MATERIALS AND METHODS RELATING TO PROTEINS THAT INTERACT WITH CASEIN KINASE I

Abstract: The present invention relates generally to identification of proteins, designated TIH proteins, that interact with casein kinase I isoforms and to isolation of polynucleotides encoding the same.

Description: Materials and Methods Relating To Proteins That Interact With Casein Kinase I This application is a continuation-in-partof U.S. Patent Application Serial No.08/184,605, filed January 21, 1994. FIELD OF THE INVENTION The present invention relates generally to identification of proteins, herein designated TEH proteins, that interact with casein kinase I isoforms and to isolation of polynucleotides encoding the same. BACKGROUND Protein kinases are post-translational, enzymatic regulators of cellular metabolism. Once activated, these enzymes transfer phosphate from ATP onto substrate proteins and in doing so affect the properties of substrate molecules. There are four broad classes of protein kinases including serine/threonine kinases, tyrosine kinases, multi-specific or dual-specific kinases, and histidine kinases [Hunter, et ah, Meth.Enzymol. 200:3-31 (1991)]. In addition to the amino acid residue(s) of the substrate preferentially phosphorylated by the kinase, assignment of an enzyme to a particular class is based on its primary structure, its requirement for regulatory subunits, its requirement for second messengers, and its specific biochemical activity. See Hunter et ah, supra, and Hanks and Quinn, Meth. Enzymol, 200: 38-62 (1991). Serine/threonine protein kinases have been further divided into families of enzymes based on the mode of regulation of the enzymes and the quaternary structure of the active enzymes [Edelman, et al. , Ann. Rev. Biochem. 55:567-613 (1987)]. Enzymes within the serine/threonine protein kinase family can differ in the substrates they phosphorylate, the specific phosphorylation sites they recognize, their mode of regulation and their subcellular distribution. Protein kinase A (PKA), for example, phosphorylates target substrates with the recognition/phosphorylation sequence R-R-X-S(P)-Y (SEQ ID NO: 1) [Pearson and Lemp, Meth.Enzymol. 200:62-81 (1991)], where S(P) represents the phosphorylated residue. The activity of PKA is localized by targeting subunits (called anchoring proteins or AKAPs, reviewed in Hubbard and Cohen, T.I.B.S. 18: 172-177, 1993). Members of the casein kinase I (CKI) family, on the other hand, recognize and phosphorylate serines and threonines near acidic residues in substrate proteins. The genes which encode yeast, rat, bovine and human isoforms of casein kinase I activity are structurally similar and the isoforms exhibit greater than 35%, and frequently greater than 50%, homology (identity) over their catalytic domains when compared to the prototypical S. cerevisiae CKI protein, HRR25, and are referred to herein as "HRR25-like" proteins. This degree of identity is significantly greater than the expected 25% found for comparing two randomly chosen protein kinases [Hanks and Quinn, supra]. The HRR25 DNA sequence is disclosed in Hoekstra, et al., Science 255:1031-1034 (1991); yeast CKIl and CKI2 DNA sequences in Wang et al., J. Mol. Biol. Cell, 5:275-286 (1992) corresponding respectively to yeast sequences YCK2 and YCK1 in Robinson et al , Proc. Natl. Acad. Sci. (USA) 89:28-32 (1992); partial bovine CKIα, CKI/3, CKIγ and CKIδ DNA sequences and a full length homolog CKIα DNA sequence in Rowles, et al., Proc. Natl. Acad. Sci. (USA) 88:9548-9552 (1991); a full length rat CKIδ DNA sequence in Graves, et al, J. Biol. Chem., 268: 6394-6401 (1993); and a partial human erythroid CKIα DNA sequence in Brockman et al , Proc. Natl Acad. Sci. (USA) 8 :9454-9458 (1992). The S. cerevisiae protein kinase HRR25 is one of the more extensively characterized isoforms of the CKI family [Hoekstra, supra]. Mutations in the HRR25 gene result in a variety of defects that include cell cycle delays, the inability to properly repair DNA strand breaks and characteristic morphological changes. The nature of these defects implies that HRR25 and other CKI isoforms play a significant role in cellular growth. The importance of protein phosphorylation and protein kinases in health and disease states is evident in cases where expression of a particular kinase has gone awry; for example, chronic myelogenous leukemia arises from a translocation that places the breakpoint cluster region (BCR) gene next to the ABL tyrosine kinase gene, resulting in a fusion protein comprising the activated protein kinase [see review, Bishop, et al, Cell 64:235-288 (1991)]. In addition, many oncogenes, such as Mos [Watson, et al, Proc. Natl Acad. Sci. (USA) 79:4078-4082 (1982)], Src [Anderson, etal, Mol Cell Biol. 5:1122-1129 (1985)] and Raf [Bonner, et al, Nucl.Acids Res. 14: 1009-1015 (1986)] are protein kinases. Most protein kinases phosphorylate a variety of substrates in vivo allowing diversity in responses to physiological stimuli [reviewed in Edelman, et al, supra]. However, the broader substrate specificity seen for many protein kinases in vitro, including activity towards non-physiological substrates, indicates that cellular mechanisms to control the specificity of these enzymes must exist in vivo. Understanding the regulatory mechanisms that govern these kinases and the specific role of the kinases in health and disease states requires the identification of substrates, regulatory proteins, and localizing/targeting proteins that interact with the kinases. There thus exists a need in the art to identify proteins which interact with members of the casein kinase I family of enzymes and to characterize the interacting proteins in terms of their amino acid and encoding DNA sequences. Such information would provide for the large scale production of the proteins, allow for identification of cells which produce the kinases naturally and permit production of antibodies specifically reactive with the kinases. Moreover, elucidation of the substrates, regulation, and localization of these protein kinases would contribute to an understanding of the control of normal and malignant cell growth and provide information essential for the development of therapeutic agents useful for intervention in abnormal and/or malignant cell growth. SUMMARY OF THE INVENTION In one of its aspects, the present invention provides methods for identifying proteins, designated TIH proteins, that interact with CKI isoforms [i. e. , S. cerevisiae HRR25 casein kinase I and HRR25-like protein kinases having at least 35 % amino acid homology to HRR25 within the catalytic domain] and for isolating polynucleotides encoding the TIH proteins. A presently preferred method comprises the steps of: a) transforming or transfecting appropriate host cells with a DNA construct comprising a reporter gene under the control of a promoter regulated by a transcription factor having a DNA-binding domain and an activating domain; b) expressing in the host cells a first hybrid DNA sequence encoding a first fusion of part or all of a CKI isoform and either the DNA-binding domain or the activating domain of the transcription factor; c) expressing in the host cells a library of second hybrid DNA sequences encoding second fusions of part or all of putative CKI isoform-binding proteins and either the DNA-binding domain or DNA activating domain of the transcription factor which is not incorporated in the first fusion; d) detecting binding of CKI isoform-binding proteins to the CKI isoform in a particular host cell by detecting the production of reporter gene product in the host cell; and e) isolating second hybrid DNA sequences encoding CKI isoform-binding protein from the particular host cell. Variations of the method altering the order in which the CKI isoforms and putative CKI isoform-binding proteins are fused to transcription factor domains, i.e. , at the amino terminal or carboxy terminal ends of the transcription factor domains, are contemplated. In a preferred version of the method, the promoter is the lexA promoter, the DNA-binding domain is the lexA DNA-binding domain, the activating domain is the GAL4 transactivation domain, the reporter gene is the lacZ gene and the host cell is a yeast host cell. Variations of the method permit identification of either small molecules which inhibit the interaction between a CKI isoform and a CKI- interacting protein. A preferred method to identify small molecule inhibitors comprises the steps of: a) transforming or transfecting appropriate host cells with a DNA construct comprising a reporter gene under the control of a promoter regulated by a transcription factor having a DNA-binding domain and an activating domain; b) expressing in the host cells a first hybrid DNA sequence encoding a first fusion of part or all of a CKI isoform and either the DNA-binding domain or the activating domain of the transcription factor; c) expressing in the host cells a second hybrid DNA sequence encoding second fusion of part or all of a known CKI isoform-binding protein and either the DNA-binding domain or DNA activating domain of the transcription factor which is not incorporated in the first fusion; d) contacting the cells with a putative inhibitor compound; and e) identifying modulating compounds as those compounds altering production of the reporter gene product in comparison to production of the reporter gene product in the absence of the modulating compound. An alternative identification method contemplated by the invention for detecting proteins which bind to a CKI isoform comprises the steps of: a) transforming or transfecting appropriate host cells with a hybrid DNA sequence encoding a fusion between a putative CKI isoform-binding protein and a ligand capable of high affinity binding to a specific counterreceptor;b) expressing the hybrid DNA sequence in the host cells under appropriate conditions ;c) immobilizing fusion protein expressed by the host cells by exposing the fusion protein to the specific counterreceptor in immobilized form; d) contacting a CKI isoform with the immobilized fusion protein; and e) detecting the CKI isoform bound to the fusion protein using a reagent specific for the CKI isoform. Presently preferred ligands/counterreceptor combinations for practice of the method are glutathione-S-transferase/glutathione, hemagglutinin/hemagglutinin- specific antibody, polyhistidine/nickel and maltose-binding protein/amylose. The present invention also provides novel, purified and isolated polynucleotides (e.g., DNA sequences and RNA transcripts, both sense and antisense strands) encoding the TIH proteins and variants thereof (i.e. , deletion, addition or substitution analogs) which possess CKI and/or HRR25-binding properties inherent to the TIH proteins. Preferred DNA molecules of the invention include cDNA, genomic DNA and wholly or partially chemically synthesized DNA molecules. Presently preferred polynucleotides are the DNA molecules set forth in SEQ ID NOS: 2 (TIH1), 4 (TIH2), and 6 (TIH3), encoding the polypeptides of SEQ ID NOS: 3 (TIH1), 5 (TIH2), and 7 (TIH3), respectively. Also provided are recombinant plasmid and viral DNA constructs (expression constructs) which comprise TIH polypeptide-encoding sequences operatively linked to a homologous or heterologous transcriptional regulatory element or elements. As another aspect of the invention, prokaryotic or eukaryotic host cells transformed or transfected with DNA sequences of the invention are provided which express TIH polypeptides or variants thereof. Host cells of the invention are particularly useful for large scale production of TIH polypeptides, which can be isolated from the host cells or the medium in which the host cells are grown. Also provided by the present invention are purified and isolated TIH polypeptides, fragments and variants thereof. Preferred ΗH polypeptides are as set forth in SEQ ID NOS: 3 (ΗHl), 5 (TIH2), and 7 (TIH3). Novel ΗH and TIH variant products of the invention may be obtained as isolates from natural sources, but are preferably produced by recombinant procedures involving host cells of the invention. Post-translational processing variants of TIH polypeptides may be generated by varying the host cell selected for recombinant production and/or post-isolation processing. Variant TIH polypeptides of the invention may comprise analogs wherein one or more of the amino acids are deleted or replaced: (1) without loss, and preferably with enhancement, of biological properties or biochemical characteristics specific for TIH polypeptides or (2) with specific disablement of a characteristic protein/protein interaction. Also comprehended by the invention are antibody substances (e.g., monoclonal and polyclonal antibodies, single chain antibodies, chimeric antibodies, CDR-grafted antibodies and the like) which are specifically immunoreactive with TIH polypeptides. Antibody substances are useful, for example, for purification of TIH polypeptides and for isolation, via immunological expression screening, of homologous and heterologous species polynucleotides encoding TIH polypeptides. Hybridoma cell lines which produce antibodies specific for TIH polypeptides are also comprehended by the invention. Techniques for producing hybridomas which secrete monoclonal antibodies are well known in the art. Hybridoma cell lines may be generated after immunizing an animal with purified TIH polypeptides or variants thereof. The scientific value of the information contributed through the disclosure of DNA and amino acids sequences of the present invention is manifest. As one series of examples, knowledge of the genomic DNA sequences which encode yeast ΗH polypeptides permits the screening of a cDNA or genomic DNA of other species to detect homologs of the yeast polypeptides. Screening procedures, including DNA/DNA and/or DNA/RNA hybridization and PCR amplification are standard in the art and may be utilized to isolate heterologous species counterparts of the yeast TIH polypeptides, as well as to determine cell types which express these homologs. DNA and amino acid sequences of the invention also make possible the analysis of ΗH epitopes which actively participate in kinase/protein interactions as well as epitopes which may regulate such interactions. Development of agents specific for these epitopes (e.g. , antibodies, peptides or small molecules) which prevent, inhibit, or mimic protein kinase-protein substrate interaction, protein kinase-regulatory subunit interaction, and/or protein kinase- protein localization molecule interaction are contemplated by the invention. Therapeutic compositions comprising the agents are expected to be useful in modulating the CKI/TIH protein interactions involved in cell growth in health and disease states, for example, cancer and virus-related pathologies. BRIEF DESCRIPTION OF THE DRAWING Numerous other aspects and advantages of the present invention will be apparent upon consideration of the following detailed description thereof, reference being made to the drawing wherein: Figure 1 is a Western blot demonstrating the association of S. cerevisiae HRR25 casein kinase I with affinity-purified TIH2. Figure 2 is an amino acid sequence comparison between TIH1 and enzymes known to participate in removal of aberrant nucleotides. DETAILED DESCRIPTION The present invention generally relates to methods for identifying proteins that interact with CKI isoforms and is illustrated by the following examples relating to the isolation and characterization of genes encoding TIH polypeptides. More particularly, Example 1 addresses isolation of DNA sequences encoding TIH polypeptides from a yeast genomic library utilizing a dihybrid screening technique. Example 2 relates to analysis of the interaction between ΗH polypeptides and various yeast CKI isoforms. Example 3 addresses interaction between a yeast CKI isoform, including mutants and fragments thereof, and kinesins. Example 4 describes analysis of the interaction between TIH polypeptides and human CKI isoforms. Example 5 addresses isolation of full length genomic DNA sequences which encode TIH polypeptides of the invention. Example 6 describes construction of a TIH knock-out mutant in yeast. Example 7 addresses analysis of S. cerevisiae HRR25/TIH polypeptides interactions utilizing affinity purification and Western blotting techniques. Example 8 provides a comparison at the amino acid level between TIH1 and enzymes identified as participating in degradation of oxidatively damaged nucleotides, thus enhancing fidelity of replication. Example 1 Cellular components that interact with CKI isoforms were identified by a dihybrid screening