THERAPEUTIC AND DIAGNOSTIC AGENTS CAPABLE OF MODULATING CELLULAR RESPONSIVENESS TO CYTOKINES

Abstract: The present invention relates generally to therapeutic and diagnostic agents. More particularly, the present invention provides therapeutic molecules capable of modulating signal transduction such as but not limited to cytokine-mediated signal transduction. The molecules of the present invention are useful, therefore, in modulating cellular responsiveness to cytokines as well as other mediators of signal transduction such as endogenous or exogenous molecules, antigens, microbes and microbial products, viruses or components thereof, ions, hormones and parasites.

Description: THERAPEUTIC AND DIAGNOSTIC AGENTS CAPABLE OF MODULATING CELLULAR RESPONSIVENESS TO CYTOKINES FIELD OF THE INVENTION The present invention relates generally to therapeutic and diagnostic agents. More particularly, the present invention provides therapeutic molecules capable of modulating signal transduction such as but not limited to cytokine-mediated signal transduction. The molecules of the present invention are useful, therefore, in modulating cellular responsiveness to cytokines as well as other mediators of signal transduction such as endogenous or exogenous molecules, antigens, microbes and microbial products, viruses or components thereof, ions, hormones and parasites. Bibliographic details of the publications referred to in this specification by author are collected at the end of the description. Sequence Identity Numbers (SEQ ID NOs.) for the nucleotide and amino acid sequences referred to in the specification are defined after the bibliography. A summary of the SEQ ID NOs is given in Table 1. Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers. BACKGROUND OF THE INVENTION Cells continually monitor their environment in order to modulate physiological and biochemical processes which in turn affects future behaviour. Frequently, a cell's initial interaction with its surroundings occurs via receptors expressed on the plasma membrane. Activation of these receptors, whether through binding endogenous ligands (such as cytokines) or exogenous ligands (such as antigens), triggers a biochemical cascade from the membrane through the cytoplasm to the nucleus. Of the endogenous ligands, cytokines represent a particularly important and versatile group. Cytokines are proteins which regulate the survival, proliferation, differentiation and function of a variety of cells within the body [Nicola, 1994]. The haemopoietic cytokines have in common a four-alpha helical bundle structure and the vast majority interact with a structurally related family of cell surface receptors, the type I and type II cytokine receptors [Bazan, 1990; Sprang, 5 1993]. In all cases, ligand-induced receptor aggregation appears to be a critical event in initiating intracellular signal transduction cascades. Some cytokines, for example growth hormone, erythropoietin (Epo) and granulocyte-colony-stimulating factor (G-CSF), trigger receptor homodimerisation, while for other cytokines, receptor heterodimerisation or heterotrimerisation is crucial. In the latter cases, several cytokines share common receptor subunits and on this basis 10 can be grouped into three subfamilies with similar patterns of intracellular activation and similar biological effects [Hilton, 1994]. Interleukin-3 (LL-3), IL-5 and granulocyte-macrophage colony- stimulating factor (GM-CSF) use the common β-receptor subunit (βc) and each cytokine stimulates the production and functional activity of granulocytes and macrophages. LL-2, IL-4, IL-7, IL-9, and LL-15 each use the common γ-chain (γc), while LL-4 and LL-13 share an 15 alternative γ-chain (γ v c or LL-13 receptor -chain). Each of these cytokines plays an important role in regulating acquired immunity in the lymphoid system. Finally, IL-6, IL-11, leukaemia inhibitory factor (LLF), oncostatin-M (OSM), ciliary neurotrophic factor (CNTF) and cardiotrophin (CT) share the receptor subunit gpl30. Each of these cytokines appears to be highly pleiotropic, having effects both within and outside the haemopoietic system [Nicola, 20 1994]. In all of the above cases at least one subunit of each receptor complex contains the conserved sequence elements, termed boxl and box2, in their cytoplasmic tails [Murakami, 1991]. Boxl is a pro line-rich motif which is located more proximal to the transmembrane domain than the 25 acidic box 2 element. The box-1 region serves as the binding site for a class of cytoplasmic tyrosine kinases termed JAKs (Janus kinases). Ligand-induced receptor dimerisation serves to increase the catalytic activity of the associated JAKs through cross-phosphorylation. Activated JAKs then tyrosine phosphorylate several substrates, including the receptors themselves. Specific phosphotyrosine residues on the receptor then serve as docking sites for SH2-containing 30 proteins, the best characterised of which are the signal transducers and activators of transcription (STATs) and the. adaptor protein, she. The STATs are then phosphorylated on tyrosines, probably by JAKs, dissociate from the receptor and form either homodimers or heterodimers through the interaction of the SH2 domain of one STAT with the phosphotyrosine residue of the other. STAT dimers then translocate to the nucleus where they bind to specific cytokine- responsive promoters and activate transcription [Darnell, 1994; Ihle, 1995; Lhle, 1995]. In a 5 separate pathway, tyrosine phosphorylated she interacts with another SH2 domain-containing protein, Grb-2, leading ultimately to activation of members of the MAP kinase family and in turn transcription factors such as fos and jun [Sato, 1993; Cutler, 1993]. These pathways are not unique to members of the cytokine receptor family since cytokines that bind receptor tyrosine kinases also being able to activate STATs and members of the MAP kinase family [David, 1996; 10 Leaman, 1996; Shual, 1993; Sato, 1993; Cutler, 1993]. Four members of the JAK family of cytoplasmic tyrosine kinases have been described, JAK1, JAK2, JAK3 and TYK2, each of which binds to a specific subset of cytokine receptor subunits. Six STATs have been described (STATl through STAT6), and these too are activated by 15 distinct cytokine/receptor complexes. For example, STATl appears to be functionally specific to the interferon system, STAT4 appears to be specific to LL-12, while STAT6 appears to be specific for LL-4 and LL-13. Thus, despite common activation mechanisms some degree of cytokine specificity may be achieved through the use of specific JAKs and STATs [Thierfelder, 1996; Kaplan, 1996; Takeda, 1996; Shimoda, 1996; Meraz, 1996; Durbin, 1996]. 20 In addition to those described above, there are clearly other mechanisms of activation of these pathways. For example, the JAK/STAT pathway appears to be able to activate MAP kinases independent of the she -induced pathway [David, 1995] and the STATs themselves can be activated without binding to the receptor, possibly by direct interaction with JAKs [Gupta, 25 1996]. Conversely, full activation of STATS may require the action of MAP kinase in addition to that of JAKs [David, 1995; Wen, 1995]. While the activation of these signalling pathways is becoming better understood, little is known of the regulation of these pathways, including employment of negative or positive feedback 30 loops. This is important since once a cell has begun to respond to a stimulus, it is critical that the intensity and duration of the response is regulated and that signal transduction is switched off. It is likewise desirable to increase the intensity of a response systemically or even locally as the situation requires. In work leading up to the present invention, the inventors sought to isolate negative regulators of signal transduction. The inventors have now identified a new family of proteins which are capable of acting as regulators of signalling. The new family of proteins is defined as the suppressor of cytokine signalling (SOCS) family based on the ability of the initially identified SOCS molecules to suppress cytokine-mediated signalling. It should be noted, however, that not all members of the SOCS family need necessarily share suppressor function nor target solely cytokine mediated signalling. The SOCS family comprises at least three classes of protein molecules based on amino acid sequence motifs located N-terminal of a C-terminal motif called the SOCS box. The identification of this new family of regulatory molecules permits the generation of a range of effector or modulator molecules capable of modulating signal transduction and, hence, cellular responsiveness to a range of molecules including cytokines. The present invention, therefore, provides therapeutic and diagnostic agents based on SOCS proteins, derivatives, homologues, analogues and mimetics thereof as well as agonists and antagonists of SOCS proteins. SUMMARY OF THE INVENTION The present invention provides inter alia nucleic acid molecules encoding members of the SOCS family of proteins as well as the proteins themselves. Reference hereinafter to "SOCS" encompasses any or all members of the SOCS family. Specific SOCS molecules are defined numerically such as, for example, SOCS1, SOCS2 and SOCS3. The species from which the SOCS has been obtained may be indicated by a preface of a single letter abbreviation where "h" is human, "m" is murine and "r" is rat. Accordingly, "mSOCSl"is a specific SOCS from a murine animal. Reference herein to "SOCS" is not to imply that the protein solely suppresses cytokine-mediated signal transduction, as the molecule may modulate other effector-mediated signal transductions such as by hormones or other endogenous or exogenous molecules, antigens, microbes and microbial products, viruses or components thereof, ions, hormones and parasites. The term "modulates" encompasses up-regulation, down-regulation as well as maintenance of particular levels. One aspect of the present invention provides a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or rnimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein comprises a SOCS box in its C- terminal region Another aspect of the present invention provides a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein comprises a SOCS box in its C- terminal region and a protein: molecule interacting region. Yet another aspect of the present invention is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein comprises a C- terminal region and a proteimmolecule interacting region located in a region N-terminal of the SOCS box. Preferably, the proteimmolecule interacting region is a protein:DNA or protein:protein binding region. Still a further aspect of the present invention provides a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein comprises a SOCS box in its C-terminal region and one or more of an SH2 domain, WD-40 repeats or ankyrin repeats N-terminal of the SOCS box. Even still a further aspect of the present invention is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein comprises a SOCS box in its C-terminal region wherein the SOCS box comprises the amino acid sequence: X, X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X n X 12 Xj 3 X 14 X 15 X 16 [XJ n X 17 X lg X 19 X 20 X 21 X 22 X 23 [Xj] n X 2 4 X 2 5 X 6 X 2 X 8 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X n is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X ]4 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X, may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; X 28 is L, I, V, M, A or P; and a protei molecule interacting region such as but not limited to one or more of an SH2 domain, WD-40 repeats and/or ankyrin repeats N-terminal of the SOCS box. Another aspect of the present invention is directed to a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein exhibits the following characteristics: (i) comprises a SOCS box in its C-terminal region having the amino acid sequence: X ! X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X n X 12 X 13 X 14 X 15 X 16 [X j ] n X 17 X 18 X 19 X 20 wherein: X ; is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X π is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X I6 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X, may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X, may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; X 28 is L, I, V, M, A or P; and (ii) comprises at least one of a SH2 domain, WD-40 repeats and/or ankyrin repeats or other protein:molecule interacting domain in a region N-terminal of the SOCS box. Preferably, the SOCS molecules modulate signal transduction such as from a cytokine or hormone or other endogenous or exogenous molecule, a microbe or microbial product, an antigen or a parasite. More preferably, the SOCS molecule modulate cytokine mediated signal transduction. Still another aspect of the present invention comprises a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or comprises a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein exhibits the following characteristics; (i) is capable of modulating signal transduction; (ii) comprises a SOCS box in its C-terminal region having the amino acid sequence: X, X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X π X 12 X 13 Xι 4 X 15 X 16 [X;] n X 17 X 18 X, 9 X 20 X 2 1 X 2 2 X 23 [XJ X 24 X 2 5 X 2 6 ^27-^28 wherein: X is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X π is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X; may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X, g is any amino acid; X, 9 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; X 28 is L, I, V, M, A or P; and (iii) comprises at least one of a SH2 domain, WD-40 repeats and/or ankyrin repeats or other protein:molecule interacting domain in a region N-terminal of the SOCS box. Preferably, the signal transduction is mediated by a cytokine such as one or more of EPO, TPO, G-CSF, GM-CSF, IL-3, IL-2, IL-4, IL-7, LL-13, IL-6, LIF, LL-12, IFNα, TNFα, LL-1 and/or M-CSF. Preferably, the signal transduction is mediated by one or more of Interleukin 6 (LL-6), Leukaemia Inhibitory Factor (LLF), Oncostatin M (OSM), Interferon (IFN)-α and/or thrombopoietin. Preferably, the signal transduction is mediated by LL-6. Particularly preferred nucleic acid molecules comprise nucleotide sequences substantially set forth in SEQ ID NO:3 (mSOCSl), SEQ ID NO:5 (mSOCS2), SEQ ID NO:7 (mSOCS3), SEQ ID NO:9 (hSOCSl), SEQ ID NO:l l (rSOCSl), SEQ ID NO:13 (mSOCS4), SEQ ID NO:15 and SEQ ID NO: 16 (hSOCS4), SEQ ID NO: 17 (mSOCS5), SEQ ID NO: 19 (hSOCS5), SEQ ID NO:20 (mSOCS6), SEQ ID NO:22 and SEQ ID NO:23 (hSOCS6), SEQ ID NO:24 (mSOCS7), SEQ ID NO:26 and SEQ ID NO:27 (hSOCS7), SEQ ID NO:28 (mSOCS8), SEQ ID NO:30 (mSOCS9), SEQ LD NO:31 (hSOCS9), SEQ ID NO:32 (mSOCSlO), SEQ ID NO:33 and SEQ ID NO:34 (hSOCSlO), SEQ ID NO:35 (hSOCSl l), SEQ ID NO:37 (mSOCS12), SEQ LD NO:38 and SEQ LD NO:39 (hSOCS12), SEQ ID NO:40 (mSOCS13), SEQ ID NO:42 (hSOCS13), SEQ ID NO: 43 (mSOCS14), SEQ ID NO:45 (mSOCS15) and SEQ ID NO:47 (hSOCS15) or a nucleotide sequence having at least about 15% similarity to all or a region of any of the listed sequences or a nucleotide acid molecule capable of hybridizing to any one of the listed sequences under low stringency conditions at 42°C. Another aspect of the present invention relates to a protein or a derivative, homologue, analogue or mimetic thereof comprising a SOCS box in its C-terminal region. Yet another aspect of the present invention is directed to a protein or a derivative, homologue, analogue or mimetic thereof comprising a SOCS box in its C-terminal region and a protein: molecule interacting region. Even yet another aspect of the present invention provides a protein or a derivative, homologue, analogue or mimetic thereof comprising an interacting region located in a region N-terminal of the SOCS box. Preferably, the protein: molecule interacting region is a protein:DNA or a protein:protein binding region. Another aspect of the present invention contemplates a protein or a derivative, homologue, analogue or mimetic thereof comprising a SOCS box in its C-terminal region and a SH2 domain, WD-40 repeats or ankyrin repeats N-terminal of the SOCS box. Still yet another aspect of the present invention provides a protein or a derivative, homologue, analogue or mimetic thereof exhibiting the following characteristics: (i) comprises a SOCS box in its C-terminal region having the amino acid sequence: X ! X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X u X 12 X I3 Xj 4 Xι 5 Xj 6 [X n X l7 X l8 Xι° X 20 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X n is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence Xi may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; X 28 is L, I, V, M, A or P; and (ii) comprises at least one of a SH2 domain, WD-40 repeats and/or ankyrin repeats or other protein:molecule interacting domain in a region N-terminal of the SOCS box. Preferably, the proteins modulate signal transduction such as cytokine-mediated signal transduction. Preferred cytokines are EPO, TPO, G-CSF, GM-CSF, IL-3, IL-2, IL-4, IL-7, LL-13, IL-6, LIF, IL-12, IFNγ, TNFα, LL-1 and/or M-CSF. A particularly preferred cytokine is LL-6. Even yet another aspect of the present invention provides a protein or derivative, homologue, analogue or mimetic thereof exhibiting the following characteristics: (i) is capable of modulating signal transduction such as cytokine-mediated signal transduction; (ii) comprises a SOCS box in its C-terminal region having the amino acid sequence: X, X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X π X 12 X 13 Xι 4 X 15 X 16 [Xj] n X 17 X 18 x 19 x 20 wherein: X] is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X n is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence Xj may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X I9 is any amino acid; X 20 L, I, V, M, A or P; X 2j is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; X 28 is L, I, V, M, A or P; and (iii) comprises at least one of a SH2 domain, WD-40 repeats and/or ankyrin repeats or other protein-molecule interacting domain in a region N-terminal of the SOCS box. Particularly preferred SOCS proteins comprise an amino acid sequence substantially as set forth in SEQ ID NO:4 (mSOCSl), SEQ ID NO:6 (mSOCS2), SEQ ID NO:8 (mSOCS3), SEQ ID NO: 10 (hSOCSl), SEQ ID NO: 12 (rSOCSl), SEQ ID NO: 14 (mSOCS4), SEQ ID NO: 18 (mSOCS5), SEQ ID NO:21 (mSOCS6), SEQ ID NO:25 (mSOCS7), SEQ ID NO:29 (mSOCS8), SEQ ID NO:36 (hSOCSl 1), SEQ ID NO:41 (mSOCS13), SEQ ID NO:44 (mSOCS 14), SEQ ID NO:46 (mSOCS15) and SEQ ID NO:48 (hSOCS15) or an amino acid sequence having at least 15% similarity to all or a region of any one of the listed sequences. Another aspect of the present invention contemplates a method of modulating levels of a SOCS protein in a cell said method comprising contacting a cell containing a SOCS gene with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time and under conditions sufficient to modulate levels of said SOCS protein. A related aspect of the present invention provides a method of modulating signal transduction in a cell containing a SOCS gene comprising contacting said cell with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time sufficient to modulate signal transduction. Yet a further related aspect of the present invention is directed to a method of influencing interaction between cells wherein at least one cell carries a SOCS gene, said method comprising contacting the cell carrying the SOCS gene with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time sufficient to modulate signal transduction. In accordance with the present invention, n in [X n and [X j ] n may, in addition from being 1-50, be from 1-30, 1-20, 1-10 and 1-5. A summary of the SEQ ID NOs referred to in the subject specification is given in Table 1. TABLE 1 SUMMARY OF SEQUENCE IDENTITY NUMBERS SEQUENCE SEQ ID NO. PCR Primer 1 PCR Primer 2 Mouse SOCS1 (nucleotide) 3 Mouse SOCS1 (amino acid) 4 Mouse SOCS2 (nucleotide) 5 Mouse SOCS2 (amino acid) 6 Mouse SOCS3 (nucleotide) 7 Mouse SOCS3 (amino acid) 8 Human SOCS1 (nucleotide) 9 Human SOCS1 (amino acid) 10 Rat SOCS 1 (nucleotide) 11 Rat SOCS 1 (amino acid) 12 nucleotide sequence of murine SOCS4 13 amino acid sequence of murine SOCS4 14 nucleotide sequence of SOCS4 cDNA human contig 4.1 15 nucleotide sequence of SOCS4 cDNA human contig 4.2 16 nucleotide sequence of murine SOCS5 17 amino acid sequence of murine SOCS5 18 nucleotide sequence of human SOCS5 19 nucleotide sequence of murine SOCS 6 20 amino acid of murine SOCS6 21 nucleotide sequence of human SOCS6 contig h6.1 22 nucleotide sequence of human SOCS6 contig h.6.2 23 nucleotide sequence of murine SOCS7 24 amino acid sequence of murine SOCS7 25 nucleotide sequence of human SOCS7 contig h7.1 26 nucleotide sequence of human SOCS7 contig 17.2 27 nucleotide sequence of murine SOCS8 28 amino acid sequence of murine SOCS 8 29 nucleotide sequence of murine SOCS9 30 nucleotide sequence of human SOCS9 31 nucleotide sequence of murine SOCS 10 32 nucleotide sequence of human SOCS10 contig hlθ.1 33 nucleotide sequence of human SOCS 10 contig hlθ.2 34 nucleotide sequence of human SOCS 11 35 amino acid sequence of human SOCS 11 36 nucleotide sequence of mouse SOCS 12 37 nucleotide sequence of human SOCS 12 contig hl2.1 38 nucleotide sequence of human SOCS 12 contig hi 2.2 39 nucleotide sequence of murine SOCS 13 40 amino acid sequence of murine SOCS13 41 nucleotide sequence of human SOCS13 cDNA contig hl3.1 42 nucleotide sequence of murine SOCS 14 cDNA 43 amino acid sequence of murine SOCS 14 44 nucleotide sequence of murine SOCS 15 cDNA 45 amino acid sequence of murine SOCS 15 46 nucleotide sequence of human SOCS 15 47 amino acid sequence of human SOCS 15 48 Single and three letter abbreviations are used to denote amino acid residues and these are summarized in Table 2. TABLE 2 Amino Acid Three-letter One-letter Abbreviation Symbol Alanine Ala A Arginine Arg R Asparagine Asn N Aspartic acid Asp D Cysteine Cys C Glutamine Gin Q Glutamic acid Glu E Glycine Gly G Histidine His H Isoleucine Tie I Leucine Leu L Lysine Lys K Methionine Met M Phenylalanine Phe F Proline Pro P Serine Ser s Threonine Thr T Tryptophan Trp w Tyrosine Tyr Y Valine Val V Any residue Xaa X BRIEF DESCRIPTION OF THE DRAWINGS In some of the Figures, abbreviations are used to denote SOCS proteins with certain binding motifs. SOCS proteins which contain WD-40 repeats are referred to as WSB1-WSB4. SOCS proteins with ankyrin repeats are referred to as ASB1-ASB3. Figure 1 is a diagrammatic representation showing generation of an LL-6-unresponsive Ml clone by retroviral infection. The RUFneo retrovirus, showing the position of landmark restriction endonuclease cleavage sites, the 4A2 cDNA insert and the position of PCR primer sequences. Figure 2 is a photographic representation of Southern and Northern analysis. (Left and Middle Panels) Southern blot analysis of genomic DNA from clone 4A2 and a control infected Ml clone. DNA was digested with BamH I, to reveal the number of retroviruses carried by each clone, and Sac I, to estimate the size of the retroviral cDNA insert. Left panel; probed with neo. Right panel; probed with the Xho I-digested 4A2 PCR product. (Right Panel) . Northern blot analysis of total RNA from clone 4A2 and a control infected Ml clone, probed with the Xho I-digested 4A2 PCR product. The two bands represent unspliced and spliced retroviral transcripts, resulting from splice donor and acceptor sites in the retroviral genome. Figure 3 is a representation of the nucleotide sequence and structure of the SOCSl gene. A. The genomic context of SOCSl in relation to the protamine gene cluster on murine chromosome 16. The accession number of this locus is MMPRMGNS (direct submission; G. Schlueter, 1995) for the mouse and BTPRMTNP2 for the rat (direct submission; G. Schlueter, 1996). B. The nucleotide sequence of the SOCSl cDNA and deduced amino acid sequence. Conventional one letter abbreviations are used for the amino acid sequence and the asterisk indicates the stop codon. The polyadenylation signal sequence is underlined. The coding region is shown in uppercase and the untranslated region is shown in lower case. Figure 4 is a graphical representation of cell differentiation in the presence of cytokines. Semi- solid agar cultures of parental Ml cells (Ml and Ml.mpl) and Ml cells expressing SOCSl (4A2 and Ml.mpLSOCSl), were used and the percentage of colonies which differentiated in response to a titration of 1 mg/ml LL-6 (•), 100 ng/ml LLF (0), 1 mg/ml OSM (D), 100 ng/ml IFN-γ (-), 500 ng/ml TPO (•), or 3xl0 "6 M dexamethasone (*) determined. Figure 5 is a photographic representation of cytospins of liquid cultures of parental Ml cells (Ml and Ml .mpl) ) and Ml cells expressing SOCS 1 (4A2 and Ml .mpl.SOCS 1) cultured for 4 days in the presence of 10 ng/ml LL-6 or saline. Unlike parental Ml cells, morphological features consistent with macrophage differentiation are not observed in Ml cells constitutively expressing SOCSl (4A2 and Ml.mpl.SOCSl) when cultured in LL-6. Figure 6 is a photographic representation showing inhibition of phosphorylation of signalling molecules by SOCSl. Parental Ml cells (Ml and Ml.mpl) and Ml cells expressing SOCSl (4A2 and Ml.mpLSOCSl) were incubated in the absence (-) or presence (+) of 10 ng/ml of LL-6 for 4 minutes at 37 °C . Cells were then lysed and extracts were either immunopreciptated using anti- mouse gρl30 antibody prior to SDS-PAGE (two upper panels) or were electrophoresed directly (two lower panels). Gels were blotted and the filters were then probed with anti- phosphotyrosine (upper panel), anti-gpl30 antibody (second top panel), anti-phospho-STAT3 (second bottom panel) or anti-STAT3 (lower panel). Blots were visualised using peroxidase- conjugated secondary antibodies and Enhanced Chemiluminescence (ECL) reagents. Figure 7 is a representation of protein extracts prepared from (A) Ml cells or Ml cells expressing SOCSl (4A2) and (B) Ml.mpl cells or Ml.mpl.SOCSl cells incubated for 10 min at 37° C in 10 ml serum-free DME containing either saline, 100 ng/ml LL-6 or 100 ng/ml LFN-γ. The binding reactions contained 4-6 μg protein (constant within a given experiment), 5 ng 32 P- labelled m67 oligonucleotide encoding the high affinity SLF (c-sis- inducible factor) binding site, and 800 ng sonicated salmon sperm DNA. For certain experiments, protein samples were preincubated with an excess of unlabelled m67 oligonucleotide, or antibodies specific for either STATl or STAT3. Figure 8 is a photographic representation of Northern hybridisation. Mice were injected intravenously with 2 μg and after various periods of time, the livers were removed and polyA+ SUBSΗTUTE SHEET (Rule 26) mRNA was purified. Ml cells were stimulated for various lengths of time with 500 ng/ml of LL- 6, after which polyA-f- mRNA was isolated. mRNA was fractionated by electrophoresis and immobilized on nylon filters. Northern blots were prehybridized, hybridized with random-primed 32 P-labelled SOCS 1 or GAPDH DNA fragments, washed and exposed to film overnight. Figure 9 is a representation of a comparison of the amino acid sequences of SOCS 1 , SOCS2, SOCS3 and CIS. Alignment of the predicted amino acid sequence of mouse (mm), human (hs) and rat (rr) SOCSl, SOCS2, SOCS3 and CIS. Those residues shaded are conserved in three or four mouse SOCS family members. The SH2 domain is boxed in solid lines, while the SOCS box is bounded by double lines. Figure 10 is a photographic representation showing the phenotype of LL-6 unresponsive Ml cell clone, 4A2. Colonies of parental Ml cells (left panel) and clone 4A2 (right panel) cultured in semi-solid agar for 7 days in saline or 100 ng/ml LL-6. Figure 11 is a photographic representation showing expression of mRNA for SOCS family members in vitro and in vivo. (A) Northern analysis of mRNA from a range of mouse organs showing constitutive expression of SOCS family members in a limited number of tissues. (B) Norther analysis of mRNA from liver and Ml cells showing induction of expression of SOCS family members following exposure to LL-6. (C) Reverse transcriptase PCR analysis of mRNA from bone marrow showing induction of expression of SOCS family members by a range of cytokines. Figure 12 is a photographic representation showing SOCS 1 suppresses the phosphorylation and activation of gpl30 and STAT-3. (A) Western blots of extracts from parental Ml cells (Ml and Ml.mpl) and Ml cells expressing SOCSl (4A2 and Ml.mpLSOCSl) stimulated with (+) or without (-) 100 ng/ml LL-6. Top: Extracts immunoprecipitated with antu-gpl30 (αgpl30) and immunoblotted with anti- phosphotyrosine (αPY-STAT3), or for STAT3 (αSTAT3) to demonstrate equal loading of protein. The molecular weights of the bands are shown on the right. (B) EMSA of Ml.mpl and Ml.mpl.SOCSl cells stimulated with (+) and without (-) 100 ng/ml LL-6 or 100 ng/ml IFNγ. The DNA-binding complexes SLF A, B, and C are indicated at the left. Figure 13 is a representation of a comparison of the amino acid sequence of the SOCS proteins (A) Schematic representation of structures of SOCS proteins including proteins which contain WD-40 repeats (WSB) and ankyrin repeats (ASB). (B) Alignment of N-terminal regions of SOCS proteins. (C) Alignment of the SH2 domains of CIS, SOCSl, 2, 3, 5, 9, 11 and 14. (D) Alignment of the WD-40 repeats of SOCS4, SOCS6, SOCS13 and SOCS15. (E) Alignment of the ankyrin repeats of SOCS7 and SOCSIO. (F) Alignment of the regions between SH2, WD-40 and ankyrin repeats and the SOCS box. (G) Alignment of the SOCS box. In each case the conventional one letter abbreviations for amino acids are used, with X denoting residues of uncertain identity and OOO denoting the beginning and the end of contigs. Amino acid sequence obtained from conceptual translation of nucleic acid sequence derived from isolated cDNAs is shown in upper case while amino acid sequence obtained by conceptual translation of ESTs is shown in lower case and is approximate only. Conserved residues, defined as (LIVMA), (FYW), (DE), (QN), (C, S, T), (KRH), (PG) are shaded in the SH2 domain, WD-40 repeats, ankyrin repeats and the SOCS box. For the alignment of SH2 domains, WD-40 repeats and ankyrin repeats a consensus sequence is shown above. In each case this has been derived from examination of a large and diverse set of domains (Neer et al, 1994; Bork, 1993). Figures 14(A) and (B) are photographic representations showing analysis of mRNA expression of mouse SOCSl and SOCS5 and SOCS containing a WD-40 repeat (WSB2) and ankyrin repeats (ASB 1). Figure 15 is a representation showing the nucleotide sequence of the mouse SOCS4 cDNA. The nucleotides encoding the mature coding region from the predicted ATG "start" codon to the stop codon is shown in upper case, while the predicted 5' and 3' untranslated regions are shown in lower case. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 17. Figure 16 is a representation showing the predicted amino acid sequence of the mouse SOCS4 protein, derived from the nucleotide sequence in Figure 15. The SOCS box, which also shown in Figure 13, is underlined. Figure 18 is a representation showing the nucleotide sequence of human SOCS4 cDNA contigs h4.1 and h4.2, derived from analysis of ESTs listed in Table 4.1. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 17. Figure 19 is a diagrammatic representation showing the relationship of mouse SOCS5 genomic (57-2) and cDNA (5-3-2) clones to contigs derived from analysis of mouse ESTs (Table 5.1) and human cDNA clone (5-94-2) and ESTs (Table 5.2). The nucleotide sequence of the mouse SOCS5 contig is shown in Figure 20, with the sequence of human SOCS5 contig (h5.1) being shown in Figure 21. The deduced amino acid sequence of mouse SOCS5 is shown in Figure 20B. The structure of the protein is shown schematically, with the SH2 domain indicated by ( ) and the SOCS box by ( ). The putative 5' and 3' translated regions are shown by the thin solid line. Figure 20A is a representation showing the nucleotide sequence of the mouse SOCS5 derived from analysis of genomic and cDNA clones. The nucleotides encoding the mature coding region from the predicted ATG "start" codon to the stop codon is shown in upper case, while the predicted 5' and 3' untranslated regions are shown in lower case. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 19. Figure 20B is a representation of the predicted amino acid sequence of mouse SOCS5 protein, derived from the nucleotide sequence in Figure 20A. The SOCS box, which also shown in Figure 13 is underlined. Figure 21 is a representation showing the nucleotide sequence of human SOCS5 cDNA contig h5.1, derived from analysis of cDNA clone 5-94-2 and the ESTs listed in Table 5.2. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 19. Figure 22 is a diagrammatic representation showing the relationship of mouse SOCS6 cDNA clones (6-1A, 6-2A, 6-5B, 6-4N, 6-18, 6-29, 6-3N and 6-5N) to contigs derived from analysis of mouse ESTs (Table 6.1) and human ESTs (Table 6.2). The nucleotide sequence of the mouse SOCS-6 contig is shown in Figure 23, with the sequence of human SOCS6 contigs (h6.1 and h6.2) being shown in Figure 24. The deduced amino acid sequence of mouse SOCS6 is shown in Figure 23B. The structure of the protein is shown schematically, while the WD-40 repeats indicated by ( ) and the SOCS box by ( ). The putative 5' and 3' untranslated regions are shown by the thin solid line. Figure 23A is a representation showing the nucleotide sequence of the mouse SOCS6 derived from analysis of cDNA clone 64-10A-11. The nucleotides encoding the part of the predicted coding region, ending in the stop codon are shown in upper case, while the predicted 3' untranslated regions are shown in lower case. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 22. Figure 23B is a representation showing the predicted amino acid sequence of mouse SOCS6 protein, derived from the nucleotide sequence in Figure 23 A. The SOCS box, which also shown in Figure 13 is underlined. Figure 24 is a representation showing the nucleotide sequence of human SOCS6 cDNA contig hό. l, derived from analysis of cDNA clone 5-94-2 and the ESTs listed in Table 6.2. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 22 Figure 25.is a diagrammatic representation showing the relationship of mouse SOCS7 cDNA clone (74-10A-11) to contigs derived from analysis of mouse ESTs (Table 7.1) and human ESTs (Table 7.2). The nucleotide sequence of the mouse SOCS7 contig is shown in Figure 26 with the sequence of human SOCS7 contigs (h7.1 and h7.2) being shown in Figure 27. The deduced amino acid sequence of mouse SOCS7 is shown in Figure 26B. The structure of the protein is shown schematically, with the ankyrin repeats indicated by ( ) and the SOCS box by ( ). The putative 5' and 3' untranslated regions are shown by the thin solid line in the mouse and by the wavy line in h7.2. Based on analysis of clones isolated to date and ESTs the 3' untranslated regions of mSOCS7 and hSOCS7 share little similarity. Figure 26A is a representation showing the nucleotide sequence of the mouse SOCS7 derived from analysis of cDNA clone 74-10A-11. The nucleotides encoding the part of the predicted coding region, ending in the stop codon are shown in upper case, while the predicted 3' untranslated regions are shown in lower case. