGATGAATCTGATGAACTGGTCACT                   GATTTTCCCACGGACCTGCCAGCAACCGAAGTTTTCACTCCAGTTGTCCCCACAGTAG                   ACACATATGATGGCCGAGGTGATAGTGTGGTTTATGGACTGAGGTCAAAATCTAAGAA                   GTTTCGCAGACCTGACATCCAGTACCCTGATGCTACAGACGAGGACATCACCTCACAC                   ATGGAAAGCGAGGAGTTGAATGGTGCATACAAGGCCATCCCCGTTGCCCAGGACCTGA                   ACGCGCCTTCTGATTGGGACAGCCGTGGGAAGGACAGTTATGAAACGAGTCAGCTGGA                   TGACCAGAGTGCTGAAACCCACAGCCACAAGCAGTCCAAAGTCAGCCGTGAATTCCAC                   AGCCATGAATTTCACAGCCATGAAGATATGCTGGTTGTAGACCCCAAAAGTAAGGAAG                   AAGATAAACACCTGAAATTTCGTATTTCTCATGAATTAGATAGTGCATCTTCTGAGGT                   CAAT TAA   AAGGAGAAAAAAATACAATTTCTCACTTTGCATTTAGTCAAAAGAAAAAAT                       GCTTTATAGCAAAATGAAAGAGAACATGAAATGCTTCT                                           ORF Start: ATG at 63   ORF Stop: TAA at 933                                         SEQ ID NO: 48   290 aa   MW at 32606.4 Da                             NOV11a,   MRIAVICFCLLGITCAIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQ           CG110725-   NAVSSEETNDFKQETLPSKSNESHDHMDDMDDEDDDDHVDSQDSIDSNDSDDVDDTDD       01 Protein   SHQSDESHHSDESDELVTDFPTDLPATEVFTPVVPTVDTYDGRGDSVVYGLRSKSKKF       Sequence   RRPDIQYPDATDEDITSHMESEELNGAYKAIPVAQDLNAPSDWDSRGKDSYETSQLDD                   QSAETHSHKQSKVSREFHSHEFHSHEDMLVVDPKSKEEDKHLKFRISHELDSASSEVN                                         SEQ ID NO: 119   834 bp                             NOV11b,   GGATCCATACCAGTTAAACAGGCTGATTCTGGAAGTTCTGAGGAAAAGCAGCTTTACAACAAATACCCAG           209934449   ATGCTGTGGCCACATGGCTAAACCCTGACCCATCTCAGAAGCAGAATCTCCTAGCCCCACAGAATGCTGT       DNA   GTCCTCTGAAGAAACCAATGACTTTAAACAAGAGACCCTTCCAAGTAAGTCCAACGAAAGCCATGACCAC       Sequence   ATGGATGATATGGATGATGAAGATGATGATGACCATGTGGACAGCCAGGACTCCATTGACTCGAACGACT                   CTGATGATGTAGATGACACTGATGATTCTCACCAGTCTGATGAGTCTCACCATTCTGATGAATCTGATGA                   ACTGGTCACTGATTTTCCCACGGACCTGCCAGCAACCGAAGTTTTCACTCCAGTTGTCCCCACAGTAGAC                   ACATATGATGGCCGAGGTGATAGTGTGGTTTATGGACTGAGGTCAAAATCTAAGAAGTTTCGCAGACCTG                   ACATCCAGTACCCTGATGCTACAGACGAGGACATCACCTCACACATGGAAAGCGAGGAGTTGAATGGTGC                   ATACAAGGCCATCCCCCTTGCCCAGGACCTGAACGCGCCTTCTGATTGGGACAGCCGTGGGAAGGACAGT                   TATGAAACGAGTCAGCTGGATGACCAGAGTGCTGAAACCCACAGCCACAAGCAGTCCAAAGTCAGCCGTG                   AATTCCACAGCCATGAATTTCACAGCCATGAAGATATGCTGGTTGTAGACCCCAAAAGTAAGGAAGAAGA                   TAAACACCTGAAATTTCGTATTTCTCATGAATTAGATAGTGCATCTTCTGAGGTCAATCTCGAG                                         ORF Start: ATG at 1   ORF Stop: at 834                                         SEQ ID NO: 120   278 aa   MW at 31282.25 Da                             NOV11b,   GSIPVKQADSGSSEEKQLYNKYPDAVATWLNPDPSQKQNLLAPQNAVSSEETNDFKQETL           209934449   PSKSNESHDHMDDMDDEDDDDHVDSQDSIDSNDSDDVDDTDDSHQSDESHHSDESDELVT       Protein   DFPTDLPATEVFTPVVPTVDTYDGRGDSVVYGLRSKSKKFRRPDIQYPDATDEDITSHME       Sequence   SEELNGAYKAIPVAQDLNAPSDWDSRGKDSYETSQLDDQSAETHSHKQSKVSREFHSHEF           HSHEDMLVVDPKSKEEDKHLKFRISHELDSASSEVNLE                  
 
     [0393] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.  
               TABLE 11B                       Protein Sequence Properties NOV11a                                        PSort   0.8200 probability located in outside; 0.1900 probability       analysis:   located in lysosome (lumen); 0.1000 probability located in           endoplasmic reticulum (membrane); 0.1000 probability           located in encloplasmic reticulum (lumen)       SignalP   Cleavage site between residues 17 and 18       analysis:                  
 
     [0394] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11C.  
               TABLE 11C                          Geneseq Results for NOV11a                                         NOV11a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB30573   A human Eta-1/osteopontin-a protein -   1 . . . 290   290/314 (92%)   e−168             Homo sapiens , 314 aa.   1 . . . 314   290/314 (92%)           [WO200063241-A2, 26 OCT. 2000]       AAE12683   Human osteopontin (OPN) -  Homo     1 . . . 290   290/314 (92%)   e−168             sapiens , 314 aa. [WO200171358-A1,   1 . . . 314   290/314 (92%)           27 SEP. 2001]       AAB01351   Human osteopontin -  Homo sapiens ,   1 . . . 290   290/314 (92%)   e−168           314aa. [WO200033865-A1, 15 JUN. 2000]   1 . . . 314   290/314 (92%)       AAB19770   Human osteopontin -  Homo sapiens ,   1 . . . 290   290/314 (92%)   e−168           314 aa. [WO200062065-A1, 19 OCT. 2000]   1 . . . 314   290/314 (92%)       AAW99779   Human osteopontin -  Homo sapiens ,   1 . . . 290   290/314 (92%)   e−168           314 aa. [WO9908730-A1, 25 FEB. 1999]   1 . . . 314   290/314 (92%)                  
 
     [0395] In a BLAST search of public sequence databases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D.  
               TABLE 11D                          Public BLASTP Results for NOV11a                                         NOV11a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               P10451   Osteopontin precursor (Bone sialoprotein   1 . . . 290   290/314 (92%)   e−167           1) (Urinary stone protein) (Secreted   1 . . . 314   290/314 (92%)           phosphoprotein 1) (SPP-1) (Nephropontin)           (Uropontin) -  Homo sapiens  (Human), 314           aa.       Q961Z1   Secreted phosphoprotein 1 (osteopontin,   1 . . . 290   276/314 (87%)   e−156           bone sialoprotein 1, early T-lymphocyte   1 . . . 300   276/314 (87%)           activation 1) -  Homo sapiens  (Human),           300 aa.       CAC16643   Sequence 5 from Patent WO0063241 -   1 . . . 290   263/314 (83%)   e−145             Homo sapiens  (Human), 287 aa.   1 . . . 287   263/314 (83%)       P31097   Osteopontin precursor (Bone sialoprotein   1 . . . 290   200/315 (63%)   e−110           1) (Secreted phosphoprotein 1) (SPP-1)   1 . . . 311   242/315 (76%)           (OC-1) -  Oryctolagus cuniculus  (Rabbit),           311 aa.       P14287   Osteopontin precursor (Bone sialoprotein   1 . . . 290   204/309 (66%)   e−104           1) (Secreted phosphoprotein 1) (SPP-1) -   1 . . . 303   231/309 (74%)             Sus scrofa  (Pig), 303 aa.                  
 
     [0396] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.  
               TABLE 11E                          Domain Analysis of NOV11a                                     Identities/           Pfam   NOV11a   Similarities   Expect       Domain   Match Region   for the Matched Region   Value               Osteopontin   1 . . . 290   245/334 (73%)   6.7e−198               290/334 (87%)                  
 
     Example 12  
     [0397] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.  
               TABLE 12A                       NOV12 Sequence Analysis                                                    SEQ ID NO: 49   1042 bp                             NOV 12a,     ATG GATGTGGGCAGCAAAGAGGTCCTGATGGAGAGCCCGCCGCCGTGTCAGGACTACT           CG111683-01   CCGCAGCTCCCCGGGGCCGATTTGGCATTCCCTGCTGCCCAGTGCACCTGAAACGCCT       DNA Sequence   TCTTATCGTGGTGGTGGTGGTGGTCTCCATCGTCGTGGTGATTGTGGGAGCCCTGCTC                   ATGGGTCTCCACATGAGCCAGAAACACTTTCCCCAGGTTCTGGAGATGAGCATTGGGG                   CGCCGGAAGCCCAGCAACGCCTGGCCCTGAGTGAGCACCTGGTTACCACTGCCACCTT                   CTCCATCGGCTCCACTGGCCTCGTGGTGTATGACTACCAGCAGCTGCTGATCGCCTAC                   AAGCCAGCCCCTGGCACCTGCTGCTACATCATGAAGATAGCTCCAGAGAGCATCCCCA                   GTCTTGAGGCTCTCACTAGAAAAGTCCACAACTTCCAGGCCAAGCCCGCAGTGCCTAC                   GTCTAAGCTGGGCCAGGCAGAGGGGCGAGATGCAGGCTCAGCACCCTCCGGAGGGGAC                   CCGGCCTTCCTGGGCATGGCCGTGAGCACCCTGTGTGGCGAGGTGCCGCTCTACTACA                   TC TAG   GACGCCTCCGGTGAGCAGGTGTGATCCCAGGGCCCCTGATCAGCAGCGGAGGA                       GCGCTCGGGCCACCTGCCCGGGCTGTGGAGGAGCGCTCGCGCTGACCAGGCGCTGGGG                       CGTCCACTGAAGCGGGGTCATCCAGGCAACTCGGGGGAGGGGAAGCTCACAGACCGGT                       ACTTCCCACTCCCCTGAATTCTCTCTGTCCATCCTCAACATTCCTTTGCTTCACAGGG                       TCAGTGGAAGCCCCAACGGGAAAGGAAACGCCCCGGGCAAAGGGTCTTTTGCAGCTTT                       TGCAGACGGGCAAGAAGCTGCTTCTGCCCACACCGCAGGGACAAACCCTGGAGAAATG                       GGAGCTTGGGGAGAGGATGGGAGTGGGCAGAGGTGGCACCCAGGGGCCCGGGAACTCC                       TGCCACAACAGAATAAAGCAGCCTGATTGAAAAGCAAAAAAAAAAAAAAAAAACTC                                           ORF Start: ATG at 1   ORF Stop: TAG at 583                                         SEQ ID NO: 50   194 aa   MW at 20634.0 Da                             NOV 12a,   MDVGSKEVLMESPPPCQDYSAAPRGRFGIPCCPVHLKRLLIVVVVVVSIVVVIVGALL           CG111683-01   MGLHMSQKHFPQVLEMSIGAPEAQQRLALSEHLVTTATFSIGSTGLVVYDYQQLLIAY       Protein Sequence   KPAPGTCCYIMKIAPESIPSLEALTRKVHNFQAKPAVPTSKLGQAEGRDAGSAPSGGD           PAFLGMAVSTLCGEVPLYYI                                         SEQ ID NO: 51   590 bp                             NOV 12b,     ATG GATGTGGGCAGCAAAGAGGTCCTGATGGAGAGCCCGCCGGACTACTCCGCAGCTC           CG111683-02   CCCGGGGCCGATTTGGCATTCCCTGCTGCCCAGTGCACCTGAAACGCCTTCTTATCGT       DNA Sequence   GGTGGTGGTGGTGGTCCTCATCGTCGTGGTGATTGTGGGAGCCCTGCTCATGGGTCTC                   CACATGAGCCAGAAACACACGGAGATGGTTCTGGAGATGAGCATTGGGGCGCCGGAAG                   CCCAGCAACGCCTGGCCCTGAGTGAGCACCTGGTTACCACTGCCACCTTCTCCATCGG                   CTCCACTGGCCTCGTGGTGTATGACTACCAGCAGCTGCTGATCGCCTACAAGCCAGCC                   CCTGGCACCTGCTGCTACATCATGAAGATAGCTCCAGAGAGCATCCCCAGTCTTGAGG                   CTCTCAATAGAAAAGTCCACAACTTCCAGGCCAAGCCCGCAGTGCCTACGTCTAAGCT                   GGGCCAGGCAGAGGGGCGAGATGCAGGCTCAGCACCCTCCGGAGGGGACCCGGCCTTC                   CTGGGCATGGCCGTGAACACCCTGTGTGGCGAGGTGCCGCTCTACTACATC TAG   GCGC                       CTCCGGTGAG                                           ORF Start: ATG at 1   ORF Stop: TAG at 574                                         SEQ ID NO: 52   191 aa   MW at 20360.8 Da                             NOV12b,   MDVGSKEVLMESPPDYSAAPRGRFGIPCCPVHLKRLLIVVVVVVLIVVVIVGALLMGL           CG111683-02   HMSQKHTEMVLEMSIGAPEAQQRLALSEHLVTTATFSIGSTGLVVYDYQQLLIAYKPA       Protein Sequence   PGTCCYIMKIAPESIPSLEALNRKVHNFQAKPAVPTSKLGQAEGRDAGSAPSGGDPAF           LGMAVNTLCGEVPLYYI                                         SEQ ID NO: 53   530 bp                             NOV12c,     TG GAT GTGGGCAGCAAAGAGGTCCTGATGGAGAGCCCGCCGGACTACTCCGCAGCTCC             CG111683-03   CCGGGGCCGATTTGGCATTCCCTGCTGCCCAGTGCACCTGAAACGCCTTCTTATCGTG       DNA Sequence   GTGGTGGTGGTCCTCATCGTCGTGGTGATTGTGGAAGCCCAGCAACGCCTGGCCCTGA                   GTGAGCACCTGGTTACCACTGCCACCTTCTCCATCGGCTCCACTGGCCTCGTGGTGTA                   TGACTACCAGCAGCTGCTGATCGCCTACAAGCCAGCCCCTGGCACCTGCTGCTACATC                   ATGAAGATAGCTCCAGAGAGCATCCCCAGTCTTGAGGCTCTCAATAGAAAAGTCCACA                   ACTTCCAGATGGAATGCTCTCTGCAGGCCAAGCCCGCAGTGCCTACGTCTAAGCTGGG                   CCAGGCAGAGGGGCGAGATGCAGGCTCAGCACCCTCCGGAGGGGACCCGGCCTTCCTG                   GGCATGGCCGTGAACACCCTGTGTGGCGAGGTGCCGCTCTACTACATC TAG   GACGCCT                       CCGGTGAG                                           ORF Start: at 3   ORF Stop: TAG at 513                                         SEQ ID NO: 54   170 aa   MW at 18158.0 Da                             NOV12c,   DVGSKEVLMESPPDYSAAPRGRFGIPCCPVHLKRLLIVVVVVLIVVVIVEAQQRLALS           CG111683-03   EHLVTTATFSIGSTGLVVYDYQQLLIAYKPAPGTCCYIMKIAPESIPSLEALNRKVHN       Protein Sequence   FQMECSLQAKPAVPTSKLGQAEGRDAGSAPSGGDPAFLGMAVNTLCGEVPLYYI                  
 
     [0398] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 12B.  
               TABLE 12B                          Comparison of NOV12a against NOV12b and NOV12c.                         Protein   NOV12a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV12b   1 . . . 194   170/194 (87%)           1 . . . 191   171/194 (87%)       NOV12c   2 . . . 194   147/199 (73%)           1 . . . 170   148/199 (73%)                  
 
     [0399] Further analysis of the NOV12a protein yielded the following properties shown in Table 12C.  
               TABLE 12C                       Protein Sequence Properties NOV12a                                        PSort   0.7900 probability located in plasma membrane;       analysis:   0.3000 probability located in microbody (peroxisome); 0.3000           probability located in Golgi body; 0.2000 probability           located in endoplasmic reticulum (membrane)       SignalP   Cleavage site between residues 57 and 58       analysis:                  
 
     [0400] A search of the NOV12a 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.  
               TABLE 12D                          Geneseq Results for NOV12a                                         NOV12a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB58144   Lung cancer associated polypeptide    1 . . . 194   187/194 (96%)    e−102           sequence SEQ ID 482 -  Homo sapiens ,   26 . . . 216   187/194 (96%)           216 aa. [WO200055180-A2,           21 SEP. 2000]       AAP82978   Human SP5 protein -  Homo sapiens , 197    1 . . . 194   187/200 (93%)    e−100           aa. [WO8805820-A, 11 AUG 1988]    1 . . . 197   187/200 (93%)       AAP70440   Sequence of a canine 5 kd alveolar    1 . . . 194   187/200 (93%)    e−100           surfactant protein (ASP) from clone    1 . . . 197   187/200 (93%)           cDNA #19 - Dog, 197 aa. [WO8706588-           A, 05 NOV. 1987]       AAR15609   SP-5 clone #19 -  Homo sapiens , 197 aa.    1 . . . 194   186/200 (93%)   2e−99           [WO9118015-A, 28 NOV. 1991]    1 . . . 197   187/200 (93%)       AAP90038   Deduced sequence of cDNA number 19    1 . . . 194   186/200 (93%)   2e−99           encoding human SP-5-derived protein -    1 . . . 197   187/200 (93%)             Homo sapiens , 197 aa. [WO8904326-A,           18 MAY 1989]                  
 
     [0401] 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.  
               TABLE 12E                          Public BLASTP Results for NOV12a                                         NOV12a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               P11686   Pulmonary surfactant-associated protein C   1 . . . 194   185/200 (92%)   2e−98           precursor (SP-C) (SP5) (Pulmonary   1 . . . 197   186/200 (92%)           surfactant-associated proteolipid           SPL(Val)) -  Homo sapiens  (Human), 197           aa.       P55152   Pulmonary surfactant-associated protein C   1 . . . 194   174/194 (89%)   5e−92           precursor (SP-C) (Pulmonary surfactant-   1 . . . 191   176/194 (90%)           associated proteolipid SPL(Val)) -  Macaca               mulatta  (Rhesus macaque), 191 aa.       Q9N276   Pulmonary surfactant-associated protein   1 . . . 193   159/193 (82%)   9e−83           C -  Ovis aries  (Sheep), 190 aa.   1 . . . 189   169/193 (87%)       Q9BDX5   Pulmonary surfactant-associated protein C   1 . . . 193   156/193 (80%)   5e−81           proSP-C -  Bos taurus  (Bovine), 190 aa.   1 . . . 189   168/193 (86%)       P35245   Pulmonary surfactant-associated protein C   1 . . . 194   154/194 (79%)   1e−80           precursor (SP-C) -  Mustela vison     1 . . . 190   167/194 (85%)           (American mink), 190 aa.                  
 