method that reconstitutes a transcriptional transactivator in yeast. [A similar "two-hybrid" assay was originally described in Fields and Song, Nature, 340: 245-246 (1989) and more recently in Yang et al, Science 257:681-682 (1992) and Vojtek et al , Cell, 74: 205-214 (1993).] In the assay, "bait" components (i.e., CKI isoforms) are fused to the DNA binding domain of a transcription factor (e.g. , the lexA protein) and "prey" components (i.e. , putative CKI interacting proteins) are fused to the transactivation domain of the transcription factor (e.g., GAL4). Recombinant DNA constructs encoding the fusion proteins are expressed in a host cell that contains a reporter gene fused to promoter regulatory elements (e.g. a lexA DNA binding site) recognized by the transcription factor. Binding of a prey fusion protein to a bait fusion protein brings together the GAL4 transactivation domain and the lexA DNA binding domain allowing interaction of the complex with the lexA DNA binding site that is located next to the j3-galactosidase reporter gene, thus reconstituting transcriptional transactivation and producing β-galactosidase activity. In variations of the method, the "prey" component can be fused to the DNA binding domain of GAL4 and the "bait" components detected and analyzed by fusion to the transactivation domain of GAL4. Likewise, variations of this method could alter the order in which "bait" and "prey" components are fused to transcription factor domains, i.e. , "bait" and "prey" components can be fused at the amino terminal or carboxy terminal ends of the transcription factor domains. To identify genes encoding proteins that interact with S. cerevisiae HRR25 CKI protein kinase, a plasmid library encoding fusions between the yeast GAL4 activation domain and S. cerevisiae genomic fragments ("prey" components) was screened for interaction with a DNA binding domain hybrid that contained the E. coli lexA gene fused to HRR25 ("bait" component). The fusions were constructed in plasmid pBTM116 (gift from Bartell and Fields, SUNY) which contains the yeast TRP1 gene, a 2μ origin of replication, and a yeast ADHI promoter driving expression of the E. coli lexA DNA binding domain (amino acids 1 to 202). Plasmid pBTM116::HRR25, which contains the lexA::HRR25 fusion gene, was constructed in several steps. The DNA sequence encoding the initiating methionine and second amino acid of HRR25 was changed to a Smal restriction site by site-directed mutagenesis using a MutaGene mutagenesis kit from BioRad (Richmond, California). The DNA sequence of HRR25 is set out in SΕQ ID NO: 8. The oligonucleotide used for the mutagenesis is set forth below, wherein the Smal site is underlined. 5'-CCT ACT CTT AGG CCC GGG TCT TTT TAA TGT ATC C-3' (SΕQ ID NO. 9) After digestion with Smal, the resulting altered HRR25 gene was ligated into plasmid pBTMllό at the Smal site to create the lexA::HRR25 fusion construct. Interactions between bait and prey fusion proteins were detected in yeast reporter strain CTY10-5d (genotype=Al-47'c ade2 trpl-901 leu2-3,112 his 3-200 gal4 gal80 URA3:. exA op-lacZ. ) [Luban, et al , Cell 73: 1067-1078 (1993)] carrying a lexA binding site that directs transcription of lacZ . Strain CTY10-5d was first transformed with plasmid pBTMl 16: :HRR25 by lithium acetate-mediated transformation [Ito, et al, J.Bacteriol 755:163-168 (1983)]. The resulting transformants were then transformed with a prey yeast genomic library prepared as GAL4 fusions in the plasmid pGAD [Chien, et al, Proc. Natl Acad. Sci (USA) 22:9578-9582 (1991)] in order to screen the expressed proteins from the library for interaction with HRR25. A total of 500,000 double transformants were assayed for β-galactosidase expression by replica plating onto nitrocellulose filters, lysing the replicated colonies by quick-freezing the filters in liquid nitrogen, and incubating the lysed colonies with the blue chromogenic substrate 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal). jS-galactosidase activity was measured using Z buffer (0.06 M Na 2 HPO 4 , 0.04 M NaH 2 PO 4 , 0.01 M KC1, 0.001 M MgSO 4 , 0.05 M /3-mercaptoethanol) containing X-gal at a concentration of 0.002% [Guarente, Meth. Enzymol 207: 181-191 (1983)]. Reactions were terminated by floating the filters on 1M Na 2 CO 3 and positive colonies were identified by their dark blue color. Library fusion plasmids (prey constructs) that conferred blue color to the reporter strain co-dependent upon the presence of the HRR25/DNA binding domain fusion protein partner (bait construct) were identified. The sequence adjacent to the fusion site in each library plasmid was determined by extending DNA sequence from the GAL4 region. The sequencing primer utilized is set forth below. 5'-GGA ATC ACT ACA GGG ATG-3' (SEQ ID NO. 10) DNA sequence was obtained using a Sequenase version II kit (US Biochemicals, Cleveland, Ohio) or by automated DNA sequencing with an ABI373A sequencer (Applied Biosy stems, Foster City, California). Four library clones were identified and the proteins they encoded are designated herein as TIH proteins 1 through 4 for Targets Interacting with HRR25-like protein kinase isoforms. The TTH1 portion of the TIH1 clone insert corresponds to nucleotides 1528 to 2580 of SEQ ID NO: 2; the TIH2 portion of the TIH2 clone insert corresponds to nucleotides 2611 to 4053 of SEQ ID NO: 4; the TTH3 portion of the TIH3 clone insert corresponds to nucleotides 248 to 696 of SEQ ID NO: 6; and the TIH4 portion of the TIH4 clone insert is set out in SEQ ID NO: 11 and corresponds to nucleotides 1763 to 2305 of SEQ ID NO: 28. Based on DNA sequence analysis of the TIH genes, it was determined that TIH1 and TIH3 were novel sequences that were not representative of any protein motif present in the GenBank database (July 8, 1993). TIH2 sequences were identified in the database as similar to a yeast open reading frame having no identified function. (GenBank Accession No. Z23261, open reading frame YBL0506) TIH4 represented a fusion protein between GAL4 and the carboxy- terminal portion of the kinesin-like protein KIP2. KIP2 has a highly conserved region which contains a kinesin-like microtubule-based motor domain [Roof et al. , J. Cell Biol. 228(1):95-108 (1992)]. The isolation of corresponding full length genomic clones for TIH1 through TIH3 is described in Example 5. Example 2 To investigate the specificity of interaction and regions of interaction between CKI isoforms and the TIH proteins, bait constructs comprising mutant or fragment HRR25 isoforms or other yeast (NUF1 and Hhpl) CKI isoforms fused to the lexA DNA binding domain were examined for transcription transactivation potential in the dihybrid assay. Plasmid Constructions To construct a plasmid containing a catalytically-inactive HRR25 protein kinase, HRR25 DNA encoding a lysine to arginine mutation at residue 38 (the ATP binding site) of HRR25 [DeMaggio et al. , Proc. Natl. A " cad. Sci. (USA) 89(15): 7008-7012 (1992)] was generated by standard site-directed mutagenesis techniques. The resulting DNA was then amplified by a PCR reaction which inserted a Smal restriction site (underlined in SEQ ID NO. 12) before the HRR25 ATG using a mutagenic oligonucleotide: 5'-CCTTCC TACTCTTAAGCC CGG GCC GCA GGAATT CG-3' (SEQIDNO 12), and the downstream oligonucleotide which inserted a BamRl site (underlined): 5'-AGC AAT ATA GGA TCC TTA CAA CCA AAT TGA-3' (SEQ ID NO: 13). Reactions included 200mM Tris-Hcl (pH 8.2), lOOmM KC1, 60 mM (NH 4 ) 2 SO 4 , 15mM MgCl 2 , 1 % Triton X-100, 0.5 μM primer, 100 ng template, 200 μM dNTP and 2.5 units polymerase. The reactions were performed for 30 cycles. Reactions were started with a 4 minute treatment at 94 ° C and all cycles were 1 minute at 94 °C for denaturing, 2 minutes at 50 °C for annealing, and 4 minutes at 72 °C for extension. The resulting amplification product was digested with Smal and ligated at the Smal site of pBTMllό to produce the plasmid designated pBTM116::HRR25K-*R encoding lex A sequences fused 5' to HRR25 sequences. To construct a pBTMllό plasmid encoding a catalytic domain fragment of HRR25, two rounds of site-directed mutagenesis were performed to introduce a Smal site in place of the initiating ATG and second codon of HRR25 DNA and a -ScmHI site at nucleotide 1161 (refer to SEQ ID NO. 8) or amino acid 397 of HRR25. The mutagenic oligonucleotide used to introduce the 5' Smal restriction site (underlined) was: 5'-CCT ACT CTT AAG CCC GGGTCT TTT TAA TGT ATC C-3' (SEQID NO.14), and the oligonucleotide used to create the 3', or downstream, BamΗl site (underlined) at residue 397 was: 5'-GTC TCA AGT TTT GGG ATC CTT AAT CTA GTG CG-3' (SEQ ID NO. 15). The resulting product was digested with Smal-BamΗ and the fragment encoding the HRR25 catalytic domain (corresponding to nucleotides 2 to 1168 of SEQ ID NO: 8) was subcloned into plasmid pBTMllό linearized with the same enzymes to produce the plasmid designated pBTM 116:: Kinase domain encoding lex A sequences fused 5' to HRR25 sequences. To construct a pBTMllό plasmid containing the non-catalytic domain fragment of HRR25, a Smal site (underlined) was introduced at nucleotide 885 (amino acid 295) using site-directed mutagenesis with the following oligonucleotide: 5'-CAC CAT CGC CCC CGG GTA ACG CAA CATTGT CC-3' (SEQID NO: 16). The resulting product was digested with Smal and BamHl and the fragment encoding the HRR25 non-catalytic domain (corresponding to nucleotides 885 to 1485 of SEQ ID NO: 8) was subcloned into plasmid pBTMl 16 linearized with the same enzymes to produce the plasmid designated pBTM116::Non-catalytic encoding lex A sequences fused 5' to HRR25 sequences. To construct a fusion with the S. cerevisiae NUFl isoform of CKI in plasmid pBTMllό, a Smal site (underlined) was introduced by site-directed mutagenesis in place of the initiating ATG and second codon of NUFl DNA (SEQ ID NO: 17) using the oligonucleotide: 5'-TGAAGATCGTTG GCC CGG GTTTCC TTA TCGTCC-3' (SEQIDNO.18). The resulting product was digested with Smal and j-tamHI and the NUFl fragment was ligated into pBTMl 16 linearized with the same enzymes sites to produce the plasmid designated pBTM116::NUFl encoding lex A sequences fused 5' to NUFl sequences. To construct a fusion with the S. pombe Hh l isoform of CKI in plasmid pBTMllό, a Smal site (underlined) was introduced by site-directed mutagenesis in place of the initiating ATG and second codon of Hhpl DNA (SEQ ID NO: 19) using the oligonucleotide: 5'-GGGTTA TAATAT TAT CCC GGG TTT GGA CCT CCG G-3' (SEQID NO.20). The resulting product was digested with Smal and BamHl and the Hhpl fragment was ligated into pBTMllό linearized with the same enzymes to produce plasmid pBTM116::Hhpl encoding lexA sequences fused 5' to Hhpl sequences. Assays To measure protein/protein interaction levels between wild-type and mutant CKI isoforms and TIH proteins of the invention, standard yeast mating techniques were used to generate yeast strains containing all pairwise combinations of the isoforms and TIH proteins. All CKI isoform-encoding pBTMl 16-based plasmids were transformed into yeast by lithium acetate-mediated transformation methods and transformants were selected on SD-tryptophan medium (BiolOl, La Jolla, CA). The yeast strain CTY10-5d used for pBTMl 16- based transformations was mating type α. All TIH protein-encoding pGAD-based plasmids described in Example 1 were transformed using the lithium acetate method into yeast and transformants were selected on SD-leucine medium. The yeast strain used for pGAD-based transformations was mating type a. This MATa strain is isogeneic to CTY10-5d and was constructed by introducing the HO gene using plasmid pGALHO [Jenson and Herskowitz, Meth.Enzymol 194: 132-146 (1991)] in lithium acetate-mediated transformation, inducing the HO gene with galactose to cause a mating-type interconversion, and growing the strain non- selectively to isolate a derivative that had switched mating type. To construct pairwise combinations between pBTMl 16-based plasmids and pGAD-based plasmids, yeast strains of opposite mating types were replica plated in a crossed pattern on YEPD medium (BiolOl) and were allowed to mate for 18 hours. Diploid cells were selected by a second replica plating onto SD-leucine, -tryptophan medium to select for cells that contained both pBTMl 16- type and pGAD-type plasmids. The isolated diploids were grown in liquid SD- leucine, -tryptophan medium to a cell density of 2 x 10 7 cells/ml and the level of interaction of the kinase and interacting protein, as determined by beta- galactosidase activity, was determined from cells that were lysed by adding 3 drops of chloroform and 50 μl of 0.1 % SDS to 2 x 10 s cells suspended in 0.1 ml of Z buffer and subsequently adding 0.2 ml of the chromogenic substrate o- nitrophenyl-/3-D-galactoside. β-galactosidase assays were terminated by adding 0.5 ml of IM Na 2 CO 3 and activity was measured by reading absorbance at 420 nm using a Milton Roy spectrophotometer (Rochester, New York). In this assay, the degree of protein/protein interaction is directly proportional to the level of β- galactosidase activity. The relative β-galactosidase activity measurements obtained are given in Table 1 , wherein a value of < 5 indicates that the level of (8-galactosidase activity was not greater than background and a value of 10 indicates a easily detectable level of activity. Values were normalized to vector alone controls. Table 1 Yeast CKI/TIH Protein Interactions pGAD pGAD pGAD PLASMID CONSTRUCTS ASSAYED ::TIH1 ::TIH2 ::TIH3 pBTMllό <5 <5 <5 pBTM116:HRR25 850 650 100 pBTM116::HRR25 K→R 100 150 30 pBTM116::Kinase Domain 820 160 130 pBTMl 16: : Non-catalytic <5 <5 <5 pBTM116::NUFl <5 <5 10 pBTM116::Hhpl <5 20 450 The results show significant interaction between HRR25 protein kinase and the TIH genes. Furthermore, the interaction appeared to require an active protein kinase; the region of HRR25 that interacted with the TIH proteins is localized to the protein kinase domain of HRR25. ΗH proteins of the invention also interacted with other CKI isoforms. For example, TIH3 interacted with NUFl, and TIH2 and TIH3 interacted with Hhpl. Example 3 Because HRR25 mutants (hrr25) show chromosome segregation defects and because kinesins are involved in chromosome segregation, the interaction of several different kinesins with the CKI bait fusions described in Example 2 was examined. To date, the kinesin gene family in yeast includes proteins designated KIP1 (Roof et al. supra), KIP2 (Roof et al , supra), CIN8 [Hoyt et al , J. Cell. Biol. 22(1): 109-120 (1992)] and KAR3 [Meluh et al, Cell 60(6): 1029-1041 (1990)]. To construct the prey kinesin fusion plasmids, genomic clones of KIP1, KIP2, CIN8, and KAR3 were first isolated and then subcloned into plasmid pGAD which contains the transactivating domain of GAL4. Interactions of the CKI bait fusions with the TIH4 prey fusion (pGAD::TIH4) described in Example 1 were examined concurrently. Plasmid Construction KIP1 sequences were amplified from S. cerevisiae genomic DNA using the following two primers: 5'-TCC CTC TCT AGA TAT GGC GAG ATA GTT A-3' (SEQ ID NO: 21) and 5'-GTT TAC ACT CGA GGC ATA TAG TGA TAC A-3' (SEQ ID NO: 22). The amplified fragment was labelled with 32 P by random primed labelling (Boehringer Mannheim, Indianapolis, Indiana) and used to screen a yeast genomic library constructed in the plasmid pRS200 (ATCC 77165) by colony hybridization. Hybridizations were performed at 65°C for 18 hours in 6X SSPE (20X SSPE is 175.3 g/1 NaCl, 27.6 g/1 NaH2PO4.H2), 7.4 g.l EDTA, pH7.4, 100 μg/ml salmon sperm carrier DNA, 5X Denhardts Reagent (50X Denhardts is 5% ficoll, 5% polyvinyl pyrolidone, 5% bovine serum albumin), 0.1 % SDS, and 5 % sodium dextran sulfate. Filters were washed four times in 0. IX SSPE, 1 % SDS. Each wash was at 65 °C for 30 minutes. Two rounds of site-directed mutagenesis were then performed as described in Example 2 to introduce BamΑl sites at the start and end of KIP1 coding sequences (SEQ ID NO: 23). Mutagenesis was performed using a Muta-gene Mutagenesis Kit, Version 2 (BioRad). The oligonucleotide for introducing a BamHl site (underlined) in place of the KIPl ATG and second codon was: 5'-GAT AGT TAA GGA TCC ATG GCT CGT TCT TCC TTG CCC AAC CGC-3' (SEQ ID NO: 24), and the oligonucleotide encoding a stop codon (double underlined) and BamHl site (underlined) was: 5'-AAA CTT CAT CAA TGC GGC CGC TAA GGG GAT CCA GCC ATX GTA AAT-3' (SEQ ID NO: 25). The resulting KIPl product was digested with BamHl and cloned into pGAD immediately downstream of GAL4 sequences and the plasmid was called pGAD::KIPl. KIP2 sequences were amplified from S. cerevisiae genomic DNA using the