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 25. Figure 26B is a representation showing the predicted amino acid sequence of mouse SOCS7 protein, derived from the nucleotide sequence in Figure 26A. The SOCS box, which also shown in Figure 13 is underlined. Figure 27 is a representation showing the nucleotide sequence of human SOCS7 cDNA contig h7.1 and h7.2 derived from analysis of the ESTs listed in Table 7.2. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 25. Figure 28 is a diagrammatic representation of the relationship of sequence derived from analysis of mouse SOCS8 ESTs (Table 8.1 and Figure 29 A) to the predicted protein structure of mouse SOCS8. The deduced partial amino acid sequence of mouse SOCS8 is shown in Figure 29B. The structure of the protein is shown schematically with the SOCS box highlighted ( ). The predicted 3 ' untranslated region is shown by the thin line. Figure 29A is a representation showing the partial nucleotide sequence of mouse SOCS 8 cDNA (contig 8.1) derived from analysis of ESTs. The nucleotides encoding the part of the predicted coding region, ending in the STOP codon are shown in upper case, while the predicted 3' untranslated regions are shown in lower case. Figure 29B is a representation showing the partial predicted amino acid sequence of the mouse SOCS8 protein, derived from the nucleotide sequence in Figure 29A. The SOCS box, which also shown in Figure 13 is underlined. Figure 30 is a diagrammatic representation showing the relationship of mouse SOCS9 ESTs (Table 9.1) and human SOCS9 ESTs (Table 9.2). The nucleotide sequence of the mouse SOCS9 contig (m.9.1) is shown in Figure 31, with the sequence of human SOCS9 contig (h9.1) being shown in Figure 32. The deduced amino acid sequence of human SOCS9 is shown schematically, with the SH2 domain indicated by ( ) and the SOCS box by ( ). The putative 3' untranslated region is shown by the thin solid line. Figure 31 is a representation showing the partial nucleotide sequence of mouse SOCS9 cDNA (contig m9.1), derived from analysis of the ESTs listed in Table 9.1. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 30. Figure 32 is a representation showing the partial nucleotide sequence of human SOCS9 cDNA (contig h9.1), derived from analysis of the ESTs listed in Table 9.2. Although it is clear that contig h9.1 encodes a protein with an SH2 domain and a SOCS box, the quality of the sequence is not high enough to derive a single unambiguous open reading frame. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 30. Figure 33 is a representation showing the relationship of mouse SOCSIO cDNA clones (10-9, 10-12, 10-23 and 10-24) to contigs derived from analysis of mouse ESTs (Table 10.1) and human ESTs (Table 10.2). The nucleotide sequence of the mouse SOCS 10 contig is shown in Figure 10.2, with the sequence of human SOCSIO contigs (hlθ.1 and hlθ.2) being shown in Figure 35. The predicted structure of the protein is shown schematically, with the ankyrin repeats indicated by ( ) and the SOCS box by ( ). The putative 3 ' untranslated regions is shown by the thin line solid line in the mouse and by the wavy line in hlθ.2. Based on analysis of clones isolated to date and ESTs the 3' untranslated regions of mSOCS-10 and hSOCS-10 share little similarity. Figure 34 is a representation showing the nucleotide sequence of the mouse SOCSIO derived from analysis of cDNA clone 10-9, 10-12, 10-23 and 10-24. The nucleotides encoding the part of the predicted coding region, ending in the stop codon are shown in upper case, while the predicted 3' untranslated regions are shown in lower case. Although it is clear that contig mlO.1 encodes a protein with a series of ankyrin repeats and a SOCS box, the quality of the sequence is not high enough to derive a single unambiguous open reading frame. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 33. Figure 35 is a representation showing the nucleotide sequence of human SOCS 10 cDNA contig hlθ.2 and hlθ.2 derived from analysis of the ESTs listed in Table 10.2. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 33. Figure 36A is a representation showing the partial nucleotide sequence of the human SOCSl 1 cDNA derived from analysis of ESTs listed in Table 11.1 The nucleotides encoding the mature coding region from the predicted ATG "start" codon to the stop codon is shown in upper case, while the predicted 5' and 3' untranslated regions are shown in lower case. The relationship of the partial cDNA sequence, derived from ESTs, to the predicted protein is shown in Figure 37. Figure 36B is a representation showing the partial predicted amino acid sequence of human SOCSl 1 protein, derived from the nucleotide sequence in Figure 36A. The SOCS box, which also shown in Figure 13, is underlined. Figure 37 is a diagrammatic representation showing the relationship of sequence derived from analysis of human SOCS- 11 ESTs (Table 11.1 and Figure 36A) to the predicted protein structure of human SOCSl 1. The deduced partial amino acid sequence of human SOCSl 1 is shown in Figure 36B. The structure of the protein is shown schematically with the SH2 domain shown by ( ) and the SOCS box highlighted by ( ). The predicted 3 ' untranslated region is shown by the thin line. Figure 38 is a diagrammatic representation showing the relationship of mouse SOCS 12 cDNA clones (12-1) to contigs derived from analysis of mouse ESTs (Table 12.1) and human ESTs (Table 12.2). The nucleotide sequence of the mouse SOCS 12 contig is shown in Figure 12.2, with the sequence of human SOCS12 contigs (hl2.1 and hl2.2) being shown in Figure 40. The deduced partial amino acid sequence of mouse SOCS 12 is shown in Figure 39. The structure of the protein is sown schematically, with the ankyrin repeats indicated by ( ) and the SOCS box by ( ). The putative 3' untranslated region is shown by the thin line solid line in the mouse and by the wavy line in hl2.2. Based on analysis of clones isolated to date and ESTs the 3' untranslated regions of mSOCS12 and hSOCSl 2 share little similarity. Figure 39 is a representation showing the nucleotide sequence of the mouse SOCS 12 derived from analysis of cDNA clone 12-1 and the ESTs listed in Table 12.1. The nucleotides encoding the part of the predicted coding region, including the stop codon are shown in upper case, while the predicted 3' untranslated region is shown in lower case. By homology with human SOCS 12 it is clear that contig ml2.1 encodes a protein with a series of ankyrin repeats and a SOCS box, the quality of the sequence is not high enough to derive a single unambiguous open reading frame. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 38. Figure 40 is a representation showing the nucleotide sequence of human SOCS 12 cDNA contig hl2.1 and hl2.2 derived from analysis of the ESTs listed in Table 12.2. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 38. Figure 41 is a diagrammatic representation showing the relationship of contig ml3.1 derived from analysis of mouse SOCS13 cDNA clones (62-1, 62-6-7, 62-14) and mouse ESTs (Table 13.1) to contig hl3.1 derived from analysis of human ESTs (Table 13.2). The nucleotide sequence of the mouse SOCS 13 contig is shown in Figure 42, with the sequence of human SOCS 13 contig (hl3.1) being shown in Figure 43. The deduced amino acid sequence of mouse SOCS 13 is shown in Figure 42B. The structure of the protein is shown schematically, with the WD-40 repeats highlighted by ( ) and the SOCS box highlighted by ( ). The 3' untranslated region is shown by the thin line solid line. Figure 42A is a representation showing the nucleotide sequence of the mouse SOCS 13 derived from analysis of cDNA clones 62-1, 62-6-7 and 62-14. The nucleotides encoding part of the predicted coding region, ending in the stop codon are shown in upper case, while those encoding the predicted 3' untranslated regions are shown in lower case. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 41. Figure 42B is a representation showing the predicted amino acid sequence of mouse SOCS 13 protein, derived from the nucleotide sequence in Figure 42A. The SOCS box, which also shown in Figure 13 is underlined. Figure 43 is a representation showing the nucleotide sequence of human SOCS 13 cDNA contig hl3.1 derived from analysis of the ESTs listed in Table 13.2. The relationship of these contigs to the mouse cDNA sequence is illustrated in Figure 41. Figure 44 is a diagrammatic representation showing the relationship of a partial mouse SOCS 14 cDNA clone (14-1) to contigs derived from analysis of mouse ESTs (Table 14.1). The nucleotide sequence of the mouse SOCS 14 contig is shown in Figure 45. The deduced partial amino acid sequence of mouse SOCS 14 is shown in Figure 45B. The structure of the protein is shown schematically, with the SH3 domain indicated by ( ) and the SOCS box by ( ). The putative 3' untranslated region is shown by the thin line. Figure 45 A is a representation showing the nucleotide sequence of the mouse SOCS 14 derived from analysis of genomic and cDNA clones. The nucleotides encoding the mature coding region from the predicted ATG "start" codon to the stop codon is shown in upper case, while the predicted 5' and 3' untranslated regions are shown in lower case. The relationship of mouse cDNA sequence to mouse and human EST contigs is illustrated in Figure 44. Figure 45B is a representation showing the predicted amino acid sequence of mouse SOCS 14 protein, derived from the nucleotide sequence in Figure 45B. The SOCS box, which also shown in Figure 13 is underlined. Figure 46 is a diagrammatic representation showing the relationship of contig ml 5.1 derived from analysis of mouse BAC and mouse ESTs (Table 15.1) to contig hi 5.1 derived from analysis of the human BAC and human ESTs (Table 15.2). The nucleotide sequence of the mouse SOCS15 contig is shown in Figure 47, with the sequence of human SOCS15 contig (hl5.1) being shown in Figure 47. The deduced amino acid sequence of mouse SOCS 15 is shown in Figure 47B. The structure of the protein is shown schematically, with the WD-40 repeats highlighted by ( ) and the SOCS box highlighted by ( ). The 5' and 3' untranslated region are shown by the thin line solid line. The introns which interrupt the coding region are shown by Λ . Figure 47A is a representation showing the nucleotide sequence covering the mouse SOCS 15 gene derived from analysis the mouse BAC listed in Table 15.1. The nucleotides encoding the predicted coding region, beginning with the ATG and ending in the stop codon are shown in upper case, while those encoding the predicted 5' untranslated region, the introns and the 3' untranslated region are shown in lower case. The relationship of mouse BAC to mouse and human ESTs contigs is illustrated in Figure 46. Figure 47B is a representation showing the predicted amino acid sequence of mouse SOCS 15 protein, derived from the nucleotide sequence in Figure 47 A. The SOCS box, which also shown in Figure 13 is underlined. Figure 48A is a representation showing the nucleotide sequence covering the human SOCS 15 gene derived from analysis the human BAC listed in Table 15.2. The nucleotides encoding the predicted coding region, beginning with the ATG and ending in the stop codon are shown in upper case, while those encoding the predicted 5' untranslated region, the introns and the 3' untranslated region are shown in lower case. The relationship of the human BAC to mouse and human ESTs contigs is illustrated in Figure 46. Figure 48B is a representation showing the predicted amino acid sequence of human SOCS 15 protein, derived from the nucleotide sequence in Figure 48A. The SOCS box, which also shown in Figure 13 is underlined. Figure 49 is a photographic representation showing SOCSl inhibition of JAK2 kinase activity. (A) Upper panel. Cos M6 cells were transiently transfected with either Flag-tagged mJAK2 and mSOCS-1 DNA (SOCSl) or Flag-mJAK2 DNA alone (-), lysed, JAK2 proteins immunoprecipitated using anti-JAK2 antibody and subjected to an in vitro kinase assay. Lower panel. A portion of the JAK2 immunoprecipitates were Western blotted with anti-JAK2 antibody. (B) Upper panel. Cos M6 cells were transiently transfected with Flag- mJAK2 and Flag- mSOCS-1 DNA or Flag-mJAK2 DNA alone, lysed, JAK2 proteins immunoprecipitated using anti-JAK2 (UBI) and separated by SDS/PAGE gel. Immunoprecipitates were then analysed by Western blot with anti-phosphotyrosine antibody. Lower panel; JAK2 expression. Cos cell lysates were separated by SDS/PAGE gel and analysed by Western blot with anti-FLAG antibody (M2). Figure 50 is a photographic representation showing interaction between JAK2 and SOCS protein. (A) Cos M6 cells were transiently transfected with Flag-tagged mJAK2 and various Hag-tagged SOCS DNAs (SOCS-l;Sl, SOCS-2;S2, SOCS-3;S3, CIS) or Flag-mJAK2 alone, lysed, JAK2 proteins immunoprecipitated using anti-JAK2 (UBI) and separated by SDS/PAGE. Immunoprecipitates were then analysed by Western blot with anti-FLAG antibody (M2). (B) Cos cell lysates described in (A) were separated by SDS/PAGE and expression levels of the various proteins were determined by Western blot with anti-FLAG antibody (M2). (C) JAK2 tyrosine phosphorylation. Cos cell lysates described in (A) were separated by SDS/PAGE and proteins analysed by Western blot with anti-phosphotyrosine antibody. Figure 51 is a diagrammatic representation of pβgalpAloxneo. Figure 52 is a diagrammatic representation of pβgalpAloxneoTK. Figure 53 is a diagrammatic representation of SOCSl knockout construct. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS The present invention provides a new family of modulators of signal transduction. As the initial members of this family suppressed cytokine signalling, the family is referred to as the 5 "suppressors of cytokine signalling" family of "SOCS". The SOCS family is defined by the presence of a C-terminal domain referred to as a "SOCS box". Different classes of SOCS molecules are defined by a motif generally but not exclusively located N-terminal to the SOCS box and which is involved by protein:molecule interaction such as protein:DNA or protein:protein interaction. Particularly preferred motifs are selected from an SH2 domain, WD- 10 40 repeats and ankyrin repeats. WD-40 repeats were originally recognised in the β-subunit of G-proteins. WD-40 repeats appear to form a β-propeller-like structure and may be involved in protein-protein interactions. Ankyrin repeats were originally recognised in the cytoskeletal protein ankryin. 15 Members of the SOCS family may be identified by any number of means. For example, SOCS 1 to SOCS3 were identified by their ability to suppress cytokine-mediated signal transduction and, hence, were identified based on activity. SOCS4 to SOCS 15 were identified as nucleotide sequences exhibiting similarity at the level of the SOCS box. 0 The SOCS box is a conserved motif located in the C-terminal region of the SOCS molecule. In accordance with the present invention, the amino acid sequence of the SOCS box is: Xj X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X n X 12 X 13 X 14 X I5 X 16 [X,] n X π X 18 X 19 X 20 5 X 21 X 22 X 23 [Xj] n X 24 X 25 X 26 X 27 X 28 wherein: X j is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; 0 X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X,, is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X, 4 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [Xj] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X may comprise the same or different amino acids selected from any amino acid residue; X π is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 2I is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; and X 2g is L, I, V, M, A or P. accordance with the present invention, SOCS proteins are divided into separate classes based on the presence of a protein:molecule interacting region such as but not limited to an SH2 domain, WD-40 repeats and ankyrin repeats located N-terminal of the SOCS box. The latter three domains are protein:protein interacting domains. Examples of SH2 containing SOCS proteins include SOCSl, SOCS2, SOCS3, SOCS5, SOCS9, SOCSl 1 and SOCS 14. Examples of SOCS containing WD-40 repeats include SOCS4, SOCS6 and SOCS 15. Examples of SOCS containing ankyrin repeats include SOCS7, SOCSIO and SOCS12. The present invention provides inter alia nucleic acid molecules encoding SOCS proteins, purified naturally occurring SOCS proteins as well as recombinant forms of SOCS proteins and methods of modulating signal transduction by modulating activity of SOCS proteins or expression of SOCS genes. Preferably, signal transduction is mediated by a cytokine, examples of which include EPO, TPO, G-CSF, GM-CSF, LL-3, LL-2, IL-4, IL-7, LL-13, LL-6, LIF, IL-12, IFNγ, TNFα, IL-1 and/or M-CSF. Particularly preferred cytokines include LL-6, LLF, OSM, LFN-γ and/or thrombopoietin. Accordingly, one aspect of the present invention provides an isolated nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or comprises a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42°C wherein said protein comprises a SOCS box in its C-terminal region and optionally a protei molecule interacting domain N-terminal of the SOCS box. Preferably, the protein: molecule interacting domain is a protein:DNA or protein: protein interacting domain. Most preferably, the protein: molecule interacting domain is one of an SH2 domain, WD-40 repeats and/or ankyrin repeats. As stated above, preferably the subject SOCS modulate cytokine-mediated signal transduction. The present invention extends, however, to SOCS molecules modulating other effector-mediated signal transduction such as mediated by other endogenous or exogenous molecules, antigens, microbes and microbial products, viruses or components thereof, ions, hormones and parasites. Endogenous molecules in this context are molecules produced within the cell carrying the SOCS molecule. Exogenous molecules are produced by other cells or are introduced to the body. Preferably, the nucleic acid molecule or SOCS protein is in isolated or purified form. The terms "isolated" and "purified" mean that a molecule has undergone at least one purification step away from other material. Preferably, the nucleic acid molecule is in isolated form and is DNA such as cDNA or genomic DNA. The DNA may encode the same amino acid sequence as the naturally occurring SOCS or the SOCS may contain one or more amino acid substitutions, deletions and/or additions. The nucleotide sequence may correspond to the genomic coding sequence (including exons and introns) or to the nucleotide sequence in cDNA from mRNA transcribed from the genomic gene or it may carry one or more nucleotide substitutions, deletions and/or additions thereto. In a preferred embodiment, the nucleic acid molecule comprises a sequence of nucleotide encoding or complementary to a sequence encoding a SOCS protein or a derivative, homologue, analogue or mimetic thereof wherein the amino acid sequence of said SOCS protein is selected from SEQ ID NO:4 (mSOCSl), SEQ ID NO:6 (mSOCS2), SEQ ID NO:8 (mSOCS3), SEQ ID NO:10 (hSOCSl), SEQ ID NO: 12 (rSOCSl), SEQ ID NO: 14 (mSOCS4), SEQ ID NO:18 (mSOCS5), SEQ ID NO:21 (mSOCS6), SEQ ID NO:25 (mSOCS27), SEQ ID NO:29 (mSOCS8), SEQ ID NO:36 (hSOCSl 1), SEQ ID NO:41 (mSOCS13), SEQ ID NO:44 (mSOCS14), SEQ LD NO:46 (mSOCS15) and SEQ D NO:48 (mSOCS15) or encodes an amino acid sequence with a single or multiple amino acid substitution, deletion and/or addition to the listed sequences or is a nucleotide sequence capable of hybridizing to the nucleic acid molecule under low stringency conditions at 42°C. In an even more preferred embodiment, the present invention provides a nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a SOCS protein or a derivative, homologue, analogue or mimetic thereof wherein the nucleotide sequence is selected from a nucleotide sequence substantially set forth in SEQ ID NO: 3 (mSOCSl), SEQ ID NO:5 (mSOCS2), SEQ ID NO:7 (mSOCS3), SEQ ID NO:9 (hSOCSl 1), SEQ ID NO: 11 (rSOCSl), SEQ ID NO: 13 (mSOCS4), SEQ ID NO: 15 and SEQ ID NO: 16 (hSOCS4), SEQ ID NO: 17 (mSOCS5), SEQ LD NO: 19 (hSOCS5), SEQ ID NO:20 (mSOCS6), SEQ ID NO:22 and SEQ LD NO:23 (hSOCS6), SEQ ID NO:24 (mSOCS7), SEQ ID NO:26 and SEQ ID NO:27 (hSOCS7), SEQ ID NO:28 (mSOCS8), SEQ ID NO:30 (mSOCS9), SEQ ID NO:31 (hSOCS9), SEQ ID NO:32 (mSOCSlO), SEQ ID NO:33 and SEQ ID NO:34 (hSOCS lO), SEQ ID NO:35 (hSOCSl 1), SEQ ID NO:37 (mSOCS12), SEQ ID NO:38 and SEQ ID NO:39 (hSOCS12), SEQ ID NO:40 (mSOCS13), SEQ ID NO:42 (hSOCSl 3), SEQ ID NO:43 (mSOCS14), SEQ ID NO:45 (mSOCS15) and SEQ ID NO:47 (hSOCS15) or a nucleotide sequence having at least about 15% similarity to all or a region of any of the listed sequences or a nucleic acid molecule capable of hybridizing to any of the listed sequences under low stringency conditions at 42°C. Reference herein to a low stringency at 42 °C includes and encompasses from at least about 1% v/v to at least about 15% v/v formamide and from at least about IM to at least about 2M salt for hybridisation, and at least about IM to at least about 2M salt for washing conditions. Alternative stringency conditions may be applied where necessary, such as medium stringency, which includes and encompasses from at least about 16% v/v to at least about 30% v/v formamide and from at least about 0.5M to at least about 0.9M salt for hybridisation, and at least about 0.5M to at least about 0.9M salt for washing conditions, or high stringency, which includes and encompasses from at least about 31% v/v to at least about 50% v/v formamide and from at least about 0.01M to at least about 0.15M salt for hybridisation, and at least about 0.01M to at least about 0.15M salt for washing conditions. In another embodiment, the present invention is directed to a SOCS protein or a derivative, homologue, analogue or mimetic thereof wherein said SOCS protein is identified as follows: human SOCS4 characterised by EST81149, EST180909, EST182619, ya99H09, ye70co4, yh53c09, yh77gl l, yh87h05, yi45h07, yj04e06, yql2h06, yq56a06, yq60e02, yq92g03, yq97h06, yr90f01 , yt69c03, yv30a08, yv55f07, yv57h09, yv87h02, yv98el 1 , yw68dl0, yw82a03, yx08a07, yx72h06, yx76b09, yy37h08, yy66b02, za81f08, zbl8f07, zc06e08, zdl4g06, zd51hl2, zd52b09, ze25gl l, ze69f02, zf54f03, zh96e07, zv66hl2, zs83a08 and zs83g08; mouse SOCS-4 characterised by mc65f04, mf42e06, mplOclO, mr81g09, and mtl9hl2; human SOCS-5 characterised by EST15B103, EST15B105, EST27530 and zf50f01; mouse SOCS-5 characterised by mc55a01, mh98f09, my26hl2 and ve24e06; human SOCS-6 characterised by yf61e08, yf93a09, yg05fl2, yg41f04, yg45c02, yhl lflO, yhl3b05, zc35al2, ze02h08, zl09a03, zl69el0, zn39d08 and zo39e06; mouse SOCS-6 characterised by mc04c05, md48a03, mf31d03, mh26b07, mh78el l, mh88h09, mh94h07, mi27h04 and mj29c05, mp66g04, mw75g03, va53b05, vb34h02, vc55d07, vc59e05, vc67d03, vc68dl0, vc97h01, vc99c08, vd07h03, vd08c01, vd09bl2, vdl9b02, vd29a04 and vd46d06; human SOCS-7 characterised by STS WI30171, EST00939, EST12913, yc29b05, yp49fl0, ztlOf03 and zx73g04; mouse SOCS-7 characterised by mj39a01 and vi52h07; mouse SOCS-8 characterised by mj6e09 and vj27a029; human SOCS-9 characterised by CSRL-82f2-u, EST114054, yy06b07, yy06g06, zr40c09, zr72h01, yx92c08, yx93b08 and hfe0662; mouse SOCS-9 characterised by me65d05; human SOCS-10 characterised by aa48hl0, zp35h01, zp97hl2, zq08h01, zr34g05, EST73000 and HSDHEI005; SUBSTTTUTE SHEET (Rule 26) mouse SOCS-10 characterised by mbl4dl2, mb40f06, mg89bl l, mq89el2, mp03gl2 and vh53cl l; human SOCS- 11 characterised by zt24h06 and zr43b02; human SOCS- 13 characterised by EST59161; mouse SOCS-13 characterised by ma39a09, me60c05, mi78g05, mklOcl 1, mo48gl2, mp94a01, vb57c07 and vh07cl 1; and human SOCS-14 characterised by mi75e03, vd29hl 1 and vd53g07; or a derivative or homologue of the above ESTs characterised by a nucleic acid molecule being capable of hybridizing to any of the listed ESTs under low stringency conditions at 42°C. er embodiment, the nucleotide sequence encodes the following amino acid sequence: Xj X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X n X I2 X 13 X I4 X 15 X 16 [XJ n X 17 X 18 X 19 x 20 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X n is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X, 5 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X t may comprise the same or different amino acids selected from any amino acid residue; X is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; and X 28 is L, I, V, M, A or P. The above sequence comparisons are preferably to the whole molecule but may also be to part thereof. Preferably, the comparisons are made to a contiguous series of at least about 21 nucleotides or at least about 5 amino acids. More preferably, the comparisons are made against at least about 21 contiguous nucleotides or at least 7 contiguous amino acids. Comparisons may also only be made to the SOCS box region or a region encompassing the proteimmolecule interacting region such as the SH2 domain WD-40 repeats and/or ankyrin repeats. SUBSTTΓUTE SHEET (RULE 26) Still another embodiment of the present invention contemplates an isolated polypeptide or a derivative, homologue, analogue or mimetic thereof comprising a SOCS box in its C-terminal region. Preferably the polypeptide further comprises a protein: molecule interacting domain such as a protein:DNA or protein:protein interacting domain. Preferably, this domain is located N-terminal of the SOCS box. It is particularly preferred for the protein: molecule interacting domain to be at least one of an SH2 domain, WD-40 repeats and/or ankyrin repeats. Preferably, the signal transduction is mediated by a cytokine selected from EPO, TPO, G-CSF, GM-CSF, IL-3, IL-2, IL-4, IL-7, LL-13, LL-6, LIF, IL-12, IFNγ, TNFα, IL-1 and/or M-CSF. Preferred cytokines are IL-6, LLF, OSM, LFN-γ or thrombopoietin. More preferably, the protein comprises a SOCS box having the amino acid sequence: X, X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X π X 12 X 13 X ]4 X 15 X 16 [X,] n X 17 X 18 X 19 X 20 X 21 X 22 X 23 [Xj] n X 24 X 25 X 26 X 27 X 28 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X n is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X ]4 is any amino acid; X, 5 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X ; may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; and X 28 is L, I, V, M, A or P. Still another embodiment provides an isolated polypeptide or a derivative, homologue, analogue or mimetic thereof comprising a sequence of amino acids substantially as set forth in SEQ ID NO:4 (mSOCSl), SEQ ID NO:6 (mSOCS2), SEQ ID NO:8 (mSOCS3), SEQ ID NO: 10 (hSOCSl), SEQ LD NO: 12 (rSOCSl), SEQ ID NO: 14 (mSOCS4), SEQ ID NO: 18 (mSOCS5), SEQ LD NO:21 (mSOCS6), SEQ ID NO:25 (mSOCS7), SEQ ID NO:29 (mSOCS8), SEQ ID NO:36 (hSOCSl l), SEQ ID NO:41 (rnSOCSB), SEQ ID NO:44 (mSOCS14), SEQ ID NO:46 (mSOCS 15) and SEQ ID NO:48 (hSOCS15) or an amino acid sequence having at least 15% similarity to all or a part of the listed sequences. Preferred nucleotide percentage similarities include at least about 20%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or above such as 93%, 95%, 98% or 99%. Preferred amino acid similarities include at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97% or 98% or above. As stated above, similarity may be measured against an entire molecule or a region comprising at least 21 nucleotides or at least 7 amino acids. Preferably, similarity is measured in a conserved region such as SH2 domain, WD-40 repeats, ankyrin repeats or other protei molecule interacting domains or a SOCS box. The term "similarity" includes exact identity between sequences or, where the sequence differs, different amino acids are related to each other at the structural, functional, biochemical and/or conformational levels. The nucleic acid molecule may be isolated from any animal such as humans, primates, livestock animals (e.g. horses, cows, sheep, donkeys, pigs), laboratory test animals (e.g. mice, rats, rabbits, hamsters, guinea pigs), companion animals (e.g. dogs, cats) or captive wild animals (e.g. deer, foxes, kangaroos). The terms "derivatives" or its singular form "derivative" whether in relation to a nucleic acid molecule or a protein includes parts, mutants, fragments and analogues as well as hybrid or fusion molecules and glycosylation variants. Particularly useful derivatives comprise single or multiple amino acid substitutions, deletions and/or additions to the SOCS amino acid sequence. Preferably, the derivatives have functional activity or alternatively act as antagonists or agonists. The present invention further extends to homologues of SOCS which include the functionally or structurally related molecule from different animal species. The present invention also encompasses analogues and mimetics. Mimetics include a class of molecule generally but not necessarily having a non-amino acid structure and which functionally are capable of acting in an analogous manner to the protein for which it is a mimic, in this case, a SOCS. Mimetics may comprise a carbohydrate, aromatic ring, lipid or other complex chemical structure or may also be proteinaceous in composition. Mimetics as well as agonists and antagonists contemplated herein are conveniently located through systematic searching of environments, such as coral, marine and freshwater river beds, flora and microorganisms. This is sometimes referred to as natural product screening. Alternatively, libraries of synthetic chemical compounds may be screened for potentially useful molecules. As stated above, the present invention contemplates agonists and antagonists of the SOCS. One example of an antagonist is an antisense oligonucleotide sequence. Useful oligonucleotides are those which have a nucleotide sequence complementary to at least a portion of the protein- coding or "sense" sequence of the nucleotide sequence. These anti-sense nucleotides can be used to effect the specific inhibition of gene expression. The antisense approach can cause inhibition of gene expression apparently by forming an anti-parallel duplex by complementary base pairing between the antisense construct and the targeted mRNA, presumably resulting in hybridisation arrest of translation. Ribozymes and co-suppression molecules may also be used. Antisense and other nucleic acid molecules may first need to be chemically modified to permit penetration of cell membranes and/or to increase their serum half life or otherwise make them more stable for in vivo administration. Antibodies may also act as either antagonists or agonists although are more useful in diagnostic applications or in the purification of SOCS proteins. Antagonists and agonists may also be identified following natural product screening or screening of libraries of chemical compounds or may be derivatives or analogues of the SOCS molecules. Accordingly, the present invention extends to analogues of the SOCS proteins of the present invention. Analogues may be used, for example, in the treatment or prophylaxis of cytokine mediated dysfunction such as autoimmunity, immune suppression or hyperactive immunity or other condition including but not limited to dysfunctions in the haemopoietic, endocrine, hepatic and neural systems. Dysfunctions mediated by other signal transducing elements such as hormones or endogenous or exogenous molecules, antigens, microbes and microbial products, viruses or components thereof, ions, hormones and parasites are also contemplated by the present invention. Analogues of the proteins contemplated herein include, but are not limited to, modification to side chains, incoφorating of unnatural amino acids and/or their derivatives during peptide, polypeptide or protein synthesis and the use of crosslinkers and other methods which impose conformational constraints on the proteinaceous molecule or their analogues. Examples of side chain modifications contemplated by the present invention include modifications of amino groups such as by reductive alkylation by reaction with an aldehyde followed by reduction with NaBH j. ; amidination with methylacetimidate; acylation with acetic anhydride; carbamoylation of amino groups with cyanate; trinitrobenzylation of amino groups with 2, 4, 6-trinitrobenzene sulphonic acid (TNBS); acylation of amino groups with succinic anhydride and tetrahydrophthalic anhydride; and pyridoxylation of lysine with pyridoxal-5- phosphate followed by reduction with NaBHφ The guanidine group of arginine residues may be modified by the formation of heterocyclic condensation products with reagents such as 2,3-butanedione, phenylglyoxal and glyoxal. The carboxyl group may be modified by carbodiimide activation via O-acylisourea formation followed by subsequent derivitisation, for example, to a corresponding amide. Sulphydryl groups may be modified by methods such as carboxymethylation with iodoacetic acid or iodoacetamide; performic acid oxidation to cysteic acid; formation of a mixed disulphides with other thiol compounds; reaction with maleimide, maleic anhydride or other substituted maleimide; formation of mercurial derivatives using 4-chloromercuribenzoate, 4- chloromercuriphenylsulphonic acid, phenylmercury chloride, 2-chloromercuri-4-nitrophenol and other mercurials; carbamoylation with cyanate at alkaline pH. Tryptophan residues may be modified by, for example, oxidation with N-bromosuccinimide or alkylation of the indole ring with 2-hydroxy-5-nitrobenzyl bromide or sulphenyl halides. Tyrosine residues on the other hand, may be altered by nitration with tetranitromethane to form a 3-nitrotyrosine derivative. Modification of the imidazole ring of a histidine residue may be accomplished by alkylation with iodoacetic acid derivatives or N-carbethoxylation with diethylpyrocarbonate. Examples of incorporating unnatural amino acids and derivatives during peptide synthesis include, but are not limited to, use of norleucine, 4-amino butyric acid, 4-amino-3-hydroxy-5- phenylpentanoic acid, 6-aminohexanoic acid, t-butylglycine, norvaline, phenylglycine, ornithine, sarcosine, 4-amino-3-hydroxy-6-methylheptanoic acid, 2-thienyl alanine and/or D-isomers of amino acids. A list of unnatural amino acid, contemplated herein is shown in Table 3. TABLE 3 Non-conventional Code Non-conventional Code amino acid amino acid α-aminobutyric acid Abu L-N-methylalanine Nmala α-amino-α-methylbutyrate Mgabu L-N-methylarginine Nmarg aminocyclopropane- Cpro L-N-methylasparagine Nmasn carboxylate L-N-methylaspartic acid Nmasp aminoisobutyric acid Aib L-N-methylcysteine Nmcys aminonorbornyl- Norb L-N-methylglutamine Nmgln carboxylate L-N-methylglutamic acid Nmglu cyclohexylalanine Chexa L-N-methylhistidine Nmhis cyclopentylalanine Cpen L-N-methylisolleucine Nmile D-alanine Dal L-N-methylleucine Nmleu D-arginine Darg L-N-methyllysine Nmlys D-aspartic acid Dasp L-N-methylmethionine Nmmet D-cysteine Dcys L-N-methylnorleucine Nmnle D-glutamine Dgln L-N-methylnorvaline Nmnva D-glutamic acid Dglu L-N-methylornithine Nmorn D-histidine Dhis L-N-methylphenylalanine Nmphe D-isoleucine Dile L-N-methylproline Nmpro D-leucine Dleu L-N-mefhylserine Nmser D-lysine Dlys L-N-methylthreonine Nmthr D-methionine Dmet L-N-methyltryptophan Nmtφ D-ornithine Dorn L-N-methyltyrosine Nmtyr D-phenylalanine Dphe L-N-methylvaline Nmval D-proline Dpro L-N-methylethylglycine Nmetg D-serine Dser L-N-methyl-t-butylglycine Nmtbug D-threonine Dthr L-norleucine Nle D-tryptophan Dtrp L-norvaline Nva D-tyrosine Dtyr α-methyl-aminoisobutyrate Maib D-valine Dval α-methyl-γ-aminobutyrate Mgabu D-α-methylalanine Dmala α-methylcyclohexylalanine Mchexa D-α-methylarginine Dmarg α-methylcylcopentylalanine Mcpen D-α-methylasparagine Dmasn α-methyl-α-napthylalanine Manap D-α-methylaspartate Dmasp α-methylpenicillamine Mpen D-α-methylcysteine Dmcys N-(4-aminobutyl)glycine Nglu D-α-methylglutamine Dmgln N-(2-aminoethyl)glycine Naeg D-α-methylhistidine Dmhis N-(3-aminopropyl)glycine Norn D-α-methylisoleucine Dmile N-amino-α-methylbutyrate Nmaabu D-α-methylleucine Dmleu α-napthylalanine Anap D-α-methyllysine Dmlys N-benzylglycine Nphe D-α-methylmethionine Dmmet N-(2-carbamylethyl)glycine Ngln D-α-methylornithine Dmorn N-(carbamylmethyl)glycine Nasn D-α-methylphenylalanine Dmphe N-(2-carboxyethyl)glycine Nglu D-α-methylproline Dmpro N-(carboxymethyl)glycine Nasp D-α-methylserine Dmser N-cyclobutylglycine Ncbut D-α-methylthreonine Dmthr N-cycloheptylglycine Nchep D-α-methyltryptophan Dmtφ N-cyclohexylglycine Nchex D-α-methyltyrosine Dmty N-cyclodecylglycine Ncdec D-α-methylvaline Dmval N-cylcododecylglycine Ncdod D-N-methylalanine Dnmala N-cyclooctylglycine Ncoct D-N-methylarginine Dnmarg N-cyclopropylglycine Ncpro D-N-methylasparagine Dnmasn N-cycloundecylglycine Ncund D-N-methylaspartate Dnmasp N-(2,2-diphenylethyl)glycine Nbhm D-N-methylcysteine Dnmcys N-(3,3-diphenylpropyl)glycine Nbhe D-N-methylglutamine Dnmgln N-(3-guanidinopropyl)glycine Narg D-N-methylglutamate Dnmglu N-( 1 -hydroxyethyl)glycine Nthr D-N-methylhistidine Dnmhis N-(hydroxyethyl))glycine Nser D-N-methylisoleucine Dnmile N-(imidazolylethyl))glycine Nhis D-N-methylleucine Dnmleu N-(3-indolylyethyl)glycine Nhtrp D-N-methyllysine Dnmlys N-methyl-γ-aminobutyrate Nmgabu N-methylcyclohexylalanine Nmchexa D-N-methylmethionine Dnmmet D-N-methylornithine Dnmorn N-methylcyclopentylalanine Nmcpen N-methylglycine Nala D-N-methylphenylalanine Dnmphe N-methylaminoisobutyrate Nmaib D-N-methylproline Dnmpro N-(l-methylpropyl)glycine Nile D-N-methylserine Dnmser N-(2-methylpropyl)glycine Nleu D-N-methylthreonine Dnmthr D-N-methyltryptophan Dnmtrp N-(l-methylethyl)glycine Nval D-N-methyltyrosine Dnmtyr N-methyla-napthylalanine Nmanap D-N-methylvaline Dnmval N-memylpenicillamine Nmpen γ-aminobutyric acid Gabu N-(/?