     [0402] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12F.  
               TABLE 12F                          Domain Analysis of NOV12a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV12a Match Region   for the Matched Region   Value               PSAP   27 . . . 194   150/171 (88%)   6.2e−126               164/171 (96%)                  
 
     Example 13  
     [0403] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A.  
               TABLE 13A                       NOV13 Sequence Analysis                                                    SEQ ID NO: 55   1659 bp                             NOV13a,     CGGGCCATGGCCAGAGACCCCCTCCTCTGGGCTCCCTGAAGTCCTGGGGAGCCGTGAC             CG112655-01     CC   ATG GGATCGTCGAGCAGCCGGGTGCTGGGCCAGCCGAGGCGAGCCCTTGCCCAGCA       DNA Sequence   GGAACAGGGTGCCAGGGCCAGGGGCTCGGCCCGGAGGCCGGACACTGGAGACGATGCG                   GCGAGCTACGGCTTCTGTTACTGCCCGGGCAGTCACAAGCGCAAGCGGAGCAGCGGGG                   CCTGCCGCTACTGTGACCCGGACTCGCACAGGGAGGAGCATGAGGAGGAGGGGGACAA                   GCAGCAGCCGCTCCTCAACACCCCTGCAAGGAAAAAATTAAGGAGTACATCCAAATAT                   ATTTATCAAACATTATTTTTGAATGGTGAAAACAGTGACATTAAGATTTGTGCTCTAG                   GAGAAGAATGGCGATTACACAAAATATATTTATGTCAATCTGGCTACTTTTCTAGTAT                   GTTCAGTGGTTCTTGGAAAGAATCCAGCATGAATATTATTGAACTGGAGATTCCTGAC                   CAGAACATTGATGTAGACGCACTGCAGGTTGCGTTTGGTTCACTGTATCGAGATGATG                   TCTTGATAAAACCCAGTCGAGTTGTTGCCATTTTGGCAGCAGCTTGTATGCTGCAGCT                   GGATGGTTTAATACAGCAGTGTGGTGAGACAATGAAGGAAACAATTAATGTGAAAACT                   GTATGCGGTTATTACACATCAGTAGAGATCTATGGATTAGATTCTGTAAAGAAAAAGT                   GCCTTGAATGGCTTCTAAACAATTTGATGACTCACCAGAATGTTAAACTTTTTAAAGA                   ACTCGGTATAAATGTCATGAAACAGCTCATTGGTTCCTCTAACTTATTTGTGATGCAA                   GTGGAGATGGATGTATACACCACTCTAAAAAAGTGGATGTTCCTTCAACTTGTGCCTT                   CTTGGAATGGATCTTTAAAACAGCTTTTGACAGAAACAGATGTCTGGTTTTCTAAACA                   GAGAAAAGATTTTGAAGGTATGGCCTTTCTTGAAACTGAACCAGGAAAACCATTTGTG                   TCAGTATTCAGACATTTAAGGTTACAATATATTATCAGTGACCTAGCTTCTGCAAGAA                   TTATTGAACAAGATGGTATAGTACCTTCAGAATGGCTGTCTTCTGTGTATAAACAGCA                   GTGGTTTGCTATGCTGCGGGCAGAACAAGACCATGAGGTAGGGCCTCAAGAAATCAAT                   AAAGAAGACCTAGAGGGAAGTAGCATGAGGTGTGGTAGAAAGCTTGCCAAAGATGGTG                   AATACTACTGGTGTTGGACGGGTTTTAACTTCGGCTTTGACCTACTTGTAATTTACAC                   CAATGGATACATCATTTTCAAACGCAATACACTGAATCAGCCATGCAGCGGGTCTGTC                   AGTTTACGGCCTCGAAGGAGCATAGCATTTAGATTACGCTTGGCTTCTTTTGATAGTA                   GTGGAAAACTAGTATGTAGTAGAACAACTGGCTATCAAATACTTATACTTAAAAAGGA                   TCAGGAACAAGTGGTGATGAACTTGGACAGCAGGTTTCTGACCTTCCCTTTATATATC                   TGCTGTAACTTCTTGTATATATCACCAGAAAAAGGAATTGAAAATAATCGCCACCCAG                   AAGATCCAGAAAAC TGA   AGATCTCATCAGTTGGAA                                           ORF Start: ATG at 61   ORF Stop: TGA at 1639                                         SEQ ID NO: 56   526 aa   MW at 60200.2 Da                             NOV13a,   MGSSSSRVLGQPRRALAQQEQGARARGSARRPDTGDDAASYGFCYCPGSHKRKRSSGA           CG112655-01   CRYCDPDSHREEHEEEGDKQQPLLNTPARKKLRSTSKYIYQTLFLNGENSDIKICALG       Protein Sequence   EEWRLHKIYLCQSGYFSSMFSGSWKESSMNIIELEIPDQNIDVDALQVAFGSLYRDDV                   LIKPSRVVAILAAACMLQLDGLIQQCGLTMKETINVKTVCGYYTSVEIYGLDSVKKKC                   LEWLLNNLMTHQNVKLFKELGINVMKQLIGSSNLFVMQVEMDVYTTLKKWMFLQLVPS                   WNGSLKQLLTETDVWFSKQRKDFEGMAFLETEPGKPFVSVFRHLRLQYIISDLASARI                   IEQDGIVPSEWLSSVYKQQWFAMLRAEQDHEVGPQEINKEDLEGSSMRCGRKLAKDGE                   YYWCWTGFNFGFDLLVIYTNGYIIFKRNTLNQPCSGSVSLRPRRSIAFRLRLASFDSS                   GKLVCSRTTGYQILILKKDQEQVVMNLDSRFLTFPLYICCNFLYISPEKGIENNRHPE                   DPEN                  
 
     [0404] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.  
               TABLE 13B                       Protein Sequence Properties NOV13a                                        PSort   0.6850 probability located in plasma membrane;       analysis:   0.4605 probability located in mitochondrial inner membrane;           0.3500 probability located in nucleus; 0.2000           probability located in endoplasmic reticulum (membrane)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0405] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13C.  
               TABLE 13C                          Geneseq Results for NOV13a                                         NOV13a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB944442   Human protein sequence SEQ ID    1 . . . 513   465/513 (90%)   0.0           NO: 15072 -  Homo sapiens , 515 aa.    1 . . . 513   482/513 (93%)           [EP1074617-A2, 07 FEB. 2001]       AAB95625   Human protein sequence SEQ ID    1 . . . 510   462/510 (90%)   0.0           NO: 18346 -  Homo sapiens , 510 aa.    1 . . . 510   477/510 (92%)           [EP1074617-A2, 07 FEB. 2001]       AAY18025   Murine DIP protein sequence -  Mus sp ,    1 . . . 524   442/524 (84%)   0.0           524 aa. [WO9927091-A1, 03 JUN. 1999]    1 . . . 522   470/524 (89%)       AAY01080   Human testis specific growth factor,    48 . . . 513   427/466 (91%)   0.0           ZGCL-1, protein sequence -  Homo      12 . . . 477   442/466 (94%)             sapiens , 478 aa. [WO9909168-A1,           25 FEB. 1999]       AAB94515   Human protein sequence SEQ ID   135 . . . 513   352/379 (92%)   0.0           NO: 15231 -  Homo sapiens , 381 aa.    1 . . . 379   362/379 (94%)           [EP1074617-A2, 07 FEB. 2001]                  
 
     [0406] 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 13D.  
               TABLE 13D                          Public BLASTP Results for NOV13a                                         NOV13a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q8TC88   Hypothetical 60.2 kDa protein -  Homo     1 . . . 526   525/526 (99%)   0.0             sapiens  (Human), 526 aa.   1 . . . 526   526/526 (99%)       Q8TC89   Hypothetical 60.2 kDa protein -  Homo     1 . . . 526   524/526 (99%)   0.0             sapiens  (Human), 526 aa.   1 . . . 526   525/526 (99%)       Q961K5   Hypothetical 58.7 kDa protein -  Homo     1 . . . 513   466/513 (90%)   0.0             sapiens  (Human), 515 aa.   1 . . . 513   482/513 (93%)       Q9H927   CDNA FLJ13057 fis, clone   1 . . . 513   465/513 (90%)   0.0           NT2RP3001580, highly similar to  Mus     1 . . . 513   482/513 (93%)             musculus  strain C57BL/J germ cell-less           protein (Gel) mRNA -  Homo sapiens             (Human), 515 aa.       Q9H826   CDNA FLJ13980 fis, clone   1 . . . 511   463/511 (90%)   0.0           Y79AA1001692, weakly similar to germ   1 . . . 511   478/511 (92%)           cell-LESS protein -  Homo sapiens             (Human), 511 aa (fragment).                  
 
     [0407] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.  
               TABLE 13E                          Domain Analysis of NOV13a                                     Identities/           Pfam       Similarities   Expect       Domain   NOV13a Match Region   for the Matched Region   Value               BTB   92 . . . 208   23/144 (16%)   1.5e−11               83/144 (58%)                  
 