following two primers: 5'-TTT CCT TGTTTA TCC TTT TCC AA-3' (SEQID NO: 26)and 5'-GATCACTTCGGATCCGTCACACCCAGTTAG-3' (SEQIDNO:27). The amplified fragment was labelled with 32 P by random primed labelling and used to screen a yeast genomic library constructed in the plasmid YCp50 (ATCC 37415) by colony hybridization. Hybridizations and washes were as described above for KIPl. Two rounds of site-directed mutagenesis were performed to introduce BamHl sites at the start and end of KIP2 coding sequences (SEQ ID NO: 28). The oligonucleotide for introducing a BamHl site (underlined) in place of the KIP2 ATG and second codon was: 5'-ACCATAATACCAGGATCCATGATTCAAAAA-3' (SEQIDNO:29) and the oligonucleotide encoding a BamHl site (underlined) was: 5'-CCT GTC GTG GAT AGC GGC CGC TAG GAT CCT GAG GGT CCC AGA-3' (SEQ ID NO: 30). The resulting KIP2 product was digested with -SαmHI and cloned into pGAD immediately downstream of GAL4 sequences and the plasmid was called pGAD::KIP2. CIN8 sequences were amplified from S. cerevisiae genomic DNA using the following two primers: 5'-ACA TCA TCT AGA GAC TTC CTT TGT GAC C-3' (SEQ ID NO: 31) and 5'-TAT ATA ATC GAT TGA AAG GCA ATA TC-3' (SEQ ID NO: 32). The amplified fragment was labelled with 32 P by random primed labelling and used to screen a yeast genomic library constructed in the plasmid pRS200 (ATCC 77165) by colony hybridization. Hybridizations and washes were as described above for KIPl. Two rounds of site-directed mutagenesis were performed to introduce BamHl sites at the start and end of CIN8 coding sequences (SEQ ID NO: 33). The oligonucleotide utilized for introducing a BamHl site (underlined) in place of the CIN8 ATG and second codon was: 5'-CGG GTG TAG GAT CCA TGG TAT GGC CAG AAA GTA ACG-3' (SEQ ID NO: 34) and the downstream oligonucleotide encoding a BamHl site (underlined) and a stop codon (double underlined) was: 5'-GTG GAC AAT GGC GGC CGC AGA AAA AGG ATC CAG ATT GAA TAGTTG ATATTG CC-3' (SEQIDNO: 35). The resulting CIN8 product was digested with BamHl and cloned into pGAD immediately downstream of GAL* sequences and the plasmid was called pGAD::CIN8. KAR3 was amplified from S. cerevisiae genomic DNA using the following two primers: 5'-GAATATTCTAGAACAACTATCAGGAGTC-3'(SEQIDNO: 36)and 5'-TTGTCA CTC GAGTGAAAAAGACCAG-3' (SEQIDNO: 37). The amplified fragment was labelled with 32 P by random primed labelling and used to screen a yeast genomic library constructed in the plasmid pRS200 (ATCC 77165) by colony hybridization. Hybridizations and washes were .as described above for KIPl. Two rounds of site-directed mutagenesis were performed to introduce -BamHl sites at the start and end of KAR3 coding sequences (SEQ ID NO: 38). The oligonucleotide for introducing a BamHl site (underlined) in place of the KAR3 ATG and second codon was: 5' -GAT AGT TAA GGA TCC ATG GCT CGT TCT TCC TTG CCC AAC CGC-3' (SEQ ID NO: 39) and the oligonucleotide encoding a BamHl site (underlined) and a stop codon (double underlined) was: 5'-AAA CTT CAT CAA TGC GGC CGC TAA GGG GAT CCA GCC ATT GTA AAT-3' (SEQ ID NO: 40). The resulting KAR3 product was digested with BamHl and cloned into pGAD immediately downstream of GAL4 sequences and the plasmid was called pGAD::KAR3. The prey plasmids were transformed into yeast by lithium acetate- mediated transformation and the transformants were mated to CKI isoform- encoding yeast strains as described in Example 2. β-galactosidase activity of CKI isoform/TIH-containing strains was determined from cells that were lysed by adding 3 drops of chloroform and 50 μl of 0.1 % SDS to 2 x 10 6 cells suspended in 0.1 ml of Z buffer and subsequently adding 0.2 ml of the chromogenic substrate o-nitrophenyl-3-D-galactoside. β-galactosidase assays were terminated by adding 0.5 ml of IM Na 2 CO 3 and activity was measured by reading absorbance at 420 nm using a Milton Roy spectrophotometer (Rochester, New York). In this assay, the degree of protein/protein interaction is directly proportional to the level of jS-galactosidase activity. The results of the assay are presented as units of β- galactosidase activity in Table 2. Table 2 -Galactosidase Activity Resulting From CKI Isoform/Kinesin Interaction pGAD:: pGAD:: pGAD:: pGAD:: pGAD:: KIPl KIP2 ΗH4 KAR3 CIN8 pBTMllό 16 10 70 15 5 ::HRR25 pBTMllό: 55 16 66 75 28 :HRR25 K→R pBTMllό 70 <0.1 <0.1 60 <0.1 : : Non- Catalytic The results indicate that HRR25 can interact with all four yeast kinesins and TIH4. Kinesins KIP2 and CIN8 interact with the catalytic domain of HRR25 while kinesins KIPl and KAR3 interact with kinase-inactive HRR25 and with the non-catalytic domain of HRR25, suggesting that kinase/substrate interaction progresses through strong binding to enzymatic activity. In addition, the results show that HRR25 interacts with the carboxy-terminal portion of TIH4 or, because TIH4 corresponds to KIP2, KIP2. Example 4 Assays were also performed to determine whether human CKI isoforms would interact with the TIH proteins of the invention. Two human CKI isoforms, CKIα3 (CKIα3Hu) and CKIδ (CKIδHu), were selected for this analysis. The human CKI genes were fused to the GAL4 DNA binding domain previously inserted into plasmid pAS [Durfee, et al, Genes and Development 7:555-569 (1993)] to produce pAS::CKIα3 and pAS::CKIδ. Specifically, the CKIα3Hu isoform-encoding DNA (SEQ ID NO: 41) was subjected to site-directed mutagenesis using the mutagenic oligonucleotide: 5'-CTTCGT CTC TCA CATATG GGC GAGTAG CAG CGG C-3' (SEQID NO.42) to create Ndel site (underlined) in the place of the CKIα 3Hu initiating methionine and second codon, and the resulting DNA was digested with Ndel and ligated into plasmid pAS at a Ndel site located immediately downstream of GAL4 sequences. CKIδHu DNA (SEQ ID NO: 43) was introduced into pAS by amplifying the CKIδ cDNA with mutagenic oligonucleotide primers that contained BamHl sites. The oligonucleotides, with BamHl sites underlined, used were: 5 '-CGC GGA TCC TAA TGG AGG TGA GAG TCG GG-3 ' (SEQ ID NO. 44), replacing the initiating methionine and second codon, and 5 '-CGC GGA TCC GCT CAT CGG TGC ACG ACA GA-3 ' (SEQ ID NO. 45). Reactions included 200mM Tris HC1 (pH 8.2), lOOmM KC1, 60mM (NH^SO^ 15 mM MgCl 2 , 1 % Triton X-100, 0.5 μM primer, 100 ng template, 200 μM dNTP and 2.5 units polymerase. The reactions were performed for 30 cycles. Reactions were started at 94 ° C for 4 minutes and all subsequent cycles were 1 minute at 94 °C for denaturing, 2 minutes at 50 °C for annealing, and 4 minutes at 72 "C for extension. The amplified product was digested with -SαmHI and ligated into -BamHI-digested pAS immediately downstream of GAL4 sequences to create plasmid pAS:CKIδ. The resulting bait plasmids were transformed into yeast by lithium acetate-mediated transformation and the transformants were mated to TTH- encoding yeast strains as described in Example 2. jS-galactosidase activity of CKIα3Hu- or CKIδHu-containing/TIH-containing strains was detected by replica plating cells onto Hybond-N° Λ5μ filters (Amersham, Arlington Heights, IL), growing cells on the filters at 30°C for 18 hours, lysing the colonies by freezing the filters in liquid nitrogen, and incubating the filters on Whatman filter paper soaked in Z buffer containing 0.002% X-gal. Reactions were terminated by soaking the filters in IM Na 2 CO 3 and protein/protein interaction was evaluated by examining for a chromogenic conversion of X-gal to blue by β-galactosidase activity. The results of the assay, as determined by visual screening for development of blue color are presented below in Table 3. Table 3 /3-Galactosidase Activity Resulting From Human CKI/TIH Interaction PLASMID CONSTRUCTS USED ΗHl TIH2 TIH3 pAS::CKIα3 pAS::CKIδ - + These results indicate that interaction between TIH proteins of the invention and CKI isoforms is not limited to yeast isoforms. CKIδHu interacted with TIH2. Thus, CKI/TIH interactions can be expected to occur between human CKIs and their cognate TIH proteins. Example -S Full length genomic clones encoding the yeast ΗHl, TIH2, and TIH3 proteins were isolated from a yeast genomic library. To identify genomic clones, radiolabelled PCR fragments were prepared from the pGAD plasmids containing TIH1, TIH2, and TIH3 fusion genes described in Example 1. The sequence of the unidirectional oligonucleotide used to amplify the clones was: 5'-GGA ATC ACT ACA GGG ATG-3' (SEQ ID NO. 46). PCR reactions included 200mM Tris HCl (pH 8.2), lOOmM KCl, 60mM (NH 4 ) 2 SO 4 , 15mM MgCl 2 , 1 % Triton X-100, 0.5 μM primer, 100 ng template, 200 μM dNTP and 2.5 units polymerase. The reactions were performed for 30 cycles. The first five cycles contained 50 μCi each 32 P-dCTP and 32 P-TTP. At the start of the sixth cycle, non-radiolabeled dCTP and dTTP were each added to 200μM final concentration. Reactions were started at 94 °C for 4 minutes and all subsequent cycles were performed for 1 minute at 94 °C for denaturation, 2 minutes at 50 'C for annealing, and 4 minutes at 72 °C for extension. The resulting PCR products were then used as probes in colony hybridization screening. The full length TIH1 genomic clone was isolated from a YCp50 plasmid library (ATCC 37415). The full length TIH2 and TIH3 genomic clones were isolated from a λ genomic library [Riles, et al, Genetics 254:81-150 (1993)]. Hybridization for YCp50 library screening were performed at 65°C for 18 hours in 6X SSPE (20X SSPE is 175.3 g/1 NaCl, 27.6 g/1 NaH 2 PO 4 .H2), 7.4 g.l EDTA, pH7.4, 100 μg/ml salmon sperm carrier DNA, 5X Denhardts Reagent (50X Denhardts is 5% ficoll, 5% polyvinyl pyrolidone, 5% bovine serum albumin), 0.1% SDS, and 5% sodium dextran sulfate. Filters were washed four times in 0.1X SSPE, 1% SDS. Each wash was at 65 °C for 30 minutes. Hybridization conditions for λ library screening were 18 hours at 64°C in IX HPB (0.5M NaCl, lOOmM Na 2 HPO 4 , 5mM Na 2 EDTA), 1 % sodium sarkosyl, 100 μg/ml calf thymus DNA. Filters were washed two times for 15 seconds, one time for 15 minutes, and one time for 15 seconds, all at room temperature in ImM Tris-HCl (pH 8.0). The sequences of TIH1, TIH2, and TIH3 genomic clones were determined by automated DNA sequencing with an ABI 373A sequencer (Applied Biosy stems). Nucleotide sequences determined for the full length ΗHl , TIH2 and TIH3 genomic clones are set out in SEQ ID NOS: 2, 4, and 6, respectively; the deduced amino acid sequences for ΗHl, TIH2, and TTH3 are set out in SEQ ID NOS: 3, 5, and 7, respectively. Database searches confirmed the results from Example 1 that the TIH1 and TIH3 genes encoded novel proteins showing no significant homology to any protein in the GenBank database. Example 6 To characterize activity of the TIH proteins and to determine if the TIH proteins participate in a HRR25 signalling pathway, a chromosomal TIH1 deletion mutant was constructed by homologous recombination. Specifically, the TIH1 mutation was constructed by subcloning a 1.7 kb Satl-BamHl fragment that encompasses the genomic TIH1 gene into plasmid pBluescript II SK (Stratagene, La Jolla, CA). The resulting subclone was digested with EcøRV and Pstl to delete 0.5 kb of the TIH1 gene (nucleotides 1202 to 1635 of SΕQ ID NO: 2) and into this region was ligated a 2.2 kb Smάl-Pstl fragment that contained the S. cerevisiae LΕU2 gene. Isolated DNA from the resulting plasmid construct was digested with jBamHI to linearize the plasmid and 10 μg of this sample were used to transform a diploid yeast strain that is heterozygous for HRR25 (MAT a/MAT a ade2/ade2 canl/canl his3-ll,15/his3- 11,15 Ieu2-3,112/leu2-3,112 trpl-l/trpl-1 ura3-l/ura3-l HRR25/hrr25::URA3) to Leu + . Transformation was carried out using lithium acetate-mediated procedures and transformants were selected on SD-Leucine medium (BiolOl). Yeast transformation with linearized DNA results in homologous recombination and gene replacement [Rothstein, Meth. Enzymol. 294:281-301 (1991)]. Stable Leu + colonies were replica plated onto sporulation medium (BiolOl) and grown at 30°C for five days. Spores were microdissected on YEPD medium (BiolOl) using a tetrad dissection apparatus [Sherman and Hicks, Meth. Enzymol. 294:21- 37 (1991)] and isolated single spores were allowed to germinate and grow into colonies for three days. Four colony types were detected due to random meiotic segregation of the heterozygous TIH1 and HRR25 mutations present in the strain. The hrr25 deletion mutation in the parent strain was due to a replacement of the HRR25 gene with the yeast URA3 gene and the TIH1 mutation is due to a replacement with LEU2. URA3 and LEU2 confer uracil and leucine prototropy, respectively. The colony types are represented by segregation of the mutations into following genotypic configurations: (i) wild type cells are HRR25 TIH1; (ii) HRR25 mutants are hrr25::URA3 TIH1; (iii) TIH1 mutants are HRR25 tihl::LEU2; and (iv) HRR25 TIH1 double mutants are hrr25::URA3 tihl::LEU2. Standard physiological analyses of yeast mutant defects were performed [Hoekstra et al. , supra]. TIH1 deletion mutants exhibited phenotypes identical to mutations in HRR25 including slow growth rate, DNA repair defects, and aberrant cellular morphology, indicating that the TIH proteins participate in the same pathway as HRR25 or in pathways having similar effects. Furthermore, tihl hrr25 double mutants were in viable. Example 7 To confirm the dihybrid screen analysis of interaction between CKI protein kinases and ΗH proteins, a biochemical method was developed to detect the interaction. This method was based on affinity purification of one component in the interaction, followed by Western blotting to detect the presence of the interacting component in the affinity purified mixture. The TIH2 gene was used to construct a TIH2/glutathione-S-transferase (GST) fusion protein which could be affinity purified with glutathione agarose (Pharmacia, Uppsala, Sweden) Other useful ligand/counterreceptor combinations include, for example, influence virus hemagglutinin [Field et al, Mol Cell Biol. 8(5): 2159-2165 (1988)]/hemagglutinin-specificantibody (Berkeley Antibody Company, Richmond, CA), polyhistidine/nickel affinity chromatography (Novagen, Madison, WI), and maltose-binding protein/amylose chromatography (New England Biolabs, Beverly, Massachusetts). To construct the GST: :TIH2 fusion protein, the 5 ' and 3 ' termini of the TIH2 gene were modified by DNA amplification-based mutagenesis procedures. The amplifying oligonucleotides introduced Xbal and Hindm sites for ease in subcloning. The oligonucleotides, with restriction sites underlined, used for amplification were: 5'-ATT CTA GAC ATG GAG ACC AGTTCT TTT GAG-3' (SEQID NO.47) and, 5'-TGG AAG CTT ATA TTA CCA TAG ATT CTT CTT G-3' (SEQID NO.48). Reactions included 200mM Tris-HCl (pH 8.2), lOOmM KCl, 60 mM (NH») 2 SO 4 , 15mM MgCl 2 , 1 % Triton-X-100, 0.5 μM primer, 100 ng template, 200 μM dNTP and 2.5 units polymerase. The reactions were performed for 30 cycles. Reactions were started at 94 °C for 4 minutes and all subsequent cycles were 1 minute at 94 °C for denaturation, 2 minutes at 50 °C for annealing, and 4 minutes at 72 °C for extension. The resulting amplified product was digested with Xbal and Hindϊll and the fragment was subcloned into the GST-containing plasmid pGEXKG, which contained a galactose-inducible GST gene, to create pGEXKG: :TIH2. This plasmid contains, in addition to the GST sequences fused immediately upstream of TIH2 sequences, URA3 and LEU2 selectable markers for yeast transformation. Plasmid pGEXKG: :TIH2 was then transformed by lithium acetate-mediated transformation into yeast strain W303 [Wallis, et al. , Cell 58:409-419 (1989)] and Ura + transformants were selected on SD-URA medium (BiolOl). To isolate the GST::ΗH2 fusion protein, 100 ml SD-URA broth was inoculated with the transformed yeast and grown to a density of 1 x 10 7 cells/ml in the presence of galactose. The cells were then pelleted by centrifugation, washed in lysis buffer [lOmM sodium phosphate pH 7.2, 150mM NaCl, 1 % Nonidet P-40, 1 % Trasylol (Miles), ImM dithiothreitol, ImM benzamidine, ImM phenylmethyl sulphonyl fluoride, 5mM EDTA, 1 μg/ml pepstatin, 2 μg/ml pepstatin A, 1 μg/ml leupeptin, lOOmM sodium vanadate, and 50mM NaF], resuspended in 1 ml lysis buffer, and lysed by vortexing for 5 minutes with 10 g of glass beads. The crude lysate was clarified by centrifugation at 100,000 x g for 30 minutes. Fifty μl of 50% slurry glutathione agarose (Pharmacia) was added to the extract and the mixture incubated for 1 hour. The agarose was pelleted by a 10 second spin in an Eppendorf microcentrifuge, the supernate removed, and the agarose-containing pellet washed with phosphate-buffered saline (PBS). The pellet was resuspended in 50 μl of 2X protein gel sample buffer, boiled for 2 minutes, and 12.5 μl was electrophoresed through a 10% polyacrylamide gel. Gel fractionated proteins were transferred by electroblotting to Immobilon-P membranes (Millipore, Bedord, MA) and HRR25 was detected by probing the membrane with a rabbit antibody [DeMaggio et al, Proc. Natl Acad. Sci. (USA) 89: 7008-7012 (1992)] raised to HRR25. The Western blot was developed for immunoreactivity using an alkaline phosphatase-conjugated secondary antibody and colorimetric development (BioRad). A photograph of the gel is presented in Figure 1, wherein the approximately 58 kD HRR25 protein was detected in association with TIH2 protein. Example 8 In order to confirm the novelty of the identified TIH1 protein, a data base search of previously reported protein sequences was performed. As shown in Figure 2, wherein portions of the amino acids sequence of ΗHl (amino acids 128 to 161 in SEQ ID NO: 3), human HumδODP (amino acids 31 to 63) [Sakumi, et al , J.Biol.Chem. 268:23524-23530 (1993)], E.coli MutT (amino acids 32- to 64) [Akiyama, et al, Mol.Gen.Genet. 