-hydroxyphenyl)glycine Nhtyr L-t-butylglycine Tbug N-(thiomethyl)glycine Ncys L-ethylglycine Etg penicillamine Pen L-homophenylalanine Hphe L-α-methylalanine Mala L-α-methylarginine Marg L-α-methylasparagine Masn L-α-methylaspartate Masp L-α-methyl-t-butylglycine Mtbug L-α-methylcysteine Mcys L-methylethylglycine Metg L-α-methylglutamine Mgln L-α-methylglutamate Mglu L-α-methylhistidine Mhis L-α-methylhomophenylalanine Mhphe L-α-methylisoleucine Mile N-(2-methylthioethyl)glycine Nmet L-α-methylleucine Mleu L-α-methyllysine Mlys L-α-methylmethionine Mmet L-α-methylnorleucine Mnle L-α-methylnorvaline Mnva L-α-methylornithine Morn L-α-methylphenylalanine Mphe L-α-methylproline Mpro L-α-methylserine Mser L-α-methylthreonine Mthr L-α-methyltryptophan Mtrp L-α-methyltyrosine Mtyr L-α-methylvaline Mval L-N-methylhomophenylalanine Nmhphe N-(N-(2,2-diphenylethyl) Nnbhm N-(N-(3,3-diphenylpropyl) Nnbhe carbamylmethyl)glycine carbamylmethyl)glycine 1 -carboxy- 1 -(2,2-diphenyl- Nmbc ethylamino)cyclopropane Crosslinkers can be used, for example, to stabilise 3D conformations, using homo-bifunctional crosslinkers such as the bifunctional irnido esters having (CH2) n spacer groups with n=l to n=6, glutaraldehyde, N-hydroxysuccinimide esters and hetero-bifunctional reagents which usually contain an amino-reactive moiety such as N-hydroxysuccinimide and another group specific- reactive moiety such as maleimido or dithio moiety (SH) or carbodiimide (COOH). In addition, peptides can be conformationally constrained by, for example, incorporation of C α and N„ - methylamino acids, introduction of double bonds between C α and C β atoms of amino acids and the formation of cyclic peptides or analogues by introducing covalent bonds such as forming an amide bond between the N and C termini, between two side chains or between a side chain and the N or C terminus. These types of modifications may be important to stabilise the cytokines if administered to an individual or for use as a diagnostic reagent. Other derivatives contemplated by the present invention include a range of glycosylation variants from a completely unglycosylated molecule to a modified glycosylated molecule. Altered glycosylation patterns may result from expression of recombinant molecules in different host cells. Another embodiment of the present invention contemplates a method for modulating expression of a SOCS protein in a mammal, said method comprising contacting a gene encoding a SOCS or a factor/element involved in controlling expression of the SOCS gene with an effective amount of a modulator of SOCS expression for a time and under conditions sufficient to up-regulate or down-regulate or otherwise modulate expression of SOCS. An example of a modulator is a cytokine such as LL-6 or other transcription regulators of SOCS expression. Expression includes transcription or translation or both. Another aspect of the present invention contemplates a method of modulating activity of SOCS in a human, said method comprising administering to said mammal a modulating effective amount of a molecule for a time and under conditions sufficient to increase or decrease SOCS activity. The molecule may be a proteinaceous molecule or a chemical entity and may also be a derivative of SOCS or a chemical analogue or truncation mutant of SOCS. A further aspect of the present invention provides a method of inducing synthesis of a SOCS or transcription/translation of a SOCS comprising contacting a cell containing a SOCS gene with an effective amount of a cytokine capable of inducing said SOCS for a time and under conditions sufficient for said SOCS to be produced. For example, SOCSl may be induced by LL-6. Still a further aspect of the present invention contemplates a method of modulating levels of a SOCS protein in a cell said method comprising contacting a cell containing a SOCS gene with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time and under conditions sufficient to modulate levels of said SOCS protein. Yet a further aspect of the present invention contemplates a method of modulating signal transduction in a cell containing a SOCS gene comprising contacting said cell with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time sufficient to modulate signal transduction. Even yet a further aspect of the present invention contemplates a method of influencing interaction between cells wherein at least one cell carries a SOCS gene, said method comprising contacting the cell carrying the SOCS gene with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time sufficient to modulate signal transduction. As stated above, of the present invention contemplates a range of mimetics or small molecules capable of acting as agonists or antagonists of the SOCS. Such molecules may be obtained from natural product screening such as from coral, soil, plants or the ocean or antarctic environments. Alternatively, peptide, polypeptide or protein libraries or chemical libraries may be readily screened. For example, Ml cells expressing a SOCS do not undergo differentiation in the presence of LL-6. This system can be used to screen molecules which permit differentiation in the presence of LL-6 and a SOCS. A range of test cells may be prepared to screen for antagonists and agonists for a range of cytokines. Such molecules are preferably small molecules and may be of amino acid origin or of chemical origin. SOCS molecules interacting with signalling proteins (eg. JAKS) provide molecular screens to detect molecules which interfere or promote this interaction. Once such screening protocol involves natural product screening. Accordingly, the present invention contemplates a pharmaceutical composition comprising SOCS or a derivative thereof or a modulator of SOCS expression or SOCS activity and one or more pharmaceutically acceptable carriers and/or diluents. These components are referred to as the "active ingredients". These and other aspects of the present invention apply to any SOCS molecules such as but not limited to SOCSl to SOCS 15. The pharmaceutical forms containing active ingredients suitable for injectable use include sterile aqueous solutions (where water soluble) sterile powders for the extemporaneous preparation of sterile injectable solutions. 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), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating such as licithin, by the maintenance of the required particle size in the case of dispersion and by the use of superfactants. The preventions of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thirmerosal and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin. SUBSTTTIΓΠE SHEET (RULE 26) Sterile injectable solutions are prepared by incoφorating the active compounds in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filtered sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and the freeze-drying technique which yield a powder of the active ingredient plus any additional desired ingredient from previously sterile-filtered solution thereof. When the active ingredients are suitably protected they may be orally administered, for example, with an inert diluent or with an assimilable edible carrier, or it may be enclosed in hard or soft shell gelatin capsule, or it may be compressed into tablets. For oral therapeutic administration, the active compound may be incorporated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers and the like. Such compositions and preparations should contain at least 1 % by weight of active compound. The percentage of the compositions and preparations may, of course, be varied and may conveniently be between about 5 to about 80% of the weight of the unit. The amount of active compound in such therapeutically useful compositions in such that a suitable dosage will be obtained. Preferred compositions or preparations according to the present invention are prepared so that an oral dosage unit form contains between about 0.1 μg and 2000 mg of active compound. The tablets, troches, pills, capsules and the like may also contain the components as listed hereafter. A binder such as gum, acacia, corn starch or gelatin; excipients such as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; a lubricant such as magnesium stearate; and a sweetening agent such a sucrose, lactose or saccharin may be added or a flavouring agent such as peppermint, oil of wintergreen or cherry flavouring. When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier. Various other materials may be present as coatings or to otherwise modify the physical form of the dosage unit. For instance, tablets, pills, or capsules may be coated with shellac, sugar or both. A syrup or elixir may contain the active compound, sucrose as a sweetening agent, methyl and propylparabens as preservatives, a dye and flavouring such as cherry or orange flavour. Of course, any material used in preparing any dosage unit form should be pharmaceutically pure and substantially non-toxic in the amounts employed. In addition, the active compound(s) may be incorporated into sustained-release preparations and formulations. The present invention also extends to forms suitable for topical application such as creams, lotions and gels. Pharmaceutically acceptable carriers and/or diluents include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutical active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, use thereof in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. It is especially advantageous to formulate 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 mammalian subjects to be treated; each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the novel dosage unit forms of the invention are dictated by and directly dependent on (a) the unique characteristics of the active material and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such an active material for the treatment of disease in living subjects having a diseased condition in which bodily health is impaired as herein disclosed in detail. The principal active ingredient is compounded for convenient and effective administration in effective amounts with a suitable pharmaceutically acceptable carrier in dosage unit form as hereinbefore disclosed. A unit dosage form can, for example, contain the principal active compound in amounts ranging from 0.5 μg to about 2000 mg. Expressed in proportions, the active compound is generally present in from about 0.5 μg to about 2000 mg/ml of carrier. In the case of compositions containing supplementary active ingredients, the dosages are determined by reference to the usual dose and manner of administration of the said ingredients. The effective amount may also be conveniently expressed in terms of an amount per kg of body weight. For example, from about 0.01 ng to about 10,000 mg/kg body weight may be administered. The pharmaceutical composition may also comprise genetic molecules such as a vector capable of transfecting target cells where the vector carries a nucleic acid molecule capable of modulating SOCS expression or SOCS activity. The vector may, for example, be a viral vector. In this regard, a range of gene therapies are contemplated by the present invention including isolating certain cells, genetically manipulating and returning the cell to the same subject or to a genetically related or similar subject. Still another aspect of the present invention is directed to antibodies to SOCS and its derivatives. Such antibodies may be monoclonal or polyclonal and may be selected from naturally occurring antibodies to SOCS or may be specifically raised to SOCS or derivatives thereof. In the case of the latter, SOCS or its derivatives may first need to be associated with a carrier molecule. The antibodies and/or recombinant SOCS or its derivatives of the present invention are particularly useful as therapeutic or diagnostic agents. For example, SOCS and its derivatives can be used to screen for naturally occurring antibodies to SOCS. These may occur, for example in some autoimmune diseases. Alternatively, specific antibodies can be used to screen for SOCS. Techniques for such assays are well known in the art and include, for example, sandwich assays and ELISA. Knowledge of SOCS levels may be important for diagnosis of certain cancers or a predisposition to cancers or monitoring cytokine mediated cellular responsiveness or for monitoring certain therapeutic protocols. Antibodies to SOCS of the present invention may be monoclonal or polyclonal. Alternatively, fragments of antibodies may be used such as Fab fragments. Furthermore, the present invention extends to recombinant and synthetic antibodies and to antibody hybrids. A "synthetic antibody" is considered herein to include fragments and hybrids of antibodies. The antibodies of this aspect of the present invention are particularly useful for immunotherapy and may also be used as a diagnostic tool for assessing apoptosis or monitoring the program of a therapeutic regimin. For example, specific antibodies can be used to screen for SOCS proteins. The latter would be important, for example, as a means for screening for levels of SOCS in a cell extract or other biological fluid or purifying SOCS made by recombinant means from culture supernatant fluid. Techniques for the assays contemplated herein are known in the art and include, for example, sandwich assays and ELISA. It is within the scope of this invention to include any second antibodies (monoclonal, polyclonal or fragments of antibodies or synthetic antibodies) directed to the first mentioned antibodies discussed above. Both the first and second antibodies may be used in detection assays or a first antibody may be used with a commercially available anti-immunoglobulin antibody. An antibody as contemplated herein includes any antibody specific to any region of SOCS. Both polyclonal and monoclonal antibodies are obtainable by immunization with the enzyme or protein and either type is utilizable for immunoassays. The methods of obtaining both types of sera are well known in the art. Polyclonal sera are less preferred but are relatively easily prepared by injection of a suitable laboratory animal with an effective amount of SOCS, or antigenic parts thereof, collecting serum from the animal, and isolating specific sera by any of the known immunoadsorbent techniques. Although antibodies produced by this method are utilizable in virtually any type of immunoassay, they are generally less favoured because of the potential heterogeneity of the product. The use of monoclonal antibodies in an immunoassay is particularly preferred because of the ability to produce them in large quantities and the homogeneity of the product. The preparation of hybridoma cell lines for monoclonal antibody production derived by fusing an immortal cell line and lymphocytes sensitized against the immunogenic preparation can be done by techniques which are well known to those who are skilled in the art. Another aspect of the present invention contemplates a method for detecting SOCS in a biological sample from a subject said method comprising contacting said biological sample with an antibody specific for SOCS or its derivatives or homologues for a time and under conditions sufficient for an antibody-SOCS complex to form and then detecting said complex. The presence of SOCS may be accomplished in a number of ways such as by Western blotting and ELISA procedures. A wide range of immunoassay techniques are available as can be seen by reference to US Patent Nos. 4,016,043, 4, 424,279 and 4,018,653. These, of course, include both single-site and two-site or "sandwich" assays of the non-competitive types, as well as in the traditional competitive binding assays. These assays also include direct binding of a labelled antibody to a target. Sandwich assays are among the most useful and commonly used assays and are favoured for use in the present invention. A number of variations of the sandwich assay technique exist, and all are intended to be encompassed by the present invention. Briefly, in a typical forward assay, an unlabelled antibody is immobilized on a solid substrate and the sample to be tested brought into contact with the bound molecule. After a suitable period of incubation, for a period of time sufficient to allow formation of an antibody-antigen complex, a second antibody specific to the antigen, labelled with a reporter molecule capable of producing a detectable signal is then added and incubated, allowing time sufficient for the formation of another complex of antibody- antigen-labelled antibody. Any unreacted material is washed away, and the presence of the antigen is determined by observation of a signal produced by the reporter molecule. The results may either be qualitative, by simple observation of the visible signal, or may be quantitated by comparing with a control sample containing known amounts of hapten. Variations on the forward assay include a simultaneous assay, in which both sample and labelled antibody are added simultaneously to the bound antibody. These techniques are well known to those skilled in the art, including any minor variations as will be readily apparent. In accordance with the present invention the sample is one which might contain SOCS including cell extract, tissue biopsy or possibly serum, saliva, mucosal secretions, lymph, tissue fluid and respiratory fluid. The sample is, therefore, generally a biological sample comprising biological fluid but also extends to fermentation fluid and supernatant fluid such as from a cell culture. In the typical forward sandwich assay, a first antibody having specificity for the SOCS or antigenic parts thereof, is either covalently or passively bound to a solid surface. The solid surface Is typically glass or a polymer, the most commonly used polymers being cellulose, polyacrylamide, nylon, polystyrene, polyvinyl chloride or polypropylene. The solid supports may be in the form of tubes, beads, discs of microplates, or any other surface suitable for conducting an immunoassay. The binding processes are well-known in the art and generally consist of cross-linking covalently binding or physically adsorbing, the polymer-antibody complex is washed in preparation for the test sample. An aliquot of the sample to be tested is then added to the solid phase complex and incubated for a period of time sufficient (e.g. 2-40 minutes or overnight if more convenient) and under suitable conditions (e.g. room temperature to 37°C) to allow binding of any subunit present in the antibody. Following the incubation period, the antibody subunit solid phase is washed and dried and incubated with a second antibody specific for a portion of the hapten. The second antibody is linked to a reporter molecule which is used to indicate the binding of the second antibody to the hapten. An alternative method involves immobilizing the target molecules in the biological sample and then exposing the immobilized target to specific antibody which may or may not be labelled with a reporter molecule. Depending on the amount of target and the strength of the reporter molecule signal, a bound target may be detectable by direct labelling with the antibody. Alternatively, a second labelled antibody, specific to the first antibody is exposed to the target- first antibody complex to form a target-first antibody-second antibody tertiary complex. The complex is detected by the signal emitted by the reporter molecule. By "reporter molecule" as used in the present specification, is meant a molecule which, by its chemical nature, provides an analytically identifiable signal which allows the detection of antigen-bound antibody. Detection may be either qualitative or quantitative. The most commonly used reporter molecules in this type of assay are either enzymes, fluorophores or radionuclide containing molecules (i.e. radioisotopes) and chemiluminescent molecules. In the case of an enzyme immunoassay, an enzyme is conjugated to the second antibody, generally by means of glutaraldehyde or periodate. As will be readily recognized, however, a wide variety of different conjugation techniques exist, which are readily available to the skilled artisan. Commonly used enzymes include horseradish peroxidase, glucose oxidase, beta- galactosidase and alkaline phosphatase, amongst others. The substrates to be used with the specific enzymes are generally chosen for the production, upon hydrolysis by the corresponding enzyme, of a detectable colour change. Examples of suitable enzymes include alkaline phosphatase and peroxidase. It is also possible to employ fluorogenic substrates, which yield a fluorescent product rather than the chromogenic substrates noted above. In all cases, the enzyme-labelled antibody is added to the first antibody hapten complex, allowed to bind, and then the excess reagent is washed away. A solution containing the appropriate substrate is then added to the complex of antibody-antigen-antibody. The substrate will react with the enzyme linked to the second antibody, giving a qualitative visual signal, which may be further quantitated, usually spectrophotometrically, to give an indication of the amount of hapten which was present in the sample. "Reporter molecule" also extends to use of cell agglutination or inhibition of agglutination such as red blood cells on latex beads, and the like. Alternately, fluorescent compounds, such as fluorescein and rhodamine, may be chemically coupled to antibodies without altering their binding capacity. When activated by illumination with light of a particular wavelength, the fluorochrome-labelled antibody adsorbs the light energy, inducing a state to excitability in the molecule, followed by emission of the light at a characteristic colour visually detectable with a light microscope. As in the EIA, the fluorescent labelled antibody is allowed to bind to the first antibody-hapten complex. After washing off the unbound reagent, the remaining tertiary complex is then exposed to the light of the appropriate wavelength the fluorescence observed indicates the presence of the hapten of interest. Immunofluorescene and EIA techniques are both very well established in the art and are particularly preferred for the present method. However, other reporter molecules, such as radioisotope, chemiluminescent or bioluminescent molecules, may also be employed. The present invention also contemplates genetic assays such as involving PCR analysis to detect SOCS gene or its derivatives. Alternative methods or methods used in conjunction include direct nucleotide sequencing or mutation scanning such as single stranded conformation polymorphisms analysis (SSCP) as specific oligonucleotide hybridisation, as methods such as direct protein truncation tests. Since cytokines are involved in transcription of some SOCS molecules, the detection of SOCS provides surrogate markers for cytokines or cytokine activity. This may be useful in assessing subjects with a range of conditions such as those will autoimmune diseases, for example, rheumatoid arthritis, diabetes and stiff man syndrome amongst others. The nucleic acid molecules of the present invention may be DNA or RNA. When the nucleic acid molecule is in DNA form, it may be genomic DNA or cDNA. RNA forms of the nucleic acid molecules of the present invention are generally mRNA. Although the nucleic acid molecules of the present invention are generally in isolated form, they may be integrated into or ligated to or otherwise fused or associated with other genetic molecules such as vector molecules and in particular expression vector molecules. Vectors and expression vectors are generally capable of replication and, if applicable, expression in one or both of a prokaryotic cell or a eukaryotic cell. Preferably, prokaryotic cells include E. coli, Bacillus sp and Pseudomonas sp. Preferred eukaryotic cells include yeast, fungal, mammalian and insect cells. Accordingly, another aspect of the present invention contemplates a genetic construct comprising a vector portion and a mammalian and more particularly a human SOCS gene portion, which SOCS gene portion is capable of encoding a SOCS polypeptide or a functional or immunologically interactive derivative thereof. Preferably, the SOCS gene portion of the genetic construct is operably linked to a promoter on the vector such that said promoter is capable of directing expression of said SOCS gene portion in an appropriate cell. In addition, the SOCS gene portion of the genetic construct may comprise all or part of the gene fused to another genetic sequence such as a nucleotide sequence encoding glutathione-S- transferase or part thereof. The present invention extends to such genetic constructs and to prokaryotic or eukaryotic cells comprising same. The present invention also extends to any or all derivatives of SOCS including mutants, part, fragments, portions, homologues and analogues or their encoding genetic sequence including single or multiple nucleotide or amino acid substitutions, additions and/or deletions to the naturally occurring nucleotide or amino acid sequence. The present invention also extends to mimetics and agonists and antagonists of SOCS. The SOCS and its genetic sequence of the present invention will be useful in the generation of a range of therapeutic and diagnostic reagents and will be especially useful in the detection of a cytokine involved in a particular cellular response or a receptor for that cytokine. For example, cells expressing SOCS gene such as Ml cells expressing the SOCSl gene, will no longer be responsive to a particular cytokine such as, in the case of SOCSl, LL-6. Clearly, the present invention further contemplates cells such as Ml cells expressing any SOCS gene such as from SOCS 1 to SOCS 15. Furthermore, the present invention provides the use of molecules that regulate or potentiate the ability of therapeutic cytokines. For example, molecules which block some SOCS activity, may act to potential therapeutic cytokine activity (eg. G-CSF). Soluble SOCS polypeptides are also contemplated to be particularly useful in the treatment of disease, injury or abnormality involving cytokine mediated cellular responsiveness such as hyperimmunity, immunosuppression, allergies, hypertension and the like. A further aspect of the present invention contemplates the use of SOCS or its functional derivatives in the manufacture of a medicament for the treatment of conditions involving cytokine mediated cellular responsiveness. The present invention further contemplates transgenic mammalian cells expressing a SOCS gene. Such cells are useful indicator cell lines for assaying for suppression of cytokine function. One example is Ml cells expressing a SOCS gene. Such cell lines may be useful for screening for cytokines or screening molecules such as naturally occurring molecules from plants, coral, microorganisms or bio-organically active soil or water capable of acting as cytokine antagonists or agonists. The present invention further contemplates hybrids between different SOCS from the same or different animal species. For example, a hybrid may be formed between all or a functional part of mouse SOCSl and human SOCSl. Alternatively, the hybrid may be between all or part of mouse SOCSl and mouse SOCS2. All such hybrids are contemplated herein and are particularly useful in developing pleiotropic molecules. The present invention further contemplates a range of genetic based diagnostic assays screening for individuals with defective SOCS genes. Such mutations may result in cell types not being responsive to a particular cytokine or resulting in over responsiveness leading to a range of conditions. The SOCS genetic sequence can be readily verified using a range of PCR or other techniques to determine whether a mutation is resident in the gene. Appropriate gene therapy or other interventionist therapy may then be adopted. The present invention is further described by the following non-limiting Examples. Examples 1-16 relate to SOCSl, SOCS2 and SOCS3 which were identified on the basis of activity. Examples 17-24 relate to various aspects of SOCS4 to SOCS 15 which were cloned initially on the basis of sequence similarity. Examples 25-36 relate to specific aspects of SOCS4 to SOCS 15, respectively. EXAMPLE 1 CELL CULTURE AND CYTOKINES The Ml cell line was derived from a spontaneously arising leukaemia in SL mice [Ichikawa, 1969]. Parental Ml cells used in this study have been in passage at the Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia, for approximately 10 years. Ml cells were maintained by weekly passage in Dulbecco's modified Eagle's medium (DME) containing 10% (v/v) foetal bovine serum (FCS). Recombinant cytokines are generally available from commercial sources or were prepared by published methods. Recombinant murine LIF was produced in Escherichia coli and purified, as previously described [Gearing, 1989]. Purified human oncostatin M was purchased from PeproTech Inc (Rocky Hill, NJ, USA), and purified mouse LFN-γ was obtained from Genzyme Diagnostics (Cambridge, MA, USA). Recombinant murine thrombopoietin was produced as a FLAGTM-tagged fusion protein in CHO cells and then purified. EXAMPLE 2 AGAR COLONY ASSAYS In order to assay the differentiation of Ml cells in response to cytokines, 300 cells were cultured in 35 mm Petri dishes containing 1 ml of DME supplemented with 20% (v/v) fϊtal calf serum (FCS), 0.3%(w/v) agar and 0.1 ml of serial dilutions of LL-6, LIF, OSM, LFN-γ, tpo or dexamethasone (Sigma Chemical Company, St Louis, MI). After 7 days culture at 37° C in a fully humidified atmosphere, containing 10% (v/v) CO 2 in air, colonies of Ml cells were counted and classified as differentiated if they were composed of dispersed cells or had a corona of dispersed cells around a tightly packed centre. EXAMPLE 3 GENERATION OF RETROVIRAL LIBRARY A cDNA expression library was constructed from the factor-dependent haemopoietic cell line FDC-Pl, essentially as described [Rayner, 1994]. Briefly, cDNA was cloned into the retroviral vector pRUFneo and then transfected into an amphotrophic packaging cell fine (PA317). Transiently generated virus was harvested from the cell supernatant at 48 hr posttransfection, and used to infect Y2 ecotropic packaging cells, to generate a high titre virus-producing cell fine. EXAMPLE 4 RETROVIRAL INFECTION OF Ml CELLS Pools of 10 6 infected Ψ2 cells were irradiated (3000 rad) and cocultivated with 10 6 Ml cells in DME supplemented with 10%(v/v) FCS and 4 μg/ml Polybrene, for 2 days at 37°C. To select for LL-6-unresponsive clones, retrovirally-infected Ml cells were washed once in DME, and cultured at approximately 2xl0 4 cells/ml in 1 ml agar cultures containing 400 μg/ml geneticin (GibcoBRL, Grand Island, NY) and 100 ng/ml LL-6. The efficiency of infection of Ml cells was 1-2%, as estimated by agar plating the infected cells in the presence of geneticin only. EXAMPLE 5 PCR Genomic DNA from retrovirally-infected Ml cells was digested with Sac I and 1 μg of phenol chloroform extracted DNA was then amplified by polymerase chain reaction (PCR). Primers used for amplification of cDNA inserts from the integrated retrovirus were GAG3 (5' CACGCCGCCCACGTGAAGGC 3' [SEQ ID NO: 1]), which corresponds to the vector gag sequence approximately 30 bp 5' of the multiple cloning site, and HSVTK (5' TTCGCCAATGACAAGACGCT 3' [SEQ ID NO:2]), which corresponds to the pMClneo sequence approximately 200 bp 3 ' of the multiple cloning site. The PCR entailed an initial denaturation at 94°C for 5 min, 35 cycles of denaturation at 94°C for 1 min, annealing at 56°C for 2 min, and extension at 72 °C for 3 min, followed by a final 10 min extension. PCR products were gel purified and then ligated into the pGEM-T plasmid (Promega, Madison, WI), and sequenced using an ABI PRISM Dye Terminator Cycle Sequencing Kit and a Model 373 Automated DNA Sequencer (Applied Biosystems Inc., Foster City, CA). EXAMPLE 6 CLONING OF cDNAs Independent cDNA clones encoding mouse SOCSl were isolated from a murine thymus cDNA library essentially as described (Hilton et al, 1994). The nucleotide and predicted amino acid sequences of mouse SOCSl cDNA were compared to databases using the BLASTN and TFASTA algorithms (Pearson and Lipman, 1988; Pearson, 1990; Altshcul et al, 1990). Oligonucleotides were designed from the ESTs encoding human SOCS 1 and mouse SOC-1 and SOCS3 and used to probe commercially available mouse thymus and spleen cDNA libraries. Sequencing was performed using an ABI automated