     Example 14  
     [0408] The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A.  
               TABLE 14A                       NOV14 Sequence Analysis                                                    SEQ ID NO: 57   1225 bp                             NOV14a,     TGGCACC   ATG GCCCCCAAACTCATCACCGTCCTGTGTCTGGGATTCTGCCTGAACCAG           CG112813-01   AAGATCTGCCCACATGCGGGTGCTCAGGACAAGTTCTCCCTGTCAGCCTGGCCGAGCC       DNA Sequence   CTGTGGTTCCCCTAGGAGGACGTGTGACTCTCTCCTGTCATTCCCATCTTCGGTTTGT                   CATATGGACAATATTCCAAACAACTGGGACCCGAAGCCATGAGTTGCACACTGGCCTT                   TCCAACAACATCACCATCAGCCCTGTGACCCCAGAACACGCAGGGACCTACAGATGTG                   TTGGAATTTACAAGCACGCCTCAAAGTGGTCAGCTGAGAGCAACTCCCTGAAGATCAT                   CGTCACAGGCTTGTTCACAAAACCCTCCATCTCAGCGCACCCAAGCTCCCTGGTGCAT                   GCAGGAGCCAGGGTGAGCCTGCGCTGTCACTCAGAACTGGCCTTTGATGAATTTATCT                   TATACAAAGAGGGGCACATACAGCATTCCCAGCAGCTTGACCAGGGGATGGAGGCTGG                   GATCCATTACGTCGAGGCTGTCTTTTCCATGGGTCCTGTAACGCCTGCCCATGCAGGA                   GCCTACAGATGCTGTGGTTGTTTCAGTCACTCCCGCTATGAGTGGTCGGCTCCCAGTG                   ACCCCCTGGACATTGTGATCACAGGAAAATACAAAAAGCCTTCTCTCTCCACCCAGGT                   GGACCCCATGATGAGGCTGGGAGAGAAGTTGACCCTCTTCTGCAGCTCTGAAATCTCA                   TTTGACCAGTACCATCTGTTCAGACACGGGGTTGCTCATGGACAGTGGCTCAGTGGAG                   GGCAGAGACACAGGGAAGCATTCCAGGCCAATTTTTCTGTGGGCCGTGCAACGCCAGT                   CCCTGGCGGGACCTATAGATGCTATGGTTCCTTCAATGACTCTCCCTATAAGCCCCCA                   GTGACCCGCTGCAACTTTACACCACAGGAAACACTAAGAGTACTCCTCTGTCATTCAC                   AGAATCCACCCCTGAATCTGGAGCCTGCAGCAGAAGAGACACAGGAGATCATATATGC                   CCAGTTAAACCACCAGGCCCTCTCACAGACAGGATTCCCTCCTGCCTCCCAGTGTCCC                   CACTACCTCTCGGAGGATCCTAGTATCTACATCACTGTCCACCAAGCCCAGGCTGAGG                   CCAGAGCTGCCCCCAGTCTTTGGCACAAAGGGCAT TAA   TACGCAAGGACCTGGATCTA                       TTCCTAG                                           ORF Start: ATG at 8   ORF Stop: TAA at 1196                                         SEQ ID NO: 58   396 aa   MW at 43739.2 Da                             NOV14a,   MAPKLITVLCLGFCLNQKICPHAGAQDKFSLSAWPSPVVPLGGRVTLSCHSHLRFVIW           CG112813-01   TIFQTTGTRSHELHTGLSNNITISPVTPEHAGTYRCVGIYKHASKWSAESNSLKIIVT       Protein Sequence   GLFTKPSISAHPSSLVHAGARVSLRCHSELAFDEFILYKEGHIQHSQQLDQGMEAGIH                   YVEAVFSMGPVTPAHAGAYRCCGCFSHSRYEWSAPSDPLDIVITGKYKKPSLSTQVDP                   MMRLGEKLTLFCSSEISFDQYHLFRHGVAHGQWLSGGQRHREAFQANFSVGRATPVPG                   GTYRCYGSFNDSPYKPPVTRCNFTPQETLRVLLCHSQNPPLNLEPAAEETQEIIYAQL                   NHQALSQTGFPPASQCPHYLSEDPSIYITVHQAQAEARAAPSLWHKGH                                         SEQ ID NO: 59   1399 bp                             NOV14b,     TGGCACC   ATG GCCCCCAAACTCATCACCGTCCTGTGTCTGGGATTCTGCCTGAACCAG           CG112813-02   AAGATCTGCCCACATGCGGGTGCTCAGGACAAGTTCTCCCTGTCAGCCTGGCCGAGCC       DNA Sequence   CTGTGGTTCCCCTAGGAGGACGTGTGACTCTCTCCTGTCATTCCCATCTTCGGTTTGT                   CATATGGACAATATTCCAAACAACTGGGACCCGAAGCCATGAGTTGCACACTGGCCTT                   TCCAACAACATCACCATCAGCCCTGTGACCCCAGAACACGCAGGGACCTACAGATGTG                   TTGGAATTTACAAGCACGCCTCAAAGTGGTCAGCTGAGAGCAACTCCCTGAAGATCAT                   CGTCACAGGCTTGTTCACAAAACCCTCCATCTCAGCGCACCCAAGCTCCCTGGTGCAT                   GCAGGAGCCAGGGTGAGCCTGCGCTGTCACTCAGAACTGGCCTTTGATGAATTTATCT                   TATACAAAGAGGGGCACATACAGCATTCCCAGCAGCTTGACCAGGGGATGGAGGCTGG                   GATCCATTACGTCGAGGCTGTCTTTTCCATGGGTCCTGTAACGCCTGCCCATGCAGGA                   GCCTACAGATGCTGTGGTTGTTTCAGTCACTCCCGCTATGAGTGGTCGGCTCCCAGTG                   ACCCCCTGGACATTGTGATCACAGGAAAATACAAAAAGCCTTCTCTCTCCACCCAGGT                   GGACCCCATGATGAGGCTGGGAGAGAAGTTGACCCTCTTCTGCAGCTCTGAAATCTCA                   TTTGACCAGTACCATCTGTTCAGACACGGGGTTGCTCATGGACAGTGGCTCAGTGGAG                   GGCAGAGACACAGGGAAGCATTCCAGGCCAATTTTTCTGTGGGCCGTGCAACGCCAGT                   CCCTGGCGGGACCTATAGATGCTATGGTTCCTTCAATGACTCTCCCTATAAGCCCCCA                   GTGACCCACTGCAACTTTACACCACAGGAAACACTAAGAGTACTCCTCTGTCATTCAC                   AGAATCCACCCCTGAATCTGACACACCTCGCCCTCAAGGACAGTCCAGCAACCTGCAT                   ATGCTCACTGGACTCTCAG TAG   CCATCATCTCCATTGGCGTTTGCCTCTCTGCTTTTA                       TTGGTTTCTGGTGTTACATAAAATATCACACCACCATGGCAAACACAGAGCCCACGGA                       AGGCCAACGGACGGATGAAGAGGAGCCTGCAGCAGAAGAGACACAGGAGATCATATAT                       GCCCAGTTAAACCACCAGGCCCTCTCACAGACAGGATTCCCTCCTGCCTCCCAGTGTC                       CCCACTACCTCTCGAAGGATCCTAGTATCTACATCACTGTCCACCAAGCCCAGGCTGA                       GGCCAGAGCTGCCCCCAGTCTTTGGCACAAAGGGCATTAATACGCAAGGACCTGGATC                       TATTCCT                                           ORF Start: ATG at 8   ORF Stop: TAG at 1064                                         SEQ ID NO: 60   352 aa   MW at 38757.9 Da                             NOV14b,   MAPKLITVLCLGFCLNQKICPHAGAQDKFSLSAWPSPVVPLGGRVTLSCHSHLRFVIW           CG112813-02   TIFQTTGTRSHELHTGLSNNITISPVTPEHAGTYRCVGIYKHASKWSAESNSLKIIVT       Protein Sequence   GLFTKPSISAHPSSLVHAGARVSLRCHSELAFDEFILYKEGHIQHSQQLDQGMEAGIH                   YVEAVFSMGPVTPAHAGAYRCCGCFSHSRYEWSAPSDPLDIVITGKYKKPSLSTQVDP                   MMRLGEKLTLFCSSEISFDQYHLFRHGVAHGQWLSGGQRHREAFQANFSVGRATPVPG                   GTYRCYGSFNDSPYKPPVTHCNFTPQETLRVLLCHSQNPPLNLTHLALKDSPATCICS                   LDSQ                                         SEQ ID NO 61   1369 bp                             NOV14c,     ATG GCCCCCAAACTCATCACCGTCCTGTGTCTGGGATTCTGCCTGAACCAGAAGATCT           CG112813-04   GCCCACATGCGGGTGCTCAGGACAAGTTCTCCCTGTCAGCCTGGCCGAGCCCTGTGGT       DNA Sequence   TCCCCTAGGAGGACGTGTGACTCTCTCCTGTCATTCCCATCTTCGGTTTGTCATATGG                   ACAATATTCCAAACAACTGGGACCCGAAGCCATGAGTTGCACACTGGCCTTTCCAACA                   ACATCACCATCAGCCCTGTGACCCCAGAACACGCAGGGACCTACAGATGTGTTGGAAT                   TTACAAGCACGCCTCAAAGTGGTCAGCTGAGAGCAACTCCCTGAAGATCATCGTCACA                   GGCTTGTTCACAAAACCCTCCATCTCAGCGCACCCAAGCTCCCTGGTGCATGCAGGAG                   CCAGGGTGAGCCTGCGCTGTCACTCAGAACTGGCCTTTGATGAATTTATCTTATACAA                   AGAGGGGCACATACAGCATTCCCAGCAGCTTGACCAGGGGATGGAGGCTGGGATCCAC                   TACGTCGAGGCTGTCTTTTCCATGGGTCCTGTAACGCCTGCCCATGCAGGAGCCTACA                   GATGCTGTGGTTGTTTCAGTCACTCCCGCTATGAGTGGTCGGCTCCCAGTGACCCCCT                   GGACATTGTGATCACAGGAAAATACAAAAAGCCTTCTCTCTCCACCCAGGTGGACCCC                   ATGATGAGGCTGGGAGAGAAGTTGACCCTCTTCTGCAGCTCTGAAATCTCATTTGACC                   AGTACCATCTGTTCAGACACGGGGTTGCTCATGGACAGTGGCTCAGTGGAGGGCAGAG                   ACACAGGGAAGCATTCCAGGCCAATTTTTCTGTGGGCCGTGCAACGCCAGTCCCTGGC                   GGGACCTATAGATGCTATGGTTCCTTCAATGACTCTCCCTATAAGCCCCCAGTGACCC                   ACTGCAACTTTACACCACAGGAAACACTAAGAGTACTCCTCTGTCATTCACAGAATCC                   ACCCCTGAATCTGACACACCTCGCCCTCAAGGACAGTCCAGCAACCTGCATATGCTCA                   CTGGACTCTCAG TAG   CCATCATCTCCATTGGCGTTTGCCTCTCTGCTTTTATTGGTTT                       CTGGTGTTACATAAAATATCACACCACCATGGCAAACACAGAGCCCACGGAAGGCCAA                       CGGACGGATGAAGAGGAGCCTGCAGCAGAAGAGACACAGGAGATCATATATGCCCAGT                       TAAACCACCAGGCCCTCTCACAGACAGGATTCCCTCCTGCCTCCCAGTGTCCCCACTA                       CCTCTCGAAGGATCCTAGTATCTACATCACTGTCCACCAAGCCCAGGCTGAGGCCAGA                       GCTGCCCCCAGTCTTTGGCACAAAGGGCATTAATA                     ORF Start: ATG at 1   ORF Stop: TAG at 1057                                             SEQ ID NO: 62   352 aa   MW at 38757.9 Da                             NOV14c,   MAPKLITVLCLGFCLNQKICPHAGAQDKFSLSAWPSPVVPLGGRVTLSCHSHLRFVIW           CG112813-04   TIFQTTGTRSHELHTGLSNNITISPVTPEHAGTYRCVGIYKHASKWSAESNSLKIIVT       Protein Sequence   GLFTKPSISAHPSSLVHAGARVSLRCHSELAFDEFILYKEGHIQHSQQLDQGMEAGIH                   YVEAVFSMGPVTPAHAGAYRCCGCFSHSRYEWSAPSDPLDIVITGKYKKPSLSTQVDP                   MMRLGEKLTLFCSSEISFDQYHLFRHGVAHGQWLSGGQRHREAFQANFSVGRATPVPG                   GTYRCYGSFNDSPYKPPVTHCNFTPQETLRVLLCHSQNPPLNLTHLALKDSPATCICS                   LDSQ                                         SEQ ID NO: 63   1502 bp                             NOV14d,     ATG GCCCCCAAACTCATCACCGTCCTGTGCCTAGGATTCTGCCTGAACCAGAAGATCT           ICG112813-05   GCCCACATGCGGGTGCTCAGGACAAGTTCTCCCTGTCAGCCTGGCCGAGCCCTGTGGT       DNA Sequence   TCCCCTAGGAGGACGTGTGACTCTCTCCTGTCATTCCCATCTTCGGTTTGTCATATGG                   ACAATATTCCAAACAACTGGGACCCGAAGCCATGAGTTGCACACTGGCCTTTCCAACA                   ACATCACCATCAGCCCTGTGACCCCAGAACACGCAGGGACCTACAGATGTGTTGGAAT                   TTACAAGCACGCCTCAAAGTGGTCAGCTGAGAGCAACTCCCTGAAGATCATCGTCACA                   GGCTTGTTCACAAAACCCTCCATCTCAGCGCACCCAAGCTCCCTGGTGCATGCAGGAG                   CCAGGGTGAGCCTGCGCTGTCACTCAGAACTGGCCTTTGATGAATTTATCTTATACAA                   AGAGGGGCACATACAGCATTCCCAGCAGCTTGACCAGGGGATGGAGGCTGGGATCCAT                   TACGTCGAGGCTGTCTTTTCCATGGGTCCTGTAACGCCTGCCCATGCAGGAGCCTACA                   GATGCTGTGGTTGTTTCAGTCACTCCCGCTATGAGTGGTCGGCTCCCAGTGACCCCCT                   GGACATTGTGATCACAGGAAAATACAAAAAGCCTTCTCTCTCCACCCAGGTGGACCCC                   ATGATGAGGCTGGGAGAGAAGTTGACCCTCTTCTGCAGCTCTGAAATCTCATTTGACC                   AGTACCATCTGTTCAGACACGGGGTTGCTCATGGACAGTGGCTCAGTGGAGGGCAGAG                   ACACAGGGAAGCATTCCAGGCCAATTTTTCTGTGGGCCGTGCAACGCCAGTCCCTGGC                   GGGACCTATAGATGCTATGGTTCCTTCAATGACTCTCCCTATAAGCCCCCAGTGACCC                   GCTGCAACTTTACACCACAGGAAACACTAAGAGTACTCCTCTGTCATTCACAGAATCC                   ACCCCTGAATCTGACACCACCATGGCAAACACAGAGCCCACGGAAGGCCAACGGACGG                   ATGAAGAGGAGCCTGCAGCAGAAGAGACACAGGAGATCATATATGCCCAGT TAA   ACCA                       CCAGGCCCTCTCACAGACAGGATTCCCTCCTGCCTCCCAGTGTCCCCACTACCTCTCG                       GAGGATCCTAGTATCTACATCACTGTCCACCAAGCCCAGGCTGAGGCCAGAGCTGCCC                       CCAGTCTTTGGCACAAAGGGCATTAATACGCAAGGACCTGGATCTATTCCTAGGAGGA                       TTTTTTTTCCACGGACATTCTTCCTCCTTCTGGTACCATCTTGACACCTCGAAGCTGG                       CAACAGCAGTGTCTGAATGCTTGTGGGATTATCTTAAAATTCCAGCACTGCTGAACAG                       ACAACTAGCCATTCTACAATTCTATTTTGAGCATCCAACCATTTCAGGTGATTTGACT                       CTTACCACACACTCATCCTGGATATCTCATTAATATCATCTGAATTATCCTG                     ORF Start: ATG at 1   ORF Stop: TAA at 1096                                             SEQ ID NO: 64   365 aa   MW at 40669.1 Da                             NOV14d,   MAPKLITVLCLGFCLNQKICPHAGAQDKFSLSAWPSPVVPLGGRVTLSCHSHLRFVIW           CG112813-05   TIFQTTGTRSHELHTGLSNNITISPVTPEHAGTYRCVGIYKHASKWSAESNSLKIIVT       Protein Sequence   GLFTKPSISAHPSSLVHAGARVSLRCHSELAFDEFILYKEGHIQHSQQLDQGMEAGIH                   YVEAVFSMGPVTPAHAGAYRCCGCFSHSRYEWSAPSDPLDIVITGKYKKPSLSTQVDP                   MMRLGEKLTLFCSSEISFDQYHLFRHGVAHGQWLSGGQRHREAFQANFSVGRATPVPG                   GTYRCYGSFNDSPYKPPVTRCNFTPQETLRVLLCHSQNPPLNLTPPWQTQSPRKANGR                   MKRSLQQKRHRRSYMPS                                         SEQ ID NO: 65   1327 bp                             NOV14e,     AATAGAAGTGGCACC   ATG GCCCCCAAACTCATCACCGTCCTGTGCCTAGGATTCTGCC           CG112813-06   TGAACCAGAAGATCTGCCCACATGCGGGTGCTCAGGACAAGTTCTCCCTGTCAGCCTG       DNA Sequence   GCCGAGCCCTGTGGTTCCCCTAGGAGGACGTGTGACTCTCTCCTGTCATTCCCATCTT                   CGGTTTGTCATATGGACAATATTCCAAACAACTGGGACCCGAAGCCATGAGTTGCACA                   CTGGCCTTTCCAACAACATCACCATCAGCCCTGTGACCCCAGAACACGCAGGGACCTA                   CAGATGTGTTGGAATTTACAAGCACGCCTCAAAGTGGTCAGCTGAGAGCAACTCCCTG                   AAGATCATCGTCACAGGTAGGTTCACAAAACCCTCCATCTCAGCGCACCCAAGCTCCC                   TGGTGCATGCAGGAGCCAGGGTGAGCCTGCGCTGTCACTCAGAACTGGCCTTTGATGA                   ATTTATCTTATACAAAGAGGGGCACATACAGCATTCCCAGCAGCTTGACCAGGGGATG                   GAGGCTGGGATCCATTACGTCGAGGCTGTCTTTTCCATGGGTCCTGTAACGCCTGCCC                   ATGCAGGAGCCTACAGATGCTGTGGTTGTTTCAGTCACTCCCGCTATGAGTGGTCGGC                   TCCCAGTGACCCCCTGGACATTGTGATCACAGGTAAATACAAAAAGCCTTCTCTCTCC                   ACCCAGGTGGACCCCATGATGAGGCTGGGAGAGAAGTTGACCCTCTTCTGCAGCTCTG                   AAATCTCATTTGACCAGTACCATCTGTTCAGACACGGGGTTGCTCATGGACAGTGGCT                   CAGTGGAGGGCAGAGACACAGGGAAGCATTCCAGGCCAATTTTTCTGTGGGCCGTGCA                   ACGCCAGTCCCTGGCGGGACCTATAGATGCTATGGTTCCTTCAATGACTCTCCCTATA                   AGACAGACACACCTCGCCCTCAAGGACAGTCCAGCAACCTGCATATGCTCACTGGACT                   CTCAGTAGCCATCATCTCCATTGGCGTTTGCCTCTCTGCTTTTATTGGTTTCTGGTGT                   TACATAAAATATCACACCACCATGGCAAACACAGAGCCCACGGAAGGCCAACGGACGG                   ATGAAGAGGAGCCTGCAGCAGAAGAGACACAGGAGATCATATATGCCCAGTTAAACCA                   CCAGGCCCTCTCACAGACAGGATTCCCTCCTGCCTCCCAGTGTCCCCACTACCTCTCG                   AAGGATCCTAGTATCTACATCACTGTCCACCAAGCCCAGGCTGAGGCCAGAGCTGCCC                   CCAGTCTTTGGCACAAAGGGCAT TAA   TACGCAAGGACCTGGATCTATTCCT                     ORF Start: ATG at 16   ORF Stop: TAA at 1300                                             SEQ ID NO: 66   428 aa   MW at 47211.0 Da                             NOV14e,   MAPKLITVLCLGFCLNQKICPHAGAQDKFSLSAWPSPVVPLGGRVTLSCHSHLRFVIW           CG112813-06   TIFQTTGTRSHELHTGLSNNITISPVTPEHAGTYRCVGIYKHASKWSAESNSLKIIVT       Protein Sequence   GRFTKPSISAHPSSLVHAGARVSLRCHSELAFDEFILYKEGHIQHSQQLDQGMEAGIH                   YVEAVFSMGPVTPAHAGAYRCCGCFSHSRYEWSAPSDPLDIVITGKYKKPSLSTQVDP                   MMRLGEKLTLFCSSEISFDQYHLFRHGVAHGQWLSGGQRHREAFQANFSVGRATPVPG                   GTYRCYGSFNDSPYKTDTPRPQGQSSNLHMLTGLSVAIISIGVCLSAFIGFWCYIKYH                   TTMANTEPTEGQRTDEEEPAAEETQEIIYAQLNHQALSQTGFPPASQCPHYLSKDPSI                   YITVHQAQAEARAAPSLWHKGH                                         SEQ ID NO: 67   780 bp                             NOV14f,     AAG CTTGGAGGACGTGTGACTCTCTCCTGTCATTCCCATCTTCGGTTTGTCATATGGA           209886463 DNA   CAATATTCCAAACAACTGGGACCCGAAGCCATGAGTTGCACACTGGCCTTTCCAACAA       Sequence   CATCACCATCAGCCCTGTGACCCCAGAACACGCAGGGACCTACAGATGTGTTGGAATT                   TACAAGCACGCCTCAAAGTGGTCAGCTGAGAGCAACTCCCTGAAGATCATCGTCACAG                   GCTTGTTCACAAAACCCTCCATCTCAGCGCACCCAAGCTCCCTGGTGCATGCAGGAGC                   CAGGGTGAGCCTGCGCTGTCACTCAGAACTGGCCTTTGATGAATTTATCTTATACAAA                   GAGGGGCACATACAGCATTCCCAGCAGCTTGACCAGGGGATGGAGGCTGGGATCCATT                   ACGTCGAGGCTGTCTTTTCCATGGGTCCTGTAACGCCTGCCCATGTAGGAGCCTACAG                   ATGCTGTGGTTGTTTCAGTCACTCCCGCTATGAGTGGTCGGCTCCCAGTGACCCCCTG                   GACATTGTGATCACAGGAAAATACAAAAAGCCTTCTCTCTCCACCCAGGTGGACCCCA                   TGATGAGGCTGGGAGAGAAGTTGACCCTCTTCTGCAGCTCTGAAATCTCATTTGACCA                   GTACCATCTGTTCAGACACGGGGTTGCTCATGGACAGTGGCTCAGTGGAGGGCAGAGA                   CACAGGGAAGCATTCCAGGCCAACTTTTCTGTGGGCCGTGCAACGCCAGTCCCTGGCG                   GGACCTATAGATGCTATGGTCTCGAG                                         ORF Start: at 1   ORF Stop: end of sequence                                         SEQ ID NO: 68   260 aa   MW at 28816.5 Da                             NOV14f   KLGGRVTLSCHSHLRFVIWTIFQTTGTRSHELHTGLSNNITISPVTPEHAGTYRCVGI           209886463 Protein   YKHASKWSAESNSLKIIVTGLFTKPSISAHPSSLVHAGARVSLRCHSELAFDEFILYK       Sequence   EGHIQHSQQLDQGMEAGIHYVEAVFSMGPVTPAHVGAYRCCGCFSHSRYEWSAPSDPL                   DIVITGKYKKPSLSTQVDPMMRLGEKLTLFCSSEISFDQYHLFRHGVAHGQWLSGGQR                   HREAFQANFSVGRATPVPGGTYRCYGLE                                         SEQ ID NO: 69   871 bp                             NOV14g,     GCC AAGCTTCATGAGTTGCACACTGGCCTTTCCAACAACATCACCATCAGCCCTGTGA           277731421 DNA   CCCCAGAACACGCAGGGACCTACAGATGTGTTGGAATTTACAAGCACGCCTCAAAGTG       Sequence   GTCAGCTGAGAGCAACTCCCTGAAGATCATCGTCACAGGCTTGTTCACAAAACCCTCC                   ATCTCAGCGCACCCAAGCTCCCTGGTGCATGCAGGAGCCAGGGTGAGCCTGCGCTGTC                   ACTCAGAACTGGCCTTTGATGAATTTATCTTATACAAAGAGGGGCACATACAGCATTC                   CCAGCAGCTTGACCAGGGGATGGAGGCTGGGATCCACTACGTCGAGGCTGTCTTTTCC                   ATGGGTCCTGTAACGCCTGCCCATGCAGGAGCCTACAGATGCTGTGGTTGTTTCAGTC                   ACTCCCGCTATGAGTGGTCGGCTCCCAGTGACCCCCTGGACATTGTGATCACAGGAAA                   ATACAAAAAGCCTTCTCTCTCCACCCAGGTGGACCCCATGATGAGGCTGGGAGAGAAG                   TTGACCCTCTTCTGCAGCTCTGAAATCTCATTTGACCAGTACCATCTGTTCAGACACG                   GGGTTGCTCATGGACAGTGGCTCAGTGGAGGGCAGAGACACAGGGAAGCATTCCAGGC                   CAATTTTTCTGTGGGCCGTGCAACGCCAGTCCCTGGCGGGACCTATAGATGCTATGGT                   TCCTTCAATGACTCTCCCTATAAGCCCCCAGTGACCCACTGCAACTTTACACCACAGG                   AAACACTAAGAGTACTCCTCTGTCATTCACAGAATCCACCCCTGAATCTGACACACCT                   CGCCCTCAAGGACAGTCCAGCAACCTGCATATGCTCACTGGACTCTCAGCTCGAGGGT                   G                                         ORF Start: at 1   ORF Stop: at 871                                         SEQ ID NO: 70   290 aa   MW at 31948.9 Da                             NOV14g,   AKLHELHTGLSNNITISPVTPEHAGTYRCVGIYKHASKWSAESNSLKIIVTGLFTKPS           277731421 Protein   ISAHPSSLVHAGARVSLRCHSELAFDEFILYKEGHIQHSQQLDQGMEAGIHYVEAVFS       Sequence   MGPVTPAHAGAYRCCGCFSHSRYEWSAPSDPLDIVITGKYKKPSLSTQVDPMMRLGEK                   LTLFCSSEISFDQYHLFRHGVAHGQWLSGGQRHREAFQANFSVGRATPVPGGTYRCYG                   SFNDSPYKPPVTHCNFTPQETLRVLLCHSQNPPLNLTHLALKDSPATCICSLDSQLEG                  
 