206:9-16 (1989)], viral Cll (amino acids 122 to 154) [Strayer, et al, Virol 285:585-595 (1991)] and viral VD10 (amino acids 122 to 154) [Strayer, et al, (1991), supra)] are respectively set out, sequence comparison indicated that ΗHl contains a signature sequence motif associated with enzymes which actively participate in removal of oxidatively damaged nucleotides from the nucleus, thus increasing the fidelity of DNA replication. Enzymes with this activity have been identified in a wide range of organisms, including prokaryotes, eukaryotes and viruses [Koonin, Nucl. Acids Res. 22:4847 (1993)]. HRR25 enzyme activity has been shown to participate in repair of DNA damaged by radiation, however the role of HRR25 in the repair process has not been determined. The fact that TTH1 has an amino acid sequence similar to that of enzymes capable of degrading damaged indicates that TTH1 is likely to interact with HRR25 in the DNA repair process. Inhibitor compounds which are capable of interfering, or abolishing, the interaction between HRR25 and TIH1 would thus be particularly useful in targeted cancer and antiviral therapy. Delivery of an inhibitor to cancerous or virus-infected cells would increase the rate of replicative mutation in the cells, thus increasing the likelihood of induced cell suicide. In addition, targeted delivery of an inhibitor would selectively confer enhanced sensitivity of cancerous or virus-infected cells to treatment with conventional chemotherapy and/or radiation therapy, thus enhancing the chemotherapy and/or radiotherapy therapeutic index. While the present invention has been described in terms of specific methods and compositions, it is understood that variations and modifications will occur to those skilled in the art. Therefore, only such limitations as appear in the claims should be placed on the invention. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANT: DeMaggio, Anthony J. Hoekstra, Merl> F. (ii) TITLE OF INVENTION: Materials and Methods Relating to Proteins that Interact with Casein Kinase I (iii) NUMBER OF SEQUENCES: 53 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: Marshall, O'Toole, Gerstein, Murray & Borun (B) STREET: 6300 Sears Tower, 233 South Wacker Drive (C) CITY: Chicago (D) STATE: Illinois (E) COUNTRY: United States of America (F) ZIP: 60606-6402 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentln Release #1.0, Version #1.25 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (C) CLASSIFICATION: (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: US 08/184,605 (B) FILING DATE: 21-JAN-1994 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Noland, Greta E. (B) REGISTRATION NUMBER: 35,302 (C) REFERENCE/DOCKET NUMBER: 27866/32437 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: 312/474-6300 (B) TELEFAX: 312/474-0448 (C) TELEX: 25-3856 (2) INFORMATION FOR SEQ ID NO:l: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: Arg Arg Xaa Ser Tyr 1 5 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2625 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 796..2580 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: CATTTTCTTA ATTCTTTTAT GTGCTTTTAC TACTTTGTTT AGTTCAAAAC AATAGTCGTT 60 ATTCTTAGGT ACTATAGCAT AAGACAAGAA AAGAAAAATA AGGGACAAAT AACATTAGCA 120 GAAGTACGGT ATATTTTACT GTTACTTATA TACTTTCAAG AAGATGAGTT AAATCGGTAG 180 CCAGTGTAGA AAAATAATAA TAAGGGTCAT CGATCCTTCG CATTTTATTA TCCAATTAAA 240 GATACGAATC ACGGCAAACT ATATTCAAAG CTCATAGATA ATCGTCGTAA GGCTGACACT 300 GCAGAAGAAA AGTCATAATT TGAATACTAG CCGGTATGAA ACTGTGATTG ATTAACCTGG 360 GGTTACCTAA AGAGAACATA AGTAATACTC ATGACAGAAT CAAAACACAA TACAAAATTT 420 ATCCGAACCT CGGCCCGACT GCGGCTCGCC GGGAAAGGGG ACAACCGCTT CTATCCGTCG 480 ACTAACTTCA TCGGCCCAAT GGAAGCTATG ATATGGGGAT TTCCATTGAG CCGATAGCAA 540 TGTAGGGTAA TACTGTTGCG TATATAGTGA TAGTTATTGA ATTTTATTAC CCTGCGGGAA 600 TATTGAGACA TCACTAAGCA CGAATTTTAC GTCTGAGGAA AGTTGAATGA TGGCCAAATA 660 ACCAGGAAAA ACAAATATTG AATCCTTGTG AAGGATTCCA CAGTTGTTTA ATCCTCCTTA 720 AGCTCACTTA GTATCAATTG TCTAAATAAT ATTGCTTTGA ATCTGAAAAA AATAAAAGTA 780 CCTTCGCATT AGACA ATG TCA CTG CCG CTA CGA CAC GCA TTG GAG AAC GTT 831 Met Ser Leu Pro Leu Arg His Ala Leu Glu Asn Val 1 5 10 ACT TCT GTT GAT AGA ATT TTA GAG GAC TTA TTA GTA CGT TTT ATT ATA 879 Thr Ser Val Asp Arg lie Leu Glu Asp Leu Leu Val Arg Phe lie lie 15 20 25 AAT TGT CCG AAT GAA GAT TTA TCG AGT GTC GAG AGA GAG TTA TTT CAT 927 Asn Cys Pro Asn Glu Asp Leu Ser Ser Val Glu Arg Glu Leu Phe His 30 35 40 TTT GAA GAA GCC TCA TGG TTT TAC ACG GAT TTC ATC AAA TTG ATG AAT 975 Phe Glu Glu Ala Ser Trp Phe Tyr Thr Asp Phe lie Lys Leu Met Asn 45 50 55 60 CCA ACT TTA CCC TCC CTA AAG ATT AAA TCA TTT GCT CAA TTG ATC ATA 1023 Pro Thr Leu Pro Ser Leu Lys lie Lys Ser Phe Ala Gin Leu lie lie 65 70 75 AAA CTA TGT CCT CTG GTT TGG AAA TGG GAC ATA AGA GTG GAT GAG GCA 1071 Lys Leu Cys Pro Leu Val Trp Lys Trp Asp lie Arg Val Asp Glu Ala 80 85 90 CTC CAG CAA TTC TCC AAG TAT AAG AAA AGT ATA CCG GTG AGG GGC GCT 1119 Leu Gin Gin Phe Ser Lys Tyr Lys Lys Ser He Pro Val Arg Gly Ala 95 100 105 GCC ATA TTT AAC GAG AAC CTG AGT AAA ATT TTA TTG GTA CAG GGT ACT 1167 Ala He Phe Asn Glu Asn Leu Ser Lys He Leu Leu Val Gin Gly Thr 110 115 120 GAA TCG GAT TCT TTG TCA TTC CCA AGG GGG AAG ATA TCT AAA GAT GAA 1215 Glu Ser Asp Ser Leu Ser Phe Pro Arg Gly Lys He Ser Lys Asp Glu 125 130 135 140 AAT GAC ATA GAT TGT TGC ATT AGA GAA GTG AAA GAA GAA ATT GGT TTC 1263 Asn Asp He Asp Cys Cys He Arg Glu Val Lys Glu Glu He Gly Phe 145 150 155 GAT TTG ACG GAC TAT ATT GAC GAC AAC CAA TTC ATT GAA AGA AAT ATT 1311 Asp Leu Thr Asp Tyr He Asp Asp Asn Gin Phe He Glu Arg Asn He 160 165 170 CAA GGT AAA AAT TAC AAA ATA TTT TTG ATA TCT GGT GTT TCA GAA GTC 1359 Gin Gly Lys Asn Tyr Lys He Phe Leu He Ser Gly Val Ser Glu Val 175 180 185 TTC AAT TTT AAA CCT CAA GTT AGA AAT GAA ATT GAT AAG ATA GAA TGG 1407 Phe Asn Phe Lys Pro Gin Val Arg Asn Glu He Asp Lys He Glu Trp 190 195 200 TTC GAT TTT AAG AAA ATT TCT AAA ACA ATG TAC AAA TCA AAT ATC AAG 1455 Phe Asp Phe Lys Lys He Ser Lys Thr Met Tyr Lys Ser Asn He Lys 205 210 215 220 TAT TAT CTG ATT AAT TCC ATG ATG AGA CCC TTA TCA ATG TGG TTA AGG 1503 Tyr Tyr Leu He Asn Ser Met Met Arg Pro Leu Ser Met Trp Leu Arg 225 230 235 CAT CAG AGG CAA ATA AAA AAT GAA GAT CAA TTG AAA TCC TAT GCG GAA 1551 His Gin Arg Gin He Lys Asn Glu Asp Gin Leu Lys Ser Tyr Ala Glu 240 245 250 GAA CAA TTG AAA TTG TTG TTG GGT ATC ACT AAG GAG GAG CAG ATT GAT 1599 Glu Gin Leu Lys Leu Leu Leu Gly He Thr Lys Glu Glu Gin He Asp 255 260 265 CCC GGT AGA GAG TTG CTG AAT ATG TTA CAT ACT GCA GTG CAA GCT AAC 1647 Pro Gly Arg Glu Leu Leu Asn Met Leu His Thr Ala Val Gin Ala Asn 270 275 280 AGT AAT AAT AAT GCG GTC TCC AAC GGA CAG GTA CCC TCG AGC CAA GAG 1695 Ser Asn Asn Asn Ala Val Ser Asn Gly Gin Val Pro Ser Ser Gin Glu 285 290 295 300 CTT CAG CAT TTG AAA GAG CAA TCA GGA GAA CAC AAC CAA CAG AAG GAT 1743 Leu Gin His Leu Lys Glu Gin Ser Gly Glu His Asn Gin Gin Lys Asp 305 310 315 CAG CAG TCA TCG TTT TCT TCT CAA CAA CAA CCT TCA ATA TTT CCA TCT 1791 Gin Gin Ser Ser Phe Ser Ser Gin Gin Gin Pro Ser He Phe Pro Ser 320 325 330 CTT TCT GAA CCG TTT GCT AAC AAT AAG AAT GTT ATA CCA CCT ACT ATG 1839 Leu Ser Glu Pro Phe Ala Asn Asn Lys Asn Val He Pro Pro Thr Met 335 340 345 CCA ATG GCT AAC GTA TTC ATG TCA AAT CCT CAA TTG TTT GCG ACA ATG 1887 Pro Met Ala Asn Val Phe Met Ser Asn Pro Gin Leu Phe Ala Thr Met 350 355 360 AAT GGC CAG CCT TTT GCA CCT TTC CCA TTT ATG TTA CCA TTA ACT AAC 1935 Asn Gly Gin Pro Phe Ala Pro Phe Pro Phe Met Leu Pro Leu Thr Asn 365 370 375 380 AAT AGT AAT AGC GCT AAC CCT ATT CCA ACT CCG GTC CCC CCT AAT TTT 1983 Asn Ser Asn Ser Ala Asn Pro He Pro Thr Pro Val Pro Pro Asn Phe 385 390 395 AAT GCT CCT CCG AAT CCG ATG GCT TTT GGT GTT CCA AAC ATG CAT AAC 2031 Asn Ala Pro Pro Asn Pro Met Ala Phe Gly Val Pro Asn Met His Asn 400 405 410 CTT TCT GGA CCA GCA GTA TCT CAA CCG TTT TCC TTG CCT CCT GCT CCT 2079 Leu Ser Gly Pro Ala Val Ser Gin Pro Phe Ser Leu Pro Pro Ala Pro 415 420 425 TTA CCG AGG GAC TCT GGT TAC AGC AGC TCC TCC CCT GGG CAG TTG TTA 2127 Leu Pro Arg Asp Ser Gly Tyr Ser Ser Ser Ser Pro Gly Gin Leu Leu 430 435 440 GAT ATA CTA AAT TCG AAA AAG CCT GAC AGC AAC GTG CAA TCA AGC AAA 2175 Asp He Leu Asn Ser Lys Lys Pro Asp Ser Asn Val Gin Ser Ser Lys 445 450 455 460 AAG CCA AAG CTT AAA ATC TTA CAG AGA GGA ACG GAC TTG AAT TCA CTC 2223 Lys Pro Lys Leu Lys He Leu Gin Arg Gly Thr Asp Leu Asn Ser Leu 465 470 475 AAG CAA AAC AAT AAT GAT GAA ACT GCT CAT TCA AAC TCT CAA GCT TTG 2271 Lys Gin Asn Asn Asn Asp Glu Thr Ala His Ser Asn Ser Gin Ala Leu 480 485 490 CTA GAT TTG TTG AAA AAA CCA ACA TCA TCG CAG AAG ATA CAC GCT TCC 2319 Leu Asp Leu Leu Lys Lys Pro Thr Ser Ser Gin Lys He His Ala Ser 495 500 505 AAA CCA GAT ACT TCC TTT TTA CCA AAT GAC TCC GTA TCT GGT ATA CAA 2367 Lys Pro Asp Thr Ser Phe Leu Pro Asn Asp Ser Val Ser Gly He Gin 510 515 520 GAT GCA GAA TAT GAA GAT TTC GAG AGT AGT TCA GAT GAA GAG GTG GAG 2415 Asp Ala Glu Tyr Glu Asp Phe Glu Ser Ser Ser Asp Glu Glu Val Glu 525 530 535 540 ACA GCT AGA GAT GAA AGA AAT TCA TTG AAT GTA GAT ATT GGG GTG AAC 2463 Thr Ala Arg Asp Glu Arg Asn Ser Leu Asn Val Asp He Gly Val Asn 545 550 555 GTT ATG CCA AGC GAA AAA GAC AGC CGA AGA AGT CAA AAG GAA AAA CCA 2511 Val Met Pro Ser Glu Lys Asp Ser Arg Arg Ser Gin Lys Glu Lys Pro 560 565 570 AGG AAC GAC GCA AGC AAA ACA AAC TTG AAC GCT TCT GCA GAA TCT AAT 2559 Arg Asn Asp Ala Ser Lys Thr Asn Leu Asn Ala Ser Ala Glu Ser Asn 575 580 585 AGT GTA GAA TGG GGG GCT GGG TAAATCTTCA CCCTCCGACT TCAGAGTAAC 2610 Ser Val Glu Trp Gly Ala Gly 590 595 ACAGAATCCA CAGTA 2625 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 595 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: Met Ser Leu Pro Leu Arg His Ala Leu Glu Asn Val Thr Ser Val Asp 1 5 10 15 Arg He Leu Glu Asp Leu Leu Val Arg Phe He He Asn Cys Pro Asn 20 25 30 Glu Asp Leu Ser Ser Val Glu Arg Glu Leu Phe His Phe Glu Glu Ala 35 40 45 Ser Trp Phe Tyr Thr Asp Phe He Lys Leu Met Asn Pro Thr Leu Pro 50 55 60 Ser Leu Lys He Lys Ser Phe Ala Gin Leu He He Lys Leu Cys Pro 65 70 75 80 Leu Val Trp Lys Trp Asp He Arg Val Asp Glu Ala Leu Gin Gin Phe 85 90 95 Ser Lys Tyr Lys Lys Ser He Pro Val Arg Gly Ala Ala He Phe Asn 100 105 110 Glu Asn Leu Ser Lys He Leu Leu Val Gin Gly Thr Glu Ser Asp Ser 115 120 125 Leu Ser Phe Pro Arg Gly Lys He Ser Lys Asp Glu Asn Asp He Asp 130 135 140 Cys Cys He Arg Glu Val Lys Glu Glu He Gly Phe Asp Leu Thr Asp 145 150 155 160 Tyr He Asp Asp Asn Gin Phe He Glu Arg Asn He Gin Gly Lys Asn 165 170 175 Tyr Lys He Phe Leu He Ser Gly Val Ser Glu Val Phe Asn Phe Lys 180 185 190 Pro Gin Val Arg Asn Glu He Asp Lys He Glu Trp Phe Asp Phe Lys 195 200 205 Lys He Ser Lys Thr Met Tyr Lys Ser Asn He Lys Tyr Tyr Leu He 210 215 220 Asn Ser Met Met Arg Pro Leu Ser Met Trp Leu Arg His Gin Arg Gin 225 230 235 240 He Lys Asn Glu Asp Gin Leu Lys Ser Tyr Ala Glu Glu Gin Leu Lys 245 250 255 Leu Leu Leu Gly He Thr Lys Glu Glu Gin He Asp Pro Gly Arg Glu 260 265 270 Leu Leu Asn Met Leu His Thr Ala Val Gin Ala Asn Ser Asn Asn Asn 275 280 285 Ala Val Ser Asn Gly Gin Val Pro Ser Ser Gin Glu Leu Gin His Leu 290 295 300 Lys Glu Gin Ser Gly Glu His Asn Gin Gin Lys Asp Gin Gin Ser Ser 305 310 315 320 Phe Ser Ser Gin Gin Gin Pro Ser He Phe Pro Ser Leu Ser Glu Pro 325 330 335 Phe Ala Asn Asn Lys Asn Val He Pro Pro Thr Met Pro Met Ala Asn 340 345 350 Val Phe Met Ser Asn Pro Gin Leu Phe Ala Thr Met Asn Gly Gin Pro 355 360 365 Phe Ala Pro Phe Pro Phe Met Leu Pro Leu Thr Asn Asn Ser Asn Ser 370 375 380 Ala Asn Pro He Pro Thr Pro Val Pro Pro Asn Phe Asn Ala Pro Pro 385 390 395 400 Asn Pro Met Ala Phe Gly Val Pro Asn Met His Asn Leu Ser Gly Pro 405 410 415 Ala Val Ser Gin Pro Phe Ser Leu Pro Pro Ala Pro Leu Pro Arg Asp 420 425 430 Ser Gly Tyr Ser Ser Ser Ser Pro Gly Gin Leu Leu Asp He Leu Asn 435 440 445 Ser Lys Lys Pro Asp Ser Asn Val Gin Ser Ser Lys Lys Pro Lys Leu 450 455 460 Lys He Leu Gin Arg Gly Thr Asp Leu Asn Ser Leu Lys Gin Asn Asn 465 470 475 480 Asn Asp Glu Thr Ala His Ser Asn Ser Gin Ala Leu Leu Asp Leu Leu 485 490 495 Lys Lys Pro Thr Ser Ser Gin Lys He His Ala Ser Lys Pro Asp Thr 500 505 510 Ser Phe Leu Pro Asn Asp Ser Val Ser Gly He Gin Asp Ala Glu Tyr 515 520 525 Glu Asp Phe Glu Ser Ser Ser Asp Glu Glu Val Glu Thr Ala Arg Asp 530 535 540 Glu Arg Asn Ser Leu Asn Val Asp He Gly Val Asn Val Met Pro Ser 545 550 555 560 Glu Lys Asp Ser Arg Arg Ser Gin Lys Glu Lys Pro Arg Asn Asp Ala 565 570 575 Ser Lys Thr Asn Leu Asn Ala Ser Ala Glu Ser Asn Ser Val Glu Trp 580 585 590 Gly Ala Gly 595 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 6854 base pairs (B) TYPE: nucleic, acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) ( ix ) FEATURE : (A) NAME/KEY: CDS (B) LOCATION: 2050..4053 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: : AGCTTCTCCC TTTTCCTTCA GTGCTGCTAC TCTCTGCTCT CCACTTAAGT GTTACAATTA 60 ATTTGCAGCT AGTTTGCAGT TCGTACAACC TCGCCTATTC TTGTAACGAA GAAGAACGTA 120 TTTATAATAT TGGGCTGTAA TGTGTTGAGT TTAGTAATAG ATAAAGTAGG ACAGAGTTCT 180 GTCTTTGTTT ATCTATGGGG TTCAGAGTGA TAAGGGGCAG GATAAGGAAG TTAAAAAAAA 240 AAAGGTTACG TTATATAACG AAAGAAAAGA AACGAGCGAA GTGCCAACTA TAGCCCAATA 300 TCAAGAATGC AAGTCAGCAA AGTACAGTAA TCGTATGAAG ATACGCGATG CGTAATATCC 360 CTCAAGGGCT CCGGATCAGA AAAGCTAAGG GAAGATCCTT ACATTACACG GCGTGCGACA 420 GACTCGAACC ACAGCTAACT TCTCGTGAAA AGATGGCTTC AACTTCGCTC TTGCAATAAC 480 TTTGAAACAC ACGAACAAAG GTTTATTGCG CTTGATTAAC GTTGGAAGTA TATGATACTA 540 ATACTACTTT GTTCTCTAAG TCATCGCTAT ATGTTTATCT CGAGGAAAAG GTGCACGGCG 600 GTACACAATT ACTTCGCCGT TTCGGGTAAA ACAAGTGTTA CATTTATAAT ATATATGTAT 660 ATATGTATGT GCGCGTAAGT ATATGCCGTT CATAACAAAT CATCTTCTTG TTGCTGGATG 720 GACTCCTTAA TTTTATTCAA AATGGTAATT TTCCATTTAT CTAGTCTCAT AAAATTGTCA 780 AACTCCTTAC AGTGTTCGCT TAGCTGCTCG CTATCACCTT CATTAACAGC ATCGATTAAA 840 CTTTTCAAGA AATTTGACTC CCTTGAATCC GCAAAATTCG GATCTTCACT TTGACCCTCT 900 TGTAAAGTTC TTGCAGCAGC GACTGCATCA GTAGCAGCTA GCTGACAAAG CCCTTTTTTT 960 AGGAAGTAAT CCTTCAAACT CCATTGGCTC AATCTATTGC CCATGCTGCT CTTGATCAAC 1020 TTCGAATATA TATCACTTGC TTCAATATAT TGACCGTCAA GAGCCTTTAG ATCTGCGCAT 1080 TTGATAAAAC ACTTATTCGA TAATGCTACC GACTGGTCTT GGGCATACCA CTCACCAGCG 1140 AGCTCATAGC AATCTATAGC TTTTGCATAG TCATGCAAAT CATTTTCTAG AATTTCTCCA 1200 AGCTCAAACT TGAAATTAGC ACCTCTCCGG AACTGCCCCC TATGAGTAAA AATTTGAATA 1260 GCATTTTCTA ATGAATCCAC GGCGTTCACA GAGTTTCCAC CGCTTTTAAA GCATTTATAA 1320 GCCTCTACGT AGGTATTTCC TGCTTCGTCT TCATTACCAG CCTTTTTCTG ATAGTCAGCA 1380 GCTTTCAAAA ACGAGTCTCC TGCCAAGTTT AACTCTTTTC TTAGACGGTA AATGGTGGCT 1440 GCTTGGACAC AAAGATCAGC AGCCTCCTCA AACTTGTATG AATCAGAACC GCTAAACAAT 1500 TTCATGAAAC CCGATGAAGG AACACCCTTC TTCTCAGCCT TAACACAACG GGAAATATCA 1560 ATTCCCGTAT TTCAATGTTA GTAATTTGCC TTCGTAAATT ACGGAATCAC ATAGCTTTCA 1620 TTTTGTTCCT TTGATATATT TCCCTACTAC ATACTCTTTT CAATAACTCT ACAGGGTCTG 1680 ACATTTTTAA CTTTCAGGTT AATGATGGTG TTCTTACTAT ATTCTCGAGT CGTACAGAAG 1740 TTAGTTCAGA TAAACTGCTT CGGTGCTGCC CACTTCTTAT CATTACTTCA ACTTTACCTT 1800 CCCTATACCT GTGTGTCCTT ATTAATTCAA GTTAATCCGA GGTAATAGAT TAGGGTAACC 1860 TTCAATGATG TCACGAAACA CGGATGCTGC AACTTTGCGA TTTTTTCCTG GAAAAGAATA 1920 ACAATTAAAG GCAGCCTTTC AGCTGAGATT ACCAGCAGGT CTTTGGAGAT TAGCGCAAGA 1980 AGAAGTGTGA TATAGTACTC ATAGAGGCAG GCTACAGACT AGGGAAAGCG TGTTCAACAA 2040 CAATAAGAA ATG GAG ACC AGT TCT TTT GAG AAT GCT CCT CCT GCA GCC 2088 Met Glu Thr Ser Ser Phe Glu Asn Ala Pro Pro Ala Ala 1 5 10 ATC AAT GAT GCT CAG GAT AAT AAT ATA AAT ACG GAG ACT AAT GAC CAG 2136 He Asn Asp Ala Gin Asp Asn Asn He Asn Thr Glu Thr Asn Asp Gin 15 20 25 GAA ACA AAT CAG CAA TCT ATC GAA ACT AGA GAT GCA ATT GAC AAA GAA 2184 Glu Thr Asn Gin Gin Ser He Glu Thr Arg Asp Ala He Asp Lys Glu 30 35 40 45 AAC GGT GTG CAA ACG GAA ACT GGT GAG AAC TCT GCA AAA AAT GCC GAA 2232 Asn Gly Val Gin Thr Glu Thr Gly Glu Asn Ser Ala Lys Asn Ala Glu 50 55 60 CAA AAC GTT TCT TCT ACA