sequencer according to the manufacturer's instructions. EXAMPLE 7 SOUTHERN AND NORTHERN BLOT ANALYSES AND RT-PCR 32 P-labelled probes were generated using a random decanucleotide labelling kit (Bresatec, Adelaide, South Australia) from a 600 bp Pst I fragment encoding neomycin phophotransfease from the plasmid pPGKneo, 1070 bp fragment of the SOCS 1 gene obtained by digestion of the 1.4 kbp PCR product with Xho I, SOCS2, SOCS3, CIS and a 1.2 kbp fragment of the chicken glyceraldehyde 3-phosphate dehydrogenase gene [Dugaiczyk, 1983]. Genomic DNA was isolated from cells using a proteinase K-sodium dodecyl sulfate procedure essentially as described. Fifteen micrograms of DNA was digested with either BamH I or Sac I, fractionated on a 0.8%(w/v) agarose gel, transferred to GeneScreenPlus membrane (Du Pont NEN, Boston MA), prehybridised, hybridised with random-primed 32 P-labelled DNA fragments and washed essentially as described [Sambrook, 1989]. Total RNA was isolated from cells and tissues using Trizol Reagent, as recommended by the manufacturer (GibcoBRL,Grand Island, NY). When required polyA+ mRNA was purified essentially as described [Alexander, 1995]. Northern blots were prehybridised, hybridized with random-primed 32P-labelled DNA fragments and washed as described [Alexander, 1995]. To assess the induction of SOCS genes by LL-6, mice (C57BL6) were injected intravenously with 5 μg LL-6 followed by harvest of the liver at the indicated timepoints after injection. Ml cells were cultured in the presence of 20 ng/ml LL-6 and harvested at the indicated times. For RT-PCR analysis, bone marrow cells were harvested as described (Metacalf et al, 1995) and stimulated for 1 hr at 37 °C with 100 ng/ml of a range of cytokines. RT-PCR was performed on total RNA as described (Metcalf et al, 1995). PCR products were resolved on an agarose gel and Southern blots were hybridised with probes specific for each SOCS family member. Expression of β-actin was assessed to ensure uniformity of amplification. EXAMPLE 8 DNA CONSTRUCTS AND TRANSFECTION A cDNA encoding epitope-tagged SOCS 1 was generated by subcloning the entire SOCS 1 coding region into the pEF-BOS expression vector [Mizushima, 1990], engineered to encode an inframe FLAG epitope downstream of an initiation methionine (pF-SOCSl). Using electroporation as described previously [Hilton, 1994], Ml cells expressing the thrombopoietin receptor (M 1.mpl) were transfected with the 20 μg of Aat Il-digested pF-SOCS 1 expression plasmid and 2 μg of a Sea I-digested plasmid in which transcription of a cDNA encoding puromycin N-acetyl transferase was driven from the mouse phosphoglycerokinase promoter (pPGKPuropA). After 48 hours in culture, transfected cells were selected with 20 μg/ml puromycin (Sigma Chemical Company, St Louis MO), and screened for expression of SOCS 1 by Western blotting, using the M2 anti-FLAG monoclonal antibody according to the manafacturer's instructions (Eastman Kodak, Rochester NY). In other experiments Ml cells were transfected with only the pF-SOCSl plasmid or a control and selected by their ability to grow in agar in the presence of 100 ng/ml of LL-6. SUBSTTΓUTE SHEET (Rule 26) EXAMPLE 9 IMMUNOPRECIPITATION AND WESTERN BLOTTING Prior to either immunoprecipitaion or Western blotting, 10 7 Ml cells or their derivatives were washed twice, resuspended in 1ml of DME, and incubated at 37°C for 30 min. The cells were then stimulated for 4 min at 37 °C with either saline or 100 ng/ml IL-6, after which sodium vanadate (Sigma Chemical Co., St Louis, MI) was added to a concentration of 1 mM. Cells were placed on ice, washed once with saline containing 1 mM sodium vanadate, and then solubilised for 5 min on ice with 300 μl 1% (v/v) Triton X-100, 150 mM NaCl, 2 mM EDTA, 50 mM Tris-HCl pH 7.4, containing Complete protease inhibitors (Boehringer Mannheim, Mannheim, Germany) and 1 mM sodium vanadate. Lysates were cleared by centrifugation and quantitated using a Coomassie Protein Assay Reagent (Pierce, Rockford IL). For immunoprecipitations, equal concentrations of protein extracts (1-2 mg) were incubated for 1 hr or overnight at 4°C with either 4 μg of anti-gpl30 antibody (M20; Santa Cruz Biotechnology Inc., Santa Cruz, CA) or 4 μg of anti-phosphotyrosine antibody (4G10; Upstate Biotechnology Inc., Lake Placid NY), and 15 μl packed volume of Protein G Sepharose (Pharmacia, Uppsala, Sweden) [Hilton et al, 1996]. Immunoprecipitates were washed twice in 1% (v/v) NP40, 150 mM NaCl , 50 mM Tris-HCl pH 8.0, containing Complete protease inhibitors (Boehringer Mannheim, Mannheim, Germany and 1 mM sodium vanadate. The samples were heated for 5 min at 95 °C in SDS sample buffer (625 mM Tris-HCl pH 6.8, 0.05% (w/v) SDS, 0.1% (v/v) glycerol, bromophenol blue, 0.125% (v/v) 2-mercaptoethanol), fractionated by SDS-PAGE and immunoblotted as described above. For Western blotting, 10 μg of protein from a cellular extract or material from an immunoprecipitation reaction was loaded onto 4-15% Ready gels (Bio-Rad Laboratories, Hercules CA), and resolved by sodium dodecyl sulfate poly aery lamide gel electrophoresis (SDS-PAGE). Proteins were transferred to PVDF membrane (Micron Separations Inc., Westborough MA) for 1 hr at 100 V. The membranes were probed with the following primary antibodies; anti-tyrosine phosphorylated STAT3 (1:1000 dilution; New England Biolabs, Beverly, MA); anti-STAT3 (C-20; 1:100 dilution; Santa Cruz Biotechnology Inc., Santa Cruz CA); anti-gpl30 (M20, 1: 100 dilution; Santa Cruz Biotechnology Inc., Santa Cruz CA); anti- SU3STITUTE SHEET Rule 26 phosphotyrosine (horseradish peroxidase-conjugated RC20, 1:5000 dilution; Transduction Laboratories, Lexington KY); anti -tyrosine phosphorylated MAP kinase and anti-MAP kinase antibodies (1: 1000 dilution; New England Biolabs, Beverly, MA). Blots were visualised using peroxidase-conjugated secondary antibodies and Enhanced Chemiluminescence (ECL) reagents according to the manafacturer's instructions (Pierce, Rockford LL). EXAMPLE 10 ELECTROPHORETIC MOBILITY SHIFT ASSAYS Assays were performed as described [Novak, 1995], using the high affinity SLF (c-sis- inducible factor) binding site m67 [Wakao, 1994]. Protein extracts were prepared from Ml cells incubated for 4-10 min at 37° C in 10 ml serum-free DME containing either saline, 100 ng/ml LL-6 or 100 ng/ml IFN-γ. The binding reactions contained 4-6 μg protein (constant within a given experiment), 5 ng 32 P-labelled m67 oligonucleotide, and 800 ng sonicated salmon sperm DNA. For certain experiments, protein samples were preincubated with an excess of unlabelled m67 oligonucleotide, or antibodies specific for either STATl (Transduction Laboratories, Lexington, KY) or STAT3 (Santa Cruz Biotechnology Inc., Santa Cruz CA), as described [Novak, 1995]. Western blots were performed using anti-tyrosine phosphorylated STAT3 or anti-STAT3 (New England Biolabs, Beverly, MA) or anti-gpl30 (Santa Cruz Biotechnology Inc.) as described (Nicola et al, 1996). EMS A were performed using the m67 oligonucleotide probe, as described (Novak et al, 1995). EXAMPLE 11 EXPRESSION CLONING OF A NOVEL SUPPRESSOR OF CYTOKINE SIGNAL TRANSDUCTION In order to identify cDNAs capable of suppressing cytokine signal transduction, an expression cloning approach was adopted. This strategy centred on Ml cells, a monocytic leukaemia cell line that differentiates into mature macrophages and ceases proliferation in response to the cytokines LL-6, LLF, OSM and LFN-γ, and the steroid dexamethasone. Parental Ml cells were infected with the RUFneo retrovirus, into which cDNAs from the factor-dependent haemopoietic cell line FDC-P1 had been cloned. In this retrovirus, transcription of both the neomycin resistance gene and the cloned cDNA was driven off the powerful constitutive promoter present in the retroviral LTR (Figure 1). When cultured in semi-solid agar, parental Ml cells form large tightly packed colonies. Upon stimulation with LL-6, Ml cells undergo rapid differentiation, resulting in the formation in agar of only single macrophages or small dispersed clusters of cells . Retrovirally-infected Ml cells that were unresponsive to LL-6 were selected in semi-solid agar culture by their ability to form large, tightly packed colonies in the presence of LL-6 and geneticin. A single stable LL-6-unresponsive clone, 4A2, was obtained after examining 10 4 infected cells. A fragment of the neomycin phosphotransferase (neo) gene was used to probe a Southern blot of genomic DNA from clone 4A2 and this revealed that the cell line was infected with a single retrovirus containing a cDNA approximately 1.4 kbp in length (Figure 2). PCR amplification using primers from the retroviral vector which flanked the cDNA cloning site enabled recovery of a 1.4 kbp cDNA insert, which we have named suppressor of cytokine signalling- 1, or SOCSl. This PCR product was used to probe a similar Southern blot of 4A2 genomic DNA and hybridised to two fragments, one which corresponded to the endogenous SOCS 1 gene and the other, which matched the size of the band seen using the neo probe, corresponded to the SOCSl cDNA cloned into the integrated retrovirus (Figure 2). The latter was not observed in an Ml cell clone infected with a retrovirus containing an irrelevant cDNA. Similarly, Northern blot analysis revealed that SOCS 1 mRNA was abundant in the cell line 4A2, but not in the control infected Ml cell clone (Figure 2). EXAMPLE 12 SOCSl, SOCS2, SOCS3 AND CIS DEFINE A NEW FAMILY OF SH2-CONTAINING PROTEINS The SOCS 1 PCR product was used as a probe to isolate homologous cDNAs from a mouse thymus cDNA library. The sequence of the cDNAs proved to be identical to the PCR product, suggesting that constitutive or over expression, rather than mutation, of the SOCS 1 protein was sufficient for generating an LL-6-unresponsive phenotype. Comparison of the sequence of SOCS 1 cDNA with nucleotide sequence databases revealed that it was present on mouse and rat genomic DNA clones containing the protamine gene cluster found on mouse chromosome 16. Closer inspection revealed that the 1.4 kb SOCSl sequence was not homologous to any of the protamine genes, but rather represented a previously unidentified open reading frame located at the extreme 3' end of these clones (Figure 3). There were no regions of discontinuity between the sequences of the SOCS 1 cDNA and genomic locus, suggesting that SOCS 1 is encoded by a single exon. In addition to the genomic clone containing the protamine genes, a series of murine and human expressed sequenced tags (ESTs) also revealed large blocks of nucleotide sequence identity to mouse SOCSl. The sequence information provided by the human ESTs allowed the rapid cloning of cDNAs encoding human SOCSl. The mouse and rat SOCSl gene encodes a 212 amino acid protein whereas the human SOCSl gene encodes a 211 amino acid protein. Mouse, rat and human SOCS 1 proteins share 95-99% amino acid identity (Figure 9). A search of translated nucleic acid databases with the predicted amino acid sequence of SOCSl showed that it was most related to a recently cloned cytokine- inducible immediate early gene product, CIS, and two classes of ESTs. Full length cDNAs from the two classes of ESTs were isolated and found to encode proteins of similar length and overall structure to SOCSl and CIS. These clones were given the names SOCS2 and SOCS3. Each of the four proteins contains a central SH2 domain and a C-terminal region termed the SOCS motif. The SOCSl proteins exhibit an extremely high level of amino acid sequence similarity (95-99% identity) amongst different species. However, the forms of the SOCSl, SOCS2, SOCS3 and CIS from the same animal, while clearly defining a new family of SH2- containing proteins, exhibited a lower amino acid identity. SOCS2 and CIS exhibit approximately 38% amino acid identity, while the remaining members of the family share approximately 25% amino acid identity (Figure 9). The coding region of the genes for SOCS 1 and SOC3 appear to contain no introns while the coding region of the genes for SOCS2 and CIS contain one and two introns, respectively. The Genbank Accession Numbers for the sequences referred to herein are mouse SOCS 1 cDNA (U88325), human SOCSl cDNA (U88326), mouse SOCS2 cDNA (U88327), mouse SOCS3 cDNA (U88328). EXAMPLE 13 CONSTITUTIVE EXPRESSION OF SOCSl SUPPRESSES THE ACTION OF A RANGE OF CYTOKINES To formally establish that the phenotype of the 4A2 cell line was directly related to expression of SOCS 1, and not to unrelated genetic changes which may have occurred independently in these cells, a cDNA encoding an epitope-tagged version of SOCSl under the control of the EFlα promoter was transfected into parental Ml cells, and Ml cells expressing the receptor for thrombopoietin, c-mpl (Ml .mpl). Transfection of the SOCS 1 expression vector into both cell lines resulted in an increase in the frequency of LL-6 unresponsive Ml cells. Multiple independent clones of Ml cells expression SOCSl, as detected by Western blot, displayed a cytokine-unresponsive phenotype that was indistinguishable from 4A2. Further, if transfectants were not maintained in puromycin, expression of SOCSl was lost over time and cells regained their cytokine responsiveness. In the absence of cytokine, colonies derived from 4A2 and other SOCS 1 expressing clones characteristically grew to a smaller size than colones formed by control Ml cells (Figure 10). The effect of constitutive SOCSl expression on the response of Ml cells to a range of cytokines was investigated using the 4A2 cell line and a clone of Ml.mpl cells expressing SOCS l (Ml.mpl.SOCSl). Unlike parental Ml cells and Ml.mpl cells, the two cell lines expressing SOCSl continued to proliferate and failed to form differentiated colonies in response to either LL-6, LLF, OSM, LFN-γ or, in the case of the Ml.mpl.SOCS 1 cell line, thrombopoietin (Figure 4). For both cell lines, however, a normal response to dexamethasone was observed, suggesting that SOCSl specifically affected cytokine signal transduction rather than differentiation per se. Consistent with these data, while parental Ml cells and Ml.mpl cells became large and vacuolated in response to LL-6, 4A2 and Ml.mpl.SOCSl cells showed no evidence of morphological differentiation in response to LL-6 or other cytokines (Figure 5). EXAMPLE 14 SOCSl INHIBITS A RANGE OF IL-6 SIGNAL TRANSDUCTION PROCESSES, INCLUDING STAT3 PHOSPHORYLATION AND ACTIVATION Phosphorylation of the cell surface receptor component gpl30, the cytoplasmic tyrosine kinase JAK1 and the transcription factor STAT3 is thought to play a central role in LL-6 signal transduction. These events were compared in the parental Ml and Ml.mpl cell lines and their SOCSl -expressing counterparts. As expected, gpl30 was phosphorylated rapidly in response to LL-6 in both parental lines, however, this was reduced five- to ten-fold in the cell lines expressing SOCSl (Figure 6). Likewise, STAT3 phosphorylation was also reduced by approximately ten-fold in response to LL-6 in those cell lines expressing SOCSl (Figure 6). Consistent with a reduction in STAT3 phosphorylation, activation of specific STAT DNA binding complexes, as determined by electrophoretic mobility shift assay, was also reduced. Notably, there was a reduction in the formation of SLF-A (containing STAT3), SIF-B (STAT1/STAT3 heterodimer) and SIF-C (containing STATl), the three STAT complexes induced in Ml cells stimulated with LL-6 (Figure 7). Similarly, constitutive expression of SOCSl also inhibited IFN-γ-stimulated formation of p91 homodimers (Figure 7). STAT phosphorylation and activation were not the only cytoplasmic processes to be effected by SOCS 1 expression, as the phosphorylation of other proteins, including she and MAP kinase, was reduced to a similar extent (Figure 7). EXAMPLE 15 TRANSCRIPTION OF THE SOCSl GENE IS STIMULATED BY IL-6 IN VITRO AND IN VIVO Although SOCSl can inhibit cytokine signal transduction when constitutively expressed in Ml cells, this does not necessarily indicate that SOCS 1 normally functions to negatively regulate an IL-6 response. In order to investigate this possibility the inventors determined whether transcription of the SOCSl gene is regulated in the response of Ml cells to LL-6 and, because of the critical role LL-6 plays in regulating the acute phase response to injury and infection, the response of the liver to intravenous injection of 5 mg LL-6. In the absence of LL-6, SOCS 1 mRNA was undetectable in either Ml cells or in the liver. However, for both cell types, a 1.4 kb SOCSl transcript was induced within 20 to 40 minutes by LL-6 (Figure 8). For Ml cells, where the LL-6 was present throughout the experiment, the level of SOCS 1 mRNA remained elevated (Figure 8). In contrast, LL-6 was administered in vivo by a single intravenous injection and was rapidly cleared from the circulation, resulting in a pulse of LL-6 stimulation to the liver. Consistent with this, transient expression of SOCSl mRNA was detectable in the liver, peaking approximately 40 minutes after injection and declining to basal levels within 4 hours (Figure 8). EXAMPLE 16 REGULATION OF SOCS GENES Since CIS was cloned as a cytokine-inducible immediate early gene the inventors examined whether SOCS 1 , SOCS2 and SOCS3 were similarly regulated. The basal pattern of expression of the four SOCS genes was examined by Northern blot analysis of mRNA from a variety of tissues from male and female C57B 1/6 mice (Figure 11 A). Constitutive expression of SOCS 1 was observed in the thymus and to a lesser extend in the spleen and the lung. SOCS2 expression was restricted primarily to the testis and in some animals the liver and lung; for SOCS 3 a low level of expression was observed in the lung, spleen and thymus, while CIS expression was more widespread, including the testis, heart, lung, kidney and, in some animals, the liver. The inventors sought to determine whether expression of the four SOCS genes was regulated by IL-6. Northern blots of mRNA prepared from the livers of untreated and LL-6-injected mice, or from unstimulated and LL-6-stimulated Ml cells, were hybridised with labelled fragments of SOCS 1, SOCS2, SOCS3 and CIS cDNAs (Figure 1 IB). Expression of all four SOCS genes was increased in the liver following LL-6 injection, however the kinetics of induction appeared to differ. Expression of SOCSl and SOCS3 was transient in the liver, with mRNA detectable after 20 minutes of LL-6 injection and declining to basal levels within 4 hours for SOCS and 8 hours for SOCS3. Induction of SOCS2 and CIS mRNA in the liver followed similar initial kinetics to that of SOCSl, but was maintained at an elevated level for at least 24 hours. A similar induction of SOCS gene mRNA was observed in other organs, notably the lung and the spleen. In contrast, in Ml cells, while SOCSl and CIS mRNA were induced by LL-6, no induction of either SOCS2 or SOCS3 expression was detected. This result highlights cell type-specific differences in the expression of the genes of SOCS family members in response to the same cytokine. In order to examine the spectrum of cytokines that was capable of inducing transcription of the various members of the SOCS gene family, bone marrow cells were stimulated for an hour with a range of cytokines, after which mRNA was extracted and cDNA was synthesised. PCR was then used to assess the expression of SOCS 1, SOCS2, SOCS3 and CIS (Figure 1 IC). In the absence of stimulation, little or no expression of any of the SOCS genes was detectable in bone marrow by PCR. Stimulation of bone marrow cells with a broad array of cytokines appeared capable of up regulating mRNA for one or more members of the SOCS family. IFNγ, for example, induced expression of all four SOCS genes, while erythropoietin, granulocyte colony- stimulating factor, granulocyte-macrophage colony stimulating factor and interleukin-3 induced expression of SOCS2, SOCS3 and CIS. Interestingly, tumor necrosis factor alpha, macrophage colony-stimulating factor and interleukin- 1, which act through receptors that do not fall into the type I cytokine receptor class also appeared capable of inducing expression of SOCS3 and CIS, suggesting that SOCS proteins may play a broader role in regulating signal transduction. As constitutive expression of SOCSl inhibited the response of Ml cells to a range of cytokines, the inventors examined whether phosphorylation of the cell surface receptor component gpl30 and the transcription factor STAT3, which are though to play a central role in LL-6 signal transduction, were affected. These events were compared in the parental Ml and Ml.mpl cell lines and their SOCSl -expressing counterparts. As expected, gpl30 was phyosphorylated rapidly in response to LL-6 in both parental lines, however, this was reduced in the cell lines expressing SOCSl (Figure 12A). Likewise, STAT3 phosphorylation was also reduced in response to LL-6 in those cell lines expressing SOCS l (Figure 12A). Consistent with a reduction in STAT3 phosphorylation, activation of specific STAT/DNA binding complexes, as determined by electrophoretic mobility shift assay, was also reduced. Notably, there was a failure to form SLF-A (containing STAT3) and SIF-B(STAT1/STAT3 heterodimer), the major STAT complexes induced in Ml cells stimulated with LL-6 (Figure 12B). Similarly, constitutive expression of SOCSl also inhibited LFNγ-stimulating formation of SIF-C (STATl homodimer; Figure 12B). These experiments are consistent with the proposal that SOCSl inhibits signal transduction upstream of receptor and STAT phosphorylation, potentially at the level of the JAK kinases. The ability of SOCS 1 to inhibit signal transduction and ultimately the biological response to cytokines suggest that, like the SH2-containing phosphatase SHP-1 [Ihle et al, 1994; Yi et al, 1993], the SOCS proteins may play a central role in controlling the intensity and/or duration of a cell's response to a diverse range of extracellular stimuli by suppressing the signal transduction process. The evidence provided here indicates that the SOCS family acts in a classical negative feedback loop for cytokine signal transduction. Like other genes such as OSM, expression of genes encoding the SOCS proteins is induced by cytokines through the activation of STATs. Once expressed, it is proposed that the SOCS proteins inhibit the activity of JAKs and so reduce the phosphorylation of receptors and STATs, thereby suppressing signal transduction and any ensuing biological response. Importantly, inhibition of STAT activation will, over time, lead to a reduction in SOCS gene expression, allowing cells to regain responsiveness to cytokines. EXAMPLE 17 DATABASE SEARCHES The NCBI genetic sequence database (Genbank), which encompasses the major database of expressed sequence tags (ESTs) and TIGR database of human expressed sequence tags, were searched for sequences with similarity to a concensus SOCS box sequence using the TFASTA and MOTIF/PATTERN algorithms [Pearson, 1990; Cockwell and Giles, 1989]. Using the software package SRS [Etzold et al, 1996], ESTs that exhibited similarity to the SOCS box (and their partners derived from sequencing the other end of cDNAs) were retrieved and assembled into contigs using Autoassembler (Applied Biosystems, Foster City, CA). Consensus nucleotide sequences derived from overlapping ESTs were then used to search the various databases using BLASTN [Altschul et al, 1990]. Again, positive ESTs were retrieved and added to the contig. This process was repeated until no additional ESTs could be recovered. Final consensus nucleotide sequences were then translated using Sequence Navigator (Applied Biosystems, Foster City, CA). The ESTs encoding the new SOCS proteins are as follows: human SOCS4 (EST81149, EST180909, EST182619, ya99H09, ye70co4, yh53c09, ytϊ77gl 1, yh87h05, yi45h07, yj04e06, yql2h06, yq56a06, yq60e02, yq92g03, yq97h06, yr90f01, yt69c03, yv30a08, yv55f07, yv57h09, yv87h02, yv98el l, yw68dl0, yw82a03, yx08a07, yx72h06, yx76b09, yy37h08, yy66b02, za81f08, zbl8f07, zc06e08, zdl4g06, zd51hl2, zd52b09, ze25gl 1, ze69f02, zf54f03, zh96e07, zv66hl2, zs83a08 and zs83g08). mouse SOCS-4 (mc65f04, mf42e06, mplOclO, mr81g09, and mtl9hl2). human SOCS-5 (EST15B103, EST15B105, EST27530 and zf50f01). mouse SOCS-5 (mc55a01, mh98f09, my26hl2 and ve24e06). human SOCS-6 (yf61e08, yf93a09, yg05fl2, yg41fD4, yg45c02, yhl lflO, yhl3b05, zc35al2, ze02h08, zl09a03, zl69el0, zn39d08 and zo39e06). mouse SOCS-6 (mc04c05, md48a03, mf31d03, mh26b07, mh78el l, mh88h09, mh94h07, mi27h04 and mj29c05, mp66g04, mw75g03, va53b05, vb34h02, vc55d07, vc59e05, vc67d03, vc68dl0, vc97h01, vc99c08, vd07h03, vd08c01, vd09bl2, vdl9b02, vd29a04 and vd46d06). human SOCS-7 (STS WI30171, EST00939, EST12913, yc29b05, yp49fl0, ztl0f03 and zx73g04). mouse SOCS-7 (mj39a01 and vi52h07). mouse SOCS-8 (mj6e09 and vj27a029). human SOCS-9 (CSRL-82f2-u, EST114054, yy06b07, yy06g06, zr40c09, zr72h01, yx92c08, yx93b08 and hfe0662). mouse SOCS-9 (me65d05). human SOCS-10 (aa48hl0, zp35h01, zp97hl2, zq08h01, zr34g05, EST73000 and HSDHEI005). mouse SOCS-10 (mbl4dl2, mb40f06, mg89bl 1, mq89el2, mp03gl2 and vh53cl l). human SOCS-11 (zt24h06 and zr43b02). human SOCS-13 (EST59161). mouse SOCS-13 (ma39a09, me60c05, mi78g05, mklOcl 1, mo48gl2, mp94a01, vb57c07 and vh07cl 1). human SOCS-14 (mi75e03, vd29hl 1 and vd53g07). SUBSΉTUTE SHEET (Rule 26) EXAMPLE 18 cDNA CLONING Based on the concensus sequences derived from overlapping ESTs, oligonucleotides were designed that were specific to various members of the SOCS family. As described above, oligonucleotides were labelled and used to screen commerically available genomic and cDNA libraries cloned with λ bacteriophage. Genomic and/or cDNA clones covering the entire coding region of mouse SOCS4, mouse SOCS5 and mouse SOCS6 were isolated. The entire gene for SOCS 15 is on the human 12pl3 BAC (Genbank Accession Number HSU47924) and the mouse chromosome 6 BAC (Genbank Accession Number AC002393). Partial cDNAs for mouse SOCS7, SOCS9, SOCSIO, SOCSl 1, SOCS 12, SOCS 13 and SOCS 14 were also isolated. EXAMPLE 19 NORTHERN BLOTS AND rtPCR Northern blots were performed as described above. The sources of hybridisation probes were as follows; (i) the entire coding region of the mouse SOCSl cDNA, (ii) a 1059 bp PCR product derived from coding region of SOCS5 upstream of the SH2 domain, (iii) the entire coding region of the mouse SOCS6 cDNA, (iv) a 790 bp PCR product derived from the coding region of a partial SOCS7 cDNA and (v) a 1200 bp Pst I fragment of the chicken glyceraldehyde 3- phosphate dehydrogenase (GAPDH) cDNA. EXAMPLE 20 ADDITIONAL MEMBERS OF SOCS FAMILY SOCSl, SOCS2 and SOCS3 are members of the SOCS protein family identified in Examples 1-16. Each contains a central SH2 domain and a conserved motif at the C-terminus, named the SOCS box. In order to isolate further members of this protein family, various DNA databases were searched with the amino acid sequence corresponding to conserved residues of the SOCS box. This search revealed the presence of human and mouse ESTs encoding twelve further members of the SOCS protein family (Figure 13). Using this sequence information cDNAs encoding SOCS4, SOCS5, SOCS6, SOCS7, SOCS9, SOCSIO, SOCSl 1, SOCS 12, SOCS 13, SOCS 14 and SOCS 15 have been isolated. Further analysis of contigs derived from ESTs and cDNAs revealed that the SOCS proteins could be placed into three groups according to their predicted structure N-terminal of the SOCS box. The three groups are those with (i) SH2 5 domains, (ii) WD-40 repeats and (iii) ankyrin repeats. 10 EXAMPLE 21 SOCS PROTEIN WITH SH2 DOMAINS Eight SOCS proteins with SH2 domains have been identified. These include SOCSl, SOCS2 15 and SOCS3, SOCS5, SOCS9, SOCSl 1 and SOCS14 (Figure 13). Full length cDNAs were isolated for mouse SOCS5 and SOCS 14 and partial clones encoding mouse SOCS9 and SOCS 14. Analysis of primary amino acid sequence and genomic structure suggest that pairs of these proteins (SOCSl and SOCS3, SOCS2 and CIS, SOCS5 and SOCS 14 and SOCS9 and SOCSl 1) are most closely related (Figure 13). Indeed, the SH2 domains of SOCS5 and 20 SOCS14 are almost identical (Figure 13B), and unlike CIS, SOCSl, SOCS2 and SOCS3, SOCS5 and SOCS 14 have an extensive, though less well conserved, N-terminal region preceding their SH2 domains (Figure 13 A). EXAMPLE 22 25 SOCS PROTEINS WITH WD-40 REPEATS Four SOCS proteins with WD-40 repeats were identified. As with the SOCS proteins with SH2 domains, pairs of these proteins appeared to be closely related. Full length cDNAs of mouse SOCS4 and SOCS6 were isolated and shown to encode proteins containing eight WD- 30 40 repeats N-terminal of the SOCS box (Figure 13) and SOCS4 and SOCS6 share 65% amino acid similarity. SOCS 15 was recognised as an open reading frame upon sequencing B ACs from human chromosome 12pl3 and the syntenic region of mouse chromosome 6 [Ansari-Lari et al, 1997]. In the human, chimp and mouse, SOCS 15 is encoded by a gene with two coding exons that lies within a few hundred base pairs of the 3 ' end of the triose phosphate isomerase (TPI) gene, but which is encoded on the opposite strand to TPI (9). In addition to a C-terminal SOCS box, the SOCS 15 protein contains four WD-40 repeats. Interestingly, within the EST databases, there is a sequence of a nematode, an insect and a fish relative of SOCS 15. SOCS 15 appears most closely related to SOCS 13. EXAMPLE 23 SOCS PROTEINS WITH ANKYRIN REPEATS Three SOCS proteins with ankyrin repeats were identified. Analysis of partial cDNAs of mouse SOCS7, SOCSIO and SOCS 12 demonstrated the presence of multiple ankyrin repeats. EXAMPLE 24 EXPRESSION PATTERN OF SOCS PROTEINS The expression of mRNA from representative members of each class of SOCS proteins - SOCS 1 and SOCS5 from the SH2 domain group, SOCS6 from the WD-40 repeat group and SOCS7 from the ankyrin repeat group was examined. As shown above, SOCSl mRNA is found in abundance in the thymus and at lower levels in other adult tissues. Since transcription of the SOCSl gene is induced by cytokines, the inventors sought to determine whether levels of SOCS5, SOCS6 and SOCS7 mRNA increased upon cytokine stimulation. In the livers of mice injected with LL-6, SOCS 1 mRNA is detectable after 20 min and decreases to background levels within 2 hours. In contrast, the kinetics of SOCS5 mRNA expression are quite different, being only detectable 12 to 24 hours after IL-6 injection. SOCS6 mRNA appears to be expressed constitutively while SOCS7 mRNA was not detected in the liver either before injection of LL-6 or at any time after injection. Expression of these genes was also examined after cytokine stimulation of the factor-dependent cell line FDCP-1 engineered to express bcl-w. Again, while SOCS6 mRNA was expressed constitutively. EXAMPLE 25 SOCS4 Mouse and human SOCS4 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS4 cDNAs are tabulated below (Tables 4.1 and 4.2). Using sequence information derived from mouse ESTs several oligonucleotides were designed and used to screen, in the conventional manner, a mouse thymus cDNA library cloned into λ-bacteriophage. Two cDNAs encoding mouse SOCS4 were isolated and sequenced in their entirety (Figure 15) and shown to overlap the mouse ESTs identified in the database (Table 4.1 and Figure 17). These cDNAs include a region of 5' untranslated region, the entire mouse SOCS4 coding region and a region of 3' untranslated region (Figure 17). Analysis of the sequence confirms that the SOCS4 cDNA encodes a SOCS Box at its C-terminus and a series of 8 WD-40 repeats before the SOCS Box (Figures 17 and 16). The relationship of the two sequence contigs of human SOCS4 (h4.1 and h4.2) to the experimentally determined mouse SOCS4 cDNA sequence is shown in Figure 17. The nucleotide sequence of the two human contigs is listed in Figure 18. SEQ ID NO: 13 and 14 represent the nucleotide sequence of murine SOCS4 and the corresponding amino acid sequence. SEQ ID NOs: 15 and 16 are SOCS4 cDNA human contigs h4.1 and h4.2, respectively. EXAMPLE 26 SOCS5 Mouse and human SOCS5 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS5 cDNAs are tabulated below (Tables 5.1 and 5.2). Using sequence information derived from mouse and human ESTs, several oligonucleotides were designed and used to screen, in the conventional manner, a mouse thymus cDNA library, a mouse genomic DNA library and a human thymus cDNA library cloned into λ-bacteriophage . A single genomic DNA clone (57-2) and (5-3-2) cDNA clone encoding mouse SOCS5 were isolated and sequenced in their entirety and shown to overlap with the mouse ESTs identified in the database (Figures 19 and 20A). The entire coding region, in addition to a region of 5' and 3' untranslated regions of mouse SOCS5 appears to be encoded on a single exon (Figure 19). Analysis of the sequence (Figure 20) confirms that SOCS5 genomic and cDNA clones encode a protein with a SOCS box at its C- terminus in addition to an SH2 domain (Figure 19 and 20B). The relationship of the human SOCS5 contig (h5.1; Figure 21) derived from analysis of cDNA clone 5-94-2 and the human SOCS5 ESTs (Table 5.2) to the mouse SOCS5 DNA sequence is shown in Figure 19. The nucleotide sequence and corresponding amino acid sequence of murine SOCS5 are shown in SEQ ID NOs: 17 and 18, respectively. The human SOCS5 nucleotide sequence is shown in SEQ ID NO: 19. EXAMPLE 27 SOCS6 Mouse and human SOCS6 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS6 cDNAs are tabulated below (Tables 6.1 and 6.2). Using sequence information derived from mouse ESTs, several oligonucleotides were designed and use to screen, in the conventional manner, a mouse thymus cDNA library. Eight cDNA clones (6-1 A, 6-2A, 6-5B, 6-4N, 6-18, 6-29, 6-3N, 6-5N) cDNA clone encoding mouse SOCS6 were isolated and sequenced in their entirety and shown to overlap with the mouse ESTs identified in the database (Figures 22 and 23A). Analysis of the sequence (Figure 23) confirms that the mouse SOCS6 cDNA clones encode a protein with a SOCS box at its C-terminus in addition to a eight WD-40 repeats (Figures 22 and 23B). The relationship of the human SOCS-6 contigs (h6.1 and h6.2 ; Figure 24) derived from analysis of human SOCS6 ESTs (Table 6.2) to the mouse SOCS6 DNA sequence is shown in Figure 22. The nucleotide and corresponding amino acid sequences of murine SOCS6 are shown in SEQ LD NOs: 20 and 21, respectively. SOCS6 human contigs h6.1 and h6.2 are shown in SEQ ID NOs: 22 and 23, respectively. EXAMPLE 28 SOCS7 Mouse and human SOCS7 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS-7 cDNAs are tabulated below (Tables 7.1 and 7.2). Using sequence information derived from mouse ESTs, several oligonucleotides were designed and use to screen, in the conventional manner, a mouse thymus cDNA library. One cDNA clone (74-10A-11) cDNA clone encoding mouse SOCS 7 was isolated and sequenced in its entirety and shown to overlap with the mouse ESTs identified in the database (Figures 25 and 26A). Analysis of the sequence (Figure 26) suggests that mouse SOCS7 encodes a protein with a SOCS box at its C-terminus, in addition to several ankyrin repeats (Figure 25 and 26B). The relationship of the human SOCS7 contigs (h7.1 and h7.2 ; Figure 27) derived from analysis