     [0409] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 14B.  
               TABLE 14B                          Comparison of NOV14a against NOV14b through NOV14g.                         Protein   NOV14a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV14b    1 . . . 333   332/333 (99%)            1 . . . 333   332/333 (99%)       NOV14c    1 . . . 333   332/333 (99%)            1 . . . 333   332/333 (99%)       NOV14d    1 . . . 335   334/335 (99%)            1 . . . 335   334/335 (99%)       NOV14e    1 . . . 396   366/428 (85%)            1 . . . 428   370/428 (85%)       NOV14f   41 . . . 297   256/257 (99%)            2 . . . 258   256/257 (99%)       NOV14g   69 . . . 333   264/265 (99%)            4 . . . 268   264/265 (99%)                  
 
     [0410] Further analysis of the NOV14a protein yielded the following properties shown in Table 14C.  
               TABLE 14C                       Protein Sequence Properties NOV14a                                        PSort   0.4489 probability located in lysosome (lumen);       analysis:   0.3700 probability located in outside; 0.2307 probability           located in microbody (peroxisome); 0.1000 probability located           in endoplasmic reticulum (membrane)       SignalP   Cleavage site between residues 69 and 70       analysis:                  
 
     [0411] 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.  
               TABLE 14D                          Geneseq Results for NOV14a                                         NOV14a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               ABG10169   Novel human diagnostic protein #10160 -    1 . . . 305   145/307 (47%)   53−71             Homo sapiens , 444 aa.    1 . . . 303   190/307 (61%)           [WO200175067-A2, 11 OCT. 2001]       ABG10165   Novel human diagnostic protein #10156 -    1 . . . 386   165/426 (38%)   53−71             Homo sapiens , 491 aa.   65 . . . 486   228/426 (52%)           [WO200175067-A2, 11 OCT. 2001]       AAM25638   Human protein sequence SEQ ID    1 . . . 305   145/307 (47%)   53−71           NO: 1153 -  Homo sapiens , 444 aa.    1 . . . 303   190/307 (61%)           [WO200153455-A2, 26 JUL. 2001]       ABG10169   Novel human diagnostic protein #10160 -    1 . . . 305   145/307 (47%)   53−71             Homo sapiens , 444 aa.    1 . . . 303   190/307 (61%)           [WO200175067-A2, 11 OCT. 2001]       ABG10167   Novel human diagnostic protein #10158 -    1 . . . 305   142/307 (46%)   73−70             Homo sapiens , 388 aa.    1 . . . 303   191/307 (61%)           [WO200175067-A2, 11 OCT. 2001]                  
 
     [0412] 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.  
               TABLE 14E                          Public BLASTP Results for NOV14a                                         NOV14a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organsism/Length   Residues   Portion   Value               Q9H7L2   FLJ00060 protein -  Homo sapiens     114 . . . 333   217/220 (98%)    e−131           (Human), 227 aa (fragment).    5 . . . 224   220/220 (99%)       Q99563   NK receptor -  Homo sapiens      1 . . . 382   171/439 (38%)   1e−71           (Human), 436 aa.    1 . . . 435   228/439 (50%)       AAK30061   Killer cell immunoglobulin-like    5 . . . 305   144/303 (47%)   3e−71           receptor 3DL1 -  Homo sapiens      5 . . . 303   191/303 (62%)           (Human), 444 aa.       Q9UER1   KIR3DL1-like natural killer cell    5 . . . 305   144/303 (47%)   3e−71           receptor -  Homo sapiens  (Human),    5 . . . 303   191/303 (62%)           444 aa.       AAF61292   Killer cell immunoglobulin receptor    5 . . . 305   143/303 (47%)   3e−70           variant -  Homo sapiens  (Human), 444    5 . . . 303   190/303 (62%)           aa.                  
 
     [0413] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14F.  
               TABLE 14F                          Domain Analysis of NOV14a                                     Identities/                   Similarities       Pfam   NOV14   for the       Domain   Match Region   for the Matched Region   Expect Value               ig    42 . . . 96   17/59 (29%)   5e−07               42/59 (71%)       ig   135 . . . 197   11/67 (16%)   0.00019               44/67 (66%)       ig   237 . . . 297   14/65 (22%)   0.0018               42/65 (65%)                  
 
     Example 15  
     [0414] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.  
               TABLE 15A                       NOV15 Sequence Analysis                                                    SEQ ID NO 71   4380 bp                             NOV15a,     ATATCTGTGGATGCT   ATG CATGTCTTCATTGATGAACATGGTGAGGGGGAAATTAGAT           CG112869-01   CCTGTTATTTAAAATCTGGAAATCAGAAAGAAGGCCCTTTACAGCCTCTACCATCAAA       DNA Sequence   TAATGACTGTCTCTCTCAGGCTAGAGAGATGCAGGTCAGCTCCTCCAGTACCACAACT                   TCTGAGAGTCAAGATCCGTCTTCTGGGGACCCTGCCGTCAGTGCCCTTCAGCAACAGC                   TGTTACTGATGGTGGCTCGCAGGACCCAGTCGGAAACCCCACGGCATGTGAGTCAGGA                   TCTGGAAGCCTCGTCATGTTCTTCAACACAAGGAAAATTTAACCGAGAGCAGTTTTAC                   AAATTTATCATTTTCCCTGGCAAGTGGATTAAAGTCTGGTATGATCGACTGACCTTGC                   TGGCATTACTTGATCGGACTGAAGACATCAAGGAGAATGTACTGGCGATTTTACTCAT                   TGTCCTGGTTTCCCTCCTTGGATTTCTGACCTTGAGCCAAGGCTTTTGCAAAGATATG                   TGGGTGCTCCTCTTCTGCCTCGTCATGGCCAGCTGCCAGTACTCCCTGCTAAAGAGTG                   TTCAGCCTGACCCCGCCTCACCAATACACGGACACAACCAAATCATAACATATAGCAG                   ACCAATCTATTTTTGTGTGCTGTGTGGCCTTATTTTGCTTCTTGATACAGGGGCCAAA                   GCCAGGCACCCTCCCAGTTACGTTGTGTATGGCCTGAAGCTCTTCTCTCCAGTGTTTC                   TACAATCAGCTAGGGACTACTTAATAGTATTTTTATATTGCTTCCCTGCTATTTCCCT                   CCTTGGGCTCTTCCCGCAAATCAACACTTTCTGCACTTATCTTTTGGAGCAAATTGAC                   ATGCTGTTTTTTGGTGGTTCTGCTGTGTCTGGGATAACCTCGGCTGTTTACAGTGTGG                   CCCGGAGCGTCTTGGCTGCCGCCCTGCTCCACGCAGTCTGCTTCAGTGCAGTGAAGGA                   ACCGTGGAGCATGCAACACATCCCGGCACTGTTTTCGGCCTTCTGTGGCCTCTTGGTC                   GCCCTTTCTTACCATCTGAGCCGTCAGAGCAGTGACCCATCTGTACTCTTTTCCACTT                   TCAGGTCCTTCATCCAATGCAGGCTGTTTCCTAAATTTTTACATCAAAATCTGGCAGA                   GTCAGCTGCTGACCCTCTCCCCAAGAAGATGAAAGATTCAGTGGTGAGACATTTGCGT                   TTAAAATGGGATCTCATCGTCTGCGCAGTGGTTGCTGTCCTCTCATTTGCAGTCAGCG                   CCAGCACTGTATTCCTGTCATTGCAGCCATTTCTCAGCATCGTGCTGTTTGCCTTGGC                   TGGAGCCGTGGGGTTTGTAACACATTACGTGCTCCCTCAGCTCCGCAAGCATCATCCC                   TGGATGTGGATTTCACACCCCATTCTCAAAAACAAAGAGTATCATCAACGGGAAGTGA                   GAGATGTTGCCCATTTAATGTGGTTCGAAAGACTCTATGTTTGGCTTCAGTGTTTTGA                   AAAATACATCTTGTACCCAGCGCTAATTTTGAATGCCCTCACTATTGATGCATTTTTA                   ATAAGCAATCACCGGAGACTTGGTACCCAGCTGATGATCATTGCTGGCATGAAGCTGT                   TGCGGACATCATTCTGCAACCCGGTTTACCAGTTTATTAACTTGAGCTTCACTGTCAT                   CTTTTTCCACTTTGACTACAAAGATATTTCAGAGAGCTTCTTACTGGATTTCTTCATG                   GTGTCCATTTTATTTAGCAAGGCAAGTGAATTACTTCACAAGTTACAGTTCGTCCTGA                   CATATGTGGCTCCTTGGCAGATGGCTTGGGGTTCTTCGTTTCACGTGTTTGCTCAGCT                   CTTTGCCATTCCTCGTATCCTTTCTGCCATGCTTTTCTTTCAGACGATTGCCACATCA                   ATCTTTTCTACCCCATTGAGCCCATTTCTTGGGAGTGTCATTTTCATCACATCATATG                   TCAGGCCAGTGAAATTCTGGGAGAAAAACTACAGTACAAGGCGAGTGGATAATTCCAA                   CACAAGACTGGCAGTCCAAATTGAAAGAGATCCAGGGAATGATGACAACAATCTCAAT                   TCCATTTTTTATGAACACTTGACAAGGACCCTCCAGGAGTCCCTCTGTGGAGACTTAG                   TTCTTGGACGTTGGGGCAACTACAGCTCTGGCGATTGCTTTATTTTGGCTTCAGATGA                   CCTCAATGCCTTTGTTCACCTGATTGAAATTGGAAATGGTCTTGTCACCTTTCAACTT                   CGAGGACTGGAATTCCGAGGAACCTACTGCCAGCAGAGGGAGGTAGAAGCCATCATGG                   AGGGCGACGAGGAGGACAGAGGCTGCTGCTGCTGCAAACCAGGCCACTTGCCTCACCT                   GCTGTCCTGCAACGCTGCCTTTCACCTCCGCTGGCTCACCTGGGAAATCACGCAGACC                   CAGTACATCCTGGAGGGCTACAGCATCCTGGACAACAACGCGGCCACCATGCTGCAGG                   TGTTTGACCTCCGAAGGATCCTCATCCGCTACTACATCAAGAGTATAATATACTATAT                   GGTAACGTCTCCCAAACTCCTCTCCTGGATCAAAAATGAATCACTTCTGAAGTCCCTG                   CAGCCCTTTGCCAAGTGGCATTACATTGAGCGTGACCTTGCAATGTTCAACATTAACA                   TTGATGATGACTACGTCCCGTGTCTCCAGGGGATCACACGAGCTAGCTTCTGCAATGT                   TTATCTAGAATGGATTCAACACTGTGCACGGAAAAGACAAGAGCCTTCAACGACCCTG                   GACAGTGACGAGGACTCTCCCTTGGTGACTCTGTCCTTCGCCCTGTGCACCCTGGGGA                   GGAGAGCTCTGGGAACAGCCGCTCACAATATGGCCATCAGCCTGGATTCTTTCCTGTA                   TGGCCTCCATGTCCTCTTCAAAGGTGACTTCAGAATAACAGCACGTGACGAGTGGGTA                   TTTGCTGACATGGACCTACTGCATAAAGTTGTAGCTCCAGCTATCAGGATGTCCCTGA                   AACTTCACCAGGACCAGTTCACTTGCCCTGACGAGTATGAAGACCCAGCAGTCCTCTA                   CGAGGCCATCCAGTCCTTCGAGAAGAAGGTGGTCATCTGCCACGAGGGCGACCCGGCC                   TGGCGGGGCGCAGTGCTGTCCAACAAGGAAGAGCTGCTCACCCTGCGGCACGTGGTGG                   ACGAGGGTGCCGACGAGTACAAGGTCATCATGCTCCACAGAAGCTTCCTGAGCTTCAA                   GGTGATCAAGGTTAACAAAGAATGCGTCCGAGGACTTTGGGCCGGGCAGCAGCAGGAG                   CTTATATTTCTTCGCAACCGCAATCCGGAGCGCGGCAGTATCCAGAACAATAAGCAGG                   TCCTGCGGAACTTGATTAACTCCTCCTGCGATCAGCCCCTGGGGTACCCCATGTATGT                   CTCCCCACTAACCACATCCTACCTAGGGACACACAGGCAGCTGAAGAACATCTGGGGT                   GGACCCATCACTTTGGACAGAATTAGGACCTGGTTCTGGACCAAGTGGGTAAGGATGC                   GGAAGGATTGCAATGCCCGCCAGCACAGTGGCGGCAACATTGAAGACGTGGACGGAGG                   AGGGGCCCCGACGACAGGTGGCAACAATGCCCCGAATGGTGGCAGCCAGGAGAGCAGC                   GCAGAACAGCCCAGAAAAGGCGGTGCTCAGCACGGGGTGTCATCCTGTGAAGGGACAC                   AGAGAACAGGCAGGAGGAAAGGCAGGAGCCAGTCCGTGCAGGCACACTCAGCGCTAAG                   CCAAAGGCCGCCCATGCTGAGCTCATCTGGCCCCATCTTAGAGAGCCGCCAAACATTC                   CTCCAGACGTCCACCTCAGTGCACGAGCTGGCCCAGAGGCTCTCGGGCAGCCGGCTCT                   CCTTGCACGCCTCGGCCACGTCCCTGCACTCTCAGCCCCCGCCCGTCACCACCACCGG                   CCACCTGAGTGTCCGTGAGCGGGCCGAGGCGCTCATCAGGTCCAGCCTGGGCTCCTCC                   ACCAGCTCCACCCTGAGCTTCCTCTTCGGCAAGAGGAGCTTTTCCAGCGCGCTCGTCA                   TTTCCGGACTCTCTGCTGCGGAGGGGGGCAATACCAGTGACACCCAGTCATCCAGCAG                   CGTCAACATCGTGATGGGCCCCTCAGCCAGGGCTGCCAGCCAGGCCACTCGGGTAAGG                   GGCTGGGCAGGGCTCACCAGGACAGGCTGGGATGGTGGCACGGGCTCCTGGCCTGAGC                   GTGGCACCTGCCTTGCGTTCCCACCCTTCTGCCTGCAGAACCCCATCCCCTTCTCTAT                   GGGGCTCCCAGAG TGA   CAAAGGACAGTGATTAGACACGAAGTGGCTTAGCTGCTCTTG                       AAAGCAGACAAGATACAGAGCAGATATCCT                                           ORF Start: ATG at 16   ORF Stop: TGA at 4306                                         SEQ ID NO: 72   1430 aa   MW at 160787.0 Da                             NOV15a,   MHVFIDEHGEGEIRSCYLKSGNQKEGPLQPLPSNNDCLSQAREMQVSSSSTTTSESQD           CG112869-01   PSSGDPAVSALQQQLLLMVARRTQSETPRHVSQDLEASSCSSTQGKFNREQFYKFIIF       Protein Sequence   PGKWIKVWYDRLTLLALLDRTEDIKENVLAILLIVLVSLLGFLTLSQGFCKDMWVLLF                   CLVMASCQYSLLKSVQPDPASPIHGHNQIITYSRPIYFCVLCGLILLLDTGAKARHPP                   SYVVYGLKLFSPVFLQSARDYLIVFLYCFPAISLLGLFPQINTFCTYLLEQIDMLFFG                   GSAVSGITSAVYSVARSVLAAALLHAVCFSAVKEPWSMQHIPALFSAFCGLLVALSYH                   LSRQSSDPSVLFSTFRSFIQCRLFPKFLHQNLAESAADPLPKKMKDSVVRHLRLKWDL                   IVCAVVAVLSFAVSASTVFLSLQPFLSIVLFALAGAVGFVTHYVLPQLRKHHPWMWIS                   HPILKNKEYHQREVRDVAHLMWFERLYVWLQCFEKYILYPALILNALTIDAFLISNHR                   RLGTQLMIIAGMKLLRTSFCNPVYQFINLSFTVIFFHFDYKDISESFLLDFFMVISILF                   SKASELLHKLQFVLTYVAPWQMAWGSSFHVFAQLFAIPRILSAMLFFQTIATSIFSTP                   LSPFLGSVIFITSYVRPVKFWEKNYSTRRVDNSNTRLAVQIERDPGNDDNNLNSIFYE                   HLTRTLQESLCGDLVLGRWGNYSSGDCFILASDDLNAFVHLIEIGNGLVTFQLRGLEF                   RGTYCQQREVEAIMEGDEEDRGCCCCKPGHLPHLLSCNAAFHLRWLTWEITQTQYILE                   GYSILDNNAATMLQVFDLRRILIRYYIKSIIYYMVTSPKLLSWIKNESLLKSLQPFAK                   WHYIERDLAMFNINIDDDYVPCLQGITRASFCNVYLEWIQHCARKRQEPSTTLDSDED                   SPLVTLSFALCTLGRRALGTAAHNMAISLDSFLYGLHVLFKGDFRITARDEWVFADMD                   LLHKVVAPAIRMSLKLHQDQFTCPDEYEDPAVLYEAIQSFEKKVVICHEGDPAWRGAV                   LSNKEELLTLRHVVDEGADEYKVIMLHRSFLSFKVIKVNKECVRGLWAGQQQELIFLR                   NRNPERGSIQNNKQVLRNLINSSCDQPLGYPMYVSPLTTSYLGTHRQLKNIWGGPITL                   DRIRTWFWTKWVRMRKDCNARQHSGGNIEDVDGGGAPTTGGNNAPNGGSQESSAEQPR                   KGGAQHGVSSCEGTQRTGRRKGRSQSVQAHSALSQRPPMLSSSGPILESRQTFLQTST                   SVHELAQRLSGSRLSLHASATSLHSQPPPVTTTGHLSVRERAEALIRSSLGSSTSSTL                   SFLFGKRSFSSALVISGLSAAEGGNTSDTQSSSSVNIVMGPSARAASQATRVRGWAGL                   TRTGWDGGTGSWPERGTCLAFPPFCLQNPIPFSMGLPE                  
 