AAT TTG AAT AAT GCC CCC ACC AAT GGT GCT 2280 Gin Asn Val Ser Ser Thr Asn Leu Asn Asn Ala Pro Thr Asn Gly Ala 65 70 75 TTG GAC GAT GAT GTT ATC CCA AAT GCT ATT GTT ATT AAA AAC ATT CCG 2328 Leu Asp Asp Asp Val He Pro Asn Ala He Val He Lys Asn He Pro 80 85 90 TTT GCT ATT AAA AAA GAG CAA TTG TTA GAC ATT ATT GAA GAA ATG GAT 2376 Phe Ala He Lys Lys Glu Gin Leu Leu Asp He He Glu Glu Met Asp 95 100 105 CTT CCC CTT CCT TAT GCC TTC AAT TAC CAC TTT GAT AAC GGT ATT TTC 2424 Leu Pro Leu Pro Tyr Ala Phe Asn Tyr His Phe Asp Asn Gly He Phe 110 115 120 125 AGA GGA CTA GCC TTT GCG AAT TTC ACC ACT CCT GAA GAA ACT ACT CAA 2472 Arg Gly Leu Ala Phe Ala Asn Phe Thr Thr Pro Glu Glu Thr Thr Gin 130 135 140 GTG ATA ACT TCT TTG AAT GGA AAG GAA ATC AGC GGG AGG AAA TTG AAA 2520 Val He Thr Ser Leu Asn Gly Lys Glu He Ser Gly Arg Lys Leu Lys 145 150 155 GTG GAA TAT AAA AAA ATG CTT CCC CAA GCT GAA AGA GAA AGA ATC GAG 2568 Val Glu Tyr Lys Lys Met Leu Pro Gin Ala Glu Arg Glu Arg He Glu 160 165 170 AGG GAG AAG AGA GAG AAA AGA GGA CAA TTA GAA GAA CAA CAC AGA TCG 2616 Arg Glu Lys Arg Glu Lys Arg Gly Gin Leu Glu Glu Gin His Arg Ser 175 180 185 TCA TCT AAT CTT TCT TTG GAT TCT TTA TCT AAA ATG AGT GGA AGC GGA 2664 Ser Ser Asn Leu Ser Leu Asp Ser Leu Ser Lys Met Ser Gly Ser Gly 190 195 200 205 AAC AAT AAT ACT TCT AAC AAT CAA TTA TTC TCG ACT CTA ATG AAC GGC 2712 Asn Asn Asn Thr Ser Asn Asn Gin Leu Phe Ser Thr Leu Met Asn Gly 210 215 220 ATT AAT GCT AAT AGC ATG ATG AAC AGT CCA ATG AAT AAT ACC ATT AAC 2760 He Asn Ala Asn Ser Met Met Asn Ser Pro Met Asn Asn Thr He Asn 225 230 235 AAT AAC AGT TCT AAT AAC AAC AAT AGT GGT AAC ATC ATT CTG AAC CAA 2808 Asn Asn Ser Ser Asn Asn Asn Asn Ser Gly Asn He He Leu Asn Gin 240 245 250 CCT TCA CTT TCT GCC CAA CAT ACT TCT TCA TCG TTG TAC CAA ACA AAC 2856 Pro Ser Leu Ser Ala Gin His Thr Ser Ser Ser Leu Tyr Gin Thr Asn 255 260 265 GTT AAT AAT CAA GCC CAG ATG TCC ACT GAG AGA TTT TAT GCG CCT TTA 2904 Val Asn Asn Gin Ala Gin Met Ser Thr Glu Arg Phe Tyr Ala Pro Leu 270 275 280 285 CCA TCA ACT TCC ACT TTG CCT CTC CCA CCC CAA CAA CTG GAC TTC AAT 2952 Pro Ser Thr Ser Thr Leu Pro Leu Pro Pro Gin Gin Leu Asp Phe Asn 290 295 300 GAC CCT GAC ACT TTG GAA ATT TAT TCC CAA TTA TTG TTA TTT AAG GAT 3000 Asp Pro Asp Thr Leu Glu He Tyr Ser Gin Leu Leu Leu Phe Lys Asp 305 310 315 AGA GAA AAG TAT TAT TAC GAG TTG GCT TAT CCC ATG GGT ATA TCC GCT 3048 Arg Glu Lys Tyr Tyr Tyr Glu Leu Ala Tyr Pro Met Gly He Ser Ala 320 325 330 TCC CAC AAG AGA ATT ATC AAT GTT TTG TGC TCG TAC TTA GGG CTA GTA 3096 Ser His Lys Arg He He Asn Val Leu Cys Ser Tyr Leu Gly Leu Val 335 340 345 GAA GTA TAT GAT CCA AGA TTT ATT ATT ATC AGA AGA AAG ATT CTG GAT 3144 Glu Val Tyr Asp Pro Arg Phe He He He Arg Arg Lys He Leu Asp 350 355 360 365 CAT GCT AAT TTA CAA TCT CAT TTG CAA CAA CAA GGT CAA ATG ACA TCT 3192 His Ala Asn Leu Gin Ser His Leu Gin Gin Gin Gly Gin Met Thr Ser 370 375 380 GCT CAT CCT TTG CAG CCA AAC TCC ACT GGC GGC TCC ATG AAT AGG TCA 3240 Ala His Pro Leu Gin Pro Asn Ser Thr Gly Gly Ser Met Asn Arg Ser 385 390 395 CAA TCT TAT ACA AGT TTG TTA CAG GCC CAT GCA GCA GCT GCA GCG AAT 3288 Gin Ser Tyr Thr Ser Leu Leu Gin Ala His Ala Ala Ala Ala Ala Asn 400 405 410 AGT ATT AGC AAT CAG GCC GTT AAC AAT TCT TCC AAC AGC AAT ACT ATT 3336 Ser He Ser Asn Gin Ala Val Asn Asn Ser Ser Asn Ser Asn Thr He 415 420 425 AAC AGT AAT AAC GGT AAC GGT AAC AAT GTC ATC ATT AAT AAC AAT AGC 3384 Asn Ser Asn Asn Gly Asn Gly Asn Asn Val He He Asn Asn Asn Ser 430 435 440 445 GCC AGC TCA ACA CCA AAA ATT TCT TCA CAG GGA CAA TTC TCC ATG CAA 3432 Ala Ser Ser Thr Pro Lys He Ser Ser Gin Gly Gin Phe Ser Met Gin 450 455 460 CCA ACA CTA ACC TCA CCT AAA ATG AAC ATA CAC CAT AGT TCT CAA TAC 3480 Pro Thr Leu Thr Ser Pro Lys Met Asn He His His Ser Ser Gin Tyr 465 470 475 ' * AAT TCC GCA GAC CAA CCG CAA CAA CCT CAA CCA CAA ACA CAG CAA AAT 3528 Asn Ser Ala Asp Gin Pro Gin Gin Pro Gin Pro Gin Thr Gin Gin Asn 480 485 490 GTT CAG TCA GCT GCG CAA CAA CAA CAA TCT TTT TTA AGA CAA CAA GCT 3576 Val Gin Ser Ala Ala Gin Gin Gin Gin Ser Phe Leu Arg Gin Gin Ala 495 500 505 ACT TTA ACA CCA TCC TCA AGA ATT CCA TCC GGT TAT TCT GCC AAC CAT 3624 Thr Leu Thr Pro Ser Ser Arg He Pro Ser Gly Tyr Ser Ala Asn His 510 515 520 525 TAT CAA ATC AAT TCC GTT AAT CCC TTA CTG AGA AAT TCT CAA ATT TCA 3672 Tyr Gin He Asn Ser Val Asn Pro Leu Leu Arg Asn Ser Gin He Ser 530 535 540 CCT CCA AAT TCA CAA ATC CCA ATC AAC AGC CAA ACC CTA TCC CAA GCG 3720 Pro Pro Asn Ser Gin He Pro He Asn Ser Gin Thr Leu Ser Gin Ala 545 550 555 CAA CCA CCA GCA CAG TCC CAA ACT CAA CAA CGG GTA CCA GTG GCA TAC 3768 Gin Pro Pro Ala Gin Ser Gin Thr Gin Gin Arg Val Pro Val Ala Tyr 560 565 570 CAA AAT GCT TCA TTG TCT TCC CAG CAG TTG TAC AAC CTT AAC GGC CCA 3816 Gin Asn Ala Ser Leu Ser Ser Gin Gin Leu Tyr Asn Leu Asn Gly Pro 575 580 585 TCT TCA GCA AAC TCA CAG TCC CAA CTG CTT CCA CAG CAC ACA AAT GGC 3864 Ser Ser Ala Asn Ser Gin Ser Gin Leu Leu Pro Gin His Thr Asn Gly 590 595 600 605 TCA GTA CAT TCT AAT TTC TCA TAT CAG TCT TAT CAC GAT GAG TCC ATG 3912 Ser Val His Ser Asn Phe Ser Tyr Gin Ser Tyr His Asp Glu Ser Met 610 615 620 TTG TCC GCA CAC AAT TTG AAT AGT GCC GAC TTG ATC TAT AAA TCT TTG 3960 Leu Ser Ala His Asn Leu Asn Ser Ala Asp Leu He Tyr Lys Ser Leu 625 630 635 AGT CAC TCT GGA CTA GAT GAT GGC TTG GAA CAG GGC TTG AAT CGT TCT 4008 Ser His Ser Gly Leu Asp Asp Gly Leu Glu Gin Gly Leu Asn Arg Ser 640 645 650 TTA AGC GGA CTG GAT TTA CAA AAC CAA AAC AAG AAG AAT CTA TGG 4053 Leu Ser Gly Leu Asp Leu Gin Asn Gin Asn Lys Lys Asn Leu Trp 655 660 665 TAATATATAC TTCCATTATT CTATGATTAT AGAGTTTGTT TGGTATTTGT ATATCGCACG 4113 ATACAAGTAA TGAGGGGTGC TTACACAAGA TAAAAGATAA AAAAATATAT ATATATAATA 4173 AAAACCATCA AAAACACCAT TGAAAAAAAA TATAAAAAAA AAAAAAAATA ACCGAATATG 4233 AATATGAAAT TAATGATCAT GATGAAGTTA ATTTTTACTG AGAAACGTCA CCTAATGTCG 4293 ATGAAACGAT GATAATGAAT GAATGATGAG GCTACTTTAA GTAACGCAAT GTAATCAAGC 4353 CAAAATTATC CCTCTTTTTT TTTTTTCCCT CTTTTGAGAT TTTATTTTTA ACCTACTACT 4413 TACTTTTTTT TTTTGAACGT TCTTTTCCCA CATACTTTTA TATATGGTAT TTATATGTAC 4473 GATGTTTAAT CACAGAGATG TTTCTACCTT ACTCGATATT GTTTTTGCAT TAATTGATAT 4533 CTTGCTCACT GCATCATTGG CGGTATTTGT AGTATATAGA AAGTCGGGTA ACAATAATTT 4593 ATTGACATTT CTTTGTTTAC AATGATCAGA GAAGAGCAGA AAGTTTCATA GTCAAACGTT 4653 CAGGCCAATT GAACAAGAAA TTATTCGTTT TTTTAGTCGT TGAGTGTTCA ACTGACATGC 4713 TATTTTGGTG GTTCTTGATT AATTGGGGGC TTCATTGTTT GAAATAAAGA GTCGGGAAAA 4773 TAGCACAGAA AC AAGCATA TTAAAAGAGG CAAAAGAAGA AAGAACGAAT ATAAAAGGTA 4833 AAAAAGGAAA AGCATTGCTA TTCTTTTCTC ATAGGTGTTA TTCATACCGC CCTCTCTCTT 4893 CTTCCTTCTT CATTAATTAG TCTCCGTATA ATTTGCAGAT AATGTCATTA ACAGCAAACG 4953 ACGAATCGCC AAAACCCAAA AAAAATGCAT TATTGAAAAA CTTAGAGATC GATGATCTGA 5013 TACATTCTCA ATTTGTCAGA AGCGATACAA ATGGACATAG AACTACAAGA CGACTATTCA 5073 ACTCCGATGC CAGTATATCA CATCGAATAA GAGGAAGTGT TCGGTCTGAT AAAGGCCTTA 5133 ATAAAATAAA AAAAGGGTTG ATTTCCCAGC AGTCCAAACT TGCGTCAGAA AATTCTTCTC 5193 AAAATATCGT TAATAGGGAC AATAAGATGG GAGCAGTAAG TTTCCCCATT ATTGAACCTA 5253 ATATTGAAGT CAGCGAGGAG TTGAAGGTTA GAATTAAGTA TGATTCTATC AAATTTTTCA 5313 ATTTTGAAAG ACTAATATCT AAATCTTCAG TCATAGCACC TTTAGTTAAC AAAAATATAA 5373 CATCATCCGG TCCTCTAATC GGGTTTCAAA GAAGAGTTAA CAGGTTAAAG CAAACATGGG 5433 ATCTAGCAAC CGAAAACATG GAGTACCCAT ATTCTTCTGA TAATACGCCA TTCAGGGATA 5493 ACGATTCTTG GCAATGGTAC GTACCATACG GCGGAACAAT AAAAAAAATG AAAGATTTCA 5553 GTACAAAAAG AACTTTACCC ACCTGGGAAG ATAAAATAAA GTTTCTTACA TTTTTAGAAA 5613 ACTCTAAGTC TGCAACGTAC ATTAATGGTA ACGTATCACT TTGCAATCAT AATGAAACCG 5673 ATCAAGAAAA CGAAGATAGG AAAAAAAGGA AAGGGAAAGT ACCAAGAATC AAAAATAAAG 5733 TGTGGTTTTC CCAGATAGAA TACATTGTTC TTCGAAATTA TGAAATTAAA CCTTGGTATA 5793 CATCTCCTTT TCCGGAACAC ATCAACCAAA ATAAAATGGT TTTTATATGT GAGTTCTGCC 5853 TAAAATATAT GACTTCTCGA TATACTTTTT ATAGACACCA ACTAAAGTGT CTAACTTTTA 5913 AGCCCCCCGG AAATGAAATT TATCGCGACG GTAAGCTGTC TGTTTGGGAA ATTGATGGGC 5973 GGGAGAATGT CTTGTATTGT CAAAATCTTT GCCTGTTGGC AAAATGTTTT ATCAATTCTA 6033 AGACTTTGTA TTACGATGTT GAACCGTTTA TATTCTATAT TCTAACGGAG AGAGAGGATA 6093 CAGAGAACCA TCCCTATCAA AACGCAGCCA AATTCCATTT CGTAGGCTAT TTCTCCAAGG 6153 AAAAATTCAA CTCCAATGAC TATAACCTAA GTTGTATTTT AACTCTACCC ATATACCAGA 6213 GGAAAGGATA TGGTCAGTTT TTGATGGAAT TTTCATATTT ATTATCCAGA AAGGAGTCAA 6273 AATTTGGAAC TCCTGAAAAA CCATTGTCGG ATTTAGGATT ATTGACTTAC AGAACGTTTT 6333 GGAAGATAAA ATGTGCTGAA GTGCTATTAA AATTAAGAGA CAGTGCTAGA CGTCGATCAA 6393 ATAATAAAAA TGAAGATACT TTTCAGCAGG TTAGCCTAAA CGATATCGCT AAACTAACAG 6453 GAATGATACC AACAGACGTT GTGTTTGGAT TGGAACAACT TCAAGTTTTG TATCGCCATA 6513 AAACACGCTC ATTATCCAGT TTGGATGATT TCAACTATAT TATTAAAATC GATTCTTGGA 6573 ACAGGATTGA AAATATTTAC AAAACTTGGA GCTCAAAAAA CTATCCTCGC GTCAAATATG 6633 ACAAACTATT GTGGGAACCT ATTATATTAG GGCCGTCATT TGGTATAAAT GGGATGATGA 6693 ACTTAGAACC CACCGCATTA GCGGACGAAG CTCTTACAAA TGAAACTATG GCTCCGGTAA 6753 TTTCGAATAA CACACATATA GAAAACTATA ACAACAGTAG AGCACATAAT AAACGCAGAA 6813 GAAGAAGAAG AAGAAGTAGT GAGCACAAAA CATCCAAGCT T 6854 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 668 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: Met Glu Thr Ser Ser Phe Glu Asn Ala Pro Pro Ala Ala He Asn Asp 1 5 10 15 Ala Gin Asp Asn Asn He Asn Thr Glu Thr Asn Asp Gin Glu Thr Asn 20 25 30 Gin Gin Ser He Glu Thr Arg Asp Ala He Asp Lys Glu Asn Gly Val 35 40 45 Gin Thr Glu Thr Gly Glu Asn Ser Ala Lys Asn Ala Glu Gin Asn Val 50 55 60 Ser Ser Thr Asn Leu Asn Asn Ala Pro Thr Asn Gly Ala Leu Asp Asp 65 70 75 80 Asp Val He Pro Asn Ala He Val He Lys Asn He Pro Phe Ala He 85 90 95 Lys Lys Glu Gin Leu Leu Asp He He Glu Glu Met Asp Leu Pro Leu 100 105 110 Pro Tyr Ala Phe Asn Tyr His Phe Asp Asn Gly He Phe Arg Gly Leu 115 120 125 Ala Phe Ala Asn Phe Thr Thr Pro Glu Glu Thr Thr Gin Val He Thr 130 135 140 Ser Leu Asn Gly Lys Glu He Ser Gly Arg Lys Leu Lys Val Glu Tyr 145 150 155 160 Lys Lys Met Leu Pro Gin Ala Glu Arg Glu Arg He Glu Arg Glu Lys 165 170 175 Arg Glu Lys Arg Gly Gin Leu Glu Glu Gin His Arg Ser Ser Ser Asn 180 185 190 Leu Ser Leu Asp Ser Leu Ser Lys Met Ser Gly Ser Gly Asn Asn Asn 195 200 205 Thr Ser Asn Asn Gin Leu Phe Ser Thr Leu Met Asn Gly He Asn Ala 210 215 220 Asn Ser Met Met Asn Ser Pro Met Asn Asn Thr He Asn Asn Asn Ser 225 230 235 240 Ser Asn Asn Asn Asn Ser Gly Asn He He Leu Asn Gin Pro Ser Leu 245 250 255 Ser Ala Gin His Thr Ser Ser Ser Leu Tyr Gin Thr Asn Val Asn Asn 260 265 270 Gin Ala Gin Met Ser Thr Glu Arg Phe Tyr Ala Pro Leu Pro Ser Thr 275 280 285 Ser Thr Leu Pro Leu Pro Pro Gin Gin Leu Asp Phe Asn Asp Pro Asp 290 295 300 Thr Leu Glu He Tyr Ser Gin Leu Leu Leu Phe Lys Asp Arg Glu Lys 305 310 315 320 Tyr Tyr Tyr Glu Leu Ala Tyr Pro Met Gly He Ser Ala Ser His Lys 325 330 335 Arg He He Asn Val Leu Cys Ser Tyr Leu Gly Leu Val Glu Val Tyr 340 345 350 Asp Pro Arg Phe He He He Arg Arg Lys He Leu Asp His Ala Asn 355 360 365 Leu Gin Ser His Leu Gin Gin Gin Gly Gin Met Thr Ser Ala His Pro 370 375 380 Leu Gin Pro Asn Ser Thr Gly Gly Ser Met Asn Arg Ser Gin Ser Tyr 385 390 395 400 Thr Ser Leu Leu Gin Ala His Ala Ala Ala Ala Ala Asn Ser He Ser 405 410 415 Asn Gin Ala Val Asn Asn Ser Ser Asn Ser Asn Thr He Asn Ser Asn 420 425 430 Asn Gly Asn Gly Asn Asn Val He He Asn Asn Asn Ser Ala Ser Ser 435 440 445 Thr Pro Lys He Ser Ser Gin Gly Gin Phe Ser Met Gin Pro Thr Leu 450 455 460 Thr Ser Pro Lys Met Asn He His His Ser Ser Gin Tyr Asn Ser Ala 465 470 475 480 Asp Gin Pro Gin Gin Pro Gin Pro Gin Thr Gin Gin Asn Val Gin Ser 485 490 495 Ala Ala Gin Gin Gin Gin Ser Phe Leu Arg Gin Gin Ala Thr Leu Thr 500 505 510 Pro Ser Ser Arg He Pro Ser Gly Tyr Ser Ala Asn His Tyr Gin He 515 520 525 Asn Ser Val Asn Pro Leu Leu Arg Asn Ser Gin He Ser Pro Pro Asn 530 535 540 Ser Gin He Pro He Asn Ser Gin Thr Leu Ser Gin Ala Gin Pro Pro 545 550 555 560 Ala Gin Ser Gin Thr Gin Gin Arg Val Pro Val Ala Tyr Gin Asn Ala 565 570 575 Ser Leu Ser Ser Gin Gin Leu Tyr Asn Leu Asn Gly Pro Ser Ser Ala 580 585 590 Asn Ser Gin Ser Gin Leu Leu Pro Gin His Thr Asn Gly Ser Val His 595 600 605 Ser Asn Phe Ser Tyr Gin Ser Tyr His Asp Glu Ser Met Leu Ser Ala 610 615 620 His Asn Leu Asn Ser Ala Asp Leu He Tyr Lys Ser Leu Ser His Ser 625 630 635 640 Gly Leu Asp Asp Gly Leu Glu Gin Gly Leu Asn Arg Ser Leu Ser Gly 645 650 655 Leu Asp Leu Gin Asn Gin Asn Lys Lys Asn Leu Trp 660 665 (2 ) INFORMATION FOR SEQ ID NO:6: ( i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2814 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..696 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: GAA TTC CAA TAC ACC AAA CAG CTG CAT TTC CCT GTG GGG CCC AAA TCC 48 Glu Phe Gin Tyr Thr Lys Gin Leu His Phe Pro Val Gly Pro Lys Ser 1 5 10 15 ACA AAC TGT GAG GTA GCG GAA ATT CTT TTA CAC TGC GAC TGG GAA AGG 96 Thr Asn Cys Glu Val Ala Glu He Leu Leu His Cys Asp Trp Glu Arg 20 25 30 TAC ATA AAT GTT TTA AGT ATA ACA AGA ACA CCA AAT GTT CCT AGT GGT 144 Tyr He Asn Val Leu Ser He Thr Arg Thr Pro Asn Val Pro Ser Gly 35 40 45 ACC AGT TTC AGC ACC AGA ACG AGG TAC ATG TTC CGA TGG GAT GAC CAG 192 Thr Ser Phe Ser Thr Arg Thr Arg Tyr Met Phe Arg Trp Asp Asp Gin 50 55 60 GGG CAA GGT TGC ATA TTA AAA ATA AGT TTT TGG GTG GAC TGG AAC GCA 240 Gly Gin Gly Cys He Leu Lys He Ser Phe Trp Val Asp Trp Asn Ala 65 70 75 80 TCC AGT TGG ATC AAG CCA ATG GTA GAG AGC AAT TGT AAA AAT GGA CAA 288 Ser Ser Trp He Lys Pro Met Val Glu Ser Asn Cys Lys Asn Gly Gin 85 90 95 ATT AGC GCC ACT AAG GAC TTG GTA AAG TTA GTC GAA GAA TTT GTA GAG 336 He Ser Ala Thr Lys Asp Leu Val Lys Leu Val Glu Glu Phe Val Glu 100 105 110 AAA TAC GTG GAA TTG AGC AAA GAA AAA GCA GAT ACA CTC AAG CCG TTG 384 Lys Tyr Val Glu Leu Ser Lys Glu Lys Ala Asp Thr Leu Lys Pro Leu 115 120 125 CCC AGT GTT ACA TCT TTT GGA TCA CCT AGG AAA GTG GCA GCA CCG GAG 432 Pro Ser Val Thr Ser Phe Gly Ser Pro Arg Lys Val Ala Ala Pro Glu 130 135 140 CTG TCG ATG GTA CAG CCG GAG TCG AAA CCA GAA GCT GAG GCG GAA ATC 480 Leu Ser Met Val Gin Pro Glu Ser Lys Pro Glu Ala Glu Ala Glu He 145 150 155 160 TCA GAA ATA GGC AGC GAC AGA TGG AGG TTT AAC TGG GTG AAC ATA ATA 528 Ser Glu He Gly Ser Asp Arg Trp Arg Phe Asn Trp Val Asn He He 165 170 175 ATC TTG GTG CTC TTG GTG TTA AAT CTG CTG TAT TTA ATG AAG TTG AAC 576 He Leu Val Leu Leu Val Leu Asn Leu Leu Tyr Leu Met Lys Leu Asn 180 185 190 AAG AAG ATG GAT AAG CTG ACG AAC CTC ATG ACC CAC AAG GAC GAA GTT 624 Lys Lys Met Asp Lys Leu Thr Asn Leu Met Thr His Lys Asp Glu Val 195 200 205 GTA GCG CAC GCG ACT CTA TTG GAC ATA CCA GCC CAA GTA CAA TGG TCA 672 Val Ala His Ala Thr Leu Leu Asp He Pro Ala Gin Val Gin Trp Ser 210 215 220 AGA CCA AGA AGG GGA GAC GTG TTG TAACAGAGTA ATCATGTAAT ATTGTATGTA 726 Arg Pro Arg Arg Gly Asp Val Leu 225 230 AGGTTATGTA TGTTCGTATG GTATGGAAAA AAAAAAAAAA AAAGGATGCT ATGTGGAGAA 786 TGTAAGGCGT GGTAGCTCCG GATAATTCAG TCTGTAGGCT TCATCACGGG CAGTGGCCTG 846 ACTCTGAGAG CTTGCTCCGG TATTAAGTTG TGCGTTTGAA ATTTTCTGGA AAAAAGAAAT 906 TGATTGGTTG AAGCTATACT CGTCGAAAGA TTTCTTCGGC AGTGGTTGTT GCTCCACCTG 966 CACGGGAGTT GTGTTTGCGT TTATGTTCGG CTTGGCTATA TTATTAGCGA GTGATGTTTG 1026 CAATTTGCTG TATTGAGAAT CAATTTGGGT GCGTAAGCTT TCAATAATTT TGCAGACCGC 1086 AGGCACTTCC AACTTTATGA GTTGCAGGTA TTCTCTTTTA TGAATATACG ATGACGACGA 1146 TGACGACGAC GCATCCATGC GCAAAAGCTC AGGGTGTCTA GATAGTTTGT TAGTCAATAA 1206 ATCCACATAT CTAAAATAAT AAATAAACGA CAGCGACAAG TCGTTGGCCT GGAACGCACA 1266 CTGTGCCTTT TCCAATATGC CGATGCATGT TTTCAGGTAA ATTCTCAATG GTATCGCCGG 1326 ATTGAAGCGA TAATCCTTAG CGTCCTGAAC CAATTGCTTA CTAGACTTCA TGACCTACCG 1386 GGGCCAGATA AAGATGCGGA AGGAAGAGAA AAAATGTATA GTGGTTGGTG AACCGCAACA 1446 ATAATTCGTG CCAACACTTT AATCGAAGCA AAAATTGTCT TGTATGTTAT TAATATTATC 1506 TATCTAACCA TTGATTTACG TATAAAACTG TCGATGCTCA TCGCCTAGCA ATGAAAAAAT 1566 TTTTTCTTTT TTTTTTCATT ATTTCTCTTT GTTGCGTACT TTTTTTCATT GCGTTTCGCG 1626 GCAAAAGCGA TTCGAGTTGA CTGGAAGTGT GTTATACTAT AAAAAGTGTA TATGCCTATT 1686 TTTGGTTCTG ATCTTTACTT TACTGTTAAG TACTGGCTGA GGCAGTAGAC TCTGCCTCTG 1746 TTACGGCAGC GGTATTCGCC TCGGCATCAG CAGCCGCCCA CGGTAGAGTA GGTTCTGTTG 1806 TTTTGACGTT TGCCAAGGTA CTGTCCAAAT GCTCCTTCAG CAAGGCCTCA TTACTTTCCT 1866 TCTCCGGACC CACCGATTGC GTGATCTCCT GTACACGGTT CAAGAACTTG TTCAAATTGT 1926 AGCCCGCAGC AGCATCAGAG ACTTCTTGTG TGTAAGGGAC ACCCCTCAAC TCCTTGACTC 1986 TTCTTTTGTG CACTTTGCCC TTTAAATGCG TTTTTAACGC TATAGCAGTC TCCATGTATT 2046 TGGCACAGTG TATGCAATAG TGCTGACCAA GGCCCGGTTT GGTTTCATCC AATGGCTGGT 2106 TCAGAAGCTT CTGTACTGAT TCCTTGGTGG ACAAATCGTT ATAGATCAGG TCCAAGTCTC 2166 GTGTTCTTCT TTTAGTCTTG TATCTCTTCA CCGAATATCT ACCCATGATG CGCTATTGTT 2226 TTATCTTCAC TTGTCTGTGT GTTTAACTGC CTTTCAATTC ACCTCATCTC ATCTCCCGCT 2286 ACTTTCCATA TATAAAAGCA AAATTAATTT GCTTTTTCCC CTGTCAGTAT AAAAAAATTT 2346 TCCGCAGGAT ATAGAAAAAA AAGAAATGAA ATTATAGTAG CGGTTATTTC CGTGGGGTGC 2406 TTTTTTACAC CTGTACATCT TTTCCCTCCG TACATTTTTT TTATTTTTTT TTTGGGTTTT 2466 TTTTTTTCGA TATTTTTCCC TCCGAAACTA GTTAGCACAA TAATGCTGAC TAAGGAAACT 2526 TTTCATCTCA GAATTGATGG TCAGTTTGGT TTCTCTAGAG AATAGTTTAT AAAAAGATGT 2586 TGATGTGGAG CAACCATTTA TACATCCTTT CCGCAAGTGC TTTTGGAGTG GGACTTTCAA 2646 ACTTTAAAGT ACAGTATATC AAATAACTAA TTCAAGATGG CTAGAAGACC AGCTAGATGT 2706 TACAGATACC AAAAGAACAA GCCTTACCCA AAGTCTAGAT ACAACAGAGC