of human SOCS7 ESTs (Table 7.2) to the mouse SOCS7 DNA sequence is shown in Figure 25. The nucleotide and corresponding amino acid sequences of murine SOCS7 are shown in SEQ ID NOs: 24 and 25, respectively. The nucleotide sequence of SOCS7 human contigs h7.1 and h7.2 are shown in SEQ ID NOs: 26 and 27, respectively. EXAMPLE 29 SOCS8 ESTs derived from mouse SOCS8 cDNAs are tabulated below (Table 8.1). As described for other members of the SOCS family, it is possible to isolate cDNAs for mouse SOCS8 using sequence information derived from mouse ESTs. The relationship of the ESTs to the predicted coding region of SOCS8 is shown in Figure 28. With the nucleotide sequence obtained from the ESTs shown in Figure 29A and the partial amino acid sequence of SOCS8 shown in Figure 29B. The nucleotide sequence and corresponding amino acid sequences for murine SOCS 8 are shown in SEQ ID NOs:28 and 29, respectively. EXAMPLE 30 SOCS9 Mouse and human SOCS-9 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS9 cDNAs are tabulated below (Tables 9.1 and 9.2). The relationship of the mouse SOCS9 contigs (m9.1; Figure 9.2) derived from analysis of the mouse SOCS9 EST (Table 9.1) to the human SOCS-9 DNA contig (h9.1; Figure 32) derived from analysis of human SOCS9 ESTs (Table 9.2) is shown in Figure 31. Analysis of the sequence (Figure 32) indicates that the human SOCS9 cDNA encodes a protein with a SOCS box at its C-terminus, in addition to an SH2 domain (Figure 30). The nucleotide sequence of muring SOCS9 cDNA is shown in SEQ ID NO:30. The nucleotide sequence of human SOCS9 cDNA is shown in SEQ ID NO:31. EXAMPLE 31 SOCSIO Mouse and human SOCSIO were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS 10 cDNAs are tabulated below (Table 10.1 and 10.2). Using sequence information derived from mouse ESTs, several oligonucleotides were designed and use to screen, in the conventional manner, a mouse thymus cDNA library. Four cDNA clones (10-9, 10-12, 10-23 and 10-24) encoding mouse SOCSIO were isolated, sequenced in their entirety and shown to overlap with the mouse and human ESTs identified in the database (Figures 33 and 34). Analysis of the sequence (Figure 34) indicates that the mouse SOCSIO cDNA clone is not full length but that it does encode a protein with a SOCS box at its C-terminus, in addition to several ankyrin repeats (Figure 33). The relationship of the human SOCSIO contigs (hlθ.1 and hlθ.2 ; Figure 35) derived from analysis of human SOCSIO ESTs (Table 10.2) to the mouse SOCSIO DNA sequence is shown in Figure 33. Comparison of mouse cDNA clones and ESTs with human ESTs suggests that the 3' untranslated regions of mouse and human SOCSIO differ significantly. The nucleotide sequence of murine SOCSIO is shown in SEQ ID NO:32 and the nucleotide sequence of SOCSIO human contigs hlθ.1 and hlθ.2 are shown in SEQ ID NOs:33 and 34, respectively. EXAMPLE 32 SOCS11 Human SOCS 11 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from human SOCSl 1 cDNAs are tabulated below (Table 11.1 and 11.2). The relationship of the human SOCSl 1 contigs (hi 1.1; Figure 36A, B), derived from analysis ESTs (Table 11.2) to the predicted encoded protein, is shown in Figure 37. Analysis of the sequence indicates that the human SOCSl 1 cDNA encodes a protein with a SOCS box at its C-terminus, in addition to an SH2 domain (Figure 37 and 36B). The nucleotide sequence and corresponding amino acid sequence of human SOCS 11 are represented in SEQ ID NOs:35 and 36, respectively. EXAMPLE 33 SOCS12 Mouse and human SOCS- 12 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS12 cDNAs are tabulated below (Tables 12.1 and 12.2). Using sequence information derived from mouse ESTs, several oligonucleotides were designed and use to screen, in the conventional manner, a mouse thymus cDNA library. Four cDNA clones (10-9, 10-12, 10-23 and 10-24) encoding mouse SOCS 12 were isolated, sequenced in their entirety and shown to overlap with the mouse and human ESTs identified in the database (Figures 38 and 39). Analysis of the sequence (Figure 39 and 40) indicates that the SOCS 12 cDNA clone encodes a protein with a SOCS box at its C-terminus, in addition to several ankyrin repeats (Figure 38). The relationship of the human SOCS 12 contigs (hl2.1 and hl2.2 ; Figure 40) derived from analysis of human SOCS 12 ESTs (Table 12.2) to the mouse SOCS 12 DNA sequence is shown in Figure 38. Comparison of mouse cDNA clones and ESTs with human ESTs suggests that the 3' untranslated regions of mouse and human SOCS 12 differ significantly. The nucleotide sequence of SOCS12 is shown in SEQ ID NO:37. The nucleotide sequence of human SOCS12 contigs hi 2.1 and hi 2.2 are shown in SEQ ID NOs: 38 and 39, respectively. EXAMPLE 34 SOCS13 Mouse and human SOCS-13 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS 13 cDNAs are tabulated below (Tables 13.1 and 13.2). Using sequence information derived from mouse ESTs, several oligonucleotides were designed and use to screen, in the conventional manner, a mouse thymus and a mouse embryo cDNA library. Three cDNA clones (62-1, 62-6- 7 and 62-14) encoding mouse SOCS 13 were isolated, sequenced in their entirety and shown to overlap with the mouse ESTs identified in the database (Figure 41 and 42 A). Analysis of the sequence (Figure 42) indicates that the mouse SOCS 13 cDNA encodes a protein with a SOCS box at its C-terminus, in addition to a potential WD-40 repeat (Figure 41 and 42B). The relationship of the human SOCS 13 contigs (hi 3.1 and hi 3.2 ; Figure 43) derived from analysis of human SOCS 13 ESTs (Table 13.2) to the mouse SOCS 13 DNA sequence is shown in Figure 41. The nucleotide sequence and corresponding amino acid sequence of murine SOCS 13 and shown in SEQ ID NOs: 40 and 41, respectively. The nucleotide sequence of human SOCS 13 contig hi 3.1 is shown in SEQ ID NO:42. EXAMPLE 35 SOCS14 Mouse and human SOCS-14 were recognized through searching EST databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS 14 cDNAs are tabulated below (Tables 14.1 and 14.2). Using sequence information derived from mouse and human ESTs, several oligonucleotides were designed and use to screen, in the conventional manner, a mouse thymus cDNA library, a mouse genomic DNA library and a human thymus cDNA library cloned into λ-bacteriophage . A single genomic DNA clone (57- 2) and (5-3-2) cDNA clone encoding mouse SOCS 14 were isolated and sequenced in their entirety and shown to overlap with the mouse ESTs identified in the database (Figures 44 and 45 A). The entire coding region, in addition to a region of 5' and 3' untranslated regions, of mouse SOCS 14 appears to be encoded on a single exon (Figure 44). Analysis of the sequence (Figure 45) confirms that SOCS 14 genomic and cDNA clones encode a protein with a SOCS box at its C-terminus in addition to an SH2 domain (Figure 44 and 45B). The relationship of the human SOCS 14 contig (hl4.1; Figure 14.3) derived from analysis of cDNA clone 5-94-2 and the human SOCS 14 ESTs (Table 14.2) to the mouse SOCS 14 DNA sequence is shown in Figure 44. The nucleotide sequence and corresponding amino acid sequence of murine SOCS 14 are shown in SEQ ID NOs: 43 and 44, respectively. SU BSΠΠΠB SHEET αw, ag EXAMPLE 36 SOCS15 Mouse and human SOCS 15 were recognized through searching DNA databases using the SOCS box consensus (Figure 13). Those ESTs derived from mouse and human SOCS 15 cDNAs are tabulated below (Tables 15.1 and 15.2), as are a mouse and human BAC that contain the entire mouse and human SOCS- 15 genes. Using sequence information derived from the ESTs and the BACs it is possible to predict the entire amino acid sequence of SOCS 15 and as described for the other SOCS genes it is feasible to design specific oligonucleotide probes to allow cDNAs to be isolated. The relationship of the BACs to the ESTs is shown in Figure 46 and the nucleotide and predicted amino acid sequence of the SOCS-15, derived from the mouse and human BACs is shown in Figures 47 and 48. The nucleotide sequence and corresponding amino acid sequence of murine SOCS 15 are shown in SEQ ID NOs:46 and 47, respectively. The nucleotide and corresponding amino acid sequence of human SOCS 15 are shown in SEQ ID NO:48 and 49, respectively. EXAMPLE 37 SOCS INTERACTION WITH JAK2 KINASE These Examples show interaction between SOCS and JAK2 kinase. Interaction is mediated via the SH2 domain of SOCSl, 2, 3 and CIS. The interaction resulted in inhibition of JAK2 kinase activity by SOCSl (Figure 49). General interaction between JAK2 and SOCSl, 2, 3, and CIS is shown in Figure 50. The following methods are employed: Immunoprecipitation: Cos 6 cells were transiently transfected by electroporation and cultured for 48 hours. Cells were then lysed on ice in lysis buffer (50 mM Tris/HCL, pH 7.5, 150 mM NaCl, 1% v/v Triton-X-100, 1 mM EDTA, 1 mM Naf, 1 mM Na 3 VO 4 ) with the addition of complete protease inhibitors (Boehringer Mannheim), centrifuged at 4°C (14,000 x g, 10 min) and the supernatant retained for immunoprecipitation. JAK2 proteins were immunoprecipitated using 5 μl anti-JAK2 antibody (UBI). Antigen-antibody complexes were recovered using protein A-Sepharose (30 μl of a 50% slurry). Western blotting: Immunoprecipitates were analysed by sodium dodecyl sulphate (SDS) - 5 polyacrylamide gel electrophoresis (PAGE) under reducing conditions. Protein was then electrophoretically transferred to nitrocellulose, blocked overnight in 10% w/v skim-milk and washed in PBS/0.1% v/v Tween-20 (Sigma) (wash buffer) prior to incubation with either anti- phosphotyrosine antibody (4G10) (1:5000, UBI), anti-FLAG antibody (1.6 μg/ml) or anti-JAK2 antibody (1:2000, UBI) diluted in wash buffer/1% w/v BSA for 2 hr. Nitrocellulose blots were 10 washed and primary antibody detected with either peroxidase-conjugated sheep anti-rabbit immunoglobulin (1:5000, Silenus) or peroxidase-conjugated sheep anti-mouse immunoglobulin (1:5000, Silenus) diluted in wash buffer/1% w/v BSA. Blots were washed and antibody binding visualised using the enhanced chemiluminescence (ECL) system (Amersham, UK) according to the manufacturers' instructions. 15 In-vitro kinase assay: An in vitro kinase assy was performed to assess intrinsic JAK2 kinase catalytic activity. JAK2 protein were immunopreciptated as described, washed twice in kinase assay buffer (50 mM NaCl, 5 mM MgCl 2 , 5 mM MnC12, 1 mM NaF, 1 mM Na 3 VO 4 , 10 mM HEPES, pH 7.4) and suspended in an equal volume of kinase buffer containing 0.25 μCi/ml (γ- 20 32 P)-ATP (30 min, room temperature). Excels (γ- P)-ATP was removed and the immunoprecipitates analysed by SDS/PAGE under reducing conditions. Gels were subjected to a mild alkaline hydrolysis by treatment with 1 M KOH (55°C, 2 hours) to remove phosphoserine and phosphothreonine. Radioactive bands were visualised with IMAGEQUANT software on a Phosphorlmage system (Molecular Dynamics, Sunnyvale, CA, USA). 25 EXAMPLE 38 MAKING SOCS l KNOCKOUT CONSTRUCTS Diagrams of plasmid constructs and knockout constructs are shown in Figures 51-53. The 30 genomic SOCS-1 clone 95-11-10 was digested with the restriction enzymes BamHI and EcoRl to obtain a 3.6Kb DNA fragment 3' of the coding region (SOCS-1 exon), which was used as the 3' arm in the SOCS-1 knockout vectors. The ends of this fragment were then blunted. This fragment was then ligated into the following vectors: pBgalpAloxNeo and pBgalpAloxNeoTK which had been linearized at the unique Xhol site and then blunted. This ligation resulted in the formation of the following vectors: 3'SOCS-l arm in pBgalpAloxNeo and 3'SOCS-l arm in pBgalpAloxNeoTK The 5' arm of the SOCS-1 knockout vectors was constructed by using PCR to generate a 2.5Kb PCR product from the genomic SOCS-1 clone 95-11-10 just 5' of the SOCS-1 coding region (SOCS-1 exon). The oligo's used to generate this product were: 5' oligo (sense) (2465) AGCT AGA TCT GGA CCC TAC AAT GGC AGC [SEQ ID NO:49] 3' oligo (antisense) (2466) AGCT AG ATC TGC CAT CCT ACT CGA GGG GCC AGC TGG [SEQ ID NO:50] The PCR product was then digested with the restriction enzyme Bglll, to generate Bglll ends to the PCR product. This 5' SOCS-1 PCR product,with BglLI, ends was then ligated as follows: 3'SOCS-l arm in pBgalpAloxNeo and 3'SOCS-l arm in pBgalpAloxNeoTK, which had been linearized with the unique restriction enzyme BamHI. This resulted in the following vectors being formed: 5'&3'SOCS-l arms in pBgalpAloxNeo and 5'&3'SOCS-l arms in pBgalpAloxNeoTK These were the final SOCS-1 knockout constructs. Both these constructs lacked the entire SOCS-1 coding region (SOCS-1 EXON), being replaced with portions of the Bgal, B globin polyA, PGK promoter, neomycin and PGK polyA sequences. The 5'&3'SOCS-l arms in pBgalpAloxNeoTK vector also contained the tymidine kinase gene sequence, between the neomycin and PGK poly A sequences. The vectors: 5'&3'SOCS-l arms in pBgalpAloxNeo and 5'&3'SOCS-l arms in pBgalpAloxNeoTK were linearized with the unique restriction enzyme NotI and then transfected into Embryonic stem cells by electroporation. Clones which were resistant to neomycin were selected and analysed by southern blot to determine if they contained the correctly integrated SOCS-1 targeting sequence. In order to determine if correct integration had occurred, genomic DNA from the neomycin resistant clones was digested with the restriction enzyme EcoRl. The digested DNA was then blotted onto nylon filters and probed with a 1.5Kb EcoRl /Hind III DNA fragment, which was further 5' of the 5'arm sequence used in the knockout constructs. The band sizes expected for correct integration were: Wild type SOCS-1 allele 5.4Kb SOCS-1 knockout allele 8.2Kb in 5'&3'SOCS-l arms in pBgalpAloxNeo or 11Kb in 5'&3'SOCS-l arms in pBgalpAloxNeoTK transfomed cells. Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more of said steps or features. Table 4.1 Summary of ESTs derived from mouse SOCS-4 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-4 Mouse mc65f04 5' EST0549700 dl3.5-14.5 mouse m4.1 embryo mf42e06 5' EST0593477 dl3.5-14.5 mouse m4.1 embryo mplOclO EST0747905 d 8.5 mouse embryo m4.1 mr81g09 EST0783081 d!3 embryo m4.1 mt!9hl2 5' EST0816531 spleen m4.1 Table 4.2 Summary of ESTs derived from human SOCS-4 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-4 Human 27b5 5' EST0534081 retina h4.2 30d2 5' EST0534315 retina h4.2 J0159F 5' EST0461188 foetal heart h4.2 J3802F EST0461428 foetal heart h4.2 EST19523 5' EST0958884 retina h4.2 EST81149 5' EST1011015 placenta h4.2 EST180909 5' EST0951375 Jurkat T- h4.2 lymphocyte EST182619 EST0953220 Jurkat T- h4.1 lymphocyte ya99h09 EST0103262 placenta h4.2 ye70c04 5' EST0172673 foeatl liver/spleen h4.2 yh53c09 5' EST0197390 placenta h4.2 3' EST0197391 h4.2 yh77gl l 5' EST0203418 placenta h4.2 3' EST0203419 h4.1 yh87h05 5' EST0204888 placenta h4.1 3' EST0204773 h4.1 yi45h07 EST0246604 placenta h4.2 yj04e06 EST0258541 placenta h4.1 EST0258285 h4.1 yql2h06 EST0309968 foetal liver spleen h4.2 yq56a06 EST0346924 foetal liver spleen h4.2 yq60e02 EST0347259 foetal liver spleen h.4.2 EST0347209 h4.2 yq92g03 5' EST0355932 foetal liver spleen h4.2 3' EST0355884 h4.2 yq97h06 5' EST0357618 foetal liver spleen h4.2 3' EST0357416 h4.2 yr90f01 5' EST0372402 foetal liver spleen h4.2 yt69c03 5' EST0338395 foetal liver spleen h4.2 3' EST0338303 h4.2 yv30a08 3' EST0458506 foetal liver spleen h4.2 yv55f07 5' EST0465391 foetal liver spleen h4.2 3' EST0463331 h4.2 yv57h09 5' EST0464336 foetal liver spleen h4.2 3' EST0458765 h4.2 yv87h02 5' EST0388085 melanocyte h4.2 yv98ell 5' EST0400679 melanocyte h4.2 3' EST0400680 h4.2 ywόδdlO 5' EST0441370 placenta (8-9 wk) h.4.2 yw82a03 5' EST0463005 placenta (8-9 wk) h4.2 3' EST0433678 b.4.1 yx08a07 3' EST0407016 melanoocyte b.4.1 yx72h06 5' EST0435158 melanoocyte h4.2 3' EST0422871 melanoocyte h4.1 yx76b09 5' EST0434011 melanoocyte h4.2 yy37h08 5' EST0451704 melanoocyte h4.2 yy66b02 5' EST0505446 multiple sclerosis h4.2 lesion za81f08 5' EST0511777 foetal lung h4.2 zbl8f07 3' EST0485315 foetal lung b.4.1 zc06e08 5" EST0540473 parathyroid tumor h4.1 3' EST0540354 h4.1 zdl4g06 3' EST0564666 foetal heart h4.1 zd51hl2 3' EST0578099 foetal heart b.4.1 zd52b09 5' EST0582012 foetal heart h4.1 3' EST0581958 h4.1 ze25gl 1 3' EST0679543 foetal heart h4.1 ze69f02 5' EST0635563 retina h4,2 3' EST0635472 h4.1 zf54f03 5' EST0680111 retina h4.2 zh96e07 5' EST0616241 foetal liver spleen h4.2 3' EST0615745 h4.2 zv66hl2 5' EST1043265 8-9w foetus h4.2 zs83a08 5' EST0920072 germinal centre B h4.1 cell 3' EST0920016 h.4.1 zs83g08 5' EST0920121 germinal centre B h4.1 cell 3' EST0920122 h4.1 Table 5.1 Summary of ESTs derived from mouse SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-5 Mouse mc55a01 5' EST0541556 dl3.5-14.5 mouse m5.1 embryo mh98f09 5' EST0638237 placenta m5.1 my26hl2 5' EST0859939 mixed organs m5.1 ve24e06 5' EST0819106 heart m5.1 Table 5.2 Summary of ESTs derived from human SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-5 Human EST15B103 EST0258029 adipose tissue b.5.1 EST15B105 EST0258028 adipose tissue h5.1 EST27530 EST0965892 cerebellum h5.1 zf50f01 5' EST0679820 retina h5.1 Table 6.1 Summary of ESTs derived from mouse SOCS-6 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-6 Mouse mco4c05 5' EST0525832 dl9.5 embryo m6.1 md48a03 EST0566730 dl3.5-14.5 embryo m6.1 mf31d03 EST0675970 dl3.5-14.5 embryo mό.l mh26b07 EST0628752 dl3.5-14.5 placenta mό.l mh78el l EST0637608 dl3.5-14.5 placenta mό.l mh88h09 5' EST0644383 dl3.5-14.5 placenta mό.l mh94h07 5' EST0638078 dl3.5-14.5 placenta mό.l mi27h04 EST0644252 dl3.5-14.5 embryo mό.l mj29c05 EST0664093 dl3.5-14.5 embryo mό.l mpόόg04 5' EST0757905 thymus mό.l mw75g03 5' EST0847938 liver mό.l va53b05 5' EST0901540 dl2.5 embryo mό.l vb34h02 5' EST0930132 lymph node mό.l vc55d07 3' EST1057735 2 cell embryo mό.l vc59e05 3' EST1058201 2 cell embryo mό.l vc67d03 3' EST1057849 2 cell embryo mό.l vcόδdlO 3' EST1058663 2 cell embryo mό.l vc97h01 3' EST1059343 2 cell embryo mό.l vc99c08 EST1059410 2 cell embryo mό.l vd07h03 3' EST1058173 2 cell embryo mό.l vd08c01 3' EST1058275 2 cell embryo mό.l vd09bl2 3' EST1058632 2 cell embryo mό.l vdl9b02 3' EST1059723 2 cell embryo mό.l vd29a04 ? none found mό.l vd46d06 3' ? none found mό.l Table 6.2 Summary of ESTs derived from human SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS- 6 Human yf61e08 5' EST0184387 d73 infant brain h6. ,1 yf93a09 5 ' EST0186084 d73 infant brain h6. .1 yg05fl2 5' EST0191486 d73 infant brain h6. .1 yg41f04 5 1 EST0195017 d73 infant brain h6. .1 yg45c02 5' EST0185308 d73 infant brain h6. ,1 yhllflO 5 ' EST0236705 d73 infant brain h6. .1 yhl3b05 5' EST0237191 d73 infant brain h6. .1 3 ' EST0236958 h6. .2 zc35al2 5' EST0555518 senescent h6. .1 fibroblasts ze02h08 5' EST0603826 foetal heart hβ, .1 3 ' EST0603718 hβ, .2 zl09a03 5' EST0773936 pregnant uterus h6. .1 3 ' EST0773892 h6, .1 zl69el0 5' EST0683363 colon hβ, .1 zn39d08 5 1 EST0718885 endothelial cell hβ .1 zo39e06 5' EST0785947 endothelial cell hβ .1 Table 7.1 Summary of ESTs derived from mouse SOCS-7 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-7 Mouse mj39a01 5' EST0665627 dl3.5/14.5 embryo m7.1 vi52h07 5' EST1267404 d7.5 embryo m7.1 Table 7.2 Summary of ESTs derived from human SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-7 HUMAN STS WI-30171 (G21563) Chromosome 2 h7.2 EST00939 EST0000906 hippocampus h7.1 EST12913 EST0944382 uterus h7.2 yc29b05 ESTO 128727 liver h7.2 yp49fl0 EST0301914 retina h7.2 ztl0f03 5' EST0922932 germinal centre h7.2 B cell 3' EST0921231 h7.1 zx73g04 3' EST1102975 ovarian tumour h7.1 Table 8.1 Summary of ESTs derived from mouse SOCS-8 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-8 Mouse mjl6e09 rl EST0666240 dl3.5/14.5 embryo m8.1 vj27a029 rl EST1155973 heart mδ.l Table 9.1 Summary of ESTs derived from mouse SOCS-9 cDNAs SOCS Species EST name End EST no Library source Contig Mouse me65d05 5' EST0585211 d 13.5/14.5 embryo m9.1 Table 9.2 Summary of ESTs derived from human SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-9 Human CSRL-83f2-u (B06659) chromsome l l h9.1 EST114054 5' EST0939759 placenta h9.1 EST0434504 melanocyte h9.1 yyOόgOό 5' EST0443783 melanocyte h9.1 zr40c09 5 5'' EST0832461 melanocyte, heart, h.9.1 uterus zr72h01 5' EST0892025 melanocyte, heart, h9.1 uterus 3' EST0892026 h9.1 yx92c08 5' EST0441160 melanocyte h9.1 yx93b08 5' EST0441260 melanocyte h9.1 hfe0662 5' EST0889611 foetal heart h.9.1 Table 10.1 Summary of ESTs derived from mouse SOCS-10 cDNAs SOCS Species EST name End EST no Library source Contig Mouse mbl4dl2 EST0549887 dl9.5 embryo mlO.l mb40f06 5' EST0515064 dl9.5 embryo mlO.l mg89bl l 5' EST0630631 dl3.5-14.5 embryo mlO.l mq89el2 5' EST0776015 heart mlO.l mp03gl2 5' EST0741991 heart mlO.l vh53cl l 5' EST1154634 mammary gland mlO.l Table 10.2 Summary of ESTs derived from human SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-10 Human aa48hl0 3' EST1135220 germinal centre B cell hlθ.2 zp35h01 EST0819137 muscle hlθ.2 zp97hl2 EST0835442 muscle hlθ.2 EST0831211 hlθ.2 zqOδhOl EST0835907 muscle hlθ.1 zr34g05 5' EST0834251 melanocyte, heart, hlθ.2 uterus 3' EST0834440 hlθ.2 EST73000 5 EST1004491 ovary hlθ.2 HSDHEI005 ? EST0013906 heart hlθ.2 Table 11.1 Summary of ESTs derived from human SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS- 11 Human zt24h06 rl EST0925023 ovarian tumor 11.1 zr43b02 rl EST0873006 melanocyte, heart, uterus 11.1 si EST0872954 11.1 Table 12.1 Summary of ESTs derived from mouse SOCS-12 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-12 Mouse EST03803 5' EST1054173 day 7.5 emb ml2.1 ectoplacental cone mtl8f02 5 1 EST0817652 3NbMS spleen ml2.1 mzβOglO 5' EST0890872 lymph node ml2.1 va05cll 5' EST0909449 lymph node ml2 . 1 Table 12.2 Summary of ESTs derived from human SOCS-5 cDNAs SOCS Species EST name End EST no Library source Contig SOCS- 12 Human STS-SHGC-13867 Chromosome 2 hl2.2 EST177695 5' EST0948071 Jurkat cells hl2.1 EST64550 5' EST0997367 Jurkat cells hl2.1 EST76868 5' EST1007291 pineal body hl2.2 PMY2369 5' EST1115998 KG-1 hl2.1 yb38f04 5' EST0108807 foetal spleen hl2.1 3' hl2.2 yg74el2 5' EST0224407 d73 brain hl2.1 yhl3g04 5' EST0237226 d73 brain hl2.1 3' EST0236992 hl2.2 yh48b06 5' yh48b06 placenta hl2.2 yh53a05 5' EST0197282 placenta hl2.2 3' ESTO 197486 hl2.2 yn48h09 5' EST0278258 brain hl2.2 3' EST0278259 hl2.2 yn90a09 3' EST0302557 brain hl2.2 yo08f03 5' EST0301790 brain hl2.2 3 * EST0302059 hl2.2 yolleOl 3' ? none found hl2.2 yo63bl2 5' EST0303606 breast hl2.2 3' EST0304085 hl2.2 yq56g02 3' EST0346935 foetal liver spleen hl2.1 zh57c04 3' EST0594201 foetal liver spleen hl2.2 zh79h01 3' EST0598945 foetal liver spleen hl2.2 zh99al 1 3' EST0618570 foetal liver spleen hl2.2 zo92hl2 5' EST0803392 ovarian cancer hl2.1 3' EST0803393 hl2.2 zs48c01 5' EST0925714 germinal centre hi 2.1 B cell 3' EST0925530 hi 2.2 zs45h02 EST0932296 germinal centre hl2.2 B cell Table 13.1 Summary of ESTs derived from mouse SOCS-13 cDNAs SOCS Species EST name End EST no Library source Contig SOCS- 13 Mouse ma39c09 EST0517875 day 19.5 embryo ml3.1 me60c05 5' EST0584950 day 13.5/14.5 embryo ml3.1 mi78g05 5' EST0653834 day 19.5 embryo ml3.1 mklOcl l 5' EST0735158 day 19.5 embryo ml3.1 mo48gl2 5' EST0745111 day 10.5 embryo ml3.1 mp94a01 5' EST0762827 thymus ml3.1 vb57c07 5' EST1028976 day 11.5 embryo ml3.1 vh07cl l 5' EST1117269 mammary gland m 13.1 Table 13.2 Summary of ESTs derived from human SOCS-13 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-13 Human EST59161 5' EST0992726 infant brain hl3.1 Table 14.1 Summary of ESTs derived from mouse SOCS-14 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-14 mouse mi75e03 5' EST0651892 dl9.5 embryo ml4.1 vd29hl l EST1067080 2 cell embryo ml4.1 vd53g07 5' EST1119627 2 cell embryo ml4.1 Table 15.1 Summary of ESTs derived from mouse SOCS-15 cDNAs SOCS Species EST name End EST no Library source Contig SOCS- 15 Mouse mh29b05 5' EST0628834 placenta ml5.1 mh98h09 5' EST0638243 placenta ml5.1 ml45a02 5' EST0687171 testis ml5.1 mu43al0 5' EST851588 thymus ml5.1 my38c09 5' EST878461 pooled organs ml5.1 vj37h07 5' EST1174791 diaphragm ml5.1 AC002393 Chromosome 6 ml5.1 BAC Table 15.2 Summary of ESTs derived from human SOCS-15 cDNAs SOCS Species EST name End EST no Library source Contig SOCS-15 Human EST98889 5' EST1026568 thyroid hl5.1 ne48bo5 3' EST1138057 colon tumour hl5.1 ybl2hl2 5' EST0098885 placenta hl5.1 3' EST0098886 hl5.1 HSU47924 Chromosome 12 hi 5.1 BAC BIBLIOGRAPHY: Alexander WS, Metcalf D and Dunn AR (1995). Embo Journal 14, 5569-78. Altschul, S.F. Gish, W. Miller, W. Myers, E.W. & Lipman, D.J. (1990) J. Mol. Biol. 215, 403-10. Ansari-Lari, M.A., Shen, Y., Munzy, D.M., Lee, W. and Gibbs, R.A. (1997) Genome. Res. 7, 268-280. Bazan JF (1990). [Review]. Immunology Today 11, 350-4. Bork, P. (1993) Proteins: Struct. Funct. Genet. 17, 363-374. Cockwell, L.Y. and Giles, I.G. (1989) Comp. Appl. Biosci. 5, 227-232. Cutler RL, Liu L, Damen JE and Krystal G (1993). Journal of Biological Chemistry 268, 21463-5. Darnell J Jr., Kerr IM and Stark GR (1994). Science 264, 1415-21. David M, Petricoin E3, Benjamin C, Pine R, Weber MJ and Larner AC (1995). Science 269, 1721-3. David M, Wong L, Flavell R, Thompson SA, Wells A, Larner AC and Johnson GR (1996). Journal of Biological Chemistry 271, 9185-8. Dugaiczyk A, Haron JA, Stone EM, Dennison OE, Rothblum KN and Schwartz RJ (1983). Biochemistry 22, 1605- 13. Durbin JE, Hackenmiller R, Simon MC and Levy DE (1996). Cell 84, 443-50. SUBSΉTUTΈ SHEET (Rule 26) Etzold, T., Ulyanov, A. and Argos, P. (1996) Methods Enzymol. 266, 114-28. Gearing DP, Nicola NA, Metcalf D, Foote S, Willson TA, Gough NM and Williams L (1989). BioTechnology 7, 1157-1161. Gupta S, Yan H, Wong LH, Ralph S, Krolewski J and Schindler C (1996). Embo Journal 15, 1075-84. Hilton DJ (1994). An introduction to cytokine receptors, p8-16 in Guidebook to Cytokines and Their Receptors, Eds: N. A. Nicola. Oxford University Press: Oxford. Hilton DJ, Hilton AA, Raicevic A, Rakar S, Harrison-Smith M, Gough NM, Begley CG, Metcalf D, Nicola NA and Willson TA (1994). Embo Journal 13, 4765-75. Hilton DJ, Watowich SS, Katz L and Lodish HF (1996). J. Biol. Chem. 271, 4699-4708. Ichikawa Y (1969). Journal of Cellular Physiology 74, 223-34. Ihle JN (1995). Nature 377, 591-4. Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K and Silvennoinen O (1995). Annual Review of Immunology 13, 369-98. Kaplan MH, Schindler U, Smiley ST and Grusby MJ (1996a). Immunity 4, 313-9. Kaplan MH, Sun YL, Hoey T and Grusby MJ (1996b). Nature 382, 174-179. Levy DE and Stark GR (1996). Molecular & Cellular Biology 16, 369-75. Metcalf D, Wilson TA, Hilton DJ, DiRago L and Mifsud S. (1995) Leukaemia 9, 1556-1564. Meraz MA, White JM, Sheehan KC, Bach EA, Rodig SJ, Dighe AS, Kaplan DH, Riley JK, Greenlund AC, Campbell D, Carver-Moore K, DuBois RN, Clark R, Aguet M and Schreiber RD (1996). Cell 84, 431-42. Mizushima S and Nagata S (1990). Nucleic Acids Research 18, 5322. Murakami M, Narazaki M, Hibi M, Yawata H, Yasukawa K, Hamaguchi M, Taga T and Kishimoto T (1991). Proc. Natl. Acad. Sci. USA 88, 11349-11353. Neer, E.J., Schmidt, C.J., Nambudripad, R. and Smith, T.F. (1994) Nature 371, 297-300. Nicola NA( (1994). Guidebook to Cytokines and Their Receptors. Oxford University Press: Oxford. Nicola, NV, Viney E, Hilton DJ, Roberts B and Wilson T. (1996) Growth Factors 13, 141- 149. Novak U, Harpur AG, Paradiso L, Kanagasundaram V, Jaworowski A, Wilks AF and Hamilton JA (1995). Blood 86, 2948-56. Pearson WR and Lipman DJ. (1988) Proc. Natl. Acad. Sci. USA 85, 2444-8. Pearson WR. (1990) Methods Enzymol. 183, 63-98. Rayner JR and Gonda TJ (1994). Molecular & Cellular Biology 14, 880-7. Sambrook J, Fritsch EF and Maniatis T (1989). Molecular Cloning, A Laboratory Manual. Cold Spring Harbour Laboratory Press, Cold Spring Harbour USA. Sato N, Sakamaki K, Terada N, Arai K and Miyajima A (1993). Embo Journal 12, 4181-9. Shimoda K, van Deursen J, Sangster MY, Sarawar SR, Carson RT, Tripp RA, Chu C, Quelle FW, Nosaka T, Vignali DA, Doherty PC, Grosveld G, Paul WE and Ihle JN (1996). Nature 380, 630-3. Shual K, Ziemiecki A, Wilks AF, Harpur AG, Sadowski HB, Gilman MZ and Darnell JE (1993). Nature 366, 580-3. Sprang SR and Bazan JF (1993). Curr. Opin. Structural Biol. 3, 815-827. Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S, Nakanishi K, Yoshida N, Kishimoto T and Akira S (1996). Nature 380, 627-30. Thierfelder WE, Vandeursen JM, Yamamoto K, Tripp RA, Sarawar SR, Carson RT, Sangster MY, Vignali DDA, Doherty PC, Grosveld GC and Ihle JN (1996). Nature 382, 171- 74. Wakao H, Gouilleux F and Groner B (1994). Embo Journal 13, 2182-91. Wen Z, Zhong Z and Darnell J Jr. (1995). Cell 82, 241-50. Yi T, Mui AL, Krystal G and Ihle JN (1993). Molecular & Cellular Biology 13, 7577-86. Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T and Miyajima A (1995). Embo Journal 14, 2816-26. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: (Other than US) THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH (US Only) (ii) TITLE OF INVENTION: THERAPEUTIC AND DIAGNOSTIC AGENTS (iii) NUMBER OF SEQUENCES: 49 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: DAVIES COLLISON CAVE (B) STREET: 1 LITTLE COLLINS STREET (C) CITY: MELBOURNE (D) STATE: VICTORIA (E) COUNTRY: AUSTRALIA (F) ZIP: 3000 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version #1.25 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: PCT INTERNATIONAL (B) FILING DATE: 31-OCT-1997 (vi) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: PO5117 (B) FILING DATE: 14-FEB-1997 (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: PO 3384 (B) FILING DATE: 01-NOV-1996 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: HUGHES DR, E JOHN L (C) REFERENCE/DOCKET NUMBER: EJH/EK (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: +61 3 9254 2777 (B) TELEFAX: +61 3 9254 2770 (2) INFORMATION FOR SEQ ID NO : 1 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 1 : CACGCCGCCC ACGTGAAGGC 20 (2) INFORMATION FOR SEQ ID NO : 2 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 2 : TTCGCCAATG ACAAGACGCT 20 (2) INFORMATION FOR SEQ ID NO: 3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1236 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..636 (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 3 : CGAGGCTCAA GCTCCGGGCG GATTCTGCGT GCCGCTCTCG CTCCTTGGGG TCTGTTGGCC -101 GGCCTGTGCC ACCCGGACGC CCGGCTCACT GCCTCTGTCT CCCCCATCAG CGCAGCCCCG -41 GACGCTATGG CCCACCCCTC CAGCTGGCCC CTCGAGTAGG -1 ATG GTA GCA CGC AAC CAG GTG GCA GCC GAC AAT GCG ATC TCC CCG GCA 48 Met Val Ala Arg Asn Gin Val Ala Ala Asp Asn Ala lie Ser Pro Ala 1 5 10 15 GCA GAG CCC CGA CGG CGG TCA GAG CCC TCC TCG TCC TCG TCT TCG TCC 96 Ala Glu Pro Arg Arg Arg Ser Glu Pro Ser Ser Ser Ser Ser Ser Ser 20 25 30 TCG CCA GCG GCC CCC GTG CGT CCC CGG CCC TGC CCG GCG GTC CCA GCC 144 Ser Pro Ala Ala Pro Val Arg Pro Arg Pro Cys Pro Ala Val Pro Ala 35 40 45 CCA GCC CCT GGC GAC ACT CAC TTC CGC ACC TTC CGC TCC CAC TCC GAT 192 Pro Ala Pro Gly Asp Thr His Phe Arg Thr Phe Arg Ser His Ser Asp 50 55 60 TAC CGG CGC ATC ACG CGG ACC AGC GCG CTC CTG GAC GCC TGC GGC TTC 240 Tyr Arg Arg lie Thr Arg Thr Ser Ala Leu Leu Asp Ala Cys Gly Phe 65 70 75 80 TAT TGG GGA CCC CTG AGC GTG CAC GGG GCG CAC GAG CGG CTG CGT GCC 288 Tyr Trp Gly Pro Leu Ser Val His Gly Ala His Glu Arg Leu Arg Ala 85 90 95 GAG CCC GTG GGC ACC TTC TTG GTG CGC GAC AGT CGT CAA CGG AAC TGC 336 Glu Pro Val Gly Thr Phe Leu Val Arg Asp Ser Arg Gin Arg Asn Cys 100 105 110 TTC TTC GCG CTC AGC GTG AAG ATG GCT TCG GGC CCC ACG AGC ATC CGC 384 Phe Phe Ala Leu Ser Val Lys Met Ala Ser Gly Pro Thr Ser lie Arg 115 120 125 GTG CAC TTC CAG GCC GGC CGC TTC CAC TTG GAC GGC AGC CGC GAG ACC 432 Val His Phe Gin Ala Gly Arg Phe His Leu Asp Gly Ser Arg Glu Thr 130 135 140 TTC GAC TGC CTT TTC GAG CTG CTG GAG CAC TAC GTG GCG GCG CCG CGC 480 Phe Asp Cys Leu Phe Glu Leu Leu Glu His Tyr Val Ala Ala Pro Arg 145 150 155 160 CGC ATG TTG GGG GCC CCG CTG CGC CAG CGC CGC GTG CGG CCG CTG CAG 528 Arg Met Leu Gly Ala Pro Leu Arg Gin Arg Arg Val Arg Pro Leu Gin 165 170 175 GAG CTG TGT CGC CAG CGC ATC GTG GCC GCC GTG GGT CGC GAG AAC CTG 576 Glu Leu Cys Arg Gin Arg lie Val Ala Ala Val Gly Arg Glu Asn Leu 180 185 190 GCG CGC ATC CCT CTT AAC CCG GTA CTC CGT GAC TAC CTG AGT TCC TTC 624 Ala Arg lie Pro Leu Asn Pro Val Leu Arg Asp Tyr Leu Ser Ser Phe 195 200 205 CCC TTC CAG ATC TGA CCGGCTG CCGCTGTGCC GCAGCATTAA GTGGGGGCGC 676 Pro Phe Gin lie * 210 CTTATTATTT CTTATTATTA ATTATTATTA TTTTTCTGGA ACCACGTGGG AGCCCTCCCC 736 GCCTGGGTCG GAGGGAGTGG TTGTGGAGGG TGAGATGCCT CCCACTTCTG GCTGGAGACC 796 TCATCCCACC TCTCAGGGGT GGGGGTGCTC CCCTCCTGGT GCTCCCTCCG GGTCCCCCCT 856 GGTTGTAGCA GCTTGTGTCT GGGGCCAGGA CCTGAATTCC ACTCCTACCT CTCCATGTTT 916 ACATATTCCC AGTATCTTTG CACAAACCAG GGGTCGGGGA GGGTCTCTGG CTTCATTTTT 976 CTGCTGTGCA GAATATCCTA TTTTATATTT TTACAGCCAG TTTAGGTAAT AAACTTTATT 1036 ATGAAAGTTT TTTTTTAAAA GAAAAAAAAA AAAAAAAAA 1075 ( 2 ) INFORMATION FOR SEQ ID NO : 4 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 212 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 4 : Met Val Ala Arg Asn Gin Val Ala Ala Asp Asn Ala lie Ser Pro Ala 1 5 10 15 Ala Glu Pro Arg Arg Arg Ser Glu Pro Ser Ser Ser Ser Ser Ser Ser 20 25 30 Ser Pro Ala Ala Pro Val Arg Pro Arg Pro Cys Pro Ala Val Pro Ala 35 40 45 Pro Ala Pro Gly Asp Thr His Phe Arg Thr Phe Arg Ser His Ser Asp 50 55 60 Tyr Arg Arg lie Thr Arg Thr Ser Ala Leu Leu Asp Ala Cys Gly Phe 65 70 75 80 Tyr Trp Gly Pro Leu Ser Val His Gly Ala His Glu Arg Leu Arg Ala 85 90 95 Glu Pro Val Gly Thr Phe Leu Val Arg Asp Ser Arg Gin Arg Asn Cys 100 105 110 Phe Phe Ala Leu Ser Val Lys Met Ala Ser Gly Pro Thr Ser lie Arg 115 120 125 Val His Phe Gin Ala Gly Arg Phe His Leu Asp Gly Ser Arg Glu Thr 130 135 140 Phe Asp Cys Leu Phe Glu Leu Leu Glu His Tyr Val Ala Ala Pro Arg 145 150 155 160 Arg Met Leu Gly Ala Pro Leu Arg Gin Arg Arg Val Arg Pro Leu Gin 165 170 175 Glu Leu Cys Arg Gin Arg lie Val Ala Ala Val Gly Arg Glu Asn Leu 180 185 190 Ala Arg lie Pro Leu Asn Pro Val Leu Arg Asp Tyr Leu Ser Ser Phe 195 200 205 Pro Phe Gin lie 210 (2) INFORMATION FOR SEQ ID NO : 5 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1121 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 223..819 (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 5 : GCGATCTGTG GGTGACAGTG TCTGCGAGAG ACTTTGCCAC ACCATTCTGC CGGAATTTGG 60 AGAAAAAGAA CCAGCCGCTT CCAGTCCCCT CCCCCTCCGC CACCATTTCG GACACCCTGC 120 ACACTCTCGT TTTGGGGTAC CCTGTGACTT CCAGGCAGCA CGCGAGGTCC ACTGGCCCCA 180 GCTCGGGCGA CCAGCTGTCT GGGACGTGTT GACTCATCTC CC ATG ACC CTG CGG 234 Met Thr Leu Arg 1 TGC CTG GAG CCC TCC GGG AAT GGA GCG GAC AGG ACG CGG AGC CAG TGG 282 Cys Leu Glu Pro Ser Gly Asn Gly Ala Asp Arg Thr Arg Ser Gin Trp 5 10 15 20 GGG ACC GCG GGG TTG CCG GAG GAA CAG TCC CCC GAG GCG GCG CGT CTG 330 Gly Thr Ala Gly Leu Pro Glu Glu Gin Ser Pro Glu Ala Ala Arg Leu 25 30 35 GCG AAA GCC CTG CGC GAG CTC AGT CAA ACA GGA TGG TAC TGG GGA AGT 378 Ala Lys Ala Leu Arg Glu Leu Ser Gin Thr Gly Trp Tyr Trp Gly Ser 40 45 50 ATG ACT GTT AAT GAA GCC AAA GAG AAA TTA AAA GAG GCT CCA GAA GGA 426 Met Thr Val Asn Glu Ala Lys Glu Lys Leu Lys Glu Ala Pro Glu Gly 55 60 65 ACT TTC TTG ATT AGA GAT AGT TCG CAT TCA GAC TAC CTA CTA ACT ATA 474 Thr Phe Leu lie Arg Asp Ser Ser His Ser Asp Tyr Leu Leu Thr lie 70 75 80 TCC GTT AAG ACG TCA GCT GGA CCG ACT AAC CTG CGG ATT GAG TAC CAA 522 Ser Val