     [0415] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.  
               TABLE 15B                       Protein Sequence Properties NOV15a                                        PSort   0.8000 probability located in plasma membrane;       analysis:   0.4000 probability located in Golgi body; 0.3000 probability           located in endoplasmic reticulum (membrane); 0.3000           probability located in microbody (peroxisome)       SignalP   No Known Signal Sequence Predicted       analysis:                  
 
     [0416] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15C.  
               TABLE 15C                          Geneseq Results for NOV15a                                         NOV15a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAY57927   Human transmembrane protein   664 . . . 1430   765/767 (99%)   0.0           HTMPN-51 -  Homo sapiens , 777 aa.    11 . . . 777   765/767 (99%)           [WO9961471-A2, 02 DEC. 1999]       AAB01381   Neuron-associated protein -  Homo     529 . . . 1263   467/758 (61%)   0.0             sapiens , 796 aa. [W0200034477-A2,    1 . . . 752   574/758 (75%)           15 JUN. 2000]       AAU91404   Human secreted protein sequence #57 -   261 . . . 840   374/588 (63%)   0.0             Homo sapiens , 595 aa. [WO200216388-    2 . . . 581   463/588 (78%)           A1, 28 FEB. 2002]       AAU91356   Human secreted protein sequence #9 -   279 . . . 840   364/570 (63%)   0.0             Homo sapiens , 577 aa. [WO200216388-    2 . . . 563   451/570 (78%)           A1, 28 FEB. 2002]       AAM79539   Human protein SEQ ID NO 3185 -    89 . . . 684   333/603 (55%)   0.0             Homo sapiens , 1397 aa.    80 . . . 674   440/603 (72%)           [WO200157190-A2, 09 AUG. 2001]                  
 
     [0417] In a BLAST search of public sequence databases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15D.  
               TABLE 15D                          Public BLASTP Results for NOV15a                                         NOV15a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organsism/Length   Residues   Portion   Value               O43162   KIAA0435 protein -  Homo sapiens     664 . . . 1430   767/767 (100%)   0.0           (Human), 777 aa.    11 . . . 777   767/767 (100%)       Q8TEP4   FLJ00149 protein -  Homo sapiens     664 . . . 1385   720/722 (99%)   0.0           (Human), 792 aa (fragment).    14 . . . 735   722/722 (99%)       Q96RV3   Pecanex-like protein 1 -  Homo      89 . . . 1387   738/1316 (56%)   0.0             sapiens  (Human), 2341 aa.   952 . . . 2248   941/1316 (71%)       Q9QYC1   Pecanex 1 -  Mus musculus  (Mouse),    89 . . . 1371   737/1303 (56%)   0.0           1446 aa.    57 . . . 1340   932/1303 (70%)       Q98UF7   Pecanex -  Fugu rubripes  (Japanese    97 . . . 1299   722/1208 (59%)   0.0           pufferfish) ( Takifugu rubripes ), 1703   371 . . . 1533   898/1208 (73%)           aa.                  
 
     [0418] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.  
               TABLE 15E                          Domain Analysis of NOV14a                                     Identities/                   Similarities       Pfam   NOV14   for the       Domain   Match Region   for the Matched Region   Expect Value                         No Significant Known Matches Found                  
 
     Example 16  
     [0419] The NOV16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.  
               TABLE 16A                       NOV16 Sequence Analysis                                                SEQ ID NO: 73          11344 bp           NOV 1 6a,   GATAAGATGGCAATGTCTCTCATCCAAGCGTGCTGCAGTCTGGCTCTCTCAACATGG       CGI13377-01       DNA Sequence   CTGCTTTCCTTTTGTTTCGTGCATCTGCTCTGCCTGGACTTTACCGTGGCCGAGAGG                   AGGAATGGTACACCGCCTTCGTGAACATCACCTACGCCGAGCCCGCGCCGGACCCCGG                   GGCCGGGGCGGCGGGCGGCGGCGGCGCGGAGCTGCACACGGAGAAGACGGAGTGCGGG                   CGCTACGGAGAGCACTCGCCCAAGCAGGACGCCCGCGGGGAGGTGGTCATGGCCAGCT                   CGGCCCACGACCGCCTGGCCTGCGACCCCAACACCAAGTTCGCCGCCCCGACCCGCGG                   CAAGAACTGGATAGCCCTCATCCCCAAGGGCAACTGCACGTACAGGGATAAGATCCGG                   kACGCGTTCCTGCAGAACGCCTCAGCCGTGGTCATCTTCAACGTGGGcTcczAcAccA                   ACGAGACCATCACCATGCCCCACGCGGGTGTAGAAGACATCGTGGCCATAJATGATTC                   TGAGCCAAAAGGGAAGGAGATAGTAAGCCTGCTGGAAAGAAACATCACCGTGACAJAT                   TACATCACCATCGGAACCCGGAACTTGCAGAAATATGTGAGCCGCACTTcGGTTGTGT                   TTGTCTCCATCTCCTTCATTGTCCTGATGATCATTTCCCTCGCATGGCTCGTCTTTTA                   TTACATCCAGAGGTTTCGATATGCAAATGCCAGGGATAGGAACCAGCGCCGACTGGGG                   GATGCAGCAAAGAAGCCATCAGCAAACTCCAGATCAGA3ACCATQAAGAJAGGGTGAC                   ATGACGTTGTCCGGATCCTGCCCTGCCGGCATCTTTTCCACAAGTCCTGTGTTGACCC                   TGGCTTCTAGACCATCGTACCTGTCCCATGTGCAl\GATGAIxCATTCTTAGcCcTAG                   GGATCCCGCCCAATGCCGACTGCATCGACGACTTGCCCACTGACTTCGAGGGCTCTCT                   GGGAGGTCCACCCACCAACCAGATCACAGGTGCCAGCGACACAcAGTGIATGAj\GT                   TCAGTCACTTTGGACCCTGCTGTCCGGACTGTGGGAGCCTTGCAGGTGGTCCAGGATA                   CAGACCCCATCCCCCAGGAGGGAGACGTCATCTTTACTACTPJ\CAGTGAGcAGGAGC                   CAGCTGTAAGCAGTGATTCTGACATTTCCTTGATCATGGCAATGGAGGTTGGACTGTC                   TGATGTAGAACTTTCCACTGACCACGACTGTGAGpJAGTGITC TTGA   AACGACAAAT                       CCAGAAGCAA                     ORF Start: ATG at 8    ORF Stop: TGA at 1322           SEQ ID NO: 74          438 aa      MW at 48071.3 Da       NOV I 6a,   MANSLIQACCSLALSTWLLSFCFVHLLCLDFTVAEKEEWYTAFVNITYAEPAPDPGAGA       CG113377-01       Protein Sequence   AGGGGAELHTEKTECGRYGEHSPKQDARGEVMASSAjDRLAcDpNTKFApTRGaaaA                   WIALIPKGNCTYRDKIRNAFLQNASAVVIFNXTGSNTNETITMPHAGvEDIvAIMIREpA                   KGKEIVSLLERNITVTMYITIGTRNLQKYvsRTsVVFvsIsFIvLMIIsLAwLvFyyI                   QRFRYANARDRNQRRLCDAAKKAISKLQIRTIKKGDKETESDFDNCAVCIEGYKPNDVA                   VRILPCRHLFHKSCVDPWLLDHRTCPMCKMNILKALGIPPNADCMDDLPTDFEGSLGG                   PPTNQITGASDTTVNESSVTLDPAVRTVGALQvVQDTDPIPQEGDVIFTTNSEQEPAV:                   SSDSDISLIMAMEVGLSDVELSTDQDCEEVKS                  
 
     [0420] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.  
               TABLE 16B                       Protein Sequence Properties NOV16a                                        PSort   0.6400 probability located in plasma membrane;       analysis:   0.4600 probability located in Golgi body; 0.3700 probability           located in endoplasmic reticulum (membrane); 0.1080           probability located in microbody (peroxisome)       SignalP   Cleavage site between residues 35 and 36       analysis:                  
 
     [0421] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16C.  
               TABLE 16C                          Geneseq Results for NOV16a                                         NOV16a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAU74919   Human goliath protein sequence -  Homo      1 . . . 438   396/438 (90%)   0.0             sapiens , 462 aa. [WO200193681-A1,    67 . . . 462   396/438 (90%)           13 DEC. 2001]       AAB41793   Human ORFX ORF1557 polupeptide   135 . . . 343   207/209 (99%)   e−118           sequence SEQ ID NO: 3114 -  Homo      2 . . . 210   207/209 (99%)             sapiens , 210 aa. [WP200058473-A2,           05 OCT. 2000]       ABB90389   Human polypeptide SEQ ID NO 2765 -    37 . . . 401   198/368 (53%)   e−105             Homo sapiens , 419 aa. [WO200190304-A2,    32 . . . 385   249/368 (66%)           29 NOV. 2001]       AAB88558   Human hydrophobic domain containing    37 . . . 401   198/368 (53%)   e−105           protein clone HP03424 #2 -  Homo      32 . . . 385   249/368 (66%)             sapiens , 419 aa. [WO200112660-A2,           22 FEB. 2001]       AAU74921   Mouse fl protein sequence -  Mus sp , 419    37 . . . 401   196/368 (53%)   e−104           aa. [WO200193681-A1, 13 DEC. 2001]    32 . . . 385   247/368 (66%)                  
 
     [0422] In a BLAST search of public sequence databases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.  
               TABLE 16D                          Public BLASTP Results for NOV16a                                         NOV16a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9ULK6   KIAA1214 protein -  Homo sapiens      1 . . . 438   396/438 (90%)   0.0           (Human), 462 aa (fragment).    67 . . . 462   396/438 (90%)       CAC33273   Sequence 22 from Patent WO0112660 -    37 . . . 401   198/368 (53%)    e−04             Homo sapiens  (Human), 419 aa.    32 . . . 385   249/368 (66%)       Q8VEM1   G1-related zinc finger protein -  Mus      37 . . . 401   197/368 (53%)    e−104             musculus  (Mouse), 419 aa.    32 . . . 385   247/368 (66%)       Q9QZQ6   G1-related zinc finger protein -  Mus      37 . . . 401   196/368 (53%)    e−104           musculus (Mouse), 419 aa.    32 . . . 385   247/368 (66%)       Q9P0J9   Goliath protein (Likely ortholog of   158 . . . 401   145/244 (59%)   3e−77           mouse g1-related zinc finger protein) -    1 . . . 242   178/244 (72%)             Homo sapiens  (Human), 276 aa.                  
 
     [0423] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.  
               TABLE 16E                          Domain Analysis of NOV16a                                     Identities/           Pfam   NOV16a   Similarities   Expect       Domain   Match Region   for the Matched Region   Value               PA    81 . . . 183   26/115 (23%)   7.1e−18               77/115 (67%)       zf-C3HC4   278 . . . 318   14/54 (26%)   1.8e−10               31/54 (57%)       PHD   277 . . . 321   12/51 (24%)   0.35               29/51 (57%)                  
 
     Example 17  
     [0424] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.  
               TABLE 17A                       NOV17 Sequence Analysis                                                    SEQ ID NO: 75   1419 bp                             NOV17a,     GCTGCTGAGGCCCAGGATATAAGGGCTGGAGGTGCTGCTTTCAGGCCTGGCCAGCCCA             CG113730-01     CC   ATG CACGCCCACTGCCTGCCCTTCCTTCTGCACGCCTGGTGGGCCCTACTCCAGGC       DNA Seuence   GGGTGCTGCGACGGTGGCCACTGCGCTCCTGCGTACGCGGGGGCAGCCCTCGTCGCCA                   TCCCCTCTGGCGTACATGCTGAGCCTCTACCGCGACCCGCTGCCGAGGGCAGACATCA                   TCCGCAGCCTACAGGCAGAAGATGTGGCAGTGGATGGGCAGAACTGGACGTTTGCTTT                   TGACTTCTCCTTCCTGAGCCAACAAGAGGATCTGGCATGGGCTGAGCTCCGGCTGCAG                   CTGTCCAGCCCTGTGGACCTCCCCACTGAGGGCTCACTTGCCATTGAGATTTTCCACC                   AGCCAAAGCCCGACACAGAGCAGGCTTCAGACAGCTGCTTAGAGCGGTTTCAGATGGA                   CCTATTCACTGTCACTTTGTCCCAGGTCACCTTTTCCTTGGGCAGCATGGTTTTGGAG                   GTGACCAGGCCTCTCTCCAAGTGGCTGAAGCACCCTGGGGCCCTGGAGAAGCAGATGT                   CCAGGGTAGCTGGAGAGTGCTGGCCGCGGCCCCCCACACCGCCTGCCACCAATGTGCT                   CCTTATGCTCTACTCCAACCTCTCGCAGGAGCAGAGGCAGCTGGGTGGGTCCACCTTG                   CTGTGGGAAGCCGAGAGCTCCTGGCGGGCCCAGGAGGGACAGCTGTCCTGGGAGTGGG                   GCAAGAGGCACCGTCGACATCACTTGCCAGACAGAAGTCAACTGTGTCGGAAGGTCAA                   GTTCCAGGTGGACTTCAACCTGATCGGATGGGGCTCCTGGATCATCTACCCCAAGCAG                   TACAACGCCTATCGCTGTGAGGGCGAGTGTCCTAATCCTGTTGGGGAGGAGTTTCATC                   CGACCAACCATGCATACATCCAGAGTCTGCTGAAACGTTACCAGCCCCACCGAGTCCC                   TTCCACTTGTTGTGCCCCAGTGAAGACCAAGCCGCTGAGCATGCTGTATGTGGATAAT                   GGCAGAGTGCTCCTAGATCACCATAAAGACATGATCGTGGAAGAATGTGGGTGCCTCT                     GA   TGACATCCTGGAGGGAGACTGGATTTGCCTGCACTCTGGAAGGCTGGGAAACTCCT                       GGAAGACATGATAACCATCTAATCCAGTAAGGAGAAACAGAGAGGGGCAAAGTTGCTC                       TGCCCACCAGAACTGAAGAGGAGGGGCTGCCCACTCTGTAAATGAAGGGCTCAGTGGA                       GTCTGGCCAAGCACAGAGGCTGCTGTCAGGAAGAGGGAGGAAGAAGCCTGTGCAGGGG                       GCTGGCTGGATGTTCTCTTTACTGAAAAGACAGTGGCAAGGAAAAGCACAAGTGCATG                       AGTTCTTTACTGGATTTTTTAAAAACC                                           ORF Start: ATG at 61   ORF Stop: TGA at 1102                                         SEQ ID NO: 76   347 aa   MW at 39560.8 Da                             NOV17a,   MHAHCLPFLLHAWWALLQAGAATVATALLRTRGQPSSPSPLAYMLSLYRDPLPRADII           CG113730-01   RSLQAEDVAVDGQNWTFAFDFSFLSQQEDLAWAELRLQLSSPVDLPTEGSLAIEIFHQ       Protein sequence   PKPDTEQASDSCLERFQMDLFTVTLSQVTFSLGSMVLEVTRPLSKWLKHPGALEKQMS                   RVAGECWPRPPTPPATNVLLMLYSNLSQEQRQLGGSTLLWEAESSWRAQEGQLSWEWG                   KRHRRHHLPDRSQLCRKVKFQVDFNLIGWGSWIIYPKQYNAYRCEGECPNPVGEEFHP                   TNHAYIQSLLKRYQPHRVPSTCCAPVKTKPLSMLYVDNGRVLLDHHKDMIVEECGCL                                         SEQ ID NO: 77   954 bp                             NOV17b,     GGA TCCCAGCCCTCGTCGCCATCCCCTCTGGCGTACATGCTGAGCCTCTACCGCGACC           210982580 DNA   CGCTGCCGAGGGCAGACATCATCCGCAGCCTACAGGCAGAACATGTGGCAGTGGATGG       Sequence   GCAGAACTGGACGTTTGCTTTTGACTTCTCCTTCCTGAGCCAACAAGAGGATCTGGCA                   TGGGCTGAGCTCCGGCTGCAGCTGTCCAGCCCTGTGGACCTCCCCACTGAGGGCTCAC                   TTGCCATTGAGATTTTCCACCAGCCAAAGCCCGACACAGAGCAGGCTTCAGACAGCTG                   CTTAGAGCGGTTTCAGATGGACCTATTCACTGTCACTTTGTCCCAGGTCACCTTTTCC                   TTGGGCAGCATGGTTTTGGAGGTGACCAGGCCTCTCTCCAAGTGGCTGAAGCACCCTG                   GGGCCCTGGAGAAGCAGATGTCCAGGGTAGCTGGAGAGTGCTGGCCACGGCCCCCCAC                   ACCGCCTGCCACCAATGTGCTCCTTATGCTCTACTCCAACCTCTCGCAGGAGCAGAGG                   CAGCTGGGTGGGTCCACCTTGCTGTGGGAAGCCGAGAGCTCCTGGCGGGCCCAGGAGG                   GACAGCTGTCCTGGGAGTGGGGCAAGAGGCACCGTCGACATCACTTGCCAGACAGAAG                   TCAACTGTGTCGGAAGGTCAAGTTCCAGGTGGACTTCAACCTGATCGGATGGGGCTCC                   TGGATCATCTACCCCAAGCAGTACAACGCCTATCGCTGTGAGGGCGAGTGTCCTAATC                   CTGTTGGGGAGGAGTTTCATCCGACCAACCATGCATACATCCAGAGTCTGCTGAAACG                   TTACCAGCCCCACCGAGTTCCTTCCACTTGTTGTGCCCCAGTGAAGACCAAGCCGCTG                   AGCATGCTGTATGTGGATAATGGCAGAGTGCTCCTAGATCACCATAAAGACATGATCG                   TGGAAGAATGTGGGTGCCTCCTCGAG                                         ORF Start: at 1   ORF Stop: end of sequence                                         SEQ ID NO: 78   318 aa   MW at 36367.0 Da                             NOV17b,   GSQPSSPSPLAYMLSLYRDRLPRADIIRSLQAEDVAVDGQNWTFAFDFSFLSQQEDLA           210982580 Protein   WAELRLQLSSPVDLPTEGSLAIEIFHQPKPDTEQASDSCLERFQMDLFTVTLSQVTFS       Sequence   LGSMVLEVTRPLSKWLKHPGALEKQMSRVAGECWPRPPTPPATNVLLMLYSNLSQEQR                   QLGGSTLLWEAESSWRAQEGQLSWEWGKRHRRHHLPDRSQLCRKVKFQVDFNLIGWGS                   WIIYPKQYNAYRCEGECPNPVGEEFHPTNHAYIQSLLKRYQPHRVPSTCCAPVKTKPL                   SMLYVDNGRVLLDHHKDMIVEECGCLLE                                         SEQ ID NO: 79   579 bp                             NOV17c,     ATG GTCCCCGGCGCCGCGGGCTGGTGTTGTCTCGTGCTCTGGCTCCCCGCGTGCGTCG           CG113794-02   CGGCCCACGGCTTCCGTATCCATGATTATTTGTACTTTCAAGTGCTGAGTCCTGGGGA       DNA Sequence   CATTCGATACATCTTCACAGCCACACCTGCCAAGGACTTTGGTGGTATCTTTCACACA                   AGGTATGAGCAGATTCACCTTGTCCCCGCTGAACCTCCAGAGGCCTGCGGGGAACTCA                   GCAACGGTTTCTTCATCCAGGACCAGATCGCTCTGGTGGAGAGTGGGGGCTGCTCCCT                   CCTCTCCAAGACTCGGGTGGTCCAGGAGCACGGCGGGCGGGCGGTGATCATCTCTGAC                   AATGCGGTTGACAATGACAGCTTCTATGTGGCGATGATCCAGGACAGTACCCAGCGCA                   CAGCTGACATCCCCGCCCTCTTCCTGCTCGGCCGAGACGGCTACATGATCCGCCGCTC                   TCTGGAACAGCCTGGGCTGCCATGGGCCATCATTTCCATCCCAGTCAATGTCACCAGC                   ATCCCCACCTTTGAGCTGCAGCAACCGTCCTGGTCCTTCTGG TAG   AAGGGCGATTCC                                           ORF Start: ATG at 1   ORF Stop: TAG at 565                                         SEQ ID NO: 80   188 aa   Mw at 20831.6 Da                             NOV17c,   MVPGAAGWCCLVLWLPACVAAHGFRIHDYLYFQVLSPGDIRYIFTATPAKDFGGIFHT           CG113794-02   RYEQIHLVPAEPPEACGELSNGFFIQDQIALVESGGCSLLSKTRVVQEHGGRAVIISD       Protein Sequence   NAVDNDSFYVAMIQDSTQRTADIPALFLLGRDGYMIRRSLEQPGLPWAIISIPVNVTS           IPTFELQQPSWSFW                  
 