TGTTCCAGAC 2766 TCCAAGATCA GAATCTACGA TTTGGGTAAG AAGAAGGCTA CCGTCGAT 2814 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 232 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: Glu Phe Gin Tyr Thr Lys Gin Leu His Phe Pro Val Gly Pro Lys Ser 1 5 10 15 Thr Asn Cys Glu Val Ala Glu He Leu Leu His Cys Asp Trp Glu Arg 20 25 30 Tyr He Asn Val Leu Ser He Thr Arg Thr Pro Asn Val Pro Ser Gly 35 40 45 Thr Ser Phe Ser Thr Arg Thr Arg Tyr Met Phe Arg Trp Asp Asp Gin 50 55 60 Gly Gin Gly Cys He Leu Lys He Ser Phe Trp Val Asp Trp Asn Ala 65 70 75 80 Ser Ser Trp He Lys Pro Met Val Glu Ser Asn Cys Lys Asn Gly Gin 85 90 95 He Ser Ala Thr Lys Asp Leu Val Lys Leu Val Glu Glu Phe Val Glu 100 105 110 Lys Tyr Val Glu Leu Ser Lys Glu Lys Ala Asp Thr Leu Lys Pro Leu 115 120 125 Pro Ser Val Thr Ser Phe Gly Ser Pro Arg Lys Val Ala Ala Pro Glu 130 135 140 Leu Ser Met Val Gin Pro Glu Ser Lys Pro Glu Ala Glu Ala Glu He 145 150 155 160 Ser Glu He Gly Ser Asp Arg Trp Arg Phe Asn Trp Val Asn He He 165 170 175 He Leu Val Leu Leu Val Leu Asn Leu Leu Tyr Leu Met Lys Leu Asn 180 185 190 Lys Lys Met Asp Lys Leu Thr Asn Leu Met Thr His Lys Asp Glu Val 195 200 205 Val Ala His Ala Thr Leu Leu Asp He Pro Ala Gin Val Gin Trp Ser 210 215 220 Arg Pro Arg Arg Gly Asp Val Leu 225 230 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1485 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: ATGGACTTAA GAGTAGGAAG GAAATTTCGT ATTGGCAGGA AGATTGGGAG TGGTTCCTTT 60 GGTGACATTT ACCACGGCAC GAACTTAATT AGTGGTGAAG AAGTAGCCAT CAAGCTGGAA 120 TCGATCAGGT CCAGACATCC TCAATTGGAC TATGAGTCCC GCGTCTACAG ATACTTAAGC 180 GGTGGTGTGG GAATCCCGTT CATCAGATGG TTTGGCAGAG AGGGTGAATA TAATGCTATG 240 GTCATCGATC TTCTAGGCCC ATCTTTGGAA GATTTATTCA ACTACTGTCA CAGAAGGTTC 300 TCCTTTAAGA CGGTTATCAT GCTGGCTTTG CAAATGTTTT GCCGTATTCA GTATATACAT 360 GGAAGGTCGT TCATTCATAG AGATATCAAA CCAGACAACT TTTTAATGGG GGTAGGACGC 420 CGTGGTAGCA CCGTTCATGT TATTGATTTC GGTCTATCAA AGAAATACCG AGATTTCAAC 480 ACACATCGTC ATATTCCTTA CAGGGAGAAC AAGTCCTTGA CAGGTACAGC TCGTTATGCA 540 AGTGTCAATA CGCATCTTGG AATAGAGCAA AGTAGAAGAG ATGACTTAGA ATCACTAGGT 600 TATGTCTTGA TCTATTTTTG TAAGGGTTCT TTGCCATGGC AGGGTTTGAA AGCAACCACC 660 AAGAAACAAA AGTATGATCG TATCATGGAA AAGAAATTAA ACGTTAGCGT GGAAACTCTA 720 TGTTCAGGTT TACCATTAGA GTTTCAAGAA TATATGGCTT ACTGTAAGAA TTTGAAATTC 780 GATGAGAAGC CAGATTATTT GTTCTTGGCA AGGCTGTTTA AAGATCTGAG TATTAAACTA 840 GAGTATCACA ACGACCACTT GTTCGATTGG ACAATGTTGC GTTACACAAA GGCGATGGTG 900 GAGAAGCAAA GGGACCTCCT CATCGAAAAA GGTGATTTGA ACGCAAATAG CAATGCAGCA 960 AGTGCAAGTA ACAGCACAGA CAACAAGTCT GAAACTTTCA ACAAGATTAA ACTGTTAGCC 1020 ATGAAGAAAT TCCCCACCCA TTTCCACTAT TACAAGAATG AAGACAAACA TAATCCTTCA 1080 CCAGAAGAGA TCAAACAACA AACTATCTTG AATAATAATG CAGCCTCTTC TTTACCAGAG 1140 GAATTATTGA ACGCACTAGA TAAAGGTATG GAAAACTTGA GACAACAGCA GCCGCAGCAG 1200 CAGGTCCAAA GTTCGCAGCC ACAACCACAG CCCCAACAGC TACAGCAGCA ACCAAATGGC 1260 CAAAGACCAA ATTATTATCC TGAACCGTTA CTACAGCAGC AACAAAGAGA TTCTCAGGAG 1320 CAACAGCAGC AAGTTCCGAT GGCTACAACC AGGGCTACTC AGTATCCCCC ACAAATAAAC 1380 AGCAATAATT TTAATACTAA TCAAGCATCT GTACCTCCAC AAATGAGATC TAATCCACAA 1440 CAGCCGCCTC AAGATAAACC AGCTGGCCAG TCAATTTGGT TGTAA 1485 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: 1inear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: CCTACTCTTA GGCCCGGGTC TTTTTAATGT ATCC 34 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: GGAATCACTA CAGGGATG 18 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 543 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: ' GATCTCTGAA TTGAAGAACC GTTCAAACAT TGGCGAGCCC TTAACCAAAT CTTCCAATGA 60 AAGTACTTAT AAAGACATTA AAGCCACCGG CAATGATGGT GATCCGAATT TGGCTCTAAT 120 GAGAGCGGAG AATCGAGTAT TAAAATATAA ACTAGAGAAT TGTGAAAAAC TACTAGATAA 180 AGATGTGGTT GATTTGCAAG ATTCTGAGAT TATGGAAATT GTAGAAATGC TTCCCTTTGA 240 GGTCGGCACC CTTTTGGAAA CAAAGTTCCA AGGTTTGGAA TCACAAATAA GGCAATATAG 300 GAAATACACT CAAAAACTTG AAGACAAGAT CATGGCGCTA GAAAAAAGTG GTCATACTGC 360 AATGTCGCTA ACTGGGTGTG ACGGCACTGA AGTGATCGAA TTACAGAAGA TGCTCGAGAG 420 GAAGGATAAA ATGATTGAGG CCCTGCAGAG TGCCAAACGA CTGCGGGATA GGGCTTTGAA 480 ACCACTCATT AATACACAGC AATCACCGCA CCCTGTCGTG GATAACGATA AATGATTAGG 540 TGA 543 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 35 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: CCTTCCTACT CTTAAGCCCG GGCCGCAGGA ATTCG 35 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: AGCAATATAG GATCCTTACA ACCAAATTGA 30 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: CCTACTCTTA AGCCCGGGTC TTTTTAATGT ATCC 34 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 32 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: GTCTCAAGTT TTGGGATCCT TAATCTAGTG CG 32 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 32 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: CACCATCGCC CCCGGGTAAC GCAACATTGT CC 32 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3628 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: GATCAGATGA TATAGCTTTT TGTGTGCCGT ACCTTTCCGC GATTCTGCCC GTATATCTTG 60 GTCCCTGAGC TATTTTCTGA GATTCTTTTT GTTGCTTTGC CAAATCATTG GCGTCATTCA 120 TGGTCATACC AAATCCCAAT TTGGCAAACT TGGGTGTTAA AGTATCTTGC TGTTCTTTTC 180 TAGTTGTGTC GAAGCTGTTT GAAGTGTCAT TTAAAAAATC ATTGAATTCA TCAGGCTGGG 240 TATTAATATC ATCTATACTG TTATTATTGT TGCCTTTACT GTTATTCATA AATTGGGAAT 300 CGTAATCATT TGTCTAATTT TGGTGCTAGA AGACGAATTA GTGAACTCGT CCTCCTTTTC 360 TTGTTGAGCC TCTTTTTTAA ATTGATCAAA CAAGTCTTCT GCCTGTGATT TGTCGACTTT 420 CTTTGCGGTT AGTCTAGTGG GCTTTCTTGA CGAAGACAAA ATTGAATGTT TCTTTTTATC 480 TTGCGAGTTT AATACCGGTT TCTTTCTGCA TGCCGTTAAG ATGGAACTTC TCGTTTTAGT 540 GACAGTGGTC TTGGGTGTGC TGCCTGTGGT GTTGTTTTTT GGGGCGAGAG AGCCTGTATT 600 TACATTGAGT TTAGAACTGG AATTGGAGCT TGGTTTTTGC CAATTAGAGA AAAAATCGTC 660 AACACTATTT TCTTTGGAAG TCGACCTGGA AGCGTCTGAA TCGGTGTCCA ACGGTGAGTC 720 CGAAGAATCT TGACCGTTCA AGACTAATTC TGATGGGTAT AACTCCATAT CCTTTTGAAC 780 CTTCTTGTCG AGATGTATCT TATATTTCTT AGCAACAGGG CTCGTATATT TTGTTTTCGC 840 GTCAACATTT GCTGTATTTA GTAGCTGTTT CCCATTGTTC TTTAAGAAAA AATCACGAGC 900 CTTATGGTTC CCACCCAACT TAAACCTTCT TAAATTGTTA ATTGTCCATT TATCTAATGT 960 AGAAGACTTT ACAAAGGTGA TATGAACACC CATGTTTCTA TGCACAGCAG AGCATTGAAT 1020 ACACAGCATC ACACCAAAAG GTACCGAAGT CCAGTAGGAT TCTTGTTACC ACAATCAAAA 1080 CAAACTCGAT TTTCCATGTT GCTACCTAGC TTCTGAAAAA CTTGTTGAGT AGTCTGTTCC 1140 GTGGCAAATG TTTCTCCTTC ATCGTTACTC ATTGTCGCTA TGTGTATACT AAATTGCTCA 1200 AGAAGACCGG ATCAACAAGT ACTTAACAAA TACCCTTTCT TTGCTATCGC CTTGATCTCC 1260 TTTTATAAAA TGCCAGCTAA ATCGTGTTTA CGAAGAATAG TTGTTTTCTT TTTTTTTTTT 1320 TTTTTTCGAA ACTTTACCGT GTCGTCGAAA ATGACCAAAC GATGTTACTT TTCCTTTTGT 1380 GTCATAGATA ATACCAATAT TGAAAGTAAA ATTTTAAACA TTCTATAGGT GAATTGAAAA 1440 GGGCAGCTTA GAGAGTAACA GGGGAACAGC ATTCGTAACA TCTAGGTACT GGTATTATTT 1500 GCTGTTTTTT AAAAAAGAAG GAAATCCGTT TTGCAAGAAT TGTCTGCTAT TTAAGGGTAT 1560 ACGTGCTACG GTCCACTAAT CAAAAGTGGT ATCTCATTCT GAAGAAAAAG TGTAAAAAGG 1620 ACGATAAGGA AAGATGTCCC AACGATCTTC ACAACACATT GTAGGTATTC ATTATGCTGT 1680 AGGACCTAAG ATTGGCGAAG GGTCTTTCGG AGTAATATTT GAGGGAGAGA ACATTCTTCA 1740 TTCTTGTCAA GCGCAGACCG GTAGCAAGAG GGACTCTAGT ATAATAATGG CGAACGAGCC 1800 AGTCGCAATT AAATTCGAAC CGCGACATTC GGACGCACCC CAGTTGCGTG ACGAATTTAG 1860 AGCCTATAGG ATATTGAATG GCTGCGTTGG AATTCCCCAT GCTTATTATT TTGGTCAAGA 1920 AGGTATGCAC AACATCTTGA TTATCGATTT ACTAGGGCCA TCATTGGAAG ATCTCTTTGA 1980 GTGGTGTGGT AGAAAATTTT CAGTGAAAAC AACCTGTATG GTTGCCAAGC AAATGATTGA 2040 TAGAGTTAGA GCAATTCATG ATCACGACTT AATCTATCGC GATATTAAAC CCGATAACTT 2100 TTTAATTTCT CAATATCAAA GAATTTCACC TGAAGGAAAA GTCATTAAAT CATGTGCCTC 2160 CTCTTCTAAT AATGATCCCA ATTTAATATA CATGGTTGAC TTTGGTATGG CAAAACAATA 2220 TAGAGATCCA AGAACGAAAC AACATATACC ATACCGTGAA CGAAAATCAT TGAGCGGTAC 2280 CGCCAGATAT ATGTCTATTA ATACTCATTT TGGAAGAGAA CAGTCACGTA GGGATGATTT 2340 AGAATCGCTA GGTCACGTTT TTTTTTATTT CTTGAGGGGA TCCTTGCCAT GGCAAGGTTT 2400 GAAAGCACCA AACAACAAAC TGAAGTATGA AAAGATTGGT ATGACTAAAC AGAAATTGAA 2460 TCCTGATGAT CTTTTATTGA ATAATGCTAT TCCTTATCAG TTTGCCACAT ATTTAAAATA 2520 TGCACGTTCC TTGAAGTTCG ACGAAGATCC GGATTATGAC TATTTAATCT CGTTAATGGA 2580 TGACGCTTTG AGATTAAACG ACTTAAAGGA TGATGGACAC TATGACTGGA TGGATTTGAA 2640 TGGTGGTAAA GGCTGGAATA TCAAGATTAA TAGAAGAGCT AACTTGCATG GTTACGGAAA 2700 TCCAAATCCA AGAGTCAATG GCAATACTGC AAGAAACAAT GTGAATACGA ATTCAAAGAC 2760 ACGAAATACA ACGCCAGTTG CGACACCTAA GCAACAAGCT CAAAACAGTT ATAACAAGGA 2820 CAATTCGAAA TCCAGAATTT CTTCGAACCC GCAGAGCTTT ACTAAACAAC AACACGTCTT 2880 GAAAAAAATC GAACCCAATA GTAAATATAT TCCTGAAACA CATTCAAATC TTCAACGGCC 2940 AATTAAAAGT CAAAGTCAAA CGTACGACTC CATCAGTCAT ACACAAAATT CACCATTTGT 3000 ACCATATTCA AGTTCTAAAG CTAACCCTAA AAGAAGTAAT AATGAGCACA ACTTACCAAA 3060 CCACTACACA AACCTTGCAA ATAAGAATAT CAATTATCAA AGTCAACGAA ATTACGAACA 3120 AGAAAATGAT GCTTATTCTG ATGACGAGAA TGATACATTT TGTTCTAAAA TATACAAATA 3180 TTGTTGTTGC TGTTTTTGTT GCTGTTGATA AAGCGATTTT TATACTTTTC TCTTTTTCCT 3240 TTTTTTTTTT GATTGGCTGT TTCCTTATGC CGCTCTTTCC CAATTTATGA CTTTCCAATA 3300 ATGTATTATT TTGTTTCTCT TTCTCTCTGT TACCCTTTAT TTTATCATCT ACAATAATTG 3360 AATTCCGGAG AGGGTAAAGA AACAGGAAAA AGAAGAAAAT GAGACATAGT CAGCATCGTA 3420 ATCGTTTTCC TTCTGTATAT TCCTTTATCA AAAGACTACA CGCACATATA TATTAATCCC 3480 GGTATGTTTT TGGTGTGCTA AATCTATCTT CAAGCACTAT TATAGCATTT TTTTAAGAAT 3540 ATCCAAAATA ATATGTAATT TATGATTAAT CAAGGTTCAA GAATTGGAGA AACCGTGAGC 3600 GACTTCTTTG ATACTTGGAT GTAAGCTT 3628 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 33 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: TGAAGATCGT TGGCCCGGGT TTCCTTATCG TCC 33 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2468 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: AATATTTCAA GCTATACCAA GCATACAATC AACTCCAAGC TTCGAGCGGC CGCCAGTGTG 60 CTCTAAAGGA AAAAGCGAGT GCCTTTAGCC TTAAAAGCGT TATAATATTA TTATGGCTTT 120 GGACCTCCGG ATTGGGAACA AGTATCGCAT TGGTCGTAAA ATTGGCAGTG GATCTTTCGG 180 AGACATTTAT CTTGGGACTA ATGTCGTTTC TGGTGAAGAG GTCGCTATCA AGCTAGAATC 240 AACTCGTGCT AAACACCCTC AATTGGAGTA TGAATACAGA GTTTATCGCA TTTTGTCAGG 300 AGGGGTCGGA ATCCCGTTTG TTCGTTGGTT CGGTGTAGAA TGTGATTACA ACGCTATGGT 360 GATGGATTTA TTGGGTCCTT CGTTGGAAGA CTTGTTTAAT TTTTGCAATC GAAAGTTTTC 420 TTTGAAAACA GTTCTTCTCC TTGCGGACCA GCTCATTTCT CGAATTGAAT TCATTCATTC 480 AAAATCTTTT CTTCATCGTG ATATTAAGCC TGATAACTTT TTAATGGGAA TAGGTAAAAG 540 AGGAAATCAA GTTAACATAA TTGATTTCGG ATTGGCTAAG AAGTATCGTG ATCACAAAAC 600 TCACCTGCAC ATTCCTTATC GCGAGAACAA GAATCTTACA GGTACTGCAC GCTATGCTAG 660 CATCAATACT CATTTAGGTA TTGAACAATC CCGCCGTGAT GACCTCGAAT CTTTAGGTTA 720 TGTGCTCGTC TACTTTTGTC GTGGTAGCCT GCCTTGGCAG GGATTGAAGG CTACCACGAA 780 AAAGCAAAAG TATGAAAAGA TTATGGAGAA GAAGATCTCT ACGCCTACAG AGGTCTTATG 840 TCGGGGATTC CCTCAGGAGT TCTCAATTTA TCTCAATTAC ACGAGATCTT TACGTTTCGA 900 TGACAAACCT GATTACGCCT ACCTTCGCAA GCTTTTCCGA GATCTTTTTT GTCGGCAATC 960 TTATGAGTTT GACTATATGT TTGATTGGAC CTTGAAGAGA AAGACTCAAC AAGACCAACA 1020 ACATCAGCAG CAATTACAGC AACAACTGTC TGCAACTCCT CAAGCTATTA ATCCGCCGCC 1080 AGAGAGGTCT TCATTTAGAA ATTATCAAAA ACAAAACTTT GATGAAAAAG GCGGAGACAT 1140 TAATACAACC GTTCCTGTTA TAAATGATCC ATCTGCAACC GGAGCTCAAT ATATCAACAG 1200 ACCTAATTGA TTAGCCTTTC ATATTATTAT TATATAGCAT GGGCACATTA TTTTTATATT 1260 TTCTTCTCAT CTGGAGTCTT CCAATACTTG CCTTTTATCC TCCAGACGTC CTTTAATTTT 1320 GTTGATAGCG CAGGGCTTTT TCCTTGGGAT GGCGAAAGTT ACTTTGCTTA TAGTTTATTG 1380 AGGGTTCATA GCTTATTTGG CTGAAGATCT TGTGTTGACT TAAATTCTAT GCTAACCTCA 1440 TGATCATATC CTCATTATGG CAAGTTTTGG TGAAAAATTT TTTAATATTA GTACATTTGC 1500 TAATAATACA TTTGGTATTT GTTTTTACTA CCTGTGAATC TATTCATACA TTATCATATA 1560 TGTTTCGAGC CAGGAACAGA AAAAAGTGAG AGAATTTTCT GCAGAAATGA TCATAATTTT 1620 ATCTTCGCTT AACACGAATC CTGGTGACAG ATTATCGTGG TTTAAAGCCT TTTTTTTACG 1680 ACGCCATAAG CAAATTGGTT ACTTTTTTAT GTGTGATGAG CCTTGGGGTT TAATCTAATT 1740 AGAAGGCATT GCATTCATAT ACTTTTAATA ATATATTATC AGCTATTTGC TGCTTTTCTT 1800 TATAGATACC GTCTTTTCCA AGCTGAACTC ATTTAATCAG CGTCGTTTAA CCTTAGGATG 1860 CTTAAGATGC GTTTAAATTC AATGACTTAA TGCTCGAGGG ATGAATGGTT TGTTTTAGTT 1920 CGTGTTCTGG GTGCATGATC TCGTGCTTGA CTGTTTTATT GAAGCGTTCA TTTCATGAAG 1980 TGTCTTTCGA TGTTGTTCAC ACTTCTGTTT GCTAAATATA ATAAATATTT TGCTTTTCAC 2040 TTTAGAGCAC ACTGGCGGCC GCTCGAAGCT TTGGACTTCT TCGCCATTGG TCAAGTCTCC 2100 AATCAAGGTT GTCGGCTTGT CTACCTTGCC AGAAATTTAC GAAAAGATGG AAAAGGGATC 2160 CAAATCGTTG GTAGATACTT GTTGACACTT CTAAATAAGC GAATTTCTTA TGATTTATGA 2220 TTTTTATTAT TAAATAAGTT ATAAAAAAAA TAAGGTATAC AAATTTTAAA GTGACTCTTA 2280 GGTTTTAAAA CGAAAATTCT TATTCTTGAG TAACTCTTTC CTGTAGGTCA GGTTGCTTTC 2340 TCAGGTATAG CATGAGGTCG CTCTTATTGA CCACACCTCT ACCGGCATGC CGAGCAAATG 2400 CCTGCAAATC GCTCCCCATT TCACCCAATT GTAGATATGC TAACTCCAGC AATGAGCCGA 2460 TGAATCTC 2468 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: GGGTTATAAT ATTATCCCGG GTTTGGACCT CCGG 34 (2) INFORMATION FOR SEQ ID NO:21: (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:21: TCCCTCTCTA GATATGGCGA GATAGTTA 28 (2) INFORMATION FOR SEQ ID NO:22: (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:22: GTTTACACTC GAGGCATATA GTGATACA 28 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5093 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: GCTAGCTTTT GCCGGGGAAC CCATCCCGAA AAAATTGCAA AAAAAAAAAT AGCCGCCGAC 60 CGTTGGTCGC TATTCACGGA ATGATAGAAA AATAGCCGCG CTGCTCGTCC TGGGTGACCT 120 TTTGTATATT GTATAAAGAT AAACATAGTG CTATCAGGAA TATCTTTATA TACACACGCA 180 TACTGAATGT GGTTGAAGTT CAAAAAATAT CACAAACGTT AAGAAGTTTT ACTGGTAAAC 240 ATATAGACAT AGTGGAGCGC TTGCTCGAGG TCAAATGCAG ACGGATACGA GAGCGCGGGA 300 GGGAAACCGG AGAAGGTCAA TATGCCCATA ATTCTTCTTC TTTGAGGTTG GCAATTATAT 360 ATTGTATCTG AATTAGGCAA ATAGAAAAGA GACCTTACCA TTAGCGCCAT CGTAGAGTCC 420 CATTTCACCT TTTCTTAGTT CTTTATATAT GTCTGCGTAT GGCCCACATA TGCGCGCACA 480 GTGCGCGCCA CCCTCTAAGA ACGATAAACA TAAAATAAAC ACATAAACAA TCAACGACAG 540 TTCGCGCTTC CCTCACTAAA TATGGCGAGA TAGTTAAACA ATCATGGCTC GTTCTTCCTT 600 GCCCAACCGC CGCACCGCCC AGTTCGAAGC GAACAAGAGG AGGACCATTG CACATGCTCC 660 ATCTCCAAGT CTTTCAAATG GGATGCACAC TCTAACGCCG CCCACCTGTA ACAATGGTGC 720 TGCCACTTCA GACTCCAATA TACATGTATA TGTAAGGTGC AGATCGCGTA ATAAGCGAGA 780 AATAGAGGAA AAAAGTAGTG TAGTTATATC TACACTAGGC CCACAAGGGA AAGAAATCAT 840 TCTGTCCAAC GGTTCTCACC AATCGTATTC GTCCTCGAAG AAAACTTACC AATTTGATCA 900 GGTGTTCGGC GCAGAATCTG ACCAGGAAAC AGTGTTTAAT GCCACTGCAA AAAACTACAT 960 TAAGGAAATG TTGCACGGGT ACAATTGTAC AATATTTGCA TACGGTCAAA CGGGAACAGG 1020 TAAAACCTAC ACTATGTCTG GCGATATAAA TATTCTCGGT GATGTGCAAT CTACCGATAA 1080 TCTATTATTA GGAGAGCATG CAGGTATCAT ACCACGGGTT CTGGTCGATT TGTTTAAAGA 1140 ATTGAGCTCC TTAAATAAAG AGTACTCCGT AAAAATATCC TTTTTAGAGT TGTACAATGA 1200 AAATTTGAAA GATCTGCTCT CTGATAGTGA GGACGATGAT CCTGCAGTCA ACGATCCCAA 1260 GAGGCAGATT CGTATTTTTG ACAATAACAA CAATAATTCA TCCATCATGG TCAAGGGGAT 1320 GCAGGAAATC TTTATTAACT CTGCACACGA AGGCTTGAAT TTGCTAATGC AGGGTTCGTT 1380 AAAAAGGAAA GTGGCCGCTA CTAAATGCAA CGATCTTTCA TCAAGGTCTC ACACCGTCTT 1440 TACAATCACA ACAAACATAG TTGAGCAAGA TAGCAAAGAC CATGGACAAA ACAAAAATTT 1500 TGTTAAAATT GGCAAATTGA ATTTGGTGGA TTTGGCAGGC AGTGAAAACA TCAACAGATC 1560 GGGTGCGGAG AATAAAAGGG CTCAAGAAGC TGGCCTAATA AACAAATCGC TGCTAACACT 1620 AGGCCGTGTT ATCAACGCAC TCGTTGATCA TTCTAACCAT ATACCTTACA GAGAATCTAA 1680 GCTAACAAGA TTGCTACAAG ACTCTTTAGG TGGTATGACG AAAACATGCA TTATCGCAAC 1740 TATATCACCT GCGAAAATAT CCATGGAAGA GACTGCAAGT ACGCTAGAAT ATGCAACGAG 1800 AGCCAAATCA ATTAAGAATA CTCCACAAGT AAATCAGTCT TTATCGAAGG ATACATGTCT 1860 CAAAGACTAC ATTCAAGAGA TTGAAAAATT AAGAAATGAT TTGAAAAATT CAAGAAACAA 1920 ACAAGGTATA TTTATAACTC AAGATCAGTT GGACCTTTAC GAGAGCAATT CTATCTTGAT 1980 TGATGAGCAA AATCTAAAAA TACATAACCT GCGAGAACAA ATTAAAAAAT TCAAAGAAAA 2040 CTACCTGAAC CAATTAGATA TCAATAATCT TTTACAGTCT GAAAAGGAAA AACTAATTGC 2100 CATAATACAG AATTTTAATG TCGATTTTTC TAACTTTTAC TCGGAAATCC AAAAAATTCA 2160 CCATACTAAT CTCGAACTAA TGAATGAAGT CATACAACAG AGAGATTTTT CACTAGAAAA 2220 TTCTCAAAAA CAGTATAATA CGAACCAGAA CATGCAATTA AAAATCTCTC AACAAGTTTT 2280 ACAGACTTTG AACACTTTAC AGGGCTCTTT AAATAATTAT AACTCTAAAT GTTCCGAAGT 2340 TATCAAAGGC GTCACCGAAG AACTAACCAG GAACGTAAAT ACCCATAAGG CGAAACACGA 2400 TTCTACTCTC AAATCGTTAT TAAACATTAC TACTAACTTA TTGATGAATC AGATGAACGA 2460 ACTGGTGCGT AGTATTTCGA CTTCATTGGA AATATTTCAG AGTGATTCTA CTTCTCACTA 2520 TCGTAAAGAT TTGAATGAAA TCTACCAATC ACATCAACAA TTTCTAAAAA ATTTACAAAA 2580 CGATATTAAA AGCTGTCTTG ATTCGATAGG CAGTTCAATT CTAACTTCCA TAAACGAAAT 2640 ATCGCAAAAT TGCACCACTA ACTTGAATAG TATGAATGTT TTAATAGAAA ACCAGCAGTC 2700 AGGATCATCG AAATTAATTA AAGAGCAAGA TTTAGAAATA AAAAAACTGA AAAACGATCT 2760 GATCAATGAG CGCAGGATTT CTAACCAATT CAACCAACAG TTGGCTGAAA TGAAGCGATA 2820 TTTTCAGGAT CACGTTTCCA GGACGCGTAG TGAATTCCAC GACGAACTTA ACAAATGTAT 2880 CGATAACCTA AAAGATAAAC AATCTAAGTT GGATCAAGAT ATCTGGCAGA AGACGGCCTC 2940 TATTTTCAAC GAAACAGATA TCGTAGTTAA TAAAATTCAT TCCGACTCAA TAGCATCCCT 3000 CGCTCATAAT GCTGAAAACA CTTTGAAAAC GGTTTCTCAG AACAATGAAA GCTTTACTAA 3060 CGATTTAATC AGTCTATCAC GCGGAATGAA CATGGACATA TCCTCCAAAC TGAGAAGTTT 3120 GCCCATCAAT GAATTTTTAA ACAAGATATC ACAAACCATT TGTGAAACCT GTGGCGATGA 3180 TAACACAATC GCATCAAATC CAGTATTGAC CTCTATTAAA AAATTTCAAA ATATAATTTG 3240 TTCAGACATT GCCCTAACAA ATGAGAAGAT CATGTCATTA ATAGATGAAA TACAATCACA 3300 AATTGAAACC ATATCTAATG AAAACAATAT CAATTTGATT GCAATAAATG AAAATTTTAA 3360 TTCTTTGTGC