Lys Thr Ser Ala Gly Pro Thr Asn Leu Arg lie Glu Tyr Gin 85 90 95 100 GAT GGG AAA TTC AGA TTG GAT TCT ATC ATA TGT GTC AAG TCC AAG CTT 570 Asp Gly Lys Phe Arg Leu Asp Ser lie lie Cys Val Lys Ser Lys Leu 105 110 115 AAA CAG TTT GAC AGT GTG GTT CAT CTG ATT GAC TAC TAT GTC CAG ATG 618 Lys Gin Phe Asp Ser Val Val His Leu lie Asp Tyr Tyr Val Gin Met 120 125 130 TGC AAG GAT AAA CGG ACA GGC CCA GAA GCC CCA CGG AAT GGG ACT GTT 666 Cys Lys Asp Lys Arg Thr Gly Pro Glu Ala Pro Arg Asn Gly Thr Val 135 140 145 CAC CTG TAC CTG ACC AAA CCT CTG TAT ACA TCA GCA CCC ACT CTG CAG 714 His Leu Tyr Leu Thr Lys Pro Leu Tyr Thr Ser Ala Pro Thr Leu Gin 150 155 160 CAT TTC TGT CGA CTC GCC ATT AAC AAA TGT ACC GGT ACG ATC TGG GGA 762 His Phe Cys Arg Leu Ala lie Asn Lys Cys Thr Gly Thr lie Trp Gly 165 170 175 180 CTG CCT TTA CCA ACA AGA CTA AAA GAT TAC TTG GAA GAA TAT AAA TTC 810 Leu Pro Leu Pro Thr Arg Leu Lys Asp Tyr Leu Glu Glu Tyr Lys Phe 185 190 195 CAG GTA TAAGTATTTC TCTCTCTTTT TCGTTTTTTT TTAAAAAAAA AAAAACACAT 866 Gin Val GCCTCATATA GACTATCTCC GAATGCAGCT ATGTGAAAGA GAACCCAGAG GCCCTCCTCT 926 GGATAACTGC GCAGAATTCT CTCTTAAGGA CAGTTGGGCT CAGTCTAACT TAAAGGTGTG 986 AAGATGTAGC TAGGTATTTT AAAGTTCCCC TTAGGTAGTT TTAGCTGAAT GATGCTTTCT 1046 TTCCTATGGC TGCTCAAGAT CAAATGGCCC TTTTAAATGA AACAAAACAA AACAAAACAA 1106 AAAAAAAAAA AAAAA 1121 (2) INFORMATION FOR SEQ ID NO : 6 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 198 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 6 : Met Thr Leu Arg Cys Leu Glu Pro Ser Gly Asn Gly Ala Asp Arg Thr 1 5 10 15 Arg Ser Gin Trp Gly Thr Ala Gly Leu Pro Glu Glu Gin Ser Pro Glu 20 25 30 Ala Ala Arg Leu Ala Lys Ala Leu Arg Glu Leu Ser Gin Thr Gly Trp 35 40 45 Tyr Trp Gly Ser Met Thr Val Asn Glu Ala Lys Glu Lys Leu Lys Glu 50 55 60 Ala Pro Glu Gly Thr Phe Leu lie Arg Asp Ser Ser His Ser Asp Tyr 65 70 75 80 Leu Leu Thr lie Ser Val Lys Thr Ser Ala Gly Pro Thr Asn Leu Arg 85 90 95 lie Glu Tyr Gin Asp Gly Lys Phe Arg Leu Asp Ser lie lie Cys Val 100 105 110 Lys Ser Lys Leu Lys Gin Phe Asp Ser Val Val His Leu lie Asp Tyr 115 120 125 Tyr Val Gin Met Cys Lys Asp Lys Arg Thr Gly Pro Glu Ala Pro Arg 130 135 140 Asn Gly Thr Val His Leu Tyr Leu Thr Lys Pro Leu Tyr Thr Ser Ala 145 150 155 160 Pro Thr Leu Gin His Phe Cys Arg Leu Ala lie Asn Lys Cys Thr Gly 165 170 175 Thr lie Trp Gly Leu Pro Leu Pro Thr Arg Leu Lys Asp Tyr Leu Glu 180 185 190 Glu Tyr Lys Phe Gin Val 195 (2) INFORMATION FOR SEQ ID NO : 7 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2187 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA ( ix) FEATURE : (A) NAME/KEY: CDS (B) LOCATION: 18..695 (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 7 : CGCTGGCTCC GTGCGCC ATG GTC ACC CAC AGC AAG TTT CCC GCC GCC GGG 50 Met Val Thr His Ser Lys Phe Pro Ala Ala Gly 1 5 10 ATG AGC CGC CCC CTG GAC ACC AGC CTG CGC CTC AAG ACC TTC AGC TCC 98 Met Ser Arg Pro Leu Asp Thr Ser Leu Arg Leu Lys Thr Phe Ser Ser 15 20 25 AAA AGC GAG TAC CAG CTG GTG GTG AAC GCC GTG CGC AAG CTG CAG GAG 146 Lys Ser Glu Tyr Gin Leu Val Val Asn Ala Val Arg Lys Leu Gin Glu 30 35 40 AGC GGA TTC TAC TGG AGC GCC GTG ACC GGC GGC GAG GCG AAC CTG CTG 194 Ser Gly Phe Tyr Trp Ser Ala Val Thr Gly Gly Glu Ala Asn Leu Leu 45 50 55 CTC AGC GCC GAG CCC GCG GGC ACC TTT CTT ATC CGC GAC AGC TCG GAC 242 Leu Ser Ala Glu Pro Ala Gly Thr Phe Leu lie Arg Asp Ser Ser Asp 60 65 70 75 CAG CGC CAC TTC TTC ACG TTG AGC GTC AAG ACC CAG TCG GGG ACC AAG 290 Gin Arg His Phe Phe Thr Leu Ser Val Lys Thr Gin Ser Gly Thr Lys 80 85 90 AAC CTA CGC ATC CAG TGT GAG GGG GGC AGC TTT TCG CTG CAG AGT GAC 338 Asn Leu Arg lie Gin Cys Glu Gly Gly Ser Phe Ser Leu Gin Ser Asp 95 100 105 CCC CGA AGC ACG CAG CCA GTT CCC CGC TTC GAC TGT GTA CTC AAG CTG 386 Pro Arg Ser Thr Gin Pro Val Pro Arg Phe Asp Cys Val Leu Lys Leu 110 115 120 GTG CAC CAC TAC ATG CCG CCT CCA GGG ACC CCC TCC TTT TCT TTG CCA 434 Val His His Tyr Met Pro Pro Pro Gly Thr Pro Ser Phe Ser Leu Pro 125 130 135 CCC ACG GAA CCC TCG TCC GAA GTT CCG GAG CAG CCA CCT GCC CAG GCA 482 Pro Thr Glu Pro Ser Ser Glu Val Pro Glu Gin Pro Pro Ala Gin Ala 140 145 150 155 CTC CCC GGG AGT ACC CCC AAG AGA GCT TAC TAC ATC TAT TCT GGG GGC 530 Leu Pro Gly Ser Thr Pro Lys Arg Ala Tyr Tyr lie Tyr Ser Gly Gly 160 165 170 GAG AAG ATT CCG CTG GTA CTG AGC CGA CCT CTC TCC TCC AAC GTG GCC 578 Glu Lys lie Pro Leu Val Leu Ser Arg Pro Leu Ser Ser Asn Val Ala 175 180 185 ACC CTC CAG CAT CTT TGT CGG AAG ACT GTC AAC GGC CAC CTG GAC TCC 626 Thr Leu Gin His Leu Cys Arg Lys Thr Val Asn Gly His Leu Asp Ser 190 195 200 TAT GAG AAA GTG ACC CAG CTG CCT GGA CCC ATT CGG GAG TTC CTG GAT 674 Tyr Glu Lys Val Thr Gin Leu Pro Gly Pro lie Arg Glu Phe Leu Asp 205 210 215 CAG TAT GAT GCT CCA CTT TAAGGAGCAA AAGGGTCAGA GGGGGGCCTG 722 Gin Tyr Asp Ala Pro Leu 220 225 GGTCGGTCGG TCGCCTCTCC TCCGAGGCAC ATGGCACAAG CACAAAAATC CAGCCCCAAC 782 GGTCGGTAGC TCCCAGTGAG CCAGGGGCAG ATTGGCTTCT TCCTCAGGCC CTCCACTCCC 842 GCAGAGTAGA GCTGGCAGGA CCTGGAATTC GTCTGAGGGG AGGGGGAGCT GCCACCTGCT 902 TTCCCCCCTC CCCCAGCTCC AGCTTCTTTC AAGTGGAGCC AGCCGGCCTG GCCTGGTGGG 962 ACAATACCTT TGACAAGCGG ACTCTCCCCT CCCCTTCCTC CACACCCCCT CTGCTTCCCA 1022 AGGGAGGTGG GGACACCTCC AAGTGTTGAA CTTAGAACTG CAAGGGGAAT CTTCAAACTT 1082 TCCCGCTGGA ACTTGTTTGC GCTTTGATTT GGTTTGATCA AGAGCAGGCA CCTGGGGGAA 1142 GGATGGAAGA GAAAAGGGTG TGTGAAGGGT TTTTATGCTG GCCAAAGAAA TAACCACTCC 1202 CACTGCCCAA CCTAGGTGAG GAGTGGTGGC TCCTGGCTCT GGGGAGAGTG GCAAGGGGTG 1262 ACCTGAAGAG AGCTATACTG GTGCCAGGCT CCTCTCCATG GGGCAGCTAA TGAAACCTCG 1322 CAGATCCCTT GCACCCCAGA ACCCTCCCCG TTGTGAAGAG GCAGTAGCAT TTAGAAGGGA 1382 GACAGATGAG GCTGGTGAGC TGGCCGCCTT TTCCAACACC GAAGGGAGGC AGATCAACAG 1442 ATGAGCCATC TTGGAGCCCA GGTTTCCCCT GGAGCAGATG GAGGGTTCTG CTTTGTCTCT 1502 CCTATGTGGG GCTAGGAGAC TCGCCTTAAA TGCCCTCTGT CCCAGGGATG GGGATTGGCA 1562 CACAAGGAGC CAAACACAGC CAATAGGCAG AGAGTTGAGG GATTCACCCA GGTGGCTACA 1622 GGCCAGGGGA AGTGGCTGCA GGGGAGAGAC CCAGTCACTC CAGGAGACTC CTGAGTTAAC 1682 ACTGGGAAGA CATTGGCCAG TCCTAGTCAT CTCTCGGTCA GTAGGTCCGA GAGCTTCCAG 1742 GCCCTGCACA GCCCTCCTTT CTCACCTGGG GGGAGGCAGG AGGTGATGGA GAAGCCTTCC 1802 CATGCCGCTC ACAGGGGCCT CACGGGAATG CAGCAGCCAT GCAATTACCT GGAACTGGTC 1862 CTGTGTTGGG GAGAAACAAG TTTTCTGAAG TCAGGTATGG GGCTGGGTGG GGCAGCTGTG 1922 TGTTGGGGTG GCTTTTTTCT CTCTGTTTTG AATAATGTTT ACAATTTGCC TCAATCACTT 1982 TTATAAAAAT CCACCTCCAG CCCGCCCCTC TCCCCACTCA GGCCTTCGAG GCTGTCTGAA 2042 GATGCTTGAA AAACTCAACC AAATCCCAGT TCAACTCAGA CTTTGCACAT A ATTTATAT 2102 TTATACTCAG AAAAGAAACA TTTCAGTAAT TTATAATAAA AGAGCACTAT TTTTTAATGA 2162 AAAAAAAAAA AAAAAAAAAA AAAAA 2187 (2) INFORMATION FOR SEQ ID NO : 8 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 225 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 8 : Met Val Thr His Ser Lys Phe Pro Ala Ala Gly Met Ser Arg Pro Leu 1 5 10 15 Asp Thr Ser Leu Arg Leu Lys Thr Phe Ser Ser Lys Ser Glu Tyr Gin 20 25 30 Leu Val Val Asn Ala Val Arg Lys Leu Gin Glu Ser Gly Phe Tyr Trp 35 40 45 Ser Ala Val Thr Gly Gly Glu Ala Asn Leu Leu Leu Ser Ala Glu Pro 50 55 60 Ala Gly Thr Phe Leu He Arg Asp Ser Ser Asp Gin Arg His Phe Phe 65 70 75 80 Thr Leu Ser Val Lys Thr Gin Ser Gly Thr Lys Asn Leu Arg He Gin 85 90 95 Cys Glu Gly Gly Ser Phe Ser Leu Gin Ser Asp Pro Arg Ser Thr Gin 100 105 110 Pro Val Pro Arg Phe Asp Cys Val Leu Lys Leu Val His His Tyr Met 115 120 125 Pro Pro Pro Gly Thr Pro Ser Phe Ser Leu Pro Pro Thr Glu Pro Ser 130 135 140 Ser Glu Val Pro Glu Gin Pro Pro Ala Gin Ala Leu Pro Gly Ser Thr 145 150 155 160 Pro Lys Arg Ala Tyr Tyr He Tyr Ser Gly Gly Glu Lys He Pro Leu 165 170 175 Val Leu Ser Arg Pro Leu Ser Ser Asn Val Ala Thr Leu Gin His Leu 180 185 190 Cys Arg Lys Thr Val Asn Gly His Leu Asp Ser Tyr Glu Lys Val Thr 195 200 205 Gin Leu Pro Gly Pro He Arg Glu Phe Leu Asp Gin Tyr Asp Ala Pro 210 215 220 Leu 225 (2) INFORMATION FOR SEQ ID NO : 9 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1094 base pairs (B) TYPE: nucleic acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO : 9 : CTCCGGCTGG CCCCTTCTGT AGGATGGTAG CACACAACCA GGTGGCAGCC GACAATGCAG 60 TCTCCACAGC AGCAGAGCCC CGACGGCGGC CAGAACCTTC CTCCTCTTCC TCCTCCTCGC 120 CCGCGGCCCC CGCGCGCCCG CGGCCGTGCC CCGCGGTCCC GGCCCCGGCC CCCGGCGACA 180 CGCACTTCCG CACATTCCGT TCGCACGCCG ATTACCGGCG CATCACGCGC GCCAGCGCGC 240 TCCTGGACGC CTGCGGATTC TACTGGGGGC CCCTGAGCGT GCACGGGGCG CACGAGCGGC 300 TGCGCGCCGA GCCCGTGGGC ACCTTCCTGG TGCGCGACAG CCGCCAGCGG AACTGCTTTT 360 TCGCCCTTAG CGTGAAGATG GCCTCGGGAC CCACGAGCAT CCGCGTGCAC TTTCAGGCCG 420 GCCGCTTTCA CCTGGATGGC AGCCGCGAGA GCTTCGACTG CCTCTTCGAG CTGCTGGAGC 480 ACTACGTGGC GGCGCCGCGC CGCATGCTGG GGGCCCCGCT GCGCCAGCGC CGCGTGCGGC 540 CGCTGCAGGA GCTGTGCCGC CAGCGCATCG TGGCCACCGT GGGCCGCGAG AACCTGGCTC 600 GCATCCCCCT CAACCCCGTC CTCCGCGACT ACCTGAGCTC CTTCCCCTTC CAGATTTGAC 660 CGGCAGCGCC CGCCGTGCAC GCAGCATTAA CTGGGATGCC GTGTTATTTT GTTATTACTT 720 GCCTGGAACC ATGTGGGTAC CCTCCCCGGC CTGGGTTGGA GGGAGCGGAT GGGTGTAGGG 780 GCGAGGCGCC TCCCGCCCTC GGCTGGAGAC GAGGCCGCAG ACCCCTTCTC ACCTCTTGAG 840 GGGGTCCTCC CCCTCCTGGT GCTCCCTCTG GGTCCCCCTG GTTGTTGTAG CAGCTTAACT 900 GTATCTGGAG CCAGGACCTG AACTCGCACC TCCTACCTCT TCATGTTTAC ATATACCCAG 960 TATCTTTGCA CAAACCAGGG GTTGGGGGAG GGTCTCTGGC TTTATTTTTC TGCTGTGCAG 1020 AATCCTATTT TATATTTTTT AAAGTCAGTT TAGGTAATAA ACTTTATTAT GAAAGTTTTT 1080 TTTTTTAAAA AAAA 1094 (2) INFORMATION FOR SEQ ID NO: 10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 211 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10: Met Val Ala His Asn Gin Val Ala Ala Asp Asn Ala Val Ser Thr Ala 1 5 10 15 Ala Glu Pro Arg Arg Arg Pro Glu Pro Ser Ser Ser Ser Ser Ser Ser 20 25 30 Pro Ala Ala Pro Ala Arg Pro Arg Pro Cys Pro Ala Val Pro Ala Pro 35 40 45 Ala Pro Gly Asp Thr His Phe Arg Thr Phe Arg Ser His Ala Asp Tyr 50 55 60 Arg Arg He Thr Arg Ala Ser Ala Leu Leu Asp Ala Cys Gly Phe Tyr 65 70 75 80 Trp Gly Pro Leu Ser Val His Gly Ala His Glu Arg Leu Arg Ala Glu 85 90 95 Pro Val Gly Thr Phe Leu Val Arg Asp Ser Arg Gin Arg Asn Cys Phe 100 105 110 Phe Ala Leu Ser Val Lys Met Ala Ser Gly Pro Thr Ser He Arg Val 115 120 125 His Phe Gin Ala Gly Arg Phe His Leu Asp Gly Ser Arg Glu Ser Phe 130 135 140 Asp Cys Leu Phe Glu Leu Leu Glu His Tyr Val Ala Ala Pro Arg Arg 145 150 155 160 Met Leu Gly Ala Pro Leu Arg Gin Arg Arg Val Arg Pro Leu Gin Glu 165 170 175 Leu Cys Arg Gin Arg He Val Ala Thr Val Gly Arg Glu Asn Leu Ala 180 185 190 Arg He Pro Leu Asn Pro Val Leu Arg Asp Tyr Leu Ser Ser Phe Pro 195 200 205 Phe Gin He 210 (2) INFORMATION FOR SEQ ID NO: 11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2807 base pairs (B) TYPE: nucleic acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11: GGAAACCGAG GCGGGGAGAC CAGGAGGCCT TGGCCTCAGA GCTTCAGAGT CGCGTGGCAG 60 CAAACAGAGA AACCTGTAGA GGGCAGTGTG CGTCACTTAG CTCAGGGAAG CTGCACGCGA 120 AACTCACCCG CCTTCATTCA TAAACATCGT CAGCTAGGCA CCTACTCCTG GGCTTTCAGG 180 ACAAACTGAA TCACGAAACC ACAGTGTCCT TAAAATAGGT CTGACCGCCT GAATCCCTGG 240 CCAAGGTGTG TACGGGGCAT GGGAGCCCTT GTGCAGAGAT GCTTGCAGGA GCCTTGAGGG 300 GCTCTGTAAG ACAGAGGCTA GGAAGACAAA GTTGGGGGCT ACAGCTTCTT GTCCTGCCCG 360 GGGCCTCAGT TTCTTCGGTT GCCCACGTAG GAGTGCAGAG AGTCCAGCCC CTGGGGACCC 420 AACCCAACCC CGCCCAGTTT CCGAGGAACT CGTCCGGGAG CGGGGGCGCC CCTCCCGCAC 480 CGCCTTAGGC TTCCTTTGAA GCCTCTGCGG TCAGGCCACC GCTTCCTGGG AAGCCCAAGC 540 CAAGGCCAGG CCGAGTGGCC AACGGGAGGG GCCCGCGCGC GATTCTGGAG GAGGGCGGCG 600 GCCCCACAGG TCTCCAGGGC TGGCTAGCCG GGCTCCTAGA GCGGAGACTG CCAAGGCCTT 660 CGGGTCCTGG GCAGGAAGGA TCCTGGCAGG GAGGAGTTGC TTGGGGGGTG GGGGGGAAAG 720 GCTCCAGGCG CGGTGGAGCT CTGACCAGGA GAATGCACAC ACTCGGAGGG GAGGAGGCGT 780 GTCAGCCCCA AGCTAGCATC CCACCCGGGG AGCAGCGATG TGGGGCGAAG GTAGCCAGAG 840 CAAAAGAGCA GGCACCAGGT GACACGAAAC AGAAGATTCC GGGTAGAGCC AGAACCCCAG 900 AAGTCCCATT CAGGGAAGGT GCGAGGCGAG AACGAGTTAG GTGGACCCTC TCCAGGGGCA 960 GCCAAAGAAA TCTAAAGAGA ACCCGAAGGA CTTGCCGGAA AGAGAAACCG AAAGCGGCGG 1020 TGGGCGGGAT CGGTGGGCGG GGCCTCCCTG GTTTAAGAGC TTGATGCAGG GGCGGGCAGC 1080 AGCAGAGAGA ACTGCGGCCG TGGCAGCGGC ACGGCTCCCG GCCCCGGAGC ATGCGCGACA 1140 GCAGCCCCGG AACCCCCAGC CGCGGCGCCC CGCGTCCCGC CGCCAGGTGA GCCGAGGCAG 1200 CTGCGAAGGA GCAGGCGGGA GGGGATGGGA GGAAGGGGAG CAGAGCCTGG CAGGACTATC 1260 CTCGCAGACT GCATGGCGGG GTCGTGGATG CTATGCCTCT GGCGCCCGCC CCACCGGCTG 1320 GCCCAGGCGG CCCCTCGCGC GCGCGGGGCG CCGTCAGCCC CTCCTCTCCG GCCCTGAGCC 1380 CGGATCGTCC GCCCGGGTTC CAGTTCCCGG CGTGGCCAGT AGGCGGCAAC CGCGAGGCGG 1440 CAAGCCACCC AGCGGGGACG GCCTGGAGTC GGGCCCCTCT CCACGCCCCC TTCTCCACGC 1500 GCGCGGGGAG GCAGGGCTCC ACCGCCAGTC TGGAAGGGTT CCACATACAG GAACGGCCTA 1560 CTTCGCAGAT GAGCCCACCG AGGCTCAGGC TCCGGGCGGA TTCTGCGTGT CACCCTCGCT 1620 CCTTGGGGTC CGCTGGCCGG CCTGTGCCAC CCGGACGCCC GGTTCACTGC CTCTGTCTCC 1680 CCCATCAGCG CAGCCCCGGA CGCTATGGCC CACCCCTCCA GCTGGCCCCT CGAGTAGGAT 1740 GGTAGCACGT AACCAGGTGG AAGCCGACAA TGCGATCTCC CCGGCATCAG AGCCCCGACG 1800 GCGGCCAGAG CCATCCTCGT CCTCGTCTTC GTCCTCGCCG GCGGCCCCGG CGCGTCCCCG 1860 GCCCTGCCCG GTGGTCCCGG CCCCGGCTCC GGGCGACACT CACTTCCGCA CCTTCCGCTC 1920 CCACTCTGAT TACCGGCGCA TCACGCGGAC CAGCGCTCTC CTGGACGCCT GCGGCTTCTA 1980 CTGGGGACCC CTGAGCGTGC ATGGGGCGCA CGAACGGCTG CGTTCCGAAC CCGTGGGCAC 2040 CTTCTTGGTG CGCGACAGTC GCCAGCGGAA CTGCTTCTTC GCGCTCAGCG TGAAGATGGC 2100 TTCGGGCCCC ACGAGCATTC GTGTGCACTT CCAGGCCGGC CGCTTCCACC TGGACGGCAA 2160 CCGCGAGACC TTCGACTGCC TCTTCGAGCT GCTGGAGCAC TACGTGGCGG CGCCGCGCCG 2220 CATGTTGGGG GCCCCACTGC GCCAGCGCCG CGTGCGGCCG CTGCAGGAGC TGTGTCGCCA 2280 GCGCATCGTG GCCGCCGTGG GTCGCGAGAA CCTGGCACGC ATCCCTCTTA ACCCGGTACT 2340 CCGTGACTAC CTGAGTTCCT TCCCCTTCCA GATCTGACCG GCTGCCGCCG TGCCCGCAGA 2400 ATTAAGTGGG AGCGCCTTAT TATTTCTTAT TATTAATTAT TATTATTTTT CTGGAACCAC 2460 GTGGGAGCCC TCCCCGCCTA GGTCGGAGGG AGTGGGTGTG GAGGGTGAGA TCCCTCCCAC 2520 TTCTGGCTGG AGACCTTATC CCGCCTCTCG GGGGGCCTCC CCTCCTGGTG CTCCCTCCCG 2580 GTCCCCCTGG TTGTAGCAGC TTGTGTCTGG GGCCAGGACC TGAACTCCAC GCCTACCTCT 2640 CCATGTTTAC ATGTTCCCAG TATCTTTGCA CAAACCAGGG GTGGGGGAGG GTCTCTGGCT 2700 TCATTTTTCT GCTGTGCAGA ATATTCTATT TTATATTTTT ACATCCAGTT TAGATAATAA 2760 ACTTTATTAT GAAAGTTTTT TTTTTTAAAG AAACAAAGAT TTCTAGA 2807 (2) INFORMATION FOR SEQ ID NO: 12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 212 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: Met Val Ala Arg Asn Gin Val Glu Ala Asp Asn Ala He Ser Pro Ala 1 5 10 15 Ser Glu Pro Arg Arg Arg Pro Glu Pro Ser Ser Ser Ser Ser Ser Ser 20 25 30 Ser Pro Ala Ala Pro Ala Arg Pro Arg Pro Cys Pro Val Val Pro Ala 35 40 45 Pro Ala Pro Gly Asp Thr His Phe Arg Thr Phe Arg Ser His Ser Asp 50 55 60 Tyr Arg Arg He Thr Arg Thr Ser Ala Leu Leu Asp Ala Cys Gly Phe 65 70 75 80 Tyr Trp Gly Pro Leu Ser Val His Gly Ala His Glu Arg Leu Arg Ser 85 90 95 Glu Pro Val Gly Thr Phe Leu Val Arg Asp Ser Arg Gin Arg Asn Cys 100 105 110 Phe Phe Ala Leu Ser Val Lys Met Ala Ser Gly Pro Thr Ser He Arg 115 120 125 Val His Phe Gin Ala Gly Arg Phe His Leu Asp Gly Asn Arg Glu Thr 130 135 140 Phe Asp Cys Leu Phe Glu Leu Leu Glu His Tyr Val Ala Ala Pro Arg 145 150 155 160 Arg Met Leu Gly Ala Pro Leu Arg Gin Arg Arg Val Arg Pro Leu Gin 165 170 175 Glu Leu Cys Arg Gin Arg He Val Ala Ala Val Gly Arg Glu Asn Leu 180 185 190 Ala Arg He Pro Leu Asn Pro Val Leu Arg Asp Tyr Leu Ser Ser Phe 195 200 205 Pro Phe Gin He 210 (2) INFORMATION FOR SEQ ID NO: 13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1611 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 263..1529 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13: CGAATTCCGG GCGGGCTGTG TGAGTCTGTG AGTGGAAGGC GCGCCGGCTC TTTTGTCTGA 60 GTGTGACCCG GTGGCTTTGT TCCAGGCATT CCGGTGATTT CCTCCGGGCA GTCCGCAGAA 120 GCCGCAGCGG CCGCCCGCGC TCTCTCTGCA GTCTCCACAC CCGGGAGAGC CTGAGCCCGC 180 GTCACGCCCC TCAGCCCCCG CTGAGTCCCT TCTCTGTTGT CGCGTCCGAA TCGAGTTCCC 240 GGAATCAGAC GGTGCCCCAT AG ATG GCC AGC TTT CCC CCG AGG GTT AAC GAG 292 Met Ala Ser Phe Pro Pro Arg Val Asn Glu 1 5 10 AAA GAG ATC GTG AGA TCA CGT ACT ATA GGG GAA CTC TTG GCT CCA GCA 340 Lys Glu He Val Arg Ser Arg Thr He Gly Glu Leu Leu Ala Pro Ala 15 20 25 GCT CCT TTT GAC AAG AAA TGT GGT GGT GAG AAC TGG ACG GTT GCT TTT 388 Ala Pro Phe Asp Lys Lys Cys Gly Gly Glu Asn Trp Thr Val Ala Phe 30 35 40 GCT CCT GAT GGT TCC TAC TTT GCG TGG TCA CAA GGA TAT CGC ATA GTG 436 Ala Pro Asp Gly Ser Tyr Phe Ala Trp Ser Gin Gly Tyr Arg He Val 45 50 55 AAG CTT GTC CCG TGG TCC CAG TGC CGT AAG AAC TTT CTT TTG CAT GGT 484 Lys Leu Val Pro Trp Ser Gin Cys Arg Lys Asn Phe Leu Leu His Gly 60 65 70 TCC AAA AAT GTT ACC AAT TCA AGC TGT CTA AAA TTG GCA AGA CAA AAC 532 Ser Lys Asn Val Thr Asn Ser Ser Cys Leu Lys Leu Ala Arg Gin Asn 75 80 85 90 AGT AAT GGT GGT CAG AAA AAC AAG CCT CCT GAG CAC GTT ATA GAC TGT 580 Ser Asn Gly Gly Gin Lys Asn Lys Pro Pro Glu His Val He Asp Cys 95 100 105 GGA GAC ATA GTC TGG AGT CTT GCT TTT GGG TCT TCA GTT CCA GAA AAA 628 Gly Asp He Val Trp Ser Leu Ala Phe Gly Ser Ser Val Pro Glu Lys 110 115 120 CAG AGT CGT TGC GTT AAT ATA GAA TGG CAT CGG TTC CGA TTT GGA CAG 676 Gin Ser Arg Cys Val Asn He Glu Trp His Arg Phe Arg Phe Gly Gin 125 130 135 GAT CAG CTA CTC CTT GCC ACA GGA TTA AAC AAT GGT CGC ATC AAA ATC 724 Asp Gin Leu Leu Leu Ala Thr Gly Leu Asn Asn Gly Arg He Lys He 140 145 150 TGG GAT GTA TAT ACA GGA AAA CTC CTC CTT AAT TTG GTA GAC CAC ATT 772 Trp Asp Val Tyr Thr Gly Lys Leu Leu Leu Asn Leu Val Asp His He 155 160 165 170 GAA ATG GTT AGA GAT TTA ACT TTT GCT CCA GAT GGG AGC TTA CTC CTT 820 Glu Met Val Arg Asp Leu Thr Phe Ala Pro Asp Gly Ser Leu Leu Leu 175 180 185 GTA TCA GCT TCA AGA GAC AAA ACT CTA AGA GTG TGG GAC CTG AAA GAT 868 Val Ser Ala Ser Arg Asp Lys Thr Leu Arg Val Trp Asp Leu Lys Asp 190 195 200 GAT GGA AAC ATG GTG AAA GTA TTG CGG GCA CAT CAG AAT TGG GTG TAC 916 Asp Gly Asn Met Val Lys Val Leu Arg Ala His Gin Asn Trp Val Tyr 205 210 215 AGT TGT GCA TTC TCT CCC GAC TGT TCT ATG CTG TGT TCA GTG GGC GCC 964 Ser Cys Ala Phe Ser Pro Asp Cys Ser Met Leu Cys Ser Val Gly Ala 220 225 230 AGT AAA GCA GTT TTC CTT TGG AAT ATG GAT AAA TAC ACC ATG ATT AGG 1012 Ser Lys Ala Val Phe Leu Trp Asn Met Asp Lys Tyr Thr Met He Arg 235 240 245 250 AAG CTG GAA GGT CAT CAC CAT GAT GTT GTA GCT TGT GAC TTT TCT CCT 1060 Lys Leu Glu Gly His His His Asp Val Val Ala Cys Asp Phe Ser Pro 255 260 265 GAT GGA GCA TTG CTA GCT ACT GCA TCC TAT GAC ACT CGT GTG TAT GTC 1108 Asp Gly Ala Leu Leu Ala Thr Ala Ser Tyr Asp Thr Arg Val Tyr Val 270 275 280 TGG GAT CCA CAC AAT GGA GAC CTT CTG ATG GAG TTT GGG CAC CTG TTT 1156 Trp Asp Pro His Asn Gly Asp Leu Leu Met Glu Phe Gly His Leu Phe 285 290 295 CCC TCG CCC ACT CCA ATA TTT GCT GGA GGA GCA AAT GAC CGA TGG GTG 1204 Pro Ser Pro Thr Pro He Phe Ala Gly Gly Ala Asn Asp Arg Trp Val 300 305 310 AGA GCT GTG TCT TTC AGT CAT GAT GGA CTG CAT GTT GCC AGC CTT GCT 1252 Arg Ala Val Ser Phe Ser His Asp Gly Leu His Val Ala Ser Leu Ala 315 320 325 330 GAT GAT AAA ATG GTG AGG TTC TGG AGA ATC GAT GAG GAT TGT CCG GTA 1300 Asp Asp Lys Met Val Arg Phe Trp Arg He Asp Glu Asp Cys Pro Val 335 340 345 CAA GTT GCA CCT TTG AGC AAT GGT CTT TGC TGT GCC TTT TCT ACT GAT 1348 Gin Val Ala Pro Leu Ser Asn Gly Leu Cys Cys Ala Phe Ser Thr Asp 350 355 360 GGC AGT GTT TTA GCT GCT GGG ACA CAT GAT GGA AGT GTG TAT TTT TGG 1396 Gly Ser Val Leu Ala Ala Gly Thr His Asp Gly Ser Val Tyr Phe Trp 365 370 375 GCC ACT CCA AGG CAA GTC CCT AGC CTT CAA CAT ATA TGT CGC ATG TCA 1444 Ala Thr Pro Arg Gin Val Pro Ser Leu Gin His He Cys Arg Met Ser 380 385 390 ATC CGA AGA GTG ATG TCC ACC CAA GAA GTC CAA AAA CTG CCT GTT CCT 1492 He Arg Arg Val Met Ser Thr Gin Glu Val Gin Lys Leu Pro Val Pro 395 400 405 410 TCC AAA ATA TTG GCG TTT CTC TCC TAC CGC GGT TAG A CTGAAGACTG 1539 Ser Lys He Leu Ala Phe Leu Ser Tyr Arg Gly * 415 420 CCTTTCCTGG TAGGCCTGCC AGACAGAGCG CCCTTTACAA GACACACCTC AAGCTTTACC 1599 TCGTGCCGAA TT 1611 (2) INFORMATION FOR SEQ ID NO: 14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 422 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14: Met Ala Ser Phe Pro Pro Arg Val Asn Glu Lys Glu He Val Arg Ser 1 5 10 15 Arg Thr He Gly Glu Leu Leu Ala Pro Ala Ala Pro Phe Asp Lys Lys 20 25 30 Cys Gly Gly Glu Asn Trp Thr Val Ala Phe Ala Pro Asp Gly Ser Tyr 35 40 45 Phe Ala Trp Ser Gin Gly Tyr Arg He Val Lys Leu Val Pro Trp Ser 50 55 60 Gin Cys Arg Lys Asn Phe Leu Leu His Gly Ser Lys Asn Val Thr Asn 65 70 75 80 Ser Ser Cys Leu Lys Leu Ala Arg Gin Asn Ser Asn Gly Gly Gin Lys 85 90 95 Asn Lys Pro Pro Glu His Val He Asp Cys Gly Asp He Val Trp Ser 100 105 110 Leu Ala Phe Gly Ser Ser Val Pro Glu Lys Gin Ser Arg Cys Val Asn 115 120 125 He Glu Trp His Arg Phe Arg Phe Gly Gin Asp Gin Leu Leu Leu Ala 130 135 140 Thr Gly Leu Asn Asn Gly Arg He Lys He Trp Asp Val Tyr Thr Gly 145 150 155 160 Lys Leu Leu Leu Asn Leu Val Asp His He Glu Met Val Arg Asp Leu 165 170 175 Thr Phe Ala Pro Asp Gly Ser Leu Leu Leu Val Ser Ala Ser Arg Asp 180 185 190 Lys Thr Leu Arg Val Trp Asp Leu Lys Asp Asp Gly Asn Met Val Lys 195 200 205 Val Leu Arg Ala His Gin Asn Trp Val Tyr Ser Cys Ala Phe Ser Pro 210 215 220 Asp Cys Ser Met Leu Cys Ser Val Gly Ala Ser Lys Ala Val Phe Leu 225 230 235 240 Trp Asn Met Asp Lys Tyr Thr Met He Arg Lys Leu Glu Gly His His 245 250 255 His Asp Val Val Ala Cys Asp Phe Ser Pro Asp Gly Ala Leu Leu Ala 260 265 270 Thr Ala Ser Tyr Asp Thr Arg Val Tyr Val Trp Asp Pro His Asn Gly 275 280 285 Asp Leu Leu Met Glu Phe Gly His Leu Phe Pro Ser Pro Thr Pro He 290 295 300 Phe Ala Gly Gly Ala Asn Asp Arg Trp Val Arg Ala Val Ser Phe Ser 305 310 315 320 His Asp Gly Leu His Val Ala Ser Leu Ala Asp Asp Lys Met Val Arg 325 330 335 Phe Trp Arg He Asp Glu Asp Cys Pro Val Gin Val Ala Pro Leu Ser 340 345 350 Asn Gly Leu Cys Cys Ala Phe Ser Thr Asp Gly Ser Val Leu Ala Ala 355 360 365 Gly Thr His Asp Gly Ser Val Tyr Phe Trp Ala Thr Pro Arg Gin Val 370 375 380 Pro Ser Leu Gin His He Cys Arg Met Ser He Arg Arg Val Met Ser 385 390 395 400 Thr Gin Glu Val Gin Lys Leu Pro Val Pro Ser Lys He Leu Ala Phe 405 410 415 Leu Ser Tyr Arg Gly * 420 (2) INFORMATION FOR SEQ ID NO: 15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 783 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15: CTGTCTTCCT CCGCAGCGCG AGGCTGGGTA CAGGGTCTAT TGTCTGTGGT TGACTCCGTA 60 CTTTGGTCTG AGGCCTTCGG GAGCTTTCCC GAGGCAGTTA GCAGAAGCCG CAGCGACCGC 120 CCCCGCCCGT CTCCTCTGTC CCTGGGCCCG GGAGACAAAC TTGGCGTCAC GCCCTCAGCG 180 GTCGCCACTC TCTTCTCTGT TGTTGGGTCC GCATCGTATT CCCGGAATCA GACGGTGCCC 240 CATAGATGGC CAGCTTTCCC CCGAGGGTCA ACGAGAAAGA GATCGTGAGA TCACGTACTA 300 TAGGTGAACT TTTAGCTCCT GCAGCTCCTT TTGACAAGAA ATGTGGTCGT GAAAATTGGA 360 CTGTTGCTTT TGCTCCAGAT GGTTCATACT TTGCTTGGTC ACAAGGACAT CGCACAGTAA 420 AGCTTGTTCC GTGGTCCCAG TGCCTTCAGA ACTTTCTCTT GCATGGCACC AAGAATGTTA 480 CCAATTCAAG CAGTTTAAGA TTGCCAAGAC AAAATAGTGA TGGTGGTCAG AAAAATAAGC 540 CTCGTGACAT ATTATAGACT GTGGAGATAT AGTCTGGAGT CTTGCTTTTG GGTCATCAGT 600 TCCAGAAAAA CAGAGTCGCT GTGTAAATAT AGAATGGCAT CGCTTCAGAT TTGGACAAGA 660 TCAGCTACTT CTTGCTACAG GGTTGAACAA TGGGCGTATC AAAATATGGG ATGTATATCA 720 GGAAACTCCT CCTTAACTTG GTAGATCATA CTGAAGTGGT CAGAGATTTA ACTTTTGCTC 780 CAG 783 (2) INFORMATION FOR SEQ ID NO: 16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1122 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16: CTCTGTATGT CTGAATGAAG CTATAACATT TGCCTTTTTA TTGCAGGTTT TCCTTTGGAA 60 TATGGATAAA TACACCATGA TACGGAAACT AGAAGGACAT CACCATGATG TGGTAGCTTG 120 TGACTTTTCT CCTGATGGAG CATTACTGGC TACTGCATCT TATGATACTC GAGTATATAT 180 CTGGGATCCA CATAATGGAG ACATTCTGAT GGAATTTGGG CACCTGTTTC CCCCACCTAC 240 TCCAATATTT GCTGGAGGAG CAAATGACCG GTGGGTACGA TCTGTATCTT TTAGCCATGA 300 TGGACTGCAT GTTGCAAGCC TTGCTGATGA TAAAATGGTG AGGTTCTGGA GAATTGATGA 360 GGATTATCCA GTGCAAGTTG CACCTTTGAG CAATGGTCTT TGCTGTGCCT TCTCTACTGA 420 TGGCAGTGTT TTAGCTGCTG GGACACATGA CGGAAGTGTG TATTTTTGGG CCACTCCACG 480 GCAGGTCCCT AGCCTGCAAC ATTTATGTCG CATGTCAATC CGAAGAGTGA TGCCCACCCA 540 AGAAGTTCAG GAGCTGCCGA TTCCTTCCAA GCTTTTGGAG TTTCTCTCGT ATCGTATTTA 600 GAAGATTCTG CCTTCCCTAG TAGTAGGGAC TGACAGAATA CACTTAACAC AAACCTCAAG 660 CTTTACTGAC TTCAATTATC TGTTTTTAAA GACGTAGAAG ATTTATTTAA TTTGATATGT 720 TCTTGTACTG CATTTTGATC AGTTGAGCTT TTAAAATATT ATTTATAGAC AATAGAAGTA 780 TTTCTGAACA TATCAAATAT AAATTTTTTT AAAGATCTAA CTGTGAAAAC ATACATACCT 840 GTACATATTT AGATATAAGC TGCTATATGT TGAATGGACC CTTTTGCTTT TCTGATTTTT 900 AGTTCTGACA TGTATATATT GCTTCAGTAG AGCCACAATA TGTATCTTTG CTGTAAAGTG 960 CAAGGAAATT TTAAATTCTG GGACACTGAG TTAGATGGTA AATACTGACT TACGAAAGTT 1020 GAATTGGGTG AGGCGGGCAA ATCACCTGAG GTCAGCAGTT TGAGACTAGC CTGGCAAACA 1080 TGATGAAACC CTGTCTCTAC TAAAAATACA AAAAAAAAAA AA 1122 (2) INFORMATION FOR SEQ ID NO: 17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2537 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 422..2029 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17: CGGCACGAGC CGGGCTCCGT CCGGAGGAAG CGAGGCTGCG CCGCCGGCCC GGCAGGAGCG 60 GAGGACGGGA GCGCGGGCGG TCGCGCTCGC CCTGTCGCTG ACTGCGCTGC CCCGGCCCAT 120 CCTTGCCTGG CCGCAGGTGC CCTGGATGAG GCCGCCGCGC GTGTCCCGGC CGCTGAGTGT 180 CCCCCGCGGT CGCCCGGCGC CTGCCCTCAA GCGGCCGCCT CTCCTTGCCC GGGTCCCCGT 240 TTTCCCCCGG CGCAGTCCTC CTCCGGTGGG CGCCTCCGCA CCTCGGCGCA GGCGGCACGG 300 CCCTCGGGCC GGGATGGATC CGCCGGGAAG AGGAAGACAA GCCGGGGCGT TGAGCCCCTG 360 CGCACGGTGC CGCCGCGCGT AGTGGGAGCT TACTCGCAGT AGGCTCTCGC TCTTCTAATC 420 A ATG GAT AAA GTG GGG AAA ATG TGG AAC AAC TTA AAA TAC AGA TGC 466 Met Asp Lys Val Gly Lys Met Trp Asn Asn Leu Lys Tyr Arg Cys 1 5 10 15 CAG AAT CTC TTC AGC CAC GAG GGA GGA AGC CGT AAT GAG AAC GTG GAG 514 Gin Asn Leu Phe Ser His Glu Gly Gly Ser Arg Asn Glu Asn Val Glu 20 25 30 ATG AAC CCC AAC AGA TGT CCG TCT GTC AAA GAG AAA AGC ATC AGT CTG 562 Met Asn Pro Asn Arg Cys Pro Ser Val Lys Glu Lys Ser He Ser Leu 35 40 45 GGA GAG GCA GCT CCC CAG CAA GAG AGC AGT CCC TTA AGA GAA AAT GTT 610 Gly Glu Ala Ala Pro Gin Gin Glu Ser Ser Pro Leu Arg Glu Asn Val 50 55 60 GCC TTA CAG CTG GGA CTG AGC CCT TCC AAG ACC TTT TCC AGG CGG AAC 658 Ala Leu Gin Leu Gly Leu Ser Pro Ser Lys Thr Phe Ser Arg Arg Asn 65 70 75 CAA AAC TGT GCC GCA GAG ATC CCT CAA GTG GTT GAA ATC AGC ATC GAG 706 Gin Asn Cys Ala Ala Glu He Pro Gin Val Val Glu He Ser He Glu 80 85 90 95 AAA GAC AGT GAC TCG GGT GCC ACC CCA GGA ACG AGG CTT GCA CGG AGA 754 Lys Asp Ser Asp Ser Gly Ala Thr Pro Gly Thr Arg Leu Ala Arg Arg 100 105 110 GAC TCC TAC TCG CGG CAC GCC CCG TGG GGA GGA AAG AAG AAA CAT TCC 802 Asp Ser Tyr Ser Arg His Ala Pro Trp Gly Gly Lys Lys Lys His Ser 115 120 125 TGT TCC ACA AAG ACC CAG AGT TCA TTG GAT ACC GAG AAA AAG TTT GGT 850 Cys Ser Thr Lys Thr Gin Ser Ser Leu Asp Thr Glu Lys Lys Phe Gly 130 135 140 AGA ACT CGA AGC GGC CTT CAG AGG CGA GAG CGG CGC TAT GGA GTC AGC 898 Arg Thr Arg Ser Gly Leu Gin Arg Arg Glu Arg Arg Tyr Gly Val Ser 145 150 155 TCC ATG CAG GAC ATG GAC AGC GTT TCT AGC CGC GCG GTC GGG AGC CGC 946 Ser Met Gin Asp Met Asp Ser Val Ser Ser Arg Ala Val Gly Ser Arg 160 165 170 175 TCC CTG AGG CAG AGG CTC CAG GAC ACG GTG GGT TTG TGT TTT CCC ATG 994 Ser Leu Arg Gin Arg Leu Gin Asp Thr Val Gly Leu Cys Phe Pro Met 180 185 190 AGA ACT TAC AGC AAG CAG TCA AAG CCA CTC TTT TCC AAT AAA AGA AAA 1042 Arg Thr Tyr Ser Lys Gin Ser Lys Pro Leu Phe Ser Asn Lys Arg Lys 195 200 205 ATA CAT CTT TCT GAA TTA ATG CTG GAG AAA TGC CCT TTT CCT GCT GGC 1090 He His Leu Ser Glu Leu Met Leu Glu Lys Cys Pro Phe Pro Ala Gly 210 215 220 TCG GAT TTA GCA CAA AAG TGG CAT TTG ATT AAA CAG CAT ACC GCC CCT 1138 Ser Asp Leu Ala Gin Lys Trp His Leu He Lys Gin His Thr Ala Pro 225 230 235 GTG AGC CCA CAC TCA ACA TTT TTT GAT ACA TTT GAT CCA TCA CTG GTG 1186 Val Ser Pro His Ser Thr Phe Phe Asp Thr Phe Asp Pro Ser Leu Val 240 245 250 255 TCT ACA GAA GAT GAA GAA GAT AGG CTT CGC GAG AGA AGA CGG CTT AGT 1234 Ser Thr Glu Asp Glu Glu Asp Arg Leu Arg Glu Arg Arg Arg Leu Ser 260 265 270 ATC GAA GAA GGG GTG GAT CCC CCT CCC AAC GCA CAA ATA CAC ACC TTT 1282 He Glu Glu Gly Val Asp Pro Pro Pro Asn Ala Gin He His Thr Phe 275 280 285 GAA GCT ACT GCA CAG GTC AAC CCA TTG TAT AAG CTG GGA CCA AAG TTA 1330 Glu Ala Thr Ala Gin Val Asn Pro Leu Tyr Lys Leu Gly Pro Lys Leu 290 295 300 GCT CCT GGG ATG ACA GAG ATA AGT GGA GAT GGT TCT GCA ATT CCA CAA 1378 Ala Pro Gly Met Thr Glu He Ser Gly Asp Gly Ser Ala He Pro Gin 305 310 315 GCA ATT GTG ACT CAG AAG AGG ATT CAA CCA CCC TAT GTC TGC AGT CAC 1426 Ala He Val Thr Gin Lys Arg He Gin Pro Pro Tyr Val Cys Ser His 320 325 330 335 GGA GGC AGA AGC AGC GCC AGG TGT CCG GGG ACA GCC ACG CGC ACG TTA 1474 Gly Gly Arg Ser Ser Ala Arg Cys Pro Gly Thr Ala Thr Arg Thr Leu 340 345 350 GCA GAC AGG GAG CTT GGA AAG TTC ATA CGC AGA TCG ATT ACA TAC ACT 1522 SUBSTITUTE SHEET ' (RULE 26) Ala Asp Arg Glu Leu Gly Lys Phe He Arg Arg Ser He Thr Tyr Thr 355 360 365 GCC TCG TGC CAG ATT TGC TTC AGA TCA CAG GGA ATC CCT GTT ACT GGG 1570 Ala Ser Cys Gin He Cys Phe Arg Ser Gin Gly He Pro Val Thr Gly 370 375 380 GCG TGA TGG ACC GAT ACG AGG CCG AAG CCC TTC TAG AAG GGA AAC CGG 1618 Ala * Trp Thr Asp Thr Arg Pro Lys Pro Phe * Lys Gly Asn Arg 385 390 395 AAG GCA CGT TCT TGC TCA GGG ACT CTG CAC AGG AGG ACT ACC TCT TCT 1666 Lys Ala Arg Ser Cys Ser Gly Thr Leu His Arg Arg Thr Thr Ser Ser 400 405 410 415 CTG TGA GCT TCC GCC GCT ACA ACA GGT CTC TGC ACG CCC GGA TCG AGC 1714 Leu * Ala Ser Ala Ala Thr Thr Gly Leu Cys Thr Pro Gly Ser Ser 420 425 430 AGT GGA ACC ACA ACT TCA GCT TCG ATG CCC ATG ACC CCT GCG TGT TTC 1762 Ser Gly Thr Thr Thr Ser Ala Ser Met Pro Met Thr Pro Ala Cys Phe 435 440 445 ACT CCT CCA CGT CAC GGG GCT TCT CGA ACA CTA TAA AGA CCC CAG CTC 1810 Thr Pro Pro Arg His Gly Ala Ser Arg Thr Leu * Arg Pro Gin Leu 450 455 460 TTG CAT GTT TTT TGA ACC GTT GCT AAC GAT ATC ACT GAA TAG AAC TTT 1858 Leu His Val Phe * Thr Val Ala Asn Asp He Thr Glu * Asn Phe 465 470 475 CCC TTT CAG CCT GCA GTA TAT CTG CCG CGC AGT GAT CTG CAG ATG CAC 1906 Pro Phe Gin Pro Ala Val Tyr Leu Pro Arg Ser Asp Leu Gin Met His 480 485 490 495 TAC GTA TGA TGG GAT TGA CGG GCT CCC GCT ACC GTC GAT GTT ACA GGA 1954 Tyr Val * Trp Asp * Arg Ala Pro Ala Thr Val Asp Val Thr Gly 500 505 510 τττ τττ AAA AGA GTA TCA TTA TAA ACA p j ^ AGT TAG GGT TCG CTG Qττ 2002 Phe Phe Lys Arg Val Ser Leu * Thr Lys Ser * Gly Ser Leu Val 515 520 525 AGA ACG AGA CCA GTC AAA GCA AAG TAACTCCTGT CCCCAAAGGG CACTAACTAA 2056 Arg Thr Arg Pro Val Lys Ala Lys 530 535 GTCTGCTCCT CCCGTGCATC GAACTGCACC CATAGGAGGC AGTCAGCTGC TAGGATTTCC 2116 CACCCAGAAT GGGAGCTTAG TCATTAGCCT CTGCCCTATG GGGTCCGCTG TTCCTCAGAC 2176 AAAGGTGCCT AGGGACAGCA AGATGGCTTG CAGGTGTTCG GTGGGCTGTG ACAACTGAGG 2236 GAGGCAACTC TGGGGCATTT GCTATGAAGA ATTCTATTTC TTACCGAAGA ACAAATTATT 2296 AATATTGGAT GGGTATTTCA ATAGTGTGAC TAATGTTTGA AATTATTTTT TCTAAGAATT 2356 TTTCTATAAC CTTCAGAAAA AGTAGTGATG TTTGTAGTTA CTATAAATCA AGCTTTGAAA 2416 GTTCAAAACA AACAAGTTAA ATAAAAGACT ACCTTCCTTT TAGAGAAAAC AAATGCAAGT 2476 TTTCCCAGCC ACAGGCATTG TGCACTGTTA ATGTTGCTTG TTATCAGCTC CTTTCTCCTC 2536 C 2537 (2) INFORMATION FOR SEQ ID NO: 18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 535 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: Met Asp Lys Val Gly Lys Met Trp Asn Asn Leu Lys Tyr Arg Cys Gin 1 5 10 15 Asn Leu Phe Ser His Glu Gly Gly Ser Arg Asn Glu Asn Val Glu Met 20 25 30 Asn Pro Asn Arg Cys Pro Ser Val Lys Glu Lys Ser He Ser Leu Gly 35 40 45 Glu Ala Ala Pro Gin Gin Glu Ser Ser Pro Leu Arg Glu Asn Val Ala 50 55 60 Leu Gin Leu Gly Leu Ser Pro Ser Lys Thr Phe Ser Arg Arg Asn Gin 65 70 75 80 Asn Cys Ala Ala Glu He Pro Gin Val Val Glu He Ser He Glu Lys 85 90 95 Asp Ser Asp Ser Gly Ala Thr Pro Gly Thr Arg Leu Ala Arg Arg Asp 100 105 110 Ser Tyr Ser Arg His Ala Pro Trp Gly Gly Lys Lys Lys His Ser Cys 115 120 125 Ser Thr Lys Thr Gin Ser Ser Leu Asp Thr Glu Lys Lys Phe Gly Arg 130 135 140 Thr Arg Ser Gly Leu Gin Arg Arg Glu Arg Arg Tyr Gly Val Ser Ser 145 150 155 160 Met Gin Asp Met Asp Ser Val Ser Ser Arg Ala Val Gly Ser Arg Ser 165 170 175 Leu Arg Gin Arg Leu Gin Asp Thr Val Gly Leu Cys Phe Pro Met Arg 180 185 190 Thr Tyr Ser Lys Gin Ser Lys Pro Leu Phe Ser Asn Lys Arg Lys He 195 200 205 His Leu Ser Glu Leu Met Leu Glu Lys Cys Pro Phe Pro Ala Gly Ser 210 215 220 Asp Leu Ala Gin Lys Trp His Leu He Lys Gin His Thr Ala Pro Val 225 230 235 240 Ser Pro His Ser Thr Phe Phe Asp Thr Phe Asp Pro Ser Leu Val Ser 245 250 255 Thr Glu Asp Glu Glu Asp Arg Leu Arg Glu Arg Arg Arg Leu Ser He 260 265 270 Glu Glu Gly Val Asp Pro Pro Pro Asn Ala Gin He His Thr Phe Glu 275 280 285 Ala Thr Ala Gin Val Asn Pro Leu Tyr Lys Leu Gly Pro Lys Leu Ala 290 295 300 Pro Gly Met Thr Glu He Ser Gly Asp Gly Ser Ala He Pro Gin Ala 305 310 315 320 He Val Thr Gin Lys Arg He Gin Pro Pro Tyr Val Cys Ser His Gly 325 330 335 Gly Arg Ser Ser Ala Arg Cys Pro Gly Thr Ala Thr Arg Thr Leu Ala 340 345 350 Asp Arg Glu Leu Gly Lys Phe He Arg Arg Ser He Thr Tyr Thr Ala 355 360 365 Ser Cys Gin He Cys Phe Arg Ser Gin Gly He Pro Val Thr Gly Ala 370 375 380 * Trp Thr Asp Thr Arg Pro Lys Pro Phe * Lys Gly Asn Arg Lys 385 390 395 400 Ala Arg Ser Cys Ser Gly Thr Leu His Arg Arg Thr Thr Ser Ser Leu 405 410 415 * Ala Ser Ala Ala Thr Thr Gly Leu Cys Thr Pro Gly Ser Ser Ser 420 425 430 Gly Thr Thr Thr Ser Ala Ser Met Pro Met Thr Pro Ala Cys Phe Thr 435 440 445 Pro Pro Arg His Gly Ala Ser Arg Thr Leu * Arg Pro Gin Leu Leu 450 455 460 His Val Phe * Thr Val Ala Asn Asp He Thr Glu * Asn Phe Pro 465 470 475 480 Phe Gin Pro Ala Val Tyr Leu Pro Arg Ser Asp Leu Gin Met His Tyr 485 490 495 Val * Trp Asp * Arg Ala Pro Ala Thr Val Asp Val Thr Gly Phe 500 505 510 Phe Lys Arg Val Ser Leu * Thr Lys Ser * Gly Ser Leu Val Arg 515 520 525 Thr Arg Pro Val Lys Ala Lys 530 535 SUBSTTTUTE SHEET (RULE 26) (2) INFORMATION FOR SEQ ID NO: 19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1221 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19: GATTAAACAG CATACAGCTC CTGTGAGCCC ACATTCAACA TTTTTTGATA CTTTGATCCA 60 TCTTTGGTTT CTACAGAAGA TGAAGAAGAT AGGCTTAGAG AGAGAAGGCG GCTTAGTATT 120 GAAGAAGGGG TTGATCCCCC TCCCAATGCA CAAATACATA CATTTGAAGC TACTGCACAG 180 GTTAATCCAT TATTAAACTG GGACCAAAAT TAGCTCCTGG AATGACTGAA ATAAGTGGGG 240 ACAGTTCTGC AATTCCACAA GCTAATTGTG ACTCGGAAGA GGATACAACC ACCCTGTGTT 300 GCAGTCACGG AGGCAGAAGC AGCGTCAGAT ATCTGGAGAC AGCCATACCC ATGTTAGCAG 360 ACAGGGAGCT TGGAAAGTCC ACACACAGAT TGATTACATA CACTGCTTCG TGCCTGATTT 420 GCTTCAAATT ACAGGGAATC CCTGTTACTG GGGAGTGATG GACCGTTATG AAGCAGAAGC 480 CCTTCTCGAA GGGAAACCTG AAGGCACGTT TTTGCTCAGG GACTCTGCGC AAGAGGACTA 540 CTTCTTCTCT GTGAGCTTCC GCCGATACAA CAGATCCCTG CATGCCCGAA TTGAGCAGTG 600 GAATCACAAC TTTAGTTTCG ACGCCCATGA CCCGTGTGTA TTTCACTCCT CCACTGTAAC 660 GGGACTTTTA GAACATTATA AAGATCCCAG TTCGTGCATG TTTTTTGAAC CATTGCTTAC 720 TATATCACTA AATAGGACTT TCCCTTTTAG CCTGCAGTAT ATCTGTCGCG CGGTAATCTG 780 CAGGTGCACT ACGTATGATG GAATTGATGG GCTCCCTCTA CCCTCAATGT TACAGGATTT 840 TTTAAAAGAG TATCATTATA AACAAAAAGT TAGAGTTCGC TGGTTGGAAC GAGAACCAGT 900 CAAGGCAAAG TAAACTCTCC GGTCCCCAAA GGGTGTTAAC TAGGTCCGCT TTCATGTGCA 960 TCAGACAGTA CACCTATAGC AAGCACACGT AGCAGTGTTA GGCTTTTTCA TACAGTATGT 1020 AAGCTTAGTG TTAGTATCTG TCAGATGCTA CCTGCTGTTA CTTATTCAGA TAAACATGGT 1080 GCCTATTGGA ACAATAGCGG ATAGAGCTAC AGGTGTTCAG TAAGACTACA AAAACATTTT 1140 GCCTATTTCG CTAACAGTTT GGTTTTTAAT GGCTGTGGTA TTTGAGTGAG GCAACTCTGG 1200 GGCATTTGTT ATGAAGAAAT G 1221 (2) INFORMATION FOR SEQ ID NO: 20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2369 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 116..1330 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20: GGCACGAGGC GGTGGTGGCG GCGGCGGGCG CGGCCGCGGC GGGGCGGGCG CGGAATGAAG 60 GCCCACGGCC CTGGGGGCTG AGGCGCCCGC CGCCTGGGGC GGGCCGCGCG TCCTC ATG 118 Met 1 GAG GCC GGA GAG GAG CCG CTG CTG CTG GCT GAA CTC AAG CCT GGG CGC 166 Glu Ala Gly Glu Glu Pro Leu Leu Leu Ala Glu Leu Lys Pro Gly Arg 5 10 15 CCC CAC CAG TTC GAC TGG AAG TCA AGC TGC GAG ACC TGG AGC GTG GCC 214 Pro His Gin Phe Asp Trp Lys Ser Ser Cys Glu Thr Trp Ser Val Ala 20 25 30 TTC TCG CCA GAC GGT TCC TGG TTC GCC TGG TCT CAA GGA CAC TGC GTG 262 SUBSTTTUTE SHEET (RULE 26) Phe Ser Pro Asp Gly Ser Trp Phe Ala Trp Ser Gin Gly His Cys Val 35 40 45 GTC AAG CTG GTC CCC TGG CCC TTA GAG GAA CAG TTC ATC CCT AAA GGA 310 Val Lys Leu Val Pro Trp Pro Leu Glu Glu Gin Phe He Pro Lys Gly 50 55 60 65 TTC GAA GCC AAG AGC CGA AGC AGC AAG AAT GAC CCA AAA GGA CGG GGC 358 Phe Glu Ala Lys Ser