     [0425] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B.  
               TABLE 17B                          Comparison of NOV17a against NOV17b and NOV17c.                                             NOV17a Residues/   Identities/Similarites for       Protein Sequence   Match Residues   the Matched Region               NOV17b    34 . . . 347   314/314 (100%)            3 . . . 316   314/314 (100%)       NOV17c   340 . . . 346    4/7 (57%)            89 . . . 95    5/7 (71%)                  
 
     [0426] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C.  
               TABLE 17C                       Protein Sequence Properties NOV17a                                        PSort   0.3700 probability located in outside; 0.1900 probability       analysis:   located in lysosome (lumen); 0.1800 probability located in           nucleus; 0.1000 probability located in endoplasmic           reticulum (membrane)       SignalP   Cleavage Site between residues 34 and 35       analysis:                  
 
     [0427] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Fable 17D.  
               TABLE 17D                          Geneseq Results for NOV17a                                         NOV17a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAY03849   Human nodal protein -  Homo sapiens,      65 . . . 347   282/283 (99%)    e−172           283 aa. [WO9909198-A1, 25 FEB. 1999]    1 . . . 283   282/283 (99%)       AAW56477   Amino acid sequence of human bone    68 . . . 347   279/280 (99%)    e−170           morphogenetic protein - 16 (BMP-16)-    1 . . . 280   279/280 (99%)             Homo sapiens , 280 aa. [WO9812322-A1,           26 MAR. 1998]       AAY03851   Murine nodal protein -  Mus sp , 354 aa.    1 . . . 347   279/355 (78%)    e−160           [WO9909198-A1, 25 FEB 1999]    1 . . . 354   298/355 (83%)       AAW84595   Amino acid sequence of the human   134 . . . 297   163/164 (99%)   2e−97           Tango-78 protein -  Homo sapiens , 169 aa.    1 . . . 164   163/164 (99%)           [WO9906427-A1, 11 FEB. 1999]       AAY16702   WO9914235 Seq ID No: 155-   247 . . . 347    99/101 (98%)   1e−58           Unidentified, 101 aa. [WO9914235-A1,    1 . . . 101   101/101 (99%)           25 MAR. 1999]                  
 
     [0428] 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.  
               TABLE 17E                          Public BLASTP Results for NOV17a                                         NOV17a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q96S42   Nodal-related protein -  Homo sapiens      1 . . . 347   346/347 (99%)   0.0           (Human), 347 aa.    1 . . . 347   346/347 (99%)       P43021   Nodal precursor -  Mus musculus      1 . . . 347   279/355 (78%)    e−160           (Mouse), 354 aa.    1 . . . .354   298/355 (83%)       O13048   Xnr-4 -  Xenopus laevis  (African    31 . . . 346   123/344 (35%)   2e−47           clawed frog), 402 aa.    72 . . . 401   170/344 (48%)       O13144   Nodal-related-2 (ZNR-2) -    43 . . . 346   123/347 (35%)   1e−46             Brachydanio rerio  (Zebrafish) (Zebra    58 . . . 391   171/347 (48%)           danio), 392 aa.       P87358   ZNR-1 (CYCLOPS precursor) -   243 . . . 347    71/105 (67%)   1e−41             Brachydanio rerio  (Zebrafish) (Zebra   397 . . . 501    86/105 (81%)           danio). 501 aa.                  
 
     [0429] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17F.  
               TABLE 17F                          Domain Analysis of NOV17a                                 NOV17a   Identities/           Pfam   Match   Similarities   Expect       Domain   Region   for the Matched Region   Value               TGFb_propeptide    4 . . . 213    43/256 (17%)   0.028               122/256 (48%)       TGF-beta   244 . . . 347    46/112 (41%)   1.5e−34                73/112 (65%)                  
 
     Example 18  
     [0430] The NOV18 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A. Note that the NOV18c nucleic acid (SEQ ID NO: 121) is the reverse complement of the NOV18a residues 247-349 (SEQ ID NO: 81). The NOV18e polypeptide contains additional amino acids at the ends of the ORF asssembly that are encoded by restriction endonuclease sites incorporated into amplicification primers, as described in Example B.  
               TABLE 18A                       NOV18 Sequence Analysis                                                    SEQ ID NO: 81   1056 bp                             NOV18a,     CACC   ATG CATCAGTCCCTGACTCAGCAGCGGTCCAGCGACATGTCCCTGCCCGATTCC           CG115187-   ATGGGTGCATTCAATCGGAGGAAACGAAACTCCATCTATGTCACCGTGACTTTGCTTA       01 DNA   TTGTGTCCGTGTTAATTCTCACAGTGGGCCTTGCTGCAACCACCAGGACCCAGAATGT       Sequence   GACTGTAGGAGGTTATTACCCCGGAGTTATTCTCGGCTTTGGATCGTTCCTTGGAATC                   ATTGGATCAAACCTTATTGAGAACAAAAGGCAGATGCTGGTGGCTTCTATCGTGTTTA                   TCAGCTTTGGTGTGATTGCGGCTTTTTGTTGTGCCATAGTTGACGGGGTCTTTGCTGC                   CAGACACATTGATCTGAAACCACTCTACGCTAACCGGTGCCATTATGTTCCCAAGACA                   TCACAGAAGGAAGCTGAGGAGGTGATAAGTTCCTCAACCAAAAATTCTCCTTCCACGA                   GGGTTATGAGGAACCTTACCCAGGCAGCTAGAGAGGTAAACTGCCCTCACCTCAGCCG                   TGAATTCTGCACACCTCGCATCCGGGGCAACACCTGCTTCTGCTGTGACCTCTACAAC                   TGTGGCAACCGGGTGGAGATCACTGGTGGGTACTACGAATACATCGATGTCAGCAGTT                   GCCAAGATATCATCCACCTCTACCACCTGCTCTGGTCTGCCACCATCCTCAACATTGT                   TGGCCTGTTCCTGGGCATCATCACTGCCGCTGTCCTTGGAGGCTTTAAGGACATGAAC                   CCAACTCTCCCAGCACTGAACTGTTCTGTTGAAAATACCCATCCAACAGTTTCTTACT                   ATGCTCATCCCCAAGTGGCATCCTACAATACCTACTACCATAGCCCTCCTCACCTGCC                   ACCATATTCTGCTTATGACTTTCAGCATTCCGGTGTCTTTCCATCCTCCCCTCCCTCT                   GGACTTTCTGATGAGCCCCAGTCTGCCTCTCCCTCACCCAGCTACATGTGGTCCTCAA                   GTGCACCGCCCCGTTACTCTCCACCCTACTATCCACCTTTTGAAAAGCCACCACCTTA               CAGTCCC TAA   AG                                           ORF Start: ATG at 5   ORF Stop: TAA at 1052                                         SEQ ID NO: 82   349 aa   MW at 38448.4 Da                             NOV18a,   MHQSLTQQRSSDMSLPDSMGAFNRRKRNSIYVTVTLLIVSVLILTVGLAATTRTQNVT           CG115187-   VGGYYPGVILGFGSFLGIIGSNLIENKRQMLVASIVFISFGVIAAFCCAIVDGVFAAR       01 Protein   HIDLKPLYANRCHYVPKTSQKEAEEVISSSTKNSPSTRVMRNLTQAAREVNCPHLSRE       Sequence   FCTPRIRGNTCFCCDLYNCGNRVEITGGYYEYIDVSSCQDIIHLYHLLWSATILNIVG                   LFLGIITAAVLGGFKDMNPTLPALNCSVENTHPTVSYYAHPQVASYNTYYHSPPHLPP                   YSAYDFQHSGVFPSSPPSGLSDEPQSASPSPSYMWSSSAPPRYSPPYYPPFEKPPPYS                                         SEQ ID NO: 83   1049 bp                             NOV18b,     CATCAGTCCCTGACTCAGCAGCGGTCCAGCGAC   ATG TCCCTGCCCGATTCCATGGGTG           CG115187-   CATTCAATCGGAGGAAACGAAACTCCATCTATGTCACCGTGACTTTGCTTATTGTGTC       02 DNA   CGTGTTAATTCTCACAGTGGGCCTTGCTGCAACCACCAGGACCCAGAATGTGACTGTA       Sequence   GGAGGTTATTACCCCGGAGTTATTCTCGGCTTTGGATCGTTCCTTGGAATCATTGGAT                   CAAACCTTATTGAGAACAAAAGGCAGATGCTGGTGGCTTCTATCGTGTTTATCAGCTT                   TGGTGTGATTGCGGCTTTTTGTTGTGCCATAGTTGACGGGGTCTTTGCTGCCAGACAC                   ATTGATCTGAAACCACTCTACGCTAACCGGTGCCATTATGTTCCCAAGACATCACAGA                   AGGAAGCTGAGGAGGTGATAAGTTCCTCAACCAAAAATTCTCCTTCCACGAGGGTTAT                   GAGGAACCTTACCCAGGCAGCTAGAGAGGTAAACTGCCCTCACCTCAGCCGTGAATTC                   TGCACACCTCGCATCCGGGGCAACACCTGCTTCTGCTGTGACCTCTACAACTGTGGCA                   ACCGGGTGGAGATCACTGGTGGGTACTACGAATACATCGATGTCAGCAGTTGCCAAGA                   TATCATCCACCTCTACCACCTGCTCTGGTCTGCCACCATCCTCAACATTGTTGGCCTG                   TTCCTGGGCATCATCACTGCCGCTGTCCTTGGAGGCTTTAAGGACATGAACCCAACTC                   TCCCAGCACTGAACTGTTCTGTTGAAAATACCCATCCAACAGTTTCTTACTATGCTCA                   TCCCCAAGTGGCATCCTACAATACCTACTACCATAGCCCTCCTCACCTGCCACCATAT                   TCTGCTTATGACTTTCAGCATTCCGGTGTCTTTCCATCCTCCCCTCCCTCTGGACTTT                   CTGATGAGCCCCAGTCTGCCTCTCCCTCACCCAGCTACATGTGGTCCTCAAGTGCACC                   GCCCCGTTACTCTCCACCCTACTATCCACCTTTTGAAAAGCCACCACCTTACAGTCCC                     TAA   AG                                           ORF Start: ATG at 34   ORF Stop: TAA at 1045                                         SEQ ID NO: 84   337 aa   MW at 37048.9 Da                             NOV18b,   MSLPDSMGAFNRRKRNSIYVTVTLLIVSVLILTVGLAATTRTQNVTVGGYYPGVILGF           CG115187-   GSFLGIIGSNLIENKRQMLVASIVFISFGVIAAFCCAIVDGVFAARHIDLKPLYANRC       02 Protein   HYVPKTSQKEAEEVISSSTKNSPSTRVMRNLTQAAREVNCPHLSREFCTPRIRGNTCF       Sequence   CCDLYNCGNRVEITGGYYEYIDVSSCQDIIHLYHLLWSATILNIVGLFLGIITAAVLG                   GFKDMNPTLPALNCSVENTHPTVSYYAHPQVASYNTYYHSPPHLPPYSAYDFQHSGVF                   PSSPPSGLSDEPQSASPSPSYMWSSSAPPRYSPPYYPPFEKPPPYSP                                         SEQ ID NO: 85   980 bp                             NOV18c,     ATG CATCAGTCCCTGACTCAGCAGCGGTCCAGCGACATGTCCCTGCCCGATTCCATGG           CG115187-   GAGCATTCAATCGGAGGAAACGAAACTCCATCTATGTCACCGTGACTTTGCTTATTGT       03 DNA   GTCCGTGTTAATTCTCACAGTGGGCCTTGCTGCAACCACCAGGACCCAGAATGTGACT       Sequence   GTAGGAGGTTATTACCCCGGAGTTATTCTCGGCTTTGGATCGTTCCTTGGAATCATTG                   GATCAAACCTTATTGAGAACAAAAGGCAGATGCTGGTGGCTTCTATCGTGTTTATCAG                   CTTTGGTGTGATTGCGGCTTTTTGTTGTGCCATAGTTGACGGGGTCTTTGCTGCCAGA                   CACATTGATCTGAAACCACTCTACGCTAACCGGTGCCATTATGTTCCCAAGACATCAC                   AGAAGGAAGCTGAGGAGGTTAACTGCCCTCACCTCAGCCGTGAATTCTGCACACCTCG                   CATCCGGGGCAACACCTGCTTCTGCTGTGACCTCTACAACTGTGGCAACCGGGTGGAG                   ATCACTGGTGGGTACTACGAATACATCGATGTCAGCAGTTGCCAAGATATCATCCACC                   TCTACCACCTGCTCTGGTCTGCCACCATCCTCAACATTGTTGGCCCGTTCCTGGGCAT                   CATCACTGCCGCTGTCCTTGGAGGCTTTAAGGACATGAACCCAACTCTCCCAGCACTG                   AACTGTTCTGTTGAAAATACCCATCCAACAGTTTCTTACTATGCTCATCCCCAAGTGG                   CATCCTACAATACCTACTACCATAGCCCTCCTCACCTGCCACCATATTCTGCTTATGA                   CTTTCAGCATTCCGGTGTCTTTCCATCCTCCCCTCCCTCTGGACTTTCTGATGAGCCC                   CAGTCTGCCTCTCCCTCACCCAGCTACATGTGGTCCTCAAGTCCACCGCCCCGTTACT                   CTCCACCCTACTATCCACCTTTTGAAAAGCCACCACCTTACAGTCCC TAA   AG                                           ORF Start: ATG at 1   ORF Stop: TAA at 976                                         SEQ ID NO: 86   325 aa   MW at 35816.4 Da                             NOV18c,   MHQSLTQQRSSDMSLPDSMGAFNRRKRNSIYVTVTLLIVSVLILTVGLAATTRTQNVT           CG115187-   VGGYYPGVILGFGSFLGIIGSNLIENKRQMLVASIVFISFGVIAAFCCAIVDGVFAAR       03 Protein   HIDLKPLYANRCHYVPKTSQKEAEEVNCPHLSREFCTPRIRGNTCFCCDLYNCGNRVE       Sequence   ITGGYYEYIDVSSCQDIIHLYHLLWSATILNIVGPFLGIITAAVLGGFKDMNPTLPAL                   NCSVENTHPTVSYYAHPQVASYNTYYHSPPHLPPYSAYDFQHSGVFPSSPPSGLSDEP                   QSASPSPSYMWSSSAPPRYSPPYYPPFEKPPPYSP                                         SEQ ID NO: 87   847 bp                             NOV18d,     C   ACC GGATCCGCAACCACCAGGACCCAGAATGTGACTGTAGGAGGTTATTACCCCGGA           262770580   GTTATTCTCGGCTTTGGATCGTTCCTTGGAATCATTGGATCAAACCTTATTGAGAACA       DNA   AAAGGCAGATGCTGGTGGCTTCTATCGTGTTTATCAGCTTTGGTGTGATTGCGGCTTT       Sequence   TTGTTGTGCCATAGTTGACGGGGTCTTTGCTGCCAGACACATTGATCTGAAACCACTC                   TACGCTAACCGGTGCCATTATGTTCCCAAGACATCACAGAAGGAAGCTGAGGAGGTTA                   ACTGCCCTCACCTCAGCCGTGAATTCTGCACACCTCGCATCCGGGGCAACACCTGCTT                   CTGCTGTGACCTCTACAACTGTGGCAACCGGGTGGAGATCACTGGTGGGTACTACGAA                   TACATCGATGTCAGCAGTTGCCAAGATATCATCCACCTCTACCACCTGCTCTGGTCTG                   CCACCATCCTCAACATTGTTGGCCTGTTCCTGGGCATCATCACTGCCGCTGTCCTTGG                   AGGCTTTAAGGACATGAACCCAACTCTCCCAGCACTGAACTGTTCTGTTGAAAATACC                   CATCCAACAGTTTCTTACTATGCTCATCCCCAAGTGGCATCCTACAATACCTACTACC                   ATAGCCCTCCTCACCTGCCACCATATTCTGCTTATGACTTTCAGCATTCCGGTGTCTT                   TCCATCCTCCCCTCCCTCTGGACTTTCTGATGAGCCCCAGTCTGCCTCTCCCTCACCC                   AGCTACATGTGGTCCTCAAGTGCACCGCCCCGTTACTCTCCACCCTACTATCCACCTT                   TTGAAAAGCCACCACCTTACAGTCCCCTCGAGGGC                                         ORF Start: at 2   ORF Stop: end of sequence                                         SEQ ID NO: 88   282 aa   MW at 30945.7 D                             NOV18d,   TGSATTRTQNVTVGGYYPGVILGFGSFLGIIGSNLIENKRQMLVASIVFISFGVIAAF           262770580   CCAIVDGVFAARHIDLKPLYANRCHYVPKTSQKEAEEVNCPHLSREFCTPRIRGNTCF       Protein   CCDLYNCGNRVEITGGYYEYIDVSSCQDIIHLYHLLWSATILNIVGLFLGIITAAVLG       Sequence   GFKDMNPTLPALNCSVENTHPTVSYYAHPQVASYNTYYHSPPHLPPYSAYDFQHSGVF                   PSSPPSGLSDEPQSASPSPSYMWSSSAPPRYSPPYYPPFEKPPPYSPLEG                                         SEQ ID NO: 121   328 bp                             NOV18e,   GCCCTCGAGGGGACTGTAAGGTGGTGGCTTTTCAAAAGGTGGATAGTAGGGTGGAGAGTAA           257788219   CGGGGCGGTGCACTTGAGGACCACATGTAGCTGGGTGAGGGAGAGGCAGACTGGGGCTCAT       -rev DNA   CAGAAAGTCCAGAGGGAGGGGAGGATGGAAAGACACCGGAATGCTGAAAGTCATAAGCAGA       Sequence;   GCATAGTAAGAAACTGTTGGATGGGTATTTTCAACAGAACAGTTCAGTGCTGGGAGAGTTG       (Frame -2)   GGTTCATGTCCTTGGATCCGGTG                                         ORF Start: at 328   ORF Stop: 2                                         SEQ ID NO: 122   109 aa   MW at 11964.41 Da                             NOV18e,   TGSKDMNPTLPALNCSVENTHPTVSYYAHPQVASYNTYYHSPPHLPPYSAYDFQHSGVFP           257788219   SSPPSGLSDEPQSASPSPSYMWSSSAPPRYSPPYYPPFEKPPPYSPLEG       Protein       Sequence                  
 