AATTTTATAT TAACTGATTA CGATGAGAAT ATTATGCAAA TCTCAAAAAC 3420 ACAAGATGAG GTGCTTTCTG AACATTGCGA GAAGCTACAA TCACTGAAAA TACTGGGTAT 3480 GGACATTTTC ACTGCTCACA GCATAGAAAA ACCCCTTCAT GAGCATACAA GACCTGAAGC 3540 GTCAGTAATC AAGGCTTTAC CCTTATTGGA TTATCCAAAA CAATTTCAGA TTTATAGGGA 3600 TGCTGAAAAT AAGAGCAAAG ACGACACATC TAATTCTCGT ACTTGTATAC CAAACTTGTC 3660 AACTAATGAA AATTTTCCTC TTTCACAATT CAGTCCAAAA ACCCCAGTGC CAGTGCCTGA 3720 TCAACCTCTA CCAAAAGTTC TTATACCGAA AAGCATAAAC TCGGCCAAGT CCAATAGATC 3780 AAAGACCTTA CCAAATACAG AGGGTACTGG ACGAGAATCG CAGAACAATT TGAAGAGAAG 3840 ATTTACCACC GAGCCAATAT TGAAGGGAGA AGAAACTGAA AATAATGACA TACTGCAAAA 3900 TAAAAAACTT CATCAATAAG GGGATATAGC CATTGTAAAA TATTTGTATC ACTATATGCA 3960 TTGAGTGTAA ACTGTTGCAC CTATAAAGAA TGAAAACAAT CTAGTATGTG TACTTACATA 4020 ATTACACAGT CTTTTTTTTT TTTACCTTGT TTATCCTTCT TGTTCTTCAA GCTTGTAGGT 4080 TTTTTTGACT CAGTTTTTAC TGCAGGAAAA TCTTTACGAA TCATGTTTGA ACTGCCCATA 4140 TTTGATAAAC TAACTTCTTG CTTTGCTGCC ATCGACTGCT CAGCAACTTC CCTTGACATT 4200 CCCTTTGCTG AGGAAGAACT TTTCCTGATG CTTGTATCAG AACCCGTTTT AATACCATTT 4260 CTATTCGTGT TTGAATTCAT GTTAATTTGC AAACCTTGTG GCTCACGATC ACGTTTTGGA 4320 TTTCCAGTAA AGAATGTTTC AGATTTTGAA GAAACTCTTG AATTTGACCC TACGTTACTT 4380 GTTTGACTGT CCACAGTAGA GAATAAATTC AAAGTACTGA TACTTTTATT TTTTTTATGC 4440 TGTTTTTTAC CAATGCTGGC TAGTCCACCG TCCCTTGAGC GTAGCTTATT AATCGCCCTC 4500 TTGTCCTCGT TCCCTGCAGC TTTCTCGTAC CATTTCCATG CGTATTCCAT GTTACGATCA 4560 CAGCCCTTGC CATGCTCATA GAAGTAGCCC AGAGTGAATT GGGCCTTTGG CAAACCAGCA 4620 TTAGCTGCAC GCAAGGCCCA TTGAAAAGCC TCATTTTCAT CTTTTTCAAA AGCAGGTTCT 4680 GCTCCCAGTA AGTACCATGC ACATAAACCT AACATTGCCA CAGAATCGCC TTTTAACGCT 4740 GCCTGCGTAT AATAGTGTAC AGAAAGTGAT GTATCCTGCC CTACTGTATC ATTACCTGTT 4800 TCATAAATCT GTGCCAACAA AGTTGCTGAA GGAACATGCC CTAAACTTGC TGCTTGAATA 4860 TATAGTTCCA TTGCATACTT TTCATCCGGA ATGACAACAT CTAAGAACCC TTCATGATAA 4920 ATCTTAGCCA ATTCGTATGG TGCTGCGGCC GTCAACTCAT TAGCTCTTGC TGCAGCCCTT 4980 GATAACCATT TTACCCCATT TAATTTAGTA TTAACGTCGG TTGGAAGACC CATTCTGCCG 5040 TAGAATGAAT AAAGTCCCAA TTTATACATT GCTGAGGGAT GATTCCTGCT AGC 5093 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 42 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: GATAGTTAAG GATCCATGGC TCGTTCTTCC TTGCCCAACC GC 42 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 45 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: AAACTTCATC AATGCGGCCG CTAAGGGGAT CCAGCCATTG TAAAT 45 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 23 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: TTTCCTTGTT TATCCTTTTC CAA 23 (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: GATCACTTCG GATCCGTCAC ACCCAGTTAG 30 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2870 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: AATTTCCTTG TTTATCCTTT TCCAATAGCG GAACAATTGA TAATAAAGCA ATGTAAGCAG 60 AAGCGAAAAA TAAAAAGAAA TAGGCTGCAG AGATTCACAG GCTGCGCTCT AGAAACATTT 120 GAAATCAAGG CAAACATAGA ACACTTGATA AAATTCTTAC CATAATACCA CCATTGATGA 180 TTCAAAAAAT GAGCCCAAGC TTAAGGAGGC CATCAACGAG GTCTAGTTCT GGTTCAAGTA 240 ATATCCCACA ATCGCCCTCT GTACGATCAA CTTCATCGTT TTCTAATCTG ACAAGAAACT 300 CCATACGGAG CACCTCTAAT TCGGGTTCTC AGTCGATTTC TGCATCTTCC ACTAGAAGTA 360 ACTCCCCACT AAGATCCGTA TCAGCCAAAT CCGATCCCTT CCTTCACCCA GGTAGGATAA 420 GGATCAGGCG GAGCGACAGT ATTAACAACA ACTCGAGAAA AAACGATACA TATACTGGGT 480 CAATCACTGT GACCATCCGG CCGAAACCAC GGAGCGTTGG AACTTCCCGT GACCATGTGG 540 GGCTAAAATC GCCCAGGTAC TCTCAACCAA GATCCAACTC ACATCACGGT AGCAATACAT 600 TTGTTAGAGA CCCCTGGTTT ATTACTAATG ACAAAACAAT AGTGCATGAA GAAATTGGAG 660 AGTTCAAGTT CGATCATGTT TTTGCTTCCC ATTGCACTAA TTTGGAAGTT TATGAAAGAA 720 CCAGTAAACC AATGATTGAT AAGTTATTGA TGGGGTTTAA TGCCACCATA TTTGCGTACG 780 GTATGACCGG GTCAGGTAAA ACGTTTACAA TGAGCGGAAA TGAACAAGAG CTAGGCCTAA 840 TTCCTTTATC TGTGTCGTAT TTATTTACCA ATATCATGGA ACAATCAATG AATGGCGATA 900 AAAAGTTCGA CGTTATAATA TCGTACCTCG AAATTTACAA TGAAAGGATT TACGACCTGT 960 TAGAAAGCGG ATTAGAAGAA TCCGGTAGTA GAATCAGTAC TCCTTCAAGG TTATATATGA 1020 GCAAGAGCAA CAGCAATGGA TTGGGCGTAG AATTAAAAAT CAGAGATGAC TCTCAGTATG 1080 GGGTCAAAGT TATCGGTCTC ACCGAAAGAA GATGTGAAAG TAGTGAAGAA TTATTGAGGT 1140 GGATTGCAGT TGGTGACAAA AGTAGGAAAA TTGGCGAAAC TGACTACAAT GCAAGAAGCT 1200 CACGATCTCA TGCCATTGTA CTGATTCGTT TAACAAGTAC TAACGTAAAG AACGGCACCT 1260 CAAGATCGAG TACATTGTCG TTGTGTGACC TAGCAGGTTC GGAAAGGGCT ACGGGGCAAC 1320 AAGAGAGGAG AAAGGAAGGT TCATTCATCA ACAAATCCTT ACTTGCTTTG GGGACTGTGA 1380 TATCCAAACT CAGTGCCGAC AAGATGAACT CAGTAGGCTC AAACATTCCC TCGCCATCTG 1440 CAAGTGGCAG TAGCAGCAGT AGTGGAAATG CTACCAATAA CGGCACTAGC CCAAGCAACC 1500 ACATTCCATA TCGTGATTCT AAATTGACTA GATTATTGCA GCCGGCACTA AGCGGTGACA 1560 GCATAGTGAC AACGATATGT ACAGTCGACA CCAGAAATGA TGCGGCAGCG GAAACTATGA 1620 ATACGCTGAG GTTTGCATCA AGAGCGAAAA ACGTCGCACT TCATGTATCC AAAAAATCCA 1680 TCATCAGTAA CGGGAATAAC GATGGAGATA AAGATCGCAC CATTGAGCTA CTGAGACGCC 1740 AATTGGAAGA ACAACGTAGG ATGATCTCTG AATTGAAGAA CCGTTCAAAC ATTGGCGAGC 1800 CCTTAACCAA ATCTTCCAAT GAAAGTACTT ATAAAGACAT TAAAGCCACC GGCAATGATG 1860 GTGATCCGAA TTTGGCTCTA ATGAGAGCGG AGAATCGAGT ATTAAAATAT AAACTAGAGA 1920 ATTGTGAAAA ACTACTAGAT AAAGATGTGG TTGATTTGCA AGATTCTGAG ATTATGGAAA 1980 TTGTAGAAAT GCTTCCCTTT GAGGTCGGCA CCCTTTTGGA AACAAAGTTC CAAGGTTTGG 2040 AATCACAAAT AAGGCAATAT AGGAAATACA CTCAAAAACT TGAAGACAAG ATCATGGCGC 2100 TAGAAAAAAG TGGTCATACT GCAATGTCGC TAACTGGGTG TGACGGCACT GAAGTGATCG 2160 AATTACAGAA GATGCTCGAG AGGAAGGATA AAATGATTGA GGCCCTGCAG AGTGCCAAAC 2220 GACTGCGGGA TAGGGCTTTG AAACCACTCA TTAATACACA GCAATCACCG CACCCTGTCG 2280 TGGATAACGA TAAATGATTA GGTGAGGGTC CCAGATCTCG GGTGCTTTTT TCCTTGTGCG 2340 GATTGTTCTG TAGACTGCGC CTCCGCTTCC CGGCCTTGCT TGAACGGGAT CTATTCTCAG 2400 AAGACAGCGC ATAAAAGGCA GTTTTTAGGC ACTTCTCGTT AAGAAAATAC ACAAATAATG 2460 GATTTACAGT TCGTTTCAGT GTGGTACCAA AAAATTTCAT CAGCTAATAA AGATCAAGAA 2520 GTTTTGGGGT TGTTTCGAGT CTGTCTCGGC CTTAATTGTG CAGGTACTAA AGGAATTAAT 2580 ATATAAAGAT TGTTAAGGCC AAGTGACTGA AACTTGCAAA CGTCTTTGAA TCAGGCTTAT 2640 CTCTTAAATA CTTATATATA TGTTCTTTTA TAGACTTCAT AATCTCTTGT TCCAAGAACA 2700 GTAAAGAGCA ATTAAAAAAA GGAAAATAAC AGTTAAAGAT GATAGCGGAT TCATCAGTTT 2760 TGAAAAAGCA CACAGCAATC AAGAGAAGTA CGAGAATAAT ATCGCTAACA CTCGTTTTGC 2820 TTGGCGTATT TAGCTTCTTA CTACTTACAT GGAATGACTC CTTGGAATTC 2870 (2) INFORMATION FOR SEQ ID NO:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: ACCATAATAC CAGGATCCAT GATTCAAAAA 30 (2) INFORMATION FOR SEQ ID NO:30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 42 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: CCTGTCGTGG ATAGCGGCCG CTAGGATCCT GAGGGTCCCA GA 42 (2) INFORMATION FOR SEQ ID NO:31: (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:31: ACATCATCTA GAGACTTCCT TTGTGACC 28 (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 26 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: TATATAATCG ATTGAAAGGC AATATC 26 (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3883 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: AGCAAGAATT GAACATGGAT GAATTCATTG GATCAAAGAC CGATTTAATC AAAGATCAAG 60 TGAGAGATAT TCTTGATAAA TTGAATATTA TTTAATTCTT CATTTAGAAA AATTTCAGCT 120 GCTTTTTTTT TTCTTTTTCT TTCCTTAGGC GTCTCGAGGT TACAAGTCGG AGTCCCTCTT 180 CACTATCGTT TGTCCACTTT TTTTATATCC CCATTATTTT CAATCTGAAT TTCATTTTTT 240 TTTTTTAATT CATGAAATTT ATATGTCCCA CGTATTACTA CATATTTGCG TTTTTAATTA 300 AATAAATAAC TGTTACTTTT ATTATATCTT ATTTGCAGAT CACTTATCTG ATCAAATGTT 360 TTCGTTTTCG TGTGTGGTGA CGATGTATTA GGTACGCGAA ATAAACAAAA CAAACAAACA 420 AGGCCGCAAC AATAACATCA TCTAAAGACT TCCTTTGTGA CCCGCTTCTC AACAGCGGGT 480 GTAGAACTTA TGGTATGGCC AGAAAGTAAC GTTGAGTATA GATACAGAAG CAAGCAATTC 540 AAAGGAAAAA GTAATAAAAA GTATATAAAA GCGCAAAAAA TACAACAAGA AAGAATTTGT 600 TTGATGCCAG CGGAAAACCA AAATACGGGT CAAGATAGAA GCTCCAACAG CATCAGTAAA 660 AATGGCAACT CTCAGGTTGG ATGTCACACT GTTCCTAATG AGGAACTGAA CATCACTGTA 720 GCTGTGCGAT GCAGAGGAAG GAATGAAAGG GAAATTAGTA TGAAAAGCTC CGTTGTGGTA 780 AATGTTCCAG ATATTACAGG TTCTAAAGAA ATTTCCATTA ACACGACGGG AGATACCGGT 840 ATAACTGCTC AAATGAATGC CAAGAGATAC ACAGTGGACA AAGTCTTCGG TCCCGGCGCT 900 TCCCAGGATC TAATTTTTGA TGAAGTGGCG GGCCCATTAT TCCAGGATTT CATTAAAGGT 960 TACAATTGCA CCGTACTGGT ATATGGTATG ACGTCAACAG GTAAAACATA TACAATGACG 1020 GGCGACGAAA AGTTATATAA TGGTGAATTG AGCGATGCAG CAGGAATTAT ACCGAGGGTT 1080 CTTTTGAAGT TGTTTGACAC ATTGGAACTA CAACAGAACG ATTACGTAGT AAAATGTTCG 1140 TTCATTGAAC TCTACAACGA AGAATTGAAG GACCTCTTGG ACAGCAATAG CAACGGCTCT 1200 AGTAATACTG GCTTTGACGG CCAATTTATG AAAAAATTGA GGATTTTTGC TTCAAGCACA 1260 GCAAATAATA CCACTAGCAA CAGTGCTAGT AGTTCCAGGA GTAATTCTAG GAACAGTTCT 1320 CCGAGGTCAT TAAATGATCT AACACCTAAA GCTGCTCTAT TAAGAAAAAG GTTAAGGACA 1380 AAATCACTGC CGAATACCAT CAAGCAACAG TATCAACAAC AACAGGCAGT GAATTCCAGG 1440 AACAACTCTT CCTCTAACTC TGGCTCTACC ACTAATAATG CTTCTAGTAA CACCAACACA 1500 AATAACGGTC AAAGAAGTTC GATGGCTCCA AATGACCAAA CTAATGGTAT ATACATCCAG 1560 AATTTGCAAG AATTTCACAT AACAAATGCT ATGGAGGGGC TAAACCTATT ACAAAAAGGC 1620 TTAAAGCATA GGCAAGTAGC GTCCACTAAA ATGAACGATT TTTCCAGTAG ATCTCATACC 1680 ATTTTTACAA TCACTTTGTA TAAGAAGCAT CAGGATGAAC TATTTAGAAT TTCCAAAATG 1740 AATCTTGTGG ATTTAGCTGG TTCAGAAAAC ATCAACAGAT CCGGAGCATT AAATCAACGT 1800 GCCAAAGAAG CTGGTTCAAT CAACCAAAGT CTATTGACGC TGGGCAGGGT CATAAACGCA 1860 CTCGTAGATA AAAGCGGCCA TATACCTTTC CGTGAATCGA AATTGACCCG CCTGCTTCAA 1920 GATTCCCTGG GTGGTAATAC GAAAACCGCA CTAATTGCTA CTATATCGCC TGCAAAGGTA 1980 ACTTCTGAAG AAACCTGCAG TACATTAGAG TATGCTTCGA AGGCTAAAAA CATTAAGAAC 2040 AAGCCGCAAC TGGGTTCATT TATAATGAAG GATATTTTGG TTAAAAATAT AACTATGGAA 2100 TTAGCAAAGA TTAAATCCGA TTTACTCTCT ACAAAGTCCA AAGAAGGAAT ATATATGAGC 2160 CAAGATCACT ACAAAAATTT GAACAGTGAT TTAGAAAGTT ATAAAAATGA AGTTCAAGAA 2220 TGTAAAAGAG AAATTGAAAG TTTGACATCG AAAAATGCAT TGCTAGTAAA AGATAAATTG 2280 AAGTCAAAAG AAACTATTCA ATCTCAAAAT TGCCAAATAG AATCATTGAA AACTACCATA 2340 GATCATTTAA GGGCACAACT AGATAAACAG CATAAAACTG AAATTGAAAT ATCCGATTTT 2400 AATAACAAAC TACAGAAGTT GACTGAGGTA ATGCAAATGG CCCTACATGA TTACAAAAAA 2460 AGAGAACTTG ACCTTAATCA AAAGTTTGAA ATGCATATTA CTAAAGAAAT TAAAAAATTG 2520 AAATCTACAC TGTTTTTACA ATTAAACACT ATGCAACAGG AAAGTATTCT TCAAGAGACT 2580 AATATCCAAC CAAATCTTGA TATGATCAAA AATGAAGTAC TGACTCTTAT GAGAACCATG 2640 CAAGAAAAAG CTGAACTAAT GTACAAAGAC TGTGTGAAGA AAATTTTAAA CGAATCTCCT 2700 AAATTCTTCA ATGTTGTTAT TGAGAAAATC GACATAATAA GAGTAGATTT CCAAAAATTT 2760 TATAAAAATA TAGCCGAGAA TCTTTCTGAT ATTAGCGAAG AAAATAACAA CATGAAACAG 2820 TACTTAAAAA ACCATTTTTT CAAGAATAAC CATCAAGAAT TACTGAATCG TCATGTGGAT 2880 TCTACTTATG AAAATATTGA GAAGAGAACA AACGAGTTTG TTGAGAACTT TAAAAAGGTC 2940 CTAAATGACC ACCTTGACGA AAATAAAAAA CTAATAATGC ACAATCTGAC AACTGCAACC 3000 AGCGCGGTTA TTGATCAAGA AATGGATCTG TTTGAACCCA AGCGCGTTAA ATGGGAAAAT 3060 TCATTTGATC TGATAAATGA TTGTGACTCC ATGAATAACG AATTCTATAA TAGCATGGCA 3120 GCGACGCTAT CGCAAATCAA GAGTACTGTT GATACATCAT CAAATTCGAT GAATGAGTCT 3180 ATTTCAGTCA TGAAAGGACA AGTGGAAGAA TCGGAGAACG CTATATCCCT TTTGAAGAAC 3240 AATACCAAAT TTAATGATCA ATTTGAGCAG CTTATTAACA AGCATAACAT GTTGAAAGAT 3300 AACATTAAAA ATTCGATAAC ATCAACACAC TCTCATATAA CTAATGTGGA TGATATCTAT 3360 AATACGATTG AAAACATAAT GAAAAACTAT GGTAACAAGG AAAACGCTAC CAAAGACGAA 3420 ATGATCGAGA ACATATTGAA GGAAATACCA AATCTAAGTA AGAAAATGCC GTTAAGGTTA 3480 TCAAACATAA ATAGCAATTC AGTGCAAAGT GTAATATCGC CCAAAAAGCA TGCAATTGAA 3540 GATGAAAACA AATCCAGTGA AAATGTGGAC AATGAGGGCT CGAGAAAAAT GTTAAAGATT 3600 GAATAGTTGA TATTGCCTTT CAGTCGAATA TATATTCAAA CTAGTGGTTA ATAAAAACAA 3660 AGTATGTAAA GAATACTCAG TTATTCATTA GAAGGCAAGA CAGAAGAGAA GGGTGTGAAA 3720 CCACCTCTAC CAAACACACC AAGAGATGAA CCTAAATCAA ATTTTCACAG AGCTAACTAT 3780 ATAAACGTTT GGATTCGTGT GTACTATCTT TATTTACGGA AATAAGTTGT AATATTAAAA 3840 AAAAAAAAAA ACATTTTGAT GGACAATGAA TTTCTCTAAT TTT 3883 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 36 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: CGGGTGTAGG ATCCATGGTA TGGCCAGAAA GTAACG 36 (2) INFORMATION FOR SEQ ID NO:35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 53 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: GTGGACAATG GCGGCCGCAG AAAAAGGATC CAGATTGAAT AGTTGATATT GCC 53 (2) INFORMATION FOR SEQ ID NO:36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 28 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: GAATATTCTA GAACAACTAT CAGGAGTC 28 (2) INFORMATION FOR SEQ ID NO:37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 25 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA ( xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: TTGTCACTCG AGTGAAAAAG ACCAG 25 (2) INFORMATION FOR SEQ ID NO:38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3466 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (genomic) (xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: CTGCAGCAGA AAATCCAGTA GAACCATCAT CATGTTTGCT GTTTTTCGAT TTTTTCTTTC 60 TTGGGAAGTC GTCGTCCTCT TCTTCTTCAT CATCATCTTC TTCAGCATCA CTTTGTTCGT 120 TATCTATAAT TTTAGATGAT TCATCGCTAG AGCTATTCTG CTCGTCTTCT TCGGCTTCAT 180 CACCTTCCAT TATTGTATCT TTTTCCGGCT CATTACTTAA CTCTTGGTTG CCACTATTCC 240 TTTTTTCACG CCCAAATTCT GCATTCTTTC TGGTTCTTTT CTTATCCTTA GTGTCTACTC 300 TGTGCTTGGA GCCCATGATC AATTATGTAC TGATTTTCCT TCGGCTTCTC TATCGCTTTA 360 TTCATAGCAT CTGTTTATTA CCTTTCCTTA TATCTTATGG GCATCGAATC CTAGATTTTT 420 TTCTTTCAAA ATTTTCCAAT AAGAGGGTAA TGGAGATACA CCAAAATGAA TCTCAAACAA 480 AATCAAAACA AACACTGTTT ACAATTTGAT GCGCCTCGAA TCAAAATATG ATGATGAGTA 540 TTACAGCTAA AAAAATTATC GAATATTATA TAAGCATTAA AGCTATCAAT TTTTCCGCTC 600 TTTGTGTTTC TTATTATTCT ATTTGAATAT ACCAGAACAA CTATCCGGAG TCTTTGTTTA 660 AAAAAGGTAG ATTTTGAAAT AAAGGACTTA GAGAAATTCT GGCAACTATT AAAGTATGGA 720 ATCACTTCCA CGTACTCCCA CAAAAGGCAG ATCTACGCAG CATCTCTCGA CACCATCGCC 780 GAAGAATGAT ATTTTAGCTA TGAATGGCCA CAAAAGAAGA AATACAACAA CTCCACCGCC 840 TAAGCACACT CTTCTGAAGC CGCAACGTAC GGATATTCAT AGACACTCAT TAGCTAGTCA 900 GAGTCGCATA TCCATGTCAC CTAATCGCGA GCTTTTAAAG AATTATAAAG GTACAGCAAA 960 TTTGATTTAT GGAAACCAGA AAAGCAACTC CGGTGTAACT TCCTTTTATA AAGAAAATGT 1020 TAATGAACTC AATAGAACAC AAGCAATCTT ATTTGAGAAA AAGGCAACAC TAGATTTACT 1080 CAAAGATGAA CTAACAGAAA CGAAAGAGAA AATCAATGCC GTTAATCTCA AATTTGAAAC 1140 CCTTCGTGAA GAAAAGATAA AAATTGAACA GCAACTGAAT TTGAAAAACA ATGAACTTAT 1200 CTCGATTAAA GAAGAATTTT TGTCAAAGAA GCAGTTCATG AATGAAGGAC ATGAAATACA 1260 TTTAAAGCAG CTAGCGGCAT CTAATAAAAA AGAGCTGAAA CAAATGGAAA ATGAATACAA 1320 AACAAAAATT GAGAAATTGA AATTTATGAA GATTAAACAG TTTGAAAATG AAAGAGCGTC 1380 GCTTTTAGAT AAAATAGAAG AGGTAAGAAA TAAAATCACC ATGAACCCTT CCACTTTACA 1440 GGAAATGTTG AACGATGTTG AACAAAAGCA TATGCTTGAA AAAGAAGAAT GGCTTACAGA 1500 GTACCAATCG CAGTGGAAAA AGGATATAGA GCTGAATAAT AAACATATGC AAGAAATCGA 1560 AAGCATAAAA AAGGAAATCG AAAATACATT AAAACCTGAG TTGGCAGAAA AAAAGAAGCT 1620 CTTAACAGAA AAGCGTAACG CGTATGAAGC TATCAAAGTA AAAGTTAAAG AAAAGGAAGA 1680 GGAAACTACA AGGCTGAGAG ATGAGGTGGC ATTAAAACAG AAAACTAATT TAGAAACTTT 1740 GGAAAAGATC AAAGAACTTG AGGAATATAT AAAAGACACT GAACTGGGTA TGAAGGAGTT 1800 GAATGAAATT CTGATTAAAG AGGAAACGGT TAGACGCACA TTGCATAATG AGTTACAAGA 1860 GTTAAGAGGA AATATACGAG TTTATTGTAG GATTCGTCCA GCTCTAAAAA ATTTGGAAAA 1920 TTCTGATACT AGCCTTATTA ATGTTAATGA ATTTGATGAC AATAGTGGTG TTCAATCTAT 1980 GGAAGTGACG AAAATACAAA ACACAGCGCA AGTGCATGAA TTCAAATTTG ATAAAATATT 2040 TGATCAACAG GATACAAATG TGGATGTTTT TAAAGAAGTT GGTCAGTTAG TGCAAAGTTC 2100 ATTAGATGGA TATAATGTTT GTATCTTCGC ATACGGACAA ACAGGATCTG GGAAAACTTT 2160 CACGATGTTA AATCCAGGTG ATGGTATCAT TCCGTCCACA ATATCTCATA TATTTAACTG 2220 GATCAATAAA TTAAAGACAA AAGGATGGGA TTATAAAGTT AACTGCGAAT TCATTGAGAT 2280 CTACAACGAG AACATCGTAG ACTTATTGAG AAGTGATAAT AATAATAAAG AAGACACAAG 2340 CATTGGCTTA AAGCACGAAA TACGTCATGA TCAGGAAACT AAGACTACCA CGATAACGAA 2400 TGTTACGAGT TGCAAGCTTG AGTCGGAAGA AATGGTGGAA ATAATCCTGA AAAAAGCAAA 2460 TAAATTAAGA TCCACCGCTA GCACAGCATC AAATGAGCAT TCCTCCCGTT CACACAGTAT 2520 TTTCATAATT CATTTGTCTG GATCAAATGC AAAAACTGGA GCACACTCGT ATGGCACACT 2580 AAATCTTGTT GATTTGGCCG GTTCCGAAAG AATAAATGTC TCTCAAGTTG TAGGGGATAG 2640 ATTAAGAGAA ACACAAAATA TAAATAAATC TTTAAGTTGC TTAGGTGACG TTATTCATGC 2700 TTTAGGTCAG CCTGATAGTA CCAAAAGACA TATACCGTTC AGGAACTCAA AACTGACATA 2760 CCTACTGCAA TATTCACTCA CTGGGGATTC GAAAACATTA ATGTTTGTAA ACATTTCACC 2820 AAGCTCCTCT CATATTAATG AGACTCTCAA TTCGTTAAGA TTTGCGTCTA AAGTGAATTC 2880 TACCAGATTG GTTAGTAGAA AATGAGGTCA AGGCCTTTTC TGGTCTTTTT CACTCCTTTG 2940 ACAAATGACA GAGACTGTCC ATACATTCAT CACATGTAAC TATATTATAT ATGAAACTCA 3000 TTTTAATGCG CACAGATAAA AAGCAAAGTA AGTAATGAAT ATTTGTTATG TAAAAATGAC 3060 CTCATACATG CTAGTATTTA CACGAATTTA ATTGCTTAAA TTTCAATCAT CCTTACCCTT 3120 TGGTTTACCC TCTGGAGGCA GAAACTTTTG CATCCTCCTT ATTGCCCAAT TTTCGCCAAT 3180 GACTTTAACA TCTGGGTCCG ATTTACCTTC CGTGGTGTTG AACCGCTTCC ACCATGAGGG 3240 GGATTTGAAC CTAGGGTCTT CGCGTGGTAA TTTGCGAACT TCATTTCTAA TTTCAGCAAC 3300 ATGGGCTCTC AGTTCAGCGG CTAATCTGCT TCTTAAATCT TGCGCCTCTT TACCATATTT 3360 CAATTCGTCA GAGAGGTCGT TAGGATTTTT GGGATCATAG TATTTTTCAA CCAAATGTGT 3420 CCATTCTTTT CTATACCTGT CGATTAAATC ATCATTTAAA GGATCC 3466 (2) INFORMATION FOR SEQ ID NO:39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 42 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: GATAGTTAAG GATCCATGGC TCGTTCTTCC TTGCCCAACC GC 42 (2) INFORMATION FOR SEQ ID NO:40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 45 