Arg Ser Ser Lys Asn Asp Pro Lys Gly Arg Gly 70 75 80 AGT CTG AAG GAG AAG ACG CTG GAC TGT GGC CAG ATT GTG TGG GGG CTG 406 Ser Leu Lys Glu Lys Thr Leu Asp Cys Gly Gin He Val Trp Gly Leu 85 90 95 GCC TTC AGC CCG TGG CCC TCT CCA CCC AGC AGG AAA CTC TGG GCA CGT 454 Ala Phe Ser Pro Trp Pro Ser Pro Pro Ser Arg Lys Leu Trp Ala Arg 100 105 110 CAC CAT CCC CAG GCG CCT GAT GTT TCT TGC CTG ATC CTG GCC ACA GGT 502 His His Pro Gin Ala Pro Asp Val Ser Cys Leu He Leu Ala Thr Gly 115 120 125 CTC AAC GAT GGG CAG ATC AAG ATT TGG GAG GTA CAG ACA GGC CTC CTG 550 Leu Asn Asp Gly Gin He Lys He Trp Glu Val Gin Thr Gly Leu Leu 130 135 140 145 CTT CTG AAT CTT TCT GGC CAC CAA GAC GTC GTG AGA GAT CTG AGC TTC 598 Leu Leu Asn Leu Ser Gly His Gin Asp Val Val Arg Asp Leu Ser Phe 150 155 160 ACG CCC AGC GGC AGT TTG ATT TTG GTC TCT GCA TCC CGG GAT AAG ACA 646 Thr Pro Ser Gly Ser Leu He Leu Val Ser Ala Ser Arg Asp Lys Thr 165 170 175 CTT CGA ATT TGG GAC CTG AAT AAA CAC GGT AAG CAG ATC CAG GTG TTA 694 Leu Arg He Trp Asp Leu Asn Lys His Gly Lys Gin He Gin Val Leu 180 185 190 TCC GGC CAT CTG CAG TGG GTT TAC TGC TGC TCC ATC TCC CCT GAC TGT 742 Ser Gly His Leu Gin Trp Val Tyr Cys Cys Ser He Ser Pro Asp Cys 195 200 205 AGC ATG CTG TGC TCT GCA GCT GGG GAG AAG TCG GTC TTT CTG TGG AGC 790 Ser Met Leu Cys Ser Ala Ala Gly Glu Lys Ser Val Phe Leu Trp Ser 210 215 220 225 ATG CGG TCC TAC ACA CTA ATC CGG AAA CTA GAA GGC CAC CAA AGC AGT 838 Met Arg Ser Tyr Thr Leu He Arg Lys Leu Glu Gly His Gin Ser Ser 230 235 240 GTT GTC TCC TGT GAT TTC TCT CCT GAT TCA GCC TTG CTT GTC ACA GCT 886 Val Val Ser Cys Asp Phe Ser Pro Asp Ser Ala Leu Leu Val Thr Ala 245 250 255 TCG TAT GAC ACC AGT GTG ATT ATG TGG GAC CCC TAC ACC GGC GCG AGG 934 Ser Tyr Asp Thr Ser Val He Met Trp Asp Pro Tyr Thr Gly Ala Arg 260 265 270 CTG AGG TCA CTT CAT CAC ACA CAA CTT GAA CCC ACC ATG GAT GAC AGT 982 Leu Arg Ser Leu His His Thr Gin Leu Glu Pro Thr Met Asp Asp Ser 275 280 285 GAC GTC CAC ATG AGC TCC CTG AGG TCC GTG TGC TTC TCA CCT GAA GGC 1030 Asp Val His Met Ser Ser Leu Arg Ser Val Cys Phe Ser Pro Glu Gly 290 295 300 305 TTG TAT CTC GCT ACG GTG GCA GAT GAC AGG CTG CTC AGG ATC TGG GCT 1078 Leu Tyr Leu Ala Thr Val Ala Asp Asp Arg Leu Leu Arg He Trp Ala 310 315 320 CTG GAA CTG AAG GCT CCG GTT GCC TTT GCT CCG ATG ACC AAT GGT CTT 1126 Leu Glu Leu Lys Ala Pro Val Ala Phe Ala Pro Met Thr Asn Gly Leu 325 330 335 TGC TGC ACG TTC TTC CCA CAC GGT GGA ATT ATT GCC ACA GGG ACG AGA 1174 Cys Cys Thr Phe Phe Pro His Gly Gly He He Ala Thr Gly Thr Arg 340 345 350 GAT GGC CAT GTC CAG TTC TGG ACA GCT CCC CGG GTC CTG TCC TCA CTG 1222 Asp Gly His Val Gin Phe Trp Thr Ala Pro Arg Val Leu Ser Ser Leu 355 360 365 AAG CAC TTA TGC AGG AAA GCC CTC CGA AGT TTC CTG ACA ACG TAT CAA 1270 Lys His Leu Cys Arg Lys Ala Leu Arg Ser Phe Leu Thr Thr Tyr Gin 370 375 380 385 GTC CTA GCA CTG CCA ATC CCC AAG AAG ATG AAA GAG TTC CTC ACA TAC 1318 Val Leu Ala Leu Pro He Pro Lys Lys Met Lys Glu Phe Leu Thr Tyr 390 395 400 AGG ACT TTC TAGCAGTGCC GGCTCCCCCA CCTCCTGCAG CAGCAGCAGT 1367 Arg Thr Phe 405 ACAAGGGACT GGCTAGGATG GAGTCAGGCA GCTCACACTG GACCAGTGTG GACCTTCCTT 1427 CCTCCCATGG CATGTGCAAG TAGGTCTGCG TGACCCCACT TCTGTGGTGC CGGCCTTACC 1487 TCGTCTTCAT CCGTGGTGAG CAGCCTTCGT CAGTCTAGTT GTGTTGAAGC CAAGTGCAGT 1547 TGTGGATGTT GCTGGGGTAA TAAAGGCAAG CGGGCTCCAG AGCCTCTCTG GTGGCGGCCA 1607 AGCCACACTC CCTTAACTGG GAAGTACCTG CCACGTAGGG CATTTCTGCT GCCTATTTCC 1667 AGCCAGCGGC TGCATGGTTT GAAGTTCCTC CGTTGTGGTC AGAAGAACTC TGGTGTTTGG 1727 TTCCCTGCTC AGCTGCGCGT GGACTGGGCT GAGCTCCTCA CCATACACTA GTGCCGGCTT 1787 TTGTTTCCTG TAAACAGTGG TTGCATGTGT AGAGAAGTAA CAAGCGAGTA TTCAGATCAT 1847 ACGAGGAGGC GTTCCTCGGT GCATGACGGT CAGATGGCCA TTTATCAGCA TATTTATTTG 1907 TATTTTCTCA GCACATAGTA AGGTACAACT GTGTTTTCTC AATTGTCTCG AAAAAACAGA 1967 GTTCTTAAGT GGCCCAGTTG TGGAGCCAAG TCTAAGTCGT GTGGAGTCAG TGCTGACATC 2027 ACTGGCTTGT GCTGTCTGTC ACATGTGTTT GTCTCTGCTG CTTGACCTCA TGGGATGTAC 2087 CCTCCAGTTC AACTGCCCAA AACAGACAGC CCCTTCCAAG CACCGTTCTT TGACAGCGGT 2147 AGCAGCTACC TATTCAAGAC GCCTCACACA AAATCTGCCT TAGAAAGTTA ATATATTTTA 2207 AATTATTTTA AAAGAAACTC AACATCTTAT TCTTTGGCCT TTCTTAATTG ATGCTTTATG 2267 GAGGCAGTGT TAACATTGTA CAGTGTATGC ATAGAGGAGT CTCCTCTATT TGAAGAACAA 2327 TGCAAAATGA GGCTTTCATT GAAGGGAAAA AAAAAAAAAA AA 2369 (2) INFORMATION FOR SEQ ID NO: 21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 404 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21: Met Glu Ala Gly Glu Glu Pro Leu Leu Leu Ala Glu Leu Lys Pro Gly 1 5 10 15 Arg Pro His Gin Phe Asp Trp Lys Ser Ser Cys Glu Thr Trp Ser Val 20 25 30 Ala Phe Ser Pro Asp Gly Ser Trp Phe Ala Trp Ser Gin Gly His Cys 35 40 45 Val Val Lys Leu Val Pro Trp Pro Leu Glu Glu Gin Phe He Pro Lys 50 55 60 Gly Phe Glu Ala Lys Ser Arg Ser Ser Lys Asn Asp Pro Lys Gly Arg 65 70 75 80 Gly Ser Leu Lys Glu Lys Thr Leu Asp Cys Gly Gin He Val Trp Gly 85 90 95 Leu Ala Phe Ser Pro Trp Pro Ser Pro Pro Ser Arg Lys Leu Trp Ala 100 105 110 Arg His His Pro Gin Ala Pro Asp Val Ser Cys Leu He Leu Ala Thr 115 120 125 Gly Leu Asn Asp Gly Gin He Lys He Trp Glu Val Gin Thr Gly Leu 130 135 140 Leu Leu Leu Asn Leu Ser Gly His Gin Asp Val Val Arg Asp Leu Ser 145 150 155 160 Phe Thr Pro Ser Gly Ser Leu He Leu Val Ser Ala Ser Arg Asp Lys 165 170 175 Thr Leu Arg He Trp Asp Leu Asn Lys His Gly Lys Gin He Gin Val 180 185 190 Leu Ser Gly His Leu Gin Trp Val Tyr Cys Cys Ser He Ser Pro Asp 195 200 205 Cys Ser Met Leu Cys Ser Ala Ala Gly Glu Lys Ser Val Phe Leu Trp 210 215 220 Ser Met Arg Ser Tyr Thr Leu He Arg Lys Leu Glu Gly His Gin Ser 225 230 235 240 Ser Val Val Ser Cys Asp Phe Ser Pro Asp Ser Ala Leu Leu Val Thr 245 250 255 Ala Ser Tyr Asp Thr Ser Val He Met Trp Asp Pro Tyr Thr Gly Ala 260 265 270 Arg Leu Arg Ser Leu His His Thr Gin Leu Glu Pro Thr Met Asp Asp 275 280 285 Ser Asp Val His Met Ser Ser Leu Arg Ser Val Cys Phe Ser Pro Glu 290 295 300 Gly Leu Tyr Leu Ala Thr Val Ala Asp Asp Arg Leu Leu Arg He Trp 305 310 315 320 Ala Leu Glu Leu Lys Ala Pro Val Ala Phe Ala Pro Met Thr Asn Gly 325 330 335 Leu Cys Cys Thr Phe Phe Pro His Gly Gly He He Ala Thr Gly Thr 340 345 350 Arg Asp Gly His Val Gin Phe Trp Thr Ala Pro Arg Val Leu Ser Ser 355 360 365 Leu Lys His Leu Cys Arg Lys Ala Leu Arg Ser Phe Leu Thr Thr Tyr 370 375 380 Gin Val Leu Ala Leu Pro He Pro Lys Lys Met Lys Glu Phe Leu Thr 385 390 395 400 Tyr Arg Thr Phe (2) INFORMATION FOR SEQ ID NO: 22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1246 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: GACACTGCAT CGTCAAACTG ATCCCCTGGC CGTTGGAGGA GCAGTTCATC CCTAAAGGGT 60 TTGAAGCCAA AAGCCGAAGT AGCAAAAATG AGACGAAAGG GCGGGGCAGC CCAAAAGAGA 120 AGACGCTGGA CTGTGGTCAG ATTGTCTGGG GGCTGGCCTT CAGCCTGTGC TTTCCCCACC 180 CAGCAGGAAG CTCTGGGCAC GCCACCACCC CCAAGTGCCC GATGTCTCTT GCCTGGTTCT 240 TGCTACGGGA CTCAACGATG GGCAGATCAA GATCTGGGAG GTGCAGACAG GGCTCCTGCT 300 TTTGAATCTT TCCGGCCACC AAGATGTCGT GAGAGATCTG AGCTTCACAC CCAGTGGCAG 360 TTTGATTTTG GTCTCCGCGT CACGGGATAA GACTCTTCGC ATCTGGGACC TGAATAAACA 420 CGGTAAACAG ATTCAAGTGT TATCGGGCCA CCTGCAGTGG GTTTACTGCT GTTCCATCTC 480 CCCAGACTGC AGCATGCTGT GCTCTGCAGC TGGAGAGAAG TCGGTCTTTC TATGGAGCAT 540 GAGGTCCTAC ACGTTAATTC GGAAGCTAGA GGGCCATCAA AGCAGTGTTG TCTCTTGTGA 600 CTTCTCCCCC GACTCTGCCC TGCTTGTCAC GGCTTCTTAC GATACCAATG TGATTATGTG 660 GGACCCCTAC ACCGGCGAAA GGCTGAGGTC ACTCCACCAC ACCCAGGTTG ACCCCGCCAT 720 GGATGACAGT GACGTCCACA TTAGCTCACT GAGATCTGTG TGCTTCTCTC CAGAAGGCTT 780 GTACCTTGCC ACGGTGGCAG ATGACAGACT CCTCAGGATC TGGGCCCTGG AACTGAAAAC 840 TCCCATTGCA TTTGCTCCTA TGACCAATGG GCTTTGCTGG CACATTTTTT CCACATGGTG 900 GAGTCATTGC CACAGGGACA AGAGATGGCC ACGTCCAGTT CTGGACAGCT CCTAGGGTCC 960 TGTCCTCACT GAAGCACTTA TGCCGGAAAG CCCTTCGAAG TTTCCTAACA ACTTACCAAG 1020 TCCTAGCACT GCCAATCCCC AAGAAAATGA AAGAGTTCCT CACATACAGG ACTTTTTAAG 1080 CAACACCACA TCTTGTGCTT CTTTGTAGCA GGGTAAATCG TCCTGTCAAA GGGAGTTGCT 1140 GGAATAATGG GCCAAACATC TGGTCTTGCA TTGAAATAGC ATTTCTTTGG GATTGTGAAT 1200 AGAATGTAGC AAAACCAGAT TCCAGTGTAC TAGTCATGGA TTTTTC 1246 (2) INFORMATION FOR SEQ ID NO: 23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 422 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: ACCATGGTTC CAAGTCCTCT CCCCTGTGGT CAAGTTGCCC GAATGTTGGG CCCAAGTGCC 60 TTTTCCTCCT TGGGCCTCCC CTTCTGACCT GCAGGACAGT TTTCCGGAGC CCATTTGGTA 120 TGAGGTATTA ATTAGCCTTA ACTAAATTAC AGGGGACTCA GAGGCCGTGC TCCTGACCGA 180 TCCAGACACT ATTTTTTTTT TTTTTTTTTA ACAATGGTGT GCATGTGCAG GAAATGACAA 240 ATTTGTATGT CAGATTATAC AAGGATGTAT TCTTAAACCG CATGACTATT CAGATGGCTA 300 CTGAGTTATC AGTGGCCATT TATTAGCATC ATATTTATTT GTATTTTCTC AACAGATGTT 360 AAGGTACAAC TGTGTTTTTC TCGATTATCT AAAAACCATA GTACTTAAAT TGAAAAAAAA 420 AA 422 (2) INFORMATION FOR SEQ ID NO: 24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2019 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24: GGCACGAGGC GGGGTCAGGG CGGAGGCTGA GGACCAAGTA GGCATGGCGG AGGGCGGGAC 60 CGGCCCCGAT GGACGGGCCG GCCCGGGACC CGCAGGTCCT AATCTGAAGG AGTGGCTGAG 120 GGAGCAGTTC TGTGACCATC CACTGGAGCA CTGTGACGAT ACAAGACTCC ATGATGCAGC 180 CTATGTAGGG GACCTCCAGA CCCTCAGGAA CCTACTGCAA GAGGAGAGCT ACCGGAGCCG 240 CATCAATGAG AAGTCTGTCT GGTGCTGCGG CTGGCTTCCC TGCACACCAC TGAGGATCGC 300 AGCCACTGCA GGCCATGGGA ACTGTGTGGA CTTCCTCATA CGCAAAGGGG CCGAGGTGGA 360 CCTGGTGGAT GTCAAGGGGC AGACTGCCCT GTATGTGGCT GTAGTGAACG GGCACTTGGA 420 GAGCACTGAG ATCCTTTTGG AAGCTGGTGC TGATCCCAAC GGCAGCCGGC ACCACCGCAG 480 CACTCCTGTG TACCATGCCT YTCGTGTGGG TAGGGACGAC ATCCTGAAGG CTCTTATCAG 540 GTATGGGGCA GATGTTGATG TCAACCATCA TCTGAATTCT GACACCCGGC CCCCTTTTTC 600 ACGGCGGCTA ACCTCCTTGG TGGTCTGTCC TCTATACATC AGTGCTGCCT ACCATAACCT 660 TCAGTGCTTC AGGCTGCTCT TGCAGGCTGG GGCAAATCCT GACTTCAATT GCAATGGCCC 720 TGTCAACACC CAGGAGTTCT ACAGGGGATC CCCTGGGTGT GTCATGGATG CTGTCCTGCG 780 CCATGGCTGT GAAGCAGCCT TCGTGAGTCT GTTGGTAGAG TTTGGAGCCA ACCTGAACCT 840 GGTGAAGTGG GAATCCCTGG GCCCAGAGGC AAGAGGCAGA AGAAAGATGG ATCCTGAGGC 900 CTTGCAGGTC TTTAAAGAGG CCAGAAGTAT TCCCAGGACC TTGCTGAGTT TGTGCCGGGT 960 GGCTGTGAGA AGAGCTCTTG GCAAATACCG ACTGCATCTG GTTCCCTCGC TGCCGCTGCC 1020 AGACCCCATA AAGAAGTTTT TGCTTTATGA GTAGCATTCA CATGCAGTGC TGACTGCAAT 1080 GTGGAAGCCG ATCACCTGCA GTGAAAACTG ACACAGACTC TGGCATCCTG GGAACCATGG 1140 CCTGTGCTGC CAGCTTGATC CTTGGCTGTC AGTGAAGAAA AAACGGCTGT GTTCTCTTGG 1200 ACTGTGATTC TATCTCAGGT GCTTGGGCCA TCGAACGCTC CTTGAGTCAT TGTCAACTGA 1260 GAGGCACATA CAAACTTAAT TTTGTTCCTC TTCAGTCTCT CTGTTTTGGA TTCTTCCTGG 1320 CAATGTGTGC AGCATGGGCT GAGCCTGGTG ATTGCCCTAG TGGGGAAGGC TTTTTTCTCC 1380 AGGCTATGCA TCTATTTATG TTCCTACTTT GCAATTTATT GTTCTTTTAA GGCTTGATAT 1440 CAAAACAGAA AGAGGTTTGT TAAGAAAAGA TATAGGGAGA AAGGAATTCC GGTTCCGTGC 1500 ACTTGCTAGC CTGCTTTCCT TGCCTGGGTT TGTCTGTCTA TGCTGCCTGG TGCACATCCC 1560 TTCTCTTTGC TGCCACTGTT CTATTTTGGG AGTTGTCTTC CGTCTAAGAT GGCTTCTGGG 1620 GTTCTATCTT ATTGCACAGA GGTCCCAGAA CAGTGTTCAT AGGGCACCAT CTGCTCTGCC 1680 AAGGGTTTTC TGATGTCTTA CCCTGGGGAT CTTCAGACAG TGGTTACCTT TAGGAGACCC 1740 ACCTGGAACT AACCATTAAG TGACTGCCCA CATTCAGATC AGGGACCATC TTAATAGTAC 1800 TCACTGCCAG TCCTCACAAG AGAAGATGAC ACGGGTGCTC TCTTCAGACA CTCCCATACA 1860 GGAAGTTGGA AAATGTCTTG GTCACCTGGG TTGTTCCCAG GCTACAACTT CTTGGTGTTC 1920 CACTAARACC AGRATATCCT AGTTTTTTGG GTTGACTGTT CCCTCCCCAC TTTCCTTGAA 1980 NCCCAATGCC CNTTTGTKTN GGTTGCTTCC CTAAAAKTT 2019 (2) INFORMATION FOR SEQ ID NO: 25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 350 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25: Ala Arg Gly Gly Val Arg Ala Glu Ala Glu Asp Gin Val Gly Met Ala 1 5 10 15 Glu Gly Gly Thr Gly Pro Asp Gly Arg Ala Gly Pro Gly Pro Ala Gly 20 25 30 Pro Asn Leu Lys Glu Trp Leu Arg Glu Gin Phe Cys Asp His Pro Leu 35 40 45 Glu His Cys Asp Asp Thr Arg Leu His Asp Ala Ala Tyr Val Gly Asp 50 55 60 Leu Gin Thr Leu Arg Asn Leu Leu Gin Glu Glu Ser Tyr Arg Ser Arg 65 70 75 80 He Asn Glu Lys Ser Val Trp Cys Cys Gly Trp Leu Pro Cys Thr Pro 85 90 95 Leu Arg He Ala Ala Thr Ala Gly His Gly Asn Cys Val Asp Phe Leu 100 105 110 He Arg Lys Gly Ala Glu Val Asp Leu Val Asp Val Lys Gly Gin Thr 115 120 125 Ala Leu Tyr Val Ala Val Val Asn Gly His Leu Glu Ser Thr Glu He 130 135 140 Leu Leu Glu Ala Gly Ala Asp Pro Asn Gly Ser Arg His His Arg Ser 145 150 155 160 Thr Pro Val Tyr His Ala Xaa Arg Val Gly Arg Asp Asp He Leu Lys 165 170 175 Ala Leu He Arg Tyr Gly Ala Asp Val Asp Val Asn His His Leu Asn 180 185 190 Ser Asp Thr Arg Pro Pro Phe Ser Arg Arg Leu Thr Ser Leu Val Val 195 200 205 Cys Pro Leu Tyr He Ser Ala Ala Tyr His Asn Leu Gin Cys Phe Arg 210 215 220 Leu Leu Leu Gin Ala Gly Ala Asn Pro Asp Phe Asn Cys Asn Gly Pro 225 230 235 240 Val Asn Thr Gin Glu Phe Tyr Arg Gly Ser Pro Gly Cys Val Met Asp 245 250 255 Ala Val Leu Arg His Gly Cys Glu Ala Ala Phe Val Ser Leu Leu Val 260 265 270 Glu Phe Gly Ala Asn Leu Asn Leu Val Lys Trp Glu Ser Leu Gly Pro 275 280 285 Glu Ala Arg Gly Arg Arg Lys Met Asp Pro Glu Ala Leu Gin Val Phe 290 295 300 Lys Glu Ala Arg Ser He Pro Arg Thr Leu Leu Ser Leu Cys Arg Val 305 310 315 320 Ala Val Arg Arg Ala Leu Gly Lys Tyr Arg Leu His Leu Val Pro Ser 325 330 335 Leu Pro Leu Pro Asp Pro He Lys Lys Phe Leu Leu Tyr Glu 340 345 350 (2) INFORMATION FOR SEQ ID NO: 26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 419 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26: GCATCCATGG CGGAGGGCGG CAGCACGACG GGCGGGCAGG GCCGGGCTCC GCAGGTCGTA 60 ATCTGAAGGA GTGGCTGAGG GAGCAATTTT GTGATCATCC GCTGGAGCAC TGTGAGGACA 120 CGAGGCTCCA TGATGCAGCT TACGTCGGGG ACCTCCAGAC CCTCAGGAGC CTATTGCAAG 180 AGGAGAGCTA CCGGAGCCGC ATCAACGAGA AGTCTGTCTG GTGCTGTGGC TGGCTCCCCT 240 GCACACCGTT GCGAATCGCG GCCACTGCAG GCCATGGGAG CTGTGTGGAC TTCCTCATCC 300 GGAAGGGGGC CGAGGTGGAT CTGGTGGACG TAAAAGGACA GACGGCCCTG TATGTGGCTG 360 TGGTGAACGG GCACCTAGAG AGTACCCAGA TCCTTCTCGA AGCTGGCGCG GACCCCAAC 419 (2) INFORMATION FOR SEQ ID NO: 27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 595 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27: GAGGAAGAAG AAAAGTGGAC CCTGAGGCCT TGCAGGTCTT TAAAGAGGCC AGAAGTGTTC 60 CCAGAACCTT GCTGTGTCTG TGCCGTGTGG CTGTGAGAAG AGCTCTTGGC AAAACCGGCT 120 TCATCTGATT CCTTCGCTGC CTCTGCCAGA CCCCATAAAG AAGTTTCTAC TCCATGAGTA 180 GACTCCAAGT GCTGCGGTTG ATTCCAGTGA GGGAGAAAGT GATCTGCAGG GAGGTGGACA 240 CCGAGCCCTG AGTGCTGTGC TGCTGCTGGT CTCCTGATGG CTGTTGCTGC AGAAGATGTC 300 CTCGTAGACT GTCATTGCTC CTCAGGTGCC TGGGCCGCTG AACAGTCCTT GGGTCATTGT 360 CAGCTGAGAG GCTTATACTA AAGTTATTAT TGTTTTTCCC AAGTTCTCTG TTCTGGATTT 420 TCAGTTGCAT ATTAATGTAA CGGGCCATGG GGTATGTACA TGTAGGGGCT GAGGTTGGAG 480 GCCTACTAAT TTCCTGTAGG GAAGACTCCC AGCACTTCTG GAACTGTGCT TCTCTTTATT 540 TTTCTACTTC TCAATTTGAT GGTTCGATTA AAGCCTTCTA GTATCTCAAT GAAAA 595 (2) INFORMATION FOR SEQ ID NO: 28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 896 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 4..396 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28: CTG ATG TCC GCA ATT CTG AAG GTT GGA CAC CAC TGC TGG CTG CCT GTG 48 Met Ser Ala He Leu Lys Val Gly His His Cys Trp Leu Pro Val 1 5 10 15 ACA TCC GCT GTC AAT CCC CAA AGG ATG CTG AGG CCA CCA CCA ACC GCT 96 Thr Ser Ala Val Asn Pro Gin Arg Met Leu Arg Pro Pro Pro Thr Ala 20 25 30 GTT TTC AAC TGT GCC GCT TGC TGC TGT CTG TGG GGG CAG ATG CTG ATG 144 Val Phe Asn Cys Ala Ala Cys Cys Cys Leu Trp Gly Gin Met Leu Met 35 40 45 AAT ACA TAC CGT GTA GTT CAG CTT CCT GAG GAG GCC AAG GGC TTG GTG 192 Asn Thr Tyr Arg Val Val Gin Leu Pro Glu Glu Ala Lys Gly Leu Val 50 55 60 CCA CCA GAG ATT CTA CAG AAG TAC CAT GGA TTC TAC TCT TCC CTC TTT 240 Pro Pro Glu He Leu Gin Lys Tyr His Gly Phe Tyr Ser Ser Leu Phe 65 70 75 GCC TTG GTG AGG CAG CCC AGG TCG CTG CAG CAT CTC TGC CGT TGT GCG 288 Ala Leu Val Arg Gin Pro Arg Ser Leu Gin His Leu Cys Arg Cys Ala 80 85 90 95 CTC CGC AGT CAC CTG GAG GGC TGT CTG CCC CAT GCA CTA CCG CGC CTT 336 Leu Arg Ser His Leu Glu Gly Cys Leu Pro His Ala Leu Pro Arg Leu 100 105 110 CCC CTG CCA CCG CGC ATG CTC CGC TTT CTG CAG CTG GAC TTT GAG GAT 384 Pro Leu Pro Pro Arg Met Leu Arg Phe Leu Gin Leu Asp Phe Glu Asp 115 120 125 CTG CTC TAC TAGGCTTGCT GCCCTGTGAA CAAAGCAGAC CCCACCCCCA 433 Leu Leu Tyr 130 CCCCAAGGGC ATCTCTCAGC AATGAATGAT GCAAGGCGGT CTGTCTTCAA GTCAGGAGTG 493 GACGCCTTGA TCCACACTTG AGAGAAGAGG CCAGATCAGC ACCYGGCTGG TAGTGATNGC 553 AGAGGGCACC TGTGCAGATC TGTGTGCGCA CTGGAAATCT CTAGGCTGAA GGCYAGAGCA 613 AATGGTGCAR GTGTTAGTCC TTGGGANGAG AGACAGANGG TGAGAAAGCA AGACAGAGGT 673 GAGAGTGCAC ATGTCAAGTG GTAGATTGCC TTAAAAGAAA GCTAAAAAAA GAAAAAGATT 733 CGGGCGAACT TCTTTAGGGG TAATGCTGCA GCGTGTTAAA CTGACTGACC AGCGTCCATA 793 TCTTTGGACC CTTCCCGGGT GAAAAAGCCC CTTCATCCTC CAGCGCTCCC CAAGGGTGCT 853 TAGCAATACC GGGTGCTTTT CTGCCGCAAA GTGAGTTACC AAA 896 (2) INFORMATION FOR SEQ ID NO: 29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 130 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 29: Met Ser Ala He Leu Lys Val Gly His His Cys Trp Leu Pro Val Thr 1 5 10 15 Ser Ala Val Asn Pro Gin Arg Met Leu Arg Pro Pro Pro Thr Ala Val 20 25 30 Phe Asn Cys Ala Ala Cys Cys Cys Leu Trp Gly Gin Met Leu Met Asn 35 40 45 Thr Tyr Arg Val Val Gin Leu Pro Glu Glu Ala Lys Gly Leu Val Pro 50 55 60 Pro Glu He Leu Gin Lys Tyr His Gly Phe Tyr Ser Ser Leu Phe Ala 65 70 75 80 Leu Val Arg Gin Pro Arg Ser Leu Gin His Leu Cys Arg Cys Ala Leu 85 90 95 Arg Ser His Leu Glu Gly Cys Leu Pro His Ala Leu Pro Arg Leu Pro 100 105 110 Leu Pro Pro Arg Met Leu Arg Phe Leu Gin Leu Asp Phe Glu Asp Leu 115 120 125 Leu Tyr 130 (2) INFORMATION FOR SEQ ID NO: 30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 436 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30: GTGGGGGCGT CATCATGACC TCCTCTAGGG CTCTGCAACA TGACTCCTGT GGTGCAAATC 60 AACAAATTGT TCACTGATGA ATCCACAAGG ATCTCTGGGC CTACAACCAG GTCCTGGTCC 120 ACATGACTGT CGTCTTCGGA GAAGGCACCA CTCGCCCCCG GCAGGTACGG CTGACACCTC 180 CATGGGAGAA GACGTATCCA GGCAGCAGCT GCGCGGCCCT TCAAGAGGGC ACATCCCGTC 240 ATCTAAAGGC ACGGTGTACT GAAGGTAGTC CTGAGACATG AGTCCGATTA CTACAGGCAC 300 GTGTTCCTCC AGGTGGAGGC TCAGGTCCCC GGGTGAGCTG GGGCTGCAGC GGGACTCAGG 360 GCGCGGCTCT GGCTGCAGGT CTCGCAGCTC CCTGGGCTGT AGCTCCCGCA GATCCTTGCG 420 CACACCGTTG ACTGGT 436 (2) INFORMATION FOR SEQ ID NO: 31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2180 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31: TTAATAGTAC CTACATAGTA GAAAATTATA ACTCCACTTT AAAACAATGT TTTCTTTCTA 60 TTCAAATCAA TTTAAAACTT TTTATAAACA TTAATGTTGC AAGAGAATCC AGTCCATTTA 120 TGAAAATTAG TTGACAATCA AGTTCACCCA AGAAAATGTT GACTAAGCTA AAGAAATCAC 180 AGATAAAACA TTTTACCAAA AGGATAGGTA ACACACAAAA AAATGCTATC ACAGGAAGCT 240 ATGATCATCT AATATTTCTT TAATAATAAT TCTAGTTCCA TAGGTTTTCA TGTTATGCCA 300 ATTTGTACCC GAGTTTAATT ACAGAAAAGG CAACAATTTC TAAATTGGTG GTATACATTT 360 CTTTACAATT TTTTAATGTA AGGCCATTTA TTAAAATAGA CAAACTAGAA GATGAAAACG 420 AAGGCAACAG AAAAATTCAA CTTTTCACAA CCAAAAGAAT TAGCACAACC TTAGAAATAA 480 TTTAGAAAAA AGTGTTGTTA AAAGATATGT TGCAGATCTC CGTTCCATTA CCCAAGATTA 540 TGTCAATTCA CGATTCTAAA TAAATCTTTT TAAAGTAAGA GATTAAAAAC TCATCTTCAG 600 TGTATATGTA AATTCCGTGG TTTTATCACA CAGGTATGTT TATTCAACAC TGCTTTGGAA 660 ATGGACCATT TAAAAGGACA TGGCAATTTC CATTCTGTTA AGTTTCATTC AACCTTTACT 720 TAGGGGTTGA TTACCACATG AAATGTGCTT TTAATGCATA AAAATCACAG TGGATTAGCC 780 AGCAAAAGGG ACTGGGCGGG GGGGGCATTG AGGAGAATTT GATAATTCAC ATTGTGATTA 840 TTCTGCACAT TGATGAAACA TAATTCACAC CTCTAAAACC TCAAGACTTC CCTTTTTTAA 900 AGAACCAAAA TAAACCCAAG ACACCTTGCT GACACTTCCC CACCCCTAAA CAAACTGATG 960 ACTCTTTTAC ACATAAAACT GAAATAGTTA TGGCAGCAAA AGATTTTGAT GGCAATGAAA 1020 GTTTGTAAAC TGTATTTCAA TCTCTTGTTC TTATTCCCAA AGTGCAAGAT GCAGGGTTCT 1080 CAATCTTTCA GTAGTGCTTC TCCTGTAAAT AATCCTTCAT TTTGTTTGGC AAAGGCAGTT 1140 TCTGAATTAA GTCTATTCTG GTATACTGAC GTATAACAAA ACGACACAGG TACTGCAACG 1200 AGCGCACCTA TGAACCCCGG AACACTGGTT GGCAAGTTCT GACGGAAGTG CAGATTCCAG 1260 GCAGCGAGAC CTTGAATAAC AAAAAGCTCC CATTTTCAGA GTCCCTGATT GAATGCTCCA 1320 ATTAGATCAA CTATGGACGT ATGTCCTTCC ACATCGGCTG TTCATAAAAG CTAAACCTAC 1380 CATTTGAGTG CTCAATTCTA GTGTGAAGTG TTTTACCATG GGAGCGAAAG TCACAGCTTA 1440 AAAGGTAACG GTCGTCAGAA CTGTCCCGAA CAAGAAAAGA ACCATCTGGC ACGTTTGCTA 1500 GCTTCCCTTC TGCCTCCCAA CGTGTGATTG GTCCCCAGTA CCATCCTTGC TTTGCAAGTT 1560 TTTTCAGCTC CTCTGTAAGG CTTGTCACAA CCATGGGACC ACTACTTTGC ACTGAGTCAT 1620 AAACTCTTGC AACCCCAGGA GCAGAGTTCG GATCAAAATT CAAATGACAG CGCATAACTT 1680 TCAGCCACGT GGGGCTTTCT GTCCAGTGAG TCCACTGAAA GTTCCCCTTT GGGATTTGGA 1740 TTATTCCTGC ATTGGAGTAA CCAATGGTGA AGATTGGAGG GACATCCATC GTGAACCCGC 1800 TCTCCGGGGT TCTGCAACAT GACTCCCGTG GTGCCAATCA ACAAGCCATT CACCGGACTG 1860 ATCCACGAAG ATCTCTGGGG CGACAACTAG GTCCTGGTCT ACCTGACTCT CATCCTCGGG 1920 GAAAGCGCGC CCTCCCACTT GAGGAGGAAC CGCAGAGACT TCCATGGGAG AAGAGCTGTC 1980 CAGACAATAG CTCCGTGATC CTTCCAAAGG ATACATCCCC TCATCTAAAG GCACAGTATA 2040 CTGAATGTAG TCCTGAGGCA TAAGTCCAAT AACGACAGGC ACATGTTCAT CCAGGTGAAG 2100 ATGCAGGTCT CCATTATGAG AAGCCGAGCT CTTCAGTGAA TTGGCTTGCT CCTGGCACGT 2160 GGTCTCAGAC TGGAGGTCGT 2180 (2) INFORMATION FOR SEQ ID NO: 32: (i) SEQUENCE CHARACTERISTICS: SUBSTTTUTE SHEET (RULE 26) (A) LENGTH: 2649 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32: GGCACGAGGC TGTGTCCAGC ACACAGAGAG GGCCCGGCCA TCTGCTTTGG TTCAGAGCCC 60 TGTGTCTGTC TGTCACTTAG ACTCTTCCTC CCGGCTCGCA GCTCACCCTC CATCCTCCTT 120 ACTGGCTCCA GCATGACTCG CTTCTCTTAT GCAGAGTACT TTGCTCTGTT TCACTCTGGC 180 TCTGCACCTT CCAGGTCCCC TTCGTCTCCC GAGAACCCAC CGGCCCGCGC ACCCCTGGGT 240 CTGTTCCAAG GGGTCATGCA GAAGTATAGC AGCAACCTGT TCAAGACCTC CCAGATGGCG 300 GCTATGGACC CCGTGCTGAA GGCCATCAAG GAAGGGGATG AAGAGGCCTT GAAGATCATG 360 ATCCAGGATG GGAAGAATCT TGCAGAGCCC AACAAGGAGG GCTGGCTGCC GCTCCACGAG 420 GCTGCCTACT ATGGCCAGCT GGGCTGCCTG AAAGTCCTGC AGCAAGCCTA CCCAGGGACC 480 ATTGACCAAC GCACACTGCA GGAAGAGACA GCATTATACC TGGCCACATG CAGAGAACAC 540 CTGGATTGCC TCCTGTCGCT GCTCCAGGCG GGGGCAGAGC CTGACATCTC TAACAAATCC 600 AGGGAGACTC CACTTTACAA AGCCTGTGAG CGCAAGAACG CGGAGGCGGT GAGGATATTG 660 GTGCGATACA ACGCAGACGC CAACCACCGC TGTAACAGGG GCTGGACCGC ACTGCACGAG 720 TCTGTCTCCC GCAATGACCT GGAGGTCATG GAGATCCTAG TGAGTGGCGG GGCCAAGGTG 780 GAGGCCAAGA ATGTCTACAG CATCACCCCT TTGTTTGTGG CTGCCCAGAG TGGGCAGCTG 840 GAGGCCCTGA GGTTCCTGGC CAAGCATGGT GCAGACATCA ACACGCAGGC CAGTGACAGT 900 GCATCAGCCC TCTACGAGGC CAGCAAGAAT GAGCATGAAG ACGTGGTAGA GTTTCTTCTC 960 TCTCAGGGCG CCGATGCTAA CAAAGCCAAC AAGGACGGCC TGCTCCCCCT GCATGTTGCC 1020 TCCAAGAAGG GCAACTATAG AATAGTGCAG ATGCTGCTGC CTGTGACCAG CCGCACGCGC 1080 GTGCGCCGTA GCGGCATCAG CCCGCTGCAC CTAGCGGCCG AGCGCAACCA CGACGCGGTG 1140 CTGGAGGCGC TGCTGGCCGC GCGCTTCGAC GTGAACGCAC CTCTGGCTCC CGAGCGCGCC 1200 CGCCTCTACG AGGACCGCCG CAGTTCTGCG CTCTACTTCG CTGTGGTCAA CAACAATGTG 1260 TACGCCACCG AGCTGTTGCT GCTGGCGGGC GCGGACCCCA ACCGCGATGT CATCAGCCCT 1320 CTGCTCGTGG CCATCCGCCA CGGCTGCCTG CGCACCATGC AGCTGCTGTT GGACCATGGC 1380 GCCAACATCG ACGCCTACAT CGCCACTCAC CCCACCGCCT TTCCAGCCAC CATCATGTTT 1440 GCCATGAAGT GCCTGTCGTT ACTCAAGTTC CTTATGGACC TCGGCTGCGA TGGCGAGCCC 1500 TGCTTCTCCT GCCTGTACGG CAACGGGCCG CACCACCCGC CCCGCGACCT GGCCGCTTCC 1560 ACGACGCACC CGTGGACGAC AAGGCACCTA GCGTGGTGCA GTTCTGTGAG TTCCTGTCGG 1620 CCCCGGAAGT GAGCCGCTGG GCGGGACCCA TCATCGATGT CCTCCTGGAC TATGTGGGCA 1680 ACGTGCAGCT GTGCTCCCGG CTGAAGGAGC ACATCGACAG CTTTGAGGAC TGGGCTGTCA 1740 TCAAGGAGAA GGCAGAACCT CCGAGACCTC TGGCTCACCT CTGCCGGCTG CGGGTTCGGA 1800 AGGCCATAGG AAAATACCGG ATAAAACTCC TGGACACACT GCCGCTTCCC GGCAGGCTAA 1860 TCAGATACTT GAAATATGAG AA ACACAGT AACCAGCCTG GAGAGGAGAT GTGGCCTTCA 1920 GACTGTTTCC GGGACGCCCC AGGTGGCCTG CATCCAGGAC CCCCTGGGGT CAGAACAGGT 1980 GTGACCTTGC TGGTTCTTTG CTGGAGCTTC ACCCAAAGTG AGAACCTGAT GTGGGGAGTG 2040 GACGTGGAAC CTCTGCTTTC ACACTGTCAG CGGATCGCAG ACCCGCTCTG CTTCTGGCCA 2100 TAGCCAGAGA CCTTCAACCT GGGGCCAGGG GAGAGCTGGT CTGGGCAAGG TGGCCCAGGC 2160 AGGAATCCTG GCCTTAAGCT GGAGAACTTG TAGGAATCCC TCACTGGACC CTCAGCTTTC 2220 AGGCTGCGAG GGAGACGCCC AGCCCAAGTA TTTTATTTCC GTGACACAAT AACGTTGTAT 2280 CAGAAAAAAA AAAAAACATG GGCGCAGCTT ATTCCTTAGT AGGGTATTTA CTTGCATGCG 2340 CGCTTAAAGC TACTGGAAAC ATGCGTTCCA CTATGCTTGA GAATCCCCTT GCACTGGTAA 2400 ACGAGAGCCG ACGTGCTTCA AGGTTGGATT TTTGGTTGCC CCTTTGGCGT TCCGCGGGTT 2460 TGTCCGACGT AATTGACCCC GTGTTTTGTC ACTTTCGAGT GTTCCGACTA TTGGGGGGCT 2520 TTTGGTTGTC CCCAAAATTG TGGGTGGTGT GCGGACGCCA CGAGAAGTGG TTCATGGGCG 2580 ATAATCATTA CTGGAGAATG TAGAGCGGCG GTTTTACGAA TAAATATTTT TTAAGCCGCC 2640 TTCCCAAAA 2649 ( 2 ) INFORMATION FOR SEQ ID NO : 33 : (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 495 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33: CCTCCTGAGA GTTCGCCGGC CCGGGCCCAA TGGGTTGTTC CAAGGGGTCA TGCAGAAATA 60 CAGCAGCAGC TTGTTCAAGA CCTCCCAGCT GGCGCCTGCG GACCCCTTGA TAAAGGCCAT 120 CAAGGATGCG ATGAAGAGGC CTTGAAGACC ATGATCAAGG AAGGGAAGAA TCTCGCAGAG 180 CCCAACAAGG AGGGCTGGCT GCCGCTGCAC GAGGCCGCAT ACTATGGCCA GGTGGGCTGC 240 CTGAAAGTCC TGCAGCGAGC GTACCCAGGG ACCATCGACC AGCGCACCCT GCAGGAGGAA 300 ACAGCCGTTT ACTTGGCAAC GTGCAGGGGC CACCTGGACT GTCTCCTGTC ACTGCTCCAA 360 GCAGGGGCAG AGCGGGACAT CTCCAACAAA TCCCGAGAGA ACCGCTCTAC AAAGCCTGTG 420 AGCGCAAGAA CGCGGAAGCC GTGAAGATTC TTGGTGCAGC ACAACGCAGA CACCAACAAC 480 GCTGCAACCG GGCTG 495 (2) INFORMATION FOR SEQ ID NO: 34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 709 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34: GTGCAGCTCT GCTCGCGGCT GAAGGAACAC ATCGACAGCT TTGAGGACTG GGCCGTCATC 60 AAGGAGAAGG CAGAACCTCC AAGACCTCTG GCTCACCTTT GCCGACTGCG GGTTCGAAAG 120 GCCATTGGGA AATACCGTAT AAAACTCCTA GACACCTTGC CGCTCCCAGG CAGGCTGATT 180 AGATACCTGA AATACGAGAA CACCCAGTAA CTGGGGCCAC GGGGAGAGAG GAGTAGCCCC 240 TCAGACTCTT CTTACTAAGT CTCAGGACGT CGGTGTTCCC AACTCCAAGG GGACCTGGTG 300 ACAGACGAGG CTGCAGGCTG CCTCCCTCTC AGCCTGGACA GCTACCAGGA TCTCACTGGG 360 TCTCAGGGCC CAGAGCTTTG GCCAGAGCAG AGAACAGAAT GTGTCAAGGA GAAGAATCAT 420 TTGTTTACAA ACTGATGAGC AGATCCCAGA CCTTCTCTAC CTTCAGGAAT GGCAGAAACC 480 TCTATTCCTG GGGCCAGGGC AGAGCTTGAG GTGTTCTGGG GAAGGTGGTG CTCAGAGCCT 540 TCCCTGTGCC CCTCCACTTG TTCTGGAAAA CTCACCACTT GACTTCAGAG CTTTCTCTCC 600 AAAGACTAAG ATGAAGACGT GGCCCAAGGT AGGGGGTAGG GGGAGCCTGG GTCTTGGAGG 660 GCTTTGTTAA GTATTAATAT AATAAATGTT ACACATGTGA AAAAAAAAA 709 (2) INFORMATION FOR SEQ ID NO: 35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 848 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..624 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35: TTG GAG AAG TGT GGT TGG TAT TGG GGG CCA ATG AAT TGG GAA GAT GCA 48 Leu Glu Lys Cys Gly Trp Tyr Trp Gly Pro Met Asn Trp Glu Asp Ala 1 5 10 15 GAG ATG AAG CTG AAA GGG AAA CCA GAT GGT TCT TTC CTG GTA CGA GAC 96 Glu Met Lys Leu Lys Gly Lys Pro Asp Gly Ser Phe Leu Val Arg Asp 20 25 30 AGT TCT GAT CCT CGT TAC ATC CTG AGC CTC AGT TTC CGA TCA CAG GGT 144 Ser Ser Asp Pro Arg Tyr He Leu Ser Leu Ser Phe Arg Ser Gin Gly 35 40 45 ATC ACC CAC CAC ACT AGA ATG GAG CAC TAC AGA GGA ACC TTC AGC CTG 192 He Thr His His Thr Arg Met Glu His Tyr Arg Gly Thr Phe Ser Leu 50 55 60 TGG TGT CAT CCC AAG TTT GAG GAC CGC TGT CAA TCT GTT GTA GAG TTT 240 Trp Cys His Pro Lys Phe Glu Asp Arg Cys Gin Ser Val Val Glu Phe 65 70 75 80 ATT AAG AGA GCC ATT ATG CAC TCC AAG AAT GGA AAG TTT CTC TAT TTC 288 He Lys Arg Ala He Met His Ser Lys Asn Gly Lys Phe Leu Tyr Phe 85 90 95 TTA AGA TCC AGG GTT CCA GGA CTG CCA CCA ACT CCT GTC CAG CTG CTC 336 Leu Arg Ser Arg Val Pro Gly Leu Pro Pro Thr Pro Val Gin Leu Leu 100 105 110 TAT CCA GTG TCC CGA TTC AGC AAT GTC AAA TCC CTC CAG CAC CTT TGC 384 Tyr Pro Val Ser Arg Phe Ser Asn Val Lys Ser Leu Gin His Leu Cys 115 120 125 AGA TTC CGG ATA CGA CAG CTC GTC AGG ATA GAT CAC ATC CCA GAT CTC 432 Arg Phe Arg He Arg Gin Leu Val Arg He Asp His He Pro Asp Leu 130 135 140 CCA CTG CCT AAA CCT CTG ATC TCT TAT ATC CGA AAG TTC TAC TAC TAT 480 Pro Leu Pro Lys Pro Leu He Ser Tyr He Arg Lys Phe Tyr Tyr Tyr 145 150 155 160 GAT CCT CAG GAA GAG GTA TAC CTG TCT CTA AAG GAA GCG CAG CGT CAG 528 Asp Pro Gin Glu Glu Val Tyr Leu Ser Leu Lys Glu Ala Gin Arg Gin 165 170 175 TTT CCA AAC AGA AGC AAG AGG TGG AAC CCT CCA CGT AGC GAG GGG CTC 576 Phe Pro Asn Arg Ser Lys Arg Trp Asn Pro Pro Arg Ser Glu Gly Leu 180 185 190 CCT GCT GGT CAC CAC CAA GGG CAT TTG GTT GCC AAG CTC CAG CTT TGAAGAACCA 631 Pro Ala Gly His His Gin Gly His Leu Val Ala Lys Leu Gin Leu 195 200 205 AATTAAGCTA CCATGAAAAG AAGAGGAAAA GTGAGGGAAC AGGAAGGTTG GGATTCTCTG 691 TGCAGAGACT TTGGTTCCCC ACGCAAGCCC TGGGGCTTGG AAGAAGCACA TGACCGTACT 751 CTGCGTGGGG CTCCACCTCA CACCCACCCC TGGGCATCTT AGGACTGGAG GGGCTCCTTG 811 GAAAACTGGA AGAAGTCTCA ACACTGTTTC TTTTTCA 848 (2) INFORMATION FOR SEQ ID NO: 36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 207 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: Leu Glu Lys Cys Gly Trp Tyr Trp Gly Pro Met Asn Trp Glu Asp Ala 1 5 10 15 Glu Met Lys Leu Lys Gly Lys Pro Asp Gly Ser Phe Leu Val Arg Asp 20 25 30 Ser Ser Asp Pro Arg Tyr He Leu Ser Leu Ser Phe Arg Ser Gin Gly 35 40 45 Ile Thr His His Thr Arg Met Glu His Tyr Arg Gly Thr Phe Ser Leu 50 55 60 Trp Cys His Pro Lys Phe Glu Asp Arg Cys Gin Ser Val Val Glu Phe 65 70 75 80 He Lys Arg Ala He Met His Ser Lys Asn Gly Lys Phe Leu Tyr Phe 85 90 95 Leu Arg Ser Arg Val Pro Gly Leu Pro Pro Thr Pro Val Gin Leu Leu 100 105 110 Tyr Pro Val Ser Arg Phe Ser Asn Val Lys Ser Leu Gin His Leu Cys 115 120 125 Arg Phe Arg He Arg Gin Leu Val Arg He Asp His He Pro Asp Leu 130 135 140 Pro Leu Pro Lys Pro Leu He Ser Tyr He Arg Lys Phe Tyr Tyr Tyr 145 150 155 160 Asp Pro Gin Glu Glu Val Tyr Leu Ser Leu Lys Glu Ala Gin Arg Gin 165 170 175 Phe Pro Asn Arg Ser Lys Arg Trp Asn Pro Pro Arg Ser Glu Gly Leu 180 185 190 Pro Ala Gly His His Gin Gly His Leu Val Ala Lys Leu Gin Leu 195 200 205 (2) INFORMATION FOR SEQ ID NO: 37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 464 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37: SUBSTΓΓUTE SHEET (RULE 26) GTTCCAAGCC TAACCCATCT TTGTCGTTTG GAAATTCGGG CCAGTCTAAA AGCAGAGCAC 60 CTTCACTCTG ACATTTTCAT CCATCAGTTG CCACTTCCCA GAAGTCTGCA GAACTATTTG 120 CTCTATGAAG AGGTTTTAAG AATGAATGAG ATTCTAGAAC CAGCAGCTAA TCAGGATGGA 180 GAAACCAGCA AGGCCACCTG ACACAGGTCC TTTAATTCTG TTTAGTCACA AAAGACGGCT 240 TGTGTGACTG TTTGGATTTG GTGATCAAAT GTCCATGTTT ACAGTTGCTT TTCCCAGTTT 300 GTGTCTTTCC CAATATTGTG AACCTTATCC ATCTTGCCTT ACTCAGTTTT ATTTCTAGTG 360 CACTTTGTTG TGTATTATTT GTTTACCTGA CCATTTTCTA CTTTATTCTG CTAATAAACT 420 GTAATTCTGA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAA 464 (2) INFORMATION FOR SEQ ID NO: 38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 747 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: GGGGATCGAA AGCGGGGGCT TCTGGGACGC AGCTCTGGAG ACGCGGCCTC GGACCAGCCA 60 TTTCGGTGTA GAAGTGGCAG CACGGCAGAC TGGTCAAACA AATGGATTTT ACAGAGGCTT 120 ACGCGGACAC GTGCTCTACA GTTGGACTTG CTGCCAGGGA AGGCAATGTT AAAGTCTTAA 180 GGAAACTGCT CAAAAAGGGC CGAAGTGTCG ATGTTGCTGA TAACAGGGGA TGGATGCCAA 240 TTCATGAAGC AGCTTATCAC AACTCTGTAG AATGTTTGCA AATGTTAATT AATGCAGATT 300 CATCTGAAAA CTACATTAAG ATGAAGACCT TTGAAGGTTT CTGTGCTTTG CATCTCGCTG 360 CAAGTCAAGG ACATTGGAAA ATCGTACAGA TTCTTTTAGA AGCTGGGGCA GATCCTAATG 420 CAACTACTTT AGAAGAAACG ACACCATTGT TTTTAGCTGT TGAAAATGGA CAGATAGATG 480 TGTTAAGGCT GTTGCTTCAA CACGGAGCAA ATGTTAATGG ATCCCATTCT ATGTGTGGAT 540 GGAACTCCTT GCACCAGGCT TCTTTTCAGG AAAATGCTGA GATCATAAAA TTGCTTCTTA 600 GAAAAGGAGC AAACAAGGAA TGCCAGGATG ACTTTGGAAT CACACCTTTA TTTGTGGCTG 660 CTCAGTATGG CCAAGCTAGA AAGCTTTGAA GCATACTTAT TTCATCCGGG TGCAAATGTC 720 AATTGTCAAG CCTTGGACAA AGCTACC 747 (2) INFORMATION FOR SEQ ID NO: 39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1018 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 39: CACAAATGGG ACCATACAAA AATCTTGGAC TTGTTAATAA CCACTTACTA ACCGGGACCT 60 GTGACACTGG GCTAAACAAA GTAAGTCCCT GTTTACTCAG CAGTGTTTGG GGGACATGAA 120 GGATTGCCTA GAAATATTAC TCCGGAATGG TCTACAGCCC AGACGCCCAG GCGTGCCTTG 180 TTTTTGGATT CAGTTCTCCT GTGTGCATGG CTTTCCAAAA GGAGGTGGAG CTGTAGTTCT 240 TTGGAATTGT GAACATTCTT TTGAAATATG GAGCCCAGAT AAATGAACTT CATTTGGCAT 300 ACTGCCTGAA GTACGAGAAG TTTTCGATAT TTCGCTACTT TTTGAGGAAA GGTTGCTCAT 360 TGGGACCATG GAACCATATA TATGAATTTG TAAATCATGC AATTAAAGCA CAAGCAAAAT 420 ATAAGGAGTG GTTGCCACAT CTTCTGGTTG CTGGATTTGA CCCACTGATT CTACTGTGCA 480 ATTCTTGGAT TGACTCAGTC AGCATTGACA CCCTTATCTT CACTTTGGAG TTTACTAATT 540 GGAAGACACT TGCACCAGCT GTTGAAAGGA TGCTCTCTGC TCGTGCCTCA AACGCTTGGA 600 TTCTACAGCA ACATATTGCC CACTGTTCCA TCCCTGACCC ATCTTTGTCG TTTGGAAATT 660 CGGTCCAGTC TAAAATCAGA ACGTCTACGG TCTGACAGTT ATATTAGTCA GCTGCCACTT 720 CCCAGAAGCC TACATAATTA TTTGCTCTAT GAAGACGTTC TGAGGATGTA TGAAGTTCCA 780 GAACTGGCAG CTATTCAAGA TGGATAAATC AGTGAAACTA CTTAACACAG CTAATTTTTT 840 TCTCTGAAAA ATCATCGAGA CAAAAGAGCC ACAGAGTACA AGTTTTTATG ATTTTATAGT 900 CAAAAGATGA TTATTGATTG TCAGATAGGT TAGGTTTTGG GGGGCCAGTA GTTCAGTGAG 960 AATGTTTATG TTTACAACTA GCCTTCCCAG TAAAAAAAAA AAAAAAAAAA AAAAAAAA 1018 (2) INFORMATION FOR SEQ ID NO: 40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1897 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 40: CGGGGGGCTG GGACCTGGGG CGTAACCGTC TCTACCACGA CGGCAAGAAC CAGCCAAGTA 60 AAACATACCC AGCCTTTCTG GAGCCGGACG AGACATTCAT TGTCCCTGAC TCCTTTTTCG 120 TGGCCCTGGA CATGRATGAT GGGACCTTAA GTTTCATCGT GGATGGACAG TACATGGGAG 180 TGGCTTTCCG GGGACTCAAG GGTAAAAAGC TGTATCCTGT AGTGAGTGCC GTCTGGGGCC 240 ACTGTGAGAT CCGCATGCGC TACTTGAACG GACTTGATCC TGAGCCCCTG CCACTCATGG 300 ACCTGTGCCG GCGTTCGGTG CGCCTAGCGC TGGGAAAAGA GCGCCTGGGT GCCATCCCCG 360 CTCTGCCGCT ACCTGCCTCC CTCAAAGCCT ACCTCCTCTA CCAGTGATCC ACATCCCAGG 420 ACCGCCATAC GACAGCCATC TGGTGCCAAR TCACTGAGCC CGTTGGGGTC CGCCGACCCC 480 TGCGCCTGGG ATGGAAGCCC ACCTCAGCCA TGGGCAGACG TGCCCCCTCA TCCTACCGGC 540 TGCCTCTGCT GGGGGAACCT ATGCCAACGG ACTTCTCCCT TCCCAACACT GGCTGAAGCA 600 GCAGCACCCA GGCCCTTCCC TGAACCAGAT GCAGAGAATA AACTATGAAA ACCTCTCTCA 660 GGCGCCTTCT GCTCTCAGGT GGAGTGGGCT GCCCCCCACT CTCTGCAGAG AGAGGCTACA 720 CCCACCTGGG GGGTCCTGGG AGGTAAGACT AGTAGGAGGT GCCAGGGCTG ARTCCAAAAG 780 CAGGAATGGC CAGGAMCAGG CCATACAGAT GAAGCTCAGG ATGTCACATA CCATGGACAM 840 TGAGACAGAA CCCCAGGTTG GAMTTCCCTT GGGCCAACGA GTGCCAGCTT TAATGTCAGC 900 TGCMGGTGCT CTGTGGCCTG TATTTATTCT TTAAACAGTA GCAAAGGCCA TTTATTTATT 960 CCACTTAGAA AGGAAACCTT GGTGGGTGGY TTCCCTCGAT GTGCTTTCCC CCACCTCCCT 1020 GGAATGTGTG TGCCACACCT GTCCTTGTCC CAGGCCAGGA CTGTGGCACA TGAGCTGGTG 1080 TGCACAGATA CACGTATGTC GTCGTGCATG ACCCCTGACT AGTTCCTAAG TAGCCCTGCA 1140 CCAAGCACCA GAGCAGACCC CAAGAGAGGC CCGTGCAAGT CCCCATGTCC CCAGGTCCCT 1200 GCTTCTGTTG CCTTGGGACT CATACACCGG CACACGTGTT TCAGCCTCTT GACTTCCATG 1260 AGCTTCGAAT TTTGCCCCCG ATTCTTCTGA TATTTCCCAT TGGCATCCTC CAAAGCTCTG 1320 GGCCTGGAGG GCATTAGGAC ACATGGAATG AGTGGGGTCT CCAGCCCCTG GGAAAGCCAC 1380 TGGCAAGGCA GGATTAGAAA GACCAAGAGC AGGGTGGGGC GCCATGAAGC CTGTATGCCT 1440 CTCAGGCTCA AGACCCCGCC ACACACCCAC TCAAGCCTCA GAAGTGGTGT GTAGGGCAGC 1500 CCCAGGAGAG GAATGCCTGT CCTAGCAGCA CGTACATGGA GCACCCCACA TGTGCTCCAG 1560 CCCTCTGGCT GTTTCTCTTG CTCTAGAATC AACTCCCTAC ATTGGGAATG TAGCCATTTG 1620 GTAGAGGACT TGCCTAGCCT GCAGGAAGCT CACGTTCCAT CCCCTGCACC AAGGAGAATC 1680 AAAGCTCAGG AGGCTGAGGC AGGAGGATTG CTGTCAGTGG TGTACAGAGG TCATGGCCAT 1740 CCTGGGCTAT ATTAAACCTT GTCCTTTAAG AAAAAGAAAA GAAATCAACT TCCATTGAAT 1800 CTGAGTTCTG CTCATTTCTG CACAGGTACA ATAGATGACT TKATTTGTTG AAAAATGKTT 1860 AATATATTTA CMTATA ATA TATTTGTAAG AAGCATT 1897 (2) INFORMATION FOR SEQ ID NO: 41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 134 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 41: Gly Gly Trp Asp Leu Gly Arg Asn Arg Leu Tyr His Asp Gly Lys Asn 1 5 10 15 Gin Pro Ser Lys Thr Tyr Pro Ala Phe Leu Glu Pro Asp Glu Thr Phe 20 25 30 He Val Pro Asp Ser Phe Phe Val Ala Leu Asp Met Xaa Asp Gly Thr 35 40 45 Leu Ser Phe He Val Asp Gly Gin Tyr Met Gly Val Ala Phe Arg Gly 50 55 60 Leu Lys Gly Lys Lys Leu Tyr Pro Val Val Ser Ala Val Trp Gly His 65 70 75 80 Cys Glu He Arg Met Arg Tyr Leu Asn Gly Leu Asp Pro Glu Pro Leu 85 90 95 Pro Leu Met Asp Leu Cys Arg Arg Ser Val Arg Leu Ala Leu Gly Lys 100 105 110 Glu Arg Leu Gly Ala He Pro Ala Leu Pro Leu Pro Ala Ser Leu Lys 115 120 125 Ala Tyr Leu Leu Tyr Gin 130 (2) INFORMATION ' FOR SEQ ID NO:42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 265 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 42: AAGGGTAAAA AACTGTATCC TGTAGTGAGT GCCGTCTGGG GCCACTGTAG ATCCGAATGC 60 GCTACTTGAA CGGACTCGAT CCCGAGACTG CCGCTCATGG ATTTGTGCCG TCGCTCGGTG 120 CGCCTGGCCC TGGGGAGGGA GCGCCTGGGG GAGAACCACA CCTGCCGCTG CCGGCTTCCC 180 TCAAGGCCTA CCTCCTCTAC