     [0431] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 18B.  
               TABLE 18B                          Comparison of NOV18a against NOV18b and NOV18d.                                             NOV18a Residues/   Identities/Similarites for       Protein Sequence   Match Residues   the Matched Region               NOV18b   13 . . . 315   257/303 (84%)            1 . . . 303   257/303 (84%)       NOV18c    1 . . . 315   244/315 (77%)            1 . . . 291   244/315 (77%)       NOV18d   49 . . . 315   215/267 (80%)            3 . . . 245   216/267 (80%)                  
 
     [0432] Further analysis of the NOV18a protein yielded the following properties shown in Table 18C.  
               TABLE 18B                       Protein Sequence Properties NOV18a                                        PSort   0.6000 probability located in plasma membrane;       analysis:   0.4000 probability located in Golgi body; 0.3000 probability           located in endoplasmic reticulum (membrane);           0.0300 probability located in mitochondrial inner membrane       SignalP   Cleavage site between residues 50 and 51       analysis:                  
 
     [0433] 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.  
               TABLE 18D                          Geneseq Results for NOV18a                                         NOV18a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAB31671   Amino acid sequence of a human protein    13 . . . 130    83/118 (70%)   1e−42           having a hydrophobic domain -  Homo      9 . . . 126   101/118 (85%)             sapiens , 166 aa. [WO200104297-A2,           18 JAN 2001]       AAE03793   Human gene 13 encoded secreted protein    13 . . . 148    88/143 (61%)   9e−41           fragment, SEQ ID NO:63 -  Homo      5 . . . 143   110/143 (76%)             sapiens , 150 aa. [WO200132837-A1,           10 MAY 2001]       AAE03776   Human gene 13 encoded secreted protein    88 . . . 148    37/68 (54%)   6e−10           HELEN05, SEQ ID NO: 46 -  Homo      1 . . . .64    47/68 (68%)             sapiens , 71 aa. [WO200132837-A1,           10 MAY 2001]       ABG06803   Novel human diagnostic protein #6794 -   271. . . 349    28/79 (35%)   4e−05             Homo sapiens , 106 aa. [WO200175067-    8 . . . 78    39/79 (48%)           A2, 11 OCT. 2001]       ABG06803   Novel human diagnostic protein #6794 -   271 . . .349    28/79 (35%)   4e−05             Homo sapiens , 106 aa. [WO200175067-    8 . . . 78    39/79 (48%)           A2, 11 OCT. 2001]                  
 
     [0434] 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.  
               TABLE 18E                          Public BLASTP Results for NOV18a                                         NOV18a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9BE63   Hypothetical 38.5 kDa protein -    1 . . . 349   346/349 (99%)   0.0             Macaca fascicularis  (Crab eating    1 . . . 349   347/349 (99%)           macaque) (Cynomolgus monkey),           349 aa.       Q9NWN8   CDNA FLJ20716 fis, clone   166 . . . 349   184/184 (100%)    e−113           HEP19742 -  Homo sapiens  (Human),    2 . . . 185   184/184 (100%)           185 aa.       Q8WV15   Hypothetical 34.6 kDa protein -  Homo      13 . . . 349   173/343 (50%)   3e−85             sapiens  (Human), 326 aa.    9 . . . 326   221/343 (63%)       CAC28404   Sequence 24 from Patent WO0104297 -    13 . . . 130    83/118 (70%)   2e−42             Homo sapiens  (Human), 166 aa.    9 . . . 126   101/118 (85%)       Q9ZWT0   Extensin -  Adiantum capillus - veneris     264 . . . 349    31/87 (35%)   4e−05           (Fern), 207 aa.    46 . . . 126    40/87 (45%)                  
 
     [0435]                              Domain Analysis of NOV18a.                                     Identities/           Pfam       Similarities   Expect       Domain   NOV18a Match Region   for the Matched Region   Value                         No Significant Known Matches Found                    
     Example 19  
     [0436] The NOV19 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19A.  
               TABLE 19A                       NOV19 Sequence Analysis                                                    SEQ ID NO: 89   11941 bp                             NOV19a,     ATG GAGGGTGGCGACCCCACCCCAACTCCACAGGGACAGAAGAAGCTCCTGCCTCAGG           CG115540-01   ACCGCCCTAGACACTGCCCTGTGGACCCCCTCATCTGGCTGTTCATTTGTATTCTTTC       DNA Sequence   TAAGCTGGTAAATGGCCCCTTGGACGGCGCGGCAAGCTTGGTAGAAGAGGCGACCCTG                   GTCCTCCAGGGCAATCAGGACGAGATGGCTACCCGGGACCCCTGGGTTTGGATGGCAA                   GCCTGGACTTTCAGGCCCGAAAGGGGAAAAGGGAGACCAAGGACAAGATGGAGCTGCT                   GGGCCTCCGGGGCCCCCTGGACCTCCTGGGGCCCGGGGCCCTCCTGGCGACACTGGGA                   AAGATGGCCCCAGGGGAGCACAAGGCCCAGCGGGCCCCAAAGGAGAGCCCGGACAAGA                   CGGCGAGATGGGCCCAAAGGGACCCCCAGGGCCCAAGGGTGAGCCTGGAGTACCTGGA                   AAGAAGATGCCAGGAGCAGACTGGTGTGCTGGGAAGTCCAGAGGAGGGAGGGGCCCAC                   TGGCCACCCGAGGGTCTGACCGGCAAGCCCCAGGTGTCCTCTCCTCAGGGCGACGATG                   GGACACCAAGCCAGCCTGGACCACCAGGGCCCAAGGGGGCCTCACTCTCTGCCCTGTC                   CCCAAGCCAGGAACTGGGTGTCATCCTCATGCCTTGCTCCCCCAACCCCTCGCAACAG                   CCACCAAATCCTGGCCAGCCAGTCTCCAAAATGTCCCTTGAGCCCCTGCGCTGCCCCA                   AGGCGAGCCAGGGAGCATGGGGCCTCGGGGAGAGAACGGTGTGGACGGTGCCCCAGGA                   CCGAAGCTGCACCTCTGGCTGCAAATGCATGTCTCCACAGGGGGAGCCTGGCCACCGA                   GGCGCGGATGGAGCTGCAGGGCCCCGGGGTGCCCCAGGCCTCAAGGGCGAGCAGGGAG                   ACACAGTGGTGATCGACTATGATGGCAGGATCTTGGATGCCCTCAAGGTAGTGTTCCT                   GGGGCCTCCCGGACCACAGGGGCCCCCAGGGCCACCAGGGATCCCTGGAGCCAAGGGC                   GAGCTTGGATTGCCCGGTGCCCCAGGAATCGATGGAGAGAAGGTCTCTGGGCCTTTCA                   TTTCCTTGGTGATGCCAGTGCCTGGTATTGGGCTCTGTGGCCCCAAAGGACAGAAAGG                   AGACCCAGGAGAGCCTGGGCCAGCAGGACTCAAAGGGGAAGCAGGCGAGATGGGCTTG                   TCCGGCCTCCCGGTGCTGGACACAAAGGACTCACAGGCCATTGCCGTCCTGCAGGGCG                   CTGACGGCCTCAAGGGGGAGAAGGGGGAGTCGGCATCTGACAGCCTACAGGAGAGCCT                   GGCTCAGCTCATAGTGGAGCCAGGGCCCCCTGGCCCCCCTGGCCCCCCAGGCCCGATG                   GGCCTCCAGGGAATCCAGGGTCCCAAGGGCTTGGATGGAGCAAAGGGAGAGAAGGGTG                   CGTCGGGTGAGAGAGGCCCCAGCGGCCTGCCTGGGCCAGTTGGCCCACCGGGCCTTAT                   TGGGCTGCCAGGAACCAAAGGAGAGAAGGGCAGACCCGGGGAGCCAGGACTAGATGGT                   TTCCCTGGACCCCGAGGAGAGAAAGGTGATCGGAGCGAGCGTGGAGAGAAGGGAGAAC                   GAGGGGTCCCCGGCCGGAAAGGAGTGAAGGGCCAGAAGGGCGAGCCGGGACCACCAGG                   CCTGGACCAGCCGTGTCCCGTGGGCCCCGACGGGCTGCCTGTGCCTGGCTGCTGGCAT                   AAGAACCTGCTCCCGCAAAACTCTGGAGTCCCTGGGACACACCCTATCCAAGAAGACC                   CAGGGGTGGAACAGCGGCTGCTGTTGCTCCTGGCCTCATCAGCCTCCAAACTCAACCA                   CAACCAGCTGCCTCTGCAGTTGGACAAGACTTGGCCCCCGGACAAGACTCGCCCAGCA                   CTTGCGGCTGGGCCCGGGGAGCAGTGA                                         ORF Start: ATG at 1   ORF Stop: TGA at 1939                                         SEQ ID NO: 90   646 aa   MW at 66246.7 Da                             NOV19a,   MEGGDPTPTPQGQKKLLPQDRPRHCPVDPLIWLFICILSKLVNGPLDGAASLVEEATL           CG115540-01   VLQGNQDEMATRDPWVWMASLDFQARKGKRETKDKMELLGLRGPLDLLGPGALLATLG       Protein Sequence   KMAPGEHKAQRAPKESPDKTARWAQRDPQGPRVSLEYLERRCQEQTGVLGSPEEGGAH                   WPPEGLTGKPQVSSPQGDDGTPSQPGPPGPKGASLSALSPSQELGVILMPCSPNPSQQ                   PPNPGQPVSKMSLEPLRCPKASQGAWGLGERTVWTVPQDRSCTSGCKCMSPQGEPGHR                   GADGAAGPRGAPGLKGEQGDTVVIDYDGRILDALKVVFLGPPGPQGPPGPPGIPGAKG                   ELGLPGAPGIDGEKVSGPFISLVMPVPGIGLCGPKGQKGDPGEPGPAGLKGEAGEMGL                   SGLPVLDTKDSQAIAVLQGADGLKGEKGESASDSLQESLAQLIVEPGPPGPPGPPGPM                   GLQGIQGPKGLDGAKGEKGASGERGPSGLPGPVGPPGLIGLPGTKGEKGRPGEPGLDG                   FPGPRGEKGDRSERGEKGERGVPGRKGVKGQKGEPGPPGLDQPCPVGPDGLPVPGCWH                   KNLLPQNSGVPGTHPIQEDPGVEQRLLLLLASSASKLNHNQLPLQLDKTWPPDKTRPA                   LAAGPGEQ                  
 
     [0437] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.  
               TABLE 198                       Protein Sequence Properties NOV19a                                        PSort   0.7900 probability located in plasma membrane;       analysis:   0.3000 probability located in microbody (peroxisome);           0.3000 probability located in Golgi body; 0.2000 probability           located in endoplasmic reticulum (membrane)       SignalP   Cleavage site between residues 45 and 46       analysis:                  
 
     [0438] 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 19C.  
               TABLE 19C                          Geneseq Results for NOV19a                                         NOV19a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Portion   Value               AAB43239   Human ORFX ORF3003 polypeptide    349 . . . 581   189/233 (81%)    e−106           sequence SEQ ID NO: 6006 -  Homo       1 . . . 200   189/233 (81%)             sapiens , 200 aa. [WO200058473-A2,           05 OCT. 2000]       AAG63332   Amino acid sequence of human collagen-    98 . . . 581   208/495 (42%)   7e−83           like protein CLAC -  Homo sapiens , 654    234 . . . 654   247/495 (49%)           aa. [WO200158943-A1, 16 AUG. 2001]       AAG63343   Amino acid sequence of murine    98 . . . 581   205/509 (40%)   1e−82           collagen-like protein CLAC -  Mus sp   ,      234 . . . 666   240/509 (46%)           666 aa. [WO200158943-A1, 16 AUG. 2001]       AAR53257   Human collagen (Type V) -  Homo      98 . . . 576   176/486 (36%)   2e−61           sapiens, 1838 aa. [JP06105687-A,   1135 . . . 1538   209/486 (42%)           19 APR. 1994]       AAY08305   Human collagen IX alpha-2 chain protein    98 . . . 605   188/545 (34%)   4e−60             Homo sapiens , 705 aa. [WO9921011-    30 . . . 518   233/545 (42%)           A1, 29 APR. 1999]                  
 