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: AAACTTCATC AATGCGGCCG CTAAGGGGAT CCAGCCATTG TAAAT 45 (2) INFORMATION FOR SEQ ID NO:41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2385 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: GAATTCCGAT AGTATTATGT GGAGTTCCAT TTTTATGTAT TTTTTGTATG AAATATTCTA 60 GTATAAGTAA ATATTTTATC AGAAGTATTT ACATATCTTT TTTTTTTTTA GTTTGAGAGC 120 GGCGGTGATC AGGTTCCCCT CTGCTGATTC TGGGCCCCGA ACCCCGGTAA AGGCCTCCGT 180 GTTCCGTTTC CTGCCGCCCT CCTCCGTAGC CTTGCCTAGT GTAGGAGCCC CGAGGCCTCC 240 GTCCTCTTCC CAGAGGTGTC GGGGCTTGGC CCCAGCCTCC ATCTTCGTCT CTCAGGATGG 300 CGAGTAGCAG CGGCTCCAAG GCTGAATTCA TTGTCGGAGG GAAATATAAA CTGGTACGGA 360 AGATCGGGTC TGGCTCCTTC GGGGACATCT ATTTGGCGAT CAACATCACC AACGGCGAGG 420 AAGTGGCAGT GAAGCTAGAA TCTCAGAAGG CCAGGCATCC CCAGTTGCTG TACGAGAGCA 480 AGCTCTATAA GATTCTTCAA GGTGGGGTTG GCATCCCCCA CATACGGTGG TATGGTCAGG 540 AAAAAGACTA CAATGTACTA GTCATGGATC TTCTGGGACC TAGCCTCGAA GACCTCTTCA 600 ATTTCTGTTC AAGAAGGTTC ACAATGAAAA CTGTACTTAT GTTAGCTGAC CAGATGATCA 660 GTAGAATTGA ATATGTGCAT ACAAAGAATT TTATACACAG AGACATTAAA CCAGATAACT 720 TCCTAATGGG TATTGGGCGT CACTGTAATA AGTGTTTAGA ATCTCCAGTG GGGAAGAGGA 780 AAAGAAGCAT GACTGTTAGT ACTTCTCAGG ACCCATCTTT CTCAGGATTA AACCAGTTAT 840 TCCTTATTGA TTTTGGTTTG GCCAAAAAGT ACAGAGACAA CAGGACAAGG CAACACATAC 900 CATACAGAGA AGATAAAAAC CTCACTGGCA CTGCCCGATA TGCTAGCATC AATGCACATC 960 TTGGTATTGA GCAGAGTCGC CGAGATGACA TGGAATCATT AGGATATGTT TTGATGTATT 1020 TTAATAGAAC CAGCCTGCCA TGGCAAGGGC TAAAGGCTGC AACAAAGAAA CAAAAATATG 1080 AAAAGATTAG TGAAAAGAAG ATGTCCACGC CTGTTGAAGT TTTATGTAAG GGGTTTCCTG 1140 CAGAATTTGC GATGTACTTA AACTATTGTC GTGGGCTACG CTTTGAGGAA GCCCCAGATT 1200 ACATGTATCT GAGGCAGCTA TTCCGCATTC TTTTCAGGAC CCTGAACCAT CAATATGACT 1260 ACACATTTGA TTGGACAATG TTAAAGCAGA AAGCAGCACA GCAGGCAGCC TCTTCCAGTG 1320 GGCAGGGTCA GCAGGCCCAA ACCCCCACAG GCAAGCAAAC TGACAAAACC AAGAGTAACA 1380 TGAAAGGTTA GTAGCCAAGA ACCAAGTGAC GTTACAGGGA AAAAATTGAA TACAAAATTG 1440 GGTAATTCAT TTCTAACAGT GTTAGATCAA GGAGGTGGTT TTAAAATACA TAAAAATTTG 1500 GCTCTGCGTT AAAAAAAAAA AAGACGTCCT TGGAAAATTT GACTACTAAC TTTAAACCCA 1560 AATGTCCTTG TTCATATATA TGTATATGTA TTTGTATATA CATATATGTG TGTATATTTA 1620 TATCATTTCT CTTGGGATTT TGGGTCATTT TTTTAACAAC TGCATCTTTT TTACTCATTC 1680 ATTAACCCCC TTTCCAAAAA TTTGGTGTTG GGAATATAAT ATAATCAATC AATCCAAAAT 1740 CCTAGACCTA ACACTTGTTG ATTTCTAATA ATGAATTTGG TTAGCCATAT TTTGACTTTA 1800 TTTCAGACTA ACAATGTTAA GATTTTTTAT TTTGCATGTT AATGCTTTAG CATTTAAAAT 1860 GGAAAATTGT GAACATGTTG TAATTTCAAG AGGTGAGTTT GGCATTACCC CCAAAGTGTC 1920 TATCTTCTCA GTTGCAGAGC ATCTCATTTT CTCTCTTAAA TGCTCAAATA AATGCAAAGC 1980 TCAGCACATC TTTTCTAGTC ACAAAAATAA TTCTTTTATT TGCAGTTTAC GTATGATCTT 2040 AATTTCAAAA CGATTTCTTT GTTTTTGGCT TGATTTTTCA CAATGTTGCA AATATCAGGC 2100 TCCCAGGGTT TAATGTGGAA TTGAAGTCTG CAGCCAGGCC TTGCAAATTG AAGGTAACTG 2160 GGGCAAATGC CATTGAAACC GCTAGTCTTA TTTCCTTTCT ACTTTTCTTT GGCACTCTTA 2220 CTGCCTGTAA GGAGTAGAAC TGTTAAGGCA CACTGTTGCT ATACAGTTAA CTCCCATTTT 2280 CATGTTTTGT CTTTCTTTTC CCATTTCTGG GGCTTACCTC CTGATACCTG CTTACTTTCT 2340 GGAAGTAGTG GGCAAGTAAG ATTTGGCTCT TGGTTTCTGG AATTC 2385 (2) INFORMATION FOR SEQ ID NO:42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: CTTCGTCTCT CACATATGGG CGAGTAGCAG CGGC 34 (2) INFORMATION FOR SEQ ID NO:43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3505 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA ( i) SEQUENCE DESCRIPTION: SEQ ID NO:43: GAATTCCGAC AGGAAAGCGA TGGTGAAAGC GGGGCCGTGA GGGGGGCGGA GCCGGGAGCC 60 GGACCCGCAG TAGCGGCAGC AGCGGCGCCG CCTCCCGGAG TTCAGACCCA GGAAGCGGCC 120 GGGAGGGCAG GAGCGAATCG GGCCGCCGCC GCCATGGAGC TGAGAGTCGG GAACAGGTAC 180 CGGCTGGGCC GGAAGATCGG CAGCGGCTCC TTCGGAGACA TCTATCTCGG TACGGACATT 240 GCTGCAGGAG AAGAGGTTGC CATCAAGCTT GAATGTGTCA AAACCAAACA CCCTCAGCTC 300 CACATTGAGA GCAAAATCTA CAAGATGATG CAGGGAGGAG TGGGCATCCC CACCATCAGA 360 TGGTGCGGGG CAGAGGGGGA CTACAACGTC ATGGTGATGG AGCTGCTGGG GCCAAGCCTG 420 GAGGACCTCT TCAACTTCTG CTCCAGGAAA TTCAGCCTCA AAACCGTCCT GCTGCTTGCT 480 GACCAAATGA TCAGTCGCAT CGAATACATT CATTCAAAGA ACTTCATCCA CCGGGATGTG 540 AAGCCAGACA ACTTCCTCAT GGGCCTGGGG AAGAAGGGCA ACCTGGTGTA CATCATCGAC 600 TTCGGGCTGG CCAAGAAGTA CCGGGATGCA CGCACCCACC AGCACATCCC CTATCGTGAG 660 AACAAGAACC TCACGGGGAC GGCGCGGTAC GCCTCCATCA ACACGCACCT TGGAATTGAA 720 CAATCCCGAA GAGATGACTT GGAGTCTCTG GGCTACGTGC TAATGTACTT CAACCTGGGC 780 TCTCTCCCCT GGCAGGGGCT GAAGGCTGCC ACCAAGAGAC AGAAATACGA AAGGATTAGC 840 GAGAAGAAAA TGTCCACCCC CATCGAAGTG TTGTGTAAAG GCTACCCTTC CGAATTTGCC 900 ACATACCTGA ATTTCTGCCG TTCCTTGCGT TTTGACGACA AGCCTGACTA CTCGTACCTG 960 CGGCAGCTTT TCCGGAATCT GTTCCATCGC CAGGGCTTCT CCTATGACTA CGTGTTCGAC 1020 TGGAACATGC TCAAATTTGG TGCCAGCCGG GCCGCCGATG ACGCCGAGCG GGAGCGCAGG 1080 GACCGAGAGG AGCGGCTGAG ACACTCGCGG AACCCGGCTA CCCGCGGCCT CCCTTCCACA 1140 GCCTCCGGCC GCCTGCGGGG GACGCAGGAA GTGGCTCCCC CCACACCCCT CACCCCTACC 1200 TCACACACGG CTAACACCTC CCCCCGGCCC GTCTCCGGCA TGGAGAGAGA GCGGAAAGTG 1260 AGTATGCGGC TGCACCGCGG GGCCCCCGTC AACATCTCCT CGTCCGACCT CACAGGCCGA 1320 CAAGATACCT CTCGCATGTC CACCTCACAG ATTCCTGGTC GGGTGGCTTC CAGTGGTCTT 1380 CAGTCTGTCG TGCACCGATG AGAACTCTCC TTATTGCTGT GAAGGGCAGA CAATGCATGG 1440 CTGATCTACT CTGTTACCAA TGGCTTTACT AGTGACACGT CCCCCGGTCT AGGATCGAAA 1500 TGTTAACACC GGGAGCTCTC CAGGCCACTC ACCCAGCGAC GCTCGTGGGG GAAACATACT 1560 AAACGGACAG ACTCCAAGAG CTGCCACCGC TGGGGCTGCA CTGCGGCCCC CCACGTGAAC 1620 TCGGTTGTAA CGGGGCTGGG AAGAAAAGCA GAGAGAGAAT TGCAGAGAAT CAGACTCCTT 1680 TTCCAGGGCC TCAGCTCCCT CCAGTGGTGG CCGCCCTGTA CTCCCTGACG ATTCCACTGT 1740 AACTACCAAT CTTCTACTTG GTTAAGACAG TTTTGTATCA TTTTGCTAAA AATTATTGGC 1800 TTAAATCTGT GTAAAGAAAA TCTGTCTTTT TATTGTTTCT TGTCTGTTTT TGCGGTCTTA 1860 CAAAAAAAAT GTTGACTAAG GAATTCTGAG ACAGGCTGGC TTGGAGTTAG TGTATGAGGT 1920 GGAGTCGGGC AGGGAGAAGG TGCAGGTGGA TCTCAAGGGT GTGTGCTGTG TTTGTTTTGC 1980 AGTGTTTTAT TGTCCGCTTT GGAGAGGAGA TTTCTCATCA AAAGTCCGTG GTGTGTGTGT 2040 GTGCCCGTGT GTGGTGGGAC CTCTTCAACC TGATTTTGGC GTCTCACCCT CCCTCCTCCC 2100 GTAATTGACA TGCCTGCTGT CAGGAACTCT TGAGGCCCTC GGAGAGCAGT TAGGGACCGC 2160 AGGCTGCCGC GGGGCAGGGG TGCAGTGGGT GTTACCAGGC AAAGCACTGC GCGCTTCTTC 2220 CCCAGGAGGT GGGCAGGCAG CTGAGAGCTT GGAAGCAGAG GCTTTGAGAC CCTAGCAGGA 2280 CAATTGGGAG TCCCAGGATT CAAGGTGGAA GATGCGTTTC TGGTCCCTTG GGAGAGGACT 2340 GTGAACCGAG AGGTGGTTAC TGTAGTGTTT GTTGCCTTGC TGCCTTTGCA CTCAGTCCAT 2400 TTTCTCAGCA CTCAATGCTC CTGTGCGGAT TGGCACTCCG TCTGTATGAA TGCCTGTGGT 2460 TAAAACCAGG AGCGGGGCTG TCCTTGCCAC GTGCCAAGAC TAGCTCAGAA AAGCCGGCAG 2520 GCCAGAAGGA CCCACCCTGA GGTGCCAAGG AGCAGGTGAC TCTCCCAACC GGACCCAGAA 2580 CCTTCACGGC CAGAAAGTAG AGTCTGCGCT GTGACCTTCT GTTGGGCGCG TGTCTGTTGG 2640 TCAGAAGTGA AGCAGCGTGC GTGGGGCCGA GTCCCACCAG AAGGCAGGTG GCCTCCGTGA 2700 GCTGGTGCTG CCCCAGGCTC CATGCTGCTG TGCCCTGAGG TTCCCAGGAT GCCTTCTCGC 2760 CTCTCACTCC GCAGCACTTG GGCGGTAGCC AGTGGCCATG TGCTCCCAAC CCCAATGCGC 2820 AGGGCAGTCT GTGTTCGTGG GCACTTCGGC TGGACCCCAT CACGATGGAC GATGTTCCCT 2880 TTGGACTCTA GGGCTTCGAA GGTGTGCACC TTGGTTCTCC CTTCTCCTCC CCAGAGTTCC 2940 CCCGGATGCC ATAACTGGCT GGCGTCCCAG AACACAGTTG TCAACCCCCC CACCAGCTGG 3000 CTGGCCGTCT GTCTGAGCCC ATGGATGCTT TCTCAATCCT AGGCTGGTTA CTGTGTAAGC 3060 GTGTTGGAGT ACGGCGCCTT GAGCGGGTGG GAGCTGTGTG TTGAAGTACA GAGGGAGGTT 3120 GGGGTGGGTC AGAGCCGAGT TAAGAGATTT TCTTTGTTGC TGGACCCCTT CTTGAAGGTA 3180 GACGTCCCCC ACCCGGAGAG ACGTCGCGCT GTGGCCTGAA GTGGCGCAAG CTTGCTTTGT 3240 AAATATCTGT GGTCCCGATG TAGTGCCCAG AACGTTTGTG CGAGGCAGCT CTGCGCCCGG 3300 GTTCCAGCCC GAGCCTCGCC GGGTCGCGTC TTCGGAGTGC TTGTGACAGT CCTTGCCCAG 3360 TATCTAGTCC CCGTCGCCCC GTGCAGGAGA CGTAGGTAGG ACGTCGTGTC AGCTGTGCAC 3420 TGACGGCCAG TCTCCGAGCT GTGCGTTTGT ATCGCCACTG TATTTGTGTA CTTTAACAAT 3480 CGTGTAAATA ATAAATTCGG AATTC 3505 (2) INFORMATION FOR SEQ ID NO:44: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: CGCGGATCCT AATGGAGGTG AGAGTCGGG 29 (2) INFORMATION FOR SEQ ID NO:45: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: CGCGGATCCG CTCATCGGTG CACGACAGA 29 (2) INFORMATION FOR SEQ ID NO:46: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 18 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: GGAATCACTA CAGGGATG 18 (2) INFORMATION FOR SEQ ID NO:47: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: ATTCTAGACA TGGAGACCAG TTCTTTTGAG 30 (2) INFORMATION FOR SEQ ID NO:48: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: DNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: TGGAAGCTTA TATTACCATA GATTCTTCTT G 31 (2) INFORMATION FOR SEQ ID NO:49: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 33 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: Ser Leu Ser Phe Pro Arg Gly Lys He Ser Lys Asp Glu Asn Asp He 1 5 10 15 Asp Cys Cys He Arg Glu Val Lys Glu Glu He Gly Phe Asp Leu Thr 20 25 30 Asp (2) INFORMATION FOR SEQ ID NO:50: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 33 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: Arg Trp Asn Gly Phe Gly Gly Tyr Val Gin Glu Gly Glu Thr He Glu 1 5 10 15 Asp Gly Ala Arg Arg Glu Leu Gin Glu Glu Ser Gly Leu Thr Val Asp 20 25 30 Ala -7i- (2) INFORMATION FOR SEQ ID NO:51: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 33 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: Lys Leu Glu Phe Pro Gly Gly Lys He Glu Met Gly Glu Thr Arg Glu 1 5 10 15 Gin Ala Val Val Arg Glu Leu Gin Glu Glu Val Gly He Thr Pro Gin 20 25 30 His (2) INFORMATION FOR SEQ ID NO:52: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 33 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: Asp He He Phe Pro Gly Gly Leu Pro Lys Asn Glu Glu Asp Pro He 1 5 10 15 Met Cys Leu Ser Arg Glu He Lys Glu Glu He Asn He Asp Ser Lys 20 25 30 Asp (2) INFORMATION FOR SEQ ID NO:53: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 33 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: Asp He He Phe Pro Gly Gly Leu Pro Lys Asn Glu Glu Asp Pro He 1 5 10 15 Met Cys Leu Ser Arg Glu He Lys Glu Glu He Asn He Asp Ser Lys 20 25 30 Asp

Claims: WHAT IS CLAIMED IS: 1. A method for isolating a polynucleotide encoding a protein that binds to a CKI isoform comprising the steps of: a) transforming or transfecting appropriate host cells with a DNA construct comprising a reporter gene under the control of a promoter regulated by a transcription factor having a DNA-binding domain and an activating domain; b) expressing in said host cells a first hybrid DNA sequence encoding a first fusion of part or all of a CKI isoform and either the DNA-binding domain or the activating domain of said transcription factor: c) expressing in said host cells a library of second hybrid DNA sequences encoding second fusions of part or all of putative CKI isoform-binding proteins and either the DNA-binding domain or activating domain of said transcription factor which is not incorporated in said first fusion; d) detecting binding of CKI isoform-binding proteins to said CKI isoform in a particular host cell by detecting the production of reporter gene product in said host cell; and e) isolating second hybrid DNA sequences encoding CKI isoform- binding protein from said particular host cell. 2. The method of claim 1 wherein said CKI isoform is S. cerevisiae HR 25. 3. The method of claim 1 or 2 wherein said promoter is the ADHI promoter, said DNA-binding domain is the lexA DNA-binding domain, said activating domain is the GAL4 transactivation domain, said reporter gene is the lacZ gene and said host cell is a yeast host cell. 4. A method for detecting proteins which bind to a CKI isoform comprising the steps of: a) transforming or transfecting appropriate host cells with a hybrid DNA sequence encoding a fusion between a putative CKI isoform-binding protein and a ligand capable of high affinity binding to a specific counterreceptor; b) expressing said hybrid DNA sequence in said host cells under appropriate conditions; c) immobilizing fusion protein from said host cells by exposing the fusion protein to said specific counterreceptor in immobilized form; d) contacting a CKI isoform with said immobilized fusion protein; and e) detecting said CKI isoform bound to said fusion protein using a reagent specific for said CKI isoform. 5. The method of claim 4 wherein the CKI isoform is S. cerevisiae HRR25. 6. The method of claim 4 or 5 wherein said ligand is glutathione- S-transferase and said counterreceptor is glutathione. 7. The method of claim 4 or 5 wherein said ligand is hemagglutinin and said counterreceptor is a hemagglutinin-specific antibody. 8. The method of claim 4 or 5 wherein said ligand is polyhistidine and said counterreceptor is nickel. 9. The method of claim 4 or 5 wherein said ligand is maltose- binding protein and said counterreceptor is amylose. 10. A purified and isolated polynucleotide encoding the TIHl amino acid sequence set out in SEQ ID NO: 3. 11. The polynucleotide of claim 10 which is a DNA. 12. The DNA of claim 10 which is a cDNA. 13. The DNA of claim 10 which is a genomic DNA. 14. The DNA of claim 10 which is a chemically synthesized DNA. 15. A full length purified and isolated TIHl-encoding polynucleotide selected from the group consisting of: a) the DNA set out in SEQ ID NO: 2, and b) a DNA which hybridizes under stringent conditions to the protein coding portion of the DNA of a). 16. A purified and isolated TIHl polynucleotide comprising the Tffll DNA sequence set out in SEQ ID NO: 2. 17. A DNA expression construct comprising a DNA according to claim 11, 15 or 16. 18. A host cell transformed with a DNA according to claim 11, 15 or 16. 19. A method for producing an TIHl polypeptide comprising growing a host cell according to claim 18 in a suitable medium and isolating TIHl polypeptide from said host cell or the medium of its growth. 20. Purified and isolated ΗHl polypeptide consisting essentially of the ΗHl amino acid sequence set out in SEQ ID NO: 3. 21. An antibody capable of specifically binding to TIHl. 22. An antibody according to claim 21 which is a monoclonal antibody. 23. A hybridoma cell line producing a monoclonal antibody according to claim 22. 24. A purified and isolated polynucleotide encoding the TTH2 amino acid sequence set out in SEQ ID NO: 5. 25. The polynucleotide of claim 24 which is a DNA. 26. The DNA of claim 24 which is a cDNA. 27. The DNA of claim 24 which is a genomic DNA. 28. The DNA of claim 24 which is a chemically synthesized DNA. 29. A full length purified and isolated TIH2-encoding polynucleotide selected from the group consisting of: a) the DNA set out in SEQ ID NO: 4, and b) a DNA which hybridizes under stringent conditions to the protein coding portion of the DNA of a). 30. A purified and isolated TIH2 polynucleotide consisting essentially of TIH2 DNA sequence set out in SEQ ID NO: 4. 31. A DNA expression construct comprising a DNA according to claim 25. 32. A host cell transformed with a DNA according to claim 25. 33. A method for producing an TIH2 polypeptide comprising growing a host cell according to claim 32 in a suitable medium and isolating TTH2 polypeptide from said host cell or the medium of its growth. 34. Purified and isolated TTH2 polypeptide consisting essentially of the ΗH2 amino acid sequence set out in SEQ ID NO: 5. 35. An antibody capable of specifically binding to TIH2. 36. An antibody according to claim 35 which is a monoclonal antibody. 37. A hybridoma cell line producing the monoclonal antibody according to claim 36. 38. A purified and isolated polynucleotide encoding the TIH3 amino acid sequence set out in SEQ ID NO: 7. 39. The polynucleotide of claim 38 which is a DNA. 40. The DNA of claim 38 which is a cDNA. 41. The DNA of claim 38 which is a genomic DNA. 42. The DNA of claim 38 which is a wholly or partially chemically synthesized DNA. 43. A full length purified and isolated TIH3 encoding polynucleotide selected from the group consisting of: a) the DNA set out in SEQ ID NO: 6, and b) a DNA which hybridizes under stringent conditions to the protein coding portion of the DNA of a). 44. A purified and isolated TIH3 polynucleotide consisting essentially of TIH3 protein coding sequence set out in SEQ ID NO: 6. 45. A DNA expression construct comprising a DNA according to claim 39. 46. A host cell transformed with a DNA according to claim 39. 47. A method for producing an TTH3 polypeptide comprising growing a host cell according to claim 46 in a suitable medium and isolating TTH3 polypeptide from said host cell or the medium of its growth. 48. Purified and isolated TIH3 polypeptide consisting essentially of the TIH3 amino acid sequence set out in SEQ ID NO: 7. 49. An antibody capable of specifically binding to TIH3. 50. An antibody according to claim 49 which is a monoclonal antibody. 51. A hybridoma cell line producing the monoclonal antibody according to claim 50.

Inventors: DEMAGGIO ANTHONY J, HOEKSTRA MERL F, DEMAGGIO, ANTHONY, J., HOEKSTRA, MERL, F.
Applicants: ICOS CORP, ICOS CORPORATION
Application year: 1995
Main classification: C07K14
IPC codes: C07K14, C07K16, C12N1, C12N5, C12N9, C12N15, C12P21, C12Q1, C12R1, G01N33