CAGTGACGTT CGCCATCATA CCGCCAGCGC GACAGCCACC 240 TGGTGCCAAC TCACTGAGCC GCCTG 265 (2) INFORMATION FOR SEQ ID NO: 43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2438 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 43: AAGTGGCGGC GGTCCCTGGA GAGCAGGCGG AGGCAGCGGC AAGTCTGACT CTGGGCTGAC 60 CGTGGAGCCG GGGCGGGGGC TGACAGCCAG GCCTCCGCCT GGCGGGAGCC GCACGAGGAG 120 CGGGAGTGGC CGGGCCTCTC TTCCGCGCTT GAGCGAGCGC CGGGTGATGG CGGTGGTGAT 180 GGCGGCAGGC GCTCGGACAG CTCCGCTTGA GCTGAGCTCG GAGAGATCCG TCCAGAAAGT 240 GCCCAGAAGA AACTTCCTCT TAGAAAAGCT GAAAAACACA RTATTTATAA CACTGGAAAT 300 TGTAAAGAAT TTGTTTAAAA TGGCTGAAAA CAATAGTAAA AATGTAGATG TACGGCCTAA 360 AACAAGTCGG AGTCGAAGTG CTGACAGGAA GGATGGTTAT GTGTGGAGTG GAAAGAAGTT 420 GTCTTGGTCC AAAAAGAGTG AGAGTTGTTC TGAATCTGAA GCCATAGGTA CTGTTGAGAA 480 TGTTGAAATT CCTCTAAGAA GCCAAGAAAG GCAGCTTAGC TGTTCGTCCA TTGAGTTGGA 540 CTTAGATCAT TCCTGTGGGC ATAGATTTTT AGGCCGATCC CTTAAACAGA AACTGCAAGA 600 TGCGGTGGGG CAGTGTTTTC CAATAAAGAA TTGTAGTGGC CGACACTCTC CAGGGCTTCC 660 ATCTAAAAGA AAGATTCATA TCAGTGAACT CATGTTAGAT AAGTGCCCTT TCCCACCTCG 720 CTCAGATTTA GCCTTTAGGT GGCATTTTAT TAAACGACAC ACTGTTCCTA TGAGTCCCAA 780 CTCAGATGAA TGGGTGAGTG CAGACCTGTC TGAGAGGAAA CTGAGAGATG CTCAGCTGAA 840 ACGAAGAAAC ACAGAAGATG ACATACCCTG TTTCTCACAT ACCAATGGCC AGCCTTGTGT 900 CATAACTGCC AACAGTGCTT CGTGTACAGG TGGTCACATA ACTGGTTCTA TGATGAACTT 960 GGTCACAAAC AACAGCATAG AAGACAGTGA CATGGATTCA GAGGATGAAA TTATAACGCT 1020 GTGCACAAGC TCCAGAAAAA GGAATAAGCC CAGGTGGGAA ATGGAAGAGG AGATCCTGCA 1080 GTTGGAGGCA CCTCCTAAGT TCCACACCCA GATCGACTAC GTCCACTGCC TTGTTCCAGA 1140 CCTCCTTCAG ATCAGTAACA ATCCGTGCTA CTGGGGTGTC ATGGACAAAT ATGCAGCCGA 1200 AGCTCTGCTG GAAGGAAAGC CAGAGGGCAC CTTTTTACTT CGAGATTCAG CGCAGGAAGA 1260 TTATTTATTC TCTGTTAGTT TTAGACGCTA CAGTCGTTCT CTTCATGCTA GAATTGAGCA 1320 GTGGAATCAT AACTTTAGCT TTGATGCCCA TGATCCTTGT GTCTTCCATT CTCCTGATAT 1380 TACTGGGCTC CTGGAACACT ATAAGGACCC CAGTGCCTGT ATGTTCTTTG AGCCGCTCTT 1440 GTCCACTCCC TTAATCCGGA CGTTCCCCTT TTCCTTGCAG CATATTTGCA GAACGGTTAT 1500 TTGTAATTGT ACGACTTACG ATGGCATCGA TGCCCTTCCC ATTCCTTCGC CTATGAAATT 1560 GTATCTGAAG GAATACCATT ATAAATCAAA AGTTAGGTTA CTCAGGATTG ATGTGCCAGA 1620 GCAGCAGTGA TGCGGAGAGG TTAGAATGTC GACCTGCATA CATATTTTCA TTTAATATTT 1680 TATTTTTCTT ATGCCTCTTT GAATTTTTGT ACAAAGGCAG TTGAATCAAA TAAAACTGTG 1740 CCCTAAGTTT TAATTCCAGA TCAATTTATT TTTTTTATGA TACACTTGTT ATATATTTTT 1800 AAGCAGGTGT TTGGTTTTGT TTTTACCATA TAAATTTACA TATGGTCCAG GCATATTTAC 1860 AATTTCAAGG CATTGCATAT ACATTTGAAT ATTCTGTATT TTTTAAATAA TCTTTTGTTC 1920 TTTCCTATGT GTGAAATATT TTGCTAATCT ATGCTATCAG TATTCTTGTA TGACCGAATA 1980 GTTACCTATT CTCTTTTCAT CTTGAAGATT TTCAGTAAAG AGTGTTGTAA TCAATCCATT 2040 ATAATGTAAT TGACTTTTGT AATTTGCCAA TAGGAGTGTT AAACAACAAA ATGATTTAAA 2100 ATGAAACTTA ATGTATTTTC ATTTTAAATA TTAACTAAAC CAAGTTTGTT TGTTAGTTAT 2160 TCTAGCCAAT AAGAAAAGAG AATGTAGCAT CCTAGAGGTG TATTTGTTCT GCAGTTTGGC 2220 AGGACCGTCA GTTAGTCCAA ATAAACATCC CCTCAGCGTG GAGGCGAATG GAACCTGTGC 2280 TCCTTTCTTA CGGGAAGCTT TGCAAAGCAA AATAGCAGGG TTACAAGCTT GGAGTTGTTA 2340 AGGCAACTAG AGTTTTCTCT ATTAATTTAT AGACTGTTGT TGCACCTACT TAGCTCTTTT 2400 TTGGGAACTC TAGTTCCCAG GGGAAAATAC CTCGTGCC 2438 (2) INFORMATION FOR SEQ ID NO: 44: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 542 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 44: Ser Gly Gly Gly Pro Trp Arg Ala Gly Gly Gly Ser Gly Lys Ser Asp 1 5 10 15 Ser Gly Leu Thr Val Glu Pro Gly Arg Gly Leu Thr Ala Arg Pro Pro 20 25 30 Pro Gly Gly Ser Arg Thr Arg Ser Gly Ser Gly Arg Ala Ser Leu Pro 35 40 45 Arg Leu Ser Glu Arg Arg Val Met Ala Val Val Met Ala Ala Gly Ala 50 55 60 Arg Thr Ala Pro Leu Glu Leu Ser Ser Glu Arg Ser Val Gin Lys Val 65 70 75 80 Pro Arg Arg Asn Phe Leu Leu Glu Lys Leu Lys Asn Thr Xaa Phe He 85 90 95 Thr Leu Glu He Val Lys Asn Leu Phe Lys Met Ala Glu Asn Asn Ser 100 105 110 Lys Asn Val Asp Val Arg Pro Lys Thr Ser Arg Ser Arg Ser Ala Asp 115 120 125 Arg Lys Asp Gly Tyr Val Trp Ser Gly Lys Lys Leu Ser Trp Ser Lys 130 135 140 Lys Ser Glu Ser Cys Ser Glu Ser Glu Ala He Gly Thr Val Glu Asn 145 150 155 160 Val Glu He Pro Leu Arg Ser Gin Glu Arg Gin Leu Ser Cys Ser Ser 165 170 175 He Glu Leu Asp Leu Asp His Ser Cys Gly His Arg Phe Leu Gly Arg 180 185 190 Ser Leu Lys Gin Lys Leu Gin Asp Ala Val Gly Gin Cys Phe Pro He 195 200 205 Lys Asn Cys Ser Gly Arg His Ser Pro Gly Leu Pro Ser Lys Arg Lys 210 215 220 He His He Ser Glu Leu Met Leu Asp Lys Cys Pro Phe Pro Pro Arg 225 230 235 240 Ser Asp Leu Ala Phe Arg Trp His Phe He Lys Arg His Thr Val Pro 245 250 255 Met Ser Pro Asn Ser Asp Glu Trp Val Ser Ala Asp Leu Ser Glu Arg 260 265 270 Lys Leu Arg Asp Ala Gin Leu Lys Arg Arg Asn Thr Glu Asp Asp He 275 280 285 Pro Cys Phe Ser His Thr Asn Gly Gin Pro Cys Val He Thr Ala Asn 290 295 300 Ser Ala Ser Cys Thr Gly Gly His He Thr Gly Ser Met Met Asn Leu 305 310 315 320 Val Thr Asn Asn Ser He Glu Asp Ser Asp Met Asp Ser Glu Asp Glu 325 330 335 He He Thr Leu Cys Thr Ser Ser Arg Lys Arg Asn Lys Pro Arg Trp 340 345 350 Glu Met Glu Glu Glu He Leu Gin Leu Glu Ala Pro Pro Lys Phe His 355 360 365 Thr Gin He Asp Tyr Val His Cys Leu Val Pro Asp Leu Leu Gin He 370 375 380 Ser Asn Asn Pro Cys Tyr Trp Gly Val Met Asp Lys Tyr Ala Ala Glu 385 390 395 400 Ala Leu Leu Glu Gly Lys Pro Glu Gly Thr Phe Leu Leu Arg Asp Ser 405 410 415 Ala Gin Glu Asp Tyr Leu Phe Ser Val Ser Phe Arg Arg Tyr Ser Arg 420 425 430 Ser Leu His Ala Arg He Glu Gin Trp Asn His Asn Phe Ser Phe Asp 435 440 445 Ala His Asp Pro Cys Val Phe His Ser Pro Asp He Thr Gly Leu Leu 450 455 460 Glu His Tyr Lys Asp Pro Ser Ala Cys Met Phe Phe Glu Pro Leu Leu 465 470 475 480 Ser Thr Pro Leu He Arg Thr Phe Pro Phe Ser Leu Gin His He Cys 485 490 495 Arg Thr Val He Cys Asn Cys Thr Thr Tyr Asp Gly He Asp Ala Leu 500 505 510 Pro He Pro Ser Pro Met Lys Leu Tyr Leu Lys Glu Tyr His Tyr Lys 515 520 525 Ser Lys Val Arg Leu Leu Arg He Asp Val Pro Glu Gin Gin 530 535 540 (2) INFORMATION FOR SEQ ID NO: 45: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 4999 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 45: CCCTCTGGGC AAGCCGCCCC CCCCCCACCC ATCTACCACA CACACACACA CACACACACA 60 CACACATTCA GACCTTGGGG CAAAAACAAA GCAAAATAAC AACAACAAAA ACACTGCCTG 120 TGGAAAGTCC TTACTTCAGG AAGGTTGGCA GATGAGGAGC AAGGGAACAT TTTATCAGGA 180 CTGCCACAAA GGAGTCTTTT TTTTTAATGG TTTTTCAAGA CAGGGTTTCT CTGTATAGCC 240 CTGGCTGTCC TGGAGCTCAC TTTGTAGACC AGGCTGGCCT CGAACTCAGA AATTCGCCTG 300 CCTCTGCCTC CTGAGTGCTG GGATTAAAGG CGTGCAGCAC CATGTCCAAC TGGCATTTTC 360 TCAATTAAGG TTCGTTCCTT TCAGATAACT CTAGGTTCTG GGTCAAGCTG ACACAAGGCT 420 ACACAGCACA GTTTGTATGC CACATTCAGT TCAGAAGACA CCCAACCTCC CTGGAACTGG 480 AACTTATGCA CATTTGTGAG CTTCCACTTG GGAGTGGGAA CCTGAACTGG GTCCTCTGCA 540 AGAGCAGCCG TGCTCTTAAC TGCTGAGCCA TTTCAGCAGC CTCACATCAG AATTAAGTTA 600 GAAATTAGCCG GGTATGAATC ATACCCTTAG AATCCTAGCA TCTGAAAGCA GAGCTAAGAG 660 AAACAGGGAT TCAAGACCAG CTCTTGGCTA CAGAGCCCGT CCTGTCCTAG GATGGGCTAC 720 AAGAGACTAT TTCAAAGCCA TCCAAACAAC AATAACTACA ACAACAACAA GGTTAAAATT 780 AGGCTGGGCA CAGGGTACAC ACCTTTAATG CCAACACTCA GGAGGCAGAG GCAGGCTGAT 840 CAGTGTGAGT TTGAGTTCAA CGTGGTCTAC ATAGGGAGTT CTAGGCCAGC AGAGGTTACA 900 GTCTCTCTCT CTCTCTCTCT CTCTCTCTCT CTCTCACACA CACACACACA CACACACACA 960 CACACACACA CACACACGGT GGCATTATGG GATTTTTTTG GGATAAGGTT TCTCTGTCTA 1020 GCCCTGGCAT AGATTCACTC TGTAGACTAG GCTAGCCTTG AACTCAGAGA TCCGCCTGCC 1080 TCTGCCTCCC AAGTGCTGGG ATTATAGGTG TTGCACCACC ACTGCCCAGC CACTTTGGGA 1140 TTTTTGAACT GTTATCAAGA GGCTTTCGAG GAGGTCAAAC TTCAACAGCA ACCTCTCCAT 1200 GATAATGTAG CTAATGATCA AACGACACTC AAAACTTAAC CCTTAAAGCA CACATCCACC 1260 AGACAGCGTG CCCACTCGTA GTTCCATTAC TCAGGAGGCT GAAGCAGGAG GATGAAGGAC 1320 TAAGGCTTCA GCAACCTAGG GAGCCGCAGG GGACAGTAGT CTCAATCCCT ACATTCTCCT 1380 GAACACAGGA GCAGGAGTTC AGGAAGGGTG TCAAGGCCGC TTACTGATCT TAGGGCCTCA 1440 GGAATGACTA GCTCAGGCAG AGAGAGCAAA GGTCTCCAGT GGAGAAGTCT ACACACACAC 1500 ACACACACAC ACACACACAC ACACACACAC AGAATCCAAG GCGATGACGT CATCAAAGGG 1560 TTAATTCTAG TCTGGGATGG GGGGGAGGGT GGGGCACGCA GCTGTCAGGT GGCTTTGGAA 1620 AAATAAACTG CTGAAGAGTC TGACGCCAGG GAGTCCTGGG AGGGACAAGA GGTTACCCAC 1680 TCAAAGAGTG TGCTCCACAA AGCATGCGCG CTTGTCCACG TCTGGAGTCG TCACTTATTT 1740 TTTGCCTGGA TTCTTTGTAG CCGGTGGGTT CTCAAGGCGG TAAGTGGTGT GGCCGCCGTG 1800 GTCTGGGAGG TGACGATAGG GTTAATCGTC CACAGAGCCC AGGGGCGGAG CGCGGGCGGG 1860 CGTCCGCAGC CCCGCTGGAG CCGGAAGCAG TGGCTGGTCA GGGGCGCTTC TAGCCTTCCC 1920 TATCTGTACT TCCACAGAGG TCTCTGCGAG CTAGGGGGAC AGTGAGGTGC GGGGTAGGGG 1980 CCCGGCGTTA GAGCCAGCAA GGGGACGGTT CACGGTAAGG TCTGAGGGAG AGAGAGCTCC 2040 TGAGAAACTT GGGGGGCGCG ACACAGATAG GGTGAAAGCA GAGTGATAGA CCTGGGATGG 2100 TTAGGGGACC AAGGGAAGAC CAGGCTGGTT GGCATACACC GGTGAACGGA TGGGAGTCCT 2160 AGGGAAAGAT GATGCGCCTA ACAGTCCTTT CTGTCTCCAC ACCACTCCAG GGGACGATCC 2220 GGAGCTCAAC TTTCAAAAGC GAGACGCCCC AGCAAGCCTG TTTTGAGAAG TTCTTCAGCG 2280 GCTCTCCTCA TGGGCCAGAC GGCCCTGGCA AGGGGCAGCA GCAGCACCCC TACCTCGCAG 2340 GCTCTGTACT CGGACTTCTC TCCTCCCGAG GGCTTGGAGG AGCTCCTGTC TGCTCCCCCT 2400 CCTGACCTGG TTGCCCAACG GCACCACGGC TGGAACCCCA AGGATTGCTC CGAGAACATC 2460 GATGTCAAGG AAGGGGGTCT GTGCTTTGAG CGGCGCCCTG TGGCCCAGAG CACTGATGGA 2520 GTCCGGGGGA AACGGGGCTA TTCGAGAGGT CTGCACGCCT GGGAGATCAG CTGGCCCCTG 2580 GAGCAAAGGG GCACACACGC CGTGGTGGGC GTGGCCACCG CCCTCGCCCC GCTGCAGGCT 2640 GACCACTATG CGGCGCTTTT GGGCAGCAAC AGCGAGTCCT GGGGCTGGGA TATTGGGCGG 2700 GGAAAATTGT ATCATCAGAG TAAGGGCCTC GAGGCCCCCC AGTATCCAGC TGGACCTCAG 2760 GGTGAGCAGC TAGTGGTGCC AGAGAGACTG CTGGTGGTTC TGGACATGGA GGAGGGGACT 2820 CTTGGCTACT CTATTGGGGG CACGTACCTG GGACCAGCCT TCCGTGGACT GAAGGGGAGG 2880 ACCCTCTATC CCTCTGTAAG TGCTGTTTGG GGCCAGTGCC AGGTCCGCAT CCGCTACATG 2940 GGCGAAAGAA GAGGTGAGAT ACGGACTAGG TGTGGGGAGA TCACTACTCT TGGCAATGGT 3000 TTGGGCTGGA AACTCATGGT TGGAGCACAG GAAGTAGGCT TCTTGTCACT TTGGCCTGTC 3060 ACTTAGATGG CCTTGGATCT AGCTTCACTC CCAATCCCTA TTGGATGTGA TGCACAAATT 3120 CAGAGCCTTT GGGTCTCCCT CAGCTGAGGT GGCGGTGGAA ATGGAGGAAG AAGGAAGGGT 3180 GCCTGAGCAG GATCTCAAGT TCAAGGATGC CTGGAGTTGC TTACTTACCT TGTCTTCCTT 3240 CTCTCTCCGC AGTGGAGGAA CCACAATCCC TTCTGCACCT GAGCCGCCTG TGTGTGCGCC 3300 ATGCTCTGGG GGACACCCGG CTGGGTCAAA TATCCACTCT GCCTTTGCCC CCTGCCATGA 3360 AGCGCTATCT GCTCTACAAA TGACCCAGTA GTACAGGGTG TGCTGGCACC CTACCGTGGG 3420 GACAGGTGGA GAGGCACCCG CTGGCCTAGA CAACTTTAAA AAGCTGGTGA AGCTGGGGGG 3480 GGGGGGCTGG ACCCCTTCAC CTCCCCTTCT CACAGGAGCA AGACATATAG AAATGATATT 3540 AAACACCATG GCAGCCTGGG ACAAAGAGGT TTTTGAAGTA AAAAATGAGA TGTATTGTCA 3600 CAACCTGTTT CATTATTGTT TTTTGTTTTG TTTTACACTC CCCCACCCCA GGCTAGAGCC 3660 CCATCACTGT CTTAAGGAAT TATGACAACC CACAAAGCTC AGGCCCAGGT GTTTATTTCC 3720 CTTACATGTA GGATGGTTCA CAAACACAAT ACAGGGGCTT TGGCACCGTG GGGGAGGGGA 3780 CTATCCCAGG CCTCTTAGGG TCTCATGTAT ACCGAATTCA GACCCGAAAG CTCTGAATTT 3840 CTGCATCAGA CATCCAGTAG AACTTGGGAG TGAAGCTAGA GCCAAGGCCA TCTAAGTGAC 3900 AGGCCAAAGT GACACGAAGC CCACTTCCTG TGCTCCAACC ATGAGTTTCC AGCCCAAACC 3960 AATGGAAGGT GATTTCACTT GTCAGGGCCC AAAGGGACAG TCAGTTCTAC TCCCTCCCCT 4020 CACTAGGAGC CACCTTGGTG ACAGTTGATT CTACCCACTG TAAGTGGTAA AGGGATTGGC 4080 CTGGTCCCAA CCATAATAGG GCGGTGGAAA CGGCTCAGGA GGGTACAGCG TGGATTAGGC 4140 CACAAGATGG GGCAGATGAT GTCATCAGAA GCATGTGACC GGTGGGAGCA GTTACTAAAC 4200 TTCTGGGCAA CCTAGTCCAT GCTATGC GG CAGGTAGAGG GATGGGCAGT GCTCATTGTT 4260 TGGCATTGAT GATGTCCACA AATTCAGGCT TGAGAGATGC GCCACCCACA AGGAAGCCGT 4320 CCACGTCAGG CTGGCTTGCC AGCTCTTTGC AGGTTGCTCC AGTCACAGAA CCTGTACCAG 4380 GAACAAGAAG ACAGTTTGGT CAGGTCTATG ATCAGAACAC TTAAGCCCCA CCTCTCTGTG 4440 CAAGGCAGCC TCAGTCTGTC TTAGCCCATT TCCGTCTTAG CTAGAGCCAA AGCCACTCAC 4500 CTCCATAAAT GATCCGGGTG CTCTGAGCCA CCCCATCATT GACATTGGAT TTCAGCCATC 4560 CCCGGAGCTT CTCGTGTACT TCCTGTGCCT AGAAGGAGGA GGCAGAGCTA CTAAGTAAGC 4620 TCCTTCCTAT CTATCATTCA AGGAGTAAAA ACCACTGGTT CTCACATAGA GTTGAGTTTC 4680 CAGAAAAGCC CCGGGACCAG AGAGTGGCAA GGCTCCAATC CCACCAGGCT TGGAATGAAC 4740 ATTTTTGGCA AAGTCACTCT CCTTGGTGAG TTTGGGGGCC CTCTGTCTCT AAAGGGGCTT 4800 GGATGGGCTC CATAGCTGTG TGAGTCTGTT AAAGCCGGAC AGGCTGAGGA GCTCTGGGTA 4860 GTTACCTGCT GAGGGGTTGC CGTCTTGCCA GTCCCAATGG CCCACACAGG TTCATAGGCC 4920 AGGACCACCT TGCTCCAGTC TTTCACATTA TCTGTGGGGC AGAGAGGAGA GTGAGTAGGA 4980 AGGAGCTGAC CCGCCAAGC 4999 (2) INFORMATION FOR SEQ ID NO: 46: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 264 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 46: Met Gly Gin Thr Ala Leu Ala Arg Gly Ser Ser Ser Thr Pro Thr Ser 1 5 10 15 Gin Ala Leu Tyr Ser Asp Phe Ser Pro Pro Glu Gly Leu Glu Glu Leu 20 25 30 Leu Ser Ala Pro Pro Pro Asp Leu Val Ala Gin Arg His His Gly Trp 35 40 45 Asn Pro Lys Asp Cys Ser Glu Asn He Asp Val Lys Glu Gly Gly Leu 50 55 60 Cys Phe Glu Arg Arg Pro Val Ala Gin Ser Thr Asp Gly Val Arg Gly 65 70 75 80 Lys Arg Gly Tyr Ser Arg Gly Leu His Ala Trp Glu He Ser Trp Pro 85 90 95 Leu Glu Gin Arg Gly Thr His Ala Val Val Gly Val Ala Thr Ala Leu 100 105 110 Ala Pro Leu Gin Ala Asp His Tyr Ala Ala Leu Leu Gly Ser Asn Ser 115 120 125 Glu Ser Trp Gly Trp Asp He Gly Arg Gly Lys Leu Tyr His Gin Ser 130 135 140 Lys Gly Leu Glu Ala Pro Gin Tyr Pro Ala Gly Pro Gin Gly Glu Gin 145 150 155 160 Leu Val Val Pro Glu Arg Leu Leu Val Val Leu Asp Met Glu Glu Gly 165 170 175 Thr Leu Gly Tyr Ser He Gly Gly Thr Tyr Leu Gly Pro Ala Phe Arg 180 185 190 Gly Leu Lys Gly Arg Thr Leu Tyr Pro Ser Val Ser Ala Val Trp Gly 195 200 205 Gin Cys Gin Val Arg He Arg Tyr Met Gly Glu Arg Arg Val Glu Glu 210 215 220 Pro Gin Ser Leu Leu His Leu Ser Arg Leu Cys Val Arg His Ala Leu 225 230 235 240 Gly Asp Thr Arg Leu Gly Gin He Ser Thr Leu Pro Leu Pro Pro Ala 245 250 255 Met Lys Arg Tyr Leu Leu Tyr Lys 260 (2) INFORMATION FOR SEQ ID NO: 47: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5615 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 47: GTACTTTCTT TATATCTCCA TAATTTTATT TACTATTACT ACATGATACA TTATTTTATA 60 AAAGTCTTTG TAACCTCCTT AAGGATTCAC TGCTTAATCT CCAGTGCTTA GCACAAATCA 120 TTAAATGCGA ACCAGAAACT CTTCCAAATG TGTTACATCT ATAACCTCAT TGGATTCTCA 180 CTACCAACCC CATGCAATAG ATACTAATGT GATCTCTGTC TTACAGAGGA AGAAACAGGC 240 ACAGGGAGGT TCAGTAATTT GCCCAAGGTC ATACACACAC TGGCCTTCAG GTATTCATGC 300 CCGGGGAGTC TGGTCCCACA GCTGGCATGT TTGCCATTAT ATTATATTGC CTCCTTATAG 360 TGTCGGCACT CATTAAGCAC ATTGACAGCT ATGCTTGGTG AGTGACTACT ATGTACCCAG 420 CTCTGTGCTA CATGCTTTAC CTGGATTATT TCAACTGCAC AACAACCCTG TGAGGTAACT 480 ACCATCATTG CTCCTATTTT ACATAACAGA AAACTACAGA AATCTGGGGC TGGGCGTAGT 540 GGCTCATGCC TGAAATCCCA GCACTTTGGG AGACCCTGTC TCTAAAAAAA ATTTTTTTTT 600 GGCCGGACGT GGTGGCTCAC ACCTGTAATC TCAGCACTTT GGGAGGCTAA GGCAGGCAGA 660 TCACAAGGTC AGGAGTTCTA GACCAGCCTG GCCAACATGG CAAAACCCTG TGTCTACTAA 720 AAATACAAAA AATAGCTAGG CGTGGTGGCA GGTGCCTGTA ATCCCAGCTA CTCAGGAGGC 780 TGAGGCAGGA GAATCCCCTG AACCTGGGAG ATGGAGGTTA CAGAGAGCCG AGATCGTGCC 840 GCTGCACTCC AGCCTGGGCA ACAAGAGCAA GACTCTGTCT CGAAAAAAAT AAAAATAAAA 900 ATAAAAATAT TTTTTTAAAA ATTAGCTGGG TGTGGTAGCA CATGCCTGTA GTCCCAGCTA 960 CTTGGGAGGC TGAGGTAGGA GGATCACTTG AGCCCAGGAG GTCAAGGCTG CAGTGGGCTG 1020 TGATGGCGCC ACTGCACTCT AGCCTTGGTG ACAGCAAGAC CCTGTCTCAA AAAAAAAAAA 1080 AAGAGAAATC GGGCAACTTC CCCAAGATCG CGCAGTTAAC TAGTGGCATA GCTTCACTCA 1140 AACTCGAAGT CTTAATCAGG ACACTCTACC AAATGAGATC AACGGCTCAG TAATGGATTG 1200 GCATCCAGTA TGAAGACTGG ACCAGCAGGG AGAACTATGA TGCGTACAGC CTAGAGCCTG 1260 AAGCAGATTT CACAGCCTCA GAGGTGGCAC AGGCTGACTC ACAACCCGGG GCAGAAAGGG 1320 ACCAGCCCAG AAACAGTGAC CCAGAATCAC AGGGAAGTAG AAATGGGATT CGGCACAATG 1380 AAGCCCCTCC TTGACCCCAT GCTCCTTACC CTCAGGGGCG CAGGAGTTAG TCGCTCAGGC 1440 GGCTCAAAGG TCTTGACGGT GGAGAACACC ATCCCCAGGG ATTCCCGACG CGGTGATGCC 1500 ATCAAAGCGT TAATTCTGAG ATGGGCCTGC CCGGGTGCGG ACTCTGCCGC AGCAAGAGAA 1560 GGGTTAACTG CCCCGGGCCT TCGCCGTGGG GGCGGGGCCT CGGGGAGGGT CACAGCCCGG 1620 GACTGAGACC CGAGGTTAAC CGCCCGGGGT GGGCTCCACG GGGGCGGGGC ATGCTCTCCG 1680 CGGCTGCTGC CGGTATAGAG CGGTAACTGC CCAGGAGGGG GCGGGGCCCC ACAGGGGCGT 1740 GGCCTCGGAG CTGCACGGCC GTGGGCGGCG ATGAGAGGGT TAAGCCCCAG AGGGCCCTGG 1800 AGGGGCGGGG CCGCGGGACG GGCTCGGCCC AAGGGAGGAG CTGGGGGCGG AAGCGGCCGG 1860 CGGTCTGCGC CCTGCGCGCC TCGGCTTCTT TCCGCCCGGC TCCTTCAGAG GCCCGGCGAC 1920 CTCCAGGGCT GGGAAGTCAA CCGAGGTTCG GGGGCAGCGG CGAGGGCTCC GGGCGAGTAA 1980 GGGGGATGGT CCATGCTGAG GCCCAAATGG GGCGAACTCG CGAGAGTCTC TGGCGACCTG 2040 GATCAGATGG GGCGAGGGCA GATGAAGGGC CCAGGAGCTT TGGGGCAGCG AGGAGGGAGG 2100 AGCGGGCCCG TTGGCAAACT TGGGTGAAAG GATGGGGTAC CTGGGTGACG AGCCCCCGCC 2160 AGGATTCTGC TCTTCACGCC CCTTTTCTCC CAGCTCCCTT CCAGGTCAAT CCAAACTGGA 2220 GCTCAACTTT CAGAAGAGAA AGACGCCCCA GCAAGCCTCT TTCGGGGAGT CCTCTAGCTC 2280 CTCACCTCCA TGGGCCAGAC AGCTCTGGCA GGGGGCAGCA GCAGCACCCC CACGCCACAG 2340 GCCCTGTACC CTGACCTCTC CTGTCCCGAG GGCTTGGAAG AGCTGCTGTC TGCACCCCCT 2400 CCTGACCTGG GGGCCCAGCG GCGCCACGGT TGGAACCCCA AAGACTGTTC AGAGAACATC 2460 GAGGTCAAGG AAGGAGGGTT GTACTTTGAG CGGCGGCCCG TGGCCCAGAG CACTGATGGG 2520 GCCCGGGGTA AGAGGGGCTA TTCAAGGGGC CTGCACGCCT GGGAGATCAG CTGGCCCCTA 2580 GAGCAGAGGG GCACGCATGC CGTGGTGGGC GTGGCCACGG CCCTCGCCCC GCTGCAGACT 2640 GACCACTACG CGGCGCTGCT GGGCAGCAAC AGCGAGTCGT GGGGCTGGGA CATCGGGCGG 2700 SUBSTfTUTE SHEET (RULE 26) GGGAAGCTGT ACCATCAGAG CAAGGGGCCC GGAGCCCCCC AGTATCCAGC GGGAACTCAG 2760 GGTGAGCAGC TGGAGGTGCC AGAGAGACTG CTGGTGGTTC TGGACATGGA GGAGGGAACT 2820 CTGGGCTACG CTATTGGGGG CACCTACCTG GGGCCAGCAT TCCGCGGACT GAAGGGCAGG 2880 ACCCTCTATC CGGCAGTAAG CGCTGTCTGG GGCCAGTGCC AGGTCCGCAT CCGCTACCTG 2940 GGCGAAAGGA GAGGTGAGGC CTGGGGCAGA CGTGGGGAGA ACTTTCTGTC CCTGGTGGCA 3000 GTGGTTTGGG ATGGAAACTC TTCTGACAAG AGCAGAGGGG ATGGACCTTC ATCCAGCCTG 3060 CCTCAACCTC TGTTCAGTGC TGGGAAAGGC TAGGGGTCTT CACAGCTGTT ATTTAATTTA 3120 ACCCAACAGC AATAGAGGTG AAACAGGCTT GAGAAAGCAA CTTTCTCAAG TTCTCTTGGC 3180 CAGTAAATGG TGAACCTTCA GAATGGAGGG AGGAACTGCA GGGATGAGAG AATTCAGGAG 3240 ATATCAACCC CTGAGCAAGA GGTGCAAAGC GTTAGGTACT GGGTTTGATG TACAGGTCCA 3300 AAAGAAGGAT GGGCAGAGCC AGGTACCCAG GCTGTATACC GGATTCCCTG GGCTCTAACC 3360 TGTCTCTGTG CCACATACCT ACTTCCTTCC TCAGCCACAC CTCTGGATGG AGACACTGGG 3420 GCCCTGGGCA CCAGGGAGGA GAGCAGTGGA GGAGGCAGGG CCTTAGGGTG GGGCAGCAGG 3480 GGAGGAGCCT CCCCAGGAAC TGACTGGGTC CAGGGCTTGG AGCTGCTCTC TGCAGTTGTG 3540 TGGGCTGTAG AGTGGAGGGC CATCCCTCCT CACCTCAGCC CCAGCTCCCA AGCCTCTGGA 3600 GTCAAAGCCT GGGCCAGCTC CACCACTGTC AGAGCCACCT TGGCCTGTTG TTTAGAGGGC 3660 CTTAGCCAGC TCTTCACCCC CAGCTCTGAC TAGGGATGTG TGAAATCTTA TCTGGGAGGC 3720 AGAACTTCCG GGTATCTCAA ATTCCCCTTT CAGCCAGGTG GGCACACTCG AAGCAGGAAA 3780 GCAGAAAGGC ATCTGAGTAG GACCCCGTAG TTTGAGGACA TCTGGCTGGT GGCTGCACCC 3840 ATACTTACAT TCCCCTCCTT CTCTCTCCCA GCGGAGCCAC ACTCCCTTCT GCACCTGAGC 3900 CGCCTGTGTG TGCGCCACAA CCTGGGGGAT ACCCGGCTCG GCCAGGTGTC TGCCCTGCCC 3960 TTGCCCCCTG CCATGAAGCG CTACCTGCTC TACCAGTGAG CCCTGTGATA CCACAGACTG 4020 TGCTGAGGTC TTGCCACCAC CCCTCCCCTT GGGGAGGTGG GGAGGCACTG CTGGCCTAGA 4080 CCAGCTGCTG AAAGCTGGTG AGGCTGAGCC CCTACCCCAA CCCAAGCTCT GCGGAAATCA 4140 ACAGCCCCAG AGCCACTTGG AGGGAGGAAG AAAGGGAGCC GGCGTTCAAG GCTATGACAG 4200 TCTGCTACGC AAAACATTTT TTCAAGTAAA AATAGTAAGA GATGTTGTTA TAGAAACCTG 4260 TTCTTGTTTT TTTTTTTTTC TTGCACAAAT GATCATTTAT ATAGCTGCCT CAAAAAGGAA 4320 GATTATCTGG GCAAGTCCAG TGAAGGCAGA CAAACCACAA GACCTAGTGC CAGGTTTATT 4380 CCCTCACATG GGTGGTTCAC ATACACAGCA CAGAGGCACG GGCACCATGG GAGAGGGCAG 4440 CACTCCTGCC TTCTGAGGGG ATCTTGGCCT CACGGTGTAA GAAGGGAGAG GATGGTTTCT 4500 CTTCTGCCCT CACTAGGGCC TAGGGAACCC AGGAGCAAAT CCCACCACGC CTTCCATCTC 4560 TCAGCCAAGG AGAAGCCACC TTGGTGACGT TTAGTTCCAA CCATTATAGT AAGTGGAGAA 4620 GGGATTGGCC TGGTCCCAAC CATTACAGGG TGAAGATATA AACAGTAAAG GAAGATACAG 4680 TTTGGATGAG GCCACAGGAA GGAGCAGATG ACACCATCAG AAGCATATGC AGGGAAAGGG 4740 CAGTTACTGG GCTTCTGGGC TGCTTAGTCC CTGGCTTGGC AGGAAGGGTA GGGAAGATGG 4800 ATGGGGCTCA TTGTTTGGCA TTGATGATGT CCACGAATTC GGGCTTGAGG GAAGCACCAC 4860 CCACAAGGAA GCCATCCACA TCAGGCTGGC TGGCCAGCTC CTTGCAGGTT GCCCCAGTCA 4920 CAGAGCCTGG GAAGGGAGCA GAACAAGGGC TTGGTCAAGA ATGGGATGAG TCTGCCCCAT 4980 CCCCACCTCC ATGTCCGAGG GCTCAGTCTA GTCCTCAGCC CACTCCACCT CAGCCGGGAA 5040 CCAAAGCCAC TCACCTCCAT AAATGATACG GGTGCTCTGA GCCACCGCAT CAGAGACGTT 5100 GGACTTCAGC CATCCTCGGA GCTTCTCGTG TACTTCCTGG GCCTAGAACA AGAAGCTGGC 5160 CTAAGTAAGA CCTTTTCTGC CTCTCTAAGA GGAAAAATCA CTGGCACCAG TGGACACTTA 5220 GTGTGGTTTC TGACTGAGTC AGAGTACCAG GGCTCTGATC CAAGCCAGGC CCTGGACTGG 5280 ATGCCCTTGG ACAAGTCACT GTCTCTGGGT TCAAGGTCTC TGTGTCTTTG AAATAAGGGG 5340 TTGCCCCATG TGGGCTGTGT CTGTCCAAAC CTATTGAGGC AGGCTGGGAT GAGGGCAGGG 5400 CTCCTGGGCC CGGTTACCTG TTGGGGTGTT GCAGTCTTGC CAGTACCAAT GGCCCACACA 5460 GGCTCATAGG CCAGGACGAC CTTGCTCCAG TCCTTCACGT TATCTGCAGG GCAGAGATAC 5520 AGATGGAGGG AAGGGTGAAC AAGAAAGAGC TCTCCAGCCA GGTTCTCCGG AGTACGAAGA 5580 ACGGTGGCCT ACTGCCCCCT AGTGGACATT GGGGG 5615 (2) INFORMATION FOR SEQ ID NO: 48: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 263 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 48: Met Gly Gin Thr Ala Leu Ala Gly Gly Ser Ser Ser Thr Pro Thr Pro 1 5 10 15 Gin Ala Leu Tyr Pro Asp Leu Ser Cys Pro Glu Gly Leu Glu Glu Leu 20 25 30 Leu Ser Ala Pro Pro Pro Asp Leu Gly Ala Gin Arg Arg His Gly Trp 35 40 45 Asn Pro Lys Asp Cys Ser Glu Asn He Glu Val Lys Glu Gly Gly Leu 50 55 60 Tyr Phe Glu Arg Arg Pro Val Ala Gin Ser Thr Asp Gly Ala Arg Gly 65 70 75 80 Lys Arg Gly Tyr Ser Arg Gly Leu His Ala Trp Glu He Ser Trp Pro 85 90 95 Leu Glu Gin Arg Gly Thr His Ala Val Val Gly Val Ala Thr Ala Leu 100 105 110 Ala Pro Leu Gin Thr Asp His Tyr Ala Ala Leu Leu Gly Ser Asn Ser 115 120 125 Glu Ser Trp Gly Trp Asp He Gly Arg Gly Lys Leu Tyr His Gin Ser 130 135 140 Lys Gly Pro Gly Ala Pro Gin Tyr Pro Ala Gly Thr Gin Gly Glu Gin 145 150 155 160 Leu Glu Val Pro Glu Arg Leu Leu Val Val Leu Asp Met Glu Glu Gly 165 170 175 Thr Leu Gly Tyr Ala He Gly Gly Thr Tyr Leu Gly Pro Ala Phe Arg 180 185 190 Gly Leu Lys Gly Arg Thr Leu Tyr Pro Ala Val Ser Ala Val Trp Gly 195 200 205 Gin Cys Gin Val Arg He Arg Tyr Leu Gly Glu Arg Arg Ala Glu Pro 210 215 220 His Ser Leu Leu His Leu Ser Arg Leu Cys Val Arg His Asn Leu Gly 225 230 235 240 Asp Thr Arg Leu Gly Gin Val Ser Ala Leu Pro Leu Pro Pro Ala Met 245 250 255 Lys Arg Tyr Leu Leu Tyr Gin 260 (2) INFORMATION FOR SEQ ID NO: 49: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 28 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 49: AGCTAGATCTGGACCCTACAATGGCAGC 28 (2) INFORMATION FOR SEQ ID NO: 50: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 50: AGCTAGATCT GCCATCCTAC TCGAGGGGCC AGCTGG 36

Claims: CLAIMS: 1. A nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42 °C wherein said protein comprises a SOCS box in its C-terminal region. 2. A nucleic acid molecule according to claim 1 wherein the protein further comprises a protein: molecule interacting region. 3. A nucleic acid molecule according to claim 1 wherein the protein:molecule interacting region is located in a region N-terminal of the SOCS box. 4. A nucleic acid molecule according to claim 2 or 3 wherein the protein:molecule interacting region is a protein:DNA binding region or a proteimprotein binding region. 5. A nucleic acid molecule according to claim 4 wherein the protei molecule interacting region is one or more of an SH2 domain, WD-40 repeats or ankyrin repeats. 6. A nucleic acid molecule according to any one of claims 1-5 wherein the SOCS box comprises the amino acid sequence: X j X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X π X 12 X 13 X 14 X 15 X 16 [X j ] n X 17 x 18 x 19 x 20 X 21 X 22 X 23 [Xj] n X 24 X 25 X 26 X 27 X 28 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X n is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence Xj may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; and X 28 is L, I, V, M, A or P. 7. A nucleic acid molecule according to claim 6 wherein the protein modulates signal transduction. 8. A nucleic acid molecule according to claim 7 wherein the signal transduction is modulated by a cytokine or a hormone, a microbe or a microbial product, a parasite, an antigen or other effector molecule. 9. A nucleic acid molecule according to claim 8 wherein the protein modulates cytokine- mediated signal transduction. 10. A nucleic acid molecule according to claim 9 wherein the signal transduction is mediated by one or more of the cytokines EPO, TPO, G-CSF, GM-CSF, IL-3, IL-2, IL-4, IL-7, IL-13, IL-6, LIF, IL-12, IFNγ, TNFα, IL-1 and/or M-CSF. 11. A nucleic acid molecule according to claim 10 wherein the signal transduction is mediated by one or more of IL-6, LIF, OSM, IFN-γ and/or thrombopoietin. 12. A nucleic acid molecule according to claim 11 wherein the signal transduction is mediated by IL-6. 13. A nucleic acid molecule according to claim 1 wherein the nucleotide sequence encodes an amino acid sequence substantially as set forth in SEQ ID NO. 4, SEQ ID NO. 6, SEQ ID NO. 8, SEQ ID NO. 10, SEQ ID NO. 12, SEQ ID NO. 14, SEQ ID NO. 18, SEQ ID NO. 21, SEQ ID NO. 25, SEQ ID NO. 29, SEQ ID NO. 36, SEQ ID NO. 41, SEQ ID NO. 44, SEQ ID NO. 46 or SEQ ID NO. 48 or an amino acid sequence having at least about 15% similarity to all or part of the listed sequences or a nucleotide sequence which hybridizes to the nucleic acid molecule under low stringency conditions at 42 °C. 14. A nucleic acid molecule according to claim 1 wherein the nucleotide sequence is substantially as set forth in SEQ ID NO. 3, SEQ ID NO. 5, SEQ ID NO. 7, SEQ ID NO. 9, SEQ ID NO. 11, SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 20, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 26, SEQ ID NO. 27, SEQ ID NO. 28, SEQ ID NO. 30, SEQ ID NO. 31, SEQ ID NO. 32, SEQ ID NO. 33, SEQ ID NO. 34, SEQ ID NO. 35, SEQ ID NO. 37, SEQ ID NO. 38, SEQ ID NO. 39, SEQ ID NO. 40, SEQ ID NO. 42, SEQ ID NO. 43, SEQ ID NO. 45 or SEQ ID NO. 47 or a nucleotide sequence having at least 15% similarity to all or a part of the listed sequences or a nucleotide sequence capable of hybridizing to the listed sequences under low stringency conditions at 42 °C. 15. A nucleic acid molecule comprising a sequence of nucleotides encoding or complementary to a sequence encoding a protein or a derivative, homologue, analogue or mimetic thereof or a nucleotide sequence capable of hybridizing thereto under low stringency conditions at 42 °C wherein said protein exhibits the following characteristics: (i) comprises a SOCS box in its C-terminal region wherein said SOCS box comprises the amino acid sequence: Xj X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X I0 X u X 12 X 13 X 14 X 15 X 16 [X n X π X lg X 19 X 20 X 21 X 22 X 23 [Xj] n X 24 X 25 X 26 X 27 X 28 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; X 10 is any amino acid; X J J is any amino acid; X I2 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X, may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X I8 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; X 28 is L, I, V, M, A or P; and (ii) comprises at least one of an SH2 domain, WD-40 repeats and/or ankyrin repeats or other protein:molecule interacting domain in a region N-terminal of the SOCS box; and (iii) modulates signal transduction. 16. An isolated protein or a derivative, homologue or mimetic thereof comprising a SOCS box in its C-terminal region. 17. An isolated protein according to claim 16 wherein the protein further comprises a proteimmolecule interacting region. 18. An isolated protein according to claim 17 wherein the protein:molecule interacting region is located in a region N-terminal of the SOCS box. 19. An isolated protein according to claim 16 or 17 wherein the protein: molecule interacting region is a protein:DNA binding region or a protei protein binding region. 20. An isolated protein according to claim 19 wherein the protein: molecule interacting region is one or more of an SH2 domain, WD-40 repeats or ankyrin repeats. 21. An isolated protein according to any one of claims 16-20 wherein the SOCS box comprises the amino acid sequence: Xj X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X JO X π X 12 X 13 X 14 X 15 X 16 [X,] n X 17 X 18 X, 9 X 20 wherein: X 1 is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; X 8 is C, T or S; X 9 is R, K or H; Xio is any amino acid; X π is any amino acid; X 12 is L, I, V, M, A or P; X 1 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X; may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; and X 28 is L, I, V, M, A or P. 22. An isolated protein according to claim 21 wherein the protein modulates signal transduction. 23. An isolated protein according to claim 22 wherein the signal transduction is modulated by a cytokine or other endogenous molecule, a hormone, a microbe or a microbial product, a parasite, an antigen or other effector molecule. 24. An isolated protein according to claim 23 wherein the protein modulates cytokine- mediated signal transduction. 25. An isolated protein according to claim 24 wherein the signal transduction is mediated by one or more of the cytokines EPO, TPO, G-CSF, GM-CSF, IL-3, IL-2, IL-4, IL-7, IL-13, IL-6, LIF, IL-12, IFNγ, TNFα, IL-1 and/or M-CSF. 26. An isolated protein according to claim 25 wherein the signal transduction is mediated by one or more of IL-6, LIF, OSM, IFN-γ and/or thrombopoietin. 27. An isolated protein according to claim 26 wherein the signal transduction is mediated by IL-6. 28. An isolated protein according to claim 16 wherein said protein comprises an amino acid sequence substantially as set forth in SEQ ID NO. 4, SEQ ID NO. 6, SEQ ID NO. 8, SEQ ID NO. 10, SEQ ID NO. 12, SEQ ID NO. 14, SEQ ID NO. 18, SEQ ID NO. 21, SEQ ID NO. 25, SEQ ID NO. 29, SEQ ID NO. 36, SEQ ID NO. 41, SEQ ID NO. 44, SEQ ID NO. 46 or SEQ ID NO. 48 or an amino acid sequence having at least about 15% similarity to all or part of the listed sequences. 29. An isolated protein according to claim 16 wherein the said protein is encoded by a nucleotide sequence substantially as set forth in SEQ ID NO. 3, SEQ ID NO. 5, SEQ ID NO. 7, SEQ ID NO. 9, SEQ ID NO. 11, SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 20, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 26, SEQ ID NO. 27, SEQ ID NO. 28, SEQ ID NO. 30, SEQ ID NO. 31, SEQ ID NO. 32, SEQ ID NO. 33, SEQ ID NO. 34, SEQ ID NO. 35, SEQ ID NO. 37, SEQ ID NO. 38, SEQ ID NO. 39, SEQ ID NO. 40, SEQ ID NO. 42, SEQ ID NO. 43, SEQ ID NO. 45 or SEQ ID NO. 47 or a nucleotide sequence having at least 15% similarity to all or a part of the listed sequences or a nucleotide sequence capable of hybridizing to the listed sequences under low stringency conditions at 42 °C. 30. An isolated protein or a derivative, homologue, analogue or mimetic thereof having the following characteristics: (i) comprises a SOCS box in its C-terminal region wherein said SOCS box comprises the amino acid sequence: Xi X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X π X 12 X 13 X ]4 X 15 X 16 [Xj] n X 17 X 18 X 19 X 20 X 2 1 X-22 X 2 3 [Xjln ^24 X 2 5 ^26 X27 28 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 is L, I, V, M, A, F, Y or W; x 8 is C, T or S; 9 is R, K or H; X 10 is any amino acid; X n is any amino acid; X 12 is L, I, V, M, A or P; X 13 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X ( may comprise the same or different amino acids selected from any amino acid residue; X 17 is L, I, V, M, A or P; X 18 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 2] is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; X 28 is L, I, V, M, A or P; and (ii) comprises at least one of an SH2 domain, WD-40 repeats and/or ankyrin repeats or other protein: molecule interacting domain in a region N-terminal of the SOCS box; and (iii) modulates signal transduction. 31. A method of modulating levels of a SOCS protein in a cell said method comprising contacting a cell containing a SOCS gene with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time and under conditions sufficient to modulate levels of said SOCS protein. 32. A method of modulating signal transduction in a cell containing a SOCS gene comprising contacting said cell with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time sufficient to modulate signal transduction. 33. A method of influencing interaction between cells wherein at least one cell carries a SOCS gene, said method comprising contacting the cell carrying the SOCS gene with an effective amount of a modulator of SOCS gene expression or SOCS protein activity for a time sufficient to modulate signal transduction. 34. A method according to any one of claims 31-33 wherein signal transduction is mediated by a cytokine, a hormone, a microbe or a microbial product, a parasite, an antigen or other effector molecule. 35. A method according to claim 34 wherein the cytokine is one or more of EPO, TPO, G- CSF, GM-CSF, IL-3, IL-2, IL-4, IL-7, IL-13, IL-6, LIF, IL-12, IFNγ, TNFα, IL-1 and/or M- CSF. 36. A method according to claim 35 wherein the cytokine is one or more of IL-6, LIF, OSM, EFN-γ and/or thrombopoietin. 37. A method according to claim 36 wherein the cytokine is IL-6. 38. A method according to any one of claims 31-37 wherein the SOCS gene encodes a protein having a SOCS box comprising the amino acid sequence: X ! X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X n X 12 X 13 X 14 X 15 X 16 [X n X 17 X 18 x 19 x 20 X 2 1 X22 X23 [XJJn X24 X 2 5 X26 X27X28 wherein: X, is L, I, V, M, A or P; X 2 is any amino acid residue; X 3 is P, T or S; X 4 is L, I, V, M, A or P; X 5 is any amino acid; X 6 is any amino acid; X 7 isL,I,V,M,A,F,YorW; X 8 is C, T or S; X 9 is R, K or H; X I0 is any amino acid; X π is any amino acid; X 12 is L, I, V, M, A or P; X I3 is any amino acid; X 14 is any amino acid; X 15 is any amino acid; X 16 is L, I, V, M, A, P, G, C, T or S; [XJ n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X, may comprise the same or different amino acids selected from any amino acid residue; X 17 isL,I,V,M, AorP; X, 8 is any amino acid; X 19 is any amino acid; X 20 L, I, V, M, A or P; X 21 is P; X 22 is L, I, V, M, A, P or G; X 23 is P or N; [X j ] n is a sequence of n amino acids wherein n is from 1 to 50 amino acids and wherein the sequence X j may comprise the same or different amino acids selected from any amino acid residue; X 24 is L, I, V, M, A or P; X 25 is any amino acid; X 26 is any amino acid; X 27 is Y or F; and X 28 is L, I, V, M, A or P. 39. A method according to claim 38 wherein the SOCS gene comprises a nucleotide sequence selected from SEQ ID NO. 3, SEQ ID NO. 5, SEQ ID NO. 7, SEQ ID NO. 9, SEQ ID NO. 11, SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 20, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 26, SEQ ID NO. 27, SEQ ID NO. 28, SEQ ID NO. 30, SEQ ID NO. 31, SEQ ID NO. 32, SEQ ID NO. 33, SEQ ID NO. 34, SEQ ID NO. 35, SEQ ID NO. 37, SEQ ID NO. 38, SEQ ID NO. 39, SEQ ID NO. 40, SEQ ID NO. 42, SEQ ID NO. 43, SEQ ID NO. 45 or SEQ ID NO. 47. 40. A method according to claim 38 wherein the SOCS gene encodes a protein comprising an amino acid sequence substantially as set forth in SEQ ID NO. 4, SEQ ID NO. 6, SEQ ID NO. 8, SEQ ID NO. 10, SEQ ID NO. 12, SEQ ID NO. 14, SEQ ID NO. 18, SEQ ID NO. 21, SEQ ID NO. 25, SEQ ID NO. 29, SEQ ID NO. 36, SEQ ID NO. 41, SEQ ID NO. 44, SEQ ID NO. 46 or SEQ ID NO. 48.

Inventors: ALEXANDER WARREN S, HILTON DOUGLAS J, METCALF DONALD, NICHOLSON SANDRA E, NICOLA NICOS A, RICHARDSON RACHAEL T, STARR ROBYN, VINEY ELIZABETH M, WILLSON TRACY A, ALEXANDER, WARREN, S., HILTON, DOUGLAS, J., METCALF, DONALD, NICHOLSON, SANDRA, E., NICOLA, NICOS, A., RICHARDSON, RACHAEL, T., STARR, ROBYN, VINEY, ELIZABETH, M., WILLSON, TRACY, A.
Applicants: ALEXANDER WARREN S, HILTON DOUGLAS J, INST MEDICAL W & E HALL, METCALF DONALD, NICHOLSON SANDRA E, NICOLA NICOS A, RICHARDSON RACHAEL T, STARR ROBYN, VINEY ELIZABETH M, WILLSON TRACY A, ALEXANDER, WARREN, S., HILTON, DOUGLAS, J., METCALF, DONALD, NICHOLSON, SANDRA, E., NICOLA, NICOS, A., RICHARDSON, RACHAEL, T., STARR, ROBYN, THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RES, VINEY, ELIZABETH, M., WILLSON, TRACY, A.
Application year: 1997
Main classification: C07K2
IPC codes: A61K31, A61K38, A61K48, A61P9, A61P35, A61P37, A61P43, C07K2, C07K14, C12N15