     [0439] 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 19D.  
               TABLE 19D                          Public BLASTP Results for NOV19a                                         NOV19a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               Q9NT93   Hypothetical 19.5 kDa protein -  Homo     349 . . . 581   201/233 (86%)    e−115             sapiens  (Human), 201 aa (fragment).    1 . . . 201   201/233 (86%)       Q99MQ5   Collagen-like alzheimer amyloid plaque    98 . . . 581   205/509 (40%)   3e−82           component precursor type I -  Mus     234 . . . 666   240/509 (46%)             musculus  (mouse), 666 aa.       Q9NQ52   Type XIII collagen -  Homo sapiens     159 . . . 581   198/488 (40%)   3e−75           (Human), 717 aa.   263 . . . 717   235/488 (47%)       O70575   Collagen type XIII alpha-1 chain -  Mus     159 . . . 581   197/495 (39%)   1e−74             musculus  (Mouse), 739 aa.   270 . . . 739   233/495 (46%)       Q14035   Alpha-1 type XIII collagen -  Homo     159 . . . 581   192/488 (39%)   3e−70             sapiens  (Human), 623 aa.   170 . . . 623   231/488 (46%)                  
 
     [0440] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.  
               TABLE 19E                          Domain Analysis of NOV19a                                     Identities/           Pfam   NOV19a   Similarities       Domain   Match Region   for the Matched Region   Expect Value               Collagen   283 . . . 341   23/60 (38%)   0.0033               41/60 (68%)       Collagen   342 . . . 401   22/60 (37%)   0.0014               36/60 (60%)       Collagen   448 . . . 506   32/60 (53%)   1.4e−07               43/60 (72%)       Collagen   307 . . . 566   27/60 (45%)   1.1e−10               46/60 (77%)                  
 
     Example 20  
     [0441] Thc NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A.  
                   TABLE 20A                       NOV20 Sequence Analysis                                                SEQ ID NO: 9                  11247 bp           NOV20a,     GCCCTACCGTGTGCGCAGAAAGAGGAGGCGCTTGCCTTCAGCTTGTGGGAAATCCCGA         CG118689-01       DNA Sequence     AG   ATG GCCAAAGACAACTCAACTGTTCGTTGCTTCCAGGGCCTGCTGATTTTTGGAAA                   TGTGATTATTGGTTGTTGCGGCATTGCCCTGACTGCGGAGTGCATCTTCTTTGTATCT                   GACCAACACAGCCTCTACCCACTGCTTGAAGCCACCGACAACGATGACATCTATGGGG                   CTGCCTGGATCGGCATATTTGTGGGCATCTGCCTCTTCTGCCTGTCTGTTCTAGGCAT                   TGTAGGCATCATGAAGTCCAGCAGGAAAATTCTTCTGGCGTATTTCATTCTGATGTTT                   ATAGTATATGCCTTTGAAGTGGCATCTTGTATCACAGCAGCAACACAACGAGACTTTT                   TCACACCCAACCTCTTCCTGAAGCAGATGCTAGAGAGGTACCAAAACAACAGCCCTCC                   AAACAATGATGACCAGTGGAAAAACAATGGAGTCACCAAAACCTGGGACAGGCTCATG                   CTCCAGGACAATTGCTGTGGCGTAAATGGTCCATCAGACTGGCAAAAATACACATCTG                   CCTTCCGGACTGAGAATAATGATGCTGACTATCCCTGGCCTCGTCAATGCTGTGTTAT                   GAACAATCTTAAAGAACCTCTCAACCTGGAGGCTTGTAAACTAGGCGTGCCTGGTTTT                   TATCACAATCAGTTTTGGGTTCTCCTGGGTACCATGTTCTACTGGAGCAGAATTGAAT                   AT TAA   GCATAAAGTGTTGCCACCATACCTCCTTCCCCGAGTGACTCTGGATTTGGTGC                       TGGAACCAGCTCTCTCCTAATATTCCACGTTTGTGCCCCACACTAACGTGTGTGTCTT                       ACATTGCCAAGTCAGATGGTACGGACTTCCTTTAGGATCTCAGGCTTCTGCAGTTCTC                       ATGACTCCTACTTTTCATCCTAGTCTAGCATTCTGCAACATTTATATAGACTGTTGAA                       AGGAGAATTTGAAAAATGCATAATAACTACTTCCATCCCTGCTTATTTTTAATTTGGG                       AAAATAAATACATTCGAAGGAAAAACAAAAAAAAGGGCGGCCCCCGATTATTGAGGGG                       TCCCGAGCCCGAACTCGTAACCATGTAAAACCCGTTCCCCGGGGTAAAATTGTAATCC                       CCCCACAATTCCCCAAAACATAGGGCCCGGAAGCCTAAAGTTTAAAACCCTGGGGGGG                       CCTAAGGAGTTTACCCAAACTCCCTTTCT                     ORF Start: ATG at 61          ORF Stop: TAA at 757           SEQ ID NO: 92                 232 aa     MW at 26502.3 Da       NOV20a,   MAKDNSTVRCFQGLLIFGNVIIGCCGIALTAECIFFVSDQHSLYPLLEATDNDDIYGA       CG118689-01       Protein Sequence   AWIGIFVGICLFCLSVLGIVGIMKSSRKILLAYFILMFIVYAFEVASCITAATQRDFF                   TPNLFLKQMLERYQNNSPPNNDDQWKNNGVTKTWDRLMLQDNCCGVNGPSDWQKYTSA                   FRTENNDADYPWPRQCCVMNNLKEPLNLEACKLGVPGFYHNQFWVLLGTMFYWSRIEY                   SEQ ID NO: 93                 851 bp       NOV20b,     GAAG   ATG GCCAAAGACAACTCAACTGTTCGTTGCTTCCAGGGCCTGCTGATTTTTGGA       CG118689-02       DNA Sequence   AATGTGATTATTGGTTGTTGCGGCATTGCCCTGACTGCGGAGTGCATCTTCTTTGTAT                   CTGACCAACACAGCCTCTACCCACTGCTTGAAGCCACCGACAACGATGACATCTATGG                   GGCTGCCTGGATCGGCATATTTGTGGGCATCTGCCTCTTCTGCCTGTCTGTTCTAGGC                   ATTGTAGGCATCATGAAGTCCAGCAGGAAAATTCTTCTGGCGTATTTCATTCTGATGT                   TTATAGTATATGCCTTTGAAGTGGCATCTTGTATCACAGCAGCAACACAACGAGACTT                   TATGCTAGAGAGGTACCAAAACAACAGCCCTCCAAATAATGATGACCAGTGGAAAAAC                   AATGGAGTCACCAAAACCTGGGACAGGCTCATGCTCCAGGACAATTGCTGTGGCGTAA                   ATGGTCCATCAGACTGGCAAAAATACACATCTGCCTTCCGGACTGAGAATAATGATGC                   TGACTATCCCTGGCCTCGTCAATGCTGTGTTATGAACAATCTTAAAGAACCTCTCAAC                   CTGGAGGCTTGTAAACTAGGCGTGCCTGGTTTTTATCACAATCAGGGCTGCTATGAAC                   TGATCTCTGGTCCAATGAACCGACACGCCTGGGGGGTTGCCTGGTTTGGATTTGCCAT                   TCTCTGCTGGACTTTTTGGGTTCTCCTGGGTACCATGTTCTACTGGAGCAGAATTGAA                   TAT TAG   GCATAAAGTGTTGCCACCATACCTCCTTCCCCCGAGTGACTCTGGATTTGGT                       GCTGGAACCAGCTCTCTCCTAATATTCCACGTTTGTGCC                     ORF Start: ATG at 5           ORF Stop: TAG at 758           SEQ ID NO: 94                 251 aa     MW at 28581.7 Da       NOV20b,   MAKDNSTVRCFQGLLIFGNVIIGCCGIALTAECIFFVSDQHSLYPLLEATDNDDIYGA       CG118689-02       Protein Sequence   AWIGIFVGICLFCLSVLGIVGIMKSSRKILLAYFILMFIVYAFEVASCITAATQRDFM                   LERYQNNSPPNNDDQWKNNGVTKTWDRLMLQDNCCGVNGPSDWQKYTSAFRTENNDAD                   YPWPRQCCVMNNLKEPLNLEACKLGVPGFYHNQGCYELISGPMNRHAWGVAWFGFAIL                   CWTFWVLLGTMFYWSRIEY                  
 
     [0442] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 20B.  
               TABLE 20B                          Comparison of NOV20a against NOV20b.                         Protein   NOV20a Residues/   Identities/       Sequence   Match Residues   Similarities for the Matched Region               NOV20b   1 . . . 232   223/260 (85%)           1 . . . 251   223/260 (85%)                  
 
     [0443] Further analysis of the NOV20a protein yielded the following properties shown in Table 20C.  
               TABLE 20C                       Protein Sequence Properties NOV20a                                        PSort   0.6850 probability located in endoplasmic reticulum       analysis:   (membrane); 0.6400 probability located in plasma membrane;           0.4600 probability located in Golgi body; 0.1000 probability           located in endoplasmic reticulum (lumen)       SignalP   Cleavage site between residues 31 and 32       analysis:                  
 
     [0444] 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/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Portion   Value               AAY94419   Human TM4P-1 protein -  Homo      1 . . . 232   232/260 (89%)    e−137             sapiens , 260 aa. [WO200026243-A2,    1 . . . 260   232/260 (89%)           11 MAY 2000]       AAE10871   Bovine uroplakin 1b protein -  Bos sp ,    1 . . . 232   214/260 (82%)    e−126           260 aa. [US6290959-B1, 18 SEP. 2001]    1 . . . 260   225/260 (86%)       AAE10870   Bovine uroplakin 1a protein -  Bos sp ,   13 . . . 208    81/198 (40%)   1e−42           258 aa. [US6290959-B1, 18 SEP. 2001]   18 . . . 208   116/198 (57%)       AAM48320   Human tetraspan -  Homo sapiens , 248    4 . . . 223    67/229 (29%)   2e−16           aa. [FR2809734-A1, 07 DEC. 2001]    2 . . . 214   111/229 (48%)       AAB49503   Clone HCE1K90 #1 -  Homo sapiens ,    4 . . . 223    67/229 (29%)   2e−16           248 aa. [WO200070076-A1, 23 NOV. 2000]    2 . . . 214   111/229 (48%)                  
 
     [0445] 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.  
               TABLE 20E                          Public BLASTP Results for NOV20a                                         NOV20a   Identities/           Protein       Residues/   Similarities for       Accession       Match   the Matched   Expect       Number   Protein/Organism/Length   Residues   Portion   Value               O75841   Uroplakin 1b (UP1b) -  Homo sapiens     2 . . . 232   231/259 (89%)   e−136           (Human), 259 aa.   1 . . . 259   231/259 (89%)       A41531   TGFbeta-regulated protein TI-1-   1 . . . 232   217/260 (83%)   e−129           American mink, 260 aa.   1 . . . 260   228/260 (87%)       P30413   Uroplakin 1b (UP1b) (TI 1 protein) -   2 . . . 232   216/259 (83%)   e−128             Mustela vison  (American mink), 259 aa.   1 . . . 259   227/259 (87%)       I46081   uroplakin 1b - bovine, 260 aa.   1 . . . 232   214/260 (82%)   e−126               1 . . . 260   225/260 (86%)       P38573   Uroplakin 1b (UPIb) -  Bos taurus     2 . . . 232   213/259 (82%)   e−125           (Bovine), 259 aa.   1 . . . 259   224/259 (86%)                  
 
     [0446] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20F.  
               TABLE 20F                          Domain Analysis of NOV20a                                     Identities/                   Similarities           NOV20a   for the   Expect       Pfam Domain   Match Region   Matched Region   Value               transmembrane4   12 . . . 225    53/256 (21%)   2.3e−43               163/256 (64%)                  
 
     Example 21  
     [0447] The NOV21 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 21A.  
                   TABLE 21A                       NOV21 Sequence Analysis                                                SEQ ID NO: 95                 1518 bp           NOV21a,     CGGGCATGAAGGAGG   ATG GAAGGGCAGGACGAGGTGTCGGCGCGGGAGCAGCACTTCC       CG120748-01       DNA Sequence   ACAGCCAAGTGCGGGAGTCCACGATATGTTTCCTTCTTTTTGCCATTCTCTACGTTGT                   TTCCTACTTCATCATCACAAGATACAAGAGAAAATCAGATGAACAAGAAGATGAAGAT                   GCCATCGTCAACAGGATTTCGTTGTTTTTGAGCACGTTCACTCTCGCAGTGTCAGCTG                   GGGCTGTTTTGCTTTTACCCTTCTCAATCATCAGCAATGAAATCCTGCTTTCTTTTCC                   TCAGAACTACTATATTCAGTGGCTAAATGGCTCCCTGATTCATGGTTTGTGGAATCTT                   GCTTCCCTTTTTTCCAACCTTTGTTTATTTGTATTGATGCCCTTTGCCTTTTTCTTTC                   TGGAATCAGAAGGCTTTGCTGGCCTGAAAAAGGGAATCCGAGCCCGCATTTTAGAGAC                   TTTGGTCATGCTTCTTCTTCTTGCGTTACTCATTCTTGGGATAGTGTGGGTAGCTTCA                   GCACTCATTGACAACGATGCCGCAAGCATGGAATCTTTATATGATCTCTGGGAGTTCT                   ATCTACCCTATTTATATTCCTGTATATCATTGATGGGATGTTTGTTACTTCTCTTGTG                   TACACCAGTTGGCCTTTCTCGTATGTTCACAGTGATGGGTCAGTTGCTAGTGAAGCCA                   ACAATTCTTGAAGACCTGGATGAACAAATTTATATCATTACCTTAGAGGAAGAAGCAC                   TCCAGAGACGACTAAATGGTCTGTCTTCATCGGTGGAATACAACATAATGGAGTTGGA                   ACAAGAACTTGAAAATGTAAAGACTCTTAAGACAAAATTAGATAGGCGAAAAAAGGCT                   TCAGCATGGGAAAGAAATTTGGTGTATCCCGCTGTTATGGTTCTCCTTCTTATTGAGA                   CATCCATCTCGGTCCTCTTGGTGGCTTGTAATATTCTTTGCCTATTGGTTGATGAAAC                   AGCAATGCCAAAAGGAACAAGGGGGCCTGGAATAGGAAATGCCTCTCTTTCTACGTTT                   GGTTTTGTGGGAGCTGCGCTTGAAATCATTTTGATTTTCTATCTTATGGTGTCCTCTG                   TTGTCGGCTTCTATAGCCTTCGATTTTTTGGAAACTTTACTCCCAAGAAAGATGACAC                   AACTATGACAAAGATCATTGGAAATTGTGTGTCCATCTTGGTTTTGAGCTCTGCTCTG                   CCTGTGATGTCGAGAACACTGGGAATCACTAGATTTGATCTACTTGGCGACTTTGGAA                   GGTTTAATTGGCTGGGAAATTTCTATATTGTATTATCCTACAATTTGCTTTTTGCTAT                   TGTGACAACATTGTGTCTGGTCCGAAAATTCACCTCTGCAGTTCGAGAAGAACTTTTC                   AAGGCCCTAGGTCTTCATAAACTTCACTTACCAAATACTTCAAGGGATTCAGAAACAG                   CCAAGCCTTCTGTAAATGGGCATCAGAAAGCACTG TGA   GACGCACAGACGGCGTCTTC                       TGCCACCAAG                     ORF Start: ATG at 16          ORF Stop: TGA at 1486           SEQ ID NO: 96                 490 aa     MW at 55083.0 Da       NOV21a,   MEGQDEVSAREQHFHSQVRESTICFLLFAILYVVSYFIITRYKRKSDEQEDEDAIVNR       CG120748-01       Protein Sequence   ISLFLSTFTLAVSAGAVLLLPFSIISNEILLSFPQNYYIQWLNGSLIHGLWNLASLFS                   NLCLFVLMPFAFFFLESEGFAGLKKGIRARILETLVMLLLLALLILGIVWVASALIDN                   DAASMESLYDLWEFYLPYLYSCISLMGCLLLLLCTPVGLSRMFTVMGQLLVKPTILED                   LDEQIYIITLEEEALQRRLNGLSSSVEYNIMELEQELENVKTLKTKLDRRKKASAWER                   NLVYPAVMVLLLIETSISVLLVACNILCLLVDETAMPKGTRGPGIGNASLSTFGFVGA                   ALEIILIFYLMVSSVVGFYSLRFFGNFTPKKDDTTMTKIIGNCVSILVLSSALPVMSR                   TLGITRFDLLGDFGRFNWLGNFYIVLSYNLLFAIVTTLCLVRKFTSAVREELFKALGL                   HKLHLPNTSRDSETAKPSVNGHQKAL                  
 
     [0448] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.  
               TABLE 21B                       Protein Sequence Properties NOV21a                                        PSort   0.6000 probability located in plasma membrane; 0.4000       analysis:   probability located in Golgi body; 0.3000 probability           located in endoplasmic reticulum (membrane); 0.0300           probability located in mitochondrial inner membrane       SignalP   Cleavage site between residues 36 and 37       analysis:                  
 
     [0449] A search of the NOV21a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication yielded several homologous proteins shown in Table 21C.  
               TABLE 21C                          Geneseq Results for NOV21a                                         NOV21a   Identities/                   Residues/   Similarities for       Geneseq   Protein/Organism/Length   Match   the Matched   Expect       Identifier   [Patent #, Date]   Residues   Region   Value               AAY91600   Human secreted protein sequence    84..490   405/407 (99%)   0.0           encoded by gene 9 SEQ ID NO:273 -    1..407   406/407 (99%)             Homo sapiens , 407 aa. [WO200006698-           A1, Feb. 10, 2000]       ABB11389   Human secreted protein homologue, SEQ    85..490   393/407 (96%)   0.0           ID NO: 1759 -  Homo sapiens , 415 aa    9..415   397/407 (96%)           [WO200157188-A2, Aug. 09, 2001]       ABB90410   Human polypeptide SEQ ID NO 2786 -   124..490   366/367 (99%)   0.0             Homo sapiens , 367 aa. [WO200190304-    1..367   367/367 (99%)           A2, Nov. 29, 2001]       AAG75542   Human colon cancer antigen protein SEQ   174..